Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants with Duchenne Muscular Dystrophy (DMD)
- Conditions
- Muscular dystrophy,
- Registration Number
- CTRI/2022/09/045929
- Lead Sponsor
- Sarepta Therapeutics Inc
- Brief Summary
This is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of SRP-4045 and SRP-4053. Eligible participants with out-of-frame deletion mutations amenable to exon 45 or 53 skipping will be randomized to receive once weekly intravenous (IV) infusions of 30 milligrams/kilograms (mg/kg) SRP-4045 or 30 mg/kg SRP-4053 respectively (combined-active group) or placebo for up to 96 weeks (the placebo-controlled period of the trial). This will be followed by an open-label extension period in which all participants will receive open-label active treatment for 48 weeks (up to Week 144 of study).
The study will enroll approximately 222 participants. Twice as many participants will be randomized to receive active treatment as will receive placebo (2:1 randomization).Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests, such as the 6-minute walk test (6MWT). All participants will undergo a muscle biopsy at baseline and a second muscle biopsy either at Week 48 or Week 96.
Safety will be assessed through the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations throughout the study.
Blood samples will be taken periodically throughout the study to assess the pharmacokinetics of both drugs.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Male
- Target Recruitment
- 222
- Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping 2.
- Stable dose of oral corticosteroids for at least 24 weeks prior to Week 1, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight).
- Intact right and left biceps or 2 alternative upper muscle groups 4.
- Mean 6MWT ≥300 meters and ≤450 meters 5.
- Stable pulmonary function: forced vital capacity (FVC) ≥50% predicted.
- 1.Treatment with gene therapy at any time 2.
- Previous treatment with SMT C1100 within 1 week prior to Week 1 and previous treatment with PRO045 (BMN 045), PRO053 (BMN 053), or PRO051 (BMN 051) within 24 weeks prior to Week 1 3.
- Current or previous treatment with any other experimental treatment within 12 weeks prior to Week 1 4.
- Major surgery within 3 months prior to Week 1 5.
- Presence of other clinically significant illness 6.
- Other inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary objective of this study is to evaluate the effect of SRP-4045 and SRP-4053 (combined-active group) compared with placebo on ambulation, endurance, and muscle function as measured by the 6-minute walk test (6MWT). Change from Baseline at Week 96 in 6MWT
- Secondary Outcome Measures
Name Time Method 1. Change from Baseline in the Total Distance Walked During 6MWT at Week 144 (Week 48 of the Open-Label Extension Period) 2. Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Weeks 48 or 96
Trial Locations
- Locations (5)
All India Institute of Medical Sciences
🇮🇳Delhi, DELHI, India
Aster RV Hospital
🇮🇳Bangalore, KARNATAKA, India
Christian Medical College
🇮🇳Vellore, TAMIL NADU, India
Deenanath Mangeshkar Hospital and Research Centre
🇮🇳Pune, MAHARASHTRA, India
Royal Institute of Child NeuroSciences
🇮🇳Ahmadabad, GUJARAT, India
All India Institute of Medical Sciences🇮🇳Delhi, DELHI, IndiaDr Shefali GulatiPrincipal investigator919810386847sheffaligulati@gmail.com