Objective
To assess safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of SAT-3247 in a first-in-human phase 1a/1b study
Background
Duchenne muscular dystrophy (DMD) is caused by dystrophin gene mutations, leading to progressive muscle degeneration, loss of ambulation, and premature mortality. SAT-3247 is an oral small molecule that modulates muscle stem cell (satellite cell) polarity and asymmetric division via regulation of adapter associated kinase 1 (AAK1), to restore regenerative capacity independent of dystrophin expression.
Design/Methods
Phase 1a was a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose trial in 72 healthy subjects assessing safety, PK, and food effect. Phase 1b was a 28-day, open-label study in five adult males (20–27 years) with genetically confirmed DMD, assessing safety, PK, and exploratory efficacy markers
Results
SAT-3247 was well tolerated at all doses in both studies, with no drug-related moderate or higher adverse events and no dose-limiting toxicities. PK in healthy volunteers and DMD participants aligned with desired exposure profiles predicted from preclinical efficacy. Exploratory PD analyses indicated a potential exposure-related mean change in grip strength of 118.6% in the dominant and 97.9% in the non-dominant hand. Percent predicted forced vital capacity improved in tested subjects with a mean change of 5.8%. All other measures displayed stability over the study period.
Conclusions
These results suggest a favorable safety and PK profile for SAT-3247 and biological activity consistent with its proposed mechanism. Participants will be invited to participate in a long-term follow-up study. Further evaluation in a Phase 2 randomized, placebo-controlled trial in pediatric ambulatory DMD patients is warranted.