Gene Therapy for Duchenne Muscular Dystrophy

(IGNITE DMD Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment called SGT-001 for children and teens with Duchenne muscular dystrophy (DMD), a genetic disorder that causes muscle weakness. The main goal is to assess the treatment's safety and patient tolerance. Participants will receive an IV infusion of SGT-001 and be monitored for about five years. Those with a confirmed DMD diagnosis, no dystrophin in their muscles, and stable heart and lung function may qualify. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

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.

Is there any evidence suggesting that SGT-001 is likely to be safe for humans?

Research has shown that SGT-001 appears safe for people with Duchenne muscular dystrophy. In one study, a patient who received SGT-001 experienced only mild and temporary side effects, which were easy to manage and not serious. The study also found that safety improved with new procedures and production methods. While these results are promising, ongoing research is necessary to fully understand the safety of SGT-001. ^{1 2 3 4 5}

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

SGT-001 is unique because it offers a new approach to treating Duchenne Muscular Dystrophy by using gene therapy to address the root cause of the disease. Unlike traditional treatments, such as corticosteroids and exon-skipping drugs that mainly manage symptoms or slightly slow disease progression, SGT-001 aims to deliver a functional version of the dystrophin gene directly into muscle cells. This gene therapy has the potential to produce dystrophin protein, which is missing in individuals with Duchenne, potentially transforming the disease outlook. Researchers are excited because this approach could lead to more robust and lasting improvements in muscle function compared to existing treatments.

What evidence suggests that SGT-001 might be an effective treatment for Duchenne muscular dystrophy?

Research shows that SGT-001, a gene therapy for Duchenne muscular dystrophy (DMD), might improve muscle function. In this trial, participants will receive SGT-001 at either a starting dose or a higher dose, while some will join an untreated control group. A study found that patients who received SGT-001 performed better in walking tests and had stronger muscles compared to typical disease progression. Long-term data, up to three years after treatment, indicated that participants maintained their mobility. The therapy provides a healthy version of the dystrophin gene, which people with DMD lack or have in a faulty form. Early results are promising, suggesting SGT-001 could be a helpful treatment for DMD. ^{1 4 6 7 8}

Who Is on the Research Team?

Solid Bio Clinical Trials

Principal Investigator

Solid Biosciences

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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. solidbio.com solidbio.com/wp-content/uploads/WMS-2022_IGNITE-DMD-Long-Term-Outcomes-and-Expression-Update_October-2022.pdf

IGNITE DMD Phase I/II Study of SGT-001 Microdystrophin ... IGNITE DMD Phase I/II clinical trial to assess the safety and efficacy of SGT-001. • Cohorts. • n=3 subjects analyzed as controls. • n=3 subjects at 5E13 vg/kg ...

2. parentprojectmd.org parentprojectmd.org/solid-biosciences-reports-2-year-efficacy-and-safety-data-from-the-ongoing-phase-i-ii-ignite-dmd-clinical-trial-of-sgt-001/

Solid Biosciences Reports 2-Year Efficacy and Safety Data ... These data enhance our understanding of the role that SGT-001 may play in improving outcomes for patients with Duchenne. We continue to advance ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0960896622004369

FP.28 IGNITE DMD phase I/II study of SGT-001 ... Here we present updated long-term functional outcomes and microdystrophin expression data. At the 1-year post-dosing timepoint, subjects in the 2E14 vg/kg group ...

4. mdaconference.org mdaconference.org/abstract-library/3-year-outcomes-update-in-the-ignite-dmd-phase-1-2-study-of-sgt-001-microdystrophin-gene-therapy/

3-Year Outcomes Update in the IGNITE DMD Phase 1/2 ... We now present data up to 3 years post-dosing demonstrating the durability of treatment effect. Subjects receiving 2E14 vg/kg maintained motor function.

5. cgtlive.com cgtlive.com/view/sgt-001-efficacy-dmd-1-5-year-data

SGT-001 Shows Efficacy in DMD in 1.5-Year Data Patient-reported outcomes, 6-minute walk test, and NSAA scores all showed improvements over natural history data.

6. investors.solidbio.com investors.solidbio.com/news-releases/news-release-details/solid-biosciences-reports-efficacy-and-safety-data-ongoing

Overview & News - : - Press Release Patient 7 in IGNITE DMD was safely dosed, with transient and manageable adverse events, none of which were serious.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03368742

NCT03368742 | Microdystrophin Gene Transfer Study in ... 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 ...

8. parentprojectmd.org parentprojectmd.org/solid-biosciences-reports-efficacy-and-safety-data-from-the-ongoing-ignite-dmd-clinical-trial-and-resumption-of-patient-dosing-in-the-2e14-vg-kg-cohort/

Solid Reports Efficacy & Safety Data from Ongoing IGNITE ... We are encouraged with the improved safety profile of SGT-001 under our previously reported amended protocol and second-generation manufacturing ...