A Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Multiregional, One Year Study to Assess the Efficacy and Safety of Twice Daily Oral Rifaximin Delayed Release Tablets for Induction of Clinical Remission With Endoscopic Response at 16 Weeks Followed by Clinical and Endoscopic Remission at 52 Weeks in Subjects With Active Moderate Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 80
- 主要终点
- Number of Participants With Endoscopic Response Between Week 16 and 17
研究概览
简要总结
The primary objective is to determine the efficacy of rifaximin DR also referred to as Extended Intestinal Release (EIR) tablets vs. placebo for the induction of clinical remission and endoscopic response following 16 weeks of treatment in participants presenting with active moderate Crohn's disease. A key secondary objective is to evaluate clinical and endoscopic remission following an additional 36 weeks of treatment.
详细描述
RECD3125 is a double-blind, placebo-controlled, parallel-group, multicenter, multiregional, 52-week study to assess the efficacy and safety of rifaximin DR tablets for the induction of clinical remission and endoscopic response at 16 weeks followed by clinical and endoscopic remission after 52 weeks of continuous therapy in participants with active moderate Crohn's disease.
Participants will be randomized in a 1:1 allocation to rifaximin or placebo at the beginning of the treatment period and will maintain treatment assignment throughout the duration of the study. Ileocolonoscopy will be performed on all participants at baseline, between Weeks 16 and 17 (end of the Induction Phase), and following completion of the 36-week Long Term Treatment Phase (Week 52).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Moderate, non-fistulizing Crohn's disease in the ileum and/or colon prior to randomization; and a SES-CD score of ≥7 (confirmed by centralized endoscopy reading).
- •During the screening period, the participant will need to have certain average daily scores for abdominal pain and average number of liquid/very soft stools.
排除标准
- •Pregnant or lactating females. Females of childbearing (reproductive) potential must have a negative serum pregnancy test at screening and agree to use a highly effective method(s) of contraception throughout their participation in the study. Diagnosis of ulcerative or indeterminate colitis.
- •Diagnosis of Celiac Disease.
- •Bowel surgery within 12 weeks prior to screening and/or has surgery planned or deemed likely for Crohn's disease during the study period.
- •Presence of an ileostomy or colostomy.
- •Known fixed symptomatic stenosis/stricture of the small or large bowel.
- •Had more than one segmental colonic resection.
- •Had more than 3 small bowel resections or symptoms associated with short bowel syndrome.
- •Current evidence of peritonitis.
- •History or evidence of colonic mucosal dysplasia.
- •History or evidence of adenomatous colonic polyps that have not been removed.
- •Unwilling to be tapered off corticosteroids by Week 8 or the participant is known by the Investigator to be steroid-dependent.
- •Has used a biologic within 12 weeks of randomization.
- •Used cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, or similar drugs within 8 weeks prior to randomization.
- •Had rectal administration of 5-aminosalicylic acid (5-ASA) or corticosteroid enemas/foams/ suppositories within 2 weeks prior to screening visit.
研究组 & 干预措施
Rifaximin EIR 800 mg
Participants will receive rifaximin EIR 400 milligrams (mg) tablets orally twice daily for 52 weeks.
干预措施: Rifaximin EIR (Drug)
Placebo
Participants will receive placebo matching to rifaximin EIR tablets orally twice daily for 52 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Endoscopic Response Between Week 16 and 17
时间窗: Baseline, Week 16 to 17
Endoscopic response defined as a ≥ 3-point decrease in the SES-CD from baseline to the SES-CD score obtained between Week 16 and Week 17. SES-CD scores were calculated from centrally-read digital video of ileocolonoscopies performed at baseline and between Week 16 and Week 17. SES-CD is a validated instrument reflecting an endoscopist's global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. The total SES-CD was calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease.
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) at Week 52
时间窗: Week 52
Clinical Symptom Remission defined by (1) the total number of liquid/very soft stools for the 7 days prior to the Week 52 visit being ≤ 10 (from CDAI Item 1); and (2) an abdominal pain (graded from 0 \[less severe\]-3 \[more severe\]) rating of ≤ 1 (from CDAI Item 2) on each day for the 7 days prior to the Week 52 visit. CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 2) at Week 16
时间窗: Week 16
Clinical Symptom Remission defined by (2) an abdominal pain (graded from 0 \[less severe\]-3 \[more severe\]) rating of ≤ 1 (from CDAI Item 2) on each day for the 7 days prior to the Week 16 visit. CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1) at Week 16
时间窗: Week 16
Clinical symptom remission defined by (1) the total number of liquid/very soft stools for the 7 days prior to the Week 16 visit being ≤ 10 (from CDAI Item 1). CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) at Week 16
时间窗: Week 16
Clinical Symptom Remission defined by (1) the total number of liquid/very soft stools for the 7 days prior to the Week 16 visit being ≤ 10 (from CDAI Item 1); and (2) an abdominal pain (graded from 0 \[less severe\]-3 \[more severe\]) rating of ≤ 1 (from CDAI Item 2) on each day for the 7 days prior to the Week 16 visit. CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1) at Week 52
时间窗: Week 52
Clinical symptom remission defined by (1) the total number of liquid/very soft stools for the 7 days prior to the Week 52 visit being ≤ 10 (from CDAI Item 1). CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 2) at Week 52
时间窗: Week 52
Clinical Symptom Remission defined by (2) an abdominal pain (graded from 0 \[less severe\]-3 \[more severe\]) rating of ≤ 1 (from CDAI Item 2) on each day for the 7 days prior to the Week 52 visit. CDAI score is a weighted, composite index of 8 items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations including fistula, use or non-use of antidiarrheal agents, presence or absence of abdominal mass, hematocrit, and body weight). Scores range from 0 to approximately 600 with higher scores indicating greater disease severity.
Number of Participants With Endoscopic Response at Week 52
时间窗: Baseline, Week 52
Endoscopic response defined as a ≥ 3-point decrease in the SES-CD from baseline to the SES-CD score obtained at Week 52. SES-CD is a validated instrument reflecting an endoscopist's global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. The total SES-CD was calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease.
次要结局
- Number of Participants With SES-CD Score of 0 at Week 52(Week 52)
- Number of Participants Who Achieved Clinical Remission (Defined as CDAI Score of <150) at Week 16(Week 16)
- Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) Over Time(From Baseline to Week 52)