Clinical trial NCT06100887: Phase 2 Study of EDG-5506 in Children and Adolescents With Duchenne Muscular Dystrophy Previously Treated With Gene Therapy
Official title: A Phase 2 Study to Evaluate the Effect of EDG-5506 on Safety, Pharmacokinetics, and Biomarkers in Children and Adolescents With Duchenne Muscular Dystrophy Previously Treated With Gene Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne Muscular Dystrophy
Lead sponsor: Edgewise Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-25
Enrollment: 43
Sex: MALE
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The FOX study is a 2-part, multicenter, Phase 2 study of safety, pharmacokinetics, and biomarkers in children and adolescents with Duchenne muscular dystrophy previously treated with gene therapy including a randomized, double-blind, placebo-controlled Part A, followed by an open-label part B.

Detailed description: The EDG-5506-215 protocol was amended to include an additional dose cohort and enroll additional participants across select cohorts.

FOX 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 48 children and adolescents with Duchenne muscular dystrophy treated with oral, once-daily sevasemten. This study will have up to a 4-week Screening period, a 12-week randomized double-blind, placebo-controlled treatment period (Part A), followed by a 40-week open-label extension period (Part B) .

Approximately forty-eight (48) participants aged 6 to 17, inclusive, will be randomized to sevasemten or placebo in a 2:1 ratio. Three dose cohorts (Cohort 1, Cohort 2 and Cohort 3) of approximately 12 participants each will be enrolled. Approximately 12 additional participants may be added to 1 of these cohorts following Data Monitoring Committee (DMC) review of emerging data.

Eligibility criteria: Key Inclusion Criteria:

* Aged 6 to 17 with a documented mutation on the DMD gene and phenotype consistent with DMD.
* Prior receipt of an AAV-based gene therapy (≥ 2 years after study drug administration in an open-label study or ≥ 3 years after randomization in a randomized study).
* Able to complete stand from supine in ≤ 8 seconds at the Screening visit and able to perform the 4-stair climb in \< 10 seconds at the Screening visit.
* Body weight ≥ 15 kg at the Screening visit.
* Treatment with a stable dose of corticosteroids for a minimum of 6 months prior to the Baseline visit.

Key Exclusion Criteria:

* 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 sampling.
* Screening visit cardiac echocardiography showing left ventricular ejection fraction (LVEF) \< 40%.
* Receipt of an investigational drug (other than the AAV-based gene therapy per Inclusion criteria) within 30 days or 5 half-lives (whichever is longer) of the Screening visit in the present study.
* Receipt of an exon-skipping therapy within 6 months prior to the Screening visit.

Primary outcomes:
measure: Number of adverse events during treatment with sevasemten or placebo
timeFrame: 12 months
measure: Severity of adverse events during treatment with sevasemten or placebo
timeFrame: 12 months
Secondary outcomes:
measure: Incidence of abnormal clinical chemistry test results
timeFrame: 12 months
measure: Incidence of abnormal hematology test results
timeFrame: 12 months
measure: Incidence of abnormal coagulation test results
timeFrame: 12 months
measure: Incidence of abnormal urinalysis test results
timeFrame: 12 months
measure: Pharmacokinetics as measured by steady state plasma concentration
timeFrame: 12 months
measure: Change from Baseline in serum creatine kinase
timeFrame: 12 weeks
measure: Change from Baseline in fast skeletal muscle troponin I
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hillsborough
country: United States
facility: Rare Disease Research
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
References: