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

PTC Therapeutics35 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Leigh Syndrome

Interventions

PlaceboDRUG

EPI-743 15 mg/kgDRUG

EPI-743 5 mg/kgDRUG

Eligibility

Sex: ALLMin age: 6 YearsMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (4)

Stanford University

Palo Alto, California, United States

Akron Children's Hospital

Akron, Ohio, United States

Baylor College of Medicine

Houston, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

Outcomes

Primary Outcomes

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

Time frame: 6 months

Secondary Outcomes

Neuromuscular function

Gross Motor Function Measure; Barry Albright Dystonia Scale

Time frame: 6 months

Respiratory function

Need for tracheostomy

Time frame: 6 months

Disease morbidity

Total number of hospitalizations

Time frame: 6 months

Glutathione cycle biomarkers

Blood levels of glutathione will be compared between placebo and treatment group

Time frame: 6 months

Number of dose limiting serious adverse events

Time frame: 6 months

Mortality

Number of deaths

Time frame: 6 months

Data from ClinicalTrials.gov

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