<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/NCT03018678</url>
  </required_header>
  <id_info>
    <org_study_id>822899</org_study_id>
    <nct_id>NCT03018678</nct_id>
  </id_info>
  <brief_title>Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia</brief_title>
  <official_title>Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this protocol is to identify and screen potential candidates for future&#xD;
      enrollment in a gene therapy clinical trial for HoFH.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder&#xD;
      characterized by markedly elevated LDL-cholesterol (LDL-C) levels, resulting in severe&#xD;
      atherosclerosis often leading to early onset of cardiovascular disease. The most frequent&#xD;
      cause is mutation in the LDL receptor gene (LDLR). LDL-C levels remain frequently above&#xD;
      acceptable levels despite treatment with multiple existing lipid lowering drugs and/or LDL&#xD;
      apheresis. Thus, the functional replacement of the defective LDLR via AAV-based&#xD;
      liver-directed gene therapy may be a viable approach to treat this disease and improve&#xD;
      response to current lipid-lowering treatments. The purpose of this protocol is to identify&#xD;
      and screen potential candidates for future enrollment in a gene therapy clinical trial. No&#xD;
      study drug will be administered in this screening study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2016</start_date>
  <completion_date type="Actual">December 3, 2019</completion_date>
  <primary_completion_date type="Actual">May 30, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>genetic analysis</measure>
    <time_frame>Screening phase</time_frame>
    <description>identification of genetic, confirmation of FH</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neutralizing antibodies</measure>
    <time_frame>Screening phase</time_frame>
    <description>identification of subjects with no or minimal neutralizing antibodies titer &lt;= 1:10</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">21</enrollment>
  <condition>Hypercholesterolemia, Familial</condition>
  <arm_group>
    <arm_group_label>Patients with HOFH</arm_group_label>
    <description>No intervention</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Nab titer samples are retained, but there is no potential for DNA extraction.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with clinical diagnosis compatible with homozygous familial hypercholesterolemia&#xD;
        (HoFH)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females ≥ 18 years of age&#xD;
&#xD;
          -  Clinical presentation consistent with homozygous FH&#xD;
&#xD;
          -  Subjects must be able to comprehend and willing to provide a signed IRB approved&#xD;
             Informed Consent Form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known to carry confirmed mutations in genes affecting LDL receptor functionality other&#xD;
             than the LDLR gene&#xD;
&#xD;
          -  History of cirrhosis based on documented histological evaluation or non-invasive&#xD;
             imaging&#xD;
&#xD;
          -  Documented diagnosis of any of the following liver diseases: Hepatitis B or C;&#xD;
             Biopsy-proven nonalcoholic steatohepatitis; Biopsy-proven alcoholic liver disease;&#xD;
             Autoimmune hepatitis; Primary biliary cirrhosis; Primary sclerosing cholangitis;&#xD;
             Wilson's disease; Hemochromatosis; alpha1 anti-trypsin deficiency&#xD;
&#xD;
          -  History of immunodeficiency diseases, including a positive HIV test result&#xD;
&#xD;
          -  Previous organ transplantation&#xD;
&#xD;
          -  Serious or unstable medical or psychological conditions that, in the opinion of the&#xD;
             investigator, would compromise the subject's safety or successful participation in the&#xD;
             study&#xD;
&#xD;
          -  Inability to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marina Cuchel, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>March 4, 2020</last_update_submitted>
  <last_update_submitted_qc>March 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperlipoproteinemia Type II</mesh_term>
    <mesh_term>Homozygous Familial Hypercholesterolemia</mesh_term>
    <mesh_term>Hypercholesterolemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The following entities may use or share information: (1) the investigator for the study and the study team, (2) the University of Pennsylvania Institutional Review Boards (the committees who oversee research on human subjects) and University of Pennsylvania Office of Regulatory Affairs, (3) The University of Pennsylvania Office of Clinical Research (the office which monitors research studies), and (4) authorized members of the University of Pennsylvania and the University of Pennsylvania Health System and School of Medicine workforce who may need to access your information in the performance of their duties (for example: to provide treatment, to ensure integrity of the research, accounting or billing matters, etc).</ipd_description>
    <ipd_time_frame>Has been open until 2015. Data is open until decided.</ipd_time_frame>
    <ipd_access_criteria>Data will be de-identified prior to sharing with other entities.</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT03018678
org study id: 822899
nct id: NCT03018678
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this protocol is to identify and screen potential candidates for future
      enrollment in a gene therapy clinical trial for HoFH.
Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder
      characterized by markedly elevated LDL-cholesterol (LDL-C) levels, resulting in severe
      atherosclerosis often leading to early onset of cardiovascular disease. The most frequent
      cause is mutation in the LDL receptor gene (LDLR). LDL-C levels remain frequently above
      acceptable levels despite treatment with multiple existing lipid lowering drugs and/or LDL
      apheresis. Thus, the functional replacement of the defective LDLR via AAV-based
      liver-directed gene therapy may be a viable approach to treat this disease and improve
      response to current lipid-lowering treatments. The purpose of this protocol is to identify
      and screen potential candidates for future enrollment in a gene therapy clinical trial. No
      study drug will be administered in this screening study.
observational model: Cohort
time perspective: Prospective
measure: genetic analysis
time frame: Screening phase
description: identification of genetic, confirmation of FH
measure: Neutralizing antibodies
time frame: Screening phase
description: identification of subjects with no or minimal neutralizing antibodies titer <= 1:10
arm group label: Patients with HOFH
description: No intervention
Nab titer samples are retained, but there is no potential for DNA extraction.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marina Cuchel, MD, PhD
role: Principal Investigator
affiliation: Associate Professor
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hyperlipoproteinemia Type II
mesh term: Homozygous Familial Hypercholesterolemia
mesh term: Hypercholesterolemia
sharing ipd: Yes
ipd description: The following entities may use or share information: (1) the investigator for the study and the study team, (2) the University of Pennsylvania Institutional Review Boards (the committees who oversee research on human subjects) and University of Pennsylvania Office of Regulatory Affairs, (3) The University of Pennsylvania Office of Clinical Research (the office which monitors research studies), and (4) authorized members of the University of Pennsylvania and the University of Pennsylvania Health System and School of Medicine workforce who may need to access your information in the performance of their duties (for example: to provide treatment, to ensure integrity of the research, accounting or billing matters, etc).
ipd time frame: Has been open until 2015. Data is open until decided.
ipd access criteria: Data will be de-identified prior to sharing with other entities.