Gene Therapy for Duchenne Muscular Dystrophy

(IGNITE DMD Trial)

Recruiting at 3 trial locations

Age: < 18

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Solid Biosciences Inc.

Must be taking: Corticosteroids

Disqualifiers: Abnormal liver, renal, cardiovascular, others

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

Compensation: Varies

Number of Visits: 6

Duration: 1 day

12 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does require a stable daily dose of oral corticosteroids for at least 12 weeks before joining. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment SGT-001 for Duchenne Muscular Dystrophy?

Research shows that gene therapy using a virus to deliver micro-dystrophin, a smaller version of the dystrophin protein, can help treat Duchenne Muscular Dystrophy. In studies, this approach has shown promise in increasing dystrophin levels in muscle cells, which is important for muscle function. ^{1 2 3 4 5}

Is gene therapy for Duchenne Muscular Dystrophy generally safe in humans?

Research shows that gene therapy using adeno-associated virus (AAV) vectors for Duchenne Muscular Dystrophy has been well tolerated in animal studies, with no significant adverse effects observed. Early human trials are focused on safety, and while some immune responses have been noted, the therapy is considered promising and generally safe. ^{1 2 6 7 8}

How is the treatment SGT-001 for Duchenne Muscular Dystrophy different from other treatments?

SGT-001 is a gene therapy that uses a viral vector to deliver a micro-dystrophin gene to muscle cells, aiming to produce a functional version of the dystrophin protein, which is missing in Duchenne Muscular Dystrophy. This approach is unique because it targets the root genetic cause of the disease, unlike traditional treatments that mainly address symptoms. ^{1 4 7 9 10}

What is the purpose of this trial?

This is a controlled, open-label, single-ascending dose study to evaluate the safety and tolerability of SGT-001 in adolescents and children with Duchenne muscular dystrophy (DMD). Participants will receive a single intravenous (IV) infusion of SGT-001 and will be followed for approximately 5 years. The protocol was amended to drop the control arm after 4 participants were dosed.

Research Team

Solid Bio Clinical Trials

Principal Investigator

Solid Biosciences

Eligibility Criteria

This trial is for children and adolescents with Duchenne muscular dystrophy (DMD), who have a confirmed diagnosis, lack dystrophin protein, and meet specific criteria regarding antibody levels, heart and lung function. Participants must be on stable corticosteroid treatment. Those with significant health issues or recent exposure to certain drugs are excluded.

Inclusion Criteria

I have been diagnosed with DMD and have a gene mutation linked to it.

I am a teenager who cannot walk.

My child can walk as required by the study.

Exclusion Criteria

I need help to breathe during the day or have a lung function test showing impaired breathing.

My BMI is in the top 5% for my age group.

I haven't taken drugs affecting dystrophin or utrophin in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous (IV) infusion of SGT-001

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular visits over 5 years

Treatment Details

Interventions

• SGT-001

Trial Overview The study tests SGT-001, a gene therapy delivered through an IV infusion once. It aims to assess safety, tolerability, and effectiveness over about 5 years in DMD patients. Initially designed as controlled study but now all new participants receive the active treatment.

Participant Groups

Group I: SGT-001 - Dose Level 2 Experimental Treatment 1 Intervention

Single IV infusion of SGT-001 at next ascending dose

Group II: SGT-001 - Dose Level 1 Experimental Treatment 1 Intervention

Single IV infusion of SGT-001 at starting dose

Group III: Untreated Control Active Control 1 Intervention

Untreated control group. After 1 year, treatment-eligible control participants will receive SGT-001 at the selected dose.

Who Is Running the Clinical Trial?

Solid Biosciences Inc.

Lead Sponsor

Trials

4

Recruited

130+

Solid Biosciences, LLC

Lead Sponsor

Trials

2

Recruited

70+

Findings from Research

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]

The study demonstrated that a recombinant adeno-associated virus vector (rAAV8) carrying a modified U7snRNA sequence is safe for use in treating Duchenne muscular dystrophy (DMD) in 18 Golden Retriever Muscular Dystrophy (GRMD) dogs, with no adverse effects observed.

A dose-dependent response was noted, with up to 80% of myofibers expressing dystrophin at the highest dose, indicating that a minimum threshold of dystrophin expression is necessary for therapeutic effects, supporting future trials in nonambulatory DMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients. Le Guiner, C., Montus, M., Servais, L., et al.[2022]

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]

The study developed a human codon-optimized version of microutrophin (µUtrn) that showed robust muscle expression and functional improvement in mdx mice, indicating its potential as a safer alternative to traditional dystrophin gene therapy for Duchenne muscular dystrophy (DMD).

Long-term administration of rAAV9-µUtrn resulted in lower immunogenicity and no adverse effects in toxicity studies, supporting its safety for clinical development as a gene therapy for DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of highly functional codon-optimized microutrophin for muscle-specific expression. Starikova, AV., Skopenkova, VV., Polikarpova, AV., et al.[2022]

The research focuses on using gene therapy to deliver the full-length dystrophin gene to skeletal muscle fibers in patients with Duchenne muscular dystrophy, which is crucial for correcting the muscle abnormalities caused by the disease.

A phase I safety clinical trial is currently underway, which aims to assess the safety of plasmid DNA administration as a method for gene therapy, potentially leading to future therapeutic trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current protocol of a research phase I clinical trial of full-length dystrophin plasmid DNA in Duchenne/Becker muscular dystrophies. Part I: rationale. Thioudellet, C., Blot, S., Squiban, P., et al.[2019]

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]

References

1. 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]

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

Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients. [2022]

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. China pubmed.ncbi.nlm.nih.gov

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

5. China pubmed.ncbi.nlm.nih.gov

[Experimental study of treating Duchenne muscular dystrophy with myoblast transplantation]. [2012]

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

Therapeutic potential of highly functional codon-optimized microutrophin for muscle-specific expression. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Current protocol of a research phase I clinical trial of full-length dystrophin plasmid DNA in Duchenne/Becker muscular dystrophies. Part I: rationale. [2019]

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

Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy. [2023]

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

Improved adenoviral vectors for gene therapy of Duchenne muscular dystrophy. [2019]

10. 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]