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

• ClinicalTrials.gov Identifier: NCT02352896
• Recruitment Status: Active, not recruiting
• First Posted: February 2, 2015
• Last Update Posted: March 1, 2023
• Sponsor: PTC Therapeutics
• Information provided by (Responsible Party): PTC Therapeutics

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Leigh Syndrome	Drug: EPI-743	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long-Term Safety and Efficacy Evaluation of Vatiquinone (EPI-743) in Children With Leigh Syndrome
• Actual Study Start Date: January 31, 2014
• Estimated Primary Completion Date: May 31, 2023
• Estimated Study Completion Date: May 31, 2023

Arms and Interventions

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 Name: Vincerinone, Vatiquinone

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Bayley Scales of Infant Development-III Score (Participants Age 0-3) [ Time Frame: Baseline up to Month 24 ]
   Effect of EPI-743 on neurodevelopment will be measured by Bayley Scales of Infant Development-III score.
2. Wechsler Scale of Intelligence and Movement Assessment Battery Score for Children (Participants Age 4-18) [ Time Frame: 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.
3. Barry-Albright Dystonia Scale Score [ Time Frame: Baseline up to Month 24 ]
   Neuromuscular function will be assessed by Barry-Albright Dystonia Scale score.
4. Gross Motor Function Measure [ Time Frame: Baseline up to Month 24 ]
   Neuromuscular function will be assessed by gross motor function measure.
5. Awake Oxygen Saturation Levels [ Time Frame: Baseline up to Month 24 ]
   Effect of EPI-743 on respiratory function will be measured by awake oxygen saturation levels.
6. Total Ventilator Days and Total Intensive Care Unit Days [ Time Frame: Baseline up to Month 24 ]
7. Number of Participants With Pneumonia Episodes and Tracheostomy [ Time Frame: Baseline up to Month 24 ]
8. Total Number of Mortalities, Medical Encounters, Hospitalizations, and Hospital Days [ Time Frame: Baseline up to Month 24 ]
9. Health-Related Quality of Life as Measured by NPMDS Section 4 Score [ Time Frame: Baseline up to Month 24 ]
10. Glutathione Cycle Biomarkers Level [ Time Frame: Baseline up to Month 24 ]

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Gregory Enns

Stanford University, California, United States, 94305

United States, Ohio

Akron Children's Hospital

Akron, Ohio, United States, 44308

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105

Sponsors and Collaborators

PTC Therapeutics

Investigators

• Principal Investigator: Bruce Cohen, MD; Akron Children's Hospital

More Information

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT02352896
• Other Study ID Numbers: EPI743-13-023
• First Posted: February 2, 2015
• Last Update Posted: March 1, 2023
• Last Verified: February 2023

Keywords provided by PTC Therapeutics:

Leigh syndrome; Mitochondrial disorders; EPI743; Vincerinone

Additional relevant MeSH terms:

Leigh Disease; Syndrome; Disease; Pathologic Processes; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Pyruvate Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Metabolic Diseases; Mitochondrial Diseases