Clinical trial NCT05096221: A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Duchenne Muscular Dystrophy
Keywords: Muscular Dystrophies
Duchenne Muscular Dystrophy
DMD
North Star Ambulatory Assessment (NSAA)
Ambulatory
Pediatric
Gene-Delivery
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2021-10-27
Enrollment: 126
Sex: MALE
Minimum age (years): 4
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52
timeFrame: Baseline, Week 52 (Part 1)
Secondary outcomes:
measure: Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by Western Blot Adjusted by Muscle Content
timeFrame: Week 12
measure: Part 1: Change From Baseline in Time to Rise From the Floor at Week 52
timeFrame: Baseline, Week 52 (Part 1)
measure: Part 1: Change From Baseline in Time to Complete 10 Meter Walk/Run (10MWR) at Week 52
timeFrame: Baseline, Week 52 (Part 1)
measure: Part 1: Change From Baseline in Time to Complete 100 Meter Walk/Run (100MWR) at Week 52
timeFrame: Baseline, Week 52 (Part 1)
measure: Part 1: Change From Baseline in the Timed Stair Ascend 4 Steps Test at Week 52
timeFrame: Baseline, Week 52 (Part 1)
measure: Part 1: Change From Baseline in Stride Velocity 95th Centile (SV95C) at Week 52
timeFrame: Baseline, Week 52 (Part 1)
measure: Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Score in Mobility to Week 52
timeFrame: Baseline, Week 52 (Part 1)
measure: Part 1: Change From Baseline in PROMIS Score in Upper Extremity Function to Week 52
timeFrame: Baseline, Week 52 (Part 1)
measure: Part 1: Number of Skills Gained or Improved at Week 52 as Measured by the NSAA
timeFrame: Week 52 (Part 1)
measure: Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 52 weeks (Part 1)
measure: Part 1: Number of Participants With Adverse Events of Special Interest (AESI)
timeFrame: Up to 52 weeks (Part 1)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's
state: Arkansas
city: La Jolla
country: United States
facility: UC San Diego Altman Clinical and Translational Research Institute
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital at Stanford
state: California
city: Sacramento
country: United States
facility: University of California, Davis
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: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Stead Family Children's Hospital
state: Iowa
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University of St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University/NYPH
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University Medical Center, Lenox Baker Children's Hospital
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Milwaukee
country: United States
facility: Children's Wisconsin
state: Wisconsin
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Bayern
country: Germany
facility: LMU - Klinikum der Universitaet Muenchen - Kinderklinik und
city: Essen
country: Germany
facility: Universitätsklinikum Essen - Klinik für Kinderheilkunde I
city: Hamburg
country: Germany
facility: University Hospital Hamburg- Eppendorf
city: Kowloon
country: Hong Kong
facility: Hong Kong Children's Hospital
city: Genoa
country: Italy
facility: IRCCS Istituto G.Gaslini, U.O.
city: Milano
country: Italy
facility: UOC Neurologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Roma
country: Italy
facility: UOC Neuropsichiatria Infantile, Area Salute del Bambino, Fondazione Policlinico Universitario A. Gamelli IRCCS
city: Kobe
country: Japan
facility: Kobe University Hospital
city: Tokyo
country: Japan
facility: National Center for Child Health and Development
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital - Pediatrics
city: Tokyo
country: Japan
facility: National Center of Neurology and Psychiatry
city: Valencia
country: Spain
facility: Hospital Universitari i Politécnico La Fe
state: Comunidad Valencia
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Headington
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
state: Oxford
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne NHS Hospital NHS Foundation Trust, Royal Victoria Infirmary
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: