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

August 24, 2020 updated by: PTC Therapeutics

A Phase 2B Randomized, Placebo Controlled, Double Blind Clinical Trial of EPI-743 in Children With Leigh Syndrome

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University
    • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
6 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PTC Therapeutics

Collaborators

Axio Research. LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 31, 2012

Primary Completion (Actual)

February 28, 2015

Study Completion (Actual)

May 31, 2015

Study Registration Dates

First Submitted

November 1, 2012

First Submitted That Met QC Criteria

November 5, 2012

First Posted (Estimate)

November 6, 2012

Study Record Updates

Last Update Posted (Actual)

August 31, 2020

Last Update Submitted That Met QC Criteria

August 24, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EPI743-12-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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