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

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)

Overview

Cohort 8 (non-ambulatory participants) is currently enrolling new participants. Enrollment for Cohorts 1 through 7 has been completed. This is an open-label gene transfer therapy study evaluating the safety of and expression from delandistrogene moxeparvovec in participants with Duchenne Muscular Dystrophy (DMD). The maximum participant duration for this study is 156 weeks.

Interventions

• Genetic delandistrogene moxeparvovec
  Single IV infusion of delandistrogene moxeparvovec

Primary outcome measures

• Part 1 (Cohorts 1 to 5): Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12, as Measured by Western Blot [Time frame: Baseline, Week 12]
• Part 1 (Cohorts 6 to 8): Quantity of Delandistrogene Moxeparvovec Dystrophin Expression at Week 12 as Measured by Western Blot [Time frame: Week 12]
• Cohort 8: Number of Participants with Acute Liver Injury (ALI) [Time frame: Baseline up to Week 72]

Secondary outcome measures (11)

• Vector Shedding, Measured in Urine, Saliva, and Stool Samples Post-Infusion [Time frame: Day 1 up to Week 104]
• Level of Antibody Titers to Recombinant Adeno-Associated Virus Serotype rh74 (rAAVrh74) [Time frame: Day 2 up to Week 156]
• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) [Time frame: Baseline up to Week 156]
• Cohort 8: Number of Participants With Infections, Edema, Wound-healing Complications, Hyperlipidemia, Angioedema, and Intestinal Lung Disease/ Non-infectious Pneumonitis [Time frame: Baseline up to Week 72]
• Change from Baseline in Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12, as Measured by Immunofluorescence (IF) Fiber Intensity [Time frame: 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) [Time frame: Baseline, Week 12]
• Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by IF Fiber Intensity [Time frame: Week 12]
• Quantity of Delandistrogene Moxeparvovec Dystrophin Protein Expression at Week 12 as Measured by IF PDPF [Time frame: Week 12]
• Cohort 8: Number of Participants With Hepatic AEs, Hepatic Biomarkers, and Laboratory Assessments Indicative of Either Acute Hepatocellular Injury or Acute Liver Dysfunction [Time frame: Baseline up to Week 72]
• Cohort 8: Number of Participants with Severe ALI [Time frame: Baseline up to Week 72]
• Cohort 8: Duration of Steroids Administered [Time frame: Baseline up to Week 72]

Eligibility criteria

Inclusion criteria

• For Cohorts 1-8: Has a definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
• Cohort 8: Non-ambulatory per protocol-specified criteria at the time of Screening, has a performance upper limb (PUL) entry item score ≥3 at the Screening visit and has a total PUL score of ≥20 and ≤40 at the time of Screening.
• Cohorts 1, 2, 3, 5, 7 and 8 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.
• 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 with time to rise from the floor ≤7 seconds at the screening visit.
• 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.
• 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.
• Genetic mutation inclusion criteria vary by cohort.

All Cohorts:

• Ability to cooperate with motor assessment testing.
• rAAVrh74 antibody titers are not elevated as per protocol-specified requirements.

Exclusion criteria

• Cohort 8: Any confounding factors that would prevent the use of oral sirolimus including a known hypersensitivity to sirolimus or any of its excipients.
• 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.

Note: Other inclusion/exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Arkansas Children's Hospital — Little Rock
• Stanford University — Palo Alto
• University of California, Davis — Sacramento
• Washington University in St. Louis — St Louis
• Nationwide Children's Hospital — Columbus
• Neurology Rare Disease Center — Flower Mound
• Children's Hospital of The King's Daughters — Norfolk

Publications

• Potter RA, Moeller IH, Khan S, Haegel H, Hollenstein A, Steiner G, Wandel C, Murphy AP, Asher DR, Palatinsky E, Griffin DA, Mason S, Iannaccone ST, Zaidman CM, Rodino-Klapac LR. Immunologic investigations into transgene directed immune-mediated myositis following delandistrogene moxeparvovec gene therapy. Sci Rep. 2025 Jan 2;15(1):4. doi: 10.1038/s41598-024-84077-w. PMID 39747998
• Zaidman CM, Proud CM, McDonald CM, Lehman KJ, Goedeker NL, Mason S, Murphy AP, Guridi M, Wang S, Reid C, Darton E, Wandel C, Lewis S, Malhotra J, Griffin DA, Potter RA, Rodino-Klapac LR, Mendell JR. Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged >/=4 to <8 Years) with Duchenne Muscular Dystrophy: 1-Year Interim Results from Study SRP-9001-103 (ENDEAVOR). Ann Neurol. 2023 No PMID 37539981

Identifiers

NCT: NCT04626674 · SRP-9001-103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