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

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

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.

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.

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