Clinical trial NCT04626674: A Gene Transfer Therapy Study to Evaluate the Safety of and Expression From Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Muscular Dystrophy, Duchenne
Keywords: Duchenne Muscular Dystrophy
Gene-Delivery
DMD
Ambulatory Non-ambulatory
Pediatric
Dystrophin
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2020-11-12
Enrollment: 55
Sex: MALE
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Part 1: Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12, as Measured by Western Blot
timeFrame: Baseline, Week 12
measure: Part 1: Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot
timeFrame: Week 12
Secondary outcomes:
measure: Vector Shedding, Measured in Urine, Saliva, and Stool Samples Post-Infusion
timeFrame: Day 1 up to Week 104
measure: Level of Antibody Titers to Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74)
timeFrame: Day 2 up to Week 156
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) of Special Interest
timeFrame: Baseline up to Week 156
measure: Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12, as Measured by Immunofluorescence (IF) Fiber Intensity
timeFrame: Baseline, Week 12
measure: Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12, as Measured by IF Percent Dystrophin Positive Fibers (PDPF)
timeFrame: Baseline, Week 12
measure: Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by IF Fiber Intensity:
timeFrame: Week 12
measure: Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by IF PDPF
timeFrame: Week 12
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: