Metoprolol Safety and Efficacy in the Prevention of Cardiomyopathy in Patients with Duchenne Muscular Dystrophy (DMD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Gdansk

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

12 Jul 2021 → 6 Oct 2025

Decision date (initial)

2024-12-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Medical Research Agency (Agencja Badań Medycznych)

External identifiers

EU CT number

2024-515057-19-00

EudraCT number

2020-004901-29

ClinicalTrials.gov

NCT05066633

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Prophylaxis, Efficacy, Safety

The primary objective of this study is to evaluate whether metoprolol succinate in addition to standard of care cardiac treatment introduced before the onset of echocardiography detectable left ventricular dysfunction, can slow the rate of progression left ventricular ejection fraction drop that leads to cardiomyopathy in males with DMD compared to placebo.

Secondary objectives 1

1. The secondary objectives of this study are to assess if metoprolol succinate in addition to standard of care treatment introduced before the onset of echocardiography detectable left ventricular dysfunction and compared to placebo: - can delay the occurrence of cardiomyopathy in children with DMD - can delay the occurrence of heart failure in children with DMD - can delay the age of onset and/or slow the rate of progression of myocardial fibrosis assessed by cardiac magnetic resonance (CMR) - can reduce the prevalence of sinus tachycardia assessed by Holter ECG - is safe and well tolerated in children with DMD

Conditions and MedDRA coding

Duchenne muscular dystrophy; Cardiomyopathy; Tachycardia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Subject's parent(s) or legal guardian(s) has (have) provided written informed consent, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to requirements (>16 years old) 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Male, ≥ 8 years and <17 years of age at time of enrolment in the study 4. Ability to take oral medication and be willing to adhere to the study intervention regimen 5. Subject has confirmed diagnosis of DMD, as defined as clinical picture consistent with typical DMD and: • Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, or • Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-offrame' or • Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e., nonsense mutation, deletion/duplication leading to a downstream stop codon) 6. Taking ACEi treatment at minimum required doses as outlined in the protocol for at least 30 days

Exclusion criteria 1

1. 1. Current or previous permanent use of any beta-blocker medication 2. Treatment with another investigational drug or other intervention within 3 months prior to screening 3. Clinically significant bradycardia at rest or by Holter ECG, based on age and sex adjusted normal values, atrioventricular block higher than first degree at rest, or second degree Wenckebach at night, pauses longer than 2.5 seconds 4. Presence of pacemaker or ICD 5. Clinical signs or symptoms of heart failure 6. Left ventricular Ejection Fraction (LVEF) <57% (assessed by Teichholtz echocardiography) 7. Inability to obtain adequate quality echocardiography images (necessary to monitor for primary endpoint and safety) 8. Known allergic reactions to components of the IMPs

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is change in left ventricular ejection fraction (LVEF) by Teichholtz method (echocardiography), compared to baseline at Interim Analysis and Final Analysis.

Secondary endpoints 1

1. • Disease Free Survival (DFS) i.e., the time to develop cardiomyopathy defined as Left Ventricular Ejection Fraction – (LVEF) <55% by echocardiography Teichholtz method. • prevalence of patients with cardiomyopathy defined as Left Ventricular Ejection Fraction – (LVEF) <55% by echocardiography Teichholtz method • Disease Free Survival (DFS) i.e., the time to develop clinically evident Heart Failure (HF)

Investigational products

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

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Gdansk

Sponsor organisation

Medical University Of Gdansk

Address

Ul. Marii Sklodowskiej-Curie 3a

City

Gdansk

Postcode

80-210

Country

Poland

Scientific contact point

Organisation

Medical University Of Gdansk

Contact name

Chief Medical Officer; Principal Investigator

Public contact point

Organisation

Medical University Of Gdansk

Contact name

Director of Clinical Research Support Centre

Locations

1 EU/EEA country · 2 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 9 files

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

Application history

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