A Randomized, Double-blind, Parallel Group Study of Safety and the Effect on Clinical Outcome of Tocilizumab Subcutaneous (sc) Versus Placebo sc in Combination With Traditional Disease Modifying Anti-rheumatic Drugs (DMARDs) in Patients With Moderate to Severe Active Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 656
- 主要终点
- Percentage of Patients With an American College of Rheumatology 20 (ACR20) Response at Week 24
研究概览
简要总结
This randomized, parallel-group, placebo-controlled, multicenter study will evaluate the reduction in disease activity and the safety of tocilizumab (RoActemra/Actemra) in combination with traditional disease-modifying anti-rheumatic drugs (DMARDs) in patients with active, moderate to severe rheumatoid arthritis. In the double-blind part of the study, patients will be randomized to receive either 162 mg tocilizumab or placebo subcutaneously every 2 weeks for 24 weeks using a pre-filled syringe. In the open-label part of the study, patients will be randomized to receive 162 mg tocilizumab subcutaneously every 2 weeks from Week 24 to Week 96 using a pre-filled syringe or an auto-injector.
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, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients, ≥ years of age.
- •Moderate to severe rheumatoid arthritis of ≥ 6 months duration.
- •Receiving treatment on an outpatient basis.
- •Swollen joint count (SJC) ≥ 6 (66 joint count) and tender joint count (TJC)≥ 8 (68 joint count) at screening and study start.
- •On a stable dose of disease-modifying anti-rheumatic drugs for at least 8 weeks prior to study start.
排除标准
- •Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
- •Rheumatic autoimmune disease other than rheumatoid arthritis, Secondary Sjögren's Syndrome with rheumatoid arthritis is allowed.
- •Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.
- •Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16 years.
- •Prior history of or current inflammatory joint disease other than rheumatoid arthritis.
- •History of malignancy, active or recurrent infections, positive to hepatitis B surface antigen or hepatitis C antibody, active tuberculosis, serious allergy to biologics, or a history of diverticular disease or other symptomatic GI conditions that might predispose to perforations.
- •Other inclusion and exclusion criteria applied to the study.
研究组 & 干预措施
Tocilizumab 162 mg sc
Patients will receive tocilizumab 162 mg subcutaneously (sc) every 2 weeks for 24 weeks.
干预措施: Tocilizumab 162 mg (Drug)
Placebo sc
Patients will receive placebo subcutaneously (sc) every 2 weeks for 24 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Patients With an American College of Rheumatology 20 (ACR20) Response at Week 24
时间窗: Baseline to Week 24
A patient had an ACR20 response if there was at least a 20% improvement, ie, reduction from baseline, in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, left end=no disease activity \[symptom-free and no arthritis symptoms\], right end=maximum disease activity; patient assessment of pain in previous 24 hours on a VAS (left end=no pain and right end=unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and acute-phase reactant (either C-reactive protein or erythrocyte sedimentation rate).
次要结局
- Change From Baseline in Erythrocyte Sedimentation Rate at Week 24(Baseline to Week 24)
- Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24(Baseline to Week 24)
- Change From Baseline in the Van Der Heijde Modified Sharp Radiographic Score at Week 24(Baseline to Week 24)
- Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Week 24(Baseline to Week 24)
- Percentage of Patients With ACR50 and ACR70 Responses at Week 24(Baseline to Week 24)
- Time to Onset of ACR20, ACR50, and ACR70 Responses(Baseline to Week 24)
- Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 24(Baseline to Week 24)
- Change From Baseline in C-reactive Protein at Week 24(Baseline to Week 24)
- Change From Baseline in the Patient's and the Physician's Global Assessment of Disease Activity Visual Analog (VAS) Score(Baseline to Week 24)
- Change From Baseline in the Patient's Pain Visual Analog Score(Baseline to Week 24)
- Percentage of Patients With an Improvement of ≥ 0.3 Units From Baseline in the HAQ-DI Score at Week 24(Baseline to Week 24)
- Change From Baseline in Disease Activity Score 28 (DAS28) at Week 24(Baseline to Week 24)
- Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24(Baseline to Week 24)
- Change From Baseline in Hemoglobin at Week 24(Baseline to Week 24)
- Percentage of Patients With a DAS28 Score ≤ 3.2 (DAS28 Low Disease Activity) at Week 24(Baseline to Week 24)
- Percentage of Patients With a DAS28 Score < 2.6 (DAS28 Remission) at Week 24(Week 24)