Date: 2016-08-01
Type of information: Completion of the trial
phase: 2
Announcement: completion of the trial
Company: Redhill Biopharma (Israel)
Product: RHB-104
Action
mechanism: antibiotic. RHB-104 is a proprietary and potentially groundbreaking antibiotic combination therapy administered by oral capsule, with potent intracellular, antimycobacterial and anti-inflammatory properties.
Disease: relapsing remitting multiple sclerosis (RRMS)
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country: Israel
Trial
details: This phase 2a proof of concept study (the CEASE-MS study) aims to assess the efficacy and safety of fixed dose combination RHB-104 as add-on therapy to interferon Beta-1a in patients treated for relapsing remitting multiple sclerosis. The investigators hypothesize that Mycobacterium avium paratuberculosis positive relapsing remitting MS subjects will have a greater response to Interferon beta-1a therapy plus RHB-104 than from interferon beta-1a alone. (NCT01717664)
Latest
news: * On August 1, 2016, RedHill Biopharma announced that the last patient has completed the final scheduled follow-up visit in the Phase IIa proof-of-concept clinical study evaluating RHB-104 in patients treated for relapsing-remitting multiple sclerosis. The CEASE-MS study enrolled eighteen patients suffering from RRMS and was designed with a series of exploratory endpoints to evaluate the safety and potential efficacy of fixed oral dose RHB-104 as an add-on therapy to interferon beta-1a. Patients received treatment with RHB-104 for 24 weeks and were evaluated for an additional 24-week follow-up period during which they were treated with interferon beta-1a without RHB-104 add-on. The analysis of the study is currently ongoing and top-line final results are expected to be announced in the fourth quarter of 2016, subject to completion of review requirements and completion of the clinical study report (CSR). RedHill announced in March 2016 encouraging top-line interim results from the single-arm, open-label CEASE-MS study. Top-line interim results, after completion of the 24-week treatment period of the study, demonstrated positive safety and efficacy signals and support further clinical development, based on encouraging preliminary data. As previously announced, the top-line interim results demonstrated an annualized relapse rate (ARR) at 24 weeks of 0.288 in the modified intent-to-treat (mITT) population and 0.0 in the per-protocol (PP) population, comparing favorably with previously reported pivotal studies of interferon beta-1a therapies Avonex® (0.67) (2) and Rebif® (0.87-0.91). 88% of the mITT patient population and 100% of the PP patient population were relapse free at 24 weeks, comparing favorably with previously reported pivotal data on the use of Rebif® (75%) in comparison with Avonex® (63%) as standalone first-line therapies(4). No patient in the CEASE-MS study relapsed after week 8 of treatment. Expanded Disability Status Scale (EDSS) scores, a standard measure of MS disability, indicated the disease was stable during the treatment period and there was a signal of improvement; No increase in total EDSS was observed in any of the patients in the study. With only a single active T1 post gadolinium lesion noted among all patients followed, combined unique active lesions (CUAs) - the primary outcome measure in the CEASE-MS study - were almost entirely MRI T2 lesions. Although not powered for efficacy, a reduction in total MRI T2 lesion volume was observed at 24 weeks, as compared to baseline, suggesting a decreased burden of disease and comparing favorably with previously reported Avonex®(5) and Rebif®(6) data. No clinically significant change was observed for total CUA lesions at week 24, which is supportive of a stable disease state. RHB-104 was found to be safe and well tolerated, with no drug-related serious adverse events or other clinically relevant or unexpected adverse events. * On March 31, 2016, RedHill Biopharma announced encouraging top-line interim results from its ongoing CEASE-MS Phase IIa proof-of-concept (PoC) clinical study evaluating fixed oral dose RHB-104 in patients treated for relapsing-remitting multiple sclerosis (RRMS). The study interim results demonstrate positive safety data and clinical signals, supporting additional studies to better investigate the therapeutic potential of RHB-104 in RRMS. 88% of the mITT patient population and 100% of the per-protocol population were relapse free at 24 weeks of treatment. Importantly, a positive efficacy signal was seen in reduction of total T2 lesion volume at 24 weeks compared to baseline. Moreover, EDSS scores were stable with suggestion of improvement. No patients experienced an increase in total EDSS, further underscoring the therapeutic potential of RHB-104 for the treatment of RRMS. RHB-104 was observed to be safe and well-tolerated with no clinically relevant or unexpected adverse events. Patients are now completing their 24 week follow up treatment period, off RHB-104, and final results of the completed 48 week study are expected during the second half of 2016. Analysis of the completed study will drive next steps in the development path of RHB-104 for MS including identification of the patient population, comparator and clinical endpoints to be investigated in the next study. * On November 30, 2015, RedHill Biopharma announced completion of the last dosing and scheduled follow-up patient visit ahead of top-line interim analysis in the Phase IIa proof-of-concept clinical study evaluating RHB-104 in patients treated for relapsing-remitting multiple sclerosis (RRMS). The open label Phase IIa study (the CEASE-MS study) is being conducted in two medical centers in Israel. Eighteen patients suffering from RRMS were enrolled in the study, which was designed to assess the efficacy and safety of RHB-104 as an add-on therapy to interferon beta-1a. Patients received 24 weeks of treatment with RHB-104 and are being evaluated for an additional period of 24 weeks after completing treatment. The primary endpoint of the Phase IIa CEASE-MS study is the number of combined unique active lesions after 24 weeks of treatment with RHB-104, as compared to baseline. Additional endpoints include changes in cytokines, relapse rate, Expanded Disability Status Scale (EDSS) and the safety and tolerability of RHB-104. Top-line interim results are expected to be announced early in the first quarter of 2016. A full analysis and the final Clinical Study Report (CSR) are expected during the second quarter of 2016.
