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

NCT04004065 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: 5051-2012019-000601-77
• Study Type: interventional
• Target: 62
• Locations: 8 countries
• Sites: 25

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.

Conditions

Duchenne Muscular Dystrophy

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• 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

Study Arms (2)

Part A: Vesleteplirsen

EXPERIMENTAL

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

Part B: Vesleteplirsen

EXPERIMENTAL

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.

Drug: Vesleteplirsen

Interventions

Vesleteplirsen DRUG

Vesleteplirsen injection, for IV use

Also known as: SRP-5051

Part A: Vesleteplirsen; Part B: Vesleteplirsen

Eligibility Criteria

• Age: 7 Years - 21 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \- Has received prior Vesleteplirsen treatment in Part A of this study or in Study 5051-102.

You may not qualify if:

• \- 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.
• 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).
• 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.

Sponsors & Collaborators

• Sarepta Therapeutics, Inc.: lead

Study Sites (25)

University of California Davis Health

Sacramento, California, 95817, United States

Location

Connecticut Children's

Farmington, Connecticut, 06032, United States

Location

Northwest Florida Clinical Research Group, LLC

Gulf Breeze, Florida, 32561, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30318, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center Research Inst.

Kansas City, Kansas, 66103, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01655, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Austin Neuromuscular Center

Austin, Texas, 78756, United States

Location

Children's Health Ambulatory Pavilion

Dallas, Texas, 75207, United States

Location

Seattle Children's

Seattle, Washington, 98105, United States

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Children's Hospital - London Health Sciences Centre (LHSC)

London, Ontario, N6A 5W9, Canada

Location

University of Essen - Children's Hospital

Essen, D-45147, Germany

Location

Klinikum der Universität München

Munich, 80337, Germany

Location

Fondazione Policlinico Universitario A Gemelli

Rome, 168, Italy

Location

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

Torino, 10139, Italy

Location

Leiden University Medical Center

Leiden, 2333, Netherlands

Location

Hospital Sant Joan de Déu. U.B.

Barcelona, 08950, Spain

Location

Hospital Universitari I Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, Lancashire, L12 2AP, United Kingdom

Location

Royal Hospital for Children (Glasgow)

Glasgow, G51 4TF, United Kingdom

Location

Great Ormond Street Hospital for Children NHS Foundation Trust

London, WC1N 3JH, United Kingdom

Location

Oxford University Hospial NHS Foundation Trust, John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Medical Director

  Sarepta Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: July 1, 2019
• Study Start: June 26, 2019
• Primary Completion: October 30, 2023
• Study Completion: February 7, 2025
• Last Updated: March 10, 2025

Record last verified: 2025-03

Locations

US (11); NL (1); IT (2); BE (2); GB (4); DE (2); CA (1); ES (2)