<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/NCT03284242</url>
  </required_header>
  <id_info>
    <org_study_id>16-0779-F6A</org_study_id>
    <secondary_id>CRAD001AUS210T</secondary_id>
    <nct_id>NCT03284242</nct_id>
  </id_info>
  <brief_title>A Pilot Study Using Autologous Regulatory T Cell Infusion Zortress (Everolimus) in Renal Transplant Recipients</brief_title>
  <official_title>Tolerance Induction Using Autologous Regulatory T Cell Infusion and Zortress (Everolimus) in Renal Transplant Recipients: a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Roberto Gedaly</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</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 study will enroll individuals who have end stage renal disease and who are undergoing a&#xD;
      solitary kidney transplant. This study is investigating/evaluating the safety and&#xD;
      effectiveness of collecting, expanding and infusing a specific certain type of immune cell&#xD;
      known as Regulatory T cells (Treg cells) to renal transplant recipients who are using&#xD;
      Zortress (Everolimus) as immunosuppressive therapy.&#xD;
&#xD;
      Treg cells, once they have been expanded in the laboratory to help prevent kidney rejection.&#xD;
      Treg cells are collected from a participant's blood through a procedure called apheresis.&#xD;
      Treg cells are a type of white blood cells that are able to suppress the activity of other&#xD;
      immune cells responsible for organ rejection. The investigator plans to enroll 12&#xD;
      participants at the University of Kentucky.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this research study is to learn alternative ways to control the body's immune&#xD;
      responses after renal transplantation. The investigator's goal is to prevent or reduce the&#xD;
      side-effects of long-term immunosuppressive therapy.&#xD;
&#xD;
      By doing this study, the investigator hopes to learn how safe and effective infusing&#xD;
      autologous Treg cells, after renal transplantation, to renal transplant recipients who are&#xD;
      taking Zortress (Everolimus) to control the immune response.&#xD;
&#xD;
      Individuals who decide to take part in this research study and are eligible to start, will be&#xD;
      followed for 1 year after their transplant. The research procedures will be conducted at the&#xD;
      University of Kentucky Medical Center and require nine study visits. One of the study visits&#xD;
      requires an overnight stay. Participants will be admitted to the University of Kentucky&#xD;
      Center for Clinical and Translational Science (CCTS) inpatient research unit for this study&#xD;
      visit. Depending on the frequency of an participant's post-transplant clinic visits, some of&#xD;
      the study visits could be done at the same time as their regular clinic visits. If not, they&#xD;
      will occur in the transplant clinic or in the University of Kentucky Center for Clinical and&#xD;
      Translational Science (CCTS) outpatient research unit.&#xD;
&#xD;
      The total amount of time required for participation in the study will be up to 40 hours over&#xD;
      1 year. The total amount of blood taken for the study will be about 14 tablespoons (200ml/6.5&#xD;
      ounces) over 1 year.&#xD;
&#xD;
      STUDY PROCEDURES:&#xD;
&#xD;
      Blood Samples: These will be collected via a needle inserted into a vein in the arm.&#xD;
&#xD;
      Human immunodeficiency virus (HIV) and hepatitis testing: Test for HIV, Hepatitis B and&#xD;
      Hepatitis C will be done as part of the participant's routine transplant evaluation. The&#xD;
      results from these tests will be used to determine study eligibility at the pre-transplant&#xD;
      study visit.&#xD;
&#xD;
      If any of these tests are positive, a qualified person will provide counseling to the&#xD;
      participant. The State of Kentucky requires that researchers must report HIV, Hepatitis B and&#xD;
      Hepatitis C positive test results to the local health department serving the jurisdiction in&#xD;
      which the participant resides, and that the information reported must include the&#xD;
      participant's full name, address, phone number, county of residence, and applicable&#xD;
      disease/condition.&#xD;
&#xD;
      Apheresis: Apheresis is a procedure in which a machine receives blood removed from a&#xD;
      participant's body and separates it into its various components: plasma, platelets, white&#xD;
      blood cells and red blood cells. This procedure is done in the Apheresis Center in the Gill&#xD;
      Heart Building at the UK Chandler Hospital. Depending on the reason for apheresis, one of&#xD;
      these components is isolated and collected by the instrument, while the others are re-infused&#xD;
      to the body.&#xD;
&#xD;
      In this particular research study the investigator is going to collect white blood cells to&#xD;
      isolate Treg cells for expansion. The process of collecting white blood cells will take&#xD;
      approximately 90 minutes. Once the blood cells are collected, the research team will isolate&#xD;
      the Treg cells. These cells will be cultured in the laboratory under special conditions and&#xD;
      will be expanded. After approximately 3 weeks in culture, the cells will have increased in&#xD;
      number and be ready for the autologous Treg cell infusion.&#xD;
&#xD;
      Autologous Treg cell infusion: This will be a single intravenous (IV) infusion. A standard IV&#xD;
      line will be started in a vein of the arm. The participant's own expanded regulatory T cells&#xD;
      will be added to a sterile infusion solution, called Albumin, and administered to to the&#xD;
      participant, and the infusion will take about 3 to 4 hours. Participant's vital signs will be&#xD;
      monitored before, during, and after the infusion.&#xD;
&#xD;
      Renal Biopsy: Two renal biopsies (removal of a piece of kidney tissue) will be performed. The&#xD;
      first one will be done in the operating room during the participant's renal transplant&#xD;
      surgery. The biopsy will come from the new kidney prior to being transplanted. The second one&#xD;
      will be done 6 weeks after the autologous Treg cell infusion and will be compared to the&#xD;
      first one. The second renal biopsy is optional. If a participant agrees to the second biopsy&#xD;
      it will be done as an outpatient procedure in the radiology department at the University of&#xD;
      Kentucky. Using an ultrasound for guidance, the investigator will pass a larger needle&#xD;
      through the skin to obtain a small sample of the transplanted kidney.&#xD;
&#xD;
      Physical Examination and Vital Sign Measurement: These will be done by a member of the study&#xD;
      team. The participant's body temperature, heart rate, respiratory rate, and blood pressure&#xD;
      will be measured and recorded.&#xD;
&#xD;
      Pregnancy Tests: A pregnancy test will be performed on women who could be pregnant prior to&#xD;
      beginning the study and again prior to receiving the autologous Treg cell infusion to exclude&#xD;
      the possibility of pregnancy. For study purposes women who could become pregnant must use two&#xD;
      effective contraceptive starting prior to renal transplant through to visit 9.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 15, 2019</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Single intravenous infusion of autologous, ex vivo, expanded Treg cells in renal transplant recipients who are on Everolimus-based immunosupressive therapy.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Tregs Infusion Toxicities</measure>
    <time_frame>Immediately following Tregs infusion and again within 24 hours after Tregs infusion</time_frame>
    <description>Laboratory measurement and observed toxicities immediately and with in 24 hours post infusion of Tregs.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Kidney Function</measure>
    <time_frame>for 2 years from the start of the study</time_frame>
    <description>Creatinine level measurement</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes In Steroid Resistance Rejection Rates</measure>
    <time_frame>1, 6 and 12 months post Tregs infusion</time_frame>
    <description>Laboratory measurement</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Infectious Complications</measure>
    <time_frame>for 2 years from the start of the study</time_frame>
    <description>Laboratory measurement</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treg cell measurements within the allograft</measure>
    <time_frame>6 to 12 weeks post transplant</time_frame>
    <description>Renal biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulating T cell subset measurements</measure>
    <time_frame>twice a week for 4 weeks then weekly for 3 months</time_frame>
    <description>laboratory analysis</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>End Stage Renal Disease</condition>
  <condition>Kidney Transplant</condition>
  <arm_group>
    <arm_group_label>Autologous Treg Infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This will be a single intravenous (IV) infusion. A participant's own expanded regulatory T cells will be added to Albumin, and administered to them. The amount of the solution will be approximately 300 ml and the infusion will take about 3 to 4 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Apheresis</intervention_name>
    <description>Collect white blood cells to isolate Treg cells for expansion. Once the blood cells are collected the cells will be cultured in the laboratory and will be expanded. After approximately 3 weeks in culture, the cells will have increased in number and be ready for the autologous Treg cell infusion.</description>
    <arm_group_label>Autologous Treg Infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Fluent in English able to understand and provide informed consent&#xD;
&#xD;
          -  End stage renal disease listed for primary solitary kidney transplant&#xD;
&#xD;
          -  Willing to participate in the study and comply with study requirements&#xD;
&#xD;
          -  Female participants must agree to use 2 different birth control methods&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of previous organ, tissue or cell transplant&#xD;
&#xD;
          -  Known sensitivity to Sirolimus, Everolimus, Tacrolimus or MMF&#xD;
&#xD;
          -  Previous chronic use of systemic glucocorticoids or other immunosuppression, or&#xD;
             biologic immunomodulators&#xD;
&#xD;
          -  Significant or active infection: HIV, Hepatitis B and C&#xD;
&#xD;
          -  Active cancer or history of cancer within 3 years of screening&#xD;
&#xD;
          -  Participation in other study that involved investigational drug or regimens in the&#xD;
             preceding 12 months&#xD;
&#xD;
          -  History of delayed or abnormal wound healing&#xD;
&#xD;
          -  Delayed graft function&#xD;
&#xD;
          -  Chronic illness or prior treatment which, in the opinion of the investigator,&#xD;
             precludes study participation&#xD;
&#xD;
          -  Pregnant or breastfeeding or refusal to us birth control&#xD;
&#xD;
          -  Inability or unwillingness to comply with study protocol or procedures&#xD;
&#xD;
          -  Chronic use of anticoagulants&#xD;
&#xD;
          -  Blood transfusion 3 months prior to transplant&#xD;
&#xD;
          -  History of non-compliance&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roberto Gedaly, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kentucky Medical Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roberto Gedaly, MD</last_name>
      <phone>859-323-1691</phone>
      <email>rgeda2@uky.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <last_update_submitted>January 13, 2023</last_update_submitted>
  <last_update_submitted_qc>January 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Roberto Gedaly</investigator_full_name>
    <investigator_title>Sponsor/Investigator</investigator_title>
  </responsible_party>
  <keyword>Kidney</keyword>
  <keyword>Transplant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03284242
org study id: 16-0779-F6A
secondary id: CRAD001AUS210T
nct id: NCT03284242
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study will enroll individuals who have end stage renal disease and who are undergoing a
      solitary kidney transplant. This study is investigating/evaluating the safety and
      effectiveness of collecting, expanding and infusing a specific certain type of immune cell
      known as Regulatory T cells (Treg cells) to renal transplant recipients who are using
      Zortress (Everolimus) as immunosuppressive therapy.

