Trial Outcomes & Findings for Efficacy, Safety, and Tolerability Study of Apremilast to Treat Early Oligoarticular Psoriatic Arthritis. (NCT NCT03747939)
NCT ID: NCT03747939
Last Updated: 2024-10-22
Results Overview
MDA is defined as tender joint counts (TJC) ≤ 1 and SJC ≤ 1 plus 3 of the following 5 criteria: 1. psoriasis body surface area (BSA) ≤ 3% 2. patient's pain visual analogue scale (VAS) on a 100 mm scale ≤ 15; where 0 indicates 'no pain' and 100 indicates 'pain as severe as can be imagined' 3. patient's global assessment of disease activity on a 100 mm scale ≤ 20, where 0 represents the lowest level of disease activity and 100 represents the highest. 4. physical function assessed by Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5; where 0 represents normal or no difficulty and 3 represents an inability to perform 5. enthesitis count ≤ 1 based on the Leeds Enthesitis Index; where 0 means nontender and 6 indicates 6 tender tendon insertions.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
310 participants
Primary outcome timeframe
Week 16
Results posted on
2024-10-22
Participant Flow
Participants were enrolled at 80 study centers in Austria, Belgium, Canada, France, Germany, Italy, Spain, the United Kingdom, and the United States from 31 December 2018 to the last participant's last study visit on 05 July 2023.
Participants with early oligoarticular psoriatic arthritis were randomized in a 2:1 ratio to receive apremilast or placebo. At week 16, participants with no swollen joint count (SJC) improvement could have escaped early to receive apremilast 30 mg BID. At week 24, eligible participants entered the open-label extension phase to receive apremilast 30 mg BID up to week 48. Of the 310 enrolled participants, 2 were enrolled in error and did not receive any dose of investigational product.
Participant milestones
| Measure |
Placebo-controlled Phase: Placebo
Participants were randomized to receive placebo twice daily (BID) from day 1. Participants could also have received stable doses of non-steroidal anti-inflammatory drugs (NSAIDs) and 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD).
|
Placebo-controlled Phase: Apremilast 30 mg
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Apremilast-extension Phase: Placebo Then Apremilast 30 mg
Participants were randomized to receive placebo in the placebo-controlled phase, and entered the open-label apremilast-extension phase to receive apremilast 30 mg BID from week 24 to week 48.
|
Apremilast-extension Phase: Continued Apremilast 30 mg
Participants were randomized to receive apremilast 30 mg BID in the placebo-controlled phase, and entered the open-label apremilast-extension phase to continue on apremilast 30 mg BID from week 24 to week 48.
|
|---|---|---|---|---|
|
Placebo-controlled Phase (Weeks 0 - 24)
STARTED
|
105
|
203
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Full Analysis Set
|
105
|
203
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Safety Analysis Set
|
104
|
204
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Escaped Early at Week 16
|
24
|
21
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Completed Week 16 and Continued
|
92
|
172
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
COMPLETED
|
87
|
162
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
NOT COMPLETED
|
18
|
41
|
0
|
0
|
|
Apremilast Extension (Weeks 24 - 48)
STARTED
|
0
|
0
|
87
|
162
|
|
Apremilast Extension (Weeks 24 - 48)
Received 1 Dose of Investigational Product
|
0
|
0
|
86
|
160
|
|
Apremilast Extension (Weeks 24 - 48)
COMPLETED
|
0
|
0
|
77
|
133
|
|
Apremilast Extension (Weeks 24 - 48)
NOT COMPLETED
|
0
|
0
|
10
|
29
|
Reasons for withdrawal
| Measure |
Placebo-controlled Phase: Placebo
Participants were randomized to receive placebo twice daily (BID) from day 1. Participants could also have received stable doses of non-steroidal anti-inflammatory drugs (NSAIDs) and 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD).
|
Placebo-controlled Phase: Apremilast 30 mg
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Apremilast-extension Phase: Placebo Then Apremilast 30 mg
Participants were randomized to receive placebo in the placebo-controlled phase, and entered the open-label apremilast-extension phase to receive apremilast 30 mg BID from week 24 to week 48.
