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

Study Overview
=================
Brief Summary
-----------------
This is an open-label gene transfer therapy study evaluating the safety of and expression from delandistrogene moxeparvovec in participants with DMD. The maximum participant duration for this study is 156 weeks.

Official Title
-----------------
An Open-Label, Systemic Gene Delivery Study Using Commercial Process Material to Evaluate the Safety of and Expression From SRP-9001 in Subjects With Duchenne Muscular Dystrophy (ENDEAVOR)

Conditions
-----------------
Muscular Dystrophy, Duchenne

Intervention / Treatment
-----------------
* Genetic: delandistrogene moxeparvovec


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: For Cohorts 1-7: Has a definitive diagnosis of DMD based on documented clinical findings and prior genetic testing. Cohort 1: Is ambulatory, and ≥4 to <8 years of age at the time of Screening. Cohort 2: Is ambulatory, and ≥8 to <18 years of age at the time of Screening. Cohort 3: Non-ambulatory per protocol specified criteria at the time of Screening. Cohort 4: Is ambulatory and ≥3 to <4 years of age at the time of Screening. Cohort 5a: Is ambulatory and ≥4 to <9 years of age. Cohort 5b: Non-ambulatory per protocol specified criteria at the time of Screening. Cohort 6: Is ambulatory, and ≥2 to <3 years of age at the time of Screening. Cohort 7: Non-ambulatory per protocol-specified criteria at the time of Screening. Ability to cooperate with motor assessment testing. Cohorts 1, 2, 3, 5, and 7 only: Stable dose equivalent of oral glucocorticoids for at least 12 weeks before screening and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the first year of the study. Cohorts 4 and 6: Do not yet require use of chronic steroids for treatment of their DMD, in the opinion of the Investigator, and are not receiving steroids at the time of Screening. rAAVrh74 antibody titers are not elevated as per protocol-specified requirements. Genetic mutation inclusion criteria vary by cohort. Exclusion Criteria: Has a concomitant illness, autoimmune disease, chronic drug treatment, and/or cognitive delay/impairment that in the opinion of the Investigator creates unnecessary risks for gene transfer. 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. Other inclusion/exclusion criteria apply.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Delandistrogene Moxeparvovec<br>Participants will receive a single intravenous (IV) infusion of delandistrogene moxeparvovec on Day 1. | Genetic: delandistrogene moxeparvovec<br>* Single IV infusion of delandistrogene moxeparvovec<br>* Other names: ELEVIDYS;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12, as Measured by Western Blot |  | Baseline, Week 12 | 
| Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vector Shedding, Measured in Urine, Saliva, and Stool Samples Post-Infusion |  | Day 1 up to Week 104 | 
| Level of Antibody Titers to Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74) |  | Day 2 up to Week 156 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) of Special Interest |  | Baseline up to Week 156 | 
| Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12, as Measured by Immunofluorescence (IF) Fiber Intensity |  | Baseline, Week 12 | 
| Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12, as Measured by IF Percent Dystrophin Positive Fibers (PDPF) |  | Baseline, Week 12 | 
| Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by IF Fiber Intensity: |  | Week 12 | 
| Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by IF PDPF |  | Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Duchenne Muscular Dystrophy, Gene-Delivery, DMD, Ambulatory Non-ambulatory, Pediatric, Dystrophin