A Phase 2b Study to Evaluate the Efficacy and Safety of Mavrilimumab in Subjects With Moderate-to-Severe Rheumatoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 420
- 试验地点
- 43
- 主要终点
- Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 85
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of 3 subcutaneous doses of mavrilimumab compared with placebo in combination with methotrexate (MTX) in subjects with moderate-to-severe adult onset Rheumatoid Arthritis (RA).
详细描述
Despite the therapeutic improvements with recent biologic agents approved for rheumatoid arthritis, there is still significant unmet medical need for the treatment of subjects with this chronic disease to achieve a faster, more complete response, and higher rates of remission. The aim of the study is to explore the optimum dose of mavrilimumab for further clinical development and more fully investigate the efficacy and safety profile of mavrilimumab after longer drug exposure (that is, 24 weeks). The results of this study will form the basis for future clinical studies with mavrilimumab.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of adult onset Rheumatoid Arthritis (RA) in line with the protocol
- •Moderately active disease in line with the protocol
- •A pre-defined number of swollen joints in line with the protocol
- •Inadequate response to one or more conventional disease-modifying anti-rheumatic drugs (DMARDs)
- •No evidence of respiratory disease.
排除标准
- •A rheumatic autoimmune disease other than RA, or significant systemic extra-articular involvement secondary to RA
- •A history of, or current, inflammatory joint disease other than RA
- •Previous treatment with the investigational drug
- •Discontinuation of a biologic DMARD due to lack of efficacy
- •Non-compliant concurrent medications
- •Non-compliance with medical history criteria.
结局指标
主要结局
Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 85
时间窗: Baseline and Day 85
DAS28 (CRP) calculated swollen joint count (SJC) and tender joint count (TJC) using the 28 joints, general health (GH) using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (milligram per liter \[mg/L\]). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) less than (\<) 3.2 = low disease activity, greater than or equal to (\>=) 3.2 to 5.1 = moderate to high disease activity and \<2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85.
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169
时间窗: Day 169
ACR20 was defined as \>=20 percent (%) improvement, in: SJC and TJC and \>=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and CRP.
次要结局
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(Baseline up to Day 169)
- Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)(Baseline up to Day 169)
- Dyspnea Score at Day 169(Day 169)
- Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169(Day 169)
- Mean Change From Baseline in Swollen and Tender Joint Count at Day 169(Baseline and Day 169)
- Ratio of Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Day 169(Baseline, Day 169)
- Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169(Day 169)
- Serum Concentrations of Mavrilimumab(Baseline, Day 8, 15, 29, 85, 141, and 169)
- Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)(Baseline up to Day 169)
- Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169(Day 169)
- Oxygen Saturation Level at Day 169(Day 169)
- Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169(Day 169)
- Change From Baseline in Continuous American College of Rheumatology (ACRn) Score at Day 169(Baseline up to Day 169)
- Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169(Baseline and Day 169)
- Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169(Baseline and Day 169)
- Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Day 169(Day 169)
- Percentage of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at Any Visit(Day 1 to Day 169)
- Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169(Day 169)
- Percentage of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169(Day 169)
- Mean Change From Baseline in Patient Assessment of Pain at Day 169(Baseline and Day 169)
- Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169(Baseline and Day 169)
- Ratio of Change From Baseline in C-Reactive Protein (CRP) at Day 169(Baseline, Day 169)
- Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-fatigue) at Day 169(Baseline and Day 169)
- Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169(Day 169)