Clinical trial NCT01721733: Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
Official title: A Phase 2B Randomized, Placebo Controlled, Double Blind Clinical Trial of EPI-743 in Children With Leigh Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leigh Syndrome
Keywords: EPI743
Leigh syndrome
respiratory chain disease
mitochondrial disorders
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Axio Research. LLC
First posted: 2012-11-06
Enrollment: 35
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) Sections 1-3
timeFrame: 6 months
Secondary outcomes:
measure: Neuromuscular function
timeFrame: 6 months
measure: Respiratory function
timeFrame: 6 months
measure: Disease morbidity
timeFrame: 6 months
measure: Glutathione cycle biomarkers
timeFrame: 6 months
measure: Number of dose limiting serious adverse events
timeFrame: 6 months
measure: Mortality
timeFrame: 6 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
References: