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)
Condition: Arthritis, Rheumatoid
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Placebo; Placebo; Sirukumab; Sirukumab; Sirukumab
Intervention description: Form=solution for injection, route=subcutaneous use; every 2 weeks from Week 0 through Week 22.; Form=solution for injection, route=subcutaneous use; Weeks 2, 6, and every 4 weeks through Week 52.; Type=exact, unit=mg, number=50 or 100, form=solution for injection, route=subcutaneous use; every 2 weeks for 100 mg and every 4 weeks for 50 mg, Week 23 through Week 52.; Type=exact, unit=mg, number=100, form=solution for injection, route=subcutaneous use; Weeks 0, 2, and every 2 weeks through Week 52.; Type=exact, unit=mg, number=50, form=solution for injection, route=subcutaneous use; Weeks 0, 4, and every 4 weeks through Week 52.
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 878.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Arthritis, Rheumatoid; Active rheumatoid arthritis despite anti-TNF-alpha therapy; Sirukumab; Human Anti-IL-6 monoclonal antibody

Summary:

      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) in patients with active RA who are
      unresponsive or intolerant to treatment with anti-TNF-alpha agents.
    

Eligibility criteria:

        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