      Treg cells, once they have been expanded in the laboratory to help prevent kidney rejection.
      Treg cells are collected from a participant's blood through a procedure called apheresis.
      Treg cells are a type of white blood cells that are able to suppress the activity of other
      immune cells responsible for organ rejection. The investigator plans to enroll 12
      participants at the University of Kentucky.
The purpose of this research study is to learn alternative ways to control the body's immune
      responses after renal transplantation. The investigator's goal is to prevent or reduce the
      side-effects of long-term immunosuppressive therapy.

      By doing this study, the investigator hopes to learn how safe and effective infusing
      autologous Treg cells, after renal transplantation, to renal transplant recipients who are
      taking Zortress (Everolimus) to control the immune response.

      Individuals who decide to take part in this research study and are eligible to start, will be
      followed for 1 year after their transplant. The research procedures will be conducted at the
      University of Kentucky Medical Center and require nine study visits. One of the study visits
      requires an overnight stay. Participants will be admitted to the University of Kentucky
      Center for Clinical and Translational Science (CCTS) inpatient research unit for this study
      visit. Depending on the frequency of an participant's post-transplant clinic visits, some of
      the study visits could be done at the same time as their regular clinic visits. If not, they
      will occur in the transplant clinic or in the University of Kentucky Center for Clinical and
      Translational Science (CCTS) outpatient research unit.

      The total amount of time required for participation in the study will be up to 40 hours over
      1 year. The total amount of blood taken for the study will be about 14 tablespoons (200ml/6.5
      ounces) over 1 year.

      STUDY PROCEDURES:

      Blood Samples: These will be collected via a needle inserted into a vein in the arm.

      Human immunodeficiency virus (HIV) and hepatitis testing: Test for HIV, Hepatitis B and
      Hepatitis C will be done as part of the participant's routine transplant evaluation. The
      results from these tests will be used to determine study eligibility at the pre-transplant
      study visit.

      If any of these tests are positive, a qualified person will provide counseling to the
      participant. The State of Kentucky requires that researchers must report HIV, Hepatitis B and
      Hepatitis C positive test results to the local health department serving the jurisdiction in
      which the participant resides, and that the information reported must include the
      participant's full name, address, phone number, county of residence, and applicable
      disease/condition.

      Apheresis: Apheresis is a procedure in which a machine receives blood removed from a
      participant's body and separates it into its various components: plasma, platelets, white
      blood cells and red blood cells. This procedure is done in the Apheresis Center in the Gill
      Heart Building at the UK Chandler Hospital. Depending on the reason for apheresis, one of
      these components is isolated and collected by the instrument, while the others are re-infused
      to the body.

      In this particular research study the investigator is going to collect white blood cells to
      isolate Treg cells for expansion. The process of collecting white blood cells will take
      approximately 90 minutes. Once the blood cells are collected, the research team will isolate
      the Treg cells. These cells will be cultured in the laboratory under special conditions and
      will be expanded. After approximately 3 weeks in culture, the cells will have increased in
      number and be ready for the autologous Treg cell infusion.

      Autologous Treg cell infusion: This will be a single intravenous (IV) infusion. A standard IV
      line will be started in a vein of the arm. The participant's own expanded regulatory T cells
      will be added to a sterile infusion solution, called Albumin, and administered to to the
      participant, and the infusion will take about 3 to 4 hours. Participant's vital signs will be
      monitored before, during, and after the infusion.

      Renal Biopsy: Two renal biopsies (removal of a piece of kidney tissue) will be performed. The
      first one will be done in the operating room during the participant's renal transplant
      surgery. The biopsy will come from the new kidney prior to being transplanted. The second one
      will be done 6 weeks after the autologous Treg cell infusion and will be compared to the
      first one. The second renal biopsy is optional. If a participant agrees to the second biopsy
      it will be done as an outpatient procedure in the radiology department at the University of
      Kentucky. Using an ultrasound for guidance, the investigator will pass a larger needle
      through the skin to obtain a small sample of the transplanted kidney.

      Physical Examination and Vital Sign Measurement: These will be done by a member of the study
      team. The participant's body temperature, heart rate, respiratory rate, and blood pressure
      will be measured and recorded.

      Pregnancy Tests: A pregnancy test will be performed on women who could be pregnant prior to
      beginning the study and again prior to receiving the autologous Treg cell infusion to exclude
      the possibility of pregnancy. For study purposes women who could become pregnant must use two
      effective contraceptive starting prior to renal transplant through to visit 9.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single intravenous infusion of autologous, ex vivo, expanded Treg cells in renal transplant recipients who are on Everolimus-based immunosupressive therapy.
primary purpose: Treatment
masking: None (Open Label)
measure: Changes in Tregs Infusion Toxicities
time frame: Immediately following Tregs infusion and again within 24 hours after Tregs infusion
description: Laboratory measurement and observed toxicities immediately and with in 24 hours post infusion of Tregs.
measure: Changes in Kidney Function
time frame: for 2 years from the start of the study
description: Creatinine level measurement
measure: Changes In Steroid Resistance Rejection Rates
time frame: 1, 6 and 12 months post Tregs infusion
description: Laboratory measurement
measure: Infectious Complications
time frame: for 2 years from the start of the study
description: Laboratory measurement
measure: Treg cell measurements within the allograft
time frame: 6 to 12 weeks post transplant
description: Renal biopsy
measure: Circulating T cell subset measurements
time frame: twice a week for 4 weeks then weekly for 3 months
description: laboratory analysis
arm group label: Autologous Treg Infusion
arm group type: Experimental
description: This will be a single intravenous (IV) infusion. A participant's own expanded regulatory T cells will be added to Albumin, and administered to them. The amount of the solution will be approximately 300 ml and the infusion will take about 3 to 4 hours.
intervention type: Procedure
intervention name: Apheresis
description: Collect white blood cells to isolate Treg cells for expansion. Once the blood cells are collected the cells will be cultured in the laboratory and will be expanded. After approximately 3 weeks in culture, the cells will have increased in number and be ready for the autologous Treg cell infusion.
arm group label: Autologous Treg Infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Roberto Gedaly, MD
role: Principal Investigator
affiliation: University of Kentucky
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Roberto Gedaly
investigator title: Sponsor/Investigator
mesh term: Kidney Failure, Chronic
sharing ipd: No