Efficacy and Safety of Anti-MAP Therapy in Adult Crohn's Disease

A Randomized, Double Blind, Placebo-controlled, Multicenter, Parallel Group Study to Assess the Efficacy and Safety of Fixed-dose Combination RHB-104 in Subjects with Moderately to Severely Active Crohn's Disease.

Inclusion criteria

• Signed fully informed consent provided as per this protocol.
• Diagnosis of Crohn's Disease confirmed by endoscopy or radiography and/or histology at least 6 months prior to randomization into the study.
• CD involving the ileum and/or colon
• 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.
• 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.

• White blood cell count greater than or equal to 3.5 x 109 at screening.
• 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. .
• 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

• Crohn's Disease involvement isolated to the mouth, upper gastrointestinal tract, or anus.
• History of total colectomy with ileorectal anastomosis or a proctocolectomy.
• Presence of active fistulizing Crohn's Disease or healed fistula within 2 months prior to screening.
• Subject has postoperative stoma, ostomy, or ileoanal pouch.
• Subject has short bowel syndrome.
• Subject is scheduled for surgical bowel resection.
• Subject has known symptomatic obstructive strictures or bowel perforation in the 6 months prior to screening.
• Change in dose or discontinuation of oral 5-acetyl salicylic acid (5-ASA) compounds less than 4 weeks prior to baseline.
• Change in dose or discontinuation of corticosteroids less than 2 weeks prior to baseline.
• Change in dose or discontinuation of azathioprine, 6-mercaptopurine (6-MP) or methotrexate less than 8 weeks prior to baseline.
• Change in dose or discontinuation of infliximab or adalimumab less than 14 weeks prior to baseline.
• 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.
• Previous treatment with rifabutin and/or clofazimine.
• Oral or parenteral antibiotics in the 4 weeks prior to baseline (topical antibiotics are permitted).
• Treatment with probiotics (excluding yogurt and yogurt-derived products) in the 4 weeks prior to baseline.
• Females who have a positive pregnancy test or are lactating.