One Year Study of Rifaximin Delayed Release (DR) Tablets in Crohn's Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Rifaximin EIR
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: 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. Major Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rifaximin EIR 800 mg<br>Participants will receive rifaximin EIR 400 milligrams (mg) tablets orally twice daily for 52 weeks. | Drug: Rifaximin EIR<br>* Rifaximin EIR tablets will be administered per the dose and schedule specified in the arm.<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo matching to rifaximin EIR tablets orally twice daily for 52 weeks. | Drug: Placebo<br>* Placebo matching to rifaximin EIR tablets will be administered per the dose and schedule specified in the arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1) at 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. | Week 16 | 
| Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 2) at 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. | Week 16 | 
| Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) at 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. | Week 16 | 
| Number of Participants With Endoscopic Response Between Week 16 and 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. | Baseline, Week 16 to 17 | 
| Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1) at 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. | Week 52 | 
| Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 2) at 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. | Week 52 | 
| Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) at 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. | Week 52 | 
| Number of Participants With Endoscopic Response at 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. | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved Clinical Remission (Defined as CDAI Score of <150) at Week 16 | Clinical remission was defined as a CDAI score of less than 150 points at Week 16. 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. | Week 16 | 
| Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) Over Time | Clinical Symptom Remission defined by (1) the total number of liquid/very soft stools for the 7 days prior to each clinical 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 last 7 days prior to each clinic visit in ≥ 80% of the study visits during the 52-week treatment period, including Week 52. 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. | From Baseline to Week 52 | 
| Number of Participants With SES-CD Score of 0 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. | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, Rifaximin, Clinical remission with endoscopic response, Inflammatory Bowel Disease