Arthritis, Psoriatic
Conditions
Keywords
Oligoarthritis, PsA, Apremilast, Oral tablet, Background therapy, Standard of care
Brief summary
This clinical study will test the effects of a drug called apremilast in oligoarticular psoriatic arthritis with less than 5 years of disease duration. In previous studies, apremilast has been shown to be safe and efficacious in reducing signs and symptoms of psoriatic arthritis, as well as improving physical function. This study will compare the effects of apremilast to placebo on psoriatic arthritis subjects in which the number of affected joints is limited (greater than 1 but less or equal to 4). About 285 patients worldwide will take part in this study.
Interventions
Subjects randomized to apremilast will receive dose-titration for the initial 5 days. Apremilast subjects will receive "dummy" titration at wk. 16 (for early escape subjects) and again at week 24 to maintain the blinding of the original treatment assignments. Investigational product (IP) will be dispensed in blinded dose cards until Week 28. Thereafter, IP will be dispensed in open-label bottles.
OTHERApremilast (CC-10004) Placebo
Subjects randomized to placebo will receive "dummy" dose-titration for the initial 5 days. Placebo subjects who meet the criteria for early escape at wk. 16 may receive apremilast beginning at wk. 16 and will receive active titration. Remaining placebo subjects will receive active dose titration at week 24. Beginning at wk 24 all subjects will be dispensed active apremilast. Investigational product will be dispensed in blinded dose cards until Week 28. to maintain the blinding of the original treatment assignments. Thereafter, IP will be dispensed in open-label bottles
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 yrs, male or female subject * Subjects must have signs and symptoms of PsA ≤5 years duration at the time of the Screening Visit * SJC AND TJC must be \>1 and ≤ 4 * For all regions, the local Regulatory Label for treatment with apremilast must be followed. * Stable doses of protocol-allowed PsA medications * General good health (except for psoriatic arthritis) as judged by the Investigator, based on medical history, physical examination, and clinical laboratories. (Note: The definition of good health means a subject does not have uncontrolled significant comorbid conditions). * Comply with protocol-required contraception measures * Subject meets the Classification Criteria for Psoriatic Arthritis \[CASPAR\] Criteria for PsA at the Screening visit
Exclusion criteria
* Prior use of \>2 csDMARD to treat PsA * Prior exposure to a JAK-inhibitor and/or a biologic DMARD. * Use of intra-articular (IA) or intra-muscular (IM) glucocorticoid injection within 8 weeks before the Baseline Visit. * Use of leflunomide within 12 weeks of randomization. Subjects who stopped leflunomide and completed 11 days of treatment with cholestyramine (8 g, 3 x daily) prior to the Baseline Visit may enter the study. * Prior use of cyclosporine. * Prior treatment with apremilast, or participation in a clinical study, involving apremilast. * Use of any investigational drug within 4 weeks of the Baseline Visit, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Clinical State of Minimal Disease Activity (MDA-Joints) Response at Week 16 | Week 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Remission or Low Disease Activity at Week 16 Based on Clinical Activity in Psoriatic Arthritis (cDAPSA) | Week 16 | 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). |
| Percentage of Participants With SJC ≤ 1 at Week 16 | Week 16 | 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. |
| Percentage of Participants With TJC ≤ 1 at Week 16 | Week 16 | 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. |
| Percentage of Participants With Patient's Global Assessments of Disease Activity Score of ≤ 20 mm in the VAS at Week 16 | Week 16 | 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. |
| Percentage of Participants With an Assessment of Pain Score ≤ 15 mm in VAS at Week 16 | Week 16 | 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. |
| Change From Baseline in Psoriatic Arthritis Impact of Disease 12-item for Clinical Trials (PsAID-12) Questionnaire Score at Week 16 | Baseline and Week 16 | 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. |
| Percentage of Participants With a Good or Moderate Psoriatic Arthritis Disease Activity (PASDAS) Score at Week 16 | Baseline and Week 16 | 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. |
Countries
Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Russia, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo-controlled Phase: Placebo Participants were randomized to receive placebo BID from day 1. Participants could also have received stable doses of NSAIDs and 1 csDMARD. | 105 |
| 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. | 203 |
| Total | 308 |
Baseline characteristics
| Characteristic | Total | Placebo-controlled Phase: Apremilast 30 mg | Placebo-controlled Phase: Placebo |
|---|---|---|---|
| Age, Continuous | 50.9 years STANDARD_DEVIATION 12.51 | 51.3 years STANDARD_DEVIATION 12.25 | 50.2 years STANDARD_DEVIATION 13.03 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 29 Participants | 16 Participants | 13 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Collected or Unknown | 5 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 276 Participants | 185 Participants | 91 Participants |
| Race/Ethnicity, Customized Not Reported | 3 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 291 Participants | 192 Participants | 99 Participants |
| Sex: Female, Male Female | 169 Participants | 118 Participants | 51 Participants |
| Sex: Female, Male Male | 139 Participants | 85 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 104 | 2 / 204 | 2 / 291 |
| other Total, other adverse events | 18 / 104 | 72 / 204 | 103 / 291 |
| serious Total, serious adverse events | 6 / 104 | 9 / 204 | 15 / 291 |
Outcome results
Primary
Percentage of Participants Who Achieved a Clinical State of Minimal Disease Activity (MDA-Joints) Response at Week 16
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.
Time frame: Week 16
Population: The full analysis set included all participants who were randomized as specified in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-controlled Phase: Placebo | Percentage of Participants Who Achieved a Clinical State of Minimal Disease Activity (MDA-Joints) Response at Week 16 | 16.0 percentage of participants |
| Placebo-controlled Phase: Apremilast 30 mg | Percentage of Participants Who Achieved a Clinical State of Minimal Disease Activity (MDA-Joints) Response at Week 16 | 33.9 percentage of participants |
Comparison: Adjusted difference in proportions is the weighted average of the treatment differences across strata formed by two stratification factors, prior/concomitant use of csDMARD and baseline glucocorticosteroid use per Interactive Web Response System (IWRS) data, using Cochran-Mantel-Haenszel (CMH) weights. Two-sided 95% CI is based on a normal approximation to the weighted average.p-value: 0.000895% CI: [8.9, 28.1]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Psoriatic Arthritis Impact of Disease 12-item for Clinical Trials (PsAID-12) Questionnaire Score at Week 16
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.
Time frame: Baseline and Week 16
Population: The full analysis set included all participants who were randomized as specified in the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo-controlled Phase: Placebo | 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 |
| Placebo-controlled Phase: Apremilast 30 mg | Change From Baseline in Psoriatic Arthritis Impact of Disease 12-item for Clinical Trials (PsAID-12) Questionnaire Score at Week 16 | -1.45 score on a scale | Standard Error 0.178 |
Comparison: Difference in LS means is based MMRM of the change from baseline.p-value: <0.000195% CI: [-1.48, -0.59]MMRM
Secondary
Percentage of Participants Who Achieved Remission or Low Disease Activity at Week 16 Based on Clinical Activity in Psoriatic Arthritis (cDAPSA)
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).
Time frame: Week 16
Population: The full analysis set included all participants who were randomized as specified in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-controlled Phase: Placebo | 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 |
| Placebo-controlled Phase: Apremilast 30 mg | Percentage of Participants Who Achieved Remission or Low Disease Activity at Week 16 Based on Clinical Activity in Psoriatic Arthritis (cDAPSA) | 70.2 percentage of participants |
Comparison: Adjusted difference in proportions is the weighted average of the treatment differences across strata formed by two stratification factors, prior/concomitant use of csDMARD and baseline glucocorticosteroid use per IWRS data, using CMH weights. Two-sided 95% CI is based on a normal approximation to the weighted average.p-value: 0.001795% CI: [7, 30.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Good or Moderate Psoriatic Arthritis Disease Activity (PASDAS) Score at Week 16
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.
Time frame: Baseline and Week 16
Population: The full analysis set included all participants who were randomized as specified in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-controlled Phase: Placebo | Percentage of Participants With a Good or Moderate Psoriatic Arthritis Disease Activity (PASDAS) Score at Week 16 | 42.7 percentage of participants |
| Placebo-controlled Phase: Apremilast 30 mg | Percentage of Participants With a Good or Moderate Psoriatic Arthritis Disease Activity (PASDAS) Score at Week 16 | 59.9 percentage of participants |
Comparison: Adjusted difference in proportions is the weighted average of the treatment differences across strata formed by two stratification factors, prior/concomitant use of csDMARD and baseline glucocorticosteroid use per IWRS data, using CMH weights. Two-sided 95% CI is based on a normal approximation to the weighted average.p-value: 0.004395% CI: [5.7, 29.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With an Assessment of Pain Score ≤ 15 mm in VAS at Week 16
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.
Time frame: Week 16
Population: The full analysis set included all participants who were randomized as specified in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-controlled Phase: Placebo | Percentage of Participants With an Assessment of Pain Score ≤ 15 mm in VAS at Week 16 | 13.1 percentage of participants |
| Placebo-controlled Phase: Apremilast 30 mg | Percentage of Participants With an Assessment of Pain Score ≤ 15 mm in VAS at Week 16 | 29.4 percentage of participants |
Comparison: Adjusted difference in proportions is the weighted average of the treatment differences across strata formed by two stratification factors, prior/concomitant use of csDMARD and baseline glucocorticosteroid use per IWRS data, using CMH weights. Two-sided 95% CI is based on a normal approximation to the weighted average.p-value: 0.002295% CI: [6.9, 25.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Patient's Global Assessments of Disease Activity Score of ≤ 20 mm in the VAS at Week 16
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.
Time frame: Week 16
Population: The full analysis set included all participants who were randomized as specified in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-controlled Phase: Placebo | 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 |
| Placebo-controlled Phase: Apremilast 30 mg | Percentage of Participants With Patient's Global Assessments of Disease Activity Score of ≤ 20 mm in the VAS at Week 16 | 30.4 percentage of participants |
Comparison: Adjusted difference in proportions is the weighted average of the treatment differences across strata formed by two stratification factors, prior/concomitant use of csDMARD and baseline glucocorticosteroid use per IWRS data, using CMH weights. Two-sided 95% CI is based on a normal approximation to the weighted average.p-value: 0.028695% CI: [1.7, 22]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With SJC ≤ 1 at Week 16
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.
Time frame: Week 16
Population: The full analysis set included all participants who were randomized as specified in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-controlled Phase: Placebo | Percentage of Participants With SJC ≤ 1 at Week 16 | 69.0 percentage of participants |
| Placebo-controlled Phase: Apremilast 30 mg | Percentage of Participants With SJC ≤ 1 at Week 16 | 74.0 percentage of participants |
Comparison: Adjusted difference in proportions is the weighted average of the treatment differences across strata formed by two stratification factors, prior/concomitant use of csDMARD and baseline glucocorticosteroid use per IWRS data, using CMH weights. Two-sided 95% CI is based on a normal approximation to the weighted average.p-value: 0.353995% CI: [-5.8, 16]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With TJC ≤ 1 at Week 16
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.
Time frame: Week 16
Population: The full analysis set included all participants who were randomized as specified in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-controlled Phase: Placebo | Percentage of Participants With TJC ≤ 1 at Week 16 | 44.4 percentage of participants |
| Placebo-controlled Phase: Apremilast 30 mg | Percentage of Participants With TJC ≤ 1 at Week 16 | 66.2 percentage of participants |
Comparison: Adjusted difference in proportions is the weighted average of the treatment differences across strata formed by two stratification factors, prior/concomitant use of csDMARD and baseline glucocorticosteroid use per IWRS data, using CMH weights. Two-sided 95% CI is based on a normal approximation to the weighted average.p-value: 0.000395% CI: [10.4, 33.7]Cochran-Mantel-Haenszel