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)

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Drug utilisation

  Effectiveness study (incl. comparative)

  Evaluation of patient-reported outcomes
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-only

Study drug and medical condition

• Medicinal product name:
  NAMUSCLA
• Study drug International non-proprietary name (INN) or common name:
  MEXILETINE HYDROCHLORIDE
• Anatomical Therapeutic Chemical (ATC) code:
  (C01BB02) mexiletine

  mexiletine
• Medical condition to be studied:
  Myotonia

  Myotonic dystrophy

Population studied

• Short description of the study population:
  Male and female children from birth to less than 6 years of age with clinical symptoms or signs of myotonic disorders, normal electrocardiogram (ECG) exam and genetic confirmation of the diagnosis i.e., non-dystrophic myotonia (NDM), or myotonic dystrophy (DM) type 1 (DM1), or DM type 2 (DM2).
• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)

Study design details

• Study design:
  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.
• Main study objective:
  To evaluate the safety and the efficacy (exploratory) of mexiletine for the treatment of myotonia in the paediatric population aged from birth to less than 6 years using real world data.
• Setting:
  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.; Dosing and treatment administration in this registry study will be done as per the treating physician standard clinical practice. Visits to the clinic will occur according to routine site´s clinical practice, or when applicable according to the treating practice physician.; 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.; ; Exclusion Criteria:; 1. Any contraindication to mexiletine as listed in the Namuscla Summary of Product Characteristics (SmPC) (NaMuscla SmPC, 2023); 2. Any other neurological or psychiatric condition that might affect the study assessments, as per the treating clinician.; ; More eligibility criteria can be found in the study protocol
• Comparators:
  N/A
• Data analysis plan:
  The following data elements will be collected as permitted by the clinical site normal clinical practice for patients with myotonic disorders and/or the patient’s age:;  Demographics;  Genetics: DM1, DM2 or NDM corresponding clinical forms;  Musculoskeletal manifestations (myotonia, Charcot-Marie-Tooth disability scale, facial hypotonia);  Orthopaedic deformities (spine, feet or hands, orthoses, back brace, specialized follow-up, surgery);  Cardiorespiratory signs (non-invasive ventilation, sleep disorders, ECG / left ventricular ejection fraction (LVEF), pacemaker/defibrillator);  Ophthalmic and endocrinologic manifestations (cataract, diabetes, thyroid disorders);  Psychomotor development disabilities;  Gastrointestinal disorders; ; Data will be entered at baseline upon patient enrolment and entered periodically thereafter for all routine clinical practice patient visits. All data will include the date each assessment was performed. Where available, additional retrospective data will be collected. Retrospective data will be focused primarily on patterns of mexiletine use and dose adjustments as well as any efficacy assessments. Retrospective safety data will also be recorded, especially in relation to any AEs that affect dosing, SAEs or AESIs, but there will be no requirement to report any retrospective AEs prior to signing the informed consent.