Trial Outcomes & Findings for Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA) (NCT NCT02833350)
NCT ID: NCT02833350
Last Updated: 2020-06-12
Results Overview
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
578 participants
Primary outcome timeframe
Day 84
Results posted on
2020-06-12
Participant Flow
578 participants were enrolled in the study and 578 were dosed. One (1) subject in Cohort 2 in the Placebo arm was incorrectly dosed with the High Dose. The ITT data set included participants according to their randomization while SAF data set included participants according to the treatment administered.
Participant milestones
| Measure |
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
40
|
109
|
110
|
110
|
111
|
49
|
49
|
|
Overall Study
Randomized
|
40
|
109
|
110
|
110
|
111
|
48
|
50
|
|
Overall Study
COMPLETED
|
37
|
100
|
102
|
102
|
108
|
48
|
44
|
|
Overall Study
NOT COMPLETED
|
3
|
9
|
8
|
8
|
3
|
1
|
5
|
Reasons for withdrawal
| Measure |
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
3
|
4
|
4
|
1
|
0
|
1
|
|
Overall Study
Death
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Lack of Efficacy
|
0
|
2
|
1
|
4
|
0
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
2
|
0
|
2
|
0
|
2
|
Baseline Characteristics
Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA)
Baseline characteristics by cohort
| Measure |
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=49 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=49 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Total
n=578 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
1 Participants
n=6 Participants
|
|
Race/Ethnicity, Customized
Black of African American
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
1 Participants
n=30 Participants
|
2 Participants
n=3 Participants
|
10 Participants
n=6 Participants
|
|
Race/Ethnicity, Customized
White
|
36 Participants
n=99 Participants
|
96 Participants
n=107 Participants
|
96 Participants
n=206 Participants
|
95 Participants
n=7 Participants
|
99 Participants
n=31 Participants
|
42 Participants
n=30 Participants
|
42 Participants
n=3 Participants
|
506 Participants
n=6 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
35 Participants
n=99 Participants
|
95 Participants
n=107 Participants
|
99 Participants
n=206 Participants
|
98 Participants
n=7 Participants
|
98 Participants
n=31 Participants
|
41 Participants
n=30 Participants
|
40 Participants
n=3 Participants
|
506 Participants
n=6 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
13 Participants
n=31 Participants
|
8 Participants
n=30 Participants
|
9 Participants
n=3 Participants
|
72 Participants
n=6 Participants
|
|
Age, Continuous
|
52.3 Years
STANDARD_DEVIATION 12.0 • n=99 Participants
|
50.4 Years
STANDARD_DEVIATION 11.0 • n=107 Participants
|
49.9 Years
STANDARD_DEVIATION 12.4 • n=206 Participants
|
50.2 Years
STANDARD_DEVIATION 11.6 • n=7 Participants
|
49.9 Years
STANDARD_DEVIATION 12.4 • n=31 Participants
|
51.3 Years
STANDARD_DEVIATION 13.2 • n=30 Participants
|
54.6 Years
STANDARD_DEVIATION 11.5 • n=3 Participants
|
50.7 Years
STANDARD_DEVIATION 12.0 • n=6 Participants
|
|
Sex: Female, Male
Female
|
35 Participants
n=99 Participants
|
92 Participants
n=107 Participants
|
85 Participants
n=206 Participants
|
90 Participants
n=7 Participants
|
87 Participants
n=31 Participants
|
37 Participants
n=30 Participants
|
37 Participants
n=3 Participants
|
463 Participants
n=6 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
20 Participants
n=7 Participants
|
24 Participants
n=31 Participants
|
12 Participants
n=30 Participants
|
12 Participants
n=3 Participants
|
115 Participants
n=6 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska native
|
0 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
11 Participants
n=7 Participants
|
9 Participants
n=31 Participants
|
6 Participants
n=30 Participants
|
5 Participants
n=3 Participants
|
51 Participants
n=6 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
3 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
7 Participants
n=6 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
5 Participants
n=6 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
8 Participants
n=99 Participants
|
38 Participants
n=107 Participants
|
40 Participants
n=206 Participants
|
38 Participants
n=7 Participants
|
39 Participants
n=31 Participants
|
17 Participants
n=30 Participants
|
15 Participants
n=3 Participants
|
195 Participants
n=6 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
31 Participants
n=99 Participants
|
68 Participants
n=107 Participants
|
69 Participants
n=206 Participants
|
72 Participants
n=7 Participants
|
70 Participants
n=31 Participants
|
32 Participants
n=30 Participants
|
33 Participants
n=3 Participants
|
375 Participants
n=6 Participants
|
|
Race/Ethnicity, Customized
Not Stated
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
1 Participants
n=3 Participants
|
3 Participants
n=6 Participants
|
PRIMARY outcome
Timeframe: Day 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1)
|
34.5 Percentage
Interval 25.66 to 43.43
|
14.5 Percentage
Interval 7.96 to 21.13
|
36.0 Percentage
Interval 27.1 to 44.97
|
—
|
—
|
17.5 Percentage
Interval 5.72 to 29.28
|
27.5 Percentage
Interval 19.14 to 35.91
|
PRIMARY outcome
Timeframe: Day 1 up to 8 weeks after last dose (up to Week 20)Population: Safety population included all participants according to treatment administered.
An Adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE was any experience that suggested a significant hazard, contraindication, side effect or precaution that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=49 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=49 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants With Adverse Events
|
50.9 Percentage
|
45.5 Percentage
|
45.0 Percentage
|
22.4 Percentage
|
44.9 Percentage
|
37.5 Percentage
|
42.2 Percentage
|
SECONDARY outcome
Timeframe: Day 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1)
|
34.5 Percentage
Interval 25.66 to 43.43
|
14.5 Percentage
Interval 7.96 to 21.13
|
36.0 Percentage
Interval 27.1 to 44.97
|
—
|
—
|
17.5 Percentage
Interval 5.72 to 29.28
|
27.5 Percentage
Interval 19.14 to 35.91
|
SECONDARY outcome
Timeframe: Day 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=48 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=50 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2)
|
—
|
—
|
—
|
—
|
—
|
25.0 Percentage
Interval 12.75 to 37.25
|
12.0 Percentage
Interval 2.99 to 21.01
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\]
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
Week 1 Day 7
|
13.6 Percentage
Interval 7.22 to 20.05
|
10.0 Percentage
Interval 4.39 to 15.61
|
25.2 Percentage
Interval 17.15 to 33.3
|
22.9 Percentage
Interval 11.03 to 34.81
|
2.0 Percentage
Interval 0.0 to 5.88
|
10.0 Percentage
Interval 0.7 to 19.3
|
14.7 Percentage
Interval 8.04 to 21.32
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
Week 2 Day 14
|
27.3 Percentage
Interval 18.95 to 35.6
|
16.4 Percentage
Interval 9.45 to 23.28
|
48.6 Percentage
Interval 39.35 to 57.95
|
25.0 Percentage
Interval 12.75 to 37.25
|
10.0 Percentage
Interval 1.68 to 18.32
|
12.5 Percentage
Interval 2.25 to 22.75
|
19.3 Percentage
Interval 11.86 to 26.67
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
Week 4 Day 28
|
41.8 Percentage
Interval 32.6 to 51.04
|
25.5 Percentage
Interval 17.31 to 33.59
|
59.5 Percentage
Interval 50.33 to 68.59
|
35.4 Percentage
Interval 21.89 to 48.95
|
24.0 Percentage
Interval 12.16 to 35.84
|
30.0 Percentage
Interval 15.8 to 44.2
|
34.9 Percentage
Interval 25.92 to 43.81
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
Week 8 Day 56
|
58.2 Percentage
Interval 48.96 to 67.4
|
37.3 Percentage
Interval 28.24 to 46.31
|
71.2 Percentage
Interval 62.74 to 79.6
|
47.9 Percentage
Interval 33.78 to 62.05
|
18.0 Percentage
Interval 7.35 to 28.65
|
50.0 Percentage
Interval 34.51 to 65.49
|
52.3 Percentage
Interval 42.92 to 61.67
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
Week 12 Day 84
|
59.1 Percentage
Interval 49.9 to 68.28
|
36.4 Percentage
Interval 27.37 to 45.35
|
72.1 Percentage
Interval 63.73 to 80.42
|
58.3 Percentage
Interval 44.39 to 72.28
|
24.0 Percentage
Interval 12.16 to 35.84
|
60.0 Percentage
Interval 44.82 to 75.18
|
56.0 Percentage
Interval 46.64 to 65.28
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Week 1 Day 7
|
3.6 Percentage
Interval 0.14 to 7.13
|
2.7 Percentage
Interval 0.0 to 5.77
|
4.5 Percentage
Interval 0.65 to 8.36
|
6.3 Percentage
Interval 0.0 to 13.1
|
2.0 Percentage
Interval 0.0 to 5.88
|
2.5 Percentage
Interval 0.0 to 7.34
|
2.8 Percentage
Interval 0.0 to 5.82
|
|
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Week 2 Day 14
|
7.3 Percentage
Interval 2.42 to 12.13
|
2.7 Percentage
Interval 0.0 to 5.77
|
9.0 Percentage
Interval 3.68 to 14.34
|
10.4 Percentage
Interval 1.77 to 19.06
|
0.00 Percentage
Interval 0.0 to 0.0
|
0.0 Percentage
Interval 0.0 to 0.0
|
1.8 Percentage
Interval 0.0 to 4.35
|
|
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Week 4 day 28
|
10.0 Percentage
Interval 4.39 to 15.61
|
6.4 Percentage
Interval 1.8 to 10.93
|
25.2 Percentage
Interval 17.15 to 33.3
|
10.4 Percentage
Interval 1.77 to 19.06
|
6.0 Percentage
Interval 0.0 to 12.58
|
5.0 Percentage
Interval 0.0 to 11.75
|
9.2 Percentage
Interval 3.76 to 14.59
|
|
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Week 8 Day 56
|
22.7 Percentage
Interval 14.9 to 30.56
|
17.3 Percentage
Interval 10.21 to 24.34
|
32.4 Percentage
Interval 23.72 to 41.14
|
22.9 Percentage
Interval 11.03 to 34.81
|
10.0 Percentage
Interval 1.68 to 18.32
|
15.0 Percentage
Interval 3.93 to 26.07
|
18.3 Percentage
Interval 11.08 to 25.62
|
|
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Week 12 Day 84
|
34.5 Percentage
Interval 25.66 to 43.43
|
14.5 Percentage
Interval 7.96 to 21.13
|
36.0 Percentage
Interval 27.1 to 44.97
|
25.0 Percentage
Interval 12.75 to 37.25
|
12.0 Percentage
Interval 2.99 to 21.01
|
17.5 Percentage
Interval 5.72 to 29.28
|
27.5 Percentage
Interval 19.14 to 35.91
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Week 1 Day 7
|
0.9 Percentage
Interval 0.0 to 2.68
|
0.0 Percentage
Interval 0.0 to 0.0
|
0.0 Percentage
Interval 0.0 to 0.0
|
0.0 Percentage
Interval 0.0 to 0.0
|
0.0 Percentage
Interval 0.0 to 0.0
|
0.0 Percentage
Interval 0.0 to 0.0
|
0.9 Percentage
Interval 0.0 to 2.71
|
|
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Week 2 Day 14
|
0.0 Percentage
Interval 0.0 to 0.0
|
0.00 Percentage
Interval 0.0 to 0.0
|
3.6 Percentage
Interval 0.14 to 7.07
|
4.2 Percentage
Interval 0.0 to 9.82
|
0.0 Percentage
Interval 0.0 to 0.0
|
0.0 Percentage
Interval 0.0 to 0.0
|
0.9 Percentage
Interval 0.0 to 2.71
|
|
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Week 4 Day 28
|
4.5 Percentage
Interval 0.65 to 8.44
|
0.9 Percentage
Interval 0.0 to 2.68
|
6.3 Percentage
Interval 1.78 to 10.83
|
2.1 Percentage
Interval 0.0 to 6.12
|
2.0 Percentage
Interval 0.0 to 5.88
|
0 Percentage
Interval 0.0 to 0.0
|
2.8 Percentage
Interval 0.0 to 5.82
|
|
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Week 8 Day 56
|
9.1 Percentage
Interval 3.72 to 14.46
|
3.6 Percentage
Interval 0.14 to 7.13
|
14.4 Percentage
Interval 7.88 to 20.95
|
6.3 Percentage
Interval 0.0 to 13.1
|
4.0 Percentage
Interval 0.0 to 9.43
|
0.0 Percentage
Interval 0.0 to 0.0
|
7.3 Percentage
Interval 2.44 to 12.24
|
|
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Week 12 Day 84
|
12.7 Percentage
Interval 6.5 to 18.96
|
7.3 Percentage
Interval 2.42 to 12.13
|
18.0 Percentage
Interval 10.87 to 25.17
|
14.6 Percentage
Interval 4.6 to 24.57
|
4.0 Percentage
Interval 0.0 to 9.43
|
5.0 Percentage
Interval 0.0 to 11.75
|
9.2 Percentage
Interval 3.76 to 14.59
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
Week 1 Day 7
|
-0.37 Score on a scale
Standard Deviation 0.80
|
-0.33 Score on a scale
Standard Deviation 0.84
|
-0.92 Score on a scale
Standard Deviation 0.71
|
-0.49 Score on a scale
Standard Deviation 0.84
|
-0.36 Score on a scale
Standard Deviation 0.63
|
-0.34 Score on a scale
Standard Deviation 0.60
|
-0.35 Score on a scale
Standard Deviation 0.66
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
Week 2 Day 14
|
-0.70 Score on a scale
Standard Deviation 0.80
|
-.54 Score on a scale
Standard Deviation 0.90
|
-1.09 Score on a scale
Standard Deviation 0.81
|
-0.65 Score on a scale
Standard Deviation 0.87
|
-0.45 Score on a scale
Standard Deviation 0.69
|
-0.47 Score on a scale
Standard Deviation 0.72
|
-0.63 Score on a scale
Standard Deviation 0.84
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
Week 4 Day 28
|
-0.91 Score on a scale
Standard Deviation 0.97
|
-0.62 Score on a scale
Standard Deviation 1.04
|
-1.45 Score on a scale
Standard Deviation 0.87
|
-0.77 Score on a scale
Standard Deviation 0.90
|
-0.44 Score on a scale
Standard Deviation 0.84
|
-0.75 Score on a scale
Standard Deviation 0.86
|
-0.90 Score on a scale
Standard Deviation 0.96
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
Week 8 Day 56
|
-1.37 Score on a scale
Standard Deviation 1.11
|
-1.08 Score on a scale
Standard Deviation 1.19
|
-1.75 Score on a scale
Standard Deviation 0.98
|
-1.33 Score on a scale
Standard Deviation 0.98
|
-0.56 Score on a scale
Standard Deviation 0.87
|
-1.14 Score on a scale
Standard Deviation 0.90
|
-1.35 Score on a scale
Standard Deviation 1.12
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
Week 12 Day 84
|
-1.70 Score on a scale
Standard Deviation 1.02
|
-1.17 Score on a scale
Standard Deviation 1.24
|
-1.87 Score on a scale
Standard Deviation 1.02
|
-1.62 Score on a scale
Standard Deviation 1.15
|
-0.86 Score on a scale
Standard Deviation 1.03
|
-1.30 Score on a scale
Standard Deviation 0.95
|
-1.72 Score on a scale
Standard Deviation 1.11
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])
Week 1 Day 7
|
-0.49 Score on a scale
Standard Deviation 0.86
|
-0.37 Score on a scale
Standard Deviation 0.91
|
-1.10 Score on a scale
Standard Deviation 0.75
|
-0.63 Score on a scale
Standard Deviation 0.91
|
-.40 Score on a scale
Standard Deviation 0.69
|
-0.43 Score on a scale
Standard Deviation 0.67
|
-0.48 Score on a scale
Standard Deviation 0.73
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])
Week 2 Day 14
|
-0.84 Score on a scale
Standard Deviation 0.86
|
-0.57 Score on a scale
Standard Deviation 1.00
|
-1.26 Score on a scale
Standard Deviation 0.89
|
-0.81 Score on a scale
Standard Deviation 0.98
|
-0.54 Score on a scale
Standard Deviation 0.80
|
-0.51 Score on a scale
Standard Deviation 0.85
|
-0.77 Score on a scale
Standard Deviation 0.86
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])
Week 4 Day 28
|
-1.08 Score on a scale
Standard Deviation 1.03
|
-0.65 Score on a scale
Standard Deviation 1.16
|
-1.61 Score on a scale
Standard Deviation 0.94
|
-0.95 Score on a scale
Standard Deviation 1.04
|
-0.55 Score on a scale
Standard Deviation 0.94
|
-0.88 Score on a scale
Standard Deviation 0.90
|
-1.06 Score on a scale
Standard Deviation 1.02
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])
Week 8 Day 56
|
-1.57 Score on a scale
Standard Deviation 1.16
|
1.20 Score on a scale
Standard Deviation 1.30
|
-1.97 Score on a scale
Standard Deviation 1.03
|
-1.51 Score on a scale
Standard Deviation 1.05
|
-0.67 Score on a scale
Standard Deviation 1.01
|
-1.31 Score on a scale
Standard Deviation 0.91
|
-1.56 Score on a scale
Standard Deviation 1.21
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])
Week 12 Day 84
|
-1.93 Score on a scale
Standard Deviation 1.11
|
-1.33 Score on a scale
Standard Deviation 1.33
|
-2.06 Score on a scale
Standard Deviation 1.08
|
-1.83 Score on a scale
Standard Deviation 1.22
|
-1.00 Score on a scale
Standard Deviation 1.11
|
-1.53 Score on a scale
Standard Deviation 0.95
|
-1.97 Score on a scale
Standard Deviation 1.20
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])
Week 1 Day 7
|
-0.39 Score on a scale
Standard Deviation 0.68
|
-0.34 Score on a scale
Standard Deviation 0.86
|
-0.72 Score on a scale
Standard Deviation 0.72
|
-0.50 Score on a scale
Standard Deviation 0.73
|
-0.31 Score on a scale
Standard Deviation 0.60
|
-0.35 Score on a scale
Standard Deviation 0.57
|
-0.42 Score on a scale
Standard Deviation 0.65
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])
Week 2 Day 14
|
-0.68 Score on a scale
Standard Deviation 0.74
|
-0.55 Score on a scale
Standard Deviation 0.92
|
-1.02 Score on a scale
Standard Deviation 0.84
|
-0.64 Score on a scale
Standard Deviation 0.81
|
-0.51 Score on a scale
Standard Deviation 0.73
|
-0.60 Score on a scale
Standard Deviation 0.89
|
-0.69 Score on a scale
Standard Deviation 0.84
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])
Week 4 Day 28
|
-0.97 Score on a scale
Standard Deviation 0.90
|
-0.75 Score on a scale
Standard Deviation 1.02
|
-1.47 Score on a scale
Standard Deviation 1.02
|
-0.85 Score on a scale
Standard Deviation 0.81
|
-0.50 Score on a scale
Standard Deviation 0.83
|
-0.88 Score on a scale
Standard Deviation 0.89
|
-0.99 Score on a scale
Standard Deviation 0.98
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])
Week 8 Day 56
|
-1.40 Score on a scale
Standard Deviation 1.06
|
-1.15 Score on a scale
Standard Deviation 1.19
|
-1.74 Score on a scale
Standard Deviation 0.98
|
-1.35 Score on a scale
Standard Deviation 0.96
|
-0.70 Score on a scale
Standard Deviation 0.98
|
-1.25 Score on a scale
Standard Deviation 0.85
|
-1.44 Score on a scale
Standard Deviation 1.14
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])
Week 12 Day 84
|
-1.80 Score on a scale
Standard Deviation 0.99
|
-1.30 Score on a scale
Standard Deviation 1.22
|
-1.85 Score on a scale
Standard Deviation 1.06
|
-1.65 Score on a scale
Standard Deviation 1.06
|
-0.94 Score on a scale
Standard Deviation 10.6
|
-1.51 Score on a scale
Standard Deviation 1.01
|
-1.80 Score on a scale
Standard Deviation 1.25
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
Week 1 Day 7
|
-0.52 Score on a scale
Standard Deviation 0.77
|
-0.37 Score on a scale
Standard Deviation 0.95
|
-0.93 Score on a scale
Standard Deviation 0.76
|
-0.65 Score on a scale
Standard Deviation 0.80
|
-0.36 Score on a scale
Standard Deviation 0.66
|
-0.45 Score on a scale
Standard Deviation 0.63
|
-0.54 Score on a scale
Standard Deviation 0.72
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
Week 2 Day 14
|
-0.84 Score on a scale
Standard Deviation 0.82
|
-0.58 Score on a scale
Standard Deviation 1.03
|
-1.22 Score on a scale
Standard Deviation 0.94
|
-0.81 Score on a scale
Standard Deviation 0.92
|
-0.60 Score on a scale
Standard Deviation 0.84
|
-0.63 Score on a scale
Standard Deviation 0.98
|
-0.85 Score on a scale
Standard Deviation 0.85
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
Week 4 Day 28
|
-1.15 Score on a scale
Standard Deviation 0.98
|
-0.79 Score on a scale
Standard Deviation 1.16
|
-1.65 Score on a scale
Standard Deviation 1.11
|
-1.04 Score on a scale
Standard Deviation 0.95
|
-0.61 Score on a scale
Standard Deviation 0.96
|
-1.00 Score on a scale
Standard Deviation 0.95
|
-1.16 Score on a scale
Standard Deviation 1.06
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
Week 8 Day 56
|
-1.63 Score on a scale
Standard Deviation 1.14
|
-1.29 Score on a scale
Standard Deviation 1.31
|
-2.00 Score on a scale
Standard Deviation 1.06
|
-1.54 Score on a scale
Standard Deviation 1.04
|
-0.81 Score on a scale
Standard Deviation 1.12
|
-1.43 Score on a scale
Standard Deviation 0.88
|
-1.67 Score on a scale
Standard Deviation 1.25
|
|
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
Week 12 Day 84
|
-2.05 Score on a scale
Standard Deviation 1.08
|
-1.46 Score on a scale
Standard Deviation 1.32
|
-2.08 Score on a scale
Standard Deviation 1.14
|
-1.89 Score on a scale
Standard Deviation 1.15
|
-1.08 Score on a scale
Standard Deviation 1.17
|
-1.76 Score on a scale
Standard Deviation 1.04
|
-2.06 Score on a scale
Standard Deviation 1.36
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDAS is defined as DAS28 ≤ 3.2
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants With DAS Low Disease Activity
Week 1 Day 7
|
1.8 Percentage of participants
Interval 0.0 to 4.31
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
1.8 Percentage of participants
Interval 0.0 to 4.28
|
2.1 Percentage of participants
Interval 0.0 to 6.12
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.9 Percentage of participants
Interval 0.0 to 2.71
|
|
Percentage of Participants With DAS Low Disease Activity
Week 2 day 14
|
1.8 Percentage of participants
Interval 0.0 to 4.31
|
0.9 Percentage of participants
Interval 0.0 to 2.68
|
4.5 Percentage of participants
Interval 0.65 to 8.36
|
2.1 Percentage of participants
Interval 0.0 to 6.12
|
2.0 Percentage of participants
Interval 0.0 to 5.88
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants With DAS Low Disease Activity
Week 4 Day 28
|
6.4 Percentage of participants
Interval 1.8 to 10.93
|
1.8 Percentage of participants
Interval 0.0 to 4.31
|
11.7 Percentage of participants
Interval 5.73 to 17.69
|
2.1 Percentage of participants
Interval 0.0 to 6.12
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
1.8 Percentage of participants
Interval 0.0 to 4.35
|
|
Percentage of Participants With DAS Low Disease Activity
Week 8 Day 56
|
11.8 Percentage of participants
Interval 5.79 to 17.85
|
3.6 Percentage of participants
Interval 0.14 to 7.13
|
18.0 Percentage of participants
Interval 10.87 to 25.17
|
2.1 Percentage of participants
Interval 0.0 to 6.12
|
2.0 Percentage of participants
Interval 0.0 to 5.88
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
8.3 Percentage of participants
Interval 3.09 to 13.42
|
|
Percentage of Participants With DAS Low Disease Activity
Week 12 Day 84
|
14.5 Percentage of participants
Interval 7.96 to 21.13
|
3.6 Percentage of participants
Interval 0.14 to 7.13
|
17.1 Percentage of participants
Interval 10.11 to 24.12
|
14.6 Percentage of participants
Interval 4.6 to 24.57
|
4.0 Percentage of participants
Interval 0.0 to 9.43
|
7.5 Percentage of participants
Interval 0.0 to 15.66
|
19.3 Percentage of participants
Interval 11.86 to 26.67
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants With DAS Remission
Week 1 Day 7
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
2.1 Percentage of participants
Interval 0.0 to 6.12
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants With DAS Remission
Week 2 Day 14
|
0.9 Percentage of participants
Interval 0.0 to 2.68
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.9 Percentage of participants
Interval 0.0 to 2.66
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants With DAS Remission
Week 4 Day 28
|
1.8 Percentage of participants
Interval 0.0 to 4.31
|
0.9 Percentage of participants
Interval 0.0 to 2.68
|
4.5 Percentage of participants
Interval 0.65 to 8.36
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants With DAS Remission
Week 8 Day 56
|
4.5 Percentage of participants
Interval 0.65 to 8.44
|
1.8 Percentage of participants
Interval 0.0 to 4.31
|
9.0 Percentage of participants
Interval 3.68 to 14.34
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
3.7 Percentage of participants
Interval 0.14 to 7.2
|
|
Percentage of Participants With DAS Remission
Week 12 Day 84
|
8.2 Percentage of participants
Interval 3.06 to 13.3
|
3.6 Percentage of participants
Interval 0.14 to 7.13
|
9.0 Percentage of participants
Interval 3.68 to 14.34
|
4.2 Percentage of participants
Interval 0.0 to 9.82
|
4.0 Percentage of participants
Interval 0.0 to 9.43
|
2.5 Percentage of participants
Interval 0.0 to 7.34
|
7.3 Percentage of participants
Interval 2.44 to 12.24
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale).
