<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/NCT03249194</url>
  </required_header>
  <id_info>
    <org_study_id>HM20010320</org_study_id>
    <nct_id>NCT03249194</nct_id>
  </id_info>
  <brief_title>Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients</brief_title>
  <official_title>Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients: A Trial of Ultra-short Duration Direct Acting Anti-viral Prophylaxis To Prevent Virus Transmission From Hepatitis C Viremic Donors To Hepatitis C Negative Kidney Transplant Recipients (DAPPER)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Virginia Commonwealth University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The development of direct acting anti-virals (DAAs) for the treatment of Hepatitis C virus&#xD;
      (HCV) has changed the landscape of HCV therapy dramatically in the last several years with&#xD;
      reported sustained virologic response (SVR) rates in excess of 95% for treatment-naïve HCV&#xD;
      positive patients including those who have received liver or kidney transplants. Since these&#xD;
      new regimens do not include interferon and have already been studied in the post-liver and&#xD;
      kidney transplant setting, they now offer a unique opportunity to expand the donor pool and&#xD;
      improve the lives of those awaiting renal transplant. The address this gap in knowledge, the&#xD;
      investigators hypothesize that pre-emptive treatment with a direct acting anti-viral HCV&#xD;
      medication to cure HCV soon after transplant would allow for safe transplantation of HCV&#xD;
      positive kidneys in disadvantaged and needy HCV negative kidney recipients with acceptable&#xD;
      risks and improved survivals compared with historical cohorts.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Traditionally, HCV+ kidneys are not offered to HCV- patients on the waiting list. The primary&#xD;
      concern with offering HCV+ kidneys to HCV- recipients is a risk of viral transmission.&#xD;
      Although data about the long-term impact of HCV+ kidney transplantation in to HCV- recipients&#xD;
      is unclear, there was a clear suggestion of an increased risk of liver disease in these&#xD;
      patients based upon studies performed in the 1990s. Traditional therapy with Interferon could&#xD;
      not be offered to these patients as it can lead of rejection if kidney transplant. It was&#xD;
      recently reported that nearly 65% (out of a total 6546) of all HCV+ kidneys were discarded&#xD;
      between the years 2005-2014. These kidneys were otherwise of excellent quality and could have&#xD;
      benefitted more than 4000 patients with 12,000 plus years of graft life.&#xD;
&#xD;
      Since the recent FDA approval of Direct Acting Anti-virals (DAA), these drugs have now been&#xD;
      shown to be safe and efficacious even in the setting of kidney transplant. They could offer a&#xD;
      unique opportunity to expand the kidney donor pool. For this study, the investigators&#xD;
      hypothesize that pre-emptive treatment with a direct acting anti-viral HCV medication to cure&#xD;
      HCV soon after transplant would allow for safe transplantation of HCV+ kidneys in&#xD;
      disadvantaged and needy HCV- kidney recipients with acceptable risks and improved survivals&#xD;
      compared with historical cohorts. This novel study will develop pilot data on the safety and&#xD;
      efficacy of utilizing HCV+ kidneys in high-risk HCV- recipients in order to expand the donor&#xD;
      pool and reduce the morbidity and mortality of hemodialysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 17, 2017</start_date>
  <completion_date type="Actual">March 15, 2020</completion_date>
  <primary_completion_date type="Actual">March 15, 2020</primary_completion_date>
  <phase>Early Phase 1</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>Sustained Virologic Response (SVR)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Among the patients who develop HCV viremia SVR rates with DAA will be measured</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Graft and Patient Survival</measure>
    <time_frame>1 year</time_frame>
    <description>Age and co-morbidity will matched historical HCV- recipients as controls. Patient survival will also be compared to a contemporary cohort of wait listed patients who declined enrollment due to personal choice</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sustained Virologic Response (SVR) Follow Up 1</measure>
    <time_frame>24 weeks</time_frame>
    <description>Among the patients who develop HCV viremia SVR rates with DAA will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sustained Virologic Response (SVR) Follow Up 2</measure>
    <time_frame>48 weeks</time_frame>
    <description>Among the patients who develop HCV viremia SVR rates with DAA will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver Disease</measure>
    <time_frame>1 year</time_frame>
    <description>Among patients who develop HCV viremia liver disease progression will be measured using non-invasive panels like fibroscan</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Kidney Transplant</condition>
  <condition>Hepatitis C</condition>
  <arm_group>
    <arm_group_label>HCV+ Donor Kidney Recipient</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All HCV- participants who receive an HCV+ donor kidney transplant will receive a first 'on-call' dose of Epclusa (sofosbuvir/velpatasvir; Gilead) and then three more doses on post-operative Day 1, 2 and 3. Donor HCV Genotype data will be available by Day 7 of transplant.&#xD;
Patients will then be followed by serial HCV PCRs. Patients who are HCV PCR positive by Day 14 will be treated with Epclusa once daily x 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Direct acting Anti-Viral Therapy using Epclusa or Zepatier</intervention_name>
    <description>All patients will receive one 'on-call' dose of SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) immediately prior to transplant and one dose on post-operative Day 1 post-transplant. Patients who develop detectable HCV viremia will be initiated on Direct Acting Anti-viral (DAA) therapy between 2-4 weeks post-transplant. Patients with GT1 will be treated with ELBASVIR/GRAZOPREVIR (Zepatier, Merck) and those with GT2 or 3 will be treated with SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) based upon donor genotyping results</description>
    <arm_group_label>HCV+ Donor Kidney Recipient</arm_group_label>
    <other_name>Epclusa, Zepatier</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  No evidence of HCV infection by HCV PCR (done at the time of the initial consent)&#xD;
&#xD;
          -  Age&gt;60 yrs with an expected waiting time&gt;2 years; or&#xD;
&#xD;
          -  Age&lt;60 yrs with any one of the following risk factors: Diabetes, coronary artery&#xD;
             disease, peripheral artery disease and/or cerebrovascular disease&#xD;
&#xD;
          -  Willingness to provide informed consent&#xD;
&#xD;
          -  Absence of a living donor.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Estimated life expectancy of less than one year based on clinical judgment of the&#xD;
             investigator&#xD;
&#xD;
          -  Prior liver or renal transplantation&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Incarcerated patients&#xD;
&#xD;
          -  Medical or social condition which in the opinion of the investigator will interfere&#xD;
             with or prevent follow-up per protocol&#xD;
&#xD;
          -  Unable or unwilling to return for follow-up visits&#xD;
&#xD;
        Donor Exclusion Criteria:&#xD;
&#xD;
          -  HBV sAg positive&#xD;
&#xD;
          -  HIV PCR or antibody positive&#xD;
&#xD;
          -  HCV RNA negative&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gaurav Gupta, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Virginia Commonwealth University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</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>August 9, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>March 26, 2020</last_update_submitted>
  <last_update_submitted_qc>March 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 27, 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>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-velpatasvir drug combination</mesh_term>
    <mesh_term>Elbasvir-grazoprevir drug combination</mesh_term>
    <mesh_term>Antiviral Agents</mesh_term>
  </intervention_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/NCT03249194
org study id: HM20010320
nct id: NCT03249194
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The development of direct acting anti-virals (DAAs) for the treatment of Hepatitis C virus
      (HCV) has changed the landscape of HCV therapy dramatically in the last several years with
      reported sustained virologic response (SVR) rates in excess of 95% for treatment-naïve HCV
      positive patients including those who have received liver or kidney transplants. Since these
      new regimens do not include interferon and have already been studied in the post-liver and
      kidney transplant setting, they now offer a unique opportunity to expand the donor pool and
      improve the lives of those awaiting renal transplant. The address this gap in knowledge, the
      investigators hypothesize that pre-emptive treatment with a direct acting anti-viral HCV
      medication to cure HCV soon after transplant would allow for safe transplantation of HCV
      positive kidneys in disadvantaged and needy HCV negative kidney recipients with acceptable
      risks and improved survivals compared with historical cohorts.
