NCT03375164

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

Completed Phase 1, PHASE2 Results posted Last updated 14 November 2024

What this trial tests

Phase 1, PHASE2 trial testing delandistrogene moxeparvovec in Duchenne Muscular Dystrophy in 4 participants. Completed in 25 April 2023.

Timeline

4 January 2018

Primary endpoint
25 April 2023

25 April 2023

Quick facts

Lead sponsor	Sarepta Therapeutics, Inc.
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	4
Start date	4 January 2018
Primary completion	25 April 2023
Estimated completion	25 April 2023
Sites	1 location across United States

Drugs / interventions tested

• delandistrogene moxeparvovec — full drug profile →

Conditions studied

• Duchenne Muscular Dystrophy — all drugs for Duchenne Muscular Dystrophy →

Sponsor

Sarepta Therapeutics, Inc. — full company profile →

Who can join

Adults 3 Months to 7, male only, with Duchenne Muscular Dystrophy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events (AEs) Primary · Up to 5 years

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.

Group	Value	95% CI
Delandistrogene Moxeparvovec	4

Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Western Blot Secondary · Baseline, Day 90

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.

Group	Value	95% CI
Delandistrogene Moxeparvovec	70.52	± 76.10

Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by Immunofluorescence (IF) Fiber Intensity Secondary · Baseline, Day 90

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

Group	Value	95% CI
Delandistrogene Moxeparvovec	93.59	± 43.86

Change From Baseline at Day 90 in Delandistrogene Moxeparvovec Dystrophin Expression as Measured by IF Percent Dystrophin Positive Fibers (PDPF) Secondary · Baseline, Day 90

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 expressi

Group	Value	95% CI
Delandistrogene Moxeparvovec	81.18	± 10.19

Change From Baseline at Year 5 in the 100 Meter Timed Test Secondary · Baseline, Year 5

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.

Group	Value	95% CI
Delandistrogene Moxeparvovec	-4.02	± 4.64

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 5 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Delandistrogene Moxeparvovec

Serious: 0/4 (0%)

Deaths: 0/4

Other adverse events (34 terms — click to expand)

Reaction	System	Delandistrogene Moxeparvovec
Upper respiratory tract infection	Infections and infestations	—
Vomiting	Gastrointestinal disorders	—
Hepatic enzyme increased	Investigations	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—
Fatigue	General disorders	—
COVID-19	Infections and infestations	—
Procedural pain	Injury, poisoning and procedural complications	—
Decreased appetite	Metabolism and nutrition disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Abdominal discomfort	Gastrointestinal disorders	—
Abdominal distension	Gastrointestinal disorders	—
Abdominal pain upper	Gastrointestinal disorders	—
Anal incontinence	Gastrointestinal disorders	—
Diarrhoea	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Asthenia	General disorders	—
Pyrexia	General disorders	—
Gastroenteritis	Infections and infestations	—
Gastroenteritis viral	Infections and infestations	—
Subcutaneous abscess	Infections and infestations	—
Viral infection	Infections and infestations	—
Clavicle fracture	Injury, poisoning and procedural complications	—
Influenza A virus test positive	Investigations	—
Back pain	Musculoskeletal and connective tissue disorders	—
Bone pain	Musculoskeletal and connective tissue disorders	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—
Cardiomyopathy	Cardiac disorders	—
Eye irritation	Eye disorders	—
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Headache	Nervous system disorders	—
Irritability	Psychiatric disorders	—
Proteinuria	Renal and urinary disorders	—
Asthma	Respiratory, thoracic and mediastinal disorders	—
Dermatitis contact	Skin and subcutaneous tissue disorders	—

Data from ClinicalTrials.gov NCT03375164 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Viral vector platforms within the gene therapy landscape.
   Bulcha JT, Wang Y, Ma H, Tai PWL, et al · · 2021 · cited 899× · PMID 33558455 · DOI 10.1038/s41392-021-00487-6
2. Severe Toxicity in Nonhuman Primates and Piglets Following High-Dose Intravenous Administration of an Adeno-Associated Virus Vector Expressing Human SMN.
   Hinderer C, Katz N, Buza EL, Dyer C, et al · · 2018 · cited 661× · PMID 29378426 · DOI 10.1089/hum.2018.015
3. Current Clinical Applications of In Vivo Gene Therapy with AAVs.
   Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, Goodspeed K, et al · · 2021 · cited 544× · PMID 33309881 · DOI 10.1016/j.ymthe.2020.12.007
4. AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer.
   Costa Verdera H, Kuranda K, Mingozzi F. · · 2020 · cited 493× · PMID 31972133 · DOI 10.1016/j.ymthe.2019.12.010
5. Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species.
   Tabebordbar M, Lagerborg KA, Stanton A, King EM, et al · · 2021 · cited 401× · PMID 34506722 · DOI 10.1016/j.cell.2021.08.028
6. Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy.
   Duan D. · · 2018 · cited 350× · PMID 30093306 · DOI 10.1016/j.ymthe.2018.07.011
7. Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial.
   Mendell JR, Sahenk Z, Lehman K, Nease C, et al · · 2020 · cited 295× · PMID 32539076 · DOI 10.1001/jamaneurol.2020.1484
8. Human Immune Responses to Adeno-Associated Virus (AAV) Vectors.
   Ronzitti G, Gross DA, Mingozzi F. · · 2020 · cited 269× · PMID 32362898 · DOI 10.3389/fimmu.2020.00670