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

• ClinicalTrials.gov Identifier: NCT03375255
• Recruitment Status: Completed
• First Posted: December 18, 2017
• Last Update Posted: July 6, 2022
• Sponsor: Sarepta Therapeutics, Inc.
• Information provided by (Responsible Party): Sarepta Therapeutics, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Muscular Dystrophy, Duchenne	Drug: SRP-5051	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 5, 2018
• Actual Primary Completion Date: August 19, 2019
• Actual Study Completion Date: August 19, 2019

Arms and Interventions

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 Name: vesleteplirsen

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Adverse Events (AEs) [ Time Frame: From signing of informed consent to 12 weeks after the last infusion of SRP-5051 (Up to 14 weeks) ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Neuromuscular Research Center

Sacramento, California, United States, 95817

United States, Florida

NW FL Clinical Research Group, LLC

Gulf Breeze, Florida, United States, 32561

United States, Georgia

Rare Disease Research, LLC

Atlanta, Georgia, United States, 30318

United States, Illinois

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States, 60611

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Pennsylvania

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States, 15224

United States, Texas

Children's Medical Center Dallas

Dallas, Texas, United States, 75207

Canada, Ontario

London Health Sciences Centre

London, Ontario, Canada, N6A 5W9

Sponsors and Collaborators

Sarepta Therapeutics, Inc.

Investigators

• Study Director: Medical Director; Sarepta Therapeutics, Inc.

More Information

• Responsible Party: Sarepta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03375255
• Other Study ID Numbers: 5051-101
• First Posted: December 18, 2017
• Last Update Posted: July 6, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sarepta Therapeutics, Inc.:

Duchenne Muscular Dystrophy; Exon Skipping; DMD; Exon 51; Ambulatory; Pediatric; Nonambulatory; Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO); Duchenne

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked