A Phase 3, Multi-Center, Randomized, Placebo-Controlled Study to Evaluate the Clinical Efficacy and Safety of Induction and Maintenance Therapy With Abatacept in Subjects With Active Crohn's Disease (CD) Who Have Had an Inadequate Clinical Response and/or Intolerance to Medical Therapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 451
- 试验地点
- 38
- 主要终点
- Open-Label Extension Period (OL); Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and Discontinuation Due to AEs
研究概览
简要总结
The purpose of this clinical research study is to learn if abatacept can improve signs and symptoms of active Crohn's Disease in patients who have not had an adequate response to other therapies. The safety of this treatment will also be studied.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •18 years or older
- •have had Crohn's Disease for at least 3 months
- •moderate to severely active Crohn's Disease
- •have had an inadequate response or intolerance to other Crohn's Disease treatments
排除标准
- 未提供
研究组 & 干预措施
1
4 arms for induction period
2 arms for maintenance period
干预措施: abatacept (Drug)
2
4 arms for induction period
2 arms for maintenance period
干预措施: placebo (Drug)
abatacept
1 arm for open-label extension phase
干预措施: abatacept (Drug)
结局指标
主要结局
Open-Label Extension Period (OL); Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and Discontinuation Due to AEs
时间窗: Between Day OL-1 and Day OL-617
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Induction Period (IP); Number of Participants With Crohn's Disease Activity Index (CDAI)-Defined Clinical Response at Both Day IP-57 and Day IP-85
时间窗: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12).
CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
Maintenance Period (MP); Number of Participants In CDAI-Defined Clinical Remission (CDAI <150) at Day MP-365 (12 Months)
时间窗: Day MP-365 (12 months) of maintenance therapy
CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
OL; Number of Participants With Adverse Events (AEs) of Special Interest
时间窗: Between Day OL-1 and Day OL-617
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).
次要结局
- MP; Number of Participants With Adverse Events (AEs) of Special Interest:(Between Day IP-85 and Day MP-365)
- MP; Number of Participants With Positive Antibody Response to Abatacept(For participants not entering OL: All measurements after Day MP-1 (including follow-up visits); For participants entering OL: From first measurement after Day MP-1 to Day MP-365 (Day OL-1))
- IP; Number of Participants With CDAI-Defined Clinical Response at Both Day IP-57 and Day IP-85 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship(At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy)
- IP; Number of Participants Who Are Anti-TNF-Inadequate Responders/Anti-TNF Intolerant With CDAI-Defined Clinical Response at Both Day IP-57 and Day IP-85 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship(At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy)
- MP; Number of Participants With CDAI-defined Clinical Response at Day MP-365.(Day MP-365)
- IP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and Discontinuation Due to AEs(Day IP-1 through Day IP-85)
- IP; Number of Participants With CDAI-Defined Clinical Response at Both Day IP-57 and Day IP-85 Among Participants With Inadequate Response and/or Intolerance to Anti-Tumor Necrosis Factor (TNF)(At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy)
- MP; Change From Baseline to Day MP-365 in Short Form-36 (SF-36)(Baseline, Day MP-365)
- OL; Number of Participants With CDAI-defined Clinical Response or Clinical Remission at Day OL-365(Day OL-365)
- IP; Number of Participants in CDAI-defined Clinical Remission at Both Day IP-57 and Day IP-85 (Key Secondary Outcome)(At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy)
- IP; Change From Baseline to Day IP-85 In Inflammatory Bowel Disease Questionnaire (IBDQ)(Baseline, Day IP-85)
- IP; Number of Participants With Adverse Events (AEs) of Special Interest(Day IP-1 through Day IP-85)
- MP; Number of Participants Who Were Not On Background Corticosteroid Therapy at Day MP-365 Among All Participants Who Received Baseline Corticosteroid Therapy(Day MP-365)
- IP; Number of Participants With Positive Antibody Response to Abatacept (ABA)(For participants treated in MP: Day IP-1 (Baseline) to Day MP-1 (Day IP-85); For participants treated in OL directly after IP: Day IP-1 to Day OL-1; For participants treated only in IP: All measurements after Day IP-1 (including follow-up visits))
- IP; Number of Participants in CDAI-Defined Clinical Remission at Both Day IP-57 and Day IP-85 Among Participants With Inadequate Response and/or Intolerance to Anti-TNF(At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy)
- MP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and Discontinuation Due To AEs(Between Day IP-85 and Day MP-365)
- MP; Number of Participants in CDAI-defined Clinical Remission at Both Day MP-169 and Day MP-365(Day MP-169)
- MP; Number of Participants in CDAI-Defined Clinical Remission Among Participants With Inadequate Response and/or Intolerance to Anti-TNF(Day MP-365)
- OL; Number of Participants Who Were Not On Background Corticosteroid Therapy Among All Participants Who Received Baseline Corticosteroid Therapy(Between Day OL-1 and Day OL-617)
- MP; Change From Baseline to Day MP-365 in Inflammatory Bowel Disease Questionnaire (IBDQ)(Baseline, Day MP-365)
- MP; Number of Participants Who Were Not On Background Corticosteroid Therapy at Day MP-365 Among Participants Who Received Baseline Corticosteroid Therapy and Who Achieved CDAI-Defined Clinical Remission(Day MP-365)
- MP; Number of Participants With CDAI-Defined Clinical Response Among Participants With Inadequate Response and/or Intolerance to Anti-Tumor Necrosis Factor (TNF)(Day MP-365)
- OL; Number of Participants With CDAI-defined Clinical Response or Clinical Remission at Day OL-169(Day OL-169)
- OL; Number of Participants With Positive Antibody Response to Abatacept(For participants receiving OL medication, all measurements starting after Day OL-1 (including follow-up visits and at 56 and 85 days after last dose))
- OL; Number of Participants With Pharmacogenomic Marker Activity(Between Day OL-1 and Day OL-617)