A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD) (EMBARK)

A Phase 3 Multinational, Randomized, Double-Blind, Placebo-Controlled Systemic Gene Delivery Study to Evaluate the Safety and Efficacy of SRP-9001 in Subjects With Duchenne Muscular Dystrophy (EMBARK)

The study will evaluate the safety and efficacy of gene transfer therapy in boys with DMD. It is a randomized, double-blind, placebo-controlled study. The participants who are randomized to the placebo arm will have an opportunity for treatment with gene transfer therapy at the beginning of the second year.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Genetic: delandistrogene moxeparvovec; Genetic: placebo

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • University Hospital Ghent
• Germany
  • Bayern, Germany, 80337
    • LMU - Klinikum der Universitaet Muenchen - Kinderklinik und
  • Essen, Germany, 45147
    • Universitätsklinikum Essen - Klinik für Kinderheilkunde I
  • Hamburg, Germany, 20251
    • University Hospital Hamburg- Eppendorf
• Hong Kong
  • Kowloon, Hong Kong
    • Hong Kong Children's Hospital
• Italy
  • Genoa, Italy, 16147
    • IRCCS Istituto G.Gaslini, U.O.
  • Milano, Italy, 20122
    • UOC Neurologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Roma, Italy, 00168
    • UOC Neuropsichiatria Infantile, Area Salute del Bambino, Fondazione Policlinico Universitario A. Gamelli IRCCS
• Japan
  • Kobe, Japan, 650-0017
    • Kobe University Hospital
  • Tokyo, Japan, 187-8551
    • National Center of Neurology and Psychiatry
  • Tokyo, Japan, 157-8535
    • National Center for Child Health and Development
  • Tokyo, Japan, 162-8666
    • Tokyo Women's Medical University Hospital - Pediatrics
• Spain
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Déu
  • Comunidad Valencia
    • Valencia, Comunidad Valencia, Spain
      • Hospital Universitari i Politécnico La Fe
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 100225
    • National Taiwan University Hospital
• United Kingdom
  • London, United Kingdom, WC1N3JK
    • Great Ormond Street Hospital for Children NHS Foundation Trust
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • The Newcastle Upon Tyne NHS Hospital NHS Foundation Trust, Royal Victoria Infirmary
  • Oxford
    • Headington, Oxford, United Kingdom, OX3 9DU
      • Oxford University Hospitals NHS Foundation Trust
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's
  • California
    • La Jolla, California, United States, 92037
      • UC San Diego Altman Clinical and Translational Research Institute
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital at Stanford
    • Sacramento, California, United States, 95817
      • University of California, Davis
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Stead Family Children's Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University of St. Louis
  • New York
    • New York, New York, United States, 10032
      • Columbia University/NYPH
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center, Lenox Baker Children's Hospital
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Children's Hospital of The King's Daughters
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 3 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is ambulatory and from 4 to under 8 years of age at time of randomization.
• Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
• Ability to cooperate with motor assessment testing.
• Stable daily dose of oral corticosteroids for at least 12 weeks prior to Screening, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight).
• rAAVrh74 antibody titers are not elevated as per protocol-specified requirements.
• A pathogenic frameshift mutation or premature stop codon contained between exons 18 and 79 (inclusive), with the exception of mutation fully contained within exon 45.

Exclusion Criteria:

• Exposure to gene therapy, investigational medication, or any treatment designed to increase dystrophin expression within protocol specified time limits.
• Abnormality in protocol-specified diagnostic evaluations or laboratory tests.
• Presence of any other clinically significant illness, medical condition, or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risk for gene transfer.

