Gene Therapy (PF-06939926) for Duchenne Muscular Dystrophy

No longer recruiting at 11 trial locations

Overseen By Pfizer CT.gov Call Center

Age: < 18

Sex: Male

Trial Phase: Phase 2

Sponsor: Pfizer

Must not be taking: Oral glucocorticoids

Disqualifiers: Gene therapy, Antibody positive, others

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

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

Compensation: Varies

Number of Visits: 11

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment, PF-06939926, for boys with Duchenne Muscular Dystrophy (DMD). Researchers aim to determine the treatment's safety and its effectiveness in promoting dystrophin production, a protein crucial for muscle health. Eligible participants have DMD confirmed by genetic testing but lack specific gene changes in certain parts of the dystrophin gene. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

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

The trial does not specify if you need to stop taking your current medications, but it excludes those who have had certain treatments to increase dystrophin expression in the past 6 months or have used oral glucocorticoids or other immunosuppressive agents for DMD.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that PF-06939926, a gene therapy for Duchenne Muscular Dystrophy (DMD), has undergone safety testing in earlier studies. One study found the treatment safe enough for boys with DMD, with manageable side effects. Another study monitored participants for a year and found the treatment well-tolerated.

As a Phase 2 trial, the treatment has already been tested for safety in humans. This provides some confidence in its safety, but further information is being gathered to ensure it is safe and effective for a broader population. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care for Duchenne Muscular Dystrophy, which often involves corticosteroids and supportive therapies, PF-06939926 is a gene therapy that aims to address the root cause of the disease by delivering a functional version of the dystrophin gene directly to muscle cells. This approach is unique because it potentially offers a long-term solution by repairing the genetic defect rather than just managing symptoms. Researchers are excited about this treatment because it could significantly improve muscle function and slow disease progression, offering hope for a more effective and lasting impact than current treatments.

What evidence suggests that this gene therapy might be an effective treatment for Duchenne Muscular Dystrophy?

Research has shown that PF-06939926, a type of gene therapy, may help treat Duchenne Muscular Dystrophy (DMD). In an earlier study, participants who received this treatment showed an increase in dystrophin, an important protein that DMD patients lack. Over a year, both ambulatory and non-ambulatory patients demonstrated improvements. Another study found that these benefits could last up to two years. Overall, PF-06939926 continues to show promise for significant benefits with an acceptable safety profile. ^{1 2 5 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for boys with a confirmed diagnosis of Duchenne Muscular Dystrophy (DMD) who haven't had gene therapy before. They must have normal blood counts and liver/kidney function, no specific genetic mutations in the dystrophin gene, and no recent treatments aimed at increasing dystrophin expression.

Inclusion Criteria

I have a confirmed genetic diagnosis of Duchenne Muscular Dystrophy.

Exclusion Criteria

My genetic test shows a specific mutation in the dystrophin gene.

I have taken steroids or other immune-weakening drugs for Duchenne Muscular Dystrophy.

I haven't had treatments to boost dystrophin in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a single IV infusion of PF-06939926 gene therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and dystrophin expression after treatment

5 years

Regular visits (in-person) at Week 9, Week 52, and annually

What Are the Treatments Tested in This Trial?

Interventions

• PF-06939926

Trial Overview

The study tests Fordadistrogene Movaparvovec (PF-06939926), a gene therapy for DMD. It's an open-label study where all participants receive the treatment to assess safety and how well it promotes dystrophin production.

How Is the Trial Designed?

Group I: PF-06939926 Experimental Treatment 1 Intervention

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

Published Research Related to This Trial

The first-in-human study of DEC cell therapy for Duchenne Muscular Dystrophy (DMD) showed no adverse events in the first 3 patients over 14 months, indicating a strong safety profile for this novel treatment.

Patients receiving DEC therapy demonstrated significant improvements in muscle function and strength, as measured by various functional tests, suggesting that this therapy could effectively enhance quality of life for DMD patients without the need for immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dystrophin Expressing Chimeric (DEC) Cell Therapy for Duchenne Muscular Dystrophy: A First-in-Human Study with Minimum 6 Months Follow-up. Heydemann, A., Bieganski, G., Wachowiak, J., et al.[2023]

Gene therapy using a 6.3 kb minidystrophin cDNA delivered via adenovirus was effective in treating muscular dystrophy in neonatal mdx mice, suggesting a potential approach for Duchenne muscular dystrophy (DMD).

