A Study Exploring the Safety, Tolerability and Efficacy of a 4 Week Course of INCB018424 in Subjects With Active Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to understand the safety and tolerability of INCB018424 in patients with rheumatoid arthritis

Official Title
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A Double-blind, Placebo-controlled Study Exploring the Safety, Tolerability and Efficacy of a 4 Week Course of INCB018424 in Subjects With Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: INCB018424
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of rheumatoid arthritis Patients receiving methotrexate must be treated with for at least 6 months and receiving a stable weekly dose between 10 and 25 mg for at least 8 consecutive weeks prior to study entry. Exclusion Criteria: Patients who have taken the following drugs within the timeframe below: Leflunomide, infliximab, etanercept, adalimumab, abatacept, or other biological therapies (except rituximab) - Within 12 weeks prior to the first dose of study medication; Rituximab - Within 12 months prior to the first dose of study medication; Disease-modifying anti-rheumatic drugs (DMARDs) or other anti-rheumatic therapies not specified above including but not limited to: gold, penicillamine, dapsone, azathioprine, 6-mercaptopurine, chlorambucil, cyclophosphamide, cyclosporin, mycophenolate mofetil - Within 12 weeks prior to the first dose of study medication; Treatment with any investigational medication within 12 weeks prior to the first dose of study medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Treatment Group A<br>INCB018424 15 mg twice daily (BID) or matching placebo | Drug: INCB018424<br> <br> |
| Experimental: Cohort 2: Treatment Group B<br>INCB018424 5 mg BID or matching placebo | Drug: INCB018424<br> <br> |
| Experimental: Cohort 2: Treatment Group C<br>INCB018424 25 mg BID or matching placebo | Drug: INCB018424<br> <br> |
| Experimental: Cohort 2: Treatment Group D<br>INCB018424 50 mg once daily (QD) or matching placebo | Drug: INCB018424<br> <br> |
| Placebo Comparator: Placebo<br>Matching placebo, oral | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Improvement | The ACR 20 is defined as ≥ 20% improvement in tender joint count plus ≥ 20% improvement in swollen joint count plus ≥ 20% improvement in 3 of the following 5 criteria: subject's assessment of pain, Subject's global assessment of disease activity (PGA), Physician's global assessment of disease activity (PHGA), subject's self-assessed disability Health Assessment Questionnaire (HAQ), and Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), whichever shows the greatest change. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects Achieving ACR 50 Improvement | The ACR 50 is defined as ≥ 50% improvement in tender joint count plus ≥ 50% improvement in swollen joint count plus ≥50% improvement in 3 of the following 5 criteria: subject's assessment of pain, PGA, PHGA, subject's self-assessed disability HAQ, and ESR or CRP, whichever shows the greatest change. | Day 28 | 
| The Percentage of Subjects Achieving ACR 70 Improvement | The ACR 70 is defined as ≥ 70% improvement in tender joint count plus ≥ 70% improvement in swollen joint count plus ≥ 70% improvement in 3 of the following 5 criteria: subject's assessment of pain, PGA, PHGA, subject's self-assessed disability HAQ, and ESR or CRP, whichever shows the greatest change. | Day 28 | 
| Change From Baseline in Disease Activity Score 28 (DAS 28) ESR Score | Calculation of the disease activity score 28 (DAS 28) score was based on the tender joint count, plus swollen joint count, plus PGA, plus Erythrocyte sedimentation rate (ESR). The DAS28-ESR is expressed as units on a scale with the minimum score=0 (best) to maximum score=10 (worst). Remission was defined as DAS28-ESR <2.6. The mean change from baseline (which represent decreases in the DAS 28 ESR scores) are shown as positive numbers in these analyses. | Baseline, Day 28 | 
| Change From Baseline in Disease Activity Score 28 (DAS 28) CRP Score | Calculation of the disease activity score 28 (DAS 28) score was based on the tender joint count, plus swollen joint count, plus PGA, plus C-reactive protein (CRP). A higher score indicated more disease activity. The mean change from baseline (which represent decreases in the DAS 28 CRP scores) are shown as positive numbers in these analyses. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission). | Baseline, Day 28 | 
| Percentage of Subjects Who Achieved DAS 28 ESR Low Disease | Subjects who achieved low disease activity based on the DAS 28 ESR (score <3.2). Subjects who achieved low disease activity were classified as responders in this analysis. | Day 28 | 
| Percentage of Subjects Who Achieved DAS 28 CRP Low Disease | Subjects who achieved low disease activity based on the DAS 28 CRP (score <3.2). Subjects who achieved low disease activity were classified as responders in this analysis. | Day 28 | 
| Percentage of Subjects Who Achieved DAS 28 ESR Inactive Disease | Subjects who achieved inactive disease based on the DAS 28 ESR (score <2.6). Subjects who achieved low disease activity were classified as responders in this analysis. | Day 28 | 
| Percentage of Subjects Who Achieved DAS 28 CRP Inactive Disease | Subjects who achieved inactive disease based on DAS 28 CRP (score <2.6). Subjects who achieved low disease activity were classified as responders in this analysis. | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis