<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02226458</url>
  </required_header>
  <id_info>
    <org_study_id>EPI743-14-025</org_study_id>
    <nct_id>NCT02226458</nct_id>
  </id_info>
  <brief_title>An Exploratory Open Label Study of EPI-743 (Vincerinone TM) in Children With Autism Spectrum Disorder</brief_title>
  <acronym>Autism</acronym>
  <official_title>An Exploratory Open-Label Phase 2 Study of EPI-743 (Vincerinone TM) in Children With Autism Spectrum Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Edison Pharmaceuticals Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Edison Pharmaceuticals Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesize that EPI-743 may provide clinical benefit to children with&#xD;
      Autism Spectrum Disorder.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An Exploratory Open Label Phase 2 Study of EPI-743 (Vincerinone TM) in Children with Autism&#xD;
      Spectrum Disorder&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    This study was halted prior to enrolling.&#xD;
  </why_stopped>
  <start_date type="Actual">October 31, 2014</start_date>
  <completion_date type="Anticipated">January 31, 2016</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Efficacy</measure>
    <time_frame>6 months</time_frame>
    <description>Change in plasma levels of reduced and oxidized glutathione from baseline to six months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint</measure>
    <time_frame>6 months</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint</measure>
    <time_frame>6 months</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint</measure>
    <time_frame>6 months</time_frame>
    <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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint</measure>
    <time_frame>6 months</time_frame>
    <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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint</measure>
    <time_frame>6 months</time_frame>
    <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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint</measure>
    <time_frame>6 months</time_frame>
    <description>Change from baseline to six months in intellectual function, attention and memory as assessed by Leiter-R test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint</measure>
    <time_frame>6 months</time_frame>
    <description>Change from baseline to six months in biomarkers of oxidative stress</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Endpoint</measure>
    <time_frame>6 months</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety Endpoint</measure>
    <time_frame>8 months</time_frame>
    <description>To examine the safety of EPI-743 in subjects with Autism Spectrum Disorder by examining drug-related adverse and serious adverse events</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Autism Spectrum Disorder</condition>
  <arm_group>
    <arm_group_label>EPI-743</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>15 mg/kg oral solution three times per day, maximum of 200 mg per dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EPI-743</intervention_name>
    <arm_group_label>EPI-743</arm_group_label>
    <other_name>Vincerinone TM</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of Autism Spectrum Disorder as defined by the DSM-V criteria for ASD and a&#xD;
             gold-standard diagnostic evaluation for ASD such as the Autism Diagnostic Observation&#xD;
             Schedule (ADOS) and/or the Autism Diagnostic Interview - Revised (ADI-R)&#xD;
&#xD;
          2. Male or female, 3 years to 14 years of age&#xD;
&#xD;
          3. Abnormal glutathione cycle biomarkers (GSH/GSSG in plasma&lt;8.0)&#xD;
&#xD;
          4. Language impairment (as defined by the CELF-2 or CELF-4 screener)&#xD;
&#xD;
          5. Ability to complete language assessment (using either CELF or PLS)&#xD;
&#xD;
          6. Subject or subject's guardian able to consent and comply with protocol requirements&#xD;
&#xD;
          7. Abstention from use of Coenzyme Q10, vitamin E, lipoic acid, folinic acid, other forms&#xD;
             of folic acid above recommended daily allowance (RDA), and idebenone 2 months prior to&#xD;
             treatment with EPI-743 and for duration of study&#xD;
&#xD;
          8. Stable regimen of medication and supplements for 2 months prior to enrollment and&#xD;
             duration of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Allergy to EPI-743 or sesame oil&#xD;
&#xD;
          2. Allergy to vitamin E&#xD;
&#xD;
          3. Clinical history of bleeding or abnormal baseline PT/PTT&#xD;
&#xD;
          4. Use of anticoagulant medications&#xD;
&#xD;
          5. Participation in any other interventional study within 90 days of treatment.&#xD;
&#xD;
          6. Use of antipsychotic medications&#xD;
&#xD;
          7. Moderate to severe positive response on ABC irritability subscale on questions:&#xD;
             Injures self on purpose, is aggressive to other children or adults (verbally or&#xD;
             physically), deliberately hurts himself/ herself, and/or does physical violence to&#xD;
             self&#xD;
&#xD;
          8. Severe impairment as defined as a Vineland Adaptive Behavioral Scales composite&#xD;
             standard score of &lt;40&#xD;
&#xD;
          9. Patients with genetic disease that gives rise to ASD (e.g. Rett syndrome, Down&#xD;
             syndrome, fragile x syndrome)&#xD;
&#xD;
         10. Abnormal liver function tests two times the upper limit of normal or renal&#xD;
             insufficiency with creatinine levels two times the upper limit of normal&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>14 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>http://edisonpharma.com/</url>
    <description>Edison Pharmaceuticals Website</description>
  </link>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <last_update_submitted>January 20, 2022</last_update_submitted>
  <last_update_submitted_qc>January 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Autism</keyword>
  <keyword>Mitochondrial Disorders</keyword>
  <keyword>EPI-743</keyword>
  <keyword>EPI743</keyword>
  <keyword>Rett syndrome</keyword>
  <keyword>Angelman syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
    <mesh_term>Child Development Disorders, Pervasive</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02226458
org study id: EPI743-14-025
nct id: NCT02226458
lead sponsor: 
has dmc: No
The investigators hypothesize that EPI-743 may provide clinical benefit to children with
      Autism Spectrum Disorder.
An Exploratory Open Label Phase 2 Study of EPI-743 (Vincerinone TM) in Children with Autism
      Spectrum Disorder
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Primary Efficacy
time frame: 6 months
description: Change in plasma levels of reduced and oxidized glutathione from baseline to six months
measure: Secondary Endpoint
time frame: 6 months
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
measure: Secondary Endpoint
time frame: 6 months
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
measure: Secondary Endpoint
time frame: 6 months
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)
measure: Secondary Endpoint
time frame: 6 months
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).
measure: Secondary Endpoint
time frame: 6 months
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)
measure: Secondary Endpoint
time frame: 6 months
description: Change from baseline to six months in intellectual function, attention and memory as assessed by Leiter-R test
measure: Secondary Endpoint
time frame: 6 months
description: Change from baseline to six months in biomarkers of oxidative stress
measure: Secondary Endpoint
time frame: 6 months
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
measure: Safety Endpoint
time frame: 8 months
description: To examine the safety of EPI-743 in subjects with Autism Spectrum Disorder by examining drug-related adverse and serious adverse events
arm group label: EPI-743
arm group type: Experimental
description: 15 mg/kg oral solution three times per day, maximum of 200 mg per dose
intervention type: Drug
intervention name: EPI-743
arm group label: EPI-743
other name: Vincerinone TM
criteria: 
gender: All
minimum age: 3 Years
maximum age: 14 Years
healthy volunteers: No
country: United States
url: http://edisonpharma.com/
description: Edison Pharmaceuticals Website
responsible party type: Sponsor
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive