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

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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02240121

Enrollment

Registered

2014-09-15

Start date

2014-08-21

Completion date

2017-08-16

Last updated

2019-09-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Crohn's Disease

Keywords

Crohn's Disease, Rifaximin, Clinical remission with endoscopic response, Inflammatory Bowel Disease

Brief summary

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

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).

Interventions

DRUGRifaximin EIR

Rifaximin EIR tablets will be administered per the dose and schedule specified in the arm.

DRUGPlacebo

Placebo matching to rifaximin EIR tablets will be administered per the dose and schedule specified in the arm.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Endoscopic Response at Week 52	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.
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1) at Week 52	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	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 Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) at Week 52	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 1) at Week 16	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 2) at Week 16	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 and 2 Both) at Week 16	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 With Endoscopic Response Between Week 16 and 17	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.

Secondary

Measure	Time frame	Description
Number of Participants Who Achieved Clinical Symptom Remission (From CDAI Item 1 and 2 Both) Over Time	From Baseline to Week 52	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.
Number of Participants With SES-CD Score of 0 at Week 52	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.
Number of Participants Who Achieved Clinical Remission (Defined as CDAI Score of <150) at Week 16	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.

Countries

United States

Participant flow

Recruitment details

A total of 80 participants were enrolled and randomized in this study.

Pre-assignment details

Participants were randomized in a 1:1 allocation to Rifaximin EIR 800 mg or Placebo at the beginning of the treatment period and were maintained on that treatment assignment for 16 weeks, followed by an open-label long-term active treatment extension of an additional 36 weeks.

Participants by arm

Arm	Count
Rifaximin EIR 800 mg Participants received rifaximin EIR 400 mg tablets orally twice daily for 52 weeks.	40
Placebo Participants received placebo matched to rifaximin EIR tablets orally twice daily for 52 weeks.	40
Total	80

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	2	4
Overall Study	Change in protocol interpretation	1	0
Overall Study	Lack of Efficacy	2	3
Overall Study	Lost to Follow-up	3	4
Overall Study	Other than specified	1	3
Overall Study	Physician Decision	0	1
Overall Study	Pregnancy	1	0
Overall Study	Protocol Violation	1	2
Overall Study	Site closed	1	1
Overall Study	Withdrawal by Subject	6	2

Baseline characteristics

Characteristic	Rifaximin EIR 800 mg	Placebo	Total
Age, Continuous	39.1 years STANDARD_DEVIATION 15.2	38.8 years STANDARD_DEVIATION 14.1	38.9 years STANDARD_DEVIATION 14.6
Crohn's Disease Activity Index (CDAI) Score	298.5 units on a scale STANDARD_DEVIATION 56.89	296.9 units on a scale STANDARD_DEVIATION 70.86	297.7 units on a scale STANDARD_DEVIATION 63.85
Duration of Disease	9.8 years STANDARD_DEVIATION 7.69	9.6 years STANDARD_DEVIATION 7.71	9.7 years STANDARD_DEVIATION 7.65
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	1 Participants	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants	39 Participants	77 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	4 Participants	5 Participants	9 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	36 Participants	34 Participants	70 Participants
Sex: Female, Male Female	25 Participants	22 Participants	47 Participants
Sex: Female, Male Male	15 Participants	18 Participants	33 Participants
Simple Endoscopic Score for Crohn's Disease (SES-CD)	12.7 units on a scale STANDARD_DEVIATION 5.85	13.8 units on a scale STANDARD_DEVIATION 6.4	13.3 units on a scale STANDARD_DEVIATION 6.11

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 40	0 / 40
other Total, other adverse events	24 / 40	24 / 40
serious Total, serious adverse events	7 / 40	7 / 40

Outcome results

Primary

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.

Time frame: Week 16