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

A Phase 2, Two-Part, Multiple-Ascending-Dose Study of SRP-5051 for Dose Determination, Then Dose Expansion, in Patients With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Vesleteplirsen

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sarepta Therapeutics Inc., For Clinical Trial Information, Select Option 4; Phone Number: 1-888-SAREPTA (1-888-727-3782); Email: SareptAlly@sarepta.com

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital - London Health Sciences Centre (LHSC)
• Germany
  • Essen, Germany, D-45147
    • University of Essen - Children's Hospital
  • Munich, Germany, 80337
    • Klinikum der Universität München
• Italy
  • Rome, Italy, 168
    • Fondazione Policlinico Universitario A Gemelli
  • Torino, Italy, 10139
    • A.O.U. Citta della Salute e della Scienza di Torino - SS Malattie Neuromuscolari, Department of Neurosciences
• Netherlands
  • Leiden, Netherlands, 2333
    • Leiden University Medical Center
• Spain
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Déu. U.B.
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Royal Hospital for Children (Glasgow)
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Children's NHS Foundation Trust
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital For Children NHS Foundation Trust
  • Oxford, United Kingdom, OX3 9DU
    • Oxford University Hospial NHS Foundation Trust, John Radcliffe Hospital
• United States
  • California
    • Sacramento, California, United States, 95817
      • Univertisty of California Davis Health
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • Connecticut Children's
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • Northwest Florida Clinical Research Group, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • University of Kansas Medical Center Research Inst.
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Texas
    • Austin, Texas, United States, 78756
      • Austin Neuromuscular Center
    • Dallas, Texas, United States, 75207
      • Children's Health Ambulatory Pavilion
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for participants previously treated with Vesleteplirsen:

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

Exclusion Criteria for participants previously treated with Vesleteplirsen and new participants enrolling into Part B:

- 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.

Inclusion Criteria for treatment-naïve participants enrolling into Part B:

• 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).

Exclusion Criteria for treatment-naive participants enrolling into Part B:

• 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.

Other inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: 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.	Drug: Vesleteplirsen; Vesleteplirsen injection, for IV use; Other Names: SRP-5051
Experimental: Part B: Vesleteplirsen; Participants will receive vesleteplirsen at the doses selected based on data from Part A every 4 weeks, via IV infusion, for up to 5 years. This includes the participants who rollover from Part A, as well as the additional participants who will be enrolled at the beginning of Part B.	Drug: Vesleteplirsen; Vesleteplirsen injection, for IV use; Other Names: SRP-5051

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
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

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Click here to access the website, clinicaltrials.sarepta.com/momentumtrial, for additional information for the study.

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2019
• Primary Completion (Actual): October 30, 2023
• Study Completion (Estimated): January 31, 2029

Study Registration Dates

• First Submitted: June 27, 2019
• First Submitted That Met QC Criteria: June 27, 2019
• First Posted (Actual): July 1, 2019

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric; Duchenne Muscular Dystrophy; DMD; Duchenne; Dystrophin; Exon Skipping; Ambulatory; Dystrophy; 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: 5051-201; 2019-000601-77 (EudraCT Number)

Drug and device information, study documents

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