Clinical trial NCT05540860: A Study of EDG-5506 in Children With Duchenne Muscular Dystrophy (LYNX)
Official title: 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
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: 2022-09-15
Enrollment: 76
Sex: MALE
Minimum age (years): 4
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The EDG-5506-210 protocol was amended to enroll additional participants across select cohorts.

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 24 months. This study will have up to a 4-week Screening period, a 12-week randomized, double-blind, placebo controlled treatment period (Part A), a 92-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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of adverse events during treatment with sevasemten or placebo
timeFrame: 24 months
measure: Severity of adverse events during treatment with sevasemten or placebo
timeFrame: 24 months
Secondary outcomes:
measure: Incidence of abnormal clinical chemistry test results
timeFrame: 24 months
measure: Incidence of abnormal hematology test results
timeFrame: 24 months
measure: Incidence of abnormal coagulation test results
timeFrame: 24 months
measure: Incidence of abnormal urinalysis test results
timeFrame: 24 months
measure: Pharmacokinetics as measured by steady state plasma concentration
timeFrame: 24 months
measure: Change from Baseline in serum creatinine kinase
timeFrame: 12 weeks
measure: Change from Baseline in fast skeletal muscle troponin I
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
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: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
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: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
Study officials:
References: