Efficacy and Safety of Anti-MAP Therapy in Adult Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Intervention: RHB-104; Placebo
Intervention description: 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine; 5 placebo capsules administered orally BID
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 331.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Crohn's Disease; moderate to severe; remission; MAP; antibiotic

Summary:

      The investigators hypothesize that RHB-104 will have greater efficacy than placebo in Crohn's
      disease.
    

Eligibility criteria:

        Inclusion Criteria

          1. Signed fully informed consent provided as per this protocol.

          2. Diagnosis of Crohn's Disease confirmed by endoscopy or radiography and/or histology at
             least 6 months prior to randomization into the study.

          3. CD involving the ileum and/or colon

          4. Moderately to severely active CD (Crohn's Disease Activity Index (CDAI) score of
             greater than or equal to 220 and less than or equal to 450) at baseline.

          5. Current treatment with at least one of the following therapies:

             A. Oral 5-acetyl salicylic acid (5-ASA) compounds. Dose must be stable for at least 4
             weeks before baseline.

             B. Corticosteroid therapy. Dose must be stable for at least 2 weeks before baseline.

             C. Azathioprine or 6-mercaptopurine (6-MP) or methotrexate. Dose must be stable for at
             least 8 weeks before baseline.

             D. Infliximab or adalimumab. Dose must be stable for at least 14 weeks before
             baseline.

          6. White blood cell count greater than or equal to 3.5 x 109 at screening.

          7. Active Crohn's disease, defined by at least one of the following: C-reactive protein
             greater than Upper Limit of Normal (ULN) at screening, fecal calprotectin greater than
             Upper Limit of Normal (ULN) at screening, OR radiographic (MRE or CTE) or endoscopic
             confirmation of the presence of active CD within 5 weeks of screening visit. .

          8. Subject agrees to use barrier contraceptive methods (i.e. diaphragm, cervical cap,
             contraceptive sponge or condom) with spermicidal foam/gel/cream/suppository, IUD/IUS
             or progestogen injection (Depo-Provera®) throughout the study and for at least 6 weeks
             after last study drug administration, unless subject is post-menopausal or otherwise
             incapable of becoming pregnant by reason of surgery or tubal ligation, or has had a
             vasectomy. In regions where local regulatory contraceptive requirements differ, the
             ICF will reflect local policies.

        Exclusion Criteria

          1. Crohn's Disease involvement isolated to the mouth, upper gastrointestinal tract, or
             anus.

          2. History of total colectomy with ileorectal anastomosis or a proctocolectomy.

          3. Presence of active fistulizing Crohn's Disease or healed fistula within 2 months prior
             to screening.

          4. Subject has postoperative stoma, ostomy, or ileoanal pouch.

          5. Subject has short bowel syndrome.

          6. Subject is scheduled for surgical bowel resection.

          7. Subject has known symptomatic obstructive strictures or bowel perforation in the 6
             months prior to screening.

          8. Change in dose or discontinuation of oral 5-acetyl salicylic acid (5-ASA) compounds
             less than 4 weeks prior to baseline.

          9. Change in dose or discontinuation of corticosteroids less than 2 weeks prior to
             baseline.

         10. Change in dose or discontinuation of azathioprine, 6-mercaptopurine (6-MP) or
             methotrexate less than 8 weeks prior to baseline.

         11. Change in dose or discontinuation of infliximab or adalimumab less than 14 weeks prior
             to baseline.

         12. Treatment with vedolizumab less than 120 days prior to baseline or biological
             therapies (apart from infliximab or adalimumab) less than 60 days prior to baseline.

         13. Previous treatment with rifabutin and/or clofazimine.

         14. Oral or parenteral antibiotics in the 4 weeks prior to baseline (topical antibiotics
             are permitted).

         15. Treatment with probiotics (excluding yogurt and yogurt-derived products) in the 4
             weeks prior to baseline.

         16. Females who have a positive pregnancy test or are lactating.