Gene Therapy for Limb-Girdle Muscular Dystrophy

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sarepta Therapeutics, Inc.

Disqualifiers: Active viral infection, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 1

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, SRP-9003, for individuals with Limb-Girdle Muscular Dystrophy, specifically LGMD2E. The goal is to improve muscle function by delivering genes directly into the body. Participants will receive a single dose of SRP-9003, with the second group's dosage determined by the first group's results. Those who struggle with activities like running, jumping, or climbing stairs due to this condition might be suitable for the trial. 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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but if you have a condition that requires ongoing treatment, it might be considered a risk for the study. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that SRP-9003 is likely to be safe for humans?

Research has shown that SRP-9003, a gene therapy for limb-girdle muscular dystrophy, has generally been well-tolerated in past studies. Over five years, most treatment-related side effects were mild or moderate and occurred mainly within the first 90 days after treatment, suggesting that serious issues are rare.

This trial is in its early stages and focuses on the treatment's safety for participants. While SRP-9003 remains under investigation, these results offer encouragement for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for limb-girdle muscular dystrophy, which primarily focus on managing symptoms with physical therapy and medications, SRP-9003 offers a new approach by using gene therapy. This treatment works by delivering a copy of a functional gene to muscle cells, aiming to address the root cause of the disease rather than just alleviating symptoms. Researchers are excited because this method could potentially provide a long-lasting effect from a single intravenous infusion, offering hope for a more effective and lasting solution.

What evidence suggests that SRP-9003 might be an effective treatment for LGMD2E?

Research has shown that SRP-9003 holds promise for treating limb-girdle muscular dystrophy Type 2E (LGMD2E). Early results found a 23.9% average improvement in muscle function in patients unable to walk after receiving the treatment. This gene therapy targets a specific gene related to the disease, aiming to restore normal muscle function. Initial studies in humans have shown positive results, suggesting that SRP-9003 could effectively address the genetic cause of LGMD2E. The therapy's potential to increase muscle strength offers hope for those affected by this condition. Participants in this trial will receive a single intravenous (IV) infusion of SRP-9003, with dosing determined based on findings from earlier cohorts. ^{2 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Sarepta Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for males and females with Limb-Girdle Muscular Dystrophy, Type 2E (LGMD2E), who have specific gene mutations and experience difficulty in physical activities like running or climbing stairs. Participants must be able to complete a 100 meter walk/run test at a minimum of 40% efficiency compared to healthy individuals.

Inclusion Criteria

I can walk or run 100 meters at least 40% as well as others my age and size.

I am of any gender and ethnicity.

I have trouble running, jumping, or climbing stairs.

Exclusion Criteria

I don't have any illnesses or need for ongoing medication that would make gene therapy risky.

My heart's pumping ability is below 40%.

I have been diagnosed with or am being treated for an autoimmune disease.

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 SRP-9003

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• SRP-9003

Trial Overview The study tests SRP-9003 (bidridistrogene xeboparvovec), which is a new gene therapy delivered once to patients with LGMD2E. It's an open-label trial, meaning both the researchers and participants know what treatment is being given.

How Is the Trial Designed?

Group I: Cohort 2: SRP-9003 Experimental Treatment 1 Intervention

Participants will receive a single IV infusion of SRP-9003. Dose will be determined based on the findings from Cohort 1.

Group II: Cohort 1: SRP-9003 Experimental Treatment 1 Intervention

Participants will receive a single intravenous (IV) infusion of SRP-9003 at a prespecified dose.

Who Is Running the Clinical Trial?

Sarepta Therapeutics, Inc.

Lead Sponsor

Trials

54

Recruited

34,000+

Published Research Related to This Trial

Gene therapy is showing promising progress in treating limb-girdle muscular dystrophies (LGMDs), particularly in conditions like calpainopathies, dysferlinopathies, and sarcoglycanopathies, with early clinical trials demonstrating safety and efficacy.

Emerging technologies such as CRISPR/Cas9 may further enhance the effectiveness of gene therapy for LGMDs, paving the way for more advanced treatment options in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unmet needs and evolving treatment for limb girdle muscular dystrophies. Pozsgai, E., Griffin, D., Potter, R., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38177855/

Gene therapy with bidridistrogene xeboparvovec for limb ... Here we report interim results from a first-in-human, open-label, nonrandomized, phase 1/2 trial evaluating the safety and efficacy of bidridistrogene ...

2. investorrelations.sarepta.com investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-completes-enrollment-emergene-phase-3

Press Release - Investor Relations | Sarepta Therapeutics, Inc. SRP-9003 is an investigational gene therapy for the treatment of limb-girdle muscular dystrophy Type 2E/R4 (LGMD2E/R4), or beta-sarcoglycanopathy.

3. institut-myologie.org institut-myologie.org/en/2024/03/01/gene-therapy-shows-encouraging-results-in-humans-for-limb-girdle-muscular-dystrophy-linked-to-sgcb/

Gene therapy shows encouraging results in humans for ... Gene therapy shows encouraging results in humans for limb-girdle muscular dystrophy linked to SGCB ... efficacy of SRP-9003 (rAAVrh74.

4. biospace.com biospace.com/drug-development/sareptas-not-done-with-gene-therapy-yet-as-lgmd-asset-yields-promising-data

Sarepta's Not Done With Gene Therapy Yet as LGMD ... Results showed that SRP-9003 hit its primary endpoint. In non-ambulatory patients, the gene therapy resulted in a 23.9% average increase in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06246513

Study Details | NCT06246513 | A Trial to Learn More About ... This is a multicenter, global study of the effects of a single systemic dose of SRP-9003 on beta-sarcoglycan (β-SG) gene expression in participants with limb- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05876780

NCT05876780 | A Gene Transfer Single Dose Study to ... A Gene Transfer Single Dose Study to Evaluate the Safety, Tolerability and Efficacy of SRP-9003 in Non-Ambulatory and Ambulatory Participants With Limb Girdle ...

7. neurologylive.com neurologylive.com/view/limb-girdle-gene-therapy-bididistrogene-xeboparvovec-demonstrates-5-year-safety-early-stage-trial

Limb-Girdle Gene Therapy Bididistrogene Xeboparvovec ... Over the 5-year period, treatment-related adverse events with the gene therapy were mild or moderate, with most occurring within the first 90 days after ...

8. cgtlive.com cgtlive.com/view/patients-treated-askbio-limb-girdle-muscular-dystrophy-gene-therapy-ab-1003-free-serious-adverse-events-52-weeks

Patients Treated With AskBio's Limb-Girdle Muscular ... Patients Treated With AskBio's Limb-Girdle Muscular Dystrophy Gene Therapy AB-1003 Free of Serious Adverse Events at Up to 52 Weeks · 1. AskBio ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10803256/

Gene therapy with bidridistrogene xeboparvovec for limb ... Here we report interim results from a first-in-human, open-label, nonrandomized, phase 1/2 trial evaluating the safety and efficacy of bidridistrogene ...