Clinical trial NCT06246513: A Trial to Learn More About an Experimental Gene Therapy Called Bidridistrogene Xeboparvovec (SRP-9003) as a Possible Treatment for Limb Girdle Muscular Dystrophy 2E/R4
Official title: A Phase 3 Multinational, Open-label, Systemic Gene Delivery Study to Evaluate the Safety and Efficacy of SRP-9003 in Subjects With Limb Girdle Muscular Dystrophy 2E/R4
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Limb-girdle Muscular Dystrophy
Keywords: Limb Girdle Muscular Dystrophy Type 2E/R4
LGMD2E/R4
Pediatric
SRP-9003
scAAVrh74.MHCK7.hSGCB
bidridistrogene xeboparvovec
Non-ambulatory
Ambulatory
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-07
Enrollment: 17
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: This is a multicenter, global study of the effects of a single systemic dose of SRP-9003 on beta-sarcoglycan (β-SG) gene expression in participants with limb-girdle muscular dystrophy, type 2E/R4 (LGMD2E/R4). This study will consist of both ambulatory participants (Cohort 1) and non-ambulatory participants (Cohort 2).


Eligibility criteria: Inclusion Criteria:

* Cohort 1, only ambulatory participants:

  * Able to walk without assistive aid
  * 10-meter walk test (10MWT) \<30 seconds
  * NSAD ≥25
* Cohort 2, only non-ambulatory participants:

  * 10MWT ≥30 seconds or unable to perform
  * PUL 2.0 entry scale score ≥3
* Participants must possess 1 homozygous or 2 heterozygous pathogenic and/or likely pathogenic β-SG DNA gene mutations
* Able to cooperate with muscle testing
* Participants must have adeno-associated virus serotype rh74 (AAVrh74) antibody titers \<1:400 (that is, not elevated) as determined by AAVrh74 antibody enzyme-linked immunosorbent assay.

Exclusion Criteria:

* Left ventricular ejection fraction \< 40% or clinical signs and/or symptoms of cardiomyopathy
* Forced vital capacity ≤40% of predicted value and/or requirement for nocturnal ventilation
* Diagnosis of (or ongoing treatment for) an autoimmune disease and on active immunosuppressant treatment
* Presence of any other clinically significant illness or medical condition (other than LGMD2E/R4)

Other inclusion/exclusion criteria apply.

Primary outcomes:
measure: Cohort 1: Change from Baseline in β-SG Expression at Day 60 Post-dose as Measured by Immunofluorescence (IF) Percent β-SG Positive Fibers
timeFrame: Baseline, Day 60
Secondary outcomes:
measure: Cohort 1 and Cohort 2: Change From Baseline in β-SG Expression at Day 60 Post-dose as Measured by Western Blot
timeFrame: Baseline, Day 60
measure: Cohort 1 and Cohort 2: Change From Baseline in β-SG Expression at Day 60 Post-dose as Measured by IF Percent Fluorescent Intensity (PFI)
timeFrame: Baseline, Day 60
measure: Cohort 2: Change From Baseline in β-SG Expression at Day 60 Post-dose as Measured by IF Percent β-SG Positive Fibers (PβSGPF)
timeFrame: Baseline, Day 60
measure: Cohort 1 and Cohort 2: Change From Baseline Through Month 60 in North Star Assessment for Dysferlinopathy (NSAD) Total Score
timeFrame: Baseline through Month 60
measure: Cohort 1 and Cohort 2: Change From Baseline Through Month 60 in Performance of Upper Limb Version 2.0 (PUL 2.0) Total Score
timeFrame: Baseline through Month 60
measure: Cohort 1: Change From Baseline Through Month 60 in the Time to Rise from the Floor Test
timeFrame: Baseline through Month 60
measure: Cohort 1: Change From Baseline Through Month 60 in the Time to Complete the 10-meter Walk/Run (10MWR) Test
timeFrame: Baseline through Month 60
measure: Cohort 1: Change From Baseline Through Month 60 in the Time to Ascend 4 Steps Test
timeFrame: Baseline through Month 60
measure: Cohort 1: Change From Baseline Through Month 60 in the Time to Complete the 100-meter Walk/Run (100MWR) Test
timeFrame: Baseline through Month 60
measure: Cohort 1: Change From Baseline Through Month 60 in the Timed Up and Go Test
timeFrame: Baseline through Month 60
measure: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline through Month 60
measure: Change From Baseline Through Month 60 in Creatine Kinase Level
timeFrame: Baseline through Month 60
measure: Time to Change of Loss of Ambulation
timeFrame: Baseline through Month 60
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego-Altman Clinical and Translational Research Institute
state: California
city: Columbus
country: United States
facility: Nationwide Childrens Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughter
state: Virginia
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle University
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: