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

A Phase 2B Randomized, Placebo Controlled, Double Blind Clinical Trial of EPI-743 in Children With Leigh Syndrome

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

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