Gene Therapy for Duchenne Muscular Dystrophy

Recruiting at 83 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

114 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment PF-06939926 for Duchenne Muscular Dystrophy?

Research shows that gene therapy, including micro-dystrophin gene transfer using adeno-associated virus vectors, is promising for treating Duchenne Muscular Dystrophy. This approach has shown potential in animal models and early trials, suggesting it could help improve muscle function in patients. ^{1 2 3 4 5}

Is gene therapy for Duchenne Muscular Dystrophy safe for humans?

The research on gene therapy for Duchenne Muscular Dystrophy, including treatments like NS-065/NCNP-01, shows a favorable safety profile with no severe adverse reactions observed in trials. However, adenovirus vectors used in some gene therapies can have dose-dependent toxic effects, indicating a narrow safety margin. ^{6 7 8 9 10}

How is the treatment PF-06939926 for Duchenne Muscular Dystrophy different from other treatments?

PF-06939926 is unique because it uses a gene therapy approach, delivering a micro-dystrophin gene via a specially designed virus (rAAVrh74) to target and improve muscle function in Duchenne Muscular Dystrophy patients, unlike traditional treatments that do not address the genetic cause of the disease. ^{1 2 3 11 12}

What is the purpose of this trial?

This trial tests a gene therapy treatment for boys aged 4 to 7 with muscle problems. The treatment aims to fix the genetic issues causing their muscle problems. Participants will receive the treatment and be monitored for safety and effectiveness. The treatment involves using a specific gene therapy, which has been researched for its potential to correct muscle issues in children with muscle problems.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

Development of therapy for Duchenne muscular dystrophy. [2012]

2. England pubmed.ncbi.nlm.nih.gov

Gene therapy research for Duchenne and Becker muscular dystrophies. [2019]

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

Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial. [2021]

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

Gene therapy for muscular dystrophy: moving the field forward. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Viral vector-mediated gene therapies. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Adenovirus-mediated dystrophin minigene transfer improves muscle strength in adult dystrophic (MDX) mice. [2021]

7. United States 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. [2019]

8. Spain pubmed.ncbi.nlm.nih.gov

Casimersen for Duchenne muscular dystrophy. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. [2022]

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

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

11. China pubmed.ncbi.nlm.nih.gov

[Study on the recombinant adeno-associated virus vector carrying LacZ gene expression in the skeletal muscle]. [2007]

12. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Adeno-Associated Virus (AAV) Mediated Dystrophin Gene Transfer Studies and Exon Skipping Strategies for Duchenne Muscular Dystrophy (DMD). [2019]