The MYODA operational seamless clinical trial design phase I to III: a new approach for rare diseases to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of BIO101 (MAS activator) in paediatric patients with a genetically confirmed diagnosis of Duchenne muscular dystrophy

Clinical development of new medications is traditionally broken down into 3 phases. This prevents patients from participating in more than one of the development phases and comes with a burden on site staff (with repeated site initiation and training) leading to prolonged development timelines (up to 10 years) and difficulties in patient recruitment, especially in rare diseases such as DMD. There is a significant need, therefore, for utilization of novel designs, which will make clinical development more amenable for patients and more efficient for study site staff. Biophytis is developing BIO101 (20-hydroxyecdysone, MAS activator) for DMD. The pre-clinical proof-of-concept (PoC) for BIO101 demonstrates combined beneficial effects on skeletal muscle and respiratory functions in DMD animal models, suggesting a range of benefit in a broad DMD population. To ensure an optimal and patient-centered clinical development of BIO101, a seamless methodology is intended to be utilized. The trial design should take into consideration the needs and struggle of the patients who participate in the study. An operational seamless design is one that can cover the requirements, in terms of needed evidence, to support a new medicine (i.e. from phase I to phase III), while offering participants an access to the trial medication and reduce the need for repeated screening procedures. Biophytis proposes a 3-part study that combines Phase I to III of the clinical development in one operational seamless study with adaptive elements. Patients with DMD with various degrees of loss of ambulation will be recruited in one of the four-ascending multiple-dose cohorts of 1 week-duration (Part1), they will continue at the same dose for 24 weeks (Part2=phase II) in order to support dose(s) that will be tested for the pivotal Part 3. Continuing patients from Part 1 and 2 with additional patients will enter a 48 week-period (Part 3) to establish longer term safety and efficacy of BIO101.