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 (LGMD2B/R2, Dysferlin [DYSF] Related)

Study Overview
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Brief Summary
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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 (DYSF related).

Official Title
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An Open-Label, Systemic Gene Transfer Study to Evaluate the Safety, Tolerability, and Efficacy of SRP 6004 Administered by Systemic Infusion in Ambulatory Subjects With Limb Girdle Muscular Dystrophy Type 2B/R2 (LGMD2B/R2, Dysferlin Related)

Conditions
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Limb Girdle Muscular Dystrophy

Intervention / Treatment
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* Genetic: SRP-6004


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Possess 1 homozygous or 2 heterozygous pathogenic and/or likely pathogenic DYSF Deoxyribonucleic acid (DNA) gene mutations as documented prior to screening visits. Participants must be ambulatory per protocol specified criteria. Ability to cooperate with motor assessment testing. Has accessible and intact lower and upper extremity musculature for biopsy. Have adeno-associated virus rhesus serotype 74 (rAAVrh74) antibody titers < 1:400 (that is, not elevated) as determined by enzyme-linked immunosorbent assay (ELISA). Exclusion Criteria: Exposure to gene therapy, investigational medication, or other protocol-specified treatment within the protocol specified time limits. Abnormality in protocol-specified diagnostic evaluations or laboratory tests. 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. Note: Other inclusion or exclusion criteria could apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SRP-6004<br>Participants will receive single IV infusion of SRP-6004 on Day 1. | Genetic: SRP-6004<br>* Single IV infusion of SRP-6004<br>* Other names: rAAVrh74.MHCK7.DYSF.DV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs) |  | Baseline up to Month 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Percent of Normal DYSF Protein Expression as Measured by Western Blot |  | Baseline, Day 90 and Month 24 | 
| Change from Baseline in Percent of Normal DYSF Protein Expression as Measured by Immunofluorescence (IF) Fiber Intensity |  | Baseline, Day 90 and Month 24 | 
| Change from Baseline in Percent of Normal DYSF Protein Expression as Assessed by IF Percent DYSF Positive Fibers (PPF: DYSF) |  | Baseline, Day 90 and Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ambulatory, Gene-Delivery, LGMD2B/R2, Dysferlin, LGMD