Gene Transfer with SRP-6004 for Limb-Girdle Muscular Dystrophy

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Sarepta Therapeutics, Inc.

Must not be taking: Gene therapy, Investigational drugs

Disqualifiers: Significant illness, Chronic drug treatment, 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 treatment called SRP-6004, a gene therapy, to determine its safety for individuals with Limb-Girdle Muscular Dystrophy (LGMD2B/R2). The treatment is administered through an IV infusion, with the primary goal of identifying any side effects. Individuals who can walk and have specific genetic changes related to this condition may qualify. Participants must have healthy arm and leg muscles for testing and should not have high levels of certain antibodies in their blood. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects on people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you require chronic drug treatment that the investigator believes poses a risk for gene transfer, it might be a concern.

Is there any evidence suggesting that SRP-6004 is likely to be safe for humans?

Research shows that SRP-6004 is a new gene therapy being tested for treating a type of limb-girdle muscular dystrophy called LGMD2B/R2. Limited safety information about SRP-6004 is currently available. Studies on similar gene therapies have produced mixed results. Some patients tolerate these treatments well, while others experience side effects like immune reactions or flu-like symptoms.

This trial is in its early stages and primarily aims to assess the safety of SRP-6004. Consequently, detailed safety information may not yet be available. However, researchers closely monitor early-phase trials to quickly identify any issues. Prospective participants should stay informed and ask questions when considering joining this 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 often focus on managing symptoms through physical therapy and corticosteroids, SRP-6004 offers a groundbreaking approach by directly addressing the genetic root of the disease. SRP-6004 is a gene therapy that delivers a modified gene via a single IV infusion, aiming to produce a functional version of the protein missing in patients with this condition. This innovative mechanism has the potential to not just alleviate symptoms but to significantly alter the disease's progression, which is why researchers are particularly excited about its prospects.

What evidence suggests that SRP-6004 might be an effective treatment for Limb-Girdle Muscular Dystrophy?

Research shows that gene therapy, such as SRP-6004, could help treat Limb-Girdle Muscular Dystrophy (LGMD2B/R2). This therapy uses a modified virus to deliver a functional version of the malfunctioning gene. Early results suggest this approach might improve muscle function by restoring missing proteins. Although detailed effectiveness data for SRP-6004 is not yet available, similar gene therapies have shown promise in other muscular dystrophies by boosting muscle strength and slowing disease progression. These early signs offer hope for positive results in treating LGMD2B/R2 with SRP-6004. ^{1 4 5 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 ambulatory individuals with Limb Girdle Muscular Dystrophy, Type 2B/R2. Participants must have specific genetic mutations related to the condition, be able to perform motor tests, and not have high levels of certain antibodies. They can't join if they've had recent gene therapy or other investigational treatments, significant health issues, or need chronic drug treatment that could pose risks.

Inclusion Criteria

I have specific genetic mutations in the DYSF gene.

My arm and leg muscles are suitable for biopsy.

I can participate in tests that measure my muscle movements.

Exclusion Criteria

Presence of any other clinically significant illness, medical condition, or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risk for gene transfer.

Abnormality in protocol-specified diagnostic evaluations or laboratory tests.

Exposure to gene therapy, investigational medication, or other protocol-specified treatment within the protocol specified time limits.

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-6004 on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SRP-6004

Trial Overview The study is testing SRP-6004's safety when given through an IV infusion to people who can walk but have LGMD2B/R2. It aims to understand how well participants tolerate this potential new treatment and its effectiveness in treating their muscular dystrophy.

How Is the Trial Designed?

Group I: SRP-6004 Experimental Treatment 1 Intervention

Participants will receive single IV infusion of SRP-6004 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

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]

AAV9-mediated delivery of the human BVES gene significantly improved muscle function and cardiac health in BVES-knockout mice, demonstrating its potential as a gene therapy for limb-girdle muscular dystrophy type R25 (LGMDR25).

The treatment showed efficacy in both neonatal and adult mice, enhancing body weight, muscle mass, and exercise performance without any observed toxicity, suggesting a promising therapeutic approach for this currently untreatable condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic AAV9.BVES delivery ameliorates muscular dystrophy in a mouse model of LGMDR25. Li, H., Wang, P., Hsu, E., et al.[2023]

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]

This study identified a new genetic locus for limb-girdle muscular dystrophy (LGMD) on chromosome 2p, specifically linked to markers D2S134 and D2S136, after excluding other known loci.

The affected individuals from two large inbred families exhibited similar symptoms, with muscle weakness starting in the pelvic girdle during late adolescence and a generally slow progression of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A gene for autosomal recessive limb-girdle muscular dystrophy maps to chromosome 2p. Bashir, R., Strachan, T., Keers, S., et al.[2022]

A single injection of a recombinant adeno-associated virus (AAV) vector into the tibialis anterior muscle of dystrophic hamsters resulted in over 97% recovery of muscle strength and nearly complete restoration of physiological function, indicating high efficacy of this gene therapy approach for Limb Girdle Muscular Dystrophy (LGMD) 2F.

The treatment not only improved muscle strength but also prevented pathological changes, such as muscle hypertrophy, and led to normal muscle weight and size, showcasing the potential of AAV-mediated gene therapy for long-term benefits in LGMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Full functional rescue of a complete muscle (TA) in dystrophic hamsters by adeno-associated virus vector-directed gene therapy. Xiao, X., Li, J., Tsao, YP., et al.[2019]

Thigh muscle fat replacement measured by proton density fat fraction (PDFF) using MRI is a sensitive indicator of disease progression in patients with limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12), particularly in those with intermediate-stage fat replacement, showing significant changes within just one year.

Biodex isometric dynamometry effectively captures the decline in muscle strength over one year in LGMDR12 patients, making it a valuable outcome measure for future clinical trials, while traditional clinical measures like the 6-minute walk distance and 10-meter walk test were less effective in detecting changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Natural History Study in 24 Adult Patients With LGMDR12 Over 2 Years of Follow-up: Quantitative MRI and Clinical Outcome Measures. De Wel, B., Huysmans, L., Peeters, R., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05906251?cond=dysferlin&

A Gene Transfer Study to Evaluate the Safety, Tolerability ... The primary purpose of this study is to evaluate the safety of SRP-6004 administered by intravenous (IV) infusion in ambulatory participants with LGMD2B/R2 ( ...

2. sarepta.com sarepta.com/community-letter-community-update-lgmd-programs-development

Community Update on LGMD Programs in Development SRP-6004 is Sarepta's investigational gene therapy being developed for the treatment of LGMD2B/R2. Sarepta's investigational LGMD gene therapy, ...

3. scge.mcw.edu scge.mcw.edu/platform/data/clinicalTrials/report/NCT05906251

Gene Therapy Trial Report A Gene Transfer Study to Evaluate the Safety, Tolerability and Efficacy of SRP-6004 in Ambulatory Participants With Limb Girdle Muscular Dystrophy, ...

4. withpower.com withpower.com/trial/phase-1-muscular-dystrophies-4-2023-1bf89

Gene Transfer with SRP-6004 for Limb-Girdle Muscular ... This trial is testing the safety of a medicine called SRP-6004, given through a vein, in people who can walk but have a specific type of muscular dystrophy ( ...

5. jain-foundation.org jain-foundation.org/patients-clinicians/how-to-take-action/clinical-trials-studies-and-surveys/

Clinical Trials, Studies And Surveys This is a 24-month, observational study of up to 1000 participants with Limb Girdle Muscular Dystrophy (LGMD), Myotonic Dystrophy Type 2 (DM2), ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05906251

NCT05906251 | A Gene Transfer Study to Evaluate the ... A Gene Transfer Study to Evaluate the Safety, Tolerability and Efficacy of SRP-6004 in Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2B/​R2 ...

7. sarepta.com sarepta.com/community-bulletin-lgmd-2br2-community

Community Bulletin for the LGMD 2B/R2 Community What is SRP-6004? SRP-6004 is Sarepta's investigational gene therapy being developed for the treatment of LGMD 2B/R2. Like all of Sarepta's investigational LGMD ...