A Study of SRP-9005 in Limb Girdle Muscular Dystrophy Type 2C/R5 Pediatric and Adult Participants

Sarepta Therapeutics, Inc.

Overview

This is a study of a single systemic dose of SRP-9005 in pediatric and adult participants with limb girdle muscular dystrophy type 2C/R5 (LGMD2C/R5). It is comprised of 2 parts (Part A, Part B) that will assess safety and efficacy.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Muscular Dystrophies, Limb-Girdle

Interventions

SRP-9005BIOLOGICAL

Solution for single IV infusion

CorticosteroidDRUG

Oral tablet (prophylactic)

Eligibility

Sex: ALLMin age: 4 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Ambulatory, defined as able to walk without assistive aid, 10MWR \<30 seconds, and NSAD total score ≥20 * Non-ambulatory, defined as 10MWR ≥30 seconds or unable to perform, and PUL 2.0 entry scale score ≥3 * Possess 1 homozygous or 2 heterozygous pathogenic and/or likely pathogenic gamma-SG deoxyribonucleic acid (DNA) gene mutations as documented prior to pre-Infusion screening. Results to be confirmed by sponsor at a CLIA/CAP/ISO15189 certified laboratory prior to dosing. * Have AAVrh74 antibody titers \<1:400 (that is, not elevated) as determined by an enzyme-linked immunoassay Key Exclusion Criteria: * Has a symptomatic infection (for example, upper respiratory tract infection, pneumonia, pyelonephritis, meningitis) within 4 weeks before study treatment infusion * Part A: Has left ventricular ejection fraction (LVEF) \<50% on the screening echocardiogram (ECHO) (without use of cardiac medication) or clinical signs and/or symptoms of cardiomyopathy or any history of cardiac disease * Part B: Has LVEF \<40% on the screening ECHO or clinical signs and/or symptoms of cardiomyopathy * Has FVC \<40% of predicted value at screening and/or requirement for nocturnal ventilation * Serological evidence of current, chronic, or active human immunodeficiency virus infection, or hepatitis B or C infection or active viral or bacterial infection based on clinical observations * Any prior treatment with gene therapy, cell-based therapy (for example, stem cell transplantation), clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), or any other form of gene editing * Treatment with human growth factor within 3 months of Day 1 * Treatment with any investigational medication within 6 months of the screening visit * Is unable to undergo or tolerate a cardiac MRI procedure for any reason Note: Other inclusion/exclusion criteria may apply.

Locations (1)

Children's Hospital of the King's Daughters

Norfolk, Virginia, United States

Outcomes

Primary Outcomes

Part A : Number of Participants with Treatment-emergent Adverse Events (TEAEs)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline in gamma-Sarcoglycan (SG) Expression at Day 60 Post-dose in Ambulatory Participants as Measured by Immunofluorescence (IF) Percent Positive Fibers (PPF)

Time frame: Baseline, Day 60

Secondary Outcomes

Part A and B: Change from Baseline Through Month 60 in North Star Assessment for Dysferlinopathy (NSAD) Total Score

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Performance of the Upper Limb (PUL) Version 2.0 Total Score

Time frame: Baseline through Month 60

Part A and B: Change from Baseline through Month 60 in Time to Rise From Floor

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Time to Ascend 4 Steps

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Time to Complete the 10-meter Walk/Run (10MWR)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Time to Complete 100-meter Walk/Run (100MWR)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Timed Up and Go

Time frame: Baseline through Month 60

Data from ClinicalTrials.gov

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Part A and B: Change from Baseline in gamma-SG Expression at Day 60 in Ambulatory Participants Post-dose as Measured by IF Percent Fiber Intensity (PFI)

Time frame: Baseline, Day 60

Part A and B: Change from Baseline in gamma-SG Expression at Day 60 in Ambulatory Participants Post-dose as Measured by Western Assay

Time frame: Baseline, Day 60

Part A and B: Change from Baseline to Day 60 in Quantity of gamma-SG Protein Expression in Non-ambulatory Participants as Measured by IF PPF

Time frame: Baseline to Day 60

Part A and B: Change from Baseline to Day 60 in Quantity of gamma-SG Protein Expression in Non-ambulatory Participants as Measured by IF PFI

Time frame: Baseline to Day 60

Part A and B: Change from Baseline to Day 60 in Quantity of gamma-SG Protein Expression in Non-ambulatory Participants as Measured by Western Assay

Time frame: Baseline to Day 60

Part A and B: Change from Baseline to Month 24 in Quantity of gamma-SG Protein Expression as Measured by IF PPF

Time frame: Baseline to Month 24

Part A and B: Change from Baseline to Month 24 in Quantity of gamma-SG Protein Expression as Measured by IF PFI

Time frame: Baseline to Month 24

Part A and B: Change from Baseline to Month 24 in Quantity of gamma-SG Protein Expression as Measured by Western Assay

Time frame: Baseline to Month 24

Part A and B: Change from Baseline Through Month 60 in Creatine Kinase Levels

Time frame: Baseline through Month 60

Part A and B: Loss of Ambulation

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Skeletal Muscle Magnetic Resonance Imaging (MRI)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Wearable Device Stride Velocity 95th Percentile (SV95C) (Ambulatory Participants Only)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Vital Capacity (FVC)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Vital Capacity Percent Predicted (FVC%p)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Expiratory Volume in 1 Second (FEV1)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Expiratory Volume in 1 Second % Predicted (FEV1%p)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Peak Expiratory Flow Rate (PEFR)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline through Month 60 in Pulmonary Functions as Assessed by Maximal Inspiratory Pressure (MIP)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Percent Predicted Maximal Inspiratory Pressure (MIP%p)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline through Month 60 in Pulmonary Functions as Assessed by Maximal Expiratory Pressure (MEP)

Time frame: Baseline through Month 60

Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Percent Predicted Maximal Expiratory Pressure (MEP%p)

Time frame: Baseline through Month 60

Part B: Number of Participants with TEAEs

Time frame: Baseline through Month 60