Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome

The purpose of this study is to evaluate the effects of EPI-743 in patient with Leigh syndrome on disease severity, neuromuscular function, respiratory function, disease morbidity and mortality and biomarkers associated with the disease.

This study is a six month prospective randomized double-blind, placebo-controlled trial with a six month extension phase of two dose levels of EPI743. The planned enrollment is for approximately 30 children with genetically confirmed Leigh syndrome. After 6 months of treatment, those children that were randomized to the placebo treatment arm will be re-randomized to one of the 2 active treatment arms.

Inclusion criteria

• Clinical and MRI diagnosis of Leigh syndrome
• Moderate disease severity based on NPMDS score
• Age under 18 years
• Documented evidence of disease progression within 12 month of enrollment
• Availability of MRI that confirms necrotizing encephalopathy
• Patient or guardian able to consent and comply with protocol requirements
• Abstention from Coenzyme Q10, Vitamins C & E, lipoic acid and Idebenone

Exclusion criteria

• Allergy to EPI-743, Vitamin E or sesame oil
• History of bleeding abnormalities or abnormal PT/PTT
• Diagnosis of concurrent inborn error of metabolism
• Previous tracheostomy
• Ventilator dependent or use of noninvasive ventilatory support w/in 1 month of enrollment
• LFTs greater than 2 times ULN
• Renal insufficiency
• End stage cardiac failure
• Fat malabsorption syndrome
• Use of anticoagulant medications
• Abstention from Botox for 6 months prior to enrollment and for duration of study