- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01721733
Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
A Phase 2B Randomized, Placebo Controlled, Double Blind Clinical Trial of EPI-743 in Children With Leigh Syndrome
Study Overview
Status
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Palo Alto, California, United States, 94304
- Stanford University
-
-
Ohio
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Akron, Ohio, United States, 44308
- Akron Children's Hospital
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Texas
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Houston, Texas, United States, 77030
- Baylor College of Medicine
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Washington
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Seattle, Washington, United States, 98105
- Seattle Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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
|
|
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.
|
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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.
|
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
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6 months
|
Number of dose limiting serious adverse events
Time Frame: 6 months
|
6 months
|
|
Mortality
Time Frame: 6 months
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Number of deaths
|
6 months
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
- Physiological Effects of Drugs
- Micronutrients
- Ubiquinone
Other Study ID Numbers
- EPI743-12-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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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