Gene Therapy for Limb-Girdle Muscular Dystrophy

Not currently recruiting at 1 trial location

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Sarepta Therapeutics, Inc.

Must not be taking: Corticosteroids

Disqualifiers: Cardiac, Pulmonary, Hepatic, Renal, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called SRP-9003, a gene therapy, to determine its safety for individuals with limb-girdle muscular dystrophy type 2E/R4 (LGMD2E/R4). The researchers aim to discover if this gene therapy can help produce a key protein in the muscles. Participants are divided into two groups: those who can walk and those who cannot. Individuals with specific gene mutations linked to this condition who can participate in muscle tests might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have a condition that requires chronic drug treatment, it might be considered a risk for the study, so 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 a type of limb-girdle muscular dystrophy, has a promising safety record. In earlier studies, most side effects were mild and occurred within the first 90 days, resolving quickly. The treatment has remained safe over several years of observation. Although this study is in an early stage, past research suggests that SRP-9003 is generally well-tolerated. However, like any new treatment, it may carry risks, and ongoing research aims to learn more about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for Limb-Girdle Muscular Dystrophy, which often includes physical therapy and corticosteroids to manage symptoms, SRP-9003 offers a gene therapy approach that aims to address the root cause of the disease. SRP-9003 works by delivering a functional copy of the mutated gene directly into the muscle cells through a single intravenous infusion. This innovative method has the potential to improve muscle strength and function by promoting the production of essential proteins that patients with this condition lack. Researchers are excited about SRP-9003 because it represents a shift from merely managing symptoms to potentially modifying the disease progression itself.

What evidence suggests that SRP-9003 might be an effective treatment for limb-girdle muscular dystrophy?

Research has shown that SRP-9003, a gene therapy studied in this trial, offers promising results for treating limb-girdle muscular dystrophy type 2E/R4 (LGMD2E/R4). In earlier studies, patients experienced significant increases in beta-sarcoglycan (β-SG) levels in their muscles, which is crucial for muscle function. Specifically, patients unable to walk had an average 23.9% increase in β-SG. Those who could walk showed 36.2% of normal β-SG levels, while those unable to walk reached 62.1%. These findings suggest that SRP-9003 could improve muscle health in individuals with LGMD2E/R4. ^{1 2 3 6 7}

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 individuals aged 4-50 with Limb Girdle Muscular Dystrophy, type 2E/R4 who are either non-ambulatory (can't walk) or ambulatory (can walk). They must have specific genetic mutations and be able to undergo muscle testing. Those with significant other illnesses, exposure to gene therapy, or conditions affecting protocol compliance cannot participate.

Inclusion Criteria

I am between 4 and 50 years old and cannot walk.

I have specific genetic mutations in the β-sarcoglycan gene.

I can participate in muscle strength tests.

Exclusion Criteria

Presence of any other clinically significant illness or medical condition, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, neuromuscular (other than LGMD2E/R4), or behavioral disease, or infection or malignancy or concomitant illness or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risks for gene transfer or a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the participant's ability to comply with the protocol required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability

I haven't had gene therapy or experimental drugs within the trial's time limits.

I cannot take corticosteroids due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single IV infusion of SRP-9003 on Day 1

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• SRP-9003

Trial Overview The study tests the safety and effectiveness of SRP-9003, a gene transfer treatment aimed at expressing β-SG in skeletal muscles of LGMD2E/R4 patients. It includes two groups: one that can walk (Cohort 1) and one that cannot (Cohort 2), assessing how well the treatment works in each.

How Is the Trial Designed?

Group I: SRP-9003 Experimental Treatment 1 Intervention

Participants will receive single IV infusion of SRP-9003 on Day 1.

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

Gene therapy with bidridistrogene xeboparvovec for limb ... Robust SGCB expression was observed: Day 60 mean (s.d.) percentage of normal expression 36.2% (2.7%) in Cohort 1 and 62.1% (8.7%) in Cohort 2.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05876780

NCT05876780 | A Gene Transfer Single Dose Study to ... The primary purpose of this study is to evaluate the safety of SRP-9003 and to quantify expression of β-SG in the skeletal muscle of participants with limb- ...

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. investorrelations.sarepta.com investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-pipeline-progress-multiple-limb

Press Release - Investor Relations | Sarepta Therapeutics, Inc. SRP-9003 is intended to deliver a full-length beta-sarcoglycan transgene and uses the MHCK7 promoter, chosen for its ability to robustly express ...

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

Limb-Girdle Gene Therapy Bididistrogene Xeboparvovec ... Bidridistrogene xeboparvovec showed a sustained safety profile over 4-5 years, with most adverse events occurring within 90 days and being mild ...

7. nationwidechildrens.org nationwidechildrens.org/research/clinical-research/gene-therapy-clinical-research/phase-3-srp-9003

A Phase 3 Multinational, Open-label, Systemic Gene ... 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- ...