Traditionally, HCV+ kidneys are not offered to HCV- patients on the waiting list. The primary
      concern with offering HCV+ kidneys to HCV- recipients is a risk of viral transmission.
      Although data about the long-term impact of HCV+ kidney transplantation in to HCV- recipients
      is unclear, there was a clear suggestion of an increased risk of liver disease in these
      patients based upon studies performed in the 1990s. Traditional therapy with Interferon could
      not be offered to these patients as it can lead of rejection if kidney transplant. It was
      recently reported that nearly 65% (out of a total 6546) of all HCV+ kidneys were discarded
      between the years 2005-2014. These kidneys were otherwise of excellent quality and could have
      benefitted more than 4000 patients with 12,000 plus years of graft life.

      Since the recent FDA approval of Direct Acting Anti-virals (DAA), these drugs have now been
      shown to be safe and efficacious even in the setting of kidney transplant. They could offer a
      unique opportunity to expand the kidney donor pool. For this study, the investigators
      hypothesize that pre-emptive treatment with a direct acting anti-viral HCV medication to cure
      HCV soon after transplant would allow for safe transplantation of HCV+ kidneys in
      disadvantaged and needy HCV- kidney recipients with acceptable risks and improved survivals
      compared with historical cohorts. This novel study will develop pilot data on the safety and
      efficacy of utilizing HCV+ kidneys in high-risk HCV- recipients in order to expand the donor
      pool and reduce the morbidity and mortality of hemodialysis.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Sustained Virologic Response (SVR)
time frame: 12 weeks
description: Among the patients who develop HCV viremia SVR rates with DAA will be measured
measure: Graft and Patient Survival
time frame: 1 year
description: Age and co-morbidity will matched historical HCV- recipients as controls. Patient survival will also be compared to a contemporary cohort of wait listed patients who declined enrollment due to personal choice
measure: Sustained Virologic Response (SVR) Follow Up 1
time frame: 24 weeks
description: Among the patients who develop HCV viremia SVR rates with DAA will be measured
measure: Sustained Virologic Response (SVR) Follow Up 2
time frame: 48 weeks
description: Among the patients who develop HCV viremia SVR rates with DAA will be measured
measure: Liver Disease
time frame: 1 year
description: Among patients who develop HCV viremia liver disease progression will be measured using non-invasive panels like fibroscan
arm group label: HCV+ Donor Kidney Recipient
arm group type: Experimental
description: All HCV- participants who receive an HCV+ donor kidney transplant will receive a first 'on-call' dose of Epclusa (sofosbuvir/velpatasvir; Gilead) and then three more doses on post-operative Day 1, 2 and 3. Donor HCV Genotype data will be available by Day 7 of transplant.
Patients will then be followed by serial HCV PCRs. Patients who are HCV PCR positive by Day 14 will be treated with Epclusa once daily x 12 weeks.
intervention type: Drug
intervention name: Direct acting Anti-Viral Therapy using Epclusa or Zepatier
description: All patients will receive one 'on-call' dose of SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) immediately prior to transplant and one dose on post-operative Day 1 post-transplant. Patients who develop detectable HCV viremia will be initiated on Direct Acting Anti-viral (DAA) therapy between 2-4 weeks post-transplant. Patients with GT1 will be treated with ELBASVIR/GRAZOPREVIR (Zepatier, Merck) and those with GT2 or 3 will be treated with SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) based upon donor genotyping results
arm group label: HCV+ Donor Kidney Recipient
other name: Epclusa, Zepatier
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Gaurav Gupta, MD
role: Principal Investigator
affiliation: Virginia Commonwealth University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis
mesh term: Sofosbuvir-velpatasvir drug combination
mesh term: Elbasvir-grazoprevir drug combination
mesh term: Antiviral Agents