However, adult mice experienced strong immune reactions to the adenovirus, indicating that using a modified adenovirus with dystrophin cDNA or upregulating endogenous utrophin could be safer and more effective strategies for treating DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gene therapy to muscle diseases: perspective and issues on basic research]. Takeda, S.[2012]

The DT-DEC01 cell therapy demonstrated a strong safety profile with no adverse events reported up to 21 months after administration, indicating it is a safe treatment option for patients with Duchenne Muscular Dystrophy (DMD).

Functional improvements were observed in patients, including better performance in the 6-Minute Walk Test and other assessments, suggesting that DT-DEC01 may effectively enhance muscle function and overall health in DMD patients over a 12-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration. Siemionow, M., Biegański, G., Niezgoda, A., et al.[2023]

Gene therapy using dystrophin cDNAs in dystrophin-deficient mice shows promise for treating Duchenne muscular dystrophy (DMD), with regional restoration of muscle morphology observed in transgenic models.

Direct injection methods yielded low expression rates of dystrophin in adult muscle fibers, but recombinant adenovirus vectors showed greater efficiency in young mice, highlighting the need for improved delivery systems for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy in Duchenne muscular dystrophy. Inui, K., Okada, S., Dickson, G.[2019]

The micro-dystrophin gene transfer using rAAVrh74.MHCK7 was found to be well tolerated in a phase 1/2a trial with four young patients, showing only mild to moderate adverse events and no serious complications over one year.

All patients demonstrated significant expression of micro-dystrophin in muscle fibers and improvements in functional measures, such as North Star Ambulatory Assessment scores and reduced creatine kinase levels, indicating potential benefits beyond standard care for Duchenne muscular dystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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., et al.[2021]

Current therapies for Duchenne muscular dystrophy (DMD) include gene therapy, cell therapy, and pharmacological therapy, each targeting different aspects of the disease's progression.

Despite advancements, there is still no cure for DMD due to challenges in gene replacement and the complex nature of the symptoms, highlighting the need for more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of therapy for Duchenne muscular dystrophy. Zhang, S., Xie, H., Zhou, G., et al.[2012]

Citations

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pfizer.com/news/press-release/press-release-detail/pfizer-provides-update-phase-3-study-investigational-gene

Pfizer Provides Update on Phase 3 Study of Investigational ...

Pfizer Provides Update on Phase 3 Study of Investigational Gene Therapy for Ambulatory Boys with Duchenne Muscular Dystrophy. Wednesday, June ...

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40579547/

AAV mini-dystrophin gene therapy for Duchenne muscular ...

We present 1-year data from ambulatory and nonambulatory participants in a phase 1b, multicenter, single-arm, open-label trial. Pediatric ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT04281485

Study to Evaluate the Safety and Efficacy of PF-06939926 ...

The primary outcome of the study will be assessed at 52 weeks. All participants will be followed in the study for 15 years after treatment with gene therapy.

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genethon.com

genethon.com/genethon-confirms-2-year-efficacy-in-duchenne-muscular-dystrophy-patients-treated-with-its-low-dose-micro-dystrophin-gene-therapy-gnt0004-at-the-esgct-32nd-annual-congress/

Genethon Confirms 2-year Efficacy in Duchenne Muscular ...

The Duchenne muscular dystrophy (DMD) patients experiencing long-term efficacy were treated with the therapeutic 3×10¹³ vg/kg dose of ...

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mdaconference.org

mdaconference.org/abstract-library/safety-and-efficacy-of-pf-06939926-gene-therapy-in-boys-with-duchenne-muscular-dystrophy-update-on-data-from-the-phase-1b-study/

Safety and Efficacy of PF-06939926 Gene Therapy in boys ...

Conclusions: PF-06939926 continues to demonstrate the potential for substantial benefit with an acceptable safety profile, and is being developed as a novel ...

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parentprojectmd.org

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Study to Evaluate the Safety and Efficacy of PF-06939926 ...

The study will assess the efficacy of PF-06939926 gene therapy on ambulatory function while also monitoring its safety. Approximately 99 boys with DMD will ...

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clinicaltrials.gov

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NCT03362502 | A Study to Evaluate the Safety and ...

A Study to Evaluate the Safety and Tolerability of PF-06939926 Gene Therapy in Duchenne Muscular Dystrophy ... Duchenne muscular dystrophy: a phase 1b trial.