A Phase IIIB Multicenter, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Abatacept Administered Subcutaneously and Intravenously in Subjects With Rheumatoid Arthritis, Receiving Background Methotrexate, and Experiencing an Inadequate Response to Methotrexate
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 2,492
- 试验地点
- 70
- 主要终点
- Double-blind Period: Number of Participants Achieving American College of Rheumatology (ACR) 20 Response at Day 169
研究概览
简要总结
The purpose of this study is to determine whether a weekly subcutaneous dose of abatacept yields clinical efficacy comparable to that of monthly intravenous doses of abatacept in participants with rheumatoid arthritis and an inadequate response to current methotrexate therapy.
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
- •Subjects who are considered methotrexate inadequate responders
- •10 or more swollen joints (66 joint count) and 12 or more tender joints (68 joint count)
排除标准
- •Subjects who failed one or multiple anti-tumor necrosis factor (TNF) therapies
- •Subjects who meet diagnostic criteria for any other rheumatic disease (e.g., lupus erythematous)
- •Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules)
- •Subjects with severe chronic or recurrent bacterial infections
- •Subjects who have received treatment with rituximab
- •An Anti-TNF Failure Sub-study was initiated (recruited separately from Main study) using the same treatment as the Main study in order to assess the immunogenicity and safety in the Anti-TNF Failure population. The Sub-study terminated due to low recruitment and participants were permitted to roll into the LT Open Label Period.
研究组 & 干预措施
Subcutaneous (SC) Abatacept
Participants received 125 mg weekly SC abatacept injections (with an intravenous [IV] abatacept loading dose on Day 1, based on weight). A double-dummy design was used to protect the blind, thus, participants also received IV injections of placebo (IV Placebo) with the exception that on Day 1 a loading dose of IV abatacept replaced the IV Placebo treatment.
干预措施: Subcutaneous (SC) Abatacept (Drug)
Intravenous (IV) Abatacept
Participants received IV abatacept infusions on Days 1, 15, 29, and every 28 days, thereafter. A double-dummy design was used to protect the blind, thus, participants also received SC injections of placebo (SC Placebo).
干预措施: Intravenous (IV) Abatacept (Drug)
结局指标
主要结局
Double-blind Period: Number of Participants Achieving American College of Rheumatology (ACR) 20 Response at Day 169
时间窗: Day 169
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joints, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein).
Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population
时间窗: Days 85, and 169 and postvisits on Days 28, 56, and 85
Serum samples from all treated adult participants with active rheumatoid arthritis who were from the Anti-TNF failure population were screened for the presence of drug-specific antibodies using Enzyme Linked Immunoabsorbant Assay (ELISA). The number of participants who had the presence of anti-abatacept antibodies or anti-CTLA-4 antibodies present in their serum are summarized.
次要结局
- Double-blind Period: Mean Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) for Participants With Assessments at Day 169(Day 169)
- Double-blind Period: Number of Participants Achieving Clinically Meaningful HAQ-DI Response at Day 169(Day 169)
- Double-blind Period: Minimum Observed Serum Concentration of Abatacept(Days 57, 85, 113, 120, 127, 134, 141, and 169)
- Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169(Day 169)
- Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation(Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.)
- Double-blind Period: Number of Participants With AEs of Special Interest(Day 1 up to 56 days post last dose in short- term period or first dose in the long -term period, whichever occurs first.)
- Double-blind Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements(Day 1 through end of short-term period (Day 169))
- Double-blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept(Dosing interval between Days 113 and 141 (TAU=28 days))
- Double-blind Period: Adjusted Mean Change From Baseline to Day 169 in HAQ-DI(Baseline to Day 169)
- Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died(Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.)
- Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality(Day 1 through end of short-term period (Day 169))
- Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept(Days 57, 85, 113, 120, 127, 134, 141, and 169 (ST Period))
- Double-blind Period: Maximum Observed Serum Concentration of Abatacept(End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous)
- Anti-TNF Failure Sub-study Double Blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept(Dosing Interval between Days 113 and 141 (TAU=28 days))
- Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period(Baseline to Days 15, 29, 57, 85, 113, 141, and 169)
- Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality(Day 1 through end of short-term period (Day 169))
- Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality(Day 1 through end of short-term period (Day 169))
- Anti-TNF Failure Substudy Double Blind Period: Geometric Mean Maximum Observed Serum Concentration of Abatacept(End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous)
- Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA)(Days 85, and 169 and postvisits on Days 28, 56, and 85)
- Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized(Days 85, and 169 and postvisits on Days 28, 56, and 85)
- Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline(Baseline to Day 169)
- Open-Label LT Period: Number of Participants Achieving ACR 20 Response at Days 169, 729, 1261, and 1821(Days 169, 729, 1261, 1821)
- Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821(Days 169, 729, 1261, 1821)
- Open-Label LT Period: Mean Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Using C-reactive Protein (CRP) at Days 169, 729, 1261, 1821(Days 169, 729, 1261, 1821)
- Open-Label LT Period: Number of Participants Achieving DAS 28 Low Disease Activity (LDA) at Days 169, 729, 1261, 1821(Days 169, 729, 1261, 1821)
- Open-Label LT Period: Number of Participants Achieving DAS 28 Remission at Days 169, 729, 1261, 1821(Days 169, 729, 1261, 1821)
- Open-Label LT Period: Number of Participants With Clinically Significant Laboratory Abnormalities(End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014))
- Open-Label LT Period: Number of Participants With HAQ-DI Response at Days 169, 729, 1261, 1821(Days 169, 729, 1261, 1821)
- Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation(End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014))
- Open-Label LT Period: Number of Participants With AEs of Special Interest(End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014))
- Open-Label LT Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements(End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014))