|
Apremilast-extension Phase: Continued Apremilast 30 mg
Participants were randomized to receive apremilast 30 mg BID in the placebo-controlled phase, and entered the open-label apremilast-extension phase to continue on apremilast 30 mg BID from week 24 to week 48.
|
|---|---|---|---|---|
|
Placebo-controlled Phase (Weeks 0 - 24)
Death
|
0
|
1
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Adverse Event
|
8
|
19
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Pregnancy
|
0
|
1
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Lack of Efficacy
|
4
|
7
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Non-compliance with study drug
|
1
|
1
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Lost to Follow-up
|
0
|
3
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Protocol Violation
|
1
|
0
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Withdrawal by Subject
|
4
|
7
|
0
|
0
|
|
Placebo-controlled Phase (Weeks 0 - 24)
Miscellaneous
|
0
|
2
|
0
|
0
|
|
Apremilast Extension (Weeks 24 - 48)
Adverse Event
|
0
|
0
|
2
|
6
|
|
Apremilast Extension (Weeks 24 - 48)
Lack of Efficacy
|
0
|
0
|
3
|
8
|
|
Apremilast Extension (Weeks 24 - 48)
Lost to Follow-up
|
0
|
0
|
4
|
1
|
|
Apremilast Extension (Weeks 24 - 48)
Withdrawal by Subject
|
0
|
0
|
1
|
7
|
|
Apremilast Extension (Weeks 24 - 48)
Other
|
0
|
0
|
0
|
7
|
Baseline Characteristics
Efficacy, Safety, and Tolerability Study of Apremilast to Treat Early Oligoarticular Psoriatic Arthritis.
Baseline characteristics by cohort
| Measure |
Placebo-controlled Phase: Placebo
n=105 Participants
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=203 Participants
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Total
n=308 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.2 years
STANDARD_DEVIATION 13.03 • n=39 Participants
|
51.3 years
STANDARD_DEVIATION 12.25 • n=41 Participants
|
50.9 years
STANDARD_DEVIATION 12.51 • n=35 Participants
|
|
Sex: Female, Male
Female
|
51 Participants
n=39 Participants
|
118 Participants
n=41 Participants
|
169 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
54 Participants
n=39 Participants
|
85 Participants
n=41 Participants
|
139 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
3 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=39 Participants
|
4 Participants
n=41 Participants
|
5 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
White
|
99 Participants
n=39 Participants
|
192 Participants
n=41 Participants
|
291 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Not Collected or Unknown
|
2 Participants
n=39 Participants
|
3 Participants
n=41 Participants
|
5 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
13 Participants
n=39 Participants
|
16 Participants
n=41 Participants
|
29 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
91 Participants
n=39 Participants
|
185 Participants
n=41 Participants
|
276 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Not Reported
|
1 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: Week 16Population: The full analysis set included all participants who were randomized as specified in the protocol.
MDA is defined as tender joint counts (TJC) ≤ 1 and SJC ≤ 1 plus 3 of the following 5 criteria: 1. psoriasis body surface area (BSA) ≤ 3% 2. patient's pain visual analogue scale (VAS) on a 100 mm scale ≤ 15; where 0 indicates 'no pain' and 100 indicates 'pain as severe as can be imagined' 3. patient's global assessment of disease activity on a 100 mm scale ≤ 20, where 0 represents the lowest level of disease activity and 100 represents the highest. 4. physical function assessed by Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5; where 0 represents normal or no difficulty and 3 represents an inability to perform 5. enthesitis count ≤ 1 based on the Leeds Enthesitis Index; where 0 means nontender and 6 indicates 6 tender tendon insertions.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=105 Participants
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=203 Participants
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
|---|---|---|
|
Percentage of Participants Who Achieved a Clinical State of Minimal Disease Activity (MDA-Joints) Response at Week 16
|
16.0 percentage of participants
|
33.9 percentage of participants
|
SECONDARY outcome
Timeframe: Week 16Population: The full analysis set included all participants who were randomized as specified in the protocol.
The cDAPSA score is based on the numerical summation of 4 disease activity variables: tender and swollen joints, patient's global assessments of disease activity and assessment of pain (VAS). The cDAPSA score ranges from 0 to 154, with a higher score indicating more disease activity. cDAPSA remission is defined as a DAPSA score ≤ 4 and low disease activity is defined as a cDAPSA score \> 4 but ≤ 13).
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=105 Participants
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=203 Participants
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
|---|---|---|
|
Percentage of Participants Who Achieved Remission or Low Disease Activity at Week 16 Based on Clinical Activity in Psoriatic Arthritis (cDAPSA)
|
51.8 percentage of participants
|
70.2 percentage of participants
|
SECONDARY outcome
Timeframe: Week 16Population: The full analysis set included all participants who were randomized as specified in the protocol.
The SJC was based on 66 joints and at week 16 is based on the sentinel joints (i.e., the joints that were affected at baseline). A SJC response is defined as a count ≤ 1.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=105 Participants
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=203 Participants
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
|---|---|---|
|
Percentage of Participants With SJC ≤ 1 at Week 16
|
69.0 percentage of participants
|
74.0 percentage of participants
|
SECONDARY outcome
Timeframe: Week 16Population: The full analysis set included all participants who were randomized as specified in the protocol.
The TJC was based on 68 joints and at week 16 was based on the sentinel joints (i.e., the joints that were affected at baseline). A TJC response is defined as a count ≤ 1.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=105 Participants
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=203 Participants
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
|---|---|---|
|
Percentage of Participants With TJC ≤ 1 at Week 16
|
44.4 percentage of participants
|
66.2 percentage of participants
|
SECONDARY outcome
Timeframe: Week 16Population: The full analysis set included all participants who were randomized as specified in the protocol.
The Patient's Global Assessments of Disease Activity is an assessment of how active a participant's psoriatic arthritis was on average during the last week. It was assessed on a VAS ranging from 0 to 100 mm, with a higher score indicating more disease activity. A response is defined as a score ≤ 20 mm.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=105 Participants
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=203 Participants
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
|---|---|---|
|
Percentage of Participants With Patient's Global Assessments of Disease Activity Score of ≤ 20 mm in the VAS at Week 16
|
19.1 percentage of participants
|
30.4 percentage of participants
|
SECONDARY outcome
Timeframe: Week 16Population: The full analysis set included all participants who were randomized as specified in the protocol.
The Patients Pain VAS is the participant's assessment of how much pain they had, on average, during the last week in their joints due to psoriatic arthritis. The VAS score ranges from 0 to 100 mm, with a higher score indicating more pain.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=105 Participants
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=203 Participants
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
|---|---|---|
|
Percentage of Participants With an Assessment of Pain Score ≤ 15 mm in VAS at Week 16
|
13.1 percentage of participants
|
29.4 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Week 16Population: The full analysis set included all participants who were randomized as specified in the protocol.
The PsAID-12 Questionnaire is a 12-item, self-administered questionnaire that reflects the impact of psoriatic arthritis from the perspective of the participant. The overall score ranges from 0 (best status) to 10 (worst status), with a cut-off ≤ 4 representing patient-acceptable symptom state. Analysis was based on a mixed-effects model for repeated measures (MMRM), which included treatment group, time, treatment group by time interaction, prior/concomitant use of csDMARD (naive, prior use only, both prior and concomitant use) and baseline glucocorticosteroid use (yes/no) per IWRS data as factors, and baseline value as a covariate.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=105 Participants
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=203 Participants
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
|---|---|---|
|
Change From Baseline in Psoriatic Arthritis Impact of Disease 12-item for Clinical Trials (PsAID-12) Questionnaire Score at Week 16
|
-0.42 score on a scale
Standard Error 0.216
|
-1.45 score on a scale
Standard Error 0.178
|
SECONDARY outcome
Timeframe: Baseline and Week 16Population: The full analysis set included all participants who were randomized as specified in the protocol.
