An Exploratory Open Label Study of EPI-743 (Vincerinone TM) in Children With Autism Spectrum Disorder (Autism)
Primary Purpose
Autism Spectrum Disorder
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
EPI-743
Sponsored by
About this trial
This is an interventional treatment trial for Autism Spectrum Disorder focused on measuring Autism, Mitochondrial Disorders, EPI-743, EPI743, Rett syndrome, Angelman syndrome
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
EPI-743
Arm Description
15 mg/kg oral solution three times per day, maximum of 200 mg per dose
Outcomes
Primary Outcome Measures
Primary Efficacy
Change in plasma levels of reduced and oxidized glutathione from baseline to six months
Secondary Outcome Measures
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
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
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)
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).
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)
Secondary Endpoint
Change from baseline to six months in intellectual function, attention and memory as assessed by Leiter-R test
Secondary Endpoint
Change from baseline to six months in biomarkers of oxidative stress
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
Safety Endpoint
To examine the safety of EPI-743 in subjects with Autism Spectrum Disorder by examining drug-related adverse and serious adverse events
Full Information
NCT ID
NCT02226458
First Posted
August 21, 2014
Last Updated
January 20, 2022
Sponsor
Edison Pharmaceuticals Inc
1. Study Identification
Unique Protocol Identification Number
NCT02226458
Brief Title
An Exploratory Open Label Study of EPI-743 (Vincerinone TM) in Children With Autism Spectrum Disorder
Acronym
Autism
Official Title
An Exploratory Open-Label Phase 2 Study of EPI-743 (Vincerinone TM) in Children With Autism Spectrum Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Withdrawn
Why Stopped
This study was halted prior to enrolling.
Study Start Date
October 31, 2014 (Actual)
Primary Completion Date
November 30, 2015 (Anticipated)
Study Completion Date
January 31, 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Edison Pharmaceuticals Inc
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The investigators hypothesize that EPI-743 may provide clinical benefit to children with Autism Spectrum Disorder.
Detailed Description
An Exploratory Open Label Phase 2 Study of EPI-743 (Vincerinone TM) in Children with Autism Spectrum Disorder
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorder
Keywords
Autism, Mitochondrial Disorders, EPI-743, EPI743, Rett syndrome, Angelman syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EPI-743
Arm Type
Experimental
Arm Description
15 mg/kg oral solution three times per day, maximum of 200 mg per dose
Intervention Type
Drug
Intervention Name(s)
EPI-743
Other Intervention Name(s)
Vincerinone TM
Primary Outcome Measure Information:
Title
Primary Efficacy
Description
Change in plasma levels of reduced and oxidized glutathione from baseline to six months
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Secondary Endpoint
Description
Change in language skills as assessed by change from baseline to six months on the Clinical Evaluation of Language Fundamentals or Preschool Language Scale
Time Frame
6 months
Title
Secondary Endpoint
Description
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
Time Frame
6 months
Title
Secondary Endpoint
Description
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)
Time Frame
6 months
Title
Secondary Endpoint
Description
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).
Time Frame
6 months
Title
Secondary Endpoint
Description
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)
Time Frame
6 months
Title
Secondary Endpoint
Description
Change from baseline to six months in intellectual function, attention and memory as assessed by Leiter-R test
Time Frame
6 months
Title
Secondary Endpoint
Description
Change from baseline to six months in biomarkers of oxidative stress
Time Frame
6 months
Title
Secondary Endpoint
Description
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
Time Frame
6 months
Title
Safety Endpoint
Description
To examine the safety of EPI-743 in subjects with Autism Spectrum Disorder by examining drug-related adverse and serious adverse events
Time Frame
8 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
12. IPD Sharing Statement
Links:
URL
http://edisonpharma.com/
Description
Edison Pharmaceuticals Website
Learn more about this trial
An Exploratory Open Label Study of EPI-743 (Vincerinone TM) in Children With Autism Spectrum Disorder
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