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants Meeting the Boolean-based Remission Criteria
Week 4 Day 28
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.9 Percentage of participants
Interval 0.0 to 2.73
|
2.8 Percentage of participants
Interval 0.0 to 5.82
|
2.1 Percentage of participants
Interval 0.0 to 6.25
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
1.0 Percentage of participants
Interval 0.0 to 2.81
|
|
Percentage of Participants Meeting the Boolean-based Remission Criteria
Week 12 Day 84
|
4.1 Percentage of participants
Interval 0.17 to 8.08
|
1.0 Percentage of participants
Interval 0.0 to 2.89
|
6.5 Percentage of participants
Interval 1.84 to 11.12
|
8.5 Percentage of participants
Interval 0.53 to 16.49
|
0.0 Percentage of participants
Interval 0.0 to 6.53
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
2.0 Percentage of participants
Interval 0.0 to 4.84
|
|
Percentage of Participants Meeting the Boolean-based Remission Criteria
Week 8 Day 56
|
1.90 Percentage of participants
Interval 0.0 to 4.56
|
1.0 Percentage of participants
Interval 0.0 to 2.86
|
3.7 Percentage of participants
Interval 0.14 to 7.2
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
2.0 Percentage of participants
Interval 0.0 to 4.7
|
|
Percentage of Participants Meeting the Boolean-based Remission Criteria
Week 1 Day 7
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.9 Percentage of participants
Interval 0.0 to 2.76
|
|
Percentage of Participants Meeting the Boolean-based Remission Criteria
Week 2 Day 14
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline, Days 7, 14, 28, 56 and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest. Negative values indicate improvement/reduction in RA disease activity.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Clinical Disease Activity Index (CDAI)
Week 1 Day 7
|
-7.40 Score on a scale
Standard Deviation 9.97
|
-4.71 Score on a scale
Standard Deviation 12.91
|
-9.64 Score on a scale
Standard Deviation 8.93
|
-8.61 Score on a scale
Standard Deviation 10.67
|
-5.26 Score on a scale
Standard Deviation 9.79
|
-5.45 Score on a scale
Standard Deviation 7.69
|
-6.70 Score on a scale
Standard Deviation 8.26
|
|
Change From Baseline in Clinical Disease Activity Index (CDAI)
Week 2 Day 14
|
-11.33 Score on a scale
Standard Deviation 10.47
|
-7.44 Score on a scale
Standard Deviation 13.39
|
-13.44 Score on a scale
Standard Deviation 10.52
|
-9.64 Score on a scale
Standard Deviation 12.17
|
-7.70 Score on a scale
Standard Deviation 10.64
|
-6.85 Score on a scale
Standard Deviation 11.10
|
-10.33 Score on a scale
Standard Deviation 10.45
|
|
Change From Baseline in Clinical Disease Activity Index (CDAI)
Week 4 Day 28
|
-13.78 Score on a scale
Standard Deviation 11.46
|
-9.43 Score on a scale
Standard Deviation 14.77
|
-17.74 Score on a scale
Standard Deviation 10.84
|
-11.83 Score on a scale
Standard Deviation 11.08
|
-7.49 Score on a scale
Standard Deviation 11.46
|
-10.36 Score on a scale
Standard Deviation 10.88
|
-13.84 Score on a scale
Standard Deviation 12.11
|
|
Change From Baseline in Clinical Disease Activity Index (CDAI)
Week 8 Day 56
|
-18.10 Score on a scale
Standard Deviation 12.99
|
-15.49 Score on a scale
Standard Deviation 15.74
|
-21.36 Score on a scale
Standard Deviation 11.69
|
-17.38 Score on a scale
Standard Deviation 12.39
|
-7.57 Score on a scale
Standard Deviation 10.51
|
-14.76 Score on a scale
Standard Deviation 10.04
|
-18.61 Score on a scale
Standard Deviation 13.48
|
|
Change From Baseline in Clinical Disease Activity Index (CDAI)
Week 12 Day 84
|
-22.10 Score on a scale
Standard Deviation 11.83
|
-17.02 Score on a scale
Standard Deviation 16.24
|
-22.22 Score on a scale
Standard Deviation 11.76
|
-20.42 Score on a scale
Standard Deviation 13.20
|
-12.23 Score on a scale
Standard Deviation 12.06
|
-16.99 Score on a scale
Standard Deviation 11.21
|
-22.05 Score on a scale
Standard Deviation 12.19
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Clinical Disease Activity Index is defined as CDAI= : SJC(28) + TJC(28) + PGA + MDG where TJC and SJC are the tender and swollen joint counts from 28 joints, PGA is the patient's global assessment of disease activity (on a 0-10 scale) and MDG is physician global assessment of disease activity (on a 0-10 scale). The cutoff value for CDAI remission is \<=2.8.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants Meeting the CDAI-based Remission Criteria
Week 1 Day 7
|
0.9 Percentage of participants
Interval 0.0 to 2.68
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.9 Percentage of participants
Interval 0.0 to 2.71
|
|
Percentage of Participants Meeting the CDAI-based Remission Criteria
Week 2 Day 14
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
1.8 Percentage of participants
Interval 0.0 to 4.28
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants Meeting the CDAI-based Remission Criteria
Week 4 Day 28
|
0.9 Percentage of participants
Interval 0.0 to 2.68
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
4.5 Percentage of participants
Interval 0.65 to 8.36
|
2.1 Percentage of participants
Interval 0.0 to 6.12
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.9 Percentage of participants
Interval 0.0 to 2.71
|
|
Percentage of Participants Meeting the CDAI-based Remission Criteria
Week 8 Day 56
|
5.5 Percentage of participants
Interval 1.21 to 9.7
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
7.2 Percentage of participants
Interval 2.4 to 12.02
|
4.2 Percentage of participants
Interval 0.0 to 9.82
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
2.8 Percentage of participants
Interval 0.0 to 5.82
|
|
Percentage of Participants Meeting the CDAI-based Remission Criteria
Week 12 Day 84
|
6.4 Percentage of participants
Interval 1.8 to 10.93
|
0.9 Percentage of participants
Interval 0.0 to 2.68
|
9.9 Percentage of participants
Interval 4.35 to 15.47
|
6.3 Percentage of participants
Interval 0.0 to 13.1
|
6.0 Percentage of participants
Interval 0.0 to 12.58
|
0.0 Percentage of participants
Interval 0.0 to 0.0
|
5.5 Percentage of participants
Interval 1.22 to 9.79
|
SECONDARY outcome
Timeframe: Baseline, Days 7, 14, 28, 56 and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Simplified Disease Activity Index (SDAI)
Week 1 Day 7
|
-6.99 Score on a scale
Standard Deviation 10.49
|
-4.75 Score on a scale
Standard Deviation 13.25
|
-10.86 Score on a scale
Standard Deviation 9.33
|
-8.73 Score on a scale
Standard Deviation 11.21
|
-5.37 Score on a scale
Standard Deviation 9.49
|
-5.36 Score on a scale
Standard Deviation 7.86
|
-6.48 Score on a scale
Standard Deviation 8.87
|
|
Change From Baseline in Simplified Disease Activity Index (SDAI)
Week 2 Day 14
|
-11.44 Score on a scale
Standard Deviation 10.85
|
-7.54 Score on a scale
Standard Deviation 13.74
|
-14.39 Score on a scale
Standard Deviation 10.99
|
-9.84 Score on a scale
Standard Deviation 12.29
|
-8.13 Score on a scale
Standard Deviation 11.01
|
-6.50 Score on a scale
Standard Deviation 10.54
|
-10.46 Score on a scale
Standard Deviation 10.97
|
|
Change From Baseline in Simplified Disease Activity Index (SDAI)
Week 4 Day 28
|
-14.21 Score on a scale
Standard Deviation 12.20
|
-8.92 Score on a scale
Standard Deviation 15.17
|
-18.87 Score on a scale
Standard Deviation 11.20
|
-12.13 Score on a scale
Standard Deviation 11.13
|
-7.74 Score on a scale
Standard Deviation 12.02
|
-10.53 Score on a scale
Standard Deviation 11.03
|
-14.47 Score on a scale
Standard Deviation 12.41
|
|
Change From Baseline in Simplified Disease Activity Index (SDAI)
Week 8 Day 56
|
-18.97 Score on a scale
Standard Deviation 13.91
|
-15.74 Score on a scale
Standard Deviation 16.18
|
-22.62 Score on a scale
Standard Deviation 11.97
|
-18.57 Score on a scale
Standard Deviation 12.80
|
-7.82 Score on a scale
Standard Deviation 11.20
|
-15.25 Score on a scale
Standard Deviation 10.41
|
-18.95 Score on a scale
Standard Deviation 13.80
|
|
Change From Baseline in Simplified Disease Activity Index (SDAI)
Week 12 Day 84
|
-23.24 Score on a scale
Standard Deviation 12.50
|
-17.47 Score on a scale
Standard Deviation 16.70
|
-23.33 Score on a scale
Standard Deviation 11.97
|
-21.97 Score on a scale
Standard Deviation 13.78
|
-12.92 Score on a scale
Standard Deviation 12.61
|
-17.54 Score on a scale
Standard Deviation 11.36
|
-22.89 Score on a scale
Standard Deviation 12.52
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
The SDAI was the numerical sum of five outcome parameter: SJC and TJC (based on a 28-joint assessment), PGA and MDG (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. The SDAI =\< 3.3 indicates disease remission
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Percentage of Participants Meeting the SDAI-based Remission Criteria
Week 1 Day 7
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.9 Percentage of participants
Interval 0.0 to 2.71
|
|
Percentage of Participants Meeting the SDAI-based Remission Criteria
Week 2 Day 14
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
1.8 Percentage of participants
Interval 0.0 to 4.28
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants Meeting the SDAI-based Remission Criteria
Week 4 Day 28
|
0.9 Percentage of participants
Interval 0.0 to 2.68
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
4.5 Percentage of participants
Interval 0.65 to 8.36
|
2.1 Percentage of participants
Interval 0.0 to 6.12
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.9 Percentage of participants
Interval 0.0 to 2.71
|
|
Percentage of Participants Meeting the SDAI-based Remission Criteria
Week 8 Day 56
|
3.6 Percentage of participants
Interval 0.14 to 7.13
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
6.3 Percentage of participants
Interval 1.78 to 10.83
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
2.8 Percentage of participants
Interval 0.0 to 5.82
|
|
Percentage of Participants Meeting the SDAI-based Remission Criteria
Week 12 Day 84
|
6.4 Percentage of participants
Interval 1.8 to 10.93
|
0.9 Percentage of participants
Interval 0.0 to 2.68
|
9.0 Percentage of participants
Interval 3.68 to 14.34
|
6.3 Percentage of participants
Interval 0.0 to 13.1
|
6.0 Percentage of participants
Interval 0.0 to 12.58
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
4.6 Percentage of participants
Interval 0.66 to 8.51
|
SECONDARY outcome
Timeframe: Day 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
The 36-Item Short Form Health Survey (SF-36v2) is a questionnaire used to assess functional health and well-being and consists of eight domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. The SF-36v2 is summarized into Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. The PCS and MCS scores range from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components
Physical component score change: baseline-week 12
|
6.59 Number on a scale
Standard Deviation 7.54
|
3.54 Number on a scale
Standard Deviation 6.81
|
6.41 Number on a scale
Standard Deviation 6.43
|
5.35 Number on a scale
Standard Deviation 7.48
|
1.75 Number on a scale
Standard Deviation 6.39
|
5.57 Number on a scale
Standard Deviation 5.98
|
5.71 Number on a scale
Standard Deviation 6.85
|
|
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components
Mental component score change: baseline-week 12
|
6.92 Number on a scale
Standard Deviation 12.06
|
4.29 Number on a scale
Standard Deviation 10.51
|
6.50 Number on a scale
Standard Deviation 10.79
|
5.76 Number on a scale
Standard Deviation 10.22
|
5.11 Number on a scale
Standard Deviation 10.10
|
7.04 Number on a scale
Standard Deviation 9.32
|
4.89 Number on a scale
Standard Deviation 10.57
|
SECONDARY outcome
Timeframe: Day 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
The FACIT-Fatigue Scale consists of 13 items designed to measure the degree of fatigue experienced by the patient in the previous 7 days. For each question, there are five possible responses: 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit), 4 (very much). A total fatigue score is calculated by summing all items, and possible total scores range from 0 (maximum fatigue) to 52 (no fatigue). A positive change from baseline indicates an improvement in the patient's fatigue (less fatigue).
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
|
8.95 Score on a scale
Standard Deviation 10.04
|
7.08 Score on a scale
Standard Deviation 10.88
|
9.59 Score on a scale
Standard Deviation 9.02
|
8.85 Score on a scale
Standard Deviation 9.57
|
5.71 Score on a scale
Standard Deviation 9.24
|
9.00 Score on a scale
Standard Deviation 10.57
|
8.21 Score on a scale
Standard Deviation 10.22
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Tender Joint Count: a total of 68 joints will be assessed for tenderness. Each joint is assessed for the presence/absence of tenderness. 68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Tender/Painful Joint Count (68 Joint Count)
Week 1 Day 7
|
-3.33 Score on a scale
Standard Deviation 9.27
|
-3.81 Score on a scale
Standard Deviation 10.85
|
-5.58 Score on a scale
Standard Deviation 9.41
|
-6.57 Score on a scale
Standard Deviation 8.66
|
-3.06 Score on a scale
Standard Deviation 11.01
|
-2.79 Score on a scale
Standard Deviation 7.25
|
-4.12 Score on a scale
Standard Deviation 8.14
|
|
Change From Baseline in Tender/Painful Joint Count (68 Joint Count)
Week 2 Day 19
|
-5.91 Score on a scale
Standard Deviation 9.38
|
-5.78 Score on a scale
Standard Deviation 11.50
|
-8.62 Score on a scale
Standard Deviation 10.46
|
-6.08 Score on a scale
Standard Deviation 8.53
|
-3.92 Score on a scale
Standard Deviation 10.77
|
-4.33 Score on a scale
Standard Deviation 12.31
|
-6.36 Score on a scale
Standard Deviation 10.88
|
|
Change From Baseline in Tender/Painful Joint Count (68 Joint Count)
Week 4 Day 28
|
-6.84 Score on a scale
Standard Deviation 9.53
|
-7.55 Score on a scale
Standard Deviation 12.97
|
-11.61 Score on a scale
Standard Deviation 11.43
|
-7.79 Score on a scale
Standard Deviation 7.93
|
-4.40 Score on a scale
Standard Deviation 12.37
|
-6.00 Score on a scale
Standard Deviation 8.89
|
-7.90 Score on a scale
Standard Deviation 11.28
|
|
Change From Baseline in Tender/Painful Joint Count (68 Joint Count)
Week 8 Day 56
|
-9.75 Score on a scale
Standard Deviation 10.93
|
-10.75 Score on a scale
Standard Deviation 14.37
|
-14.12 Score on a scale
Standard Deviation 11.33
|
-11.65 Score on a scale
Standard Deviation 10.34
|
-4.60 Score on a scale
Standard Deviation 12.41
|
-9.72 Score on a scale
Standard Deviation 8.20
|
-11.57 Score on a scale
Standard Deviation 12.18
|
|
Change From Baseline in Tender/Painful Joint Count (68 Joint Count)
Week 12 Day 84
|
-11.49 Score on a scale
Standard Deviation 11.15
|
-10.55 Score on a scale
Standard Deviation 14.37
|
-15.49 Score on a scale
Standard Deviation 12.31
|
-13.73 Score on a scale
Standard Deviation 12.81
|
-7.14 Score on a scale
Standard Deviation 13.32
|
-10.33 Score on a scale
Standard Deviation 9.40
|
-12.72 Score on a scale
Standard Deviation 12.05
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Swollen Joint Count: a total of 66 joints will be assessed for swelling. Each joint is assessed for the presence/absence of swelling. 66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Swollen Joint Count (66 Joint Count)
Week 1 Day 7
