Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
- Conditions
- Leigh Syndrome
- Interventions
- Drug: EPI-743 5 mg/kgDrug: PlaceboDrug: EPI-743 15 mg/kg
- Registration Number
- NCT01721733
- Lead Sponsor
- PTC Therapeutics
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description EPI-743 5 mg/kg EPI-743 5 mg/kg Each subjects dose will be based on their weight. 5 mg/kg with a maximum dose of 100 mg per dose, t.i.d., will be administered in this treatment arm. Placebo Placebo Each patient will receive a volume of placebo based on weight EPI-743 15 mg/kg EPI-743 15 mg/kg Each subjects dose will be based on their weight. 15 mg/kg with a maximum dose of 200 mg per dose, t.i.d., will be administered in this treatment arm.
- Primary Outcome Measures
Name Time Method Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) Sections 1-3 6 months Change from baseline to six months will be compared between subjects in active treatment group and placebo group
- Secondary Outcome Measures
Name Time Method Disease morbidity 6 months Total number of hospitalizations
Mortality 6 months Number of deaths
Respiratory function 6 months Need for tracheostomy
Neuromuscular function 6 months Gross Motor Function Measure; Barry Albright Dystonia Scale
Glutathione cycle biomarkers 6 months Blood levels of glutathione will be compared between placebo and treatment group
Number of dose limiting serious adverse events 6 months
Trial Locations
- Locations (4)
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Stanford University
🇺🇸Palo Alto, California, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States