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

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

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

Study Overview

• Status: Completed
• Conditions: Leigh Syndrome
• Intervention / Treatment: Drug: EPI-743

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford University, California, United States, 94305
      • Gregory Enns
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EPI-743; 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; EPI-743 100 milligrams/milliliter (mg/mL) oral solution 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	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

Collaborators and Investigators

• Sponsor: PTC Therapeutics
• Investigators: Principal Investigator: Bruce Cohen, MD, Akron Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2014
• Primary Completion (Actual): October 30, 2023
• Study Completion (Actual): October 30, 2023

Study Registration Dates

• First Submitted: August 21, 2014
• First Submitted That Met QC Criteria: January 27, 2015
• First Posted (Estimated): February 2, 2015

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Mitochondrial disorders; Leigh syndrome; EPI743; Vincerinone
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Mitochondrial Diseases; Brain Diseases, Metabolic, Inborn; Pyruvate Metabolism, Inborn Errors; Syndrome; Leigh Disease
• Other Study ID Numbers: EPI743-13-023