PF-06939926 Gene Therapy for Duchenne Muscular Dystrophy

No longer recruiting at 24 trial locations

Age: Any Age

Sex: Male

Trial Phase: Phase 1

Sponsor: Pfizer

Must be taking: Glucocorticoids

Must not be taking: Gene therapy agents

Disqualifiers: Live vaccines, Cardiac dysfunction, others

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

Compensation: Varies

Number of Visits: 7

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, PF-06939926, for individuals with Duchenne muscular dystrophy (DMD). The primary goal is to determine if the treatment is safe and well-tolerated, while also assessing its impact on muscle strength and function. The trial includes participants who can or cannot walk independently and have been diagnosed with DMD through medical history and genetic testing. Participants must have maintained a steady dose of certain medications and be comfortable with specific medical procedures like MRIs and muscle biopsies. This trial may be worth considering for those who meet these criteria. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial does not specify if you need to stop your current medications, but you must have been on a stable dose of glucocorticoids for at least 3 months before joining. If you are part of the sirolimus cohort, you cannot use certain other medications that interact with it.

Is there any evidence suggesting that PF-06939926 is likely to be safe for humans?

Research has shown that PF-06939926 has been promising in earlier studies for people with Duchenne muscular dystrophy (DMD). In a study involving both walking and non-walking participants, the treatment was generally well-tolerated. Most participants experienced some side effects, but these were manageable and not severe.

The study found that PF-06939926 could offer benefits without serious safety concerns, potentially improving muscle function while remaining safe for use. However, as this is early research, further studies are necessary to fully understand the safety and effects of this gene therapy.

For those considering joining a trial, it's important to know that early studies like this focus heavily on safety. Researchers closely monitor participants to manage any risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Duchenne muscular dystrophy?

PF-06939926 is unique because it uses gene therapy to target Duchenne Muscular Dystrophy (DMD) at its genetic root. Unlike current treatments like corticosteroids or physical therapy, which primarily manage symptoms, this approach aims to introduce a functional version of the dystrophin gene directly into muscle cells. Researchers are excited about this treatment because it has the potential to produce long-lasting benefits by addressing the underlying genetic cause of DMD, possibly slowing or even halting disease progression in a way that current therapies cannot.

What evidence suggests that PF-06939926 might be an effective treatment for Duchenne muscular dystrophy?

Research has shown that PF-06939926, the investigational treatment tested in this trial, is a promising gene therapy for Duchenne Muscular Dystrophy (DMD). It uses a modified virus to deliver a smaller version of the dystrophin gene, which people with DMD lack. This gene helps muscles function properly. One study found that after a year, participants had stronger muscles and improved movement. These findings suggest the treatment might slow the muscle damage caused by DMD. The therapy remains under investigation in this trial, but early results are encouraging. ^{1 2 3 5 6}

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), both walking and non-walking, who can handle MRI scans without sedation. Participants must meet specific genetic criteria, have a certain level of muscle function, and be on stable glucocorticoids. Boys should weigh under 50 kg if walking or under 75 kg if not. Those in the Sirolimus Cohort must be over 8 years old.

Inclusion Criteria

Age as follows, based on ambulatory status: FOR AMBULATORY PARTICIPANTS: Between 4 and 12 years, FOR NON-AMBULATORY PARTICIPANTS: No age restrictions so long as loss of ambulation occurs prior to the subject's 17th birthday; Diagnosis of Duchenne muscular dystrophy confirmed by medical history and genetic testing; Receipt of glucocorticoids for 6 months and a stable daily dose for at least 3 months prior to study entry; Ability to tolerate magnetic resonance imaging (MRI) without sedation and with no contraindications; Ability to tolerate muscle biopsies under anesthesia with no contraindications; Body weights as follows, based on ambulatory status: FOR AMBULATORY PARTICIPANTS: Between 15 kg and 50 kg, FOR NON-AMBULATORY PARTICIPANTS: Less than 75 kg; Functional performance as follows, based on ambulatory status: FOR AMBULATORY PARTICIPANTS: Ability to rise from floor within seven (7) seconds, FOR NON-AMBULATORY PARTICIPANTS: Percent predicted forced vital capacity greater than 40% as part of pulmonary function tests, as well as adequate upper limb function; > 8 years of age for Sirolimus Cohort

Exclusion Criteria

Receipt of live attenuated vaccination within 3 months prior to receiving PF-06939926 or exposure to an influenza (or other inactivated) vaccination or systemic antiviral and/or interferon therapy within 30 days prior to receipt of PF-06939926; Prior exposure to any gene therapy agent, including exon-skipping agents; Exposure to other investigational drugs within 30 days or 5 half-lives, whichever is longer; Neutralizing antibodies (NAb) against adeno-associated virus, serotype 9 (AAV9); Compromised cardiac function as indicated by left ventricular ejection fraction on cardiac MRI, based on ambulatory status: FOR AMBULATORY PARTICIPANTS: Less than 55%, FOR NON-AMBULATORY PARTICIPANTS: Less than 35%; Inadequate hepatic or renal function or risk factors for autoimmune disease on screening laboratory assessments; Hypersensitivity to sirolimus or intolerance to soy, including a history of angioedema; Concomitant use with strong CYP3A4/P-gp inducers or inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of PF-06939926

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Multiple visits including Day 7, Day 14, Day 180, and Day 360

What Are the Treatments Tested in This Trial?

Interventions

• PF-06939926

Trial Overview The study tests PF-06939926 gene therapy's safety in DMD patients by giving a single IV dose to about 22 participants. It includes staggered enrollment and reviews by an external committee before increasing doses. The trial also measures dystrophin levels, muscle strength, quality, and function.

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

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]

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 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]

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]

Gene therapy for Duchenne muscular dystrophy (DMD) is being actively researched, with promising results from using modified adeno-associated viruses to deliver a mini-gene of dystrophin into muscle cells, which is expected to enter clinical trials soon.

Various methods, including viral and nonviral delivery systems, have been tested in biological models, highlighting the need for collaboration among Russian laboratories to advance these gene therapy experiments towards clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current state and prospects for gene therapy of Duchenne muscular dystrophy in the world and in Russia]. Baranov, VS., Baranov, AN., Zelenin, AV.[2014]

Citations

1. 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 ...

2. 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.

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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03362502

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.