A Double-Blind, Randomized, Multicenter Study of Higher Versus Standard Adalimumab Dosing Regimens for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 952
- 试验地点
- 173
- 主要终点
- Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52
研究概览
简要总结
To evaluate safety and efficacy of two adalimumab dosing regimens for induction and maintenance (standard and higher dosing) in achieving clinical remission in subjects with moderately to severely active ulcerative colitis.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Ulcerative Colitis (UC) for at least 90 days, confirmed by endoscopy during Screening period.
- •Active UC with Mayo Score of 6 to 12 points and endoscopy subscore of 2 to 3 despite concurrent or prior treatment with a full and adequate course, in the opinion of the Investigator, with oral corticosteroids or immunosuppressants or both. Mayo Score is confirmed by central reader.
排除标准
- •Subject with Crohn's disease (CD) or indeterminate colitis (IC).
- •Current diagnosis of fulminant colitis and/or toxic megacolon.
- •Subjects with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy.
- •Chronic recurring infections or active tuberculosis (TB).
研究组 & 干预措施
Induction (Main Study + Japan Sub-study): I-SD
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
干预措施: Adalimumab (Drug)
Induction (Main Study + Japan Sub-study): I-SD
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
干预措施: Placebo (Other)
Induction (Main Study + Japan Sub-study): I-HD
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4, and 40 mg at Week 6.
干预措施: Adalimumab (Drug)
Maintenance (Main Study + Japan Sub-study): M-SD
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
干预措施: Adalimumab (Drug)
Maintenance (Main Study + Japan Sub-study): M-SD
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
干预措施: Placebo (Other)
Maintenance (Main Study + Japan Sub-study): M-HD
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
干预措施: Adalimumab (Drug)
Maintenance (Main Study): TDM Regimen
Double-blind adalimumab 40 mg eow at Week 8 and Week 10, with possible dose adjustments at Weeks 12, 24, and 37 based on criteria assessing blinded adalimumab serum concentration and rectal bleeding subscore (RBS) assessments.
干预措施: Adalimumab (Drug)
Maintenance (Main Study): TDM Regimen
Double-blind adalimumab 40 mg eow at Week 8 and Week 10, with possible dose adjustments at Weeks 12, 24, and 37 based on criteria assessing blinded adalimumab serum concentration and rectal bleeding subscore (RBS) assessments.
干预措施: Placebo (Other)
结局指标
主要结局
Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52
时间窗: Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders (per FMS) are defined as participants with a decrease in Full Mayo score of ≥ 3 points and ≥ 30% from Baseline plus a decrease from baseline in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore \> 1.
Induction Period Primary Endpoint: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 8
时间窗: Week 8
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore \> 1.
次要结局
- Induction Period Ranked Secondary Endpoint 1: Percentage of Participants With Endoscopic Improvement at Week 8(Week 8)
- Induction Period Ranked Secondary Endpoint 4: Percentage of Participants With Clinical Response Per FMS at Week 8(Week 8)
- Induction Period Ranked Secondary Endpoint 7: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 8(Week 8)
- Induction Period Ranked Secondary Endpoint 6: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 8(Week 8)
- Maintenance Period Ranked Secondary Endpoint 1: Percentage of Week 8 Responders (Per FMS) With Endoscopic Improvement at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 3: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 2: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 5: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Improvement at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 6: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 7: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission (Per FMS) at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 8: Percentage of Week 8 Responders (Per FMS) With IBDQ Response (Increase of IBDQ ≥ 16 From Baseline) at Week 52(Week 52)
- Induction Period Ranked Secondary Endpoint 2: Percentage of Participants With Fecal Calprotectin < 150 mg/kg at Week 8(Week 8)
- Maintenance Period Ranked Secondary Endpoint 9: Percentage of Week 8 Non-Responders With Clinical Remission (Per FMS) at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 10: Percentage of Week 8 Non-Remitters With Clinical Remission (Per FMS) at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 11: Percentage of Week 8 Responders (Per FMS) With Endoscopic Subscore of 0 at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 12: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Subscore of 0 at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 13: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Bowel Symptom Domain at Week 52(Week 52)
- Maintenance Period Ranked Secondary Endpoint 14: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Fatigue Item at Week 52(Week 52)
- Induction Period Ranked Secondary Endpoint 3: Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response (Increase of IBDQ ≥ 16 From Baseline) at Week 8(Week 8)
- Induction Period Ranked Secondary Endpoint 5: Percentage of Participants With Endoscopic Remission at Week 8(Week 8)
- Maintenance Period Ranked Secondary Endpoint 4: Percentage of Week 8 Remitters (Per FMS) With Clinical Remission (Per FMS) at Week 52(Week 52)