Trial Outcomes & Findings for Evaluation of the Optimal MTX Dose as an Add-on Therapy to Adalimumab for RA Patients in Japan, South Korea and Taiwan (NCT NCT03505008)
NCT ID: NCT03505008
Last Updated: 2025-03-06
Results Overview
SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 \[none\] to 10 \[most severe\]), Physician's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 \[none\] to 10 \[most severe\]), and C-reactive protein (mg/dL). Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, \> 3.4 to 11 = low disease activity, \> 11 to 26 = moderate disease activity, and \> 26 = high disease activity.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
300 participants
Primary outcome timeframe
Week 48
Results posted on
2025-03-06
Participant Flow
Participant milestones
| Measure |
MTX-Monotherapy Before Week 24 Randomization
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24.
Methotrexate: Route of Administration: Oral
|
MTX-Monotherapy Group After Week 24
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and simple disease activity index (SDAI) remission is achieved at Week 24, the MTX therapy will continue until Week 48.
Methotrexate: Route of Administration: Oral
|
ADA/MTX-Maximum Tolerated Dose Group After Week 24
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group After Week 24
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|---|---|
|
Before Week 24 Randomization
STARTED
|
291
|
0
|
0
|
0
|
|
Before Week 24 Randomization
COMPLETED
|
239
|
0
|
0
|
0
|
|
Before Week 24 Randomization
NOT COMPLETED
|
52
|
0
|
0
|
0
|
|
After Week 24 Randomization
STARTED
|
0
|
105
|
68
|
66
|
|
After Week 24 Randomization
COMPLETED
|
0
|
101
|
59
|
58
|
|
After Week 24 Randomization
NOT COMPLETED
|
0
|
4
|
9
|
8
|
Reasons for withdrawal
| Measure |
MTX-Monotherapy Before Week 24 Randomization
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24.
Methotrexate: Route of Administration: Oral
|
MTX-Monotherapy Group After Week 24
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and simple disease activity index (SDAI) remission is achieved at Week 24, the MTX therapy will continue until Week 48.
Methotrexate: Route of Administration: Oral
|
ADA/MTX-Maximum Tolerated Dose Group After Week 24
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group After Week 24
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|---|---|
|
Before Week 24 Randomization
Withdrawal by Subject
|
24
|
0
|
0
|
0
|
|
Before Week 24 Randomization
Adverse Event
|
10
|
0
|
0
|
0
|
|
Before Week 24 Randomization
Lack of Efficacy
|
8
|
0
|
0
|
0
|
|
Before Week 24 Randomization
Methotrexate <10 mg/week at Week 24
|
5
|
0
|
0
|
0
|
|
Before Week 24 Randomization
Physician Decision
|
2
|
0
|
0
|
0
|
|
Before Week 24 Randomization
Lost to Follow-up
|
1
|
0
|
0
|
0
|
|
Before Week 24 Randomization
Inadequate Methotrexate Adherence
|
1
|
0
|
0
|
0
|
|
Before Week 24 Randomization
Complication
|
1
|
0
|
0
|
0
|
|
After Week 24 Randomization
Withdrawal by Subject
|
0
|
0
|
3
|
3
|
|
After Week 24 Randomization
Lack of Efficacy
|
0
|
2
|
3
|
1
|
|
After Week 24 Randomization
Adverse Event
|
0
|
1
|
2
|
2
|
|
After Week 24 Randomization
Lost to Follow-up
|
0
|
1
|
0
|
2
|
|
After Week 24 Randomization
Protocol Violation
|
0
|
0
|
1
|
0
|
Baseline Characteristics
One person was not tested.
Baseline characteristics by cohort
| Measure |
Full-analysis Set
n=291 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24.
Methotrexate: Route of Administration: Oral
|
|---|---|
|
Age, Continuous
|
57.7 years
STANDARD_DEVIATION 15.2 • n=291 Participants
|
|
Sex: Female, Male
Female
|
217 Participants
n=291 Participants
|
|
Sex: Female, Male
Male
|
74 Participants
n=291 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=291 Participants
|
|
Race (NIH/OMB)
Asian
|
290 Participants
n=291 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=291 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=291 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=291 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=291 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=291 Participants
|
|
Region of Enrollment
Japan
|
194 Participants
n=291 Participants
|
|
Region of Enrollment
South Korea
|
55 Participants
n=291 Participants
|
|
Region of Enrollment
Taiwan
|
42 Participants
n=291 Participants
|
|
Duration from the Diagnosis of Rheumatoid Arthritis
|
21.1 days
STANDARD_DEVIATION 56.2 • n=291 Participants
|
|
Bodyweight
|
58.2 kg
STANDARD_DEVIATION 11.4 • n=291 Participants
|
|
Estimated Glomerular Filtration Rate (eGFR)
|
82.0 mL/min/1.73m²
STANDARD_DEVIATION 20.2 • n=291 Participants
|
|
Current or Past Smoker
|
102 Participants
n=291 Participants
|
|
Simplified Disease Activity Index (SDAI)
|
26.5 scores on a scale
STANDARD_DEVIATION 12.4 • n=291 Participants
|
|
28-Joint Disease Activity Score of Erythrocyte Sedimentation Rate (DAS28-ESR)
|
5.2 scores on a scale
STANDARD_DEVIATION 1.1 • n=291 Participants
|
|
Health Assessment Questionnaire - Disability Index (HAQ-DI)
|
0.9 scores on a scale
STANDARD_DEVIATION 0.7 • n=291 Participants
|
|
Rheumatoid Factor Positive
|
213 Participants
n=290 Participants • One person was not tested.
|
|
Anti-cyclic Citrullinated Peptide Antibody Positive
|
211 Participants
n=289 Participants • Two people were not tested.
|
|
Comorbidities
|
127 Participants
n=291 Participants
|
PRIMARY outcome
Timeframe: Week 48Population: In the modified Full Analysis Set based on non-responder imputation. The modified Full Analysis Set was defined as those with evaluable data set at one or more timepoints after randomization including 66 of 68 subjects in ADA/MTX-Maximum Tolerated Dose Group and 61 of 66 subjects in ADA/MTX-Reduced Dose Group. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group.
SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 \[none\] to 10 \[most severe\]), Physician's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 \[none\] to 10 \[most severe\]), and C-reactive protein (mg/dL). Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, \> 3.4 to 11 = low disease activity, \> 11 to 26 = moderate disease activity, and \> 26 = high disease activity.
Outcome measures
| Measure |
ADA/MTX-Maximum Tolerated Dose Group
n=66 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group
n=61 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|
|
Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in mFAS
|
25 Participants
|
27 Participants
|
SECONDARY outcome
Timeframe: Week 48Population: In the Per Protocol Set based on non-responder imputation. The Per Protocol Set is defined as a group of subjects among modified Full Analysis Set who adequately complied with the protocol including 58 of 66 subjects in ADA/MTX-Maximum Tolerated Dose Group and 61 of 61 subjects in ADA/MTX-Reduced Dose Group. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group.
SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 \[none\] to 10 \[most severe\]), Physician's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 \[none\] to 10 \[most severe\]), and C-reactive protein (mg/dL). Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, \> 3.4 to 11 = low disease activity, \> 11 to 26 = moderate disease activity, and \> 26 = high disease activity.
Outcome measures
| Measure |
ADA/MTX-Maximum Tolerated Dose Group
n=58 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group
n=61 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|
|
Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in PPS
|
23 Participants
|
27 Participants
|
SECONDARY outcome
Timeframe: Week 48Population: In the Full Analysis Set based on non-responder imputation. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group.
ACR 20 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 20 response will be referred to as ACR 20 response rate. * ≥20% improvement in the tender joint count (of the total 68 joints) compared to Week 0 of treatment * ≥20% improvement in the swollen joint count (of the total 66 joints) compared to Week 0 of treatment * ≥20% improvement in ≥3 of 5 parameters (physician- and patient-reported disease activities, patient-reported pain score, HAQ, and CRP) compared to Week 0 of treatment
Outcome measures
| Measure |
ADA/MTX-Maximum Tolerated Dose Group
n=68 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group
n=66 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|
|
American College of Rheumatology (ACR) 20 Response Rate at Week 48
|
47 Participants
|
47 Participants
|
SECONDARY outcome
Timeframe: Week 48Population: In the Full Analysis Set based on non-responder imputation. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group.
ACR 50 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 50 response will be referred to as ACR 50 response rate. * ≥50% improvement in the tender joint count (of the total 68 joints) compared to Week 0 of treatment * ≥50% improvement in the swollen joint count (of the total 66 joints) compared to Week 0 of treatment * ≥50% improvement in ≥3 of 5 parameters (physician- and patient-reported disease activities, patient-reported pain score, HAQ, and CRP) compared to Week 0 of treatment
Outcome measures
| Measure |
ADA/MTX-Maximum Tolerated Dose Group
n=68 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group
n=66 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|
|
American College of Rheumatology (ACR) 50 Response Rate at Week 48
|
36 Participants
|
38 Participants
|
SECONDARY outcome
Timeframe: Week 48Population: In the Full Analysis Set based on non-responder imputation. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group.
ACR 70 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 70 response will be referred to as ACR 70 response rate. * ≥70% improvement in the tender joint count (of the total 68 joints) compared to Week 0 of treatment * ≥70% improvement in the swollen joint count (of the total 66 joints) compared to Week 0 of treatment * ≥70% improvement in ≥3 of 5 parameters (physician- and patient-reported disease activities, patient-reported pain score, HAQ, and CRP) compared to Week 0 of treatment
Outcome measures
| Measure |
ADA/MTX-Maximum Tolerated Dose Group
n=68 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group
n=66 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|
|
American College of Rheumatology (ACR) 70 Response Rate at Week 48
|
22 Participants
|
26 Participants
|
SECONDARY outcome
Timeframe: Week 48Population: In the Full Analysis Set based on non-responder imputation. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group.
HAQ-DI is a patient-reported questionnaire, consists of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week as: without any difficulty (0); with some difficulty (1); with much difficulty (2); unable to do (3). Scores on each task were summed and averaged to provide an overall score from 0 to 3, where 0=no disability and 3=very severe, high-dependency disability. Normal physical function is defined by HAQ-DI score of \< 0.5.
Outcome measures
| Measure |
ADA/MTX-Maximum Tolerated Dose Group
n=68 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group
n=66 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|
|
Health Assessment Questionnaire - Disability Index ≤0.5 at Week 48
|
40 Participants
|
41 Participants
|
SECONDARY outcome
Timeframe: Week 48Population: In the Full Analysis Set based on non-responder imputation. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group.
Bone erosions will be evaluated for each region from a scale of 0 (no damage) to 5 (complete collapse of the joint). The score will be 0 to 5 for each hand joint, and 0 to 10 for each foot joint. The maximum total erosion score of both hands will be 160 points, and that of both feet will be 120 points. Joint space narrowing will be evaluated for each region from a scale of 0 (no damage) to 4 (ankylosis or luxation). The maximum total joint space narrowing score of both hands will be 120 points, and that of both feet will be 48 points. Erosion scores and joint space narrowing scores were added to obtain the mTSS (range from 0 to 448).
Outcome measures
| Measure |
ADA/MTX-Maximum Tolerated Dose Group
n=68 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group
n=66 Participants
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|
|
Change in Modified Total Sharp Score ≤ 0.5 at Week 48
|
45 Participants
|
41 Participants
|
Adverse Events
All From Week 0 to Week 48
Serious events: 23 serious events
Other events: 122 other events
Deaths: 0 deaths
MTX-Monotherapy Before Week 24 Randomization
Serious events: 9 serious events
Other events: 94 other events
Deaths: 0 deaths
MTX-Monotherapy Group After Week 24
Serious events: 6 serious events
Other events: 25 other events
Deaths: 0 deaths
ADA/MTX-Maximum Tolerated Dose Group After Week 24
Serious events: 5 serious events
Other events: 14 other events
Deaths: 0 deaths
ADA/MTX-Reduced Dose Group After Week 24
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All From Week 0 to Week 48
n=291 participants at risk
Participants in Safety Analysis Set
|
MTX-Monotherapy Before Week 24 Randomization
n=291 participants at risk
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24.
Methotrexate: Route of Administration: Oral
|
MTX-Monotherapy Group After Week 24
n=105 participants at risk
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and simple disease activity index (SDAI) remission is achieved at Week 24, the MTX therapy will continue until Week 48.
Methotrexate: Route of Administration: Oral
|
ADA/MTX-Maximum Tolerated Dose Group After Week 24
n=68 participants at risk
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group After Week 24
n=66 participants at risk
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchiectasis
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Cardiac disorders
Cardiac failure acute
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Nervous system disorders
Dizziness
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Infections and infestations
Gastroenteritis
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoproliferative disorder
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Injury, poisoning and procedural complications
Multiple fractures
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Infections and infestations
Pneumocystis jirovecii pneumonia
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Infections and infestations
Pneumonia
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Infections and infestations
Pyelonephritis
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Musculoskeletal and connective tissue disorders
Spondylolisthesis
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.34%
1/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
Other adverse events
| Measure |
All From Week 0 to Week 48
n=291 participants at risk
Participants in Safety Analysis Set
|
MTX-Monotherapy Before Week 24 Randomization
n=291 participants at risk
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24.
Methotrexate: Route of Administration: Oral
|
MTX-Monotherapy Group After Week 24
n=105 participants at risk
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and simple disease activity index (SDAI) remission is achieved at Week 24, the MTX therapy will continue until Week 48.
Methotrexate: Route of Administration: Oral
|
ADA/MTX-Maximum Tolerated Dose Group After Week 24
n=68 participants at risk
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
ADA/MTX-Reduced Dose Group After Week 24
n=66 participants at risk
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|---|---|---|---|---|---|
|
Investigations
Liver function test abnormal
|
12.7%
37/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
8.2%
24/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
7.6%
8/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
8.8%
6/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.2%
18/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
4.5%
13/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
4.8%
5/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Infections and infestations
Nasopharyngitis
|
5.8%
17/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
4.5%
13/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
2.9%
3/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Infections and infestations
Upper respiratory tract infection
|
5.5%
16/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
4.8%
14/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Gastrointestinal disorders
Nausea
|
4.5%
13/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
3.1%
9/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
5.7%
6/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.4%
7/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
2.1%
6/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.7%
5/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.4%
4/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Nervous system disorders
Dizziness
|
1.7%
5/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.7%
5/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Gastrointestinal disorders
Dyspepsia
|
1.7%
5/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.7%
5/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.4%
4/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
2.9%
2/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Investigations
Alanine aminotransferase increased
|
1.4%
4/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.9%
2/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Infections and infestations
Herpes zoster
|
1.4%
4/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.4%
4/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Infections and infestations
Influenza
|
1.4%
4/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Gastrointestinal disorders
Stomatitis
|
1.4%
4/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Gastrointestinal disorders
Dry mouth
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
3.0%
2/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Gastrointestinal disorders
Epigastric discomfort
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Gastrointestinal disorders
Mouth ulceration
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Infections and infestations
Pharyngitis
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Investigations
Transaminases increased
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Infections and infestations
Urinary tract infection
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
1.5%
1/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
1.0%
3/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.69%
2/291 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.95%
1/105 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/68 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
0.00%
0/66 • 48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place