P.406 - A phase 2 trial of the safety and pharmacokinetics of ataluren in patients aged 2 to 5 years with nonsense mutation Duchenne muscular dystrophy

Abstract

Nonsense mutation Duchenne muscular dystrophy (nmDMD) is a rare, X-linked genetic disorder that results in a decline in function, loss of ambulation and early death due to respiratory or cardiac failure. Ataluren is conditionally approved by the European Medicines Agency for the treatment of ambulatory patients aged ≥ 5 years with nmDMD. Initiation of treatment prior to substantial muscle loss may maximize benefit. It is therefore important to understand the safety and pharmacokinetics (PK) of ataluren in patients aged < 5 years, particularly since ataluren is dosed by weight. A phase 2, open-label trial has been designed to evaluate the safety and PK of ataluren in boys aged ≥ 2 to < 5 years with nmDMD with a body weight ≥ 12 kg (NCT02819557). This trial will include a 4-week assessment of the safety and PK of ataluren, and a 48-week extension period to assess the safety of long-term administration of ataluren in this younger population. Motor function will also be evaluated. Fourteen patients were enrolled and are receiving ataluren 40 mg/kg/day (given orally in three doses: 10, 10 and 20 mg/kg) for 52 weeks. The primary endpoint will be the overall safety profile of ataluren with regards to the type, frequency, severity, timing and relationship to study therapy of any adverse events (AEs); occurrence of any dose-limiting toxicities; treatment discontinuation owing to AEs; and occurrence of serious AEs. Secondary endpoints will include assessment of plasma PK parameters on days 1 and 28 of ataluren treatment; changes from baseline to week 52 in timed function tests, North Star Ambulatory Assessment total score, body weight, height and body mass index; and ataluren palatability characteristics determined by a parent/caregiver questionnaire. Available data from this ongoing trial will be presented.