Phase 2, Randomized, Multi-Center, Double-Blind, Dose-Ranging, Placebo Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety/Pharmacokinetics of BMS-986142 in Subjects With Moderate to Severe Rheumatoid Arthritis With an Inadequate Response to Methotrexate With or Without TNF Inhibitors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 508
- 试验地点
- 45
- 主要终点
- Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
研究概览
简要总结
The purpose of this study is to determine whether the study drug, BMS-986142, is safe and effective in treating moderate to severe rheumatoid arthritis in subjects with an inadequate response to methotrexate or methotrexate and up to 2 tumour necrosis factor (TNF) Inhibitors. Patients who qualify will be randomized to either one of 3 doses of BMS-986142 or placebo in 1:1:1 randomization for 12 weeks. Disease activity and safety will be assessed over the course of the study.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female age 18 and above
- •Diagnosed with active rheumatoid arthritis (RA) by standard criteria at least 16 weeks before screening, have functional ACR class I-III
- •Have an inadequate response to methotrexate
- •In addition to an inadequate response to methotrexate have an inadequate response or intolerance to 1 but not more than 2 TNF inhibitors
- •Have a minimum of 6 swollen and 6 tender joints (from 66/68 joint count)
- •Have hsCRP of ≥ 0.8 mg/dL (8mg/L) [by central laboratory values] or an ESR ≥ 28 mm/hr
- •Willing to use effective birth control for the entire length of the study
排除标准
- •Diagnosed with juvenile Rheumatoid Arthritis
- •Have been treated with other biologic treatment than a TNF inhibitor
- •Active systemic bacterial, viral or fungal infection or evidence of prior or current Hepatitis B or C infection or HIV infection, latent bacterial, viral or fungal infections
- •Have been treated with Intramuscular or Intra-articular glucocorticosteroids within 4 weeks of randomization
- •Taking Oral steroids at dose above 10 mg/day of prednisone (or prednisone equivalents)
- •Have other autoimmune disease other than RA like lupus, multiple sclerosis
- •Have significant concurrent medical condition at the time of screening or baseline visit
研究组 & 干预措施
Dose Level 2
BMS-986142 at dose level 2 + Methotrexate as specified
干预措施: BMS-986142 (Drug)
Dose Level 1
BMS-986142 at dose level 1+ Methotrexate as specified
干预措施: Methotrexate (Drug)
Placebo
Placebo + Methotrexate dose as specified
干预措施: Placebo (Drug)
Placebo
Placebo + Methotrexate dose as specified
干预措施: Methotrexate (Drug)
Dose Level 1
BMS-986142 at dose level 1+ Methotrexate as specified
干预措施: BMS-986142 (Drug)
Dose Level 2
BMS-986142 at dose level 2 + Methotrexate as specified
干预措施: Methotrexate (Drug)
结局指标
主要结局
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
时间窗: Week 12
ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant C-reactive Protein levels (CRP); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by health assessment questionnaire disability index (HAQ-DI). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. Percentage of Participants achieving ACR20 = (number of participants with measure/event of interest)/(number of particpants in the analysis)\*100
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12
时间窗: Week 12
ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR. Percentage of Participants achieving ACR70 = (number of participants with measure/event of interest)/(number of particpants in the analysis)\*100
次要结局
- Percentage of Participants Achieving American College of Rheumatology 20% Response Over Time From Baseline to Week 12(Baseline, Day 15, Day 29, Day 57, Day 85)
- Percentage of Participants Achieving American College of Rheumatology 70% Response Over Time From Baseline to Week 12(Baseline, Day 15, Day 29, Day 57, Day 85)
- Percentage of Participants Achieving <= 2.8 Response in Clinical Disease Activity Index (CDAI) Score at Week 12(Week 12)
- Percentage of Participants Achieving <= 3.3 Response in Simple Disease Activity Index (SDAI) Score at Week 12(Week 12)
- Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Osteitis at Week 4 and 12(Week 4, and Week 12)
- Percentage of Participants Achieving < 2.6 Response in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 12(Week 12)
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response Over Time From Baseline to Week 12(Baseline, Day 15, Day 29, Day 57, Day 85)
- Percentage of Participants Achieving < 2.6 Response in Disease Activity Score for 28 Joints Erythrocyte Sedimentation Rate (DAS28--ESR) Score at Week 12(Week 12)
- Change From Baseline in DAS28-CRP Score Over Time up to Week 12(Baseline, Day 85 (Week 12))
- Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Bone Erosion at Week 4 and 12(Week 4 and Week 12)
- Percentage of Participants Achieving Boolean Remission Criteria at Week 12(Week 12)
- Change From Baseline in CDAI Score Over Time up to Week 12(Baseline, Week 12)
- Change From Baseline in SDAI Score Over Time up to Week 12(Baseline, Week 12)
- Change From Baseline in DAS28-ESR Score Over Time up to Week 12(Baseline, Week 12)
- Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Synovitis at Week 4 and 12(Week 4 and Week 12)
- Number of Participants With Adverse Events (AEs), and Serious AEs (SAEs)(Up to 30 days after treatment discontinuation)
- Trough Observed Plasma Concentration (Ctrough) of BMS-986142(Week 4, 8, and 12)
- Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Cartilage Loss at Week 4 and 12(Week 4, and Week12)