EPI-743 for Mitochondrial Respiratory Chain Diseases

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

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.

Study Overview

• Status: No longer available
• Conditions: Mitochondrial Diseases
• Intervention / Treatment: Drug: EPI-743

• Study Type: Expanded Access
• Expanded Access Type: Individual Patients; Treatment IND/Protocol
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • Orange, California, United States, 92868
      • CHOC Children's Clinic
    • Palo Alto, California, United States, 94304
      • Lucille Packard Children's Hospital
    • San Diego, California, United States, 92123
      • UCSD
    • Stanford, California, United States, 94304
      • Stanford Children's Health
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Emory University
  • New York
    • New York, New York, United States, 10032
      • CUMC (Columbia University)
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • MUSC
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • UTH
  • Washington
    • Bremerton, Washington, United States, 98312
      • Naval Hospital, Bremerton
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Participants with genetic diagnosis: Genetically confirmed diagnosis of Inherited mitochondrial respiratory chain disease
2. 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
3. Deemed by principal investigator to be within 90 days of end-of-life hospice/terminal care
4. Male or female age > one year
5. Hematocrit within normal range for age group
6. Agreement to use contraception if within reproductive years
7. Participant or participant's guardian able to consent and comply with protocol requirements
8. Presence of caregiver to ensure study compliance
9. Abstention from use of all pill-form dietary supplements and non-prescribed medications (except as allowed by the investigator)
10. Abstention from foods or beverages or bars fortified with Coenzyme Q10, vitamin E, super-fortified "functional" foods or beverages
11. Abstention from use of idebenone
12. Clinically staged with a Mitochondrial Disease Scale such as the Newcastle Score

Exclusion criteria:

1. Allergy to EPI-743, vitamin E or sesame oil
2. Clinical history of bleeding or abnormal prothrombin time (PT)/partial thromboplastin time (PTT) (excluding anticoagulation Rx)
3. Hepatic insufficiency with liver function tests (LFTs) greater than two times normal
4. Renal insufficiency requiring dialysis
5. Fat malabsorption syndromes precluding drug absorption
6. Any other concurrent inborn errors of metabolism
7. Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis
8. Pregnancy

Study Plan

How is the study designed?

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: EPI-743; 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; 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.; Other Names: Vincerinone, Vatiquinone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: PTC Therapeutics
• Investigators: Principal Investigator: Gregory Enns, MB, ChB, Stanford University

Study record dates

Study Major Dates

• Study Start: February 28, 2010
• Primary Completion: September 28, 2023
• Study Completion: September 28, 2023

Study Registration Dates

• First Submitted: June 7, 2011
• First Submitted That Met QC Criteria: June 9, 2011
• First Posted (Estimated): June 10, 2011

Study Record Updates

• Last Update Posted (Estimated): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: MELAS; Friedreich's ataxia; Leigh syndrome; Kearns-Sayre; Inherited mitochondrial disease; Alper's; POLG1 deficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Mitochondrial Diseases
• Other Study ID Numbers: EPI-2009-1