A Study of CNTO 136 (Sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously, in Patients With Active Rheumatoid Arthritis Despite Anti-TNF-Alpha Therapy (SIRROUND-T)

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 68 weeks, which includes 52 weeks of
treatment. Participants who complete participation in the study will be eligible for
inclusion into the long term extension 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 24, 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 4 of 68 tender joints and 4 of 66
swollen joints, at screening and at baseline

- Have had anti-tumor necrosis factor (TNF)-alpha therapy and were unresponsive by 1 of
the following 2 reasons: Lack of benefit to at least 1 anti-TNF-alpha biologic
therapy, as assessed by the treating physician, after at least 12 weeks of etanercept,
yisaipu, adalimumab, golimumab, or certolizumab pegol therapy and/or at least a
14-week dosage regimen (ie, at least 4 doses) of infliximab; Intolerance to at least 2
anti-TNF-alpha biologic therapies, as assessed by the treating physician, to
etanercept, yisaipu, adalimumab, golimumab, certolizumab pegol, or infliximab or have
documented intolerance to an anti-TNF-alpha agent as described above that precludes
further administration of anti-TNF-alpha agents

- 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 disease modifying antirheumatic drugs (DMARDs) such as
methotrexate (MTX), sulfasalazine (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

- C-reactive protein (CRP) 8.00 mg/L or more or erythrocyte sedimentation rate (ESR) 28
mm/hr or more at screening

Exclusion Criteria:

- Has received infliximab, infliximab biosimilar, or golimumab intravenous (IV) within 8
weeks of the first study agent administration

- Has received subcutaneously (SC) golimumab, adalimumab, or certolizumab pegol within 6
weeks of the first study agent administration

- Has received etanercept or yisaipu within 4 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 tocilizumab within 8 weeks of the first study agent administration

- 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 1 week of first study agent administration

- Has used abatacept or any other biologic therapy for the treatment of RA within 8
weeks of the first study agent administration

- Has received intra-articular (IA), intramuscular (IM), 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

- 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