A Double-Blind, Randomized, Multicenter, Phase II Study of the Safety and Efficacy of Two Rituximab Regimens in Subjects With Moderate to Severe Active Rheumatoid Arthritis Receiving Stable Doses of Methotrexate
Overview
- Phase
- Phase 2
- Intervention
- folate
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Genentech, Inc.
- Enrollment
- 42
- Primary Endpoint
- Number of Participants With Either an Infection or a Grade III or IV Adverse Event (National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI CTCAE], Version 3.0)
- Status
- Completed
- Last Updated
- 14 years ago
Overview
Brief Summary
This was a Phase II, randomized, double-blind, multicenter study designed to evaluate the safety and efficacy of rituximab, administered at two different regimens for 2 years, in patients with moderate to severe active rheumatoid arthritis (RA) receiving stable doses of methotrexate (MTX).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of RA for at least 6 months.
- •Inadequate response to MTX
- •Use of folate
- •If female and of childbearing potential, have a negative serum pregnancy test within 8 weeks prior to first rituximab infusion
Exclusion Criteria
- •Diagnosis of juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis) and/or RA before age 16
- •Any surgical procedure, including bone/joint surgery or planned surgery within 8 weeks prior to screening or within 16 weeks of Week 1 (Day 1) visit
- •Inflammatory arthritis other than RA (e.g., inflammatory bowel disease, systemic lupus erythematosus (SLE), or psoriatic arthritis)
- •Functional Class IV as defined by the American College of Rheumatology (ACR) classification of functional status in RA
- •Use of disease-modifying anti-rheumatic drugs (DMARDs) other than MTX within 4 weeks prior to randomization (8 weeks prior for infliximab, adalimumab, or leflunomide)
- •Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
- •Previous treatment with Tysabri\<TM\> (natalizumab)
- •Previous treatment with rituximab
- •Previous treatment with any cell-depleting therapies, including investigational agents
- •Treatment with IV \&-globulin or Prosorba(R) Column within the previous 6 months
Arms & Interventions
Arm A: 500 mg Rituximab
Rituximab: 1000 mg intravenous (IV) on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Intervention: folate
Arm A: 500 mg Rituximab
Rituximab: 1000 mg intravenous (IV) on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Intervention: methotrexate
Arm A: 500 mg Rituximab
Rituximab: 1000 mg intravenous (IV) on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Intervention: methylprednisolone
Arm A: 500 mg Rituximab
Rituximab: 1000 mg intravenous (IV) on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Intervention: Rituximab
Arm B: 1000 mg Rituximab
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12.) For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Intervention: folate
Arm B: 1000 mg Rituximab
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12.) For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Intervention: methotrexate
Arm B: 1000 mg Rituximab
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12.) For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Intervention: methylprednisolone
Arm B: 1000 mg Rituximab
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12.) For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Intervention: Placebo
Arm B: 1000 mg Rituximab
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12.) For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Intervention: Rituximab
Outcomes
Primary Outcomes
Number of Participants With Either an Infection or a Grade III or IV Adverse Event (National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI CTCAE], Version 3.0)
Time Frame: 24 months
A Grade III Adverse Event (AE) is severe; defined as considerable interference with the subject's daily activities, medical intervention/therapy required and hospitalization possible. A Grade IV AE is life-threatening; defined as extreme limitation in activity, significant medical intervention/therapy required, hospitalization probable. Because of the small sample size and the small number of subjects who completed Week 104, the analysis were limited to descriptive statistics only.
Secondary Outcomes
- Change From Baseline in Short Form 36 (SF 36) Summary and Subscale Scores(Baseline, 24 Months)
- Number of Participants With American College of Rheumatology Responses (ACR20, ACR50, and ACR70)(Baseline, 24 months)
- Number of Participants With American College of Rheumatology (ACR) Major Clinical Response and/or Remission(24 months)
- Change From Baseline in Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F)(Baseline, 24 Months)
- Number of Participants With European League Against Rheumatism (EULAR) Response and Remission Using Disease Activity Score 28-4 (DAS28-4)C-reactive Protein (CRP)(Baseline, 24 months)
- Change From Baseline in Disease Activity Score 28-4 C-reactive Protein (DAS28-4(CRP))(Baseline, 24 months)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)(Baseline, 24 Months)
- DAS28-4 Erythrocyte Sedimentation Rate(ESR)(24 Months)
- Change From Baseline in Rheumatoid Factor (RF)(Baseline, 24 Months)
- Change From Baseline in Cyclic Citrullinated Peptide (CCP) Antibodies/Cytokines(Baseline, 24 Months)