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)

• ClinicalTrials.gov Identifier: NCT04004065
• Recruitment Status: Active, not recruiting
• First Posted: July 1, 2019
• Last Update Posted: December 1, 2023
• Sponsor: Sarepta Therapeutics, Inc.
• Information provided by (Responsible Party): Sarepta Therapeutics, Inc.

Tracking Information

• First Submitted Date: June 27, 2019
• First Posted Date: July 1, 2019
• Last Update Posted Date: December 1, 2023
• Actual Study Start Date: June 26, 2019
• Actual Primary Completion Date: October 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 28, 2023)

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

Original Primary Outcome Measures (submitted: June 27, 2019)

• Part A: Incidence of Adverse Events (AEs) [ Time Frame: From signing of informed consent until 28 days after last dose of study drug administered (up to 60 weeks) ]
  Incidence of adverse events includes clinically significant laboratory abnormalities.
• Part B: Change From Baseline Biopsy in Exon-Skipping Levels [ Time Frame: Baseline, Part B Week 24 ]
• Part B: Change From Baseline Biopsy in Dystrophin Protein Production Levels [ Time Frame: Baseline, Part B Week 24 ]

Current Secondary Outcome Measures (submitted: November 28, 2023)

• Part A: Pharmacokinetics (PK): Plasma Concentration of Vesleteplirsen [ Time Frame: Pre-dose and at multiple time points (up to 32 hours) after end of infusion ]
• Part A: PK: Urine Concentration of Vesleteplirsen [ Time Frame: 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 [ Time Frame: Part B: Baseline, Week 28 ]
• Part B: Incidence of Adverse Events (AEs) [ Time Frame: Part B: Baseline up to Week 304 ]
• Part B: PK: Plasma Concentration of Vesleteplirsen [ Time Frame: Part B predose and at multiple timepoints (up to 48 hours) after end of infusion ]
• Part B: PK: Urine Concentration of Vesleteplirsen [ Time Frame: 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 [ Time Frame: Part B: Baseline, Week 28 ]

Original Secondary Outcome Measures (submitted: June 27, 2019)

• Part A: Pharmacokinetic (PK) Plasma Concentration of SRP-5051 [ Time Frame: Predose and at multiple timepoints (up to 24 hours) after end of infusion ]
• Part B: Incidence of Adverse Events (AEs) [ Time Frame: Up to 28 weeks in Part B ]
  Incidence of adverse events includes clinically significant laboratory abnormalities.
• Part B: Change From Baseline in Forced Vital Capacity (FVC) (percent predicted) [ Time Frame: Baseline, Part B Week 24 ]
• Part B: Change From Baseline in the North Star Ambulatory Assessment (NSAA) [ Time Frame: Baseline, Part B Week 24 ]
• Part B: Change From Baseline in the Performance of Upper Limb (PUL) Scores [ Time Frame: Baseline, Part B Week 24 ]
• Part B: Change From Baseline in the Brooke Upper Extremity Scale score (Brooke score) [ Time Frame: Baseline, Part B Week 24 ]
• Part B: PK Plasma Concentration of SRP-5051 [ Time Frame: Part B predose and at multiple timepoints (up to 12 hours) after end of infusion ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy

Intervention

Drug: Vesleteplirsen

Vesleteplirsen injection, for IV use

Other Name: SRP-5051

Study Arms

• 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.
  Intervention: Drug: Vesleteplirsen
• 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.
  Intervention: Drug: Vesleteplirsen

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 27, 2023): 62
• Original Estimated Enrollment (submitted: June 27, 2019): 24
• Estimated Study Completion Date: January 31, 2029
• Actual Primary Completion Date: October 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 7 Years to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Germany, Italy, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04004065
• Other Study ID Numbers: 5051-201; 2019-000601-77 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sarepta Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Sarepta Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Sarepta Therapeutics, Inc.

• PRS Account: Sarepta Therapeutics, Inc.
• Verification Date: November 2023