RedHill Biopharma announced that an independent Data and Safety Monitoring Board (DSMB) recommended the company’s MAP US clinical trial to continue as planned without any modifications.
MAP US is an ongoing Phase 3 clinical trial (NCT01951326) testing RHB-104, a combination of antibiotics: rifabutin and clarithromycin with clofazamine, for the treatment of Crohn’s disease.
It is a randomized, double-blind placebo-controlled study, meaning the participants are randomly allocated to either the drug or a placebo, and that neither they nor the clinicians know who is receiving the drug and who is receiving a placebo. The aim of the trial is to evaluate the safety and effectiveness of RHB-104 in people with moderate to severe Crohn’s disease.
The company reported that more than half the planned number of participants (242 of 410) have already been enrolled for the study in up to 150 sites across the U.S., Canada, Europe, Israel, Australia and New Zealand.
The effectiveness of the drug will be determined by measuring disease remission defined as a reduction in the Crohn’s Disease Activity Index (CDAI) to less than 150 at week 26 (all patient had a CDAI between 220 and 450 at the beginning of the trial).
“Additional studies will be required to support a U.S. New Drug Application (NDA) for RHB-104,” the company wrote in a news release.
Two other independent DSMB meetings are expected to take place in the MAP US study. The first will take place once half of the enrolled participants complete 26 weeks of the study and the second once 75 percent of the enrolled participants complete 26 weeks of the study.
The second meeting is expected to take place in the second quarter of 2017 and will include safety and efficacy analyses for the trial. According to RedHill, “this independent DSMB meeting will evaluate the option of an early stop for success for overwhelming efficacy.”
This means that if a pre-specified threshold in CDAI for RHB-104 versus placebo is met at the second DSMB meeting, the study could be stopped for effectiveness. If the pre-specified threshold is not met, the study will continue until all 410 participants are enrolled and an analysis is conducted a week 26. In that case, it is expected that recruitment of all participants will be completed by the end of 2017.
Previous research suggests that Crohn’s disease may be caused by an infection by the Mycobacterium avium subspecies paratuberculosis (MAP) in susceptible people. It is thought that the bacterial infection may be disregulating the normal functioning of the immune system and triggering the development of autoimmune diseases such as Crohn’s disease.
RHB-104 holds intracellular, anti-mycobacterial and anti-inflammatory properties. Although the antibiotics that make up RHB-104 have been on the market for several years, the combination formulation as an oral capsule is new.
The company is also planning an open-label extension study for all participants who have failed to achieve remission at the end of the 26 weeks of treatment with RHB-104. In this study, patients with a CDAI score of more than 150 at week 26 will be offered the drug for a 52-week period.