A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Dose of SRP-5051 (Vesleteplirsen) in Patients With Duchenne Muscular Dystrophy (DMD)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of 5 escalating doses of SRP-5051 (vesleteplirsen) administered as a single dose to patients with DMD amenable to exon 51 skipping treatment.

Official Title
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A Phase 1 Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Dose of SRP-5051 in Patients With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping Treatment

Conditions
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Muscular Dystrophy, Duchenne

Intervention / Treatment
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* Drug: SRP-5051


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a genetic diagnosis of 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 with continued dosing of oral corticosteroids while participating in the study*, or has not received corticosteroids for at least 12 weeks prior to study drug administration and will not initiate dosing of oral corticosteroids while participating in the study Exclusion Criteria: Has a left ventricular ejection fraction (LVEF) less than (<) 40 percent (%) based on an echocardiogram (ECHO) performed within 3 months prior to Screening or at the Screening visit Has a QT interval corrected with Fridericia's method (QTcF) >= 450 millisecond (msec) on the Screening electrocardiogram (ECG) Initiation or change of dosing (except for modifications to accommodate changes in weight) within 12 weeks prior to Screening and while participating in the study for any of the following: angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blocking agents (ARBs), beta-blockers, or potassium Requires antiarrhythmic and/or diuretic therapy for heart failure Forced vital capacity (FVC) <40% of predicted value within 3 months of Screening or at the Screening visit Known kidney disease or had an acute kidney injury within 6 months prior to Screening Treatment with eteplirsen or drisapersen within 6 months prior to Screening, or any experimental gene therapy for the treatment of DMD at any time Use of any herbal medication/supplement containing aristolochic acid Other inclusion/exclusion criteria apply. *The dose of steroids must remain constant except for modifications to accommodate changes in weight.

Ages Eligible for Study
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Minimum Age: 12 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SRP-5051<br>Patients will be sequentially assigned to receive 1 of the 5 escalating dose levels of SRP-5051 on Day 1. Patients who complete the study and continue to meet safety eligibility criteria will have the opportunity to enroll in an open-label extension study to continue to receive SRP-5051. | Drug: SRP-5051<br>* Single dose of SRP-5051 administered as an intravenous (IV) infusion.<br>* Other names: vesleteplirsen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical trial participant, which does not necessarily have a causal relationship with the investigational drug. An AE can, therefore, be any unfavorable and unintended symptom, sign, disease, condition, or test abnormality that occurs during or after administration of the study drug, whether or not considered related to the study drug. | From signing of informed consent to 12 weeks after the last infusion of SRP-5051 (Up to 14 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma concentration (Cmax) of SRP-5051 | Plasma samples to be collected via peripheral venipuncture from the contralateral arm used for drug infusion. | Pre-dose, mid-infusion, end of infusion, post-dose (0.25, 0.5, 1, 2, 4, 8, 12 hours) | 
| Area under the plasma concentration versus time curve (AUC) of SRP-5051 | Plasma samples to be collected via peripheral venipuncture from the contralateral arm used for drug infusion. | Pre-dose, mid-infusion, end of infusion, post-dose (0.25, 0.5, 1, 2, 4, 8, 12 hours) | 

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