Conditions: Arthritis, Rheumatoid
Keywords: Arthritis, Rheumatoid Rheumatoid Arthritis Active Rheumatoid Arthritis CNTO 136 Interleukin-6 Anti-interleukin-6 monoclonal antibody Methotrexate Placebo
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 187
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the effectiveness and safety of subcutaneous (under the skin) administration of anti-interleukin-6 monoclonal antibody (CNTO 136) in reducing signs and symptoms of participants with active rheumatoid arthritis (RA) with methotrexate (MTX) therapy.

Detailed description:
This is a multicenter, double-blind (neither physician nor participants knows the treatment that the participant receives), randomized (study medication is assigned by chance), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study) study. This study will be conducted in 2 parts (Part A and Part B). Each part consists of 3 phases: screening (approximately 1 month prior to the start of study medication), treatment phase (Part A: 22 weeks and Part B: 24 weeks), and follow-up phase (approximately 4 months after the last administration of study medication). In Part A, participants will be randomly assigned to 2 groups to receive CNTO 136 100 mg and placebo for 22 weeks. All participants in Part A, will be crossed over at Week 12 from placebo to CNTO 136 (for Group 1) and from CNTO 136 to placebo (for Group 2). In Part B, participants will be randomly assigned to 5 groups to receive placebo and/or 1 of 3 doses of CNTO 136 (100mg, 50mg or 25mg) for 24 weeks. Participants in Part B, Group 1 will be crossed over at Week 12 from placebo to CNTO 136. All participants should be maintained on a stable dose of MTX for at least 6 weeks prior to the start of study medication through Week 24. Safety will be evaluated by the assessment of adverse events, vital signs, clinical findings, 12-lead electrocardiogram, and clinical laboratory tests which will be monitored throughout the study. The total duration of study participation for a participant will be approximately 42 weeks.

Arms:
arm 1: Participants will receive placebo (Week 0 to Week 10) and later CNTO 136 100 mg (Week 12 to Week 22) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24. arm 2: Participants will receive CNTO 136 100 mg (Week 0 to Week 10) and later placebo (Week 12 to Week 22) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24. arm 3: Participants will receive placebo (Week 0 to Week 10) and later CNTO 136 100 mg (Week 12 to Week 24) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24. arm 4: Participants will receive CNTO 136 100 mg (Week 0 to Week 24) every 2 weeks. Stable dose of methotrexate will be maintained through Week 24. arm 5: Participants will receive CNTO 136 100 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6, 10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24. arm 6: Participants will receive CNTO 136 50 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6,10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24. arm 7: Participants will receive CNTO 136 25 mg (Week 0 to Week 24) every 4 weeks and placebo at interim visits (Weeks 2, 6,10, 14, 18, and 22). Stable dose of methotrexate will be maintained through Week 24.

Interventions: intervention 1: CNTO 136 100 mg intervention 2: CNTO 136 50 mg intervention 3: CNTO 136 25 mg intervention 4: Placebo intervention 5: Methotrexate
Intervention descriptions: intervention 1: CNTO 136 100 mg will be administered subcutaneously (under the skin) every 2 or 4 weeks as per the appropriate randomized arm. intervention 2: CNTO 136 50 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24. intervention 3: CNTO 136 25 mg will be administered subcutaneously every 4 weeks from Week 0 to Week 24. intervention 4: Placebo will be adminstered subcutaneously as per the appropriate randomized arm. intervention 5: Stable dose of methotrexate will be maintained through Week 24.

Protocol document: