An Exploratory Open Label Study of EPI-743 (Vincerinone TM) in Children With Autism Spectrum Disorder

Study Overview
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Brief Summary
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The investigators hypothesize that EPI-743 may provide clinical benefit to children with Autism Spectrum Disorder.

Detailed Description
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An Exploratory Open Label Phase 2 Study of EPI-743 (Vincerinone TM) in Children with Autism Spectrum Disorder

Official Title
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An Exploratory Open-Label Phase 2 Study of EPI-743 (Vincerinone TM) in Children With Autism Spectrum Disorder

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: EPI-743


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Autism Spectrum Disorder as defined by the DSM-V criteria for ASD and a gold-standard diagnostic evaluation for ASD such as the Autism Diagnostic Observation Schedule (ADOS) and/or the Autism Diagnostic Interview - Revised (ADI-R) Male or female, 3 years to 14 years of age Abnormal glutathione cycle biomarkers (GSH/GSSG in plasma<8.0) Language impairment (as defined by the CELF-2 or CELF-4 screener) Ability to complete language assessment (using either CELF or PLS) Subject or subject's guardian able to consent and comply with protocol requirements Abstention from use of Coenzyme Q10, vitamin E, lipoic acid, folinic acid, other forms of folic acid above recommended daily allowance (RDA), and idebenone 2 months prior to treatment with EPI-743 and for duration of study Stable regimen of medication and supplements for 2 months prior to enrollment and duration of the study Exclusion Criteria: Allergy to EPI-743 or sesame oil Allergy to vitamin E Clinical history of bleeding or abnormal baseline PT/PTT Use of anticoagulant medications Participation in any other interventional study within 90 days of treatment. Use of antipsychotic medications Moderate to severe positive response on ABC irritability subscale on questions: Injures self on purpose, is aggressive to other children or adults (verbally or physically), deliberately hurts himself/ herself, and/or does physical violence to self Severe impairment as defined as a Vineland Adaptive Behavioral Scales composite standard score of <40 Patients with genetic disease that gives rise to ASD (e.g. Rett syndrome, Down syndrome, fragile x syndrome) Abnormal liver function tests two times the upper limit of normal or renal insufficiency with creatinine levels two times the upper limit of normal

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EPI-743<br>15 mg/kg oral solution three times per day, maximum of 200 mg per dose | Drug: EPI-743<br> <br> * Other names: Vincerinone TM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy | Change in plasma levels of reduced and oxidized glutathione from baseline to six months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint | Change in language skills as assessed by change from baseline to six months on the Clinical Evaluation of Language Fundamentals or Preschool Language Scale | 6 months | 
| Secondary Endpoint | Change from baseline to six months in adaptive behavior and social skills as assessed by the Vineland Adaptive Behavior Scale-Second Edition (VABS), Social Responsiveness Scale (SRS), and computerized eye movement analysis | 6 months | 
| Secondary Endpoint | Change from baseline to six months in stereotyped behavior and associated ASD symptoms as assessed by Aberrant Behavior Checklist (ABC), The Ohio Autism Clinical Impression Scale (OACIS), Repetitive Behavior Scale - Revised (RBS-R) and Autism symptoms questionnaire (ASQ) | 6 months | 
| Secondary Endpoint | Change from baseline to six months in gastrointestinal function as assessed by Symptom Diary (stool frequency, abdominal symptoms and medications) and six-item GI severity index (6-GSI). | 6 months | 
| Secondary Endpoint | Change from baseline to six months in caregiver strain experienced by parents of children with emotional and behavioral disorders as assessed by Caregiver Strain Questionnaire (CGSQ) | 6 months | 
| Secondary Endpoint | Change from baseline to six months in intellectual function, attention and memory as assessed by Leiter-R test | 6 months | 
| Secondary Endpoint | Change from baseline to six months in biomarkers of oxidative stress | 6 months | 
| Secondary Endpoint | Pharmacokinetic Assessment of EPI-743 including maximal plasma concentration (Cmax), area under plasma concentration curve (AUC), apparent oral clearance, apparent volume of distribution and time to peak concentration | 6 months | 
| Safety Endpoint | To examine the safety of EPI-743 in subjects with Autism Spectrum Disorder by examining drug-related adverse and serious adverse events | 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism, Mitochondrial Disorders, EPI-743, EPI743, Rett syndrome, Angelman syndrome