EPI-743 for Mitochondrial Respiratory Chain Diseases

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of EPI-743 in participants with severe mitochondrial respiratory chain diseases who are considered to be within 90 days of end-of-life care.

Official Title
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Emergency Use Protocol for EPI-743 in Acutely Ill Patients With Inherited Mitochondrial Respiratory Chain Disease Within 90 Days of End-of-Life Care

Conditions
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Mitochondrial Diseases

Intervention / Treatment
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* Drug: EPI-743


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants with genetic diagnosis: Genetically confirmed diagnosis of Inherited mitochondrial respiratory chain disease Participants with clinical diagnosis: Diagnosis of inherited mitochondrial disease absent genetic confirmation; Specifically, participants must meet the diagnostic criteria of definite or probable mitochondrial disease as defined by Bernier et al., 2002 Deemed by principal investigator to be within 90 days of end-of-life hospice/terminal care Male or female age > one year Hematocrit within normal range for age group Agreement to use contraception if within reproductive years Participant or participant's guardian able to consent and comply with protocol requirements Presence of caregiver to ensure study compliance Abstention from use of all pill-form dietary supplements and non-prescribed medications (except as allowed by the investigator) Abstention from foods or beverages or bars fortified with Coenzyme Q10, vitamin E, super-fortified functional foods or beverages Abstention from use of idebenone Clinically staged with a Mitochondrial Disease Scale such as the Newcastle Score Exclusion criteria: Allergy to EPI-743, vitamin E or sesame oil Clinical history of bleeding or abnormal prothrombin time (PT)/partial thromboplastin time (PTT) (excluding anticoagulation Rx) Hepatic insufficiency with liver function tests (LFTs) greater than two times normal Renal insufficiency requiring dialysis Fat malabsorption syndromes precluding drug absorption Any other concurrent inborn errors of metabolism Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis Pregnancy

Ages Eligible for Study
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Minimum Age: 1 Year

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 50 milligrams (mg) at Day 1, 50 mg twice daily for 13 days, 100 mg on Day 15, and 100 mg twice daily until Day 28; either by mouth with a meal or via their G-tube with feeds. In the absence of clinical or laboratory indications of any safety concerns, participants will receive 100 mg EPI-743 three times daily until end of study. | Drug: EPI-743<br>* EPI-743 (oral solution [100 mg/mL] or liquid-filled capsules [100 mg or 200 mg]) 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 |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events |  | Baseline up to Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Neurological Function, as Determined by Standard Neurological Examination at Week 13 | Neurological exams to determine neuro-muscular function, which is typically compromised in participants with inherited mitochondrial diseases. Standard clinical neurological/neuromuscular assessment scales will be used | Baseline, Week 13 | 
| Change From Baseline in Newcastle Pediatric Mitochondrial Disease Score (NPMDS) at Week 13 | NPMDS is a validated scale to assess the clinical severity of mitochondrial disease. The NPMDS will be scored at baseline and at Week 13, and the difference will be assessed as improved, stable or deteriorated. | Baseline, Week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leigh syndrome, MELAS, Kearns-Sayre, Alper's, Inherited mitochondrial disease, Friedreich's ataxia, POLG1 deficiency