A Gene Transfer Therapy Study to Evaluate the Safety of SRP-9004 (Patidistrogene Bexoparvovec) in Participants With Limb-Girdle Muscular Dystrophy, Type 2D (LGMD2D)

Study Overview
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Brief Summary
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This is an open-label, dose escalation gene transfer therapy study evaluating the safety of SRP-9004 (patidistrogene bexoparvovec) via isolated limb infusion (ILI) administration in approximately 6 participants with LGMD2D.

Official Title
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Phase I/IIA Gene Transfer Clinical Trial for LGMD2D (Alpha-Sarcoglycan Deficiency) Using scAAVrh74.tMCK.hSGCA

Conditions
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Limb-Girdle Muscular Dystrophy, Type 2D

Intervention / Treatment
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* Genetic: SRP-9004


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Cohort 1A must be adult and wheelchair-dependent; Cohorts 1B and 2 will be participants of age 7 or older. Confirmed alpha-sarcoglycan deficiency or identified sarcoglycan alpha (SGCA) deoxyribonucleic acid (DNA) mutation. Participants enrolled in Cohorts 1B or 2 must be able to walk independently, but must exhibit signs of lower extremity weakness (that is, a Gowers' sign, use a handrail for climbing stairs) and walk ≤80% of predicted distance on the 6 minute walk test (6MWT) based on normative data. Key Exclusion Criteria: Active viral infection based on clinical observations. The presence of SGCA mutations without weakness or loss of function. Symptoms or signs of cardiomyopathy. Serological evidence of human immunodeficiency virus (HIV), Hepatitis B, or C infection. Diagnosis of (or ongoing treatment for) an autoimmune disease. Participants with AAVrh74 or AAV8 binding antibody titers ≥ 1:50 as determined by enzyme-linked immunosorbent assay (ELISA) immunoassay. Other inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 7 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1A: SRP-9004 Low Dose (Single Limb Perfusion)<br>Non-ambulant participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to a single limb on Day 0. | Genetic: SRP-9004<br>* Isolated Limb Infusion (ILI)<br>* Other names: patidistrogene bexoparvovec;|
| Experimental: Cohort 1B Low Dose (Bilateral Limb Perfusion)<br>Participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to both limbs on Day 0. | Genetic: SRP-9004<br>* Isolated Limb Infusion (ILI)<br>* Other names: patidistrogene bexoparvovec;|
| Experimental: Cohort 2 High Dose (Bilateral Limb Perfusion)<br>Participants with LGMD2D will receive 1 high dose of SRP-9004 via ILI to both limbs on Day 0. | Genetic: SRP-9004<br>* Isolated Limb Infusion (ILI)<br>* Other names: patidistrogene bexoparvovec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs). | An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug related. An AE was considered serious if, in the view of the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Treatment-related Treatment Emergent Adverse Event (TEAE) is defined as an TEAE that was classified by the investigator as related to treatment. | Up to 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of the Distance Walked in 6 Minutes (6MWT) | The 6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course in 6 minutes (timed), and the distance walked (in meters) was recorded. | Baseline, Up to 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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limb girdle muscular dystrophy, LGMD2D, alpha-sarcoglycan, gene transfer, adeno-associated virus