Gene Therapy for Duchenne Muscular Dystrophy

Not currently recruiting at 92 trial locations

Overseen By Pfizer CT.gov Call Center

Age: < 18

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Prednisone, Prednisolone, Deflazacort

Must not be taking: Translarna, EXONDYS 51, VYONDYS 53

Disqualifiers: Gene therapy, Antibodies to AAV9, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a gene therapy called PF-06939926 to determine its safety and effectiveness for boys with Duchenne muscular dystrophy (DMD), a condition that weakens muscles over time. Participants will be randomly divided into two groups: two-thirds will receive the gene therapy, while one-third will receive a placebo (a treatment with no active medicine) but can switch to the real therapy after one year. Eligible boys must have a confirmed diagnosis of DMD and be able to walk. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment nearing widespread availability.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of certain medications like prednisone, prednisolone, or deflazacort for at least 3 months before joining. It doesn't specify if you need to stop other medications, so it's best to ask the trial team for more details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that PF-06939926 may be a promising treatment for Duchenne Muscular Dystrophy (DMD). Earlier studies found it to be generally safe, with most side effects reported as mild and manageable. In a previous study involving boys with DMD, the treatment was mostly well-tolerated. While some participants experienced mild to moderate side effects, serious side effects were rare, suggesting that PF-06939926 is relatively safe. Prospective trial participants should discuss potential side effects and benefits with their doctor to make an informed decision about participation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for DMD?

Researchers are excited about PF-06939926 because it represents a novel approach to treating Duchenne Muscular Dystrophy (DMD) through gene therapy. Unlike current treatments that primarily focus on managing symptoms and slowing disease progression, PF-06939926 aims to address the root cause by delivering a functional copy of the dystrophin gene directly to muscle cells. This innovative mechanism has the potential to restore muscle function and significantly alter the disease course, offering hope for more effective and long-lasting results for those with DMD.

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

Research shows that PF-06939926, a gene therapy for Duchenne Muscular Dystrophy (DMD), holds promise. Earlier studies linked this therapy to improved muscle function. It uses a virus to deliver a smaller version of the dystrophin gene, which is missing or malfunctioning in boys with DMD. Early trial results suggest this method can help produce dystrophin, a protein crucial for muscle strength. Participants in this trial will be randomized into two cohorts, with approximately two-thirds receiving PF-06939926 and one-third receiving a placebo. Specifically, some participants in that trial demonstrated better muscle function after one year, indicating the treatment might help slow DMD's progression. ^{1 2 3 4 5}

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 Duchenne muscular dystrophy (DMD) confirmed by genetic testing, who can walk and have been on a stable dose of steroids for at least 3 months. Boys with antibodies to AAV9, recent treatments increasing dystrophin expression, prior gene therapy, non-healed injuries affecting tests or certain genetic abnormalities in the dystrophin gene cannot participate.

Inclusion Criteria

I have been genetically tested and confirmed to have Duchenne muscular dystrophy.

I can walk and move around on my own.

I have been on a stable dose of steroids for at least 3 months.

Exclusion Criteria

I do not have any injuries that would affect my ability to perform physical tests.

Your blood, liver, or kidney tests show abnormal results.

I have never had gene therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PF-06939926 gene therapy or placebo via intravenous infusion

52 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

Open-label extension

Participants in the placebo group receive gene therapy after one year if safe

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• PF-06939926
• Placebo

Trial Overview

The study tests the safety and effectiveness of PF-06939926, a gene therapy for DMD. Participants are randomly assigned to receive either this gene therapy or a placebo in a blinded manner. Two-thirds will get the actual treatment while one-third receives placebo with an option to switch after one year.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 2 Interventions

Approximately one third of participants will be randomized to Cohort 2.

Group II: Cohort 1 Experimental Treatment 2 Interventions

Approximately two thirds of participants will be randomized to Cohort 1.

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

In adult mdx mice with existing muscle weakness, adenovirus-mediated dystrophin gene transfer showed a narrow therapeutic margin, where both toxicity and gene transfer efficiency were dependent on the dose of the vector used.

With optimal dosing and immunosuppressive therapy, the treatment successfully improved muscle strength and reduced disease progression over two months, highlighting its potential for treating Duchenne muscular dystrophy in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adenovirus-mediated dystrophin minigene transfer improves muscle strength in adult dystrophic (MDX) mice. Yang, L., Lochmuller, H., Luo, J., et al.[2021]

In a phase 1 clinical trial involving 10 patients with Duchenne muscular dystrophy (DMD), the morpholino antisense oligonucleotide NS-065/NCNP-01 was found to have a favorable safety profile, with no severe adverse reactions reported during the 12-week treatment period.

NS-065/NCNP-01 successfully induced exon 53 skipping in dystrophin mRNA in a dose-dependent manner, leading to increased dystrophin expression in 7 out of 10 patients, suggesting its potential efficacy and warranting further investigation in phase 2 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. Komaki, H., Nagata, T., Saito, T., et al.[2019]

Antisense-mediated exon skipping therapy, like the newly approved casimersen (Amondys 45), offers a promising treatment for Duchenne muscular dystrophy (DMD) by restoring the reading frame of dystrophin transcripts, potentially benefiting about 8% of DMD patients.

Casimersen received accelerated FDA approval in February 2021, but its continued use will depend on positive outcomes from an ongoing phase III clinical trial, highlighting the importance of ongoing research for safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Casimersen for Duchenne muscular dystrophy. Wilton-Clark, H., Yokota, T.[2021]

In a phase 3 study involving 79 patients aged 7-16 with Duchenne muscular dystrophy, eteplirsen treatment for 96 weeks resulted in a significant increase in dystrophin production (7-fold) and exon skipping (18.7-fold), indicating its efficacy in addressing the underlying cause of the disease.

The study also demonstrated a favorable safety profile, with most adverse events being mild to moderate and unrelated to the treatment, while showing a notable slowing of disease progression compared to untreated controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. McDonald, CM., Shieh, PB., Abdel-Hamid, HZ., et al.[2022]

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]

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]

Duchenne muscular dystrophy (DMD) is a rare genetic disease affecting young boys, caused by defects in the dystrophin gene, which is essential for muscle stability, and currently has no cure.

Two promising therapeutic strategies being explored are AAV-mediated gene augmentation to provide a functional dystrophin and AON-mediated exon skipping to correct the gene's defects, with ongoing preclinical and clinical trials assessing their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adeno-Associated Virus (AAV) Mediated Dystrophin Gene Transfer Studies and Exon Skipping Strategies for Duchenne Muscular Dystrophy (DMD). Kawecka, K., Theodoulides, M., Hasoglu, Y., et al.[2019]

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

1.

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.

2.

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 ...

3.

parentprojectmd.org

parentprojectmd.org/clinical-trial/study-to-evaluate-the-safety-and-efficacy-of-pf-06939926-for-the-treatment-of-duchenne-muscular-dystrophy/

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 ...

4.

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 ...

The ongoing, multicenter, open-label, Phase 1b study is evaluating the safety and tolerability of PF 06939926 in boys with DMD.

5.

nature.com

nature.com/articles/s41591-025-03750-3

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

Fordadistrogene movaparvovec (PF-06939926) is an adeno-associated virus serotype 9 gene therapy containing a miniaturized dystrophin being developed for DMD.