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

Phase 2

Terminated

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Drug: Vesleteplirsen

• Registration Number: NCT04004065
• Lead Sponsor: Sarepta Therapeutics, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-06-26
• Study First Submitted: 2019-06-27
• Study First Submitted QC: 2019-06-27
• Study First Posted: 2019-07-01
• Primary Completion: 2023-10-30
• Disposition First Posted: 2024-10-03
• Disposition First Submitted: 2024-10-28
• Study Completion: 2025-02-07
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-06
• Last Update Posted: 2025-03-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 62

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A: Vesleteplirsen	Vesleteplirsen	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.
Part B: Vesleteplirsen	Vesleteplirsen	Participants received vesleteplirsen at the doses selected based on data from Part A every 4 weeks, via IV infusion, for up to 5 years. This included the participants who rolled over from Part A, as well as the additional participants who enrolled at the beginning of Part B.

Primary Outcome Measures

Name	Time	Method
Part B: Change From Baseline in Dystrophin Protein Level at Week 28	Part B: Baseline, Week 28
Part A: Incidence of Adverse Events (AEs)	Part A: Baseline up to 75 weeks

Secondary Outcome Measures

Name	Time	Method
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 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

Trial Locations

Locations (25)

A.O.U. Citta della Salute e della Scienza di Torino - SS Malattie Neuromuscolari, Department of Neurosciences; 🇮🇹 Torino, Italy

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Hospital Sant Joan de Déu. U.B.; 🇪🇸 Barcelona, Spain

Hospital Universitari I Politecnic La Fe de Valencia; 🇪🇸 Valencia, Spain

Connecticut Children's; 🇺🇸 Farmington, Connecticut, United States

University of California Davis Health; 🇺🇸 Sacramento, California, United States

Northwest Florida Clinical Research Group, LLC; 🇺🇸 Gulf Breeze, Florida, United States

Rare Disease Research, LLC; 🇺🇸 Atlanta, Georgia, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

University of Kansas Medical Center Research Inst.; 🇺🇸 Kansas City, Kansas, United States

University of Massachusetts; 🇺🇸 Worcester, Massachusetts, United States

UPMC Children's Hospital of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Austin Neuromuscular Center; 🇺🇸 Austin, Texas, United States

Children's Health Ambulatory Pavilion; 🇺🇸 Dallas, Texas, United States

Seattle Children's; 🇺🇸 Seattle, Washington, United States

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

Children's Hospital - London Health Sciences Centre (LHSC); 🇨🇦 London, Ontario, Canada

University of Essen - Children's Hospital; 🇩🇪 Essen, Germany

Klinikum der Universität München; 🇩🇪 Munich, Germany

Fondazione Policlinico Universitario A Gemelli; 🇮🇹 Rome, Italy

Alder Hey Children's NHS Foundation Trust; 🇬🇧 Liverpool, Lancashire, United Kingdom

Royal Hospital for Children (Glasgow); 🇬🇧 Glasgow, United Kingdom

Great Ormond Street Hospital for Children NHS Foundation Trust; 🇬🇧 London, United Kingdom

Oxford University Hospial NHS Foundation Trust, John Radcliffe Hospital; 🇬🇧 Oxford, United Kingdom