Duchenne Muscular Dystrophy
Conditions
Keywords
DMD, Duchenne, Dystrophy, Dystrophin, Exon Skipping, Ambulatory, Duchenne Muscular Dystrophy, Exon 51, Nonambulatory, Pediatric, Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)
Brief summary
This study will be comprised of 2 parts: 1) Part A (Multiple Ascending Dose \[MAD\]) will be conducted to evaluate the safety and tolerability of vesleteplirsen at MAD levels to determine the maximum tolerated dose (MTD), and 2) Part B will be conducted to further evaluate the vesleteplirsen doses selected in Part A. Participants enrolling in Part B will be those who completed Part A or Study 5051-102 (NCT03675126) and meet applicable eligibility criteria for Part B, as well as additional participants who meet applicable eligibility criteria for enrollment at the beginning of Part B.
Interventions
DRUGVesleteplirsen
Vesleteplirsen injection, for IV use
Sponsors
Sarepta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
7 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
for participants previously treated with Vesleteplirsen: \- Has received prior Vesleteplirsen treatment in Part A of this study or in Study 5051-102.
Exclusion criteria
for participants previously treated with Vesleteplirsen and new participants enrolling into Part B: \- Presence of other clinically significant illness, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or infection or malignancy or any other condition that, in the Investigator's opinion, could interfere with participation in the trial. Inclusion Criteria for treatment-naïve participants enrolling into Part B: * Has a genetic diagnosis of Duchenne muscular dystrophy (DMD) and an out-of-frame deletion mutation of the DMD gene amenable to exon 51-skipping treatment. * Has been on a stable dose of oral corticosteroids for at least 12 weeks prior to study drug administration and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight), or has not received corticosteroids for at least 12 weeks prior to study drug administration. * Has stable pulmonary function (forced vital capacity \[FVC\] ≥40% of predicted and no requirement for nocturnal ventilation).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Incidence of Adverse Events (AEs) | Part A: Baseline up to 75 weeks |
| Part B: Change From Baseline in Dystrophin Protein Level at Week 28 | Part B: Baseline, Week 28 |
Secondary
| Measure | Time frame |
|---|---|
| Part B: Change From Baseline in Exon-Skipping Levels at Week 28 | Part B: Baseline, Week 28 |
| Part B: Incidence of Adverse Events (AEs) | Part B: Baseline up to Week 304 |
| Part A: Pharmacokinetics (PK): Plasma Concentration of Vesleteplirsen | Pre-dose and at multiple time points (up to 32 hours) after end of infusion |
| Part B: PK: Urine Concentration of Vesleteplirsen | Part B predose and at multiple timepoints (up to 48 hours) after end of infusion |
| Part B: Change from Baseline in Percent Dystrophin-Positive Fibers (PDPF) and Mean Intensity, as Measured by Immunofluorescence Assay at Week 28 | Part B: Baseline, Week 28 |
| Part B: PK: Plasma Concentration of Vesleteplirsen | Part B predose and at multiple timepoints (up to 48 hours) after end of infusion |
| Part A: PK: Urine Concentration of Vesleteplirsen | Pre-dose and at multiple time periods (up to 48 hours) after end of infusion |
Countries
Belgium, Canada, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Outcome results
None listed