Clinical trial NCT06747273: Study to Evaluate the Safety, Tolerability, and Efficacy of SRP-9004 Administered by Systemic Infusion in Limb Girdle Muscular Dystrophy Type 2D/R3 Participants in the United States
Official title: A Phase 1b, Multicenter, Single Dose Gene Transfer Study to Evaluate the Safety, Tolerability, and Efficacy of SRP-9004 Administered by Systemic Infusion in Limb Girdle Muscular Dystrophy Type 2D/R3 Subjects in the United States
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Limb Girdle Muscular Dystrophy
Limb Girdle Muscular Dystrophy Type 2D/R3
Keywords: Limb Girdle Muscular Dystrophy Type 2D/R3
SRP-9004
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-12-24
Enrollment: 4
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety of SRP-9004.


Eligibility criteria: Key Inclusion Criteria:

* Ambulatory participants, defined as able to walk without assistive aid, 10MWR \<30 seconds, and NSAD total score ≥25; non-ambulatory participant, defined as 10MWR ≥30 seconds or unable to perform, and PUL 2.0 entry scale score ≥3.
* Ambulatory participants must be 4 to 20 years of age and the non-ambulatory participant must be ≥4 years of age.
* All participants must be ≤70 kilograms
* Possess 1 homozygous or 2 heterozygous pathogenic and/or likely pathogenic α-SG deoxyribonucleic acid (DNA) gene mutations as documented prior to screening.
* Able to cooperate with muscle testing.
* Participants must have adeno-associated virus (AAV) serotype Rh74 (rh74) antibody titers \<1:400 (that is, not elevated) as determined by an enzyme-linked immunosorbent assay (ELISA).

Key Exclusion Criteria:

* Left ventricular ejection fraction \<40% or clinical signs and/or symptoms of cardiomyopathy
* FVC ≤40% of predicted value and/or requirement for nocturnal ventilation
* Any other clinically significant illness, including neuromuscular (other than limb girdle muscular dystrophy type 2D/R3 \[LGMD2D/R3\]), that in the opinion of the Investigator might compromise the participant's ability to comply with the protocol required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability.

Other inclusion/exclusion criteria apply.

Primary outcomes:
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESI) and Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: Up to 60 months
Secondary outcomes:
measure: Change from Baseline Through Day 60 in Quantity of Alpha-sarcoglycan (α-SG) Protein Expression
timeFrame: Baseline, Day 60
measure: Change from Baseline Through Month 24 in Quantity of α-SG Protein Expression
timeFrame: Baseline, Month 24
measure: Change from Baseline Through Month 60 in North Star Assessment for Dysferlinopathy (NSAD) Total Score
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Performance of the Upper Limb (PUL) Version 2.0 Total Score
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Time to Rise From Floor
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Time to Ascend 4 Steps
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Time to Complete 10-meter Walk/Run (10MWR)
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Time to Complete 100-meter Walk/Run (100MWR)
timeFrame: Baseline, Month 60
measure: Change from Baseline through Month 60 in Creatine Kinase (CK) Level
timeFrame: Baseline, Month 60
measure: Time to Change of Disease Milestones (Loss of Ambulation)
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Skeletal Muscle Magnetic Resonance Imagining (MRI) Findings
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Wearable Device Stride Velocity 95% (SV95C) (Ambulatory Participants Only)
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Vital Capacity (FVC)
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by FVC Percentage (%) Predicted
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by FEV1 % Predicted
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Peak Expiratory Flow Rate (PEFR)
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Maximal Inspiratory Pressure (MIP)
timeFrame: Baseline, Month 60
measure: Change from Baseline Through Month 60 in Pulmonary Functions as Assessed by Maximal Expiratory Pressure (MEP)
timeFrame: Baseline, Month 60
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
Study officials:
References: