Leigh Syndrome
Conditions
Keywords
EPI743, Leigh syndrome, respiratory chain disease, mitochondrial disorders
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.
Interventions
DRUGPlacebo
DRUGEPI-743 15 mg/kg
DRUGEPI-743 5 mg/kg
Sponsors
Axio Research. LLC
PTC Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Respiratory function | 6 months | Need for tracheostomy |
| Disease morbidity | 6 months | Total number of hospitalizations |
| Neuromuscular function | 6 months | Gross Motor Function Measure; Barry Albright Dystonia Scale |
| Number of dose limiting serious adverse events | 6 months | — |
| Mortality | 6 months | Number of deaths |
| Glutathione cycle biomarkers | 6 months | Blood levels of glutathione will be compared between placebo and treatment group |
Countries
United States
Outcome results
None listed