Clinical trial NCT06952686: A Study of SRP-9005 in Limb Girdle Muscular Dystrophy Type 2C/R5 Pediatric and Adult Participants
Official title: A Seamless Phase 1/3, Multicenter, Single Dose Systemic Gene Transfer Study to Evaluate the Safety, Tolerability, and Efficacy of SRP-9005 in Limb Girdle Muscular Dystrophy Type 2C/R5 Subjects (COMPASS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Muscular Dystrophies, Limb-Girdle
Keywords: SRP-9005
Type 2C/R5
LGMD2C/R5
Pediatric
Non-ambulatory
Ambulatory
Phase 1
Phase 3
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2025-05-01
Enrollment: 15
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study comprises 2 parts: Part A is the Phase 1 portion, Part B is the Phase 3 expansion portion.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part A : Number of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline through Month 60
measure: 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)
timeFrame: Baseline, Day 60
Secondary outcomes:
measure: Part A and B: Change from Baseline Through Month 60 in North Star Assessment for Dysferlinopathy (NSAD) Total Score
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Performance of the Upper Limb (PUL) Version 2.0 Total Score
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline through Month 60 in Time to Rise From Floor
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Time to Ascend 4 Steps
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Time to Complete the 10-meter Walk/Run (10MWR)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Time to Complete 100-meter Walk/Run (100MWR)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Timed Up and Go
timeFrame: Baseline through Month 60
measure: 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)
timeFrame: Baseline, Day 60
measure: Part A and B: Change from Baseline in gamma-SG Expression at Day 60 in Ambulatory Participants Post-dose as Measured by Western Assay
timeFrame: Baseline, Day 60
measure: 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
timeFrame: Baseline to Day 60
measure: 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
timeFrame: Baseline to Day 60
measure: 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
timeFrame: Baseline to Day 60
measure: Part A and B: Change from Baseline to Month 24 in Quantity of gamma-SG Protein Expression as Measured by IF PPF
timeFrame: Baseline to Month 24
measure: Part A and B: Change from Baseline to Month 24 in Quantity of gamma-SG Protein Expression as Measured by IF PFI
timeFrame: Baseline to Month 24
measure: Part A and B: Change from Baseline to Month 24 in Quantity of gamma-SG Protein Expression as Measured by Western Assay
timeFrame: Baseline to Month 24
measure: Part A and B: Change from Baseline Through Month 60 in Creatine Kinase Levels
timeFrame: Baseline through Month 60
measure: Part A and B: Loss of Ambulation
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Skeletal Muscle Magnetic Resonance Imaging (MRI)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Wearable Device Stride Velocity 95th Percentile (SV95C) (Ambulatory Participants Only)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Vital Capacity (FVC)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Vital Capacity Percent Predicted (FVC%p)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline through Month 60
measure: 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)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Peak Expiratory Flow Rate (PEFR)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline through Month 60 in Pulmonary Functions as Assessed by Maximal Inspiratory Pressure (MIP)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Percent Predicted Maximal Inspiratory Pressure (MIP%p)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline through Month 60 in Pulmonary Functions as Assessed by Maximal Expiratory Pressure (MEP)
timeFrame: Baseline through Month 60
measure: Part A and B: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Percent Predicted Maximal Expiratory Pressure (MEP%p)
timeFrame: Baseline through Month 60
measure: Part B: Number of Participants with TEAEs
timeFrame: Baseline through Month 60
Other outcomes:
Locations:
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: