Two-Part Study for Dose Determination of Vesleteplirsen (SRP-5051) (Part A), Then Dose Efficacy (Part B) in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Two-Part, Multiple-Ascending-Dose Study of SRP-5051 for Dose Determination, Then Dose Expansion, in Patients With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: Vesleteplirsen


Participation Criteria
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Eligibility Criteria
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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). Exclusion Criteria for treatment-naive participants enrolling into Part B: History of hypomagnesemia within 12 weeks prior to Screening. Initiation or change of dosing (except for modifications to accommodate changes in weight or changes in standard of care) within 12 weeks prior to Screening for any of the following: angiotensin-converting enzyme inhibitors, angiotensin receptor-blocking agents, β-blockers, or potassium. Initiation or change of dosing within 12 weeks prior to Screening for over-the-counter preparations, such as herbal/nonherbal supplements, vitamins, minerals, and homeopathic preparations. Has a left ventricular ejection fraction (LVEF) <40.0% based on an echocardiogram (ECHO) performed within 12 weeks prior to Screening or at the Screening Visit. Treatment with any exon 51-skipping therapy within 4 weeks prior to Screening, or with any experimental gene therapy for the treatment of DMD at any time. Other inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Vesleteplirsen<br>Participants received escalating dose levels of vesleteplirsen, every 4 weeks, via intravenous (IV) infusion for up to 75 weeks during Part A. Once the doses have been selected for Part B, all participants who have completed Part A will transition to Part B. | Drug: Vesleteplirsen<br>* Vesleteplirsen injection, for IV use<br>* Other names: SRP-5051;|
| Experimental: Part B: Vesleteplirsen<br>Participants will receive vesleteplirsen at the doses selected based on data from Part A every 4 weeks, via IV infusion, for up to 5 years. This includes the participants who rollover from Part A, as well as the additional participants who will be enrolled at the beginning of Part B. | Drug: Vesleteplirsen<br>* Vesleteplirsen injection, for IV use<br>* Other names: SRP-5051;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Pharmacokinetics (PK): Plasma Concentration of Vesleteplirsen |  | Pre-dose and at multiple time points (up to 32 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 | 
| 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 B: PK: Plasma Concentration of Vesleteplirsen |  | Part B predose and at multiple timepoints (up to 48 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DMD, Duchenne, Dystrophy, Dystrophin, Exon Skipping, Ambulatory, Duchenne Muscular Dystrophy, Exon 51, Nonambulatory, Pediatric, Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)