Other inclusion or exclusion criteria could apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delandistrogene Moxeparvovec followed by Placebo; Participants will receive single intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1. Then, participants will receive a single IV infusion of matching placebo at Year 2.	Genetic: delandistrogene moxeparvovec; Single IV infusion of delandistrogene moxeparvovec.; Other Names: SRP-9001; delandistrogene moxeparvovec-rokl; ELEVIDYS; Genetic: placebo; Single IV infusion of matching placebo.
Placebo Comparator: Placebo followed by Delandistrogene Moxeparvovec; Participants will receive matching placebo IV infusion on Day 1. Then, participants will have the opportunity to receive a single IV infusion of delandistrogene moxeparvovec at Year 2.	Genetic: delandistrogene moxeparvovec; Single IV infusion of delandistrogene moxeparvovec.; Other Names: SRP-9001; delandistrogene moxeparvovec-rokl; ELEVIDYS; Genetic: placebo; Single IV infusion of matching placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52	The NSAA is a healthcare provider administered scale that rates performance of various motor abilities in ambulant children with Duchenne Muscular Dystrophy and is used to monitor disease progression and treatment effects. During assessment, participants are asked to perform 17 different functional activities that are graded as: 2 - "Normal" - no obvious modification of activity; 1 - Modified method but achieves goal independent of assistance; 0 - Unable to achieve independently. The NSAA total score is defined as the sum of all 17 items, ranging from 0 (worst) to 34 (best). The response vector consists of the change from baseline in NSAA total score at the post-baseline visit. The model includes the covariates of treatment group, visit, treatment group by visit interaction, age group, baseline NSAA total score, and baseline NSAA total score by visit interaction. All covariates are fixed effects in this analysis. An increase in score indicates an improvement in motor function.	Baseline, Week 52 (Part 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by Western Blot Adjusted by Muscle Content	Quantity of delandistrogene moxeparvovec dystrophin protein levels (in muscle biopsy samples) were determined by Western blot at Part 1, Week 12. For this endpoint, 2 blocks of tissues were analyzed by Western blot, each with 2 technical replicates to determine the delandistrogene moxeparvovec dystrophin protein level (percent control). The block average value from 2 technical replicates was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for the analysis. Dystrophin protein was measured and then adjusted based on the percentage of muscle content in the biopsy sample. An increase in protein expression indicates production of the delandistrogene moxeparvovec dystrophin protein.	Week 12
Part 1: Change From Baseline in the Timed Stair Ascend 4 Steps Test at Week 52	The timed stair ascend 4 steps test quantifies the time required for the participant to ascend 4 standard steps (each step was 6 inches in height). Data presented is the change from baseline to Week 52 in the time (in seconds) to ascend 4 steps.	Baseline, Week 52 (Part 1)
Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Score in Mobility to Week 52	PROMIS is a family of instruments developed and validated to assess health-related quality of life, including mobility. Mobility function scores ranged from 1 (worst mobility function) to 5 (best mobility function), where higher scores indicate a better clinical outcome.	Baseline, Week 52 (Part 1)
Part 1: Change From Baseline in PROMIS Score in Upper Extremity Function to Week 52	PROMIS is a family of instruments developed and validated to assess health-related quality of life, including upper extremity function. Upper extremity function scores ranged from 1 (not able to do so [worst upper extremity function]) to 5 (no trouble [best upper extremity function]), where higher scores indicate a better clinical outcome.	Baseline, Week 52 (Part 1)
Part 1: Number of Skills Gained or Improved at Week 52 as Measured by the NSAA	The NSAA is a clinician-administered scale that rates performance on various functional activities. As measured by the NSAA, data was collected for the number of skills gained (the average item score was 0 at Baseline and > 0 at Part 1 Week 52) or improved (the average item score at Baseline was > 0 but less than the average item score at Part 1 Week 52). As pre-specified, data are presented for the combined number of skills gained or improved at Week 52.	Week 52 (Part 1)
Part 1: Change From Baseline in Time to Rise From the Floor at Week 52	The time to rise from the floor test quantifies the time required for the participant to stand in an upright position with arms by sides, starting from the supine position with arms by sides. Data are presented for the change from baseline to Week 52 in the time taken (in seconds) to rise from the floor.	Baseline, Week 52 (Part 1)
Part 1: Change From Baseline in Time to Complete 10 Meter Walk/Run (10MWR) at Week 52	The timed 10MWR quantifies the time required for the participant to run or walk 10 meters (on a straight walkway) from a standing position. Data are presented for change from baseline to Week 52 in the time (in seconds) taken to complete the 10MWR.	Baseline, Week 52 (Part 1)
Part 1: Change From Baseline in Time to Complete 100 Meter Walk/Run (100MWR) at Week 52	The timed 100MWR quantifies the time required for the participant to run or walk 100 meters (on a straight walkway) from a standing position. Data are presented for change from baseline to Week 52 in the time (in seconds) taken to complete the 100MWR.	Baseline, Week 52 (Part 1)
Part 1: Change From Baseline in Stride Velocity 95th Centile (SV95C) at Week 52	Each participant was provided with wearable devices to collect data on stride velocity. Participants wore a device on each ankle. SV95C data was derived based on stride velocity. Data are presented for change from baseline to Week 52 in SV95C.	Baseline, Week 52 (Part 1)
Parts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	TEAEs were defined as an adverse event (AE) that emerged during treatment, having been absent pre-treatment, or worsened relative to the pretreatment state. SAEs were defined as any adverse event that resulted in death, was life threatening, required or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or was an important medical event. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to 104 weeks
Parts 1 and 2: Number of Participants With Adverse Events of Special Interest (AESI)	AESIs were defined as adverse events (AEs) of special interest, based on pre-specified criteria and pertain to categories labeled hepatotoxicity, immune-mediated myositis, thrombotic microangiopathy (TMA), hypersensitivity, thrombocytopenia, rhabdomyolysis, and troponin I elevations. The data represent the number of participants who experienced an event within the specified AESI category as observed by the principal investigator (PI), after adjudication. Per prespecified analysis, AESI data were only collected based on the specified AESI categories. A Summary of all SAEs and nonserious AEs ("Other"), regardless of causality and regardless of the AESI category, is located in the "Reported Adverse Events" section.	Up to 104 weeks

Collaborators and Investigators

• Sponsor: Sarepta Therapeutics, Inc.
• Collaborators: Hoffmann-La Roche
• Investigators: Study Director: Medical Director, Sarepta Therapeutics, Inc.

Publications and helpful links

General Publications

• Mendell JR, Muntoni F, McDonald CM, Mercuri EM, Ciafaloni E, Komaki H, Leon-Astudillo C, Nascimento A, Proud C, Schara-Schmidt U, Veerapandiyan A, Zaidman CM, Guridi M, Murphy AP, Reid C, Wandel C, Asher DR, Darton E, Mason S, Potter RA, Singh T, Zhang W, Fontoura P, Elkins JS, Rodino-Klapac LR. AAV gene therapy for Duchenne muscular dystrophy: the EMBARK phase 3 randomized trial. Nat Med. 2025 Jan;31(1):332-341. doi: 10.1038/s41591-024-03304-z. Epub 2024 Oct 9.

Helpful Links

• SRP-9001-301 Plain Language Study Summary

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2021
• Primary Completion (Actual): October 4, 2023
• Study Completion (Actual): October 25, 2024

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Pediatric; Duchenne Muscular Dystrophy; DMD; Gene-Delivery; Muscular Dystrophies; Ambulatory; North Star Ambulatory Assessment (NSAA)
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: SRP-9001-301; 2019-003374-91 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No