An Efficacy And Safety Study of CNTO 6785 In Participants With Active Rheumatoid Arthritis Despite Methotrexate Therapy

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of CNTO6785 in participants with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.

Detailed Description
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This is a randomized (participants are assigned to treatment by chance), double-blind (participants and study personnel will not know which treatments are being given), placebo-controlled (a placebo appears identical to a study drug but has no active ingredients), multicenter study. The study will consist of 3 phases: a screening phase, a treatment phase, and a follow-up phase. Approximately 250 participants with active RA despite MTX therapy will be randomly assigned to receive placebo or CNTO 6785 during the double-blind treatment phase. The maximum period of active treatment will be 28 weeks. The maximum duration of study participation will be 44 weeks. Participant safety will be monitored throughout the study.

Official Title
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A Randomized, Placebo-controlled Double-blind, Multicenter, Phase 2 Dose Ranging Study To Assess The Efficacy And Safety of CNTO 6785 In Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Placebo
* Drug: CNTO 6785 200 mg
* Drug: CNTO 6785 200 mg
* Drug: CNTO 6785 100 mg
* Drug: CNTO 6785 50 mg
* Drug: CNTO 6785 15 mg
* Drug: Methotrexate (MTX)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the American Rheumatism Association) and have had RA for at least 6 months prior to the date of signing the informed consent at screening Have active RA defined study as persistent disease activity with both of the following criteria: at least 6 swollen and 6 tender joints using a 66/68 joint count at the time of screening and at baseline; and serum C-reactive protein (CRP) ≥ 0.8 mg/dL at screening or erythrocyte sedimentation rate (ESR) ≥ 28 mm in the first hour at screening or baseline Have been treated with and tolerated methotrexate (MTX) treatment at dosages from 7.5 to 25 mg/week, inclusive, for a minimum of 6 months prior to screening and must have a stable MTX dose for a minimum of 6 weeks prior to the first dosing with study agent Exclusion Criteria: Has inflammatory diseases other than RA, that might confound the evaluation of the benefit of study agent therapy Has a diagnosis of fibromyalgia Has a recent history (within 12 months prior to screening) of uncontrolled, chronic disease including, but not limited to, pulmonary, psychiatric, and metabolic disturbances, cardiovascular, endocrine, neurological, hepatic, gastrointestinal, renal, hematological, or urological diseases that the investigator believes are clinically significant At screening, the results of laboratory tests must meet protocol-specified criteria Has ever received any approved or investigational biologic agent for a rheumatic indication

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo/CNTO 6785 200 mg+Methotrexate (MTX)<br> | Drug: Placebo<br>* Placebo subcutaneous injections (SC) every 4 weeks through Week 12<br>Drug: CNTO 6785 200 mg<br>* CNTO 6785 200 mg SC every 4 weeks from Week 16 through Week 28<br>Drug: Methotrexate (MTX)<br>* MTX at the same stable dose through Week 32, that participants were receiving prior to screening.<br>|
| Experimental: CNTO 6785 200 mg+MTX<br> | Drug: CNTO 6785 200 mg<br>* CNTO 6785 200 mg SC every 4 weeks through Week 28<br>Drug: Methotrexate (MTX)<br>* MTX at the same stable dose through Week 32, that participants were receiving prior to screening.<br>|
| Experimental: CNTO 6785 100 mg+MTX<br> | Drug: CNTO 6785 100 mg<br>* CNTO 6785 100 mg SC every 4 weeks through Week 28<br>Drug: Methotrexate (MTX)<br>* MTX at the same stable dose through Week 32, that participants were receiving prior to screening.<br>|
| Experimental: CNTO 6785 50 mg+MTX<br> | Drug: CNTO 6785 50 mg<br>* CNTO 6785 50 mg SC every 4 weeks through Week 28<br>Drug: Methotrexate (MTX)<br>* MTX at the same stable dose through Week 32, that participants were receiving prior to screening.<br>|
| Experimental: CNTO 6785 15 mg+MTX<br> | Drug: CNTO 6785 15 mg<br>* CNTO 6785 15 mg SC every 4 weeks through Week 28<br>Drug: Methotrexate (MTX)<br>* MTX at the same stable dose through Week 32, that participants were receiving prior to screening.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants who achieve an ACR 20 response at Week 16 | American College of Rheumatology (ACR) 20 response is a >=20% improvement in rheumatoid arthritis (RA) symptoms. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in DAS28 (CRP) at Week 16 | DAS28 (using CRP [C-reactive protein]) is a measure of tender and swollen joints and the patient's assessment of disease activity. | Baseline to Week 16 | 
| The proportion of participants who achieve ACR 50 response at Week 16 | American College of Rheumatology (ACR) 50 response is a >=50% improvement in rheumatoid arthritis (RA) symptoms. | Week 16 | 
| The proportion of participants who achieve ACR 20 response through Week 32 |  | Week 32 | 
| The proportion of participants who achieve ACR 50 response through Week 32 |  | Week 32 | 
| The proportion of participants who achieve ACR 70 response through Week 32 | American College of Rheumatology (ACR) 70 response is a >=70% improvement in rheumatoid arthritis (RA) symptoms. | Week 32 | 
| Change from baseline of DAS28 (CRP) through Week 32 |  | Baseline to Week 32 | 
| The proportion of participants with DAS28 (CRP) response through Week 32 | DAS28 (using CRP [C-reactive protein]) response is improvement from baseline, with >1.2 indicating a good or moderate response and <=0.6 indicating no response. | Week 32 | 
| The proportion of participants with DAS28 (CRP) remission at Week 16 | DAS28 (using CRP [C-reactive protein]) remission is defined as a value of <2.6 on the Disease Activity Index, a measure of tender and swollen joints and the patient's assessment of disease activity. | Week 16 | 
| The proportion of participants with DAS28 (CRP) remission at Week 32 |  | Week 32 | 
| Change from baseline in DAS28 (ESR) at Week 16 | DAS28 (using erythrocyte sedimentation rate) is a measure of tender and swollen joints and the patient's assessment of disease activity. | Baseline to Week 16 | 
| Change from baseline in DAS28 (ESR) at Week 32 |  | Baseline to Week 32 | 
| Change from baseline in HAQ-DI score through Week 32 | The Health Assessment Questionnaire-Disability Index (HAQ-DI) assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas, each scored from 0 (no difficulty) to 3 (inability to perform a task). | Baseline to Week 32 | 
| Change from baseline in SF-36 at Week 16 | The SF-36 is a medical outcome study health measure and consists of 8 multi-item scales that are scored from 0 to 100, with higher scores indicating better health. | Baseline to Week 16 | 
| Change from baseline in SF-36 at Week 32 |  | Baseline to Week 32 | 
| Change from baseline in CDAI at Week 16 | Clinical Disease Activity Index (CDAI) score is a derived score combining tender joints (28 joints), swollen joints (28 joints), Patient's Global Assessment of Disease Activity, and Physician's Global Assessments of Disease Activity. | Baseline to Week 16 | 
| Change from baseline in CDAI at Week 32 |  | Baseline to Week 32 | 
| Change from baseline in SDAI at Week 16 | The Simplified Disease Activity Index (SDAI) score is a derived score combining tender joints (28 joints), swollen joints (28 joints), Patient's Global Assessment of Disease Activity, Physician's Global Assessments of Disease Activity, and CRP. | Baseline to Week 16 | 
| Change from baseline in SDAI at Week 32 |  | Baseline to Week 32 | 
| The proportion of participants with SDAI-based ACR/EULAR remission at Week 16 | The Simplified Disease Activity Index (SDAI)-based ACR/EULAR (European League Against Rheumatism) remission is defined as a SDAI value of <=3.3 at a visit. | Week 16 | 
| The proportion of participants with SDAI-based ACR/EULAR remission at Week 32 |  | Week 32 | 
| The proportion of participants with Boolean-based ACR/EULAR remission at Week 16 | Boolean-based ACR/EULAR remission is achieved if all of the following 4 criteria at that visit are met: tender joint count (68 joints) <=1; swollen joint count (66 joints) <=1; CRP <=1 mg/dL; and Patient's Global Assessment of Disease Activity on VAS <=1 on a 0 to 10 scale. | Week 16 | 
| The proportion of participants with Boolean-based ACR/EULAR remission at Week 32 |  | Week 32 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Active rheumatoid arthritis despite methotrexate therapy, CNTO 6785, Methotrexate