A Study Comparing Sirukumab (CNTO 136) Monotherapy With Adalimumab (HUMIRA®) Monotherapy in the Treatment of Active Rheumatoid Arthritis

Study Overview
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Brief Summary
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The primary objective is to investigate the efficacy of sirukumab monotherapy compared with adalimumab monotherapy in biologic naïve subjects with active rheumatoid arthritis who are intolerant to methotrexate, who are considered inappropriate for treatment with methotrexate or who are inadequate responders to methotrexate.

Detailed Description
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This is a randomized, double-blind, parallel-group, global, multicenter study of subcutaneous (SC) sirukumab monotherapy compared with adalimumab monotherapy in subjects with active rheumatoid arthritis. Approximately 510 subjects will be randomly assigned in a 1:1:1 ratio to receive treatment with adalimumab 40 mg SC every 2 weeks, sirukumab 100 mg SC every 2 weeks, or 50 mg SC every 4 weeks, with approximately 170 subjects per treatment group. At Week 16, subjects in all treatment groups who have < 20% improvement from baseline in both swollen and tender joint counts will qualify for early escape. The expected duration of the study is 68 weeks. This includes 52 weeks of treatment with study agent and 16 weeks of safety follow-up after the last study agent administration. The study will end when the last subject completes the last scheduled visit (Week 68 visit or completes the 16 week safety follow-up, whichever is later). Subject safety will be monitored through the end of the study.

Official Title
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A Multicenter, Randomized, Double-blind, Parallel Group Study of Sirukumab Monotherapy Compared With HUMIRA® Monotherapy Administered Subcutaneously, in Subjects With Active Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Biological: adalimumab 40 mg
* Biological: sirukumab 100 mg
* Biological: sirukumab 50 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of rheumatoid arthritis (RA) for at least 6 months before screening Have moderately to severely active RA with at least 8 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline Have previous or current treatment with methotrexate (MTX) and are considered intolerant to MTX, and/or are considered inappropriate for treatment with MTX, (including MTX-naïve subjects for whom it is inappropriate to administer MTX) and/or an inadequate responder to methotrexate Must not have received MTX or any other non-biologic DMARD including but not limited to sulfasalazine, hydroxychloroquine, chloroquine, and bucillamine for at least 2 weeks prior to the first administration of the study agent C-reactive protein >= 10.00 mg/L or erythrocyte sedimentation rate >=28 mm/hr at screening Exclusion Criteria: Has Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis Has ever received biologic therapy for RA, including but not limited to the following: TNF-alpha inhibitors, tocilizumab, rituximab, anakinra, abatacept Has ever used tofacitinib therapy or any other JAK inhibitor Has received intra-articular, intramuscular, or IV corticosteroids for RA, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent administration Has received leflunomide within 24 months before the first study agent administration and has not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable

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: Group 1 (adalimumab 40 mg)<br>Adalimumab 40 mg SC at Weeks 0, 2, and every 2 weeks through Week 52. At Week 16, subjects who have < 20% improvement from baseline in both swollen and tender joint counts will early escape in a blinded fashion and receive adalimumab 40 mg every week through Week 52. | Biological: adalimumab 40 mg<br>* SC injections<br>* Other names: HUMIRA®;|
| Experimental: Group 2 (sirukumab 100 mg)<br>Sirukumab 100 mg SC at Weeks 0, 2, and every 2 weeks through Week 52. Subjects may meet the early escape criteria at Week 16 (< 20% improvement from baseline in both swollen and tender joint counts) but no sirukumab dose adjustments will made for these subjects. However, these subjects will receive placebo injections every 2 weeks between the sirukumab injections (ie, subjects that early escape will receive a weekly injection of alternating sirukumab and placebo, to preserve the blind). | Biological: sirukumab 100 mg<br>* SC injections<br>* Other names: CNTO 136;Drug: Placebo<br>* SC injections<br>|
| Experimental: Group 3 (sirukumab 50 mg)<br>Sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52. Between sirukumab injections, placebo SC injections will be administered at Weeks 2, 6, and every 4 weeks through Week 50. At Week 16, subjects who have < 20% improvement from baseline in both swollen and tender joint counts will early escape in a blinded fashion and receive sirukumab 100 mg every 2 weeks through Week 52 and placebo injections every 2 weeks between the sirukumab injections (ie, subjects that early escape will receive a weekly injection of alternating sirukumab and placebo, to preserve the blind). | Biological: sirukumab 50 mg<br>* SC injections<br>* Other names: CNTO 136;Drug: Placebo<br>* SC injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Disease Activity Index Score 28 (DAS28) Erythrocyte Sedimentation Rate (ESR) at Week 24 | The Disease Activity Index Score 28 using ESR [DAS28 (ESR)] is a derived score combining tender joints (28 joints), swollen joints (28 joints), ESR, and Patient's Global Assessment of Disease Activity. The 28 joints evaluated for swelling and tenderness were shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of the upper right and upper left extremities as well as the knee joints of the lower right and lower left extremities. The DAS28-ESR is expressed on a score range of 0-10, with the minimum score= 0 (best) to maximum score= 10 (worst). | Baseline and Week 24 | 
| Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 | The ACR 50 Response is defined as greater than or equal to (>=) 50 percent (%) improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >= 50% improvement in 3 of following 5 assessments: subject's assessment of pain using Visual Analog Scale (VAS) (0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), subject's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP). | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Activity Index Score 28 (DAS28) Using Erythrocyte Sedimentation Rate (ESR) Remission at Week 24 | The Disease Activity Index Score 28 using ESR [DAS28 (ESR)] is a derived score combining tender joints (28 joints), swollen joints (28 joints), ESR, and Patient's Global Assessment of Disease Activity. The 28 joints evaluated for swelling and tenderness were shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of the upper right and upper left extremities as well as the knee joints of the lower right and lower left extremities. The DAS28-ESR is expressed on a score range of 0-10, with the minimum score= 0 (best) to maximum score= 10 (worst). The DAS28 (ESR) remission is defined as a DAS28 (ESR) value of less than 2.6 at a visit. | Week 24 | 
| Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 24 | The ACR 20 Response is defined as >= 20% improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20% improvement in 3 of following 5 assessments: subject's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), subject's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, subject's assessment of physical function measured by HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum CRP. | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, CNTO 136, Sirukumab, Adalimumab, HUMIRA®