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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: RHB-104
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RHB-104<br>5 RHB-104 capsules administered orally BID | Drug: RHB-104<br>* 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine<br>|
| Placebo Comparator: Placebo<br>5 placebo capsules administered orally BID | Drug: Placebo<br>* 5 placebo capsules administered orally BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission at Week 26 | Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150. Lower CDAI scores indicate a better outcome. | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response at Week 26 | Reduction of Crohn's Disease Activity Index (CDAI) score by a minimum of 100 points. Lower CDAI scores indicate a better outcome. | Week 26 | 
| Remission at Week 52 | Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150. Lower CDAI scores indicate a better outcome. | Week 52 | 
| Durable Remission Week 26 Through Week 52 | When a subject is in remission with a maximum CDAI score of 149 at every visit from Week 26 through and including Week 52 | Week 26 through week 52 | 
| Remission at Week 16 | Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150. Lower CDAI scores indicate a better outcome. | Week 16 | 
| Steroid Free Remission at Week 52 | Subjects who are maintained off steroids for a minimum of 3 weeks | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibiotic, Crohn's Disease, moderate to severe, remission, MAP