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

Phase 2

Completed

• Conditions: Leigh Syndrome
• Interventions: Drug: EPI-743

• Registration Number: NCT02352896
• Lead Sponsor: PTC Therapeutics

Brief Summary

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

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 Timeline

• Study Start: 2014-01-31
• Study First Submitted: 2014-08-21
• Study First Submitted QC: 2015-01-27
• Study First Posted: 2015-02-02
• Primary Completion: 2023-10-30
• Study Completion: 2023-10-30
• Status Verified: 2024-10
• Disposition First Submitted: 2024-10-22
• Last Update Submitted: 2024-10-22
• Disposition First Posted: 2024-10-23
• Last Update Posted: 2024-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EPI-743	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
Barry-Albright Dystonia Scale Score	Baseline up to Month 24	Neuromuscular function will be assessed by Barry-Albright Dystonia Scale score.
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.
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

Trial Locations

Locations (4)

Gregory Enns; 🇺🇸 Stanford University, California, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Akron Children's Hospital; 🇺🇸 Akron, Ohio, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States