Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome

Study Overview
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Brief Summary
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EPI-743 in Leigh syndrome participants that participated in previous EPI743-12-002 (NCT01721733) study.

Detailed Description
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To monitor the long-term safety and neurodevelopmental effects of EPI-743 on children who complete the EPI743-12-002 placebo-controlled trial.

Official Title
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Long-Term Safety and Efficacy Evaluation of Vatiquinone (EPI-743) in Children With Leigh Syndrome

Conditions
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Leigh Syndrome

Intervention / Treatment
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* Drug: EPI-743


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Leigh syndrome with genetic confirmation Completion of EPI743-12-002 protocol and initiation of treatment within 14 days of Month 12 visit in EPI743-12-002 study Participant or participant's guardian able to consent and comply with protocol requirements Continued abstention from supplements excluded in EPI743-12-002 study Botox® is allowed if approved by the sponsor Exclusion Criteria: Allergy to EPI-743 or sesame oil Allergy to vitamin E Clinical history of bleeding or abnormal baseline prothrombin time (PT)/partial thromboplastin time (PTT) Hepatic insufficiency with liver function tests (LFTs) greater than two times upper limit of normal Renal insufficiency requiring dialysis End-stage cardiac failure Fat malabsorption syndromes precluding drug absorption Use of anticoagulant medications Participation in other clinical research studies/taking other experimental agents Participation in elective procedures that required sedation

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EPI-743<br>Participants will receive EPI-743 at a dose of 15 milligrams/kilogram (mg/kg) up to a total 200 mg 3 times daily (TID) orally with meal or by using nasogastric (NG) or gastrostomy feeding tubes with liquid food for at least 36 months. | Drug: EPI-743<br>* EPI-743 100 milligrams/milliliter (mg/mL) oral solution will be administered per dose and schedule specified in the arm.<br>* Other names: Vincerinone, Vatiquinone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Severity as Measured by Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) Sections 1-3 Score | NPMDS is a validated scale to assess the mitochondrial disease progression. | Baseline up to Month 36 | 
| Number of Participants With Dose-Limiting Serious Adverse Events (SAEs) |  | Baseline up to Month 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bayley Scales of Infant Development-III Score (Participants Age 0-3) | Effect of EPI-743 on neurodevelopment will be measured by Bayley Scales of Infant Development-III score. | Baseline up to Month 24 | 
| Wechsler Scale of Intelligence and Movement Assessment Battery Score for Children (Participants Age 4-18) | Effect of EPI-743 on neuromuscular function will be assessed by Wechsler Scale of Intelligence and Movement Assessment Battery score. | Baseline up to Month 24 | 
| Barry-Albright Dystonia Scale Score | Neuromuscular function will be assessed by Barry-Albright Dystonia Scale score. | Baseline up to Month 24 | 
| Gross Motor Function Measure | Neuromuscular function will be assessed by gross motor function measure. | Baseline up to Month 24 | 
| Awake Oxygen Saturation Levels | Effect of EPI-743 on respiratory function will be measured by awake oxygen saturation levels. | Baseline up to Month 24 | 
| Total Ventilator Days and Total Intensive Care Unit Days |  | Baseline up to Month 24 | 
| Number of Participants With Pneumonia Episodes and Tracheostomy |  | Baseline up to Month 24 | 
| Total Number of Mortalities, Medical Encounters, Hospitalizations, and Hospital Days |  | Baseline up to Month 24 | 
| Health-Related Quality of Life as Measured by NPMDS Section 4 Score |  | Baseline up to Month 24 | 
| Glutathione Cycle Biomarkers Level |  | Baseline up to Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leigh syndrome, Mitochondrial disorders, EPI743, Vincerinone