Psoriatic Arthritis Dose Ranging Study for BMS-945429 in Subjects Who Are Not Responding to NSAIDs or Non-biologic Disease Modifying Anti-rheumatic Drugs (DMARDs) Therapy

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety, efficacy and dose response of BMS-945429 in subjects with active Psoriatic Arthritis and an inadequate response to Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-biologic Disease modifying anti-rheumatic drugs (DMARDs).

Official Title
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A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging, Multi-Center Study to Evaluate the Efficacy and Safety of BMS-945429 Subcutaneous Injection in Adults With Active Psoriatic Arthritis

Conditions
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Arthritis, Psoriatic

Intervention / Treatment
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* Biological: Placebo matching BMS-945429
* Biological: BMS-945429
* Biological: BMS-945429
* Biological: BMS-945429


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be on a stable background Methotrexate (MTX) therapy prior to Day1/Randomization. Subjects must have taken MTX for at least 3 months at a dose ≥ 15 mg/week to a maximum weekly dose of ≤ 25 mg/week, and be at a stable dose for 4 weeks prior to randomization (Day 1). Methotrexate dose ≥ 15 mg/week that was not efficacious and that was decreased due to toxicity as low as 10 mg/week is allowed Inadequate response to NSAID and/or non-biologic DMARD Minimum of 3 swollen and 3 tender joints Active psoriatic skin lesions over minimum 3% body surface area high sensitivity C-reactive protein (hsCRP) ≥ 0.3 mg/dL Exclusion Criteria: Previously received or currently receiving concomitant biologic therapy

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 |
| --- | --- |
| Placebo Comparator: PBO: Placebo matching BMS-945429<br> | Biological: Placebo matching BMS-945429<br>* Injection, Subcutaneous, 0 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label<br>|
| Experimental: BMS-945429 (25mg)<br> | Biological: BMS-945429<br>* Injection, Subcutaneous, 25 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label<br>|
| Experimental: BMS-945429 (100mg)<br> | Biological: BMS-945429<br>* Injection, Subcutaneous, 100 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label<br>|
| Experimental: BMS-945429 (200mg)<br> | Biological: BMS-945429<br>* Injection, Subcutaneous, 200 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants Achieving American College of Rheumatology Criteria 20% Response Rate (ACR20) | The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). | At 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response Rate | To calculate the PASI score, the psoriasis plaques found on each body region are graded for their combined redness, thickness, and scaliness. The severity of the plaques in each region is graded on a 0 to 4 scale, with 0 meaning no involvement and 4 meaning severe involvement. Next, the amount of surface area on each body region that is covered by the plaques is calculated. The total surface area affected by psoriasis is graded from 0 to 6, with 0 meaning no involvement and 6 meaning greater than 90 percent of the region covered in plaques. These grades are then fed into an equation to determine the patient's PASI score. The PASI score then is used as a clinical assessment of the patient's psoriasis involvement. A person free of psoriasis has a score of 0 and the score could be as high as 72. PASI 75 means that the person's PASI score dropped by 75 percent as a result of the psoriasis treatment. | Week 16 and Week 24 | 
| Percent of Participants Achieving ACR50 and ACR70 Response Rate | The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). | Week 16 and Week 24 | 
| Percent of Participants Achieving ACR20 Response Rate at Week 24 | The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). | Week 24 | 
| Percent of Participants Achieving a Health Assessment Questionnaire (HAQ) Response | For each item, there is a four-level difficulty scale that is scored from 0 to 3, representing normal (no difficulty) (0), some difficulty (1), much difficulty (2), and unable to do (3). There are 20 questions in eight categories of functioning - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The highest component score in each category determines the score for the category, unless aids or devices are required. Dependence on equipment or physical assistance increases a lower score to the level of 2 to more accurately represent underlying disability. The eight category scores are averaged into an overall HAQ score on a scale from zero (no disability) to three (completely disabled). The scale is not truly continuous but has 25 possible values (i.e., 0, 0.125, 0.250, 0.375 … 3). Response is measured by a reduction of at least 0.3 unit from baseline in HAQ index. | Weeks 16 and Week 24 | 
| Mean Change From Baseline at Week 16 in Short Form (36) [SF-36] Scores | The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100. Higher scores indicate better health status. | Baseline and Week 16 | 
| Mean Change From Baseline at Week 24 in SF-36 Scores | The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100. Higher scores indicate better health status. | Baseline and Week 24 | 
| Number of Participants With Anti-clazakizumab Antibodies |  | Up to 24 weeks |