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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: EPI-743

Detailed Description

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

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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)
2. Male or female, 3 years to 14 years of age
3. Abnormal glutathione cycle biomarkers (GSH/GSSG in plasma<8.0)
4. Language impairment (as defined by the CELF-2 or CELF-4 screener)
5. Ability to complete language assessment (using either CELF or PLS)
6. Subject or subject's guardian able to consent and comply with protocol requirements
7. 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
8. Stable regimen of medication and supplements for 2 months prior to enrollment and duration of the study

Exclusion Criteria:

1. Allergy to EPI-743 or sesame oil
2. Allergy to vitamin E
3. Clinical history of bleeding or abnormal baseline PT/PTT
4. Use of anticoagulant medications
5. Participation in any other interventional study within 90 days of treatment.
6. Use of antipsychotic medications
7. 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
8. Severe impairment as defined as a Vineland Adaptive Behavioral Scales composite standard score of <40
9. Patients with genetic disease that gives rise to ASD (e.g. Rett syndrome, Down syndrome, fragile x syndrome)
10. Abnormal liver function tests two times the upper limit of normal or renal insufficiency with creatinine levels two times the upper limit of normal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Edison Pharmaceuticals Inc

Publications and helpful links

Helpful Links

• Edison Pharmaceuticals Website

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2014
• Primary Completion (Anticipated): November 30, 2015
• Study Completion (Anticipated): January 31, 2016

Study Registration Dates

• First Submitted: August 21, 2014
• First Submitted That Met QC Criteria: August 25, 2014
• First Posted (Estimate): August 27, 2014

Study Record Updates

• Last Update Posted (Actual): January 21, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Autism; Rett syndrome; Angelman syndrome; Mitochondrial Disorders; EPI-743; EPI743
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurodevelopmental Disorders; Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: EPI743-14-025