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

Centocor Ortho Biotech

Status and phase: Completed; Phase 2

Conditions: Arthritis, Rheumatoid

Treatments: Drug: Methotrexate; Drug: CNTO 136 25 mg; Drug: Placebo; Drug: CNTO 136 50 mg; Drug: CNTO 136 100 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00718718

2007-006603-20 (EudraCT Number)

CR015214

C1377T04 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 187 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosed with rheumatoid arthritis (RA) for at least 4 months prior to screening
• Have been treated and having an inadequate response with the tolerated dose of methotrexate (MTX) (at least 15mg/week) for at least 4 months prior to screening. MTX doses of 10 or 12.5 mg/week are allowed if participant had intolerance of 15 mg/week
• MTX route of administration and dose (not to exceed 25 mg/week) should be stable for at least 6 weeks prior to the start of the study medication
• Have active RA as defined by persistent disease activity with at least 6 swollen and 6 tender joints, at the time of screening and baseline, and either anti-cyclic citrullinated peptide antibody-positive or rheumatoid factor positive at screening
• C-reactive protein greater than or equal to 1.0 mg/dL (10 mg/L)
• Agree to use one of the contraception methods defined in the protocol

Exclusion criteria

• Have inflammatory diseases other than RA that might confound the evaluation of the benefit of CNTO 136 therapy in arthritis
• Family history of/ have long QT syndrome; or a history of second or third-degree heart block
• Received systemic immunosuppressives or disease modifying antirheumatic drug other than MTX, sulfasalazine, hydroxychloroquine or chloroquine within 4 weeks prior to the start of study medication
• Received intra articular (into joints), intramuscular, or intravenous corticosteroids within 4 weeks prior to the start of study medication
• Positive human immunodeficiency virus test, hepatitis B or hepatitis C
• History of / have chronic or recurrent infectious disease, history of / active tuberculosis
• Have serious infection within 2 months prior to start of study medication

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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187 participants in 7 patient groups

Part A, Group 1

Experimental group

Description:

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.

Treatment:

Drug: CNTO 136 100 mg

Drug: Methotrexate

Drug: Placebo

Part A, Group 2

Experimental group

Description:

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.

Treatment:

Drug: CNTO 136 100 mg

Drug: Methotrexate

Drug: Placebo

Part B, Group 1

Experimental group

Description:

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.

Treatment:

Drug: CNTO 136 100 mg

Drug: Methotrexate

Drug: Placebo

Part B, Group 2

Experimental group

Description:

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.

Treatment:

Drug: CNTO 136 100 mg

Drug: Methotrexate

Part B, Group 3

Experimental group

Description:

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.

Treatment:

Drug: CNTO 136 100 mg

Drug: Methotrexate

Drug: Placebo

Part B, Group 4

Experimental group

Description:

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.

Treatment:

Drug: CNTO 136 50 mg

Drug: Methotrexate

Drug: Placebo

Part B, Group 5

Experimental group

Description:

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.

Treatment:

Drug: Methotrexate

Drug: CNTO 136 25 mg

Drug: Placebo