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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 主要终点
- 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)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Use of intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit
- •Receipt of a vaccine within 4 weeks prior to Day 1 infusion
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- •Primary or secondary immunodeficiency (history of or active)
- •Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, renal, hepatic, endocrine, gastrointestinal, or pulmonary disease, including any pulmonary or other condition that would preclude subject participation over the ensuing 2 years
- •Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds)
- •History of recurrent significant infection or any significant episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
- •History of significant cytopenias or other bone marrow disorders
- •History of cancer, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinoma of the skin that have been excised and cured)
- •Pregnant or nursing (breast feeding) women
- •Lack of peripheral venous access
- •Chronic daily use of narcotic analgesics
- •History of alcohol, drug, or chemical abuse within 6 months prior to screening
研究组 & 干预措施
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).
干预措施: folate (Drug)
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).
干预措施: methotrexate (Drug)
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).
干预措施: methylprednisolone (Drug)
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).
干预措施: Rituximab (Drug)
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).
干预措施: folate (Drug)
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).
干预措施: methotrexate (Drug)
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).
干预措施: methylprednisolone (Drug)
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).
干预措施: Placebo (Drug)
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).
干预措施: Rituximab (Drug)
结局指标
主要结局
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)
时间窗: 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.
次要结局
- 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)