<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/NCT03819322</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY19100082</org_study_id>
    <nct_id>NCT03819322</nct_id>
  </id_info>
  <brief_title>The Use of Hepatitis C Positive Livers in Hepatitis C Negative Liver Transplant Recipients</brief_title>
  <official_title>Transplantation of Livers of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa®)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Naudia Jonassaint. MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Pittsburgh Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, pilot trial to test the safety and efficacy of transplantation of&#xD;
      livers from Hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic&#xD;
      (HCV Ab+/NAT+) donors to HCV seronegative recipients on the liver transplant waitlist.&#xD;
      Treatment and prophylaxis will be administered, using a transmission-triggered approach for&#xD;
      the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later&#xD;
      scenario (HCV Ab+/NAT+ donors, arm 2).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, single center, pilot, open-label study of transplantation of livers of&#xD;
      HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir&#xD;
      (Epclusa®). Recipients of a liver from HCVAb+/NAT- donors will be in arm 1 (the&#xD;
      transmission-triggered arm) of the study. In this arm, the study will monitor transmission of&#xD;
      HCV by measuring HCV RNA in liver transplant recipients. If HCV RNA is detected, indicating&#xD;
      transmission of HCV, recipients will be treated with sofosbuvir/velpatasvir (Epclusa®) for 12&#xD;
      weeks. Virological response will be assessed at 4 weeks, end of treatment and 12 weeks after&#xD;
      completion of therapy.&#xD;
&#xD;
      Recipients of a liver from HCVAb+/NAT+ donors will be in arm 2 (the prophylaxis arm) of the&#xD;
      study. In this arm, patients will be started on a 12-week course of sofosbuvir/velpatasvir&#xD;
      (Epclusa®) immediately post-operatively and will undergo close monitoring of HCV RNA for&#xD;
      evidence of transmission.&#xD;
&#xD;
      To be eligible for the study, subjects need to be listed for liver transplantation, be not&#xD;
      infected with HCV, HBV or HIV, and sign informed consent.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 15, 2019</start_date>
  <completion_date type="Anticipated">May 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events</measure>
    <time_frame>5 years</time_frame>
    <description>Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in study participants in each experimental group</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HCV free at 1 year</measure>
    <time_frame>1 year</time_frame>
    <description>Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients</measure>
    <time_frame>5 years</time_frame>
    <description>Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of allograft rejection</measure>
    <time_frame>5 years</time_frame>
    <description>Incidence of allograft rejection at 5 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of graft loss</measure>
    <time_frame>5 years</time_frame>
    <description>Incidence of graft loss at 5 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>5 years</time_frame>
    <description>All-cause mortality at 5 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Waitlist time after enrollment</measure>
    <time_frame>5 years</time_frame>
    <description>Waitlist time after enrollment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">73</enrollment>
  <condition>Liver Transplant</condition>
  <condition>Hepatitis C</condition>
  <arm_group>
    <arm_group_label>HCV seropositive non-viremic (HCV Ab+/NAT-) donor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Liver recipients will be monitored for HCV for one year following transplant. When HCV RNA is detected, the transmission-triggered treatment phase will be initiated.&#xD;
Recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCV seropositive viremic (HCV Ab+/NAT+) donor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Post-operative day 1, liver recipients will be treated with 12-week oral course of sofosbuvir/ velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sofosbuvir/velpatasvir</intervention_name>
    <description>12 week, oral, fixed dose</description>
    <arm_group_label>HCV seropositive non-viremic (HCV Ab+/NAT-) donor</arm_group_label>
    <arm_group_label>HCV seropositive viremic (HCV Ab+/NAT+) donor</arm_group_label>
    <other_name>Epclusa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria (recipients):&#xD;
&#xD;
          1. Patients with end-stage liver disease listed for liver transplantation at UPMC.&#xD;
&#xD;
          2. Age ≥ 18&#xD;
&#xD;
          3. No available living liver donor&#xD;
&#xD;
          4. Listed for an isolated liver transplant at UPMC&#xD;
&#xD;
          5. Have panel reactive antibody level of &lt;98%&#xD;
&#xD;
          6. Able to travel to UPMC for routine post-transplant visits and study visits for a&#xD;
             minimum of 12 months after transplantation&#xD;
&#xD;
          7. Able to provide informed consent&#xD;
&#xD;
          8. Be willing to use a contraceptive method for a year after transplant&#xD;
&#xD;
        Exclusion criteria (recipients):&#xD;
&#xD;
          1. HIV positive&#xD;
&#xD;
          2. HCVAb or HCV RNA positive&#xD;
&#xD;
          3. Presence of behavioral risk factors for contracting HCV. These behavioral risk factors&#xD;
             are current injection drug use, current intranasal illicit drug use, current&#xD;
             percutaneous/parenteral exposures in an unregulated setting.&#xD;
&#xD;
          4. Hepatitis B surface antigen positive&#xD;
&#xD;
          5. History of atrial fibrillation requiring the use of amiodarone over the past 12m&#xD;
&#xD;
          6. Receipt of prior organ transplant&#xD;
&#xD;
          7. Waitlisted for a multi-organ transplant&#xD;
&#xD;
          8. Pregnant women&#xD;
&#xD;
          9. Known allergy to sofosbuvir/velpatasvir&#xD;
&#xD;
         10. Any condition, psychiatric or physical, that in the opinion of the investigator would&#xD;
             make it unsafe to proceed with transplantation or interfere with the ability of the&#xD;
             subject to participate in the study&#xD;
&#xD;
        Inclusion criteria (donors):&#xD;
&#xD;
          1. HCV antibody positive&#xD;
&#xD;
          2. HCV NAT negative or positive&#xD;
&#xD;
        Exclusion criteria (donors):&#xD;
&#xD;
          1. Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24&#xD;
             antigen and/or positive HIV NAT)&#xD;
&#xD;
          2. Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT)&#xD;
&#xD;
          3. Known ongoing therapy for HCV&#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>Fernanda Silviera, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Naudia Jonassaint, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>October 6, 2022</last_update_submitted>
  <last_update_submitted_qc>October 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Naudia Jonassaint. MD</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine and Surgery</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sofosbuvir</mesh_term>
    <mesh_term>Sofosbuvir-velpatasvir drug combination</mesh_term>
    <mesh_term>Velpatasvir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>We do not plan to share individual patient data outside of our investigative team. Aggregate data will be shared in publications as appropriate.</ipd_description>
  </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/NCT03819322
org study id: STUDY19100082
nct id: NCT03819322
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is an open-label, pilot trial to test the safety and efficacy of transplantation of
      livers from Hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic
      (HCV Ab+/NAT+) donors to HCV seronegative recipients on the liver transplant waitlist.
      Treatment and prophylaxis will be administered, using a transmission-triggered approach for
      the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later
      scenario (HCV Ab+/NAT+ donors, arm 2).
This is a prospective, single center, pilot, open-label study of transplantation of livers of
      HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir
      (Epclusa®). Recipients of a liver from HCVAb+/NAT- donors will be in arm 1 (the
      transmission-triggered arm) of the study. In this arm, the study will monitor transmission of
      HCV by measuring HCV RNA in liver transplant recipients. If HCV RNA is detected, indicating
      transmission of HCV, recipients will be treated with sofosbuvir/velpatasvir (Epclusa®) for 12
      weeks. Virological response will be assessed at 4 weeks, end of treatment and 12 weeks after
      completion of therapy.

      Recipients of a liver from HCVAb+/NAT+ donors will be in arm 2 (the prophylaxis arm) of the
      study. In this arm, patients will be started on a 12-week course of sofosbuvir/velpatasvir
      (Epclusa®) immediately post-operatively and will undergo close monitoring of HCV RNA for
      evidence of transmission.

      To be eligible for the study, subjects need to be listed for liver transplantation, be not
      infected with HCV, HBV or HIV, and sign informed consent.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse events
time frame: 5 years
description: Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in study participants in each experimental group
measure: HCV free at 1 year
time frame: 1 year
description: Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation
measure: Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients
time frame: 5 years
description: Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients
measure: Incidence of allograft rejection
time frame: 5 years
description: Incidence of allograft rejection at 5 years
measure: Incidence of graft loss
time frame: 5 years
description: Incidence of graft loss at 5 years
measure: All-cause mortality
time frame: 5 years
description: All-cause mortality at 5 years
measure: Waitlist time after enrollment
time frame: 5 years
description: Waitlist time after enrollment
arm group label: HCV seropositive non-viremic (HCV Ab+/NAT-) donor
arm group type: Experimental
description: Liver recipients will be monitored for HCV for one year following transplant. When HCV RNA is detected, the transmission-triggered treatment phase will be initiated.
Recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).
arm group label: HCV seropositive viremic (HCV Ab+/NAT+) donor
arm group type: Experimental
description: Post-operative day 1, liver recipients will be treated with 12-week oral course of sofosbuvir/ velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).
intervention type: Drug
intervention name: sofosbuvir/velpatasvir
description: 12 week, oral, fixed dose
arm group label: HCV seropositive non-viremic (HCV Ab+/NAT-) donor
arm group label: HCV seropositive viremic (HCV Ab+/NAT+) donor
other name: Epclusa
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Fernanda Silviera, MD
role: Study Director
affiliation: University of Pittsburgh
last name: Naudia Jonassaint, MD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Naudia Jonassaint. MD
investigator title: Assistant Professor of Medicine and Surgery
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis
mesh term: Sofosbuvir
mesh term: Sofosbuvir-velpatasvir drug combination
mesh term: Velpatasvir
sharing ipd: No
ipd description: We do not plan to share individual patient data outside of our investigative team. Aggregate data will be shared in publications as appropriate.