Prospective, Long Term, Observational Study (Patient Registry) of Paediatric Myotonic Disorders

Official title

Prospective, Long Term, Observational Study (Patient Registry) of Paediatric Myotonic Disorders From Birth to Less Than Six Years of Age Who Are Treated With Mexiletine (PEGASUS Study).

Overview

This is a prospective, open-label, multi-centre, single arm, registry study to collect standard relevant clinical and epidemiological data during routine medical evaluation and treatment in paediatric patients with myotonic disorders who are being treated with mexiletine therapy according to the physician.

Detailed description

This is a prospective, open-label, multi-centre, single arm, registry study to collect standard relevant clinical and epidemiological data during routine medical evaluation and treatment in paediatric patients with myotonic disorders who are being treated with mexiletine therapy according to the physician.

Patients who meet the eligibility criteria will be enrolled in 2 cohorts by age groups although cohorts are not enrolled sequentially (cohort definition is to assure minimum requirements for meeting PIP agreements).

Cohort 1 - Infants and children aged between 6 months to less than 6 years. Cohort 2 - Neonates and infants from birth to less than 6 months. The overall treatment duration follow-up for each cohort will be at least 2 years.

Interventions

• Drug Mexiletine
  Non interventional

Primary outcome measures

• To assess long-term safety by collection of SAEs, AEs, AESIs, changes in frequency, treatment interruptions [Time frame: Baseline to 24 months]

Secondary outcome measures (4)

• To assess the suitability of mexiletine administration [Time frame: Baseline to 24 months]
• To understand how mexiletine is used by clinicians [Time frame: Baseline to 24 months]
• Description over time of outcomes of mexiletine use [Time frame: Baseline to 24 months]
• The treating physician with elaborate a brief text with risk-benefit conclusions [Time frame: Baseline to 24 months]

Eligibility criteria

Inclusion criteria

• Male or female patients from birth to less than 6 years
• A genetically confirmed diagnosis of NDM or DM (DM1or DM2), as per the treating clinician.
• Presence of clinical symptoms of myotonia (hand grip myotonia, myotonia in the leg muscles, any other myotonia symptoms) to be confirmed by the treating clinician.
• Patients already receiving mexiletine treatment or who are clinically considered for mexiletine treatment as per the treating physician judgement.
• No history of or significant cardiac abnormalities as determined by a cardiologist's assessment of the ECG and echocardiogram performed prior to enrolment in the study or as per the treating physician standard of care (NaMuscla SmPC, 2023)
• No known history or signs and symptoms of any significant liver disorder as per treating physician.
• No known clinically relevant abnormal laboratory investigations for haematology, biochemistry, and urinalysis values at screening (or based on values obtained within 3 months prior to screening in patient's medical record) that could affect the study objectives as judged by the treating physician.
• Parent or legal guardian able to provide consent/assent to study participation and to sign the written informed consent or non-opposition as per local regulatory requirements prior to study entry and perform any study-related activity. -

Exclusion criteria

• Any contraindication to mexiletine as listed in the Namuscla Summary of Product Characteristics (SmPC) (NaMuscla SmPC, 2023)

• Hypersensitivity to the active substance, or to any of the excipients
• Hypersensitivity to any local anaesthetic
• Ventricular tachyarrhythmia
• Complete heart block (i.e., third-degree atrioventricular block) or any heart block susceptible to evolve to complete heart block (first-degree atrioventricular block with markedly prolonged PR interval (≥ 200 ms) and/or wide QRS complex (≥ 120 ms), second-degree atrioventricular block, bundle branch block, bifascicular and trifascicular block),
• QT interval > 450ms
• Myocardial infarction (acute or past), or abnormal Q-waves
• Symptomatic coronary artery disease
• Heart failure with ejection fraction <50%
• Atrial tachyarrhythmia, fibrillation or flutter
• Sinus node dysfunction (including sinus rate < 50 bpm)
• Co-administration with medicinal products inducing torsades de pointes.
• Co-administration with medicinal products with narrow therapeutic index
• Any other neurological or psychiatric condition that might affect the study assessments, as per the treating clinician.
• Any clinically significant illness, laboratory findings, ECG, or other clinical symptoms, which in the opinion of the treating physician could affect the patient's optimal participation in the study
• Receiving strong inducers or inhibitors of CYP2D6 or CYP1A2 or planned to receive them, during the subject participation (See section 4.1.5.1 Prohibited medications).
• Any concurrent illness, or medications which could affect the muscle function, and confound the results according to the treating physician.
• Seizure disorder, diabetes mellitus requiring treatment by insulin.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Cohort

Study locations

France · 1 center

• Centre Hospitalier Universitaire de Clermont-Ferrand — Clermont-Ferrand

Identifiers

NCT: NCT07154654 · MEX-NM-401

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