A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFalpha Monoclonal Antibody, Administered Intravenously, in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Overview
- Phase
- Phase 3
- Intervention
- Golimumab
- Conditions
- Arthritis, Rheumatoid
- Sponsor
- Centocor, Inc.
- Enrollment
- 592
- Primary Endpoint
- Proportion of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
The purpose of this study is to evaluate clinical effectiveness and safety of golimumab with methotrexate (MTX) in the treatment of rheumatoid arthritis (RA) when compared to MTX alone.
Detailed Description
This is a randomized (study medication is assigned by chance), double-blind (neither physician nor participants knows the treatment that the participant receives), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study), multicenter, 2-arm (2 groups) study of golimumab in participants with active RA despite concurrent MTX therapy. Approximately 564 participants will be randomly allocated to 1 of 2 treatment groups in a 2:1 ratio ie, Group 1(approximately 376 participants will receive golimumab + MTX) and Group 2 (approximately 188 participants will receive MTX + placebo). Total duration of study for each participant is 112 weeks. Safety will be evaluated by assessment of adverse events, tuberculosis testing and blood testing.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of rheumatoid arthritis (RA) for at least 3 months prior to screening
- •Have been treated with and tolerated methotrexate (MTX) at a dose of at least 15 mg/week for at least 3 months prior to screening, and have been on a stable MTX dose of 15 mg/week to 25 mg/week for at least 4 weeks prior to screening
- •Have an active RA, as defined by disease activity with at least 6 swollen and 6 tender joints, at the time of screening and at baseline
- •C-Reactive Protein greater than or equal to 1.0 mg/dL at screening
- •No history of latent or active tuberculosis prior to screening
Exclusion Criteria
- •Other inflammatory diseases, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, or lyme disease
- •Treated with disease modifying agents (other than methotrexate)/systemic immunosuppressives (eg, D-penicillamine, hydroxychloroquine, chloroquine, oral or parenteral gold, sulfasalazine, leflunomide, azathioprine, cyclosporine, mycophenolate mofetil) during the 4 weeks prior to first administration of study agent
- •Received intra-articular (in the joint), intramuscular (in the muscle), or intravenous corticosteroids, including adrenocorticotropic hormone, during the 4 weeks prior to first administration of study agent
- •Known allergy to human immunoglobulin proteins or other components of golimumab
- •Received any commercial or investigational anti-tumor necrosis factor alpha therapy such as but not exclusively infliximab, golimumab, adalimumab or etanercept
Arms & Interventions
Group I: Placebo + Methotrexate (MTX)
Participants will receive placebo at Weeks 0, 4, 12, and 16. Participants will cross over to golimumab at Week 24, and receive administrations at Weeks 24, 28, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will be eligible for early escape (receive golimumab) at Week 16 if they demonstrate a less than 10 percent improvement in both tender and swollen joint count. These participants will receive golimumab at Weeks 16, 20, and every 8 weeks thereafter.
Intervention: Golimumab
Group I: Placebo + Methotrexate (MTX)
Participants will receive placebo at Weeks 0, 4, 12, and 16. Participants will cross over to golimumab at Week 24, and receive administrations at Weeks 24, 28, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will be eligible for early escape (receive golimumab) at Week 16 if they demonstrate a less than 10 percent improvement in both tender and swollen joint count. These participants will receive golimumab at Weeks 16, 20, and every 8 weeks thereafter.
Intervention: Placebo
Group I: Placebo + Methotrexate (MTX)
Participants will receive placebo at Weeks 0, 4, 12, and 16. Participants will cross over to golimumab at Week 24, and receive administrations at Weeks 24, 28, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will be eligible for early escape (receive golimumab) at Week 16 if they demonstrate a less than 10 percent improvement in both tender and swollen joint count. These participants will receive golimumab at Weeks 16, 20, and every 8 weeks thereafter.
Intervention: methotrexate (MTX)
Group II: Golimumab + Methotrexate (MTX)
Participants will receive golimumab at Weeks 0, 4, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will receive a placebo infusion at Week 16 and Week 24 to maintain the blind.
Intervention: Golimumab
Group II: Golimumab + Methotrexate (MTX)
Participants will receive golimumab at Weeks 0, 4, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will receive a placebo infusion at Week 16 and Week 24 to maintain the blind.
Intervention: Placebo
Group II: Golimumab + Methotrexate (MTX)
Participants will receive golimumab at Weeks 0, 4, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will receive a placebo infusion at Week 16 and Week 24 to maintain the blind.
Intervention: methotrexate (MTX)
Outcomes
Primary Outcomes
Proportion of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14
Time Frame: Week 14
An ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in: 1. Swollen (66 joints) and tender (68 joints) joint counts; 2. greater than or equal to 20 percentage improvement in at least 3 of the following 5 assessments: a. Participant's assessment of pain by Visual Analog Scale (VAS), (0 \[no pain\] to 10 \[worst pain\]) b. Participant's global assessment of disease activity by VAS c. Physician's global assessment of disease activity by VAS d. Participant's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C-reactive protein.
Secondary Outcomes
- Proportion of Participants With Moderate or Good Response in Disease Activity Index Score 28 (DAS28) Using C-reactive Protein (CRP) at Week 14(Week 14)
- Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 14(Week 14)
- Proportion of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24(Week 24)
- Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 24.(Week 24)