Efficacy, Safety, and Tolerability Study of Apremilast to Treat Early Oligoarticular Psoriatic Arthritis.

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Early, Oligoarticular Psoriatic Arthritis Despite Initial Stable Treatment With Either NSAIDS and/or ≤ 1 Conventional Synthetic DMARD

Conditions
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Arthritis, Psoriatic

Intervention / Treatment
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* Drug: Apremilast (CC-10004)
* Other: Apremilast (CC-10004) Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apremilast 30 mg twice daily ± NSAIDs, ≤ 1 csDMARD<br>Subjects will take ORAL tables of apremilast for up to 48 weeks (30 mg twice daily). Subjects may also receive stable doses of background therapy (standard or care) with NSAIDs, glucorticosteroids and 1 csDMARD as permitted by protocol. After wk. 24, subjects may change the dose /type of permitted Psoriatic Arthritis medications | Drug: Apremilast (CC-10004)<br>* 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.<br>* Other names: Otezla;|
| Placebo Comparator: Placebo<br>Subjects will take placebo for up to 24 weeks (twice daily). Subjects may also receive stable doses of background therapy ( standard of care) with NSAIDs, glucocorticosteroids and 1 csDMARD as permitted by protocol. After wk 24, subjects may change the dose /type of permitted PsA medications. | Other: Apremilast (CC-10004) Placebo<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieved a clinical state of minimal disease activity defined MDA-Joints) | Minimal disease activity by MDA joints | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with cDAPSA remission or low activity | cDAPSA Remission or Low Disease Activity | Week 16 | 
| Proportion of subjects with SJC ≤ 1 | Swollen Joint Count (SJC) | Week 16 | 
| Proportion of subjects with TJC ≤ 1 | Tender Joint Count (TJC) | Week 16 | 
| Proportion of subjects with improvement in the PsAID-12 score | PsAID-12 Response | Week 16 | 
| Proportion of subjects with improvement in the PASDAS score | PASDAS Response | Week 16 | 
| Proportion of subjects with improvement in the Patient Global Assessment of Disease Activity | Patient's Global Assessment of Disease Activity | Week 16 | 
| Proportion of subjects with improvement in the Patient Global Assessment Pain | Patient's Global Assessment of Disease Pain | Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apremilast, Oral tablet, Oligoarthritis, PsA, Background therapy, Standard of care