A Study of EDG-5506 in Children With Duchenne Muscular Dystrophy (LYNX)

A 2-part Phase 2 Study of Safety, Pharmacokinetics and Biomarkers in Children With Duchenne Muscular Dystrophy Including a Randomized, Double-Blind, Placebo-Controlled Part A, Followed by an Open-Label Part B

The LYNX study is a 2-part, multicenter, Phase 2 study of safety, pharmacokinetics and biomarkers in children with Duchenne muscular dystrophy including a randomized, double-blind, placebo-controlled part A, followed by an open-label part B.

This is a 2-part, multi-center, Phase 2 study to evaluate the effect of sevasemten (EDG-5506) on safety, pharmacokinetics and biomarkers of muscle damage in approximately 72 children with DMD treated with oral, once-daily sevasemten for up to 48 months. This study will have up to a 4-week Screening period, a 12-week randomized, double-blind, placebo controlled treatment period (Part A), up to a 196-week open-label extension period (Part B), and a 2-week follow up period.

Approximately 72 participants aged 4 to 9 years inclusive will be randomized to sevasemten or placebo in a 2:1 ratio. Five dose cohorts (C1, C2, C3, C4 and C5) of approximately 9 participants each will be enrolled sequentially. Approximately 18 total additional participants may be added across Cohorts 2, 3, or 4.

An additional cohort, Cohort 2NS, to include participants (aged 4 to 7 years inclusive) not currently treated with corticosteroids, will enroll approximately 9 participants after Cohort 2 safety review and in parallel with the additional cohorts.

After review of emerging data, the protocol was amended so all dose cohorts receive the same dose in Part B.

Key Common Inclusion Criteria:

1. A documented mutation on the DMD gene and phenotype consistent with Duchenne muscular dystrophy.
2. Able to complete the stand from supine in ≤ 10 seconds and able to perform the 4-stair climb in < 10 seconds at the Screening visit.
3. Body weight greater than or equal to 15 kg at the Screening visit.

For Cohorts 1, 2, 3, 4 and 5:

Aged 4-9 years on a stable dose of corticosteroids for a minimum of 6 months prior to the Baseline visit.

For Cohort 2 Non-Steroid (Cohort 2NS):

Aged 4-7 years not on corticosteroids within 6 months prior to the Baseline visit.

Key Common Exclusion Criteria:

1. Medical history or clinically significant physical exam/laboratory result that, in the opinion of the investigator, would render the participant unsuitable for the study. This includes venous access that would be too difficult to facilitate repeated blood testing.
2. A forced vital capacity < 60% predicted at the Screening visit for those participants who are > 8 years old at Screening.
3. A cardiac echocardiography showing left ventricular ejection < 45% at the Screening visit.
4. Receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) of the Screening visit in the present study.
5. Receipt of a stable dose of an approved exon-skipping therapy with a treatment duration of less than 1 year prior to the Screening visit.

For Cohort 2 Non-Steroid (Cohort 2NS):

Receipt of oral corticosteroids for the treatment of Duchenne muscular dystrophy in the previous 6 months. Participants will not be tapered off steroids for the purpose of this study and oral corticosteroids for the treatment of Duchenne muscular dystrophy may be initiated after the Week 16 visit.