A Phase III 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
A potential cause of Crohn's disease (CD) is infection with Mycobacterium avium subsp. paratuberculosis. RedHill Biopharma is currently enrolling the MAP US study to investigate RHB-104, a new antibiotic treatment for CD. RHB-104 combines clarithromycin, rifabutin, and clofazimine - in a novel treatment regimen for CD. These three antibiotics are active against MAP, and may provide an innovative therapeutic option to patients with CD. The purpose of the study is to investigate the efficacy and safety of 26 weeks of oral RHB-104 therapy vs. placebo in inducing remission in patients with moderately to severely active Crohn's disease.
MAP US is a double blind, placebo controlled study designed to evaluate the safety and efficacy of RHB-104 compared to placebo in treating patients with moderate to severe Crohn's disease. Remission at week 26 is the primary objective of MAP US; however, as MAP grows slowly the duration of RHB-104 needed to achieve remission may vary. The Crohn's Disease Activity Index (CDAI) will be used to assess induction and maintenance of remission in patients through week 52.
RHB-104 combines clarithromycin, rifabutin, and clofazimine in a novel treatment regimen for CD. These three antibiotics are active against MAP, an infection that may cause Crohn's disease. The target dose of RHB-104 is 5 capsules taken twice per day. In order to reach this target with minimal adverse effects, the dose is gradually increased over the first 4 weeks of treatment, and remains stable thereafter. Patients will remain on their unchanged baseline CD treatment throughout the study although steroids may be tapered after Week 8 at the discretion of the investigator.
Patients will be tested for the presence of MAP prior to beginning treatment and throughout the study. The inflammatory markers C-Reactive Protein (CRP) and fecal calprotectin will be investigated as will changes in fecal microbiome and all results will be examined for correlation with MAP status.
Possible Risks and Side Effects:
During the collection of blood samples, you may experience pain and/or bruising at the needle site. Although rare, localized clot formation and infections may occur. Lightheaded feelings and/or fainting may also occur during or shortly after the blood draw.
As with all antibiotics, there may be side effects. Possible side effects include:
• Tooth discoloration, skin discoloration, and urine discoloration
• Abnormal liver function tests and joint pains
• Vaginal yeast infection
• Eye pain
• Irregular heart beats
• Diarrheal infections called C. difficile, resistance to antibiotics
• Diarrhea, nausea, changes in taste, abdominal pain/discomfort, headache, vomiting, dry mouth, and decreased appetite
• Decreased white blood cells - the cells that fight infection
Explanation of Participation:
If a participant qualifies and decides to enroll in the study, lab tests and evaluations will be provided free of charge.
The study will involve at least 14 visits to the research site over 62 weeks.
Physical examinations, blood testing for safety, the presence of MAP and RHB-104 drug levels, and electrocardiogram (ECG) monitoring will be performed often. Patients will be given standardized questionnaires that will be used to measure response to the treatment for their Crohn's Disease Activity. Survey will be assessed at baseline and after completing 26 and 52 weeks of treatment. Colonoscopy to demonstrate mucosal healing prior to and after 26 weeks of treatment will be offered to all patients, but this is not mandatory and is at the patient's discretion.
Observation Period:Participation may last up to 62 weeks including screening, 52 weeks of treatment, and 4 week safety follow-up.
• Males and females 18 to 75 years of age.
• Diagnosis of Crohn’s Disease 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 ≥ 220 and ≤450)
• Patient must be intolerant or have insufficient response to conventional therapy.
• Patients must meet concomitant medication criteria described below
o Oral 5-acetyl salicylic acid (5-ASA) compounds
• If currently being taken, dose must be stable for at least 4 weeks
• If discontinued due to lack of response or lack of tolerance, the stop-date must have been at least 4 weeks prior to baseline
o Corticosteroid therapy
• If currently being taken, dose must be stable for at least 2 weeks
• If discontinued due to lack of a response or lack of tolerance, stop date must have been at least 2 weeks prior to baseline
o Azathioprine or 6-mercaptopurine (6-MP) or methotrexate
• If currently being used, dose must be stable for at least 8 weeks
• If discontinued due to a lack of response or lack of tolerance, stop date must have been at least 4 weeks prior to baseline
• White blood cell count ≥ 3.5x109 at screening.
• Active Crohn’s disease, defined by at least one of the following: elevated C-reactive protein, fecal calprotectin, OR photographic confirmation of the presence of active CD within 4 weeks of screening visit.
• Subject agrees to use contraceptive methods or is otherwise incapable of becoming pregnant, or has had a vasectomy.
• 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.
• Patient has postoperative stoma, ostomy, or ileoanal pouch, short bowel syndrome, is scheduled for surgical bowel resection, or has has known symptomatic obstructive strictures or bowel perforation in the 6 months prior to screening.
• Treatment with anti-TNF biologic agents or other biological therapies < 8 weeks prior to baseline or within 5 half-lives of agent prior to baseline, whichever is longer.
• 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
For More Information: http://www.mapmycrohns.com/EN/screener.html
Manhattan Medical Research Practice PLLC
215 Lexington Avenue, New York, NY 10016, USA
New York, NY, 10016