Gene Transfer Clinical Study in X-Linked Myotubular Myopathy

Open to males ages up to 5 years

• Subject has a diagnosis of XLMTM resulting from a genetically confirmed mutation in the MTM1 gene as assessed by a Sponsor-approved testing facility.
• Subject is male.
• Subject is aged less than 5 years old at dosing

• Subject requires mechanical ventilatory support:

  Part 1: Subject requires some mechanical ventilatory support (e.g., ranging from 24 hours per day full time mechanical ventilation, to noninvasive support such as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) during sleeping hours). Part 2: Subject requires invasive mechanical ventilatory support ranging from 20 - 24 hours per day at screening (confirmed by daytime polysomnographic study).

• Subject requiring invasive mechanical ventilator support is fitted with or willing to be fitted with a cuffed tracheostomy tube for some respiratory assessments.
• Subject has ventilator maximum positive end-expiratory pressure (PEEP) <8 cm H2O at screening.
• UNIQUE to France: Subject's weight is ≥ 4.8 kg.

• Subject is participating in an interventional study designed to treat XLMTM.
• Subject born <35 weeks gestation who is still not term as per corrected age.
• Subject tests positive for AAV8 neutralizing antibody with titers above protocol specified threshold.
• Subject had recent surgery (<3 months before Day 1) or has planned surgery that may confound data collection during the first 48 weeks of the study.
• Subject has a clinically important condition other than XLMTM in the opinion of the investigator.
• Subject has a clinically significant underlying liver disease.
• Subject is currently experiencing a clinically important respiratory infection or other active infection.
• Subject has received pyridostigmine or any medication to treat XLMTM within 3 months before Day 1.
• Other than as required per protocol, subject has received immune-modulating agents within 3 months before Day 1 (use of inhaled corticosteroids to manage chronic respiratory conditions is allowed); use of other concomitant medications to manage chronic conditions must have been stable for at least 4 weeks before dosing.
• Subject has a contraindication to prednisolone.
• Subject has a contraindication to study drug or ingredients.
• Subject has previous scoliosis repair surgery/procedure, or planned/expected scoliosis repair surgery/procedure in the 12 months following Day 1 (Part 2 including any subjects enrolled under protocol v8 and beyond).
• Subject has contractures, scoliosis, or other medical condition that would limit the potential to achieve unassisted sitting, in the opinion of the investigator (Part 2 including any subjects enrolled under protocol V8 and beyond).
• Subject is able to sit without assistance for at least 30 seconds at screening, in the opinion of the investigator (Part 2 including any subjects enrolled under protocol V8 and beyond).
• Subject has a clinically important condition, including CTCAE v4.03 Grade ≥ 2 anemia (< 10 g/dL hemoglobin).
• Subject has a contraindication to ursodiol (ursodeoxycholic acid).
• UNIQUE to France: Subject has a prior diagnosis or history of cardiac arrhythmias, myocarditis, or any other cardiac disease.
• UNIQUE to France: Subject has a contraindication to general anesthesia and to muscle biopsy procedures.