P.403 - PhaseOut DMD: a Phase 2, proof of concept, clinical study of utrophin modulation with ezutromid

Abstract

This study investigates the hypothesis that Duchenne muscular dystrophy (DMD) can be treated by stimulating utrophin expression in muscles to replace missing or defective dystrophin. Ezutromid (SMT C1100) is an orally-available, small-molecule, utrophin modulator that enhances utrophin production in vitro and in the mdx mouse. In previous Phase I patient studies, ezutromid was shown to be safe and well tolerated. PhaseOut DMD is a Phase 2, open-label, study assessing the activity and safety of ezutromid, administered orally to ambulatory boys with DMD, aged 5–10 years. This is a multi-centre study in the UK and the US. It includes a 28-day Baseline and Screening Phase, a 48-week open-label Treatment Phase and a 30-day Safety Follow-up Phase. In Cohort 1, approximately 30 patients will receive 2.5 g ezutromid bid as a microfluidised aqueous oral suspension (F3). In Cohort 2 (US sites only) approximately 10 patients will receive 1 g ezutromid bid as a powder for oral suspension (F6). The study investigates the relationships between ezutromid levels and utrophin modulation, muscle markers of regeneration, and long-term impact on functional measures. MRI measurements of muscle adiposity and inflammation at 12 week intervals are a primary endpoint, along with plasma concentrations of ezutromid and its metabolites. Changes between baseline and 24 or 48 weeks in utrophin protein expression and in biomarkers of muscle regeneration are secondary endpoints, as are safety parameters. Functional tests, including the 6-minute walking distance (6MWD) test and the North Star Ambulatory Assessment (NSAA) global score, are exploratory endpoints. PhaseOut DMD is expected to complete enrolment in Q2 2017 and to report interim findings in Q1 2018. An extension of the study is planned. Results of this study are expected to facilitate the design of a pivotal study for the treatment of DMD. Details of the protocol and baseline data will be presented.