|
-3.45 Score on a scale
Standard Deviation 6.02
|
-3.35 Score on a scale
Standard Deviation 9.38
|
-3.94 Score on a scale
Standard Deviation 5.33
|
-3.45 Score on a scale
Standard Deviation 4.90
|
-1.49 Score on a scale
Standard Deviation 4.49
|
-1.84 Score on a scale
Standard Deviation 5.19
|
-2.89 Score on a scale
Standard Deviation 5.01
|
|
Change From Baseline in Swollen Joint Count (66 Joint Count)
Week 2 Day 14
|
-5.06 Score on a scale
Standard Deviation 5.14
|
-4.23 Score on a scale
Standard Deviation 9.88
|
-6.26 Score on a scale
Standard Deviation 5.98
|
-3.29 Score on a scale
Standard Deviation 5.69
|
-2.96 Score on a scale
Standard Deviation 6.27
|
-3.95 Score on a scale
Standard Deviation 6.44
|
-4.78 Score on a scale
Standard Deviation 5.99
|
|
Change From Baseline in Swollen Joint Count (66 Joint Count)
Week 4 Day 28
|
-5.95 Score on a scale
Standard Deviation 6.09
|
-5.47 Score on a scale
Standard Deviation 9.26
|
-8.50 Score on a scale
Standard Deviation 6.39
|
-4.21 Score on a scale
Standard Deviation 6.39
|
-3.46 Score on a scale
Standard Deviation 5.62
|
-4.38 Score on a scale
Standard Deviation 4.55
|
-6.33 Score on a scale
Standard Deviation 7.98
|
|
Change From Baseline in Swollen Joint Count (66 Joint Count)
Week 8 Day 56
|
-7.72 Score on a scale
Standard Deviation 7.44
|
-7.41 Score on a scale
Standard Deviation 10.82
|
-9.60 Score on a scale
Standard Deviation 6.94
|
-6.81 Score on a scale
Standard Deviation 6.16
|
-3.02 Score on a scale
Standard Deviation 7.76
|
-6.54 Score on a scale
Standard Deviation 5.78
|
-8.06 Score on a scale
Standard Deviation 8.13
|
|
Change From Baseline in Swollen Joint Count (66 Joint Count)
Week 12 Day 84
|
-8.48 Score on a scale
Standard Deviation 7.01
|
-8.26 Score on a scale
Standard Deviation 11.48
|
-9.94 Score on a scale
Standard Deviation 6.91
|
-7.65 Score on a scale
Standard Deviation 6.75
|
-4.86 Score on a scale
Standard Deviation 5.84
|
-7.36 Score on a scale
Standard Deviation 5.88
|
-8.89 Score on a scale
Standard Deviation 8.23
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Patient Assessment Score of Arthritis Pain
Week 12 Day 84
|
-30.63 Score on a scale
Standard Deviation 28.49
|
-17.88 Score on a scale
Standard Deviation 29.42
|
-26.30 Score on a scale
Standard Deviation 23.87
|
-26.49 Score on a scale
Standard Deviation 27.65
|
-13.98 Score on a scale
Standard Deviation 25.32
|
-23.14 Score on a scale
Standard Deviation 21.14
|
-26.48 Score on a scale
Standard Deviation 23.30
|
|
Change From Baseline in Patient Assessment Score of Arthritis Pain
Week 1 Day 7
|
-11.18 Score on a scale
Standard Deviation 21.64
|
-4.12 Score on a scale
Standard Deviation 22.43
|
-15.75 Score on a scale
Standard Deviation 18.71
|
-11.94 Score on a scale
Standard Deviation 21.25
|
-2.76 Score on a scale
Standard Deviation 18.24
|
-9.00 Score on a scale
Standard Deviation 18.66
|
-9.20 Score on a scale
Standard Deviation 20.56
|
|
Change From Baseline in Patient Assessment Score of Arthritis Pain
Week 2 Day 14
|
-17.08 Score on a scale
Standard Deviation 23.46
|
-8.22 Score on a scale
Standard Deviation 25.72
|
-18.13 Score on a scale
Standard Deviation 17.71
|
-15.08 Score on a scale
Standard Deviation 21.87
|
-4.72 Score on a scale
Standard Deviation 17.64
|
-6.08 Score on a scale
Standard Deviation 21.64
|
-12.16 Score on a scale
Standard Deviation 20.09
|
|
Change From Baseline in Patient Assessment Score of Arthritis Pain
Week 4 Day 28
|
-18.63 Score on a scale
Standard Deviation 24.87
|
-10.08 Score on a scale
Standard Deviation 27.16
|
-20.21 Score on a scale
Standard Deviation 21.97
|
-16.64 Score on a scale
Standard Deviation 27.86
|
-7.54 Score on a scale
Standard Deviation 23.80
|
-13.41 Score on a scale
Standard Deviation 16.79
|
-15.75 Score on a scale
Standard Deviation 21.97
|
|
Change From Baseline in Patient Assessment Score of Arthritis Pain
Week 8 Day 56
|
-25.95 Score on a scale
Standard Deviation 27.50
|
-16.37 Score on a scale
Standard Deviation 27.65
|
-24.70 Score on a scale
Standard Deviation 22.23
|
-21.21 Score on a scale
Standard Deviation 27.13
|
-7.13 Score on a scale
Standard Deviation 25.73
|
-18.38 Score on a scale
Standard Deviation 19.35
|
-23.21 Score on a scale
Standard Deviation 22.10
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Participant-assessed arthritis pain was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of arthritis pain (0 mm=none; 100 mm=very severe). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change indicated a decrease in participant-assessed arthritis pain.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Patient Global Assessment Score of Arthritis Pain
Week 4 Day 28
|
-17.75 Score on a scale
Standard Deviation 22.73
|
-6.36 Score on a scale
Standard Deviation 25.99
|
-21.78 Score on a scale
Standard Deviation 25.53
|
-18.26 Score on a scale
Standard Deviation 27.53
|
-10.96 Score on a scale
Standard Deviation 21.54
|
-12.11 Score on a scale
Standard Deviation 16.68
|
16.10 Score on a scale
Standard Deviation 23.48
|
|
Change From Baseline in Patient Global Assessment Score of Arthritis Pain
Week 8 Day 56
|
-22.59 Score on a scale
Standard Deviation 26.81
|
-14.19 Score on a scale
Standard Deviation 29.80
|
-26.77 Score on a scale
Standard Deviation 25.69
|
-21.17 Score on a scale
Standard Deviation 25.98
|
-11.82 Score on a scale
Standard Deviation 21.66
|
-19.19 Score on a scale
Standard Deviation 16.88
|
-24.06 Score on a scale
Standard Deviation 24.99
|
|
Change From Baseline in Patient Global Assessment Score of Arthritis Pain
Week 1 Day 7
|
-11.82 Score on a scale
Standard Deviation 22.52
|
-3.07 Score on a scale
Standard Deviation 20.83
|
-18.33 Score on a scale
Standard Deviation 20.81
|
-13.15 Score on a scale
Standard Deviation 22.17
|
-4.96 Score on a scale
Standard Deviation 19.18
|
-9.00 Score on a scale
Standard Deviation 15.88
|
-10.30 Score on a scale
Standard Deviation 20.82
|
|
Change From Baseline in Patient Global Assessment Score of Arthritis Pain
Week 2 Day 14
|
-14.84 Score on a scale
Standard Deviation 24.08
|
-5.39 Score on a scale
Standard Deviation 26.13
|
-18.94 Score on a scale
Standard Deviation 22.33
|
-15.46 Score on a scale
Standard Deviation 21.67
|
-8.64 Score on a scale
Standard Deviation 19.43
|
-5.50 Score on a scale
Standard Deviation 20.98
|
-13.70 Score on a scale
Standard Deviation 19.63
|
|
Change From Baseline in Patient Global Assessment Score of Arthritis Pain
Week 12 Day 84
|
-27.33 Score on a scale
Standard Deviation 27.33
|
-16.87 Score on a scale
Standard Deviation 28.68
|
-26.24 Score on a scale
Standard Deviation 27.02
|
-25.55 Score on a scale
Standard Deviation 27.52
|
-13.80 Score on a scale
Standard Deviation 22.17
|
-23.33 Score on a scale
Standard Deviation 22.03
|
-26.67 Score on a scale
Standard Deviation 26.89
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Physician's assessment of participant's disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's assessment of the participant's disease activity (0 mm=very good; 100 mm=very poor). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change from baseline indicated an improvement in physician-assessed disease activity.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Physician's Global Assessment Score of Arthritis
Week 2 Day 14
|
-18.30 Score on a scale
Standard Deviation 19.04
|
-9.01 Score on a scale
Standard Deviation 18.07
|
-21.33 Score on a scale
Standard Deviation 19.61
|
-14.23 Score on a scale
Standard Deviation 18.50
|
-9.85 Score on a scale
Standard Deviation 17.55
|
-11.10 Score on a scale
Standard Deviation 15.65
|
-15.86 Score on a scale
Standard Deviation 16.77
|
|
Change From Baseline in Physician's Global Assessment Score of Arthritis
Week 4 Day 28
|
-20.92 Score on a scale
Standard Deviation 17.71
|
-14.01 Score on a scale
Standard Deviation 21.03
|
-28.81 Score on a scale
Standard Deviation 19.34
|
-17.70 Score on a scale
Standard Deviation 20.49
|
-12.73 Score on a scale
Standard Deviation 20.42
|
-16.89 Score on a scale
Standard Deviation 19.06
|
-22.02 Score on a scale
Standard Deviation 18.61
|
|
Change From Baseline in Physician's Global Assessment Score of Arthritis
Week 12 Day 84
|
-34.48 Score on a scale
Standard Deviation 19.49
|
-23.19 Score on a scale
Standard Deviation 23.39
|
-37.18 Score on a scale
Standard Deviation 21.02
|
-30.82 Score on a scale
Standard Deviation 21.95
|
-18.44 Score on a scale
Standard Deviation 21.86
|
-26.81 Score on a scale
Standard Deviation 16.20
|
-32.43 Score on a scale
Standard Deviation 19.24
|
|
Change From Baseline in Physician's Global Assessment Score of Arthritis
Week 1 Day 7
|
-12.82 Score on a scale
Standard Deviation 17.03
|
-5.85 Score on a scale
Standard Deviation 15.44
|
-14.23 Score on a scale
Standard Deviation 16.13
|
-9.57 Score on a scale
Standard Deviation 17.10
|
-7.66 Score on a scale
Standard Deviation 18.33
|
-7.89 Score on a scale
Standard Deviation 13.16
|
-10.68 Score on a scale
Standard Deviation 15.41
|
|
Change From Baseline in Physician's Global Assessment Score of Arthritis
Week 8 Day 56
|
-29.67 Score on a scale
Standard Deviation 20.01
|
-20.87 Score on a scale
Standard Deviation 23.85
|
-36.16 Score on a scale
Standard Deviation 21.82
|
-22.40 Score on a scale
Standard Deviation 20.43
|
-9.91 Score on a scale
Standard Deviation 19.67
|
-24.59 Score on a scale
Standard Deviation 15.06
|
-28.52 Score on a scale
Standard Deviation 21.11
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
C-reactive protein is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL)
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in C-Reactive Protein (CRP) Levels
Week 1 Day 7
|
0.22 (ng/mL) nanograms per milliliter
Standard Deviation 2.49
|
0.01 (ng/mL) nanograms per milliliter
Standard Deviation 1.29
|
-1.21 (ng/mL) nanograms per milliliter
Standard Deviation 2.37
|
-0.12 (ng/mL) nanograms per milliliter
Standard Deviation 2.60
|
-0.10 (ng/mL) nanograms per milliliter
Standard Deviation 1.76
|
0.14 (ng/mL) nanograms per milliliter
Standard Deviation 2.09
|
0.30 (ng/mL) nanograms per milliliter
Standard Deviation 2.58
|
|
Change From Baseline in C-Reactive Protein (CRP) Levels
Week 2 Day 14
|
-0.21 (ng/mL) nanograms per milliliter
Standard Deviation 2.29
|
-0.12 (ng/mL) nanograms per milliliter
Standard Deviation 1.53
|
-0.93 (ng/mL) nanograms per milliliter
Standard Deviation 2.70
|
-0.20 (ng/mL) nanograms per milliliter
Standard Deviation 2.38
|
-0.25 (ng/mL) nanograms per milliliter
Standard Deviation 2.60
|
0.27 (ng/mL) nanograms per milliliter
Standard Deviation 1.78
|
-0.10 (ng/mL) nanograms per milliliter
Standard Deviation 1.92
|
|
Change From Baseline in C-Reactive Protein (CRP) Levels
Week 4 Day 28
|
-0.44 (ng/mL) nanograms per milliliter
Standard Deviation 2.30
|
0.14 (ng/mL) nanograms per milliliter
Standard Deviation 2.00
|
-1.11 (ng/mL) nanograms per milliliter
Standard Deviation 2.17
|
-0.30 (ng/mL) nanograms per milliliter
Standard Deviation 2.58
|
-0.24 (ng/mL) nanograms per milliliter
Standard Deviation 2.80
|
0.15 (ng/mL) nanograms per milliliter
Standard Deviation 2.45
|
-0.25 (ng/mL) nanograms per milliliter
Standard Deviation 2.55
|
|
Change From Baseline in C-Reactive Protein (CRP) Levels
Week 8 Day 56
|
-0.89 (ng/mL) nanograms per milliliter
Standard Deviation 3.16
|
-0.39 (ng/mL) nanograms per milliliter
Standard Deviation 1.64
|
-1.14 (ng/mL) nanograms per milliliter
Standard Deviation 2.39
|
-1.19 (ng/mL) nanograms per milliliter
Standard Deviation 2.18
|
-0.26 (ng/mL) nanograms per milliliter
Standard Deviation 2.55
|
-0.49 (ng/mL) nanograms per milliliter
Standard Deviation 1.66
|
-0.52 (ng/mL) nanograms per milliliter
Standard Deviation 1.83
|
|
Change From Baseline in C-Reactive Protein (CRP) Levels
Week 12 Day 84
|
-1.30 (ng/mL) nanograms per milliliter
Standard Deviation 2.88
|
-0.45 (ng/mL) nanograms per milliliter
Standard Deviation 1.71
|
-1.03 (ng/mL) nanograms per milliliter
Standard Deviation 2.01
|
-1.55 (ng/mL) nanograms per milliliter
Standard Deviation 2.35
|
-0.56 (ng/mL) nanograms per milliliter
Standard Deviation 2.75
|
-0.59 (ng/mL) nanograms per milliliter
Standard Deviation 1.43
|
-0.77 (ng/mL) nanograms per milliliter
Standard Deviation 1.89
|
SECONDARY outcome
Timeframe: Days 7, 14, 28, 56, and 84Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
The Stanford Health Assessment Questionnaire disability index is a patient-reported outcome used to assess difficulty in performing activities of daily living. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. To respond to each question, a four-level response with higher scores showing larger functional limitations, was chosen. Scoring is as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. The composite HAQ-DI score is the mean of the eight domain scores and the score ranges from 0 (no functional impairment) to 3 (maximum functional impairment). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=48 Participants
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=50 Participants
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Week 1 Day 7
|
-0.22 Score on a scale
Standard Deviation 0.48
|
-0.10 Score on a scale
Standard Deviation 0.38
|
-0.26 Score on a scale
Standard Deviation 0.42
|
-0.19 Score on a scale
Standard Deviation 0.36
|
-0.14 Score on a scale
Standard Deviation 0.46
|
-0.20 Score on a scale
Standard Deviation 0.37
|
-0.15 Score on a scale
Standard Deviation 0.35
|
|
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Week 2 Day 14
|
-0.28 Score on a scale
Standard Deviation 0.50
|
-0.17 Score on a scale
Standard Deviation 0.45
|
-0.35 Score on a scale
Standard Deviation 0.47
|
-0.23 Score on a scale
Standard Deviation 0.45
|
-0.13 Score on a scale
Standard Deviation 0.49
|
-0.24 Score on a scale
Standard Deviation 0.39
|
-0.23 Score on a scale
Standard Deviation 0.46
|
|
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Week 4 Day 28
|
-0.40 Score on a scale
Standard Deviation 0.50
|
-0.19 Score on a scale
Standard Deviation 0.56
|
-0.50 Score on a scale
Standard Deviation 0.50
|
-0.23 Score on a scale
Standard Deviation 0.42
|
-0.17 Score on a scale
Standard Deviation 0.44
|
-0.34 Score on a scale
Standard Deviation 0.47
|
-0.32 Score on a scale
Standard Deviation 0.48
|
|
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Week 8 Day 56
|
-0.56 Score on a scale
Standard Deviation 0.55
|
-0.40 Score on a scale
Standard Deviation 0.64
|
-0.60 Score on a scale
Standard Deviation 0.55
|
-0.45 Score on a scale
Standard Deviation 0.50
|
-0.23 Score on a scale
Standard Deviation 0.55
|
-0.49 Score on a scale
Standard Deviation 0.47
|
-0.44 Score on a scale
Standard Deviation 0.56
|
|
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Week 12 Day 84
|
-0.65 Score on a scale
Standard Deviation 0.60
|
-0.35 Score on a scale
Standard Deviation 0.68
|
-0.65 Score on a scale
Standard Deviation 0.61
|
-0.53 Score on a scale
Standard Deviation 0.61
|
-0.30 Score on a scale
Standard Deviation 0.62
|
-0.51 Score on a scale
Standard Deviation 0.57
|
-0.57 Score on a scale
Standard Deviation 0.57
|
SECONDARY outcome
Timeframe: Pre-dose (0 hours) up to 10 hours post-dose on Day 28Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. Data were presented only for arms in which GDC-0853 was administered.
The Pharmacokinetics (PK) evaluation may include, but will not be limited to, plasma GDC-0853 concentrations and population PK model estimated PK exposures (area under the plasma concentration-time curve \[AUC\]. AUC was measured in Nanograms(ng) per millilitre(mL)\*hour (hr)
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=108 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=48 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=39 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=106 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Area Under the Concentration Time Curve From Time 0 to Time 24 of GDC-0853 at Steady State (AUC0-24,ss)
|
9380 Ng/mL*(hr)
Standard Deviation 4860
|
9890 Ng/mL*(hr)
Standard Deviation 5480
|
—
|
—
|
—
|
1170 Ng/mL*(hr)
Standard Deviation 1600
|
2910 Ng/mL*(hr)
Standard Deviation 3180
|
SECONDARY outcome
Timeframe: Pre-dose (0 hours) up to 10 hours post-dose on Day 28Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. Data were presented only for arms in which GDC-0853 was administered.
Cmax is the maximum (peak) plasma concentration over the dosing interval at steady state (ss)
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=108 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=48 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=39 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=106 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Cmax,ss)
|
591 Nanogram per Milliliter (ng/mL)
Standard Deviation 282
|
621 Nanogram per Milliliter (ng/mL)
Standard Deviation 302
|
—
|
—
|
—
|
110 Nanogram per Milliliter (ng/mL)
Standard Deviation 116
|
280 Nanogram per Milliliter (ng/mL)
Standard Deviation 223
|
SECONDARY outcome
Timeframe: Pre-dose (0 hours) up to 10 hours post-dose on Day 28Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. Data were presented only for arms in which GDC-0853 was administered.
Cmin is the minimum concentration over the dosing interval at steady state (ss)
Outcome measures
| Measure |
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=108 Participants
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=48 Participants
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=39 Participants
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=106 Participants
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Minimum Observed Plasma Concentration of GDC-0853 at Steady State (Cmin,ss)
|
250 Nanogram per Milliliter (ng/mL)
Standard Deviation 146
|
263 Nanogram per Milliliter (ng/mL)
Standard Deviation 170
|
—
|
—
|
—
|
22.4 Nanogram per Milliliter (ng/mL)
Standard Deviation 41.0
|
54.7 Nanogram per Milliliter (ng/mL)
Standard Deviation 83.4
|
Adverse Events
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
Serious events: 1 serious events
Other events: 18 other events
Deaths: 0 deaths
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
Serious events: 3 serious events
Other events: 11 other events
Deaths: 1 deaths
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Cohort 1: GDC-0853 Placebo + Adalimumab
Serious events: 2 serious events
Other events: 16 other events
Deaths: 0 deaths
Cohort 2: GDC-0853 High Dose
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 2: GDC-0853 Placebo
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 participants at risk
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 participants at risk
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 participants at risk
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 participants at risk
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 participants at risk
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=49 participants at risk
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=49 participants at risk
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.00%
0/40 • From randomization to end of study (approximately 22 months)
|
0.00%
0/109 • From randomization to end of study (approximately 22 months)
|
0.91%
1/110 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.00%
0/111 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Gastrointestinal disorders
SMALL INTESTINAL DISORDERS
|
0.00%
0/40 • From randomization to end of study (approximately 22 months)
|
0.00%
0/109 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.90%
1/111 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Infections and infestations
CELLULITS
|
0.00%
0/40 • From randomization to end of study (approximately 22 months)
|
0.00%
0/109 • From randomization to end of study (approximately 22 months)
|
0.91%
1/110 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.00%
0/111 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Infections and infestations
PNEUMONIA
|
0.00%
0/40 • From randomization to end of study (approximately 22 months)
|
0.92%
1/109 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.91%
1/110 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/111 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Infections and infestations
PYELONEPHRITIS OBSTRUCTION
|
0.00%
0/40 • From randomization to end of study (approximately 22 months)
|
0.00%
0/109 • From randomization to end of study (approximately 22 months)
|
0.91%
1/110 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.00%
0/111 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Nervous system disorders
SEIZURE
|
0.00%
0/40 • From randomization to end of study (approximately 22 months)
|
0.00%
0/109 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.90%
1/111 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
0.00%
0/40 • From randomization to end of study (approximately 22 months)
|
0.00%
0/109 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.91%
1/110 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/111 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.00%
0/40 • From randomization to end of study (approximately 22 months)
|
0.00%
0/109 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.91%
1/110 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/111 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
Other adverse events
| Measure |
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
n=40 participants at risk
Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
n=109 participants at risk
Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
n=110 participants at risk
Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
n=110 participants at risk
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 1: GDC-0853 Placebo + Adalimumab
n=111 participants at risk
Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 High Dose
n=49 participants at risk
Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
Cohort 2: GDC-0853 Placebo
n=49 participants at risk
Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion.
|
|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
NAUSEA
|
5.0%
2/40 • Number of events 2 • From randomization to end of study (approximately 22 months)
|
4.6%
5/109 • Number of events 5 • From randomization to end of study (approximately 22 months)
|
2.7%
3/110 • Number of events 3 • From randomization to end of study (approximately 22 months)
|
4.5%
5/110 • Number of events 6 • From randomization to end of study (approximately 22 months)
|
0.90%
1/111 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
6.1%
3/49 • Number of events 4 • From randomization to end of study (approximately 22 months)
|
2.0%
1/49 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
|
Gastrointestinal disorders
VOMITING
|
5.0%
2/40 • Number of events 2 • From randomization to end of study (approximately 22 months)
|
0.92%
1/109 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.90%
1/111 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
2.5%
1/40 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
2.8%
3/109 • Number of events 3 • From randomization to end of study (approximately 22 months)
|
2.7%
3/110 • Number of events 3 • From randomization to end of study (approximately 22 months)
|
1.8%
2/110 • Number of events 2 • From randomization to end of study (approximately 22 months)
|
5.4%
6/111 • Number of events 6 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Infections and infestations
URINARY TRACT INFECTION
|
5.0%
2/40 • Number of events 3 • From randomization to end of study (approximately 22 months)
|
1.8%
2/109 • Number of events 3 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
1.8%
2/110 • Number of events 2 • From randomization to end of study (approximately 22 months)
|
7.2%
8/111 • Number of events 10 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
6.1%
3/49 • Number of events 3 • From randomization to end of study (approximately 22 months)
|
|
Investigations
ALANINE AMINOTRANFERASE INCREASED
|
5.0%
2/40 • Number of events 3 • From randomization to end of study (approximately 22 months)
|
4.6%
5/109 • Number of events 5 • From randomization to end of study (approximately 22 months)
|
3.6%
4/110 • Number of events 4 • From randomization to end of study (approximately 22 months)
|
0.91%
1/110 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.90%
1/111 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
5.0%
2/40 • Number of events 2 • From randomization to end of study (approximately 22 months)
|
3.7%
4/109 • Number of events 4 • From randomization to end of study (approximately 22 months)
|
2.7%
3/110 • Number of events 4 • From randomization to end of study (approximately 22 months)
|
0.91%
1/110 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.90%
1/111 • Number of events 1 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Nervous system disorders
HEADACHE
|
5.0%
2/40 • Number of events 2 • From randomization to end of study (approximately 22 months)
|
3.7%
4/109 • Number of events 5 • From randomization to end of study (approximately 22 months)
|
4.5%
5/110 • Number of events 5 • From randomization to end of study (approximately 22 months)
|
4.5%
5/110 • Number of events 5 • From randomization to end of study (approximately 22 months)
|
0.00%
0/111 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
|
Psychiatric disorders
ANXIETY
|
0.00%
0/40 • From randomization to end of study (approximately 22 months)
|
0.00%
0/109 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.00%
0/110 • From randomization to end of study (approximately 22 months)
|
0.00%
0/111 • From randomization to end of study (approximately 22 months)
|
0.00%
0/49 • From randomization to end of study (approximately 22 months)
|
6.1%
3/49 • Number of events 3 • From randomization to end of study (approximately 22 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER