Long-term Safety and Efficacy of Weekly Intravenous BMN 351 in Participants with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: An Open-Label Extension Study

The primary objective is to assess the long-term safety and tolerability of BMN 351 in individuals with Duchenne muscular dystrophy. The secondary objective includes:

• Evaluation of the effect of BMN 351 on physical function.

This clinical trial involves 8 male participants diagnosed with Duchenne muscular dystrophy. The study population consists of patients within specific age ranges designated by codes 2 and 3. Inclusion requires the prior completion of the 351-201 or 351-203 studies without permanent discontinuation of the investigational medicinal product or study withdrawal. Participants must be receiving a stable dose of oral corticosteroids, with the exception of dosage modifications necessitated by changes in weight. Sexually mature males are required to utilize contraception during the study period and for 90 days following the final administration of the study drug.

This phase 4, open-label extension study is designed to evaluate the long-term safety and efficacy of weekly intravenous infusion of BMN 351, an exon 51 specific phosphorothioate oligonucleotide, in individuals with Duchenne muscular dystrophy. The research methodology focuses on assessing long-term safety and tolerability through the monitoring of adverse events, physical examinations, laboratory parameters, electrocardiogram, and echocardiogram. Secondary endpoints include assessments using the North Star Ambulatory Assessment, timed 4-step climb, ventilatory capacity, and pulmonary function tests. Participants must have completed previous studies involving the investigational medicinal product without permanent discontinuation and must maintain a stable dose of corticosteroids. The study involves regular clinical monitoring, including assessments at baseline and subsequent 24-week intervals. The overall trial is expected to continue through December 2031.

The experimental treatment consists of BMN 351, which is an exon 51 specific phosphorothioate oligonucleotide. This substance is provided as a concentrate for solution for infusion. The administration involves a dosage of 12 mg/kg via intravenous infusion on a weekly basis.

Efficacy in this study of Duchenne Muscular Dystrophy is evaluated through several secondary parameters. The North Star Ambulatory Assessment, including the total score and specific components such as the timed 10-meter walk/run test and the time to rise, is measured at baseline and during subsequent quarterly visits. Additionally, the timed four-step climb is assessed at baseline and at subsequent quarterly visits. Motor function is further monitored using the PUL 2.0 at baseline and during subsequent quarterly visits. The SV95C is evaluated during 4-week monitoring periods preceding baseline and at subsequent quarterly visits.