Long-term Follow-up for Delandistrogene Moxeparvovec in Duchenne Muscular Dystrophy

(EXPEDITION Trial)

Recruiting at 37 trial locations

Overseen By Sarepta Therapeutics Inc. For Clinical Trial Information, Select Option 4

Age: Any Age

Sex: Male

Trial Phase: Phase 3

Sponsor: Sarepta Therapeutics, Inc.

Disqualifiers: Non-disclosure to physicians, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

400 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment delandistrogene moxeparvovec in Duchenne muscular dystrophy?

Research shows that delandistrogene moxeparvovec leads to the expression of a shortened dystrophin protein, which helps stabilize motor function in children with Duchenne muscular dystrophy. In a study, children treated with this therapy showed improved scores in motor function tests compared to those who received a placebo. ^{1 2 3 4 5}

What is known about the safety of delandistrogene moxeparvovec in humans?

In clinical trials for Duchenne muscular dystrophy, the most common side effects of delandistrogene moxeparvovec were vomiting, decreased appetite, and nausea, which mostly occurred within the first 90 days and resolved on their own. ^{1 2 3 4 6}

How is the treatment delandistrogene moxeparvovec different from other treatments for Duchenne muscular dystrophy?

Delandistrogene moxeparvovec is unique because it is a gene therapy that uses a virus to deliver a shortened version of the dystrophin gene directly to muscle cells, aiming to produce a functional protein that can help slow down muscle degeneration in Duchenne muscular dystrophy. It is the first gene therapy approved for this condition, specifically for young children, and is administered as a single intravenous infusion. ^{1 2 3 4 7}

What is the purpose of this trial?

The purpose of this study is to provide a single clinical study with a uniform approach to monitoring long-term safety and efficacy in participants who received delandistrogene moxeparvovec in a previous clinical study. No study drug will be administered as part of this study. Pre-infusion baseline will be defined as the timepoint just prior to infusion of delandistrogene moxeparvovec from a previous clinical study. Each participant will be followed for a minimum of 5 years post-infusion of delandistrogene moxeparvovec from a previous clinical study. The duration of participation in this study is dependent on the length of follow-up the participant completed post-infusion of delandistrogene moxeparvovec from a previous clinical study.

Eligibility Criteria

This study is for individuals with Duchenne muscular dystrophy who previously received delandistrogene moxeparvovec. Participants must either have a parent or caregiver, or be adults who understand and can follow the study's schedule and requirements.

Inclusion Criteria

I have received delandistrogene moxeparvovec for Duchenne muscular dystrophy in a past study.

Exclusion Criteria

I prefer not to share my trial participation with my doctor or other healthcare providers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Pre-infusion baseline defined as the timepoint just prior to infusion of delandistrogene moxeparvovec from a previous clinical study

Long-term Follow-up

Participants are monitored for long-term safety and efficacy after receiving delandistrogene moxeparvovec in a previous clinical study

Minimum of 5 years

Treatment Details

Interventions

• delandistrogene moxeparvovec

Trial Overview The trial monitors long-term safety and effectiveness of delandistrogene moxeparvovec in participants from an earlier study. No new drug will be given; it tracks health for at least 5 years after the initial treatment.

Participant Groups

Group I: Delandistrogene Moxeparvovec Experimental Treatment 1 Intervention

Participant received delandistrogene moxeparvovec in a previous clinical study.

Who Is Running the Clinical Trial?

Sarepta Therapeutics, Inc.

Lead Sponsor

Trials

54

Recruited

34,000+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

Delandistrogene moxeparvovec is a gene therapy that has shown a favorable safety profile in a small trial of 4 ambulatory boys aged 4 to 5 years with Duchenne muscular dystrophy, with all treatment-related adverse events resolving within 70 days.

The therapy resulted in significant functional improvements, with the North Star Ambulatory Assessment (NSAA) score increasing from 20.5 to 27.5 over 4 years, indicating that it may positively influence disease progression in DMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: A phase 1/2a nonrandomized trial. Mendell, JR., Sahenk, Z., Lehman, KJ., et al.[2023]

Delandistrogene moxeparvovec (SRP-9001) successfully induced dystrophin expression in all patients with Duchenne muscular dystrophy, achieving a mean change from baseline of 23.82% at Week 12 and 39.64% at Week 48, indicating its efficacy as a gene transfer therapy.

While the overall change in North Star Ambulatory Assessment (NSAA) scores was not statistically significant for the entire population, younger patients (4-5 years) with matched baseline motor function showed a significant improvement of +2.5 points, suggesting that age and baseline function may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of SRP-9001 dystrophin and stabilization of motor function up to 2 years post-treatment with delandistrogene moxeparvovec gene therapy in individuals with Duchenne muscular dystrophy. Mendell, JR., Shieh, PB., McDonald, CM., et al.[2023]

Delandistrogene moxeparvovec is the first gene therapy approved for Duchenne muscular dystrophy (DMD) in the USA, specifically for ambulatory children aged 4 to 5 years with a confirmed mutation in the dystrophin gene.

This therapy uses an adeno-associated virus vector to deliver a micro-dystrophin gene to muscle cells, aiming to improve muscle function in DMD patients, and is administered as a single intravenous infusion at a dose of 1.33 × 10^14 vector genomes per kg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delandistrogene Moxeparvovec: First Approval. Hoy, SM.[2023]

Adeno-associated virus-mediated gene therapy using fordadistrogene movaparvovec showed promising results in a dystrophin-deficient rat model of Duchenne muscular dystrophy (DMD), with improvements in muscle strength, tissue architecture, and cardiac function directly linked to the dose administered.

The therapy was effective even in older rats with a more severe form of DMD, indicating its potential applicability for patients at various stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an AAV9-mini-dystrophin gene therapy candidate in a rat model of Duchenne muscular dystrophy. Le Guiner, C., Xiao, X., Larcher, T., et al.[2023]

The study developed shorter 25-mer phosphorodiamidate morpholino oligonucleotides (PMOs) that can effectively induce dystrophin restoration in Duchenne muscular dystrophy (DMD), showing comparable efficacy to the longer 30-mer PMO eteplirsen.

Using shorter PMOs could allow for higher dosing, which enhances drug uptake into muscle fibers, potentially leading to greater dystrophin restoration and improved clinical outcomes for patients with DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shorter Phosphorodiamidate Morpholino Splice-Switching Oligonucleotides May Increase Exon-Skipping Efficacy in DMD. Akpulat, U., Wang, H., Becker, K., et al.[2021]

Duchenne muscular dystrophy (DMD) is a severe genetic disorder primarily affecting boys, leading to muscle degeneration and early death, highlighting the urgent need for effective treatments.

AAV-based gene therapy using shortened microdystrophin genes shows promise as a treatment for DMD, and the article advocates for using microdystrophin expression as a surrogate endpoint to facilitate accelerated approval in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdystrophin Expression as a Surrogate Endpoint for Duchenne Muscular Dystrophy Clinical Trials. Chamberlain, JS., Robb, M., Braun, S., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: A phase 1/2a nonrandomized trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Expression of SRP-9001 dystrophin and stabilization of motor function up to 2 years post-treatment with delandistrogene moxeparvovec gene therapy in individuals with Duchenne muscular dystrophy. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Delandistrogene Moxeparvovec: First Approval. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Evaluation of an AAV9-mini-dystrophin gene therapy candidate in a rat model of Duchenne muscular dystrophy. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Shorter Phosphorodiamidate Morpholino Splice-Switching Oligonucleotides May Increase Exon-Skipping Efficacy in DMD. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Microdystrophin Expression as a Surrogate Endpoint for Duchenne Muscular Dystrophy Clinical Trials. [2023]