The PASDAS is a weighted index comprising assessments of joints, function, acute-phase response, quality of life, and patient and physician VAS. The score range of the PASDAS is 0 - 10, with worse disease activity represented by higher scores. A good response is defined as a PASDAS score of ≤ 3.2 with improvement from baseline ≥ 1.6 points. A moderate response is defined as a PASDAS score \> 3.2 with improvement from baseline ≥ 1.6 points; or PASDAS score \< 5.4 with improvement from baseline ≥ 0.8 but \< 1.6 points.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=105 Participants
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=203 Participants
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
|---|---|---|
|
Percentage of Participants With a Good or Moderate Psoriatic Arthritis Disease Activity (PASDAS) Score at Week 16
|
42.7 percentage of participants
|
59.9 percentage of participants
|
Adverse Events
Placebo-controlled Phase: Placebo
Serious events: 6 serious events
Other events: 18 other events
Deaths: 0 deaths
Placebo-controlled Phase: Apremilast 30 mg
Serious events: 9 serious events
Other events: 72 other events
Deaths: 2 deaths
Apremilast-exposure: Apremilast 30 mg During Placebo-controlled and Extension Phases
Serious events: 15 serious events
Other events: 103 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Placebo-controlled Phase: Placebo
n=104 participants at risk
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=204 participants at risk
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Apremilast-exposure: Apremilast 30 mg During Placebo-controlled and Extension Phases
n=291 participants at risk
All participants who received apremilast 30 mg BID during the study, including: participants who were randomized to placebo during the placebo-controlled phase, and received apremilast 30 mg during the extension phase; and all participants who received apremilast 30 mg BID during the placebo-controlled phase.
|
|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.96%
1/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
General disorders
Sudden cardiac death
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.49%
1/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Infections and infestations
COVID-19
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.49%
1/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Infections and infestations
Cellulitis
|
0.96%
1/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.49%
1/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Infections and infestations
Post procedural infection
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Infections and infestations
Sepsis
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.49%
1/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Infections and infestations
Urosepsis
|
0.96%
1/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.49%
1/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Investigations
Troponin increased
|
0.96%
1/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.49%
1/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.98%
2/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.69%
2/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.49%
1/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.96%
1/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Nervous system disorders
Brain injury
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.49%
1/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.69%
2/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.96%
1/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Psychiatric disorders
Depression
|
0.96%
1/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.96%
1/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.49%
1/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.34%
1/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Vascular disorders
Hypertensive crisis
|
0.96%
1/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
0.00%
0/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
Other adverse events
| Measure |
Placebo-controlled Phase: Placebo
n=104 participants at risk
Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Placebo-controlled Phase: Apremilast 30 mg
n=204 participants at risk
Participants were randomized to receive apremilast 30 mg BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD.
|
Apremilast-exposure: Apremilast 30 mg During Placebo-controlled and Extension Phases
n=291 participants at risk
All participants who received apremilast 30 mg BID during the study, including: participants who were randomized to placebo during the placebo-controlled phase, and received apremilast 30 mg during the extension phase; and all participants who received apremilast 30 mg BID during the placebo-controlled phase.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
10.6%
11/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
23.0%
47/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
23.7%
69/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Gastrointestinal disorders
Nausea
|
3.8%
4/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
10.8%
22/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
9.6%
28/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Infections and infestations
COVID-19
|
2.9%
3/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
3.4%
7/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
6.5%
19/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
|
Nervous system disorders
Headache
|
2.9%
3/104 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
7.8%
16/204 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
7.2%
21/291 • Week 0 up to week 48 (end of extension phase), and a 4-week observational follow-up (up to 52 weeks).
The safety analysis set included all participants who received at least 1 dose of study medication. For the placebo-controlled phase, participants were included in the treatment group for the treatment they actually received.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER