A Phase 3b, Randomized, Active Controlled Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination With Methotrexate in Inducing Clinical Remission Compared to Methotrexate Monotherapy in Adults With Very Early RA
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 511
- 试验地点
- 16
- 主要终点
- Percentage of Participants Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18
研究概览
简要总结
The primary purpose of the protocol is to demonstrate the ability of abatacept plus methotrexate to induce remission in patients with very early rheumatoid arthritis after 12 months of treatment and to maintain remission following 6 months of drug withdrawal.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presence of active clinical synovitis in at least 2 joints, 1 of which must have been a small joint, for a minimum of 8 weeks prior to screening
- •Onset of persistent symptoms ≤ 2 years prior to screening
- •Positive test result for anticyclic citrullinated peptides 2
- •Methotrexate naive or with minimum exposure to methotrexate, defined as no more than 10 mg/week for ≤4 weeks and no methotrexate dose for 1 month prior to screening visit
- •Biologic naive, including no treatment with an investigational biologic prior to screening
- •Disease Activity Score 28 based on C-reactive protein score ≥3.2 at screening
- •Withdrawal from any treatment with chloroquine, hydroxychloroquine, and/or sulfasalazine (wash-out) for a minimum of 28 days prior to randomization
- •If receiving oral corticosteroids, on a stable low dose (≤ 10 mg/day prednisone equivalent) for at least 4 weeks
- •Able to undergo magnetic resonance imaging
排除标准
- •Meeting diagnostic criteria for other rheumatic disease (eg, lupus erythematosus)
- •Treatment with an intravenous, intramuscular, or intraarticular corticosteroid within 4 weeks prior to randomization
- •Scheduled for or anticipating joint replacement surgery
- •Presence of concomitant illness likely to require systemic glucocorticosteroid therapy during the study, in the opinion of the investigator
- •History of malignancy in the last 5 years
- •Any serious bacterial infection within the last 3 months not treated or resolved with antibiotics, or any chronic or recurrent bacterial infection
- •At risk for tuberculosis
- •Evidence of active or latent bacterial or viral infection at the time of potential enrollment, including human immunodeficiency or herpes zoster virus or cytomegalovirus that resolved less than 2 months prior to enrollment
研究组 & 干预措施
Abatacept, 125 mg, plus methotrexate, 2.5 mg
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
干预措施: Abatacept (Drug)
Abatacept, 125 mg, plus methotrexate, 2.5 mg
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
干预措施: Methotrexate (Drug)
Methotrexate, 2.5 mg, plus abatacept placebo
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
干预措施: Methotrexate (Drug)
Methotrexate, 2.5 mg, plus abatacept placebo
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
干预措施: Abatacept placebo (Drug)
Abatacept, 125 mg, plus methotrexate placebo
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
干预措施: Abatacept (Drug)
Abatacept, 125 mg, plus methotrexate placebo
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
干预措施: Methotrexate placebo (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18
时间窗: Randomization to Months 12 and 18
DAS28-CRP remission defined as \<2.6; TP=treatment phase; WP=withdrawal phase. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
次要结局
- Percentage of Participants Who Received Monotherapy and Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18(Randomization to Months 12 and 18)
- Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population(Randomization to Month 24)
- Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18(Baseline to Month 18)
- Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18(Randomization to Month 18)
- Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time(Randomization to Month 18)
- Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time(Randomization to Month 24)
- Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time(Randomization to Month 18)
- Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36)(Randomization to Months 6, 12, and 18)
- Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI)(Randomization to Month 18)
- Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period(Day 1 to up to 56 days following the last dosing day (Day 365); all deaths during study period, including those that occurred >56 days after last dose in Treatment Period)
- Adverse Events (AEs) of Interest During the Treatment Period(Day 1 to 56 days following last dosing day (Day 365))
- Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period(Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365))
- Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12(End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24))
- Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period(Randomization to Month 24)
- Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods)(Day 1 to 56 days post last dose in the study, up to Month 30)
- Adverse Events (AEs) of Interest During the Withdrawal Period(Last dose in TP + 57 days, up to Month 24)
- Adverse Events (AEs) of Interest During the Re-exposure Period(First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days)
- Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period(Last dose in TP + 57 days, up to Month 24)
- Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period(Start of re-exposure period to 56 days post last dose, up to Month 30)