A Study of CNTO 136 (Sirukumab), Administered Subcutaneously, in Patients With Active Rheumatoid Arthritis Despite Disease-Modifying Antirheumatic Drug (DMARD) Therapy (SIRROUND-D)

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of CNTO 136 (Sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active Rheumatoid Arthritis Despite DMARD Therapy

The purpose of this study is to assess the efficacy of sirukumab as measured by the reduction of the signs and symptoms of rheumatoid arthritis (RA) and inhibition of radiographic progression in patients with active RA who are unresponsive to treatment with disease-modifying antirheumatic drugs (DMARD).

Patients will be randomly assigned to treatment groups, and they and study personnel will not know the identity of the treatments given. Some patients will receive a placebo, which resembles a medication, but does not contain an active substance. This helps to determine if the study agent is effective. Patients will receive placebo or sirukumab by injection under the skin. The expected duration of the study is 120 weeks, which includes 104 weeks of treatment. Participants who complete participation in the study will be eligible for inclusion into the long-term safety and efficacy study, if enrollment at a participating site is available to them. If they do not participate in the long-term study, they will continue into the safety follow-up for approximately 16 weeks. The placebo-controlled portion of the study is through Week 52, when placebo patients will cross over to one of two sirukumab dose regimens. Patient safety will be monitored throughout the study.

Inclusion Criteria:

• Have a diagnosis of rheumatoid arthritis (RA) for at least 3 months before screening
• Have moderately to severely active RA with at least 6 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline
• Have been unresponsive to single-agent or combination disease-modifying antirheumatic drugs (DMARD) therapy that includes methotrexate (MTX) or sulfasalazine (SSZ) due to lack of benefit after at least 12 weeks of DMARD, as assessed by the treating physician
• If using oral corticosteroids, must be on a stable dose equivalent to less than or equal to 10 mg/day of prednisone for at least 2 weeks prior to the first administration of study agent. If currently not using corticosteroids, must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent
• If using non nonsteroidal anti-inflammatory drug (NSAIDs) or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent
• If using non-biologic DMARD such as MTX, SSZ, hydroxychloroquine, chloroquine, or bucillamine, must be on a stable dose for at least 4 weeks prior to the first administration of study agent and should have no serious toxic side effects attributable to the DMARD

Exclusion Criteria:

• Has a history of intolerance to at least 2 or inadequate response to at least 1 anti-tumor necrosis factor alpha agent after 3 months of therapy
• Has received infliximab, golimumab, adalimumab, or certolizumab pegol within 3 months of the first study agent administration
• Has received etanercept or yisaipu within 6 weeks of the first study agent administration
• Has a history of intolerance to tocilizumab that precluded further treatment with it, or inadequate response to 3 months of tocilizumab (anti-IL-6 receptor) therapy
• Has used B-cell-depleting therapy (eg, rituximab) within 7 months of first study agent administration or have evidence during screening of abnormally low B cell level caused by previous B-cell depletion therapy
• Has used anakinra within 4 weeks of first study agent administration
• Has used any other biologic therapy for the treatment of RA within 3 months of the first study agent administration
• Has received intra-articular (IA), intramuscular (IM), or intravenous (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 have not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable. If a drug elimination procedure is performed during screening, the M1 metabolite should be measured and found to be undetectable
• Has a history of cyclophosphamide or cytotoxic agent use
• Has received cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 4 weeks of the first study agent administration
• Has received an investigational drug (including investigational vaccines) or used an investigational medical device within 3 months or 5 half lives, whichever is longer, before the first study agent administration