A Study of the Effectiveness and Safety of CNTO 136 in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy

• The primary outcomes in Part A are the safety and the effectiveness of CNTO 136 as measured by the Disease Activity Score (DAS) 28 response at Week 12. The primary outcome in Part B is the American College of Rheumatology (ACR) 50 response at Week 12
  

• Secondary outcomes include change from baseline in Disease Activity Score (DAS) 28 response at Week 12, serum CNTO 136 concentrations, and percent change from baseline in serum C-reactive protein at Week 2.
  

Increased levels of interleukin-6 (IL-6) contribute to the arthritis symptoms and to the full body complications of rheumatoid arthritis (RA) patients. CNTO 136 is a protein (antibody) that blocks IL-6. This is a multicenter, randomized (patients are assigned different treatments based on chance), double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), placebo-controlled, parallel group study comparing safety and efficacy of subcutaneous (SC) injections every 2 or 4 weeks of CNTO 136 versus placebo in patients with active RA who have an inadequate response to methotrexate. The study hypothesis is that CNTO 136 SC injections will be more effective than placebo in terms of reducing the signs and symptoms of RA at Week 12, while maintaining an acceptable safety profile. The total duration of treatment with active drug is approximately 10 weeks. All patients are to remain on a stable, weekly dose of methotrexate during the study. Patients who complete the screening period will be randomized to CNTO 136 injections or placebo injections at the start of the study (Week 0). At Week 12, patients will switch treatment to CNTO 136 if they were on placebo, or switch to placebo if they were first on CNTO 136, and they are to continue on these treatments through Week 22. For the patients who started on CNTO 136 and switched to placebo, this 12 weeks of followup is designed to evaluate how long the effect of CNTO 136 can last after the last injection of active CNTO 136. There is a 16 week followup period after Week 22 for study visits and assessments but no further injections. This is a 2-part study in that, first, the dose of CNTO 136 100 mg SC administered every 2 weeks will be compared to placebo injections in 40 patients with active RA despite methotrexate (Part A). If, in Part A, CNTO 136 100mg SC every 2 weeks is found to be an effective treatment, then in the second part (Part B), treatment with CNTO 136 100 mg SC every 4 weeks, 50 mg SC every 4 weeks, and 25 mg SC every 4 weeks will also be evaluated for their effectiveness compared to placebo injections in patients with active RA despite methotrexate. Assessments during the study will include questionnaires, physical exams, evaluation of joint swelling and tenderness, blood samples for safety, for measuring levels of CNTO 136 in the blood and the body's response to CNTO 136, urine samples, and a few electrocardiograms (ECG). In Part A, CNTO 136 100mg, or placebo injections SC every 2 weeks from Week 0 to Week 10, then switching at Week 12 to placebo or CNTO 136 SC every 2 weeks, respectively, through Week 22. In Part B of the study, from Weeks 0 to 10, CNTO 136 100 mg every 2 weeks, 100 mg, 50 mg, or 25 mg every 4 weeks, or placebo injections SC every 2 weeks, then switching at Week 12 to placebo or CNTO 136 100 mg SC every 2 weeks, respectively, through Week 22. Duration of participation: approximately 42 weeks