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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sarepta Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

21 Aug 2020 → 7 Feb 2025

Decision date (initial)

2024-05-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Sarepta Therapeutics, Inc.

External identifiers

EU CT number

2023-509935-23-00

EudraCT number

2019-000601-77

ClinicalTrials.gov

NCT04004065

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Pharmacokinetic, Therapy, Dose response, Others

Part A: To evaluate the safety and tolerability of multiple ascending doses of SRP-5051, administered intravenously (IV) every 4 weeks, and determine the maximum tolerated dose (MTD)
Part B: To evaluate dystrophin protein level in skeletal muscle tissue following SRP-5051 treatment, administered IV every 4 weeks at the doses selected based on data from Part A

Secondary objectives 1

1. Part A To determine the pharmacokinetics (PK) of SRP-5051 in plasma and urine at each of the aforementioned multiple ascending doses of SRP-5051, administered IV every 4 weeks Part B • To evaluate exon-skipping level in skeletal muscle tissue following SRP-5051 treatment, administered IV every 4 weeks at the doses selected based on data from Part A • To evaluate the ongoing safety and tolerability of SRP-5051 treatment, administered IV every 4 weeks at the doses selected based on data from Part A • To determine the PK of SRP-5051 in plasma and urine • To evaluate, via immunohistochemistry, percent dystrophin-positive fibers (PDPF) and mean intensity following SRP-5051 treatment, administered IV every 4 weeks at the doses selected based on data from Part A

Conditions and MedDRA coding

Duchenne Muscular Dystrophy

Study design 2 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003305-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Inclusion Criteria for participants previously treated with Vesleteplirsen: - Has received prior Vesleteplirsen treatment in Part A of this study or in Study 5051-102.
2. 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 2

1. 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.
2. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part A: Incidence of Adverse Events (AEs), Baseline up to 75 weeks
2. Part B: Change From Baseline in Dystrophin Protein Level at Week 28

Secondary endpoints 7

1. Part A: Pharmacokinetics (PK): Plasma Concentration of Vesleteplirsen, Pre-dose and at multiple time points (up to 32 hours) after end of infusion
2. Part A: PK: Urine Concentration of Vesleteplirsen, Pre-dose and at multiple time periods (up to 48 hours) after end of infusion
3. Part B: Change From Baseline in Exon-Skipping Levels at Week 28
4. Part B: Incidence of Adverse Events (AEs), Baseline up to Week 304
5. Part B: PK: Plasma Concentration of Vesleteplirsen, Part B predose and at multiple timepoints (up to 48 hours) after end of infusion
6. Part B: PK: Urine Concentration of Vesleteplirsen, Part B predose and at multiple timepoints (up to 48 hours) after end of infusion
7. Part B: Change from Baseline in Percent Dystrophin-Positive Fibers (PDPF) and Mean Intensity, as Measured by Immunofluorescence Assay at Week 28

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sarepta Therapeutics Inc.

Sponsor organisation

Sarepta Therapeutics Inc.

Address

215 1st Street

City

Cambridge

Postcode

02142-1213

Country

United States

Scientific contact point

Organisation

Sarepta Therapeutics Inc.

Contact name

Patient Recruitment

Public contact point

Organisation

Sarepta Therapeutics Inc.

Contact name

Patient Recruitment

Third parties 25

Locations

5 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 98 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications