Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome

• ClinicalTrials.gov Identifier: NCT01721733
• Recruitment Status: Completed
• First Posted: November 6, 2012
• Last Update Posted: August 31, 2020
• Sponsor: PTC Therapeutics
• Collaborator: Axio Research. LLC
• Information provided by (Responsible Party): PTC Therapeutics

Study Description

Brief Summary:

The purpose of this study is to evaluate the effects of EPI-743 in children with Leigh syndrome on disease severity, neuromuscular function, respiratory function, disease morbidity and mortality and disease associated biomarkers.

Condition or disease	Intervention/treatment	Phase
Leigh Syndrome	Drug: Placebo; Drug: EPI-743 15 mg/kg; Drug: EPI-743 5 mg/kg	Phase 2

Detailed Description:

The purpose of this study is to evaluate the effects of EPI-743 in patient with Leigh syndrome on disease severity, neuromuscular function, respiratory function, disease morbidity and mortality and biomarkers associated with the disease.

This study is a six month prospective randomized double-blind, placebo-controlled trial with a six month extension phase of two dose levels of EPI743. The planned enrollment is for approximately 30 children with genetically confirmed Leigh syndrome. After 6 months of treatment, those children that were randomized to the placebo treatment arm will be re-randomized to one of the 2 active treatment arms.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2B Randomized, Placebo Controlled, Double Blind Clinical Trial of EPI-743 in Children With Leigh Syndrome
• Actual Study Start Date: October 31, 2012
• Actual Primary Completion Date: February 28, 2015
• Actual Study Completion Date: May 31, 2015

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Each patient will receive a volume of placebo based on weight	Drug: Placebo
Active Comparator: EPI-743 15 mg/kg; Each subjects dose will be based on their weight. 15 mg/kg with a maximum dose of 200 mg per dose, t.i.d., will be administered in this treatment arm.	Drug: EPI-743 15 mg/kg
Active Comparator: EPI-743 5 mg/kg; Each subjects dose will be based on their weight. 5 mg/kg with a maximum dose of 100 mg per dose, t.i.d., will be administered in this treatment arm.	Drug: EPI-743 5 mg/kg

Outcome Measures

Primary Outcome Measures :

1. Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) Sections 1-3 [ Time Frame: 6 months ]
   Change from baseline to six months will be compared between subjects in active treatment group and placebo group

Secondary Outcome Measures :

1. Neuromuscular function [ Time Frame: 6 months ]
   Gross Motor Function Measure; Barry Albright Dystonia Scale
2. Respiratory function [ Time Frame: 6 months ]
   Need for tracheostomy
3. Disease morbidity [ Time Frame: 6 months ]
   Total number of hospitalizations
4. Glutathione cycle biomarkers [ Time Frame: 6 months ]
   Blood levels of glutathione will be compared between placebo and treatment group
5. Number of dose limiting serious adverse events [ Time Frame: 6 months ]
6. Mortality [ Time Frame: 6 months ]
   Number of deaths

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Clinical and MRI diagnosis of Leigh syndrome
• Moderate disease severity based on NPMDS score
• Age under 18 years
• Documented evidence of disease progression within 12 month of enrollment
• Availability of MRI that confirms necrotizing encephalopathy
• Patient or guardian able to consent and comply with protocol requirements
• Abstention from Coenzyme Q10, Vitamins C & E, lipoic acid and Idebenone

Exclusion Criteria:

• Allergy to EPI-743, Vitamin E or sesame oil
• History of bleeding abnormalities or abnormal PT/PTT
• Diagnosis of concurrent inborn error of metabolism
• Previous tracheostomy
• Ventilator dependent or use of noninvasive ventilatory support w/in 1 month of enrollment
• LFTs greater than 2 times ULN
• Renal insufficiency
• End stage cardiac failure
• Fat malabsorption syndrome
• Use of anticoagulant medications
• Abstention from Botox for 6 months prior to enrollment and for duration of study

Contacts and Locations

Locations

United States, California

Stanford University

Palo Alto, California, United States, 94304

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

Axio Research. LLC

More Information

Additional Information:

Edison Pharmaceuticals Web Site 

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT01721733
• Other Study ID Numbers: EPI743-12-002
• First Posted: November 6, 2012
• Last Update Posted: August 31, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by PTC Therapeutics:

EPI743; Leigh syndrome; respiratory chain disease; mitochondrial disorders

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; Ubiquinone; Micronutrients; Physiological Effects of Drugs