Clinical trial NCT05881408: A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Non-Ambulatory and Ambulatory Participants With Duchenne Muscular Dystrophy (DMD)
Official title: A Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled Systemic Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of SRP- 9001 in Non-Ambulatory and Ambulatory Subjects With Duchenne Muscular Dystrophy (ENVISION)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Duchenne Muscular Dystrophy
Keywords: DMD
Gene-Delivery
Pediatric
North Star Ambulatory Assessment (NSAA)
Performance of Upper Limb (PUL)
Duchenne
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2023-05-31
Enrollment: 148
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will evaluate the safety and efficacy of delandistrogene moxeparvovec gene transfer therapy in non-ambulatory and ambulatory males with DMD. This is a randomized, double-blind, placebo-controlled 2-part study. Participants will be in the study for approximately 128 weeks. All participants will have the opportunity to receive intravenous (IV) delandistrogene moxeparvovec in either Part 1 or Part 2.


Eligibility criteria: Inclusion Criteria:

* Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
* Cohort 1 only: Non-ambulatory per protocol-specified criteria.
* Cohort 2 only: Ambulatory per protocol-specified criteria and ≥8 to \<18 years of age at the time of Screening.
* 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).
* Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74) antibody titers are not elevated as per protocol-specified requirements.
* A pathogenic frameshift mutation or premature stop codon in the DMD gene, except for any deletion mutations in exon 8 and/or 9.

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 the Total Score of Performance of Upper Limb (PUL) (Version 2.0) at Week 72
timeFrame: Baseline, Week 72
Secondary outcomes:
measure: Part 1: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 72
timeFrame: Baseline, Week 72
measure: Part 1: Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 72
timeFrame: Baseline, Week 72
measure: Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot
timeFrame: Week 12
measure: Part 1: Change From Baseline in Patient-Reported Outcomes Measurement Information (PROMIS) Score in Upper Extremity Function to Week 72
timeFrame: Baseline, Week 72
measure: Number of Participants with a Treatment Emergent Adverse Event (TEAE), Adverse Event of Special Interest (AESI), and Serious Adverse Event (SAE)
timeFrame: Baseline up to Week 124
measure: Part 1 (For Cohort 2 Only): Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 72
timeFrame: Baseline, Week 72
measure: Part 1: Change From Baseline in Global Circumferential Strain as Measured by Cardiac MRI at Week 72
timeFrame: Baseline, Week 72
measure: Part 1: Change From Baseline in the Middle Domain Score of PUL (Version 2.0) at Week 72
timeFrame: Baseline, Week 72
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford
state: California
city: Sacramento
country: United States
facility: University of California at Davis Medical Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital-San Diego
state: California
city: Gainesville
country: United States
facility: University of Florida, UF Health Center for Pediatric Neuromuscular and Rare Diseases
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics, Dept of Pediatrics
state: Iowa
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital, Charlotte R. Bloomberg Children's Center, Pediatric Clinical Research Unit
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, St. Louis Children's Hospital
state: Missouri
city: Rochester
country: United States
facility: University of Rochester, Department of Neurology
state: New York
city: Durham
country: United States
facility: Lenox Baker Children's Hospital (Duke University)
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Children's Hospital
state: Victoria
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: Ottawa
country: Canada
facility: The Children's Hospital of Eastern Ontario
state: Ontario
city: Montréal
country: Canada
facility: Research Institute McGill University Health Centre
state: Quebec
city: Québec
country: Canada
facility: Centre Hospitalier Universitaire de Québec - Université Laval (pavillon Centre Hospitalier Universitaire Laval)
city: Munchen
country: Germany
facility: LMU- Klinikum der Universitat Munchen, Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Abeteilung Neuropadiatrie, Campus Innenstadt
state: Bayern
city: Essen
country: Germany
facility: Universitatsklinikum Essen, Klinik fur Kinderheilkunde I, Abteilung Neuropadiatrie Essen
state: Nordrhein-westfalen
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg Eppendorf
city: Hong Kong
country: Hong Kong
facility: Hong Kong Children's Hospital
city: Petach Tikva
country: Israel
facility: Institute of Neruology, Schneider Children's Medical Center of Israel
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Genova
country: Italy
facility: U.O.S.D Centro Traslazionale di Miologia e Patologie Neurodegenerative, Istituto G. Gaslini, Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico
city: Milano
country: Italy
facility: UOC Neurologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: IRCCS Istituto Neurologico Carlo Besta Neurepsichiatria Infantile 2 - Epilettologia e Neurologia dello Sviluppo
city: Roma
country: Italy
facility: UOC Neuropsichiatria Infantile, Area Salute del Bambino, Fondazione Policlinico Universitario A. Gemelli IRCCS
city: Toyonaka-shi
country: Japan
facility: National Hospital Organization Osaka Toneyama Medical Center
state: Osaka
city: Kodaira
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital
state: Tokyo
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnam-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: NAP
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
city: Esplugues de LLobregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Barcelona
city: Valencia
country: Spain
facility: Hospital Universitari Politecnic La Fe
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset/Astrid Lindgrens Barnsjukhus, Barnneurologen
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children Foundation Trust
state: Greater London
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
state: Oxfordshire
city: Newcastle Upon Tyne
country: United Kingdom
facility: Institute of Translational and Clinical Research
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: