Gene Therapy for Duchenne Muscular Dystrophy

Recruiting at 11 trial locations

Overseen By Pfizer CT.gov Call Center

Age: Any Age

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Disqualifiers: Investigator site staff, family members

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

Compensation: Varies

Number of Visits: 1

7 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

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's best to discuss this with the study doctor for guidance.

What data supports the idea that Gene Therapy for Duchenne Muscular Dystrophy (also known as: fordadistrogene movaparvovec, BMB-D-001, PF 06939926) is an effective treatment?

The available research shows that fordadistrogene movaparvovec, a gene therapy, was effective in a rat model of Duchenne Muscular Dystrophy. The study found improvements in muscle strength, heart function, and muscle structure after treatment. This suggests that the therapy could be beneficial for patients at different stages of the disease. Compared to other treatments like drisapersen, which was tested in a placebo-controlled trial, gene therapy offers a more direct approach by aiming to correct the underlying genetic issue. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment fordadistrogene movaparvovec for Duchenne Muscular Dystrophy?

In a study using a rat model of Duchenne Muscular Dystrophy, fordadistrogene movaparvovec showed promising results by improving muscle strength and heart function, suggesting it could be effective for patients at different stages of the disease. ^{1 2 3 4 5}

What safety data exists for gene therapy in Duchenne Muscular Dystrophy?

The safety data for gene therapy in Duchenne Muscular Dystrophy includes findings from various studies. In a nonclinical study using a rat model, fordadistrogene movaparvovec showed therapeutic effectiveness with a correlation between dose and muscle improvement. In a Phase 1/2a trial, delandistrogene moxeparvovec was evaluated for long-term safety and functional outcomes, with common treatment-related adverse events being vomiting, decreased appetite, and nausea, all of which resolved. Another study reported robust expression of SRP-9001 dystrophin and stabilization of motor function up to 2 years post-treatment, with most adverse events occurring within the first 90 days and resolving. Delandistrogene moxeparvovec has been approved in the USA for certain pediatric patients, indicating a recognized safety profile for this age group. ^{1 2 3 4 5}

Is the gene therapy for Duchenne Muscular Dystrophy, known as fordadistrogene movaparvovec, safe for humans?

In a study of a similar gene therapy, delandistrogene moxeparvovec, the most common side effects were vomiting, decreased appetite, and nausea, which mostly occurred within the first 90 days and all resolved. This suggests that the therapy is generally safe, but monitoring for these side effects is important. ^{1 2 3 4 5}

Is the treatment fordadistrogene movaparvovec a promising treatment for Duchenne Muscular Dystrophy?

Yes, fordadistrogene movaparvovec is a promising treatment for Duchenne Muscular Dystrophy. It has shown positive results in improving muscle strength and heart function in animal studies, suggesting it could be effective for patients at all stages of the disease. ^{1 2 3 4 5}

How is the gene therapy fordadistrogene movaparvovec different from other treatments for Duchenne Muscular Dystrophy?

Fordadistrogene movaparvovec is a unique gene therapy that uses a virus to deliver a mini-dystrophin gene directly into the body, aiming to restore muscle function in Duchenne Muscular Dystrophy patients. Unlike other treatments, it involves a single intravenous injection and targets the underlying genetic cause of the disease by introducing a functional version of the dystrophin gene. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a new gene therapy called fordadistrogene movaparvovec. It aims to see if the therapy is safe and effective over a long period. The treatment works by fixing or replacing problematic genes in the body.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for individuals who have Duchenne Muscular Dystrophy and were part of previous Pfizer studies where they received the gene therapy fordadistrogene movaparvovec. Participants will be monitored for 10 years with annual onsite visits and additional remote check-ins.

Inclusion Criteria

I have previously received fordadistrogene movaparvovec in a Pfizer study.

Exclusion Criteria

Investigator site staff directly involved in the study and their family members

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Long-term Follow-up

Participants are monitored for safety and effectiveness of the gene therapy for 10 years

10 years

1 annual onsite visit and a few annual remote visits

Extension

Participants continue to be monitored for changes in ambulatory and upper limb function

5 years

Treatment Details

Interventions

• fordadistrogene movaparvovec

Trial Overview The study focuses on the long-term safety and effects of an experimental gene therapy called fordadistrogene movaparvovec, which was administered in earlier trials. The follow-up includes yearly in-person assessments alongside several virtual visits.

Participant Groups

Group I: All participants Experimental Treatment 1 Intervention

All participants enrolled in the study.

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill 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]

In a Phase 2 study involving 51 ambulant Duchenne muscular dystrophy (DMD) patients, drisapersen at a dose of 6 mg/kg/week showed a potential benefit in improving the 6-minute walking distance (6MWD) compared to placebo, with a mean difference of 27.1 meters at week 24.

Drisapersen was generally well-tolerated, with the most common side effects being injection site reactions and subclinical proteinuria, indicating a manageable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy. McDonald, CM., Wong, B., Flanigan, KM., et al.[2022]

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]

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]

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

Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy. [2022]

3. 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]

4. 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]

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

Delandistrogene Moxeparvovec: First Approval. [2023]