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

(EXPEDITION Trial)

Enrolling by invitation at 42 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on assessing the long-term safety and effectiveness of delandistrogene moxeparvovec for Duchenne muscular dystrophy, a condition that progressively weakens muscles. The trial does not involve administering any new medication; it monitors individuals who received this treatment in a past study. Researchers will follow participants for at least five years to evaluate their progress after treatment. This trial suits those who previously received delandistrogene moxeparvovec and are willing to keep their primary doctor informed. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to the treatment's validation.

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.

Is there any evidence suggesting that delandistrogene moxeparvovec is likely to be safe for humans?

Research has shown that delandistrogene moxeparvovec, a gene therapy for Duchenne muscular dystrophy, is generally safe based on past experiences. Studies have found that patients usually handle the treatment well. Some side effects were reported, but they were similar to those expected from other treatments of this kind.

For example, one study confirmed that after one year, the therapy's safety was consistent with earlier findings. Common side effects included mild issues like fever and nausea, typical for this type of treatment. The evidence suggests that while some risks exist, they are manageable and expected.

This gene therapy undergoes close monitoring over a long period to ensure it remains safe and effective. Such careful observation helps identify any long-term effects that might not appear immediately. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Delandistrogene moxeparvovec is unique because it offers a gene therapy approach to treat Duchenne Muscular Dystrophy (DMD), which is different from the usual corticosteroids and supportive treatments currently available. This therapy works by delivering a micro-dystrophin gene into the patient's muscle cells, which helps produce a functional protein that those with DMD lack. Researchers are excited because this method could potentially address the root cause of the disease, offering long-term benefits rather than just managing symptoms.

What evidence suggests that delandistrogene moxeparvovec is effective for Duchenne Muscular Dystrophy?

Research has shown that delandistrogene moxeparvovec may help treat Duchenne muscular dystrophy. In earlier studies, boys who received this gene therapy improved by 3 points on their NSAA scores, which assess physical abilities, just six months after treatment. This suggests the therapy might help patients maintain or even improve muscle function. Additionally, the treatment has proven safe over the long term and has led to positive physical outcomes. These findings offer hope that delandistrogene moxeparvovec could effectively manage symptoms of Duchenne muscular dystrophy. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. neurology.org neurology.org/doi/10.1212/WNL.0000000000213604

Delandistrogene Moxeparvovec Gene Therapy in ... This Evidence in Focus reviews the current evidence on the efficacy and adverse effects of delandistrogene moxeparvovec in patients with Duchenne muscular ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03375164

Study Details | NCT03375164 | A Gene Transfer Therapy ... This study was an open-label single-dose gene transfer therapy study evaluating the safety of delandistrogene moxeparvovec intravenous (IV) administration ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10366687/

Expression of SRP-9001 dystrophin and stabilization ... Long-term efficacy, safety, and pharmacokinetics of drisapersen in Duchenne muscular dystrophy: Results from an open-label extension study.

4. nature.com nature.com/articles/s41591-024-03304-z

AAV gene therapy for Duchenne muscular dystrophy Long-term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: a phase ...

5. musculardystrophynews.com musculardystrophynews.com/raavrh74-mhck7-micro-dystrophin/

Elevidys for Duchenne muscular dystrophy Data from the first 11 boys treated showed a significant 3-point improvement in NSAA score six months after treatment over the pretreatment ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1098360022002544

eP201: A phase 2 clinical trial evaluating the safety and ... Full analyses from Parts 1 and 2 will be presented, including 2-year functional and safety data from patients who received delandistrogene moxeparvovec in Part ...