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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

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

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

NCT ID

NCT04004065

First Posted

June 27, 2019

Last Updated

April 27, 2023

Sponsor

Sarepta Therapeutics, Inc.

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

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

Arm Title

Part B: SRP-5051

Arm Type

Experimental

Arm Description

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

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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