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

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

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.

Study Overview

• Status: Completed
• Conditions: Muscular Dystrophy, Duchenne
• Intervention / Treatment: Drug: SRP-5051

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
• United States
  • California
    • Sacramento, California, United States, 95817
      • Neuromuscular Research Center
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • NW FL Clinical Research Group, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Texas
    • Dallas, Texas, United States, 75207
      • Children's Medical Center Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SRP-5051; 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; Single dose of SRP-5051 administered as an intravenous (IV) infusion.; Other Names: vesleteplirsen

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Sarepta Therapeutics, Inc.
• Investigators: Study Director: Medical Director, Sarepta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2018
• Primary Completion (Actual): August 19, 2019
• Study Completion (Actual): August 19, 2019

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: December 14, 2017
• First Posted (Actual): December 18, 2017

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Pediatric; Duchenne Muscular Dystrophy; DMD; Duchenne; Exon Skipping; Ambulatory; Exon 51; Nonambulatory; Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: 5051-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No