Long-term registry for children with myotonic disorders on mexiletine

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).

This registry will follow infants and young children with genetically confirmed myotonic disorders who are receiving mexiletine to collect routine clinical and safety information over at least two years.

Quick facts

• Study type: Observational
• Enrollment: 10 (estimated)
• Ages: N/A to 6 Years
• Sex: All
• Sponsor: Lupin Ltd. (Industry-sponsored)
• Locations: 1 site (Clermont-Ferrand)
• Trial ID: NCT07154654 on ClinicalTrials.gov

What this trial studies

This is a prospective, open-label, multi-centre, single-arm registry that collects standard clinical and epidemiological data during routine care of pediatric patients treated with mexiletine. Participants are enrolled into two age-based cohorts (birth to <6 months, and 6 months to <6 years) to meet pediatric investigation planning requirements. Patients must have a genetic diagnosis of nondystrophic or dystrophic myotonia, clinical myotonia, and be already receiving or considered for mexiletine by their physician. Follow-up for each participant is planned for a minimum of two years with data captured during routine clinical visits.

Who should consider this trial

Good fit: Infants and children from birth to under 6 years with genetically confirmed myotonic disorders who have clinical myotonia and are already receiving or may start mexiletine, with no significant cardiac or liver disease, are ideal candidates.

Not a fit: Children with significant cardiac abnormalities, relevant liver disease, abnormal screening labs, or without genetic confirmation of myotonic disorder are unlikely to be eligible or to gain benefit from participation.

Why it matters

Potential benefit: If successful, the registry could provide important long-term, real-world safety and effectiveness information about mexiletine use in young children with myotonic disorders.

How similar studies have performed: Mexiletine is an established treatment for myotonia in adults and small pediatric case series report symptom improvement, but large, long-term pediatric registry data are limited.

Eligibility criteria

Inclusion Criteria:

1. Male or female patients from birth to less than 6 years
2. A genetically confirmed diagnosis of NDM or DM (DM1or DM2), as per the treating clinician.
3. 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.
4. Patients already receiving mexiletine treatment or who are clinically considered for mexiletine treatment as per the treating physician judgement.
5. 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)
6. No known history or signs and symptoms of any significant liver disorder as per treating physician.
7. 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.
8. 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:

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

   1. Hypersensitivity to the active substance, or to any of the excipients
   2. Hypersensitivity to any local anaesthetic
   3. Ventricular tachyarrhythmia
   4. 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),
   5. QT interval \> 450ms
   6. Myocardial infarction (acute or past), or abnormal Q-waves
   7. Symptomatic coronary artery disease
   8. Heart failure with ejection fraction \<50%
   9. Atrial tachyarrhythmia, fibrillation or flutter
   10. Sinus node dysfunction (including sinus rate \< 50 bpm)
   11. Co-administration with medicinal products inducing torsades de pointes.
   12. Co-administration with medicinal products with narrow therapeutic index
2. Any other neurological or psychiatric condition that might affect the study assessments, as per the treating clinician.
3. 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
4. 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).
5. Any concurrent illness, or medications which could affect the muscle function, and confound the results according to the treating physician.
6. Seizure disorder, diabetes mellitus requiring treatment by insulin.

Where this trial is running

Clermont-Ferrand

• Centre Hospitalier Universitaire de Clermont-Ferrand — Clermont-Ferrand, France (Recruiting)

Study contacts

• Principal investigator: Catharine Sarret, MD — University Hospital, Clermont-Ferrand
• Study coordinator: Nikki Adetoro

Conditions Myotonic Disorders