Induction of Clinical Response Using Rifaximin in Crohn's Disease

• Status: Completed
• Trial end date: 2020-11-03
• Target enrollment: 0
• Participant gender: All

Summary

Antibiotics have been used to treat Crohn's disease symptoms with the best studied antibiotics being Cipro and Flagyl. Rifaximin is a poorly absorbed oral antibiotic that is FDA approved for travelers' diarrhea. It works by inhibiting bacterial reproduction. It is very poorly absorbed and over 97% of the drug taken orally is excreted in the feces.

The purpose of this study is to evaluate the potential benefits and safety of Rifaximin for the treatment of moderate to severe symptoms of Crohn's Disease.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Scott Lee
• Collaborators: Bausch Health Americas, Inc.; Valeant Pharmaceuticals International, Inc.
• Treatments: Rifamycins; Rifaximin

Criteria

Inclusion Criteria:

• Male or female subjects, 18 to 80 years of age, inclusive, that can themselves provide written, informed consent and authorization of use of protected health information prior to any study-related procedures and who are, in the opinion of the investigator(s), likely to comply with all the requirements of the study

• Subjects must have a prior diagnosis of CD established by endoscopy and clinical parameters as determined by the investigator(s) for at least 3 months prior to randomization

• Subjects must be able to participate in all required follow-up visits and fill out all related documentation (e.g. symptom diary)

• Subjects currently with moderately active disease defined as a CDAI 250-450

• Concomitant medications:

• If subjects are taking sulfasalazine or 5-ASA products prior to entry, the dose must be stable for at least 4 weeks prior to the randomization

• If subjects are on azathioprine, 6-mercaptopurine, or methotrexate, they will have had to be on a stable dosage for at least 8 weeks

• Subjects are allowed to be on corticosteroids at a dose equivalent to 20 mg or less of prednisone, IF the dose has been stable for a minimum of 2 weeks. Steroids must be held stable throughout the induction portion of the study. The maximum dose of budesonide must not exceed 9mg per day and must also have been stable for a minimum of 2 weeks.

• No oral or intravenous antibiotics within 4 weeks prior to randomization

• No current or past use of biological treatment within 6 weeks of randomization into study (e.g. infliximab)

• If subjects have previously been on any of the above products but are no longer taking them, they should not have received any of the relevant therapeutic products within 4 weeks prior to randomization

• No other experimental or non-FDA approved medications are allowed. If the subject has previously been on an experimental therapy, they must have not received the therapy within the prior 8 weeks prior to randomization

• Subjects on concomitant medications for CD will not be allowed to change dosages during the study

• If subjects are at increased risk of colorectal cancer (defined as having an 8-year history of pan-colitis or 12 year history of left sided colitis), they will need to have undergone a colonoscopy with pan-colonic surveillance biopsies within 2 years of the screening visit. The biopsies must be negative for dysplasia

• Female or male subjects who are surgically sterilized or who are prepared to and agree to practice a double-barrier form of birth control from the screening visit through 30 days (females) and 30 days (males), respectively, from the last dose of study medication. Females who are more than 12 months post-menopausal are also eligible to participate in the study

Exclusion Criteria:

• Evidence of active infection which may include any of the following

• Febrile ( > 38.5ºC)

• Positive blood culture within 2 weeks prior to randomization

• Evidence of toxic megacolon or abscess

• Positive stool culture for enteric pathogens, pathogenic ova or parasite, or a positive assay for C. difficile toxin at screening

• Subjects with CDAI > 450

• Any current use or use within the last 8 weeks of an investigational drug

• Current or past use (within past 12 wks) of biological treatment

• Current or use within the last 4 weeks of any oral or intravenous antibiotic

• Anticipated increased dosage of any medication to treat CD

• Anticipated need for surgery within 12 weeks

• Known obstructive diseases of the gastrointestinal system

• Medical conditions requiring in-patient hospitalization

• Proctocolectomy, total colectomy, ileostomy, or stoma

• Severe cardiopulmonary disease:

• Congestive heart failure (NYHA Class III or IV)

• Severe cardiovascular or peripheral vascular disease

• Myocardial infarction, percutaneous coronary intervention, or bypass surgery within the past 6 months

• Significant liver disease:

• Levels of SGOT [AST], SGPT [ALT], or alkaline phosphatase > 2.5x the upper limit of the normal range for the laboratory performing test

• History of cirrhosis

• Renal insufficiency, defined as serum creatinine > 150% of the upper limit of the normal range for the laboratory performing the test

• Abnormal hematology parameters defined as severe anemia with hemoglobin < 8.5 g/dL and/or white blood cell count of < 3,500/ul

• Malignancy within the past 2 years other than surgically cured skin carcinoma or cervical dysplasia (CIN I-II)

• History of dysplasia or carcinoma of the colon

• Pregnant, lactating, or planning to become pregnant during the course of the investigational study

• Known history of allergic reaction to rifaximin or allergy to any of the rifamycin antimicrobial agents (which include rifampin, rifabutin, and rifapentine)