<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/NCT01721733</url>
  </required_header>
  <id_info>
    <org_study_id>EPI743-12-002</org_study_id>
    <nct_id>NCT01721733</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome</brief_title>
  <official_title>A Phase 2B Randomized, Placebo Controlled, Double Blind Clinical Trial of EPI-743 in Children With Leigh Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PTC Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Axio Research. LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>PTC Therapeutics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effects of EPI-743 in children with Leigh&#xD;
      syndrome on disease severity, neuromuscular function, respiratory function, disease morbidity&#xD;
      and mortality and disease associated biomarkers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to evaluate the effects of EPI-743 in patient with Leigh&#xD;
      syndrome on disease severity, neuromuscular function, respiratory function, disease morbidity&#xD;
      and mortality and biomarkers associated with the disease.&#xD;
&#xD;
      This study is a six month prospective randomized double-blind, placebo-controlled trial with&#xD;
      a six month extension phase of two dose levels of EPI743. The planned enrollment is for&#xD;
      approximately 30 children with genetically confirmed Leigh syndrome. After 6 months of&#xD;
      treatment, those children that were randomized to the placebo treatment arm will be&#xD;
      re-randomized to one of the 2 active treatment arms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 31, 2012</start_date>
  <completion_date type="Actual">May 31, 2015</completion_date>
  <primary_completion_date type="Actual">February 28, 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) Sections 1-3</measure>
    <time_frame>6 months</time_frame>
    <description>Change from baseline to six months will be compared between subjects in active treatment group and placebo group</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neuromuscular function</measure>
    <time_frame>6 months</time_frame>
    <description>Gross Motor Function Measure; Barry Albright Dystonia Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory function</measure>
    <time_frame>6 months</time_frame>
    <description>Need for tracheostomy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease morbidity</measure>
    <time_frame>6 months</time_frame>
    <description>Total number of hospitalizations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glutathione cycle biomarkers</measure>
    <time_frame>6 months</time_frame>
    <description>Blood levels of glutathione will be compared between placebo and treatment group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of dose limiting serious adverse events</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>6 months</time_frame>
    <description>Number of deaths</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Leigh Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each patient will receive a volume of placebo based on weight</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EPI-743 15 mg/kg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EPI-743 5 mg/kg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EPI-743 15 mg/kg</intervention_name>
    <arm_group_label>EPI-743 15 mg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EPI-743 5 mg/kg</intervention_name>
    <arm_group_label>EPI-743 5 mg/kg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical and MRI diagnosis of Leigh syndrome&#xD;
&#xD;
          -  Moderate disease severity based on NPMDS score&#xD;
&#xD;
          -  Age under 18 years&#xD;
&#xD;
          -  Documented evidence of disease progression within 12 month of enrollment&#xD;
&#xD;
          -  Availability of MRI that confirms necrotizing encephalopathy&#xD;
&#xD;
          -  Patient or guardian able to consent and comply with protocol requirements&#xD;
&#xD;
          -  Abstention from Coenzyme Q10, Vitamins C &amp; E, lipoic acid and Idebenone&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to EPI-743, Vitamin E or sesame oil&#xD;
&#xD;
          -  History of bleeding abnormalities or abnormal PT/PTT&#xD;
&#xD;
          -  Diagnosis of concurrent inborn error of metabolism&#xD;
&#xD;
          -  Previous tracheostomy&#xD;
&#xD;
          -  Ventilator dependent or use of noninvasive ventilatory support w/in 1 month of&#xD;
             enrollment&#xD;
&#xD;
          -  LFTs greater than 2 times ULN&#xD;
&#xD;
          -  Renal insufficiency&#xD;
&#xD;
          -  End stage cardiac failure&#xD;
&#xD;
          -  Fat malabsorption syndrome&#xD;
&#xD;
          -  Use of anticoagulant medications&#xD;
&#xD;
          -  Abstention from Botox for 6 months prior to enrollment and for duration of study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akron Children's Hospital</name>
      <address>
        <city>Akron</city>
        <state>Ohio</state>
        <zip>44308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.edisonpharma.com</url>
    <description>Edison Pharmaceuticals Web Site</description>
  </link>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>November 1, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <disposition_first_submitted>August 17, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>August 24, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">August 31, 2020</disposition_first_posted>
  <last_update_submitted>August 24, 2020</last_update_submitted>
  <last_update_submitted_qc>August 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EPI743</keyword>
  <keyword>Leigh syndrome</keyword>
  <keyword>respiratory chain disease</keyword>
  <keyword>mitochondrial disorders</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leigh Disease</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ubiquinone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT01721733
org study id: EPI743-12-002
nct id: NCT01721733
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate the effects of EPI-743 in children with Leigh
      syndrome on disease severity, neuromuscular function, respiratory function, disease morbidity
      and mortality and disease associated biomarkers.
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) Sections 1-3
time frame: 6 months
description: Change from baseline to six months will be compared between subjects in active treatment group and placebo group
measure: Neuromuscular function
time frame: 6 months
description: Gross Motor Function Measure; Barry Albright Dystonia Scale
measure: Respiratory function
time frame: 6 months
description: Need for tracheostomy
measure: Disease morbidity
time frame: 6 months
description: Total number of hospitalizations
measure: Glutathione cycle biomarkers
time frame: 6 months
description: Blood levels of glutathione will be compared between placebo and treatment group
measure: Number of dose limiting serious adverse events
time frame: 6 months
measure: Mortality
time frame: 6 months
description: Number of deaths
arm group label: Placebo
arm group type: Placebo Comparator
description: Each patient will receive a volume of placebo based on weight
arm group label: EPI-743 15 mg/kg
arm group type: Active Comparator
description: 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.
arm group label: EPI-743 5 mg/kg
arm group type: Active Comparator
description: 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.
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Drug
intervention name: EPI-743 15 mg/kg
arm group label: EPI-743 15 mg/kg
intervention type: Drug
intervention name: EPI-743 5 mg/kg
arm group label: EPI-743 5 mg/kg
criteria: 
gender: All
minimum age: 6 Years
maximum age: 17 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.edisonpharma.com
description: Edison Pharmaceuticals Web Site
responsible party type: Sponsor
mesh term: Leigh Disease
mesh term: Syndrome
mesh term: Ubiquinone
sharing ipd: Undecided