A Dose Range Finding Study of JNJ-39758979 in Patients With Active Rheumatoid Arthritis Currently Treated With Methotrexate

Study Overview
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Brief Summary
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The purpose of the study is to assess the efficacy, safety and tolerability of JNJ-39758979 at doses of 10, 30, 100, and 300 mg/day compared with placebo (inactive medical substance) in patients with active rheumatoid arthritis despite concomitant treatment with methotrexate (MTX).

Detailed Description
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This is a double-blind (neither physician nor patient knows if the patient is receiving JNJ-39758979 or placebo), multicenter, randomized (patients are assigned to treatment by chance), placebo-controlled, dose range finding study of JNJ-39758979 in patients with stable methotrexate treatment through Week 24. The study will consist of 4 periods: a screening period, a 24-week placebo-controlled period, a 24-week extension period, and a 5-week safety follow-up period. The duration of participation in the study for an individual patient will be up to 59 weeks (including screening). All patients will be randomly assigned in a 1:1:1:1:1 ratio to receive placebo or JNJ-39758979 10 mg, 30 mg, 100 mg, or 300 mg once daily. At Week 24, all patients remaining in the placebo group will start to receive JNJ-39758979 300 mg/day. Safety assessments and evaluations to determine the efficacy of JNJ-39758979 to reduce the signs and symptoms of rheumatoid arthritis will be performed at study visits. The extension and safety follow-up periods of this study will continue through Week 53 in order to assess the safety and for maintenance of efficacy of patients.

Official Title
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A Phase 2b Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel-group, Dose Range Finding Study of JNJ-39758979 in Subjects With Active Rheumatoid Arthritis Despite Concomitant Methotrexate Therapy

Conditions
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Active Rheumatoid Arthritis; Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Placebo/JNJ-39758979 (300 mg/d)
* Drug: JNJ-39758979 (10 mg)
* Drug: JNJ-39758979 (30 mg)
* Drug: JNJ-39758979 (100 mg)
* Drug: JNJ-39758979 (300 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a diagnosis of rheumatoid arthritis (RA) for at least 6 months before screening. Positive test for either anti-cyclic citrullinated peptide (anti-CCP) antibody or rheumatoid factor (RF) in serum at screening. Has active RA defined as persistent disease activity with the following criteria: at least 6 swollen and 6 tender joints, and serum CRP ≥ 0.70 mg/dL at screening. Has been treated with and tolerated methotrexate (MTX) treatment at dosages of 10 to 25 mg/week for a minimum of 6 months prior to screening and must be on a stable dose for a minimum of 8 weeks prior to screening Must be post-menopausal or if pre-menopausal, must use an acceptable form of birth control Has completed at least 5 days of daily pain diary in the 10 days prior to randomization. Exclusion Criteria: Has inflammatory diseases other than RA, such as Lupus. Is currently receiving treatment for RA other than methotrexate, NSAIDS, or oral corticosteroids such as prednisone, or pain medicines. Has ever received any biologic agent for a rheumatic indication. Has current signs or symptoms of liver insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive, or uncontrolled. Has moderate or severe renal insufficiency Has a recent (within 2 months) serious infection Has had an opportunistic infection. Has had cancer within the past 5 years (except certain skin or cervical conditions) Has abused substances or alcohol within the past 2 years Has active Hepatitis B or C infection Has had active tuberculosis Has had exposure to tuberculosis without preventative treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo/JNJ-39758979 (300 mg/d)<br>* Form = tablet, route = oral adminstration placebo once daily from Week 0 to Week 24 followed by JNJ-39758979 300 mg once daily from Week 24 to Week 48.<br>* Other names: Inactive medical substance;|
| Experimental: JNJ-39758979 (10 mg/d)<br> | Drug: JNJ-39758979 (10 mg)<br>* Form = tablet, route = oral adminstration once daily up to 48 weeks<br>|
| Experimental: JNJ-39758979 (30 mg/d)<br> | Drug: JNJ-39758979 (30 mg)<br>* Form = tablet, route = oral adminstration once daily up to 48 weeks<br>|
| Experimental: JNJ-39758979 (100 mg/d)<br> | Drug: JNJ-39758979 (100 mg)<br>* Form = tablet, route = oral adminstration once daily up to 48 weeks<br>|
| Experimental: JNJ-39758979 (300 mg/d)<br> | Drug: JNJ-39758979 (300 mg)<br>* Form = tablet, route = oral adminstration once daily for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end point is change from baseline in Disease Activity Score 28 (DAS28) (CRP) at Week 12 |  | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in DAS28 (CRP) at Week 24 |  | Baseline, Week 24 | 
| Change from baseline in DAS28 (ESR) at Week 12 and Week 24 |  | Baseline, Week 12 and Week 24 | 
| DAS28 (CRP) response rates at Week 12 and Week 24 |  | Week 12, Week 24 | 
| DAS28 (ESR) response rates at Week 12 and Week 24 |  | Week 12, Week 24 | 
| DAS28 (CRP) remission rates at Week 12 and Week 24 |  | Week 12, Week 24 | 
| American college of rheumatology (ACR) 20/50/70 response rates at Week 12 and Week 24 |  | Week 12, Week 24 | 
| Hybrid ACR response at Week 12 and Week 24 |  | Week 12, Week 24 | 
| ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24 |  | Week 12, Week 24 | 
| Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24 |  | Baseline, Week 12, Week 24 | 
| Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24 |  | Baseline, Week 12, Week 24 | 
| Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24 |  | Week 12, Week 24 | 
| Change from baseline in HAQ-DI score at Week 12 and Week 24 |  | Baseline, Week 12 and Week 24 | 
| Percent change from baseline in ESR levels at Week 12 and Week 24 |  | Baseline, Week 12 and Week 24 | 
| Percent change from baseline in ACR components at Week 12 and Week 24 |  | Baseline, Week 12 and Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, Swollen and tender joints, Dose range finding study, Concurrent treatment with methotrexate