A Randomized, Placebo-controlled, Double-blind, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Alpha Therapies
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 520
- 主要终点
- Number of Participants With American College of Rheumatology 20 Response at Week 24
研究概览
简要总结
This study will assess the safety and efficacy of rituximab combined with MTX in participants with active rheumatoid arthritis (RA) who have had an inadequate response to anti-Tumor Necrosis (TNF) alpha therapy. The anticipated time in the study is up to 2 years and the target sample size is 500 participants. Eligible participants may receive re-treatment with rituximab under a separate protocol WA17531.
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
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participants 18-80 years of age with active RA for at least 6 months;
- •Received treatment for RA on an outpatient basis and experienced an inadequate response or intolerance to treatment with at least 1 anti-TNF alpha therapy (etanercept, infliximab or adalimumab);
- •Must have received MTX for a minimum of 12 weeks, with the last 4 weeks, prior to screening at a stable dose;
- •Participants with swollen joint count (SJC) and tender joint count (TJC) of at least 8 joints at screening and at randomization;
- •Radiographic evidence of at least 1 joint with a definite erosion due to RA;
- •Participants of reproductive potential must be using reliable contraceptive methods.
排除标准
- •Bone or joint surgery within 8 weeks prior to screening or joint surgery planned within 24 weeks of randomization;
- •Class IV functional status of RA;
- •Previous treatment within 6 months with intravenous gamma globulin, or the Prosorba column;
- •Intraarticular or parenteral corticosteroids within 4 weeks prior to screening visit;
- •With a live vaccine within 4 weeks prior to randomization;
- •Previous treatment with rituximab or other cell-depleting therapies;
- •Concurrent treatment with any disease-modifying anti-rheumatic drug (except for MTX) or any anti-TNF alfa factor or other biologic therapy;
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
- •Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders;
- •Known contraindications to receiving rituximab;
- •Known active bacterial, viral, fungal, mycobacterial or other infection;
- •History of recurrent significant infection or history of recurrent bacterial infections;
- •Primary or secondary immunodeficiency (history of, or currently active);
- •History of cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured);
- •Women who are pregnant or breast-feeding;
- •History of alcohol, drug or chemical abuse within 6 months prior to screening;
- •Neuropathies and neurovasculopathies which might interfere with pain evaluation;
- •Participants with poor peripheral venous access;
- •Intolerance or contraindications to oral or intravenous corticosteroids.
研究组 & 干预措施
Placebo Plus Methotrexate
Participants will be administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg per os (p.o.) or parenterally once a week up to 24 weeks and will be followed up to Week 104.
干预措施: Methotrexate (Drug)
Placebo Plus Methotrexate
Participants will be administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg per os (p.o.) or parenterally once a week up to 24 weeks and will be followed up to Week 104.
干预措施: Placebo (Other)
Rituximab plus Methotrexate
Participants will be administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and will be followed up to Week 104.
干预措施: MabThera/Rituxan (Drug)
Rituximab plus Methotrexate
Participants will be administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and will be followed up to Week 104.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Number of Participants With American College of Rheumatology 20 Response at Week 24
时间窗: Week 24
American College of Rheumatology (ACR) 20 response is defined as \>= 20% improvement (reduction) in score compared with baseline for both tender joint count (TJC)-68 joints and swollen joint count (SJC)-66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) ranging from score 0 (no pain) to 100 (unbearable pain); Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging score 0 (no disease activity) to 100 (maximum disease activity); Health Assessment Questionnaire (HAQ):8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do) for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR).
次要结局
- Number of Participants With an ACR 50 Response at Week 24(Week 24)
- Number of Participants With ACR 70 Response at Week 24(Week 24)
- Mean Change From Baseline in Disease Activity Score of 28 Joints at Week 24(From Baseline (Day 1) to Week 24)
- Percentage of Participants With DAS28 Low Disease Activity and DAS28 Remission at Week 24(Week 24)
- Number of Participants With Good, Moderate, or no European League Against Rheumatism Responses at Week 24(Week 24)
- Percentage Change From Baseline in the ACR Core Set (SJC, TJC, Patient's and Physician's Global Assessments, Health Assessment Questionnaire, Pain, C-Reactive Protein, and Erythrocyte Sedimentation Rate) Score(From Baseline (Day 1) to Week 24)
- Mean Change From Baseline of Short Form 36 Total Scores at Week 24(From Baseline (Day 1) to Week 24)
- Number of Participants With Categorical Change From Baseline in the Physical Component Scores of SF-36(From Baseline (Day 1) to Week 24)
- Number of Participants With Change From Baseline in the Mental Component Scores of SF-36(From Baseline (Day 1) to Week 24)
- Mean Change From Baseline in the Genant-modified Sharp Joint Space Narrowing Score, Genant-modified Sharp Total Score, and Erosion Score(From Baseline (Day 1) to Weeks (W) 24, 56, and 104)
- Percentage of Participants Without Erosive Progression(Up to Week 104)