Gene Therapy for Duchenne Muscular Dystrophy

Recruiting at 5 trial locations

Overseen By Solid Bio Clinical Trials

Age: < 18

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Solid Biosciences Inc.

Must be taking: Prednisone, Deflazacort

Must not be taking: Dystrophin modifying drugs

Disqualifiers: Gene transfer drugs, Exon 1-11, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 1 day

43 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of prednisone or deflazacort for at least 12 weeks before joining. It does not specify if you need to stop other medications, but you cannot have taken certain drugs within 3 months before the trial.

What data supports the effectiveness of the treatment SGT-003 Gene Therapy for Duchenne Muscular Dystrophy?

Gene therapy using adeno-associated virus (AAV) to deliver dystrophin has shown promise in early studies for improving muscle function in Duchenne Muscular Dystrophy (DMD). Initial reports suggest potential benefits for movement, although more research is needed to understand its effects on heart and lung complications associated with DMD. ^{1 2 3 4 5}

How is the SGT-003 treatment for Duchenne Muscular Dystrophy different from other treatments?

SGT-003 Gene Therapy is unique because it uses a modified virus to deliver a mini-gene version of the dystrophin gene directly to muscle cells, aiming for more efficient and targeted delivery compared to traditional methods. This approach is designed to overcome challenges like immune reactions and low gene expression seen with other gene therapy techniques. ^{4 6 7 8 9}

What is the purpose of this trial?

This is a multicenter, open-label, non-randomized study to investigate the safety, tolerability, and efficacy of a single intravenous (IV) infusion of SGT-003 in participants with Duchenne muscular dystrophy. There will be 2 cohorts in this study. Cohort 1 will include participants 4 to \<7 years of age. Cohort 2 will include participants 7 to \<12 years of age. All participants will receive SGT-003 and will be enrolled in the study for 5 total years for long-term follow up.

Research Team

Solid Bio Clinical Trials

Principal Investigator

Solid Biosciences

Eligibility Criteria

The INSPIRE DUCHENNE trial is for young boys with Duchenne muscular dystrophy. Cohort 1 includes ages 4 to under 6, weighing less than 18 kg and able to walk unaided. Cohort 2 will be ages 6 to under 8, weighing less than 30 kg. Participants must not have used certain other treatments for DMD or been in another study recently.

Inclusion Criteria

I can walk on my own without needing help from any device.

I weigh less than 18 kg.

I weigh less than 30 kg.

Exclusion Criteria

I have been treated with a gene therapy drug.

I have used drugs like eteplirsen for my condition.

Exposure to another investigational drug within 3 months prior to screening or 5 half-lives since last administration, whichever is longer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of SGT-003 on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Multiple visits over 5 years

Treatment Details

Interventions

• SGT-003

Trial Overview This study tests SGT-003 gene therapy given through an IV infusion once. It's divided into two age groups dosed one after the other, with a long-term follow-up of five years to check safety and effectiveness.

Participant Groups

Group I: Cohort 2: SGT-003 Experimental Treatment 1 Intervention

All participants will receive a single IV infusion of SGT-003 on Day 1.

Group II: Cohort 1: SGT-003 Experimental Treatment 1 Intervention

All participants will receive a single IV infusion of SGT-003 on Day 1.

SGT-003 is already approved in United States for the following indications:

Approved in United States as SGT-003 for:

• Duchenne muscular dystrophy

Who Is Running the Clinical Trial?

Solid Biosciences Inc.

Lead Sponsor

Trials

4

Recruited

130+

Findings from Research

Gene therapy shows promise in preventing muscle deterioration and improving ambulation in patients with Duchenne muscular dystrophy (DMD), although clinical trials are still in early stages.

There is a significant gap in understanding how gene therapy may impact cardiomyopathy and respiratory failure, which are major causes of mortality in DMD patients, highlighting the need for future studies to include respiratory endpoints as outcome measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of emerging molecular and genetic therapies on cardiopulmonary disease in Duchenne muscular dystrophy. McKim, DA., Cripe, TP., Cripe, LH.[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]

Gene therapy using adeno-associated virus (rAAV) to deliver mini/micro-dystrophin shows promise for treating Duchenne Muscular Dystrophy (DMD), but high doses of rAAV can lead to immune responses and liver toxicity, especially in older patients.

Research suggests that using utrophin, a protein similar to dystrophin, along with a novel MyoAAV delivery system, could enhance therapeutic effects while reducing the required rAAV dose, potentially making gene therapy safer and more effective for a broader range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for Bottlenecks of rAAV-Mediated Expression in Skeletal and Cardiac Muscle of Duchenne Muscular Dystrophy. Li, N., Song, Y.[2022]

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]

Recent advancements in gene delivery methods, particularly using adeno-associated viral vectors, show great promise for treating muscular dystrophies, although a complete cure has not yet been achieved.

Systemic administration of anti-sense oligonucleotides has successfully induced dystrophin expression and improved muscle health in canine models, highlighting a potential therapeutic approach for conditions like Duchenne muscular dystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic strategy for muscular dystrophies]. Shin, JH., Takeda, S.[2013]

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]

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]

Implanting normal muscle precursor cells into dystrophin-deficient muscles in mice shows promise for treating Duchenne muscular dystrophy (DMD), but similar approaches in human patients have not been successful.

Gene therapy techniques, such as introducing dystrophin constructs via viral vectors, have been demonstrated in mice, but their efficiency and safety need thorough evaluation before being tested in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell and gene therapy in Duchenne muscular dystrophy. Morgan, JE.[2012]

Recent advancements in gene therapy for muscular dystrophy highlight the potential of plasmid DNA as a treatment option, overcoming previous challenges like low transfection efficiency and immune rejection.

A groundbreaking clinical trial using a human dystrophin plasmid and a novel intravascular delivery method has shown promise in achieving widespread muscle transfection, paving the way for effective treatments for Duchenne muscular dystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naked plasmid DNA for the treatment of muscular dystrophy. Braun, S.[2012]

References

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

The effect of emerging molecular and genetic therapies on cardiopulmonary disease in Duchenne muscular dystrophy. [2021]

2. 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]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Strategies for Bottlenecks of rAAV-Mediated Expression in Skeletal and Cardiac Muscle of Duchenne Muscular Dystrophy. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Gene therapy in Duchenne muscular dystrophy. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

[Therapeutic strategy for muscular dystrophies]. [2013]

6. Japan pubmed.ncbi.nlm.nih.gov

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

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Current state and prospects for gene therapy of Duchenne muscular dystrophy in the world and in Russia]. [2014]

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

Cell and gene therapy in Duchenne muscular dystrophy. [2012]

9. England pubmed.ncbi.nlm.nih.gov

Naked plasmid DNA for the treatment of muscular dystrophy. [2012]