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

Primary Purpose

Duchenne Muscular Dystrophy

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SRP-5051
Sponsored by
Sarepta Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring DMD, Duchenne, Dystrophy, Dystrophin, Exon Skipping, Ambulatory, Duchenne Muscular Dystrophy, Exon 51, Nonambulatory, Pediatric, Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)

Eligibility Criteria

7 Years - 21 Years (Child, Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria for participants previously treated with SRP-5051:

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

Exclusion Criteria for participants previously treated with SRP-5051 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.

Sites / Locations

  • Univertisty of California Davis Health
  • Connecticut Children's
  • Northwest Florida Clinical Research Group, LLC
  • Rare Disease Research, LLC
  • University of Iowa Hospitals and Clinics
  • University of Kansas Medical Center Research Inst.
  • University of Massachusetts
  • UPMC Children's Hospital of Pittsburgh
  • Austin Neuromuscular Center
  • Children's Health Ambulatory Pavilion
  • Seattle Children's
  • Universitair Ziekenhuis Gent
  • UZ Leuven
  • Children's Hospital - London Health Sciences Centre (LHSC)
  • University of Essen - Children's Hospital
  • Klinikum der Universität München
  • Fondazione Policlinico Universitario A Gemelli
  • A.O.U. Citta della Salute e della Scienza di Torino - SS Malattie Neuromuscolari, Department of Neurosciences
  • Leiden University Medical Center
  • Hospital Sant Joan de Déu. U.B.
  • Hospital Universitari I Politecnic La Fe de Valencia
  • Royal Hospital for Children (Glasgow)
  • Alder Hey Children's NHS Foundation Trust
  • Great Ormond Street Hospital for Children NHS Foundation Trust
  • Oxford University Hospial NHS Foundation Trust, John Radcliffe Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part A: SRP-5051

Part B: SRP-5051

Arm Description

Participants received escalating dose levels of SRP-5051, 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.

Participants will receive SRP-5051 at the doses selected based on data from Part A every 4 weeks, via IV infusion, for up to 2 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.

Outcomes

Primary Outcome Measures

Part A: Number of Adverse Events (AEs)
Number of adverse events includes clinically significant laboratory abnormalities.
Part B: Change From Baseline in Dystrophin Protein Level

Secondary Outcome Measures

Part A: Pharmacokinetics (PK): Plasma Concentration of SRP-5051 and Metabolite (SRP-5051A)
Part A: PK: Urine Concentration of SRP-5051
Part B: Change From Baseline in Exon-Skipping Levels
Part B: Number of Adverse Events (AEs)
Number of adverse events includes clinically significant laboratory abnormalities.
Part B: PK: Plasma Concentration of SRP-5051 and Metabolite (SRP-5051A)
Part B: PK: Urine Concentration of SRP-5051
Part B: Change from Baseline in Percent Dystrophin-Positive Fibers (PDPF) and Mean Intensity, as Measured by Immunofluorescence Assay
Change from baseline in PDPF and mean intensity as measured by immunofluorescence assay will be reported.

Full Information

First Posted
June 27, 2019
Last Updated
April 27, 2023
Sponsor
Sarepta Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04004065
Brief Title
Two-Part Study for Dose Determination of SRP-5051 (Vesleteplirsen) (Part A), Then Dose Expansion (Part B) in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 26, 2019 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sarepta Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 SRP-5051 (vesleteplirsen) at MAD levels to determine doses to be administered in Part B, and 2) Part B will be conducted to further evaluate the SRP-5051 doses selected in Part A. Participants enrolling in Part B will be those who completed Part A or Study 5051-102 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
Keywords
DMD, Duchenne, Dystrophy, Dystrophin, Exon Skipping, Ambulatory, Duchenne Muscular Dystrophy, Exon 51, Nonambulatory, Pediatric, Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
62 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A: SRP-5051
Arm Type
Experimental
Arm Description
Participants received escalating dose levels of SRP-5051, 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.
Arm Title
Part B: SRP-5051
Arm Type
Experimental
Arm Description
Participants will receive SRP-5051 at the doses selected based on data from Part A every 4 weeks, via IV infusion, for up to 2 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 Type
Drug
Intervention Name(s)
SRP-5051
Other Intervention Name(s)
vesleteplirsen
Intervention Description
SRP-5051 injection, for IV use
Primary Outcome Measure Information:
Title
Part A: Number of Adverse Events (AEs)
Description
Number of adverse events includes clinically significant laboratory abnormalities.
Time Frame
Part A: Baseline up to 75 weeks
Title
Part B: Change From Baseline in Dystrophin Protein Level
Time Frame
Part B: Baseline, Week 28
Secondary Outcome Measure Information:
Title
Part A: Pharmacokinetics (PK): Plasma Concentration of SRP-5051 and Metabolite (SRP-5051A)
Time Frame
Pre-dose and at multiple time points (up to 32 hours) after end of infusion
Title
Part A: PK: Urine Concentration of SRP-5051
Time Frame
Pre-dose and at multiple time periods (up to 48 hours) after end of infusion
Title
Part B: Change From Baseline in Exon-Skipping Levels
Time Frame
Part B: Baseline, Week 28
Title
Part B: Number of Adverse Events (AEs)
Description
Number of adverse events includes clinically significant laboratory abnormalities.
Time Frame
Part B: Baseline up to Week 104
Title
Part B: PK: Plasma Concentration of SRP-5051 and Metabolite (SRP-5051A)
Time Frame
Part B predose and at multiple timepoints (up to 48 hours) after end of infusion
Title
Part B: PK: Urine Concentration of SRP-5051
Time Frame
Part B predose and at multiple timepoints (up to 48 hours) after end of infusion
Title
Part B: Change from Baseline in Percent Dystrophin-Positive Fibers (PDPF) and Mean Intensity, as Measured by Immunofluorescence Assay
Description
Change from baseline in PDPF and mean intensity as measured by immunofluorescence assay will be reported.
Time Frame
Part B: Baseline, Week 28

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria for participants previously treated with SRP-5051: - Has received prior SRP-5051 treatment in Part A of this study or in Study 5051-102 Exclusion Criteria for participants previously treated with SRP-5051 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sarepta Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Univertisty of California Davis Health
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Connecticut Children's
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06032
Country
United States
Facility Name
Northwest Florida Clinical Research Group, LLC
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
Facility Name
Rare Disease Research, LLC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kansas Medical Center Research Inst.
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66103
Country
United States
Facility Name
University of Massachusetts
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
UPMC Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Austin Neuromuscular Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78756
Country
United States
Facility Name
Children's Health Ambulatory Pavilion
City
Dallas
State/Province
Texas
ZIP/Postal Code
75207
Country
United States
Facility Name
Seattle Children's
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Universitair Ziekenhuis Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Children's Hospital - London Health Sciences Centre (LHSC)
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Facility Name
University of Essen - Children's Hospital
City
Essen
ZIP/Postal Code
D-45147
Country
Germany
Facility Name
Klinikum der Universität München
City
Munich
ZIP/Postal Code
80337
Country
Germany
Facility Name
Fondazione Policlinico Universitario A Gemelli
City
Rome
ZIP/Postal Code
168
Country
Italy
Facility Name
A.O.U. Citta della Salute e della Scienza di Torino - SS Malattie Neuromuscolari, Department of Neurosciences
City
Torino
ZIP/Postal Code
10139
Country
Italy
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333
Country
Netherlands
Facility Name
Hospital Sant Joan de Déu. U.B.
City
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Universitari I Politecnic La Fe de Valencia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Royal Hospital for Children (Glasgow)
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Facility Name
Alder Hey Children's NHS Foundation Trust
City
Liverpool
ZIP/Postal Code
L12 2AP
Country
United Kingdom
Facility Name
Great Ormond Street Hospital for Children NHS Foundation Trust
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Oxford University Hospial NHS Foundation Trust, John Radcliffe Hospital
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
http://clinicaltrials.sarepta.com/momentumtrial
Description
Click here to access the website, clinicaltrials.sarepta.com/momentumtrial, for additional information for the study.

Learn more about this trial

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

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