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

Duchenne Muscular Dystrophy Clinical Trial

Official title:

Systemic Gene Delivery Phase I/IIa Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MHCK7.Micro-dystrophin (microDys-IV-001)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03375164
• Other study ID #: SRP-9001-101
• Secondary ID: 2021-000077-83
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 4, 2018
• Est. completion date: April 25, 2023

Study information

• Verified date: April 2024
• Source: Sarepta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study was an open-label single-dose gene transfer therapy study evaluating the safety of delandistrogene moxeparvovec intravenous (IV) administration in boys with DMD. This study was originally designed to consist of 12 patients across 2 Cohorts. Cohort A would have included participants ages 3 months to 3 years, and Cohort B included participants ages 4 to 7 years old. No participants were enrolled in Cohort A.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: April 25, 2023
• Est. primary completion date: April 25, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 3 Months to 7 Years

Eligibility

Inclusion Criteria:

• Cohort A participants: 3 months to 3 years of age, inclusive
• Cohort B participants: 4 to 7 years of age, inclusive
• Definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
• Ability to cooperate with motor assessment testing.
• Cohort A participants: No previous treatment with corticosteroids.
• Cohort B participants: Stable dose equivalent of oral corticosteroids for at least 12 weeks prior to screening and the dose is expected to remain constant (except for potential modifications to accommodate changes in weight) throughout the first year of the study.
• Cohorts A & B: A frameshift mutation contained between exons 18 and 58 (inclusive).

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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Genetic:
• delandistrogene moxeparvovec
Single IV infusion of delandistrogene moxeparvovec.

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Sarepta Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the study drug. An AE can, therefore, be any unfavorable and unintended symptom, sign, disease, condition, or test abnormality that occurs during or after administration of a study drug, whether or not considered related to the study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.	Up to 5 years
Secondary	Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Western Blot	Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Day 90) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin protein levels in these muscle biopsy samples was determined by Western blot. An increase in protein expression indicates production of the delandistrogene moxeparvovec dystrophin protein.	Baseline, Day 90
Secondary	Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Immunofluorescence (IF) Fiber Intensity	Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Day 90) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined using IF. Automated software was used to quantify the intensity of dystrophin expression post-treatment compared to pre-treatment (Percent Normal). The number of muscle fibers expressing micro-dystrophin was quantified by independent trained evaluators. An increase in IF fiber intensity indicates increased delandistrogene moxeparvovec dystrophin expression.	Baseline, Day 90
Secondary	Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by IF Percent Dystrophin Positive Fibers (PDPF)	Baseline muscle biopsies with ultrasound guidance were performed pre-treatment and post-treatment (Day 90) on all participants. The change from baseline in delandistrogene moxeparvovec dystrophin expression in these muscle biopsy samples was determined by IF PDPF. Automated software was used to quantify the intensity of dystrophin expression post-treatment compared to pre-treatment (Percent Normal). The number of muscle fibers expressing micro-dystrophin was quantified by independent trained evaluators. An increase in IF PDPF indicates increased delandistrogene moxeparvovec dystrophin expression.	Baseline, Day 90
Secondary	Change From Baseline at Year 5 in the 100 Meter Timed Test	This assessment measures the time needed to move 100 meters and served as the primary motor outcome measure for this study. A decrease in the time needed to move 100 meters indicates increased motor function.	Baseline, Year 5