Limb-girdle Muscular Dystrophy
Conditions
Keywords
Limb Girdle Muscular Dystrophy Type 2E/R4, LGMD2E/R4, Pediatric, SRP-9003, scAAVrh74.MHCK7.hSGCB, bidridistrogene xeboparvovec, Non-ambulatory, Ambulatory
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).
Interventions
BIOLOGICALSRP-9003
Solution for single IV infusion
DRUGGlucocorticoid
Oral tablet (prophylactic)
Sponsors
Sarepta Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cohort 1, only ambulatory participants: * Able to walk without assistive aid * 10MWR \<30 seconds * NSAD ≥25 * Cohort 2, only non-ambulatory participants: * 10MWR ≥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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohort 1: Change from Baseline in β-SG Expression at Day 60 Post-dose as Measured by Immunofluorescence (IF) Percent β-SG Positive Fibers | Baseline, Day 60 |
Secondary
| Measure | Time frame |
|---|---|
| Cohort 1 and Cohort 2: Change From Baseline in β-SG Expression at Day 60 Post-dose as Measured by Western Assay | Baseline, Day 60 |
| 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) | Baseline, Day 60 |
| Cohort 2: Change From Baseline in β-SG Expression at Day 60 Post-dose as Measured by IF Percent β-SG Positive Fibers (PβSGPF) | Baseline, Day 60 |
| Cohort 1 and Cohort 2: Change From Baseline Through Month 60 in North Star Assessment for Limb-girdle Muscular Dystrophies (NSAD) Total Score | Baseline through Month 60 |
| Cohort 1 and Cohort 2: Change From Baseline Through Month 60 in Performance of Upper Limb Version 2.0 (PUL 2.0) Total Score | Baseline through Month 60 |
| Cohort 1: Change From Baseline Through Month 60 in the Time to Rise from the Floor Test | Baseline through Month 60 |
| Cohort 1: Change From Baseline Through Month 60 in the Time to Complete the 10-meter Walk/Run (10MWR) Test | Baseline through Month 60 |
| Cohort 1: Change From Baseline Through Month 60 in the Time to Ascend 4 Steps Test | Baseline through Month 60 |
| Cohort 1: Change From Baseline Through Month 60 in the Time to Complete the 100-meter Walk/Run (100MWR) Test | Baseline through Month 60 |
| Cohort 1: Change From Baseline Through Month 60 in the Timed Up and Go Test | Baseline through Month 60 |
| Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events of Special Interests (AESIs) | Baseline through Month 60 |
| Change From Baseline Through Month 60 in Creatine Kinase Level | Baseline through Month 60 |
| Time to Change of Loss of Ambulation | Baseline through Month 60 |
Countries
Belgium, Germany, Italy, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Sarepta Therapeutics, Inc.
Outcome results
None listed