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

Duchenne Muscular Dystrophy Clinical Trial

— MOMENTUM  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04004065
• Other study ID #: 5051-201
• Secondary ID: 2019-000601-77
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 26, 2019
• Est. completion date: January 31, 2029

Study information

• Verified date: November 2023
• Source: Sarepta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: January 31, 2029
• Est. primary completion date: October 30, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 7 Years to 21 Years

Eligibility

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, ß-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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Vesleteplirsen
Vesleteplirsen injection, for IV use

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	UZ Leuven	Leuven
Canada	Children's Hospital - London Health Sciences Centre (LHSC)	London	Ontario
Germany	University of Essen - Children's Hospital	Essen
Germany	Klinikum der Universität München	Munich
Italy	Fondazione Policlinico Universitario A Gemelli	Rome
Italy	A.O.U. Citta della Salute e della Scienza di Torino - SS Malattie Neuromuscolari, Department of Neurosciences	Torino
Netherlands	Leiden University Medical Center	Leiden
Spain	Hospital Sant Joan de Déu. U.B.	Barcelona
Spain	Hospital Universitari I Politecnic La Fe de Valencia	Valencia
United Kingdom	Royal Hospital for Children (Glasgow)	Glasgow
United Kingdom	Alder Hey Children's NHS Foundation Trust	Liverpool
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 States	Rare Disease Research, LLC	Atlanta	Georgia
United States	Austin Neuromuscular Center	Austin	Texas
United States	Children's Health Ambulatory Pavilion	Dallas	Texas
United States	Connecticut Children's	Farmington	Connecticut
United States	Northwest Florida Clinical Research Group, LLC	Gulf Breeze	Florida
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	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Univertisty of California Davis Health	Sacramento	California
United States	Seattle Children's	Seattle	Washington
United States	University of Massachusetts	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Sarepta Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Incidence of Adverse Events (AEs)		Part A: Baseline up to 75 weeks
Primary	Part B: Change From Baseline in Dystrophin Protein Level at Week 28		Part B: Baseline, Week 28
Secondary	Part A: Pharmacokinetics (PK): Plasma Concentration of Vesleteplirsen		Pre-dose and at multiple time points (up to 32 hours) after end of infusion
Secondary	Part A: PK: Urine Concentration of Vesleteplirsen		Pre-dose and at multiple time periods (up to 48 hours) after end of infusion
Secondary	Part B: Change From Baseline in Exon-Skipping Levels at Week 28		Part B: Baseline, Week 28
Secondary	Part B: Incidence of Adverse Events (AEs)		Part B: Baseline up to Week 304
Secondary	Part B: PK: Plasma Concentration of Vesleteplirsen		Part B predose and at multiple timepoints (up to 48 hours) after end of infusion
Secondary	Part B: PK: Urine Concentration of Vesleteplirsen		Part B predose and at multiple timepoints (up to 48 hours) after end of infusion
Secondary	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

External Links

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