Evaluation of Safety, Tolerability, and Changes in Biomarker and Clinical Outcome Assessments of Losmapimod for FSHD1 With Extension

This study is a single-centre, open-label pilot study that will investigate the safety, tolerability, pharmacokinetics (PK), and target engagement during long-term dosing with losmapimod tablets in adult subjects with FSHD1. Subjects will be evaluated during an 8- week pre-treatment period (Visits 1 through 3) to establish pre-treatment baseline assessments. Subjects will then be treated with losmapimod for approximately 1 year (Visits 4 through 9) and assessed at relatively regular intervals for change from pre-treatment assessments. All subjects will undergo two muscle biopsies; one at baseline, pre-treatment (Visit 4, Week 8 ± 1 week) and the second on-treatment muscle biopsy approximately 4 or 8 weeks later (Visit 5, Week 14 ± 2 weeks). Up to 8 subjects will have an on-treatment biopsy at 4 weeks and up to 8 subjects will have the on-treatment biopsy at 8 weeks.

Only subjects who participated in and competed all study procedures in the OLS Study treatment period (Week 60) will be eligible to participate in the open-label extension study.

The extension of this study will enable continued investigation of the safety and tolerability of long-term dosing with losmapimod tablets in adult subjects with FSHD1. During the extension study, subjects will receive 15 mg of losmapimod by mouth twice daily for a total of 30 mg by mouth daily. All subjects will attend clinic visits approximately every 24 weeks and have a safety phone call 12 weeks between in-person clinic visits until 90 days after commercial drug is available post regulatory approval or until study termination.

The primary endpoint of the main study is to evaluate the safety and tolerability of long-term dosing of losmapimod tablets in subjects with FSHD1. Secondary endpoints include assessment of target engagement of losmapimod in blood and skeletal muscle and repeated dose pharmacokinetics in subjects with FSHD1 over long-term dosing.

The extension will continue investigation of efficacy with assessment of skeletal muscle by ultrasound as well as the safety, tolerability, pharmacokinetics (PK), and exploration of efficacy measures including whole body skeletal muscle MRI and selected clinical outcome assessments during long- term dosing with losmapimod tablets in adult subjects with FSHD1. Secondary endpoints include assessment of efficacy as evaluated by whole body skeletal muscle MRI parameters, safety and tolerability of long-term dosing, target engagement of losmapimod in blood and skeletal muscle and repeated dose pharmacokinetics in subjects with FSHD1 over long-term dosing.