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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Leigh Syndrome

Intervention / Treatment
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* Drug: Placebo
* Drug: EPI-743 15 mg/kg
* Drug: EPI-743 5 mg/kg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Each patient will receive a volume of placebo based on weight | Drug: Placebo<br> <br> |
| Active Comparator: EPI-743 15 mg/kg<br>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. | Drug: EPI-743 15 mg/kg<br> <br> |
| Active Comparator: EPI-743 5 mg/kg<br>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. | Drug: EPI-743 5 mg/kg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) Sections 1-3 | Change from baseline to six months will be compared between subjects in active treatment group and placebo group | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuromuscular function | Gross Motor Function Measure; Barry Albright Dystonia Scale | 6 months | 
| Respiratory function | Need for tracheostomy | 6 months | 
| Disease morbidity | Total number of hospitalizations | 6 months | 
| Glutathione cycle biomarkers | Blood levels of glutathione will be compared between placebo and treatment group | 6 months | 
| Number of dose limiting serious adverse events |  | 6 months | 
| Mortality | Number of deaths | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EPI743, Leigh syndrome, respiratory chain disease, mitochondrial disorders