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

NCT03375255 | Completed Phase 1 FDA Drug

• 1 other identifier: 5051-101
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 8

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.

Conditions

Muscular Dystrophy, Duchenne

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Maximum Plasma concentration (Cmax) of SRP-5051

  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

  Pre-dose, mid-infusion, end of infusion, post-dose (0.25, 0.5, 1, 2, 4, 8, 12 hours)

Study Arms (1)

SRP-5051

EXPERIMENTAL

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

Interventions

SRP-5051 DRUG

Single dose of SRP-5051 administered as an intravenous (IV) infusion.

Also known as: vesleteplirsen

SRP-5051

Eligibility Criteria

• Age: 12 Years+
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• \*The dose of steroids must remain constant except for modifications to accommodate changes in weight.

Sponsors & Collaborators

• Sarepta Therapeutics, Inc.: lead

Study Sites (8)

Neuromuscular Research Center

Sacramento, California, 95817, United States

Location

NW FL Clinical Research Group, LLC

Gulf Breeze, Florida, 32561, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30318, United States

Location

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

Chicago, Illinois, 60611, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75207, United States

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

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 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2017
• First Posted: December 18, 2017
• Study Start: February 5, 2018
• Primary Completion: August 19, 2019
• Study Completion: August 19, 2019
• Last Updated: July 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); CA (1)