<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/NCT03809533</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY19100135</org_study_id>
    <nct_id>NCT03809533</nct_id>
  </id_info>
  <brief_title>The Use of Hepatitis C Positive Kidneys in Hepatitis C Negative Kidney Transplant Recipients</brief_title>
  <official_title>Transplantation of Kidneys of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amit D Tevar, 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;
      kidneys from hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic&#xD;
      (HCV Ab+/NAT+) donors to HCV seronegative recipients on the kidney 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 kidneys&#xD;
      of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir&#xD;
      (Epclusa®). Recipients of a kidney from HCVAb+/NAT- donors will be in arm 1 (the&#xD;
      transmission-triggered arm) of the study. In this arm, the study will monitor HCV by&#xD;
      measuring HCV RNA in renal 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 kidney 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 renal 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">May 29, 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 patients 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>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of allograft rejection</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of graft loss</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Waitlist time after enrollment</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Kidney Transplantation</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>Kidney 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>Starting post-operative day 1, kidney 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 renal disease listed for kidney transplantation at UPMC.&#xD;
&#xD;
          2. On chronic hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD)&#xD;
             defined as a glomerular filtration rate &lt; 15 ml/min&#xD;
&#xD;
          3. Age ≥ 18&#xD;
&#xD;
          4. No available living kidney donor&#xD;
&#xD;
          5. Listed for an isolated kidney transplant at UPMC with &lt;60m of accrued transplant&#xD;
             waiting time and/or &lt;60m of dialysis time&#xD;
&#xD;
          6. Have panel reactive antibody level of &lt;98%&#xD;
&#xD;
          7. No obvious contraindication to kidney transplant&#xD;
&#xD;
          8. Able to travel to UPMC for routine post-transplant visits and study visits for a&#xD;
             minimum of 12 months after transplantation&#xD;
&#xD;
          9. Able to provide informed consent&#xD;
&#xD;
         10. 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 other than being on&#xD;
             hemodialysis. These behavioral risk factors are current injection drug use, current&#xD;
             intranasal illicit drug use, current percutaneous/parenteral exposures in an&#xD;
             unregulated setting.&#xD;
&#xD;
          4. Hepatitis B surface antigen positive&#xD;
&#xD;
          5. History of liver cirrhosis&#xD;
&#xD;
          6. Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the&#xD;
             upper limit of normal for a minimum of 3 consecutive months&#xD;
&#xD;
          7. History of atrial fibrillation requiring the use of amiodarone over the past 12m&#xD;
&#xD;
          8. Patients with etiology of renal failure with increased risk of causing early graft&#xD;
             failure as assessed by the investigator team&#xD;
&#xD;
          9. Receipt of prior organ transplant&#xD;
&#xD;
         10. Waitlisted for a multi-organ transplant&#xD;
&#xD;
         11. Pregnant women&#xD;
&#xD;
         12. Known allergy to sofosbuvir/velpatasvir&#xD;
&#xD;
         13. 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;
          3. Kidney donor profile index (KDPI) score &lt;85&#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>Amit Tevar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Fernanda Silviera, MD</last_name>
    <role>Study Director</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>July 2023</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>July 18, 2023</last_update_submitted>
  <last_update_submitted_qc>July 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Amit D Tevar, MD</investigator_full_name>
    <investigator_title>Associate Professor of 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/NCT03809533
org study id: STUDY19100135
nct id: NCT03809533
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
      kidneys from hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic
      (HCV Ab+/NAT+) donors to HCV seronegative recipients on the kidney 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 kidneys
      of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir
      (Epclusa®). Recipients of a kidney from HCVAb+/NAT- donors will be in arm 1 (the
      transmission-triggered arm) of the study. In this arm, the study will monitor HCV by
      measuring HCV RNA in renal 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 kidney 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 renal 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 patients 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
measure: Incidence of allograft rejection
time frame: 5 years
measure: Incidence of graft loss
time frame: 5 years
measure: All-cause mortality
time frame: 5 years
measure: Waitlist time after enrollment
time frame: 5 years
arm group label: HCV seropositive non-viremic (HCV Ab+/NAT-) donor
arm group type: Experimental
description: Kidney 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: Starting post-operative day 1, kidney 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: Amit Tevar, MD
role: Principal Investigator
affiliation: University of Pittsburgh
last name: Fernanda Silviera, MD
role: Study Director
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Amit D Tevar, MD
investigator title: Associate Professor of 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.