A Phase 2 Exploratory Study of Mavrilimumab Versus Anti-tumor Necrosis Factor in Subjects With Rheumatoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 215
- 试验地点
- 39
- 主要终点
- Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169
研究概览
简要总结
The primary objectives of this study is to explore the efficacy of mavrilimumab compared with golimumab in the treatment of adult subjects 18-80 years of age with moderate-to-severe active rheumatoid arthritis (RA) who have an inadequate response to one or more conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or one or two anti-tumor necrosis factor (TNF) agents (excluding golimumab) for efficacy or safety reasons.
详细描述
Despite the therapeutic improvements with recent biologic agents approved for rheumatoid arthritis (RA), there is still a 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 current study is to compare the efficacy and safety of a subcutaneous dose of mavrilimumab with a marketed treatment for RA (golimumab) in 120 adult subjects with moderate-to-severe active RA who have had an inadequate response to one or two anti-TNF agents with mavrilimumab. The design of the study was exploratory and not formerly statistically powered.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age 18 through 80 years
- •Written consent
- •Diagnosis of adult onset Rheumatoid Arthritis (RA) as defined by the 2010 American College of Rheumatology European League Against Rheumatism (ACR/EULAR) classification criteria
- •Moderately active disease as defined by disease activity score in 28 joints C-reactive protein (DAS28[CRP]) greater than or equal to (>=) 3.2 at screening and DAS28 erythrocyte sedimentation rate(ESR) ≥ 3.2 at Day 1
- •Inadequate response to one or more conventional disease-modifying anti-rheumatic drugs (DMARDs)
- •At least 4 swollen joints
- •Inadequate response to one or two anti-TNF agents other than the study comparator, as defined by the protocol
- •Receiving oral or injectable methotrexate, as defined by the protocol.
排除标准
- •A rheumatic autoimmune disease or other inflammatory joint disease other than RA
- •Previous treatment with biologic therapies other than anti-TNF for RA
- •Treatment with other DMARDs or non-steroidal anti-inflammatory drugs (NSAIDs), as defined by the protocol.
- •Medical history as defined by the protocol.
结局指标
主要结局
Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169
时间窗: Day 169
The ACR50 was defined as \>=50% improvement, in: SJC and TJC and \>=50% 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 HAQ); and CRP. If CRP was missing and ESR was present then ESR was to be used. The percentage of participants were calculated by logistic regression model method.
Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 169
时间窗: Day 169
The DAS28 (CRP) was calculated from the number of SJC and TJC using the 28 joints count, The DAS28(CRP) considers 28 of the 68 TJC and 28 of the 66 SJC and participant's global health (GH) using PGA of disease activity using the visual analogue scale (VAS) of 0 (= best), 100 (= worst) plus levels of CRP (milligram/Liter \[mg/L\]). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) less than (\<) 3.2 = low disease activity, \>=3.2 to 5.1 = moderate to high disease activity and \<2.6= remission. Participants with score less than 2.6 were analysed. The percentage of participants were calculated by logistic regression model method.
Percentage of Participants Who Achieved Health Assessment Questionnaire Disability Index (HAQ-DI) Score Improvement From Baseline and >= 0.25 at Day 169
时间窗: Day 169
The HAQ-DI: 20-item scale assessing participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arising, eating, hygiene, walking, reaching, grip, and errands/chores over past week. Each item was scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range from 0 to 3; where 0 = least difficulty and 3 = extreme difficulty. Participants with change from baseline more than or equal to (\>=) 0.25 were reported. The percentage of participants were calculated by logistic regression model method.
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169
时间窗: Day 169
The ACR20 was defined as greater than or equal to (\>=) 20 percent (%) improvement, in: swollen joint count (SJC) and tender joint count (TJC) and \>=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity (PGA); physician global assessment of disease activity (MDGA); self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (CRP). If CRP was missing and Erythrocyte sedimentation rate (ESR) was present then ESR was to be used.
Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169
时间窗: Day 169
The ACR70 was defined as \>=70% improvement, in: SJC and TJC and \>=70% 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 HAQ); and CRP. If CRP was missing and ESR was present then ESR was to be used. The percentage of participants were calculated by logistic regression model method.
次要结局
- Dyspnea Score at Day 169(Day 169)
- Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)(Baseline up to Day 169)
- Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) < 2.6 at Day 169(Day 169)
- Percentage of Participants Who Achieved Simplified Disease Activity Index (SDAI) Remission at Day 169(Day 169)
- Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169(Day 169)
- Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169(Baseline and Day 169)
- Ratio of Change C-Reactive Protein (CRP) at Day 169 to Baseline(Baseline and Day 169)
- Serum Concentrations of Mavrilimumab(Baseline, Day 8, 15, 29, 85, 141, and 169)
- Number of Participants With Pulmonary Function Test Values Below Threshold Values Based on Percent Change From Baseline at Day 85 and 169(Day 85 and 169)
- Change From Baseline in Continuous American College of Rheumatology (ACRn) Score at Day 169(Baseline up to Day 169)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(Baseline up to Day 169)
- Time to Onset DAS28 (CRP) Remission at Day 169(Day 169)
- Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)(Baseline up to Day 169)
- Number of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169(Day 169)
- Duration of DAS28 (CRP) Remission at Day 169(Day 169)
- Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169(Day 169)
- Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 169(Baseline and Day 169)
- Mean Change From Baseline in Swollen and Tender Joint Count at Day 169(Baseline and 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)
- American College of Rheumatology (ACR) Hybrid Score at Day 169(Day 169)
- Number of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169(Day 169)
- Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169(Baseline and Day 169)
- Erythrocyte Sedimentation Rate (ESR) at Day 169(Day 169)
- Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab(Day 1 to Day 169)