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

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

• EPI-743 (Drug), also known as Vincerinone, Vatiquinone: EPI-743 100 milligrams/milliliter (mg/mL) oral solution will be administered per dose and schedule specified in the arm.

Primary outcomes

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

Secondary outcomes

• Bayley Scales of Infant Development-III Score (Participants Age 0-3) [Baseline up to Month 24]: Effect of EPI-743 on neurodevelopment will be measured by Bayley Scales of Infant Development-III score.
• Wechsler Scale of Intelligence and Movement Assessment Battery Score for Children (Participants Age 4-18) [Baseline up to Month 24]: Effect of EPI-743 on neuromuscular function will be assessed by Wechsler Scale of Intelligence and Movement Assessment Battery score.
• Barry-Albright Dystonia Scale Score [Baseline up to Month 24]: Neuromuscular function will be assessed by Barry-Albright Dystonia Scale score.
• Gross Motor Function Measure [Baseline up to Month 24]: Neuromuscular function will be assessed by gross motor function measure.
• Awake Oxygen Saturation Levels [Baseline up to Month 24]: Effect of EPI-743 on respiratory function will be measured by awake oxygen saturation levels.
• 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]

Sex: All, ages: 1 Year to 18 Years

Inclusion Criteria:

1. Diagnosis of Leigh syndrome with genetic confirmation
2. Completion of EPI743-12-002 protocol and initiation of treatment within 14 days of Month 12 visit in EPI743-12-002 study
3. Participant or participant's guardian able to consent and comply with protocol requirements
4. Continued abstention from supplements excluded in EPI743-12-002 study
5. Botox® is allowed if approved by the sponsor

Exclusion Criteria:

1. Allergy to EPI-743 or sesame oil
2. Allergy to vitamin E
3. Clinical history of bleeding or abnormal baseline prothrombin time (PT)/partial thromboplastin time (PTT)
4. Hepatic insufficiency with liver function tests (LFTs) greater than two times upper limit of normal
5. Renal insufficiency requiring dialysis
6. End-stage cardiac failure
7. Fat malabsorption syndromes precluding drug absorption
8. Use of anticoagulant medications
9. Participation in other clinical research studies/taking other experimental agents
10. Participation in elective procedures that required sedation

• Bruce Cohen, MD, Principal investigator, Akron Children's Hospital