RedHill Biopharma Announces Positive and Unanimous DSMB Recommendation for Continuation of Phase III Study with RHB-104 for Crohn’s Disease
GlobeNewswire•December 13, 2016
Following a pre-planned review of safety data, RedHill has received a unanimous recommendation from the independent Data and Safety Monitoring Board (DSMB) to continue the MAP US Phase III study with RHB-104 for Crohn’s disease as planned, without any modifications
A second DSMB meeting, expected in Q2/2017, will include an interim efficacy analysis and will evaluate the option of an early stop for success for overwhelming efficacy, according to a pre-specified statistical significance threshold
TEL-AVIV, Israel, Dec. 13, 2016 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (RDHL) (RDHL) (“RedHill” or the “Company”), a biopharmaceutical company primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today reported that, following a pre-planned review of safety data from its ongoing Phase III study with RHB-104 for Crohn’s disease (the MAP US study) by an independent Data and Safety Monitoring Board (DSMB), it has received a unanimous recommendation to continue the study as planned, without any modifications.
RHB-104 is a proprietary and potentially groundbreaking antibiotic combination therapy in oral capsule formulation, with potent intracellular, anti-mycobacterial and anti-inflammatory properties. The development of RHB-104 is based on increasing evidence supporting the hypothesis that Crohn’s disease, and potentially other autoimmune diseases, are related to Mycobacterium avium subspecies paratuberculosis (MAP) infection in susceptible patients. The development of RHB-104 is consistent with the growing awareness of the possibility that a bacterially-induced dysregulated immune system may contribute to the pathogenesis of various autoimmune diseases of unknown etiology.
The ongoing MAP US study is a randomized, double-blind, placebo-controlled first Phase III study intended to evaluate the safety and efficacy of RHB-104 in patients with moderately to severely-active Crohn’s disease (defined as Crohn’s Disease Activity Index (CDAI) between 220 and 450). To date, 242 patients have been enrolled out of a planned total of 410 patients in up to 150 clinical sites in the U.S, Canada, Europe, Israel, Australia and New Zealand.
Subjects enrolled in the MAP US study are randomized 1:1 to receive RHB-104 or a placebo, with a primary endpoint of disease remission, defined as reduction in CDAI to less than 150 at week 26. Secondary and exploratory endpoints include, among others, state of response at week 26, maintenance of remission through week 52, endoscopic evaluation of mucosal healing and efficacy outcome measures in relation to the presence of MAP bacterial infection. Additional studies will be required to support a U.S. New Drug Application (NDA) for RHB-104.
Two additional independent DSMB meetings are expected to take place in the MAP US study after 50% and after 75% of the 410 patients planned to be enrolled in the study will complete 26 weeks of study participation. The second independent DSMB meeting is expected in the second quarter of 2017 after the first 205 patients are expected to complete 26 weeks of study participation (patient 205 was randomized in August 2016).
The second DSMB meeting will include safety and interim efficacy analysis and could potentially provide the opportunity to expedite the data locking process for the final analysis, once the study is complete. Importantly, this independent DSMB meeting will evaluate the option of an early stop for success for overwhelming efficacy, according to a pre-specified statistical significance threshold for analysis of RHB-104 versus placebo in the primary endpoint. If the pre-specified threshold is met at the second DSMB meeting, the study could be stopped for efficacy or inefficacy. If the pre-specified threshold is not met during the interim analysis, the MAP US study is planned to continue through randomization of all 410 patients and follow-up at week 26.
Taking into account the increase in the total number of patients planned in the MAP US study, and assuming the study is not stopped for success or inefficacy following the DSMB meeting in the second quarter of 2017, completion of recruitment is expected by the end of 2017.
RedHill is advancing its preparation to initiate an open-label extension study for all patients who have completed 26 weeks of treatment in the MAP US study and failed to achieve remission at week 26, the study’s primary endpoint. Patients with a Crohn’s Disease Active Index (CDAI) score of greater than 150 at week 26 will be offered the opportunity to receive treatment with active drug (RHB-104) for a 52-week period. This study is considered separate from the MAP US study and data collected will be supplemental to the MAP US study data.
