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Crohn’s MAP Antibiotic Trial Results Expected Early
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RedHill Biopharma announced it has reduced the number of participants it will enroll in its phase 3 trial of RHB-104, an oral antibiotic for Crohn’s disease, and now expects results a year early.
RHB-104 is a combination antibiotic that targets Mycobacterium avium subspecies paratuberculosis (MAP), a suspected bacterial cause of Crohn’s disease.
“After reviewing the blinded, blended data from the patients enrolled in the phase 3 MAP US study, we found that we could curtail the study and complete it earlier while still maintaining power and treatment effect,” David Graham, MD, MACG, study investigator and physician at Baylor College of Medicine, said in a press release. “If the ... study is successful and if the drug is approved after completion of the required regulatory path, this curtailment may allow the treatment to be available earlier than initially planned, potentially changing the treatment paradigm for patients suffering from Crohn’s disease.”
The company considered the blended efficacy rate of the current blinded data along with external expert feedback to determine if the rate of treatment success is consistent with expectations, and that the study has sufficient enrollment to show efficacy. They concluded that reducing the target sample size from 410 to 325 participants, of whom 322 are already enrolled, would maintain over 80% statistical power and the ability to show the drug’s efficacy within the protocol-defined 15% treatment effect (36% vs. 21% with placebo).
As a result, the company will shorten the development program by about a year, and will save an estimated $14 million. They should complete enrollment by November and expect initial results by mid-2018, according to the press release.
The company said it remains blinded to the study data, and has filed a protocol amendment with the FDA and regulators in other countries.
“We believe that curtailment to a target sample size of approximately 325 subjects is the preferred approach in our effort to bring this potentially groundbreaking new therapy to the market as soon as possible,” Ira Kalfus, MD, Medical Director at RedHill, said in the press release. “The blended remission rate of the currently blinded data has been consistently within or superior to our pre-specified protocol defined assumptions, indicating potential study success at the curtailed sample size of approximately 325 subjects, assuming the placebo and RHB-104 remission rates in our study are in line with trial assumptions.”
Kalfus noted that “similar, but not identical, pivotal studies in Crohn’s disease” showed placebo remission rates between 7% and 25%, including the two most recently approved therapies, Entyvio (vedolizumab, Takeda; 7%) and Stelara (ustekinumab, Janssen; 20%).
The MAP US study is the first phase 3 randomized, double-blind, placebo-controlled trial evaluating RHB-104’s safety and efficacy in patients with moderate-to-severe active Crohn’s disease at up to 150 clinical sites in the U.S., Canada, Europe, Israel, Australia and New Zealand.
Disease remission will serve as the primary endpoint.
The company said it expects further clinical studies to be required to support a new drug application, and plans to meet with the FDA to discuss further development in the event these trial results are positive.
As Healio Gastroenterology and Liver Disease previously reported, the independent Data and Safety Monitoring Board unanimously recommended the study should continue after reviewing study data in December 2016 and July 2017.
A phase 3 open-label extension study is also ongoing (the MAP US2 study) to evaluate the drug’s safety and efficacy at up to 52 weeks in about 50 to 70 patients with active Crohn’s disease after 26 weeks treatment in the MAP US study. RedHill also plans additional open-label studies, and it is also developing a diagnostic for detecting MAP in patients with Crohn’s disease.
Further, the company plans to begin a pivotal phase 3 study of RHB-104 for the treatment of nontuberculous mycobacteria (NTM) infections in the first quarter of 2018. The FDA fast-tracked the development of RHB-104 for NTM infections via Qualified Infectious Disease Product (QIDP) designation, according to the press release.
The company is also evaluating the drug as a supplemental therapy in patients with relapsing-remitting multiple sclerosis. – by Adam Leitenberger
Disclosures: Kalfus is employed by RedHill, and Graham is a study investigator in the MAP US study.