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

Phase 2
Active, not recruiting
Conditions
Duchenne Muscular Dystrophy
Interventions
Drug: Sevasemten Dose 2
Drug: Sevasemten Dose 3
Drug: Sevasemten Dose 4
Drug: Sevasemten Dose 5
Drug: Sevasemten Dose 1
Drug: Placebo
Registration Number
NCT05540860
Lead Sponsor
Edgewise Therapeutics, Inc.
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 include an additional dose cohort and a cohort to include participants not currently treated with corticosteroids.

This is a 2-part, multi-center, Phase 2 study to evaluate the effect of EDG-5506 on safety, pharmacokinetics and biomarkers of muscle damage in approximately 54 children with DMD treated with oral, once-daily EDG-5506 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 54 participants aged 4 to 9 years inclusive will be randomized to EDG-5506 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.

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
76
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 and less than 35 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Cohort 1PlaceboDrug: Sevasemten Drug: Placebo
Cohort 2Sevasemten Dose 2Drug: Sevasemten Drug: Placebo
Cohort 2PlaceboDrug: Sevasemten Drug: Placebo
Cohort 3Sevasemten Dose 3Drug: Sevasemten Drug: Placebo
Cohort 3PlaceboDrug: Sevasemten Drug: Placebo
Cohort 4Sevasemten Dose 4Drug: Sevasemten Drug: Placebo
Cohort 4PlaceboDrug: Sevasemten Drug: Placebo
Cohort 5Sevasemten Dose 5Drug: Sevasemten Drug: Placebo
Cohort 5PlaceboDrug: Sevasemten Drug: Placebo
Cohort 2NSSevasemten Dose 2Drug: Sevasemten Drug: Placebo
Cohort 2NSPlaceboDrug: Sevasemten Drug: Placebo
Cohort 1Sevasemten Dose 1Drug: Sevasemten Drug: Placebo
Primary Outcome Measures
NameTimeMethod
Number of adverse events during treatment with sevasemten or placebo24 months

All participants

Severity of adverse events during treatment with sevasemten or placebo24 months

All participants

Secondary Outcome Measures
NameTimeMethod
Incidence of abnormal coagulation test results24 months

All participants

Incidence of abnormal urinalysis test results24 months

All participants

Incidence of abnormal clinical chemistry test results24 months

All participants

Incidence of abnormal hematology test results24 months

All participants

Pharmacokinetics as measured by steady state plasma concentration24 months

All participants

Change from Baseline in serum creatinine kinase12 weeks

All participants

Change from Baseline in fast skeletal muscle troponin I12 weeks

All participants

Trial Locations

Locations (14)

Arkansas Children's Hospital

🇺🇸

Little Rock, Arkansas, United States

UCLA Medical Center

🇺🇸

Los Angeles, California, United States

UC Davis Medical Center

🇺🇸

Sacramento, California, United States

Children's Hospital Colorado

🇺🇸

Aurora, Colorado, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

Rare Disease Research

🇺🇸

Atlanta, Georgia, United States

University of Iowa

🇺🇸

Iowa City, Iowa, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

Kennedy Krieger Institute

🇺🇸

Baltimore, Maryland, United States

University of Massachusetts Memorial Medical Center

🇺🇸

Worcester, Massachusetts, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Cincinnati Children's Hospital

🇺🇸

Cincinnati, Ohio, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

Cook Children's Medical Center

🇺🇸

Fort Worth, Texas, United States

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