<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/NCT04477629</url>
  </required_header>
  <id_info>
    <org_study_id>22-01135</org_study_id>
    <nct_id>NCT04477629</nct_id>
  </id_info>
  <brief_title>Belatacept in De Novo Heart Transplantation</brief_title>
  <official_title>Belatacept in De Novo Heart Transplantation - Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>NYU Langone Health</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if Belatacept is safe to give to adult heart&#xD;
      transplant recipients. Belatacept (NULOJIX) is an anti-rejection medication that is available&#xD;
      through a prescription from a doctor. In this research study, belatacept is being used in an&#xD;
      investigational manner (not for the purpose that it is approved for).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Long-term outcomes after heart transplant remain suboptimal with renal failure and cardiac&#xD;
      allograft vasculopathy contributing to morbidity and mortality. Belatacept is Food and Drug&#xD;
      Administration (FDA) approved for use in kidney transplant recipients on the basis of two&#xD;
      randomized controlled trials, which demonstrated important renal sparing benefits, a&#xD;
      reduction in de novo donor-specific antibodies (DSA), and improved long-term outcomes. In&#xD;
      this study, ten (10) primary heart transplant recipients will receive belatacept in addition&#xD;
      to mycophenolate mofetil, corticosteroids, and a tacrolimus tapering regimen.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 6, 2020</start_date>
  <completion_date type="Anticipated">February 2025</completion_date>
  <primary_completion_date type="Anticipated">February 2025</primary_completion_date>
  <phase>Phase 2</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>Study population includes first-time Epstein-Barr virus (EBV) seropositive, male and non-pregnant female heart transplant recipients 18 years of age or older, who are able to provide written informed consent for the study.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Major Graft-Related Adverse Events</measure>
    <time_frame>Up to 18 months after transplantation</time_frame>
    <description>Adverse events that will be counted in the total number include: Episodes of acute cellular rejection ≥ 2R/3A, antibody mediated rejection (AMR) ≥ International Society of Heart and Lung Transplantation (ISHLT) AMR 1, hemodynamically compromised rejection, development of cardiac allograft vasculopathy, graft failure occurring ≥ 14 days post-transplant, the need for re-transplant, serious infection requiring inpatient intravenous therapies, post-transplant lymphoproliferative disorder (PTLD), or death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Estimated Glomerular Filtration Rate (eGFR)</measure>
    <time_frame>Baseline and 18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Individuals with Development of De Novo Donor Specific Antibodies (DSA)</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Heart Transplantation</condition>
  <arm_group>
    <arm_group_label>Belatacept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Belatacept along with an upfront tacrolimus taper Participants will also receive mycophenolate mofetil and corticosteroids are part of standard of care after heart transplant and will follow dosing recommendations as per standard clinical practice.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Belatacept</intervention_name>
    <description>Belatacept will be given in the following way - 10mg/kg IV day 1, 5, end of weeks 2, 4, 8, 12 then 5mg/kg every 4 weeks.</description>
    <arm_group_label>Belatacept</arm_group_label>
    <other_name>Nulojix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Non-experimental: Tacrolimus will be given in the following way - trough level at month 1, 10-12ng/mL; month 2-3, 6-10ng/mL; month 4-6, 4-6ng/mL; months 7-9 taper off.</description>
    <arm_group_label>Belatacept</arm_group_label>
    <other_name>Tacrolimus taper</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate Mofetil</intervention_name>
    <description>Non-experimental: MMF is part of standard of care after heart transplant and will follow dosing recommendations as per standard clinical practice at 500-1500mg twice a day (BID) (dosed to tolerance and effect).</description>
    <arm_group_label>Belatacept</arm_group_label>
    <other_name>MMF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Corticosteroid</intervention_name>
    <description>Non-experimental: CS is part of standard of care after heart transplant and will follow dosing recommendations as per standard clinical practice at a dose no less than 5mg/d.</description>
    <arm_group_label>Belatacept</arm_group_label>
    <other_name>CS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or non-pregnant female, age ≥18 to ≤75 years&#xD;
&#xD;
          2. Awaiting a primary heart transplant (listed for heart transplant only)&#xD;
&#xD;
          3. Epstein-Barr virus (EBV) IgG seropositive&#xD;
&#xD;
          4. Able to take oral medication and willing to adhere to the belatacept infusion regimen&#xD;
&#xD;
          5. No desensitization therapy prior to transplant&#xD;
&#xD;
          6. Vaccinations should be up to date for hepatitis B, influenza pneumococcal,&#xD;
             haemophilus, varicella zoster virus (VZV), measles, mumps and rubella (MMR), and Human&#xD;
             Papilloma Virus (HPV) (for participants &lt; 45 years of age) when available&#xD;
&#xD;
          7. Female subjects of childbearing potential must have a negative pregnancy test (serum&#xD;
             or urine) prior to randomization&#xD;
&#xD;
          8. Mechanical support or investigational drug trials where the intervention ends at the&#xD;
             time of transplantation are permitted&#xD;
&#xD;
          9. Negative virtual crossmatch&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Candidates awaiting multiorgan transplant&#xD;
&#xD;
          2. Estimated glomerular filtration rate (eGFR) &lt; 45 ml/min/m2&#xD;
&#xD;
          3. Candidates with prior organ transplant&#xD;
&#xD;
          4. Candidates actively being treated with immunosuppressive therapies&#xD;
&#xD;
          5. Candidates who have a history of treatment with cytolytic therapy (e.g. anti-thymocyte&#xD;
             globulin)&#xD;
&#xD;
          6. Candidates who are intended to be treated with cytolytic therapy in the&#xD;
             post-transplant period as induction therapy&#xD;
&#xD;
          7. EBV (IgG) seronegative&#xD;
&#xD;
          8. Active or prior infection with human immunodeficiency virus (HIV), Hepatitis C (HCV),&#xD;
             Hepatitis B (HBV)&#xD;
&#xD;
          9. Untreated latent tuberculosis (TB)&#xD;
&#xD;
         10. All potential candidates will be screened prior to enrolment for a history of&#xD;
             tuberculosis (chest radiograph and tuberculosis-Interferon Gamma Release Assay&#xD;
             (TB-IGRA) or tuberculin skin tests (TST)). Potential candidates with latent TB must be&#xD;
             treated prior to study enrolment&#xD;
&#xD;
         11. Prior history of active tuberculosis&#xD;
&#xD;
         12. Prior history of central nervous system infection&#xD;
&#xD;
         13. Known active current viral, fungal, mycobacterial, or other infections excluding&#xD;
             driveline infections - potential participants from endemic areas will additionally be&#xD;
             screened for histoplasmosis, blastomycosis, coccidioidomycosis, and strongyloidiasis&#xD;
&#xD;
         14. Vaccination with a live vaccine within the past 30 days&#xD;
&#xD;
         15. Malignancy within the last 5 years&#xD;
&#xD;
         16. Any previous treatment with alkylating agents or total lymphoid irradiation&#xD;
&#xD;
         17. Sensitized heart transplant candidates with panel-reactive antibodies (PRA) &gt;50% or&#xD;
             those receiving desensitization treatment&#xD;
&#xD;
         18. Prior treatment with belatacept or abatacept&#xD;
&#xD;
         19. History of severe allergic anaphylactic reactions to humanized or murine monoclonal&#xD;
             antibodies&#xD;
&#xD;
         20. Treatment with a disease modifying anti-rheumatic drug (DMARD) or other biologic agent&#xD;
             (monoclonal antibody) within the past year&#xD;
&#xD;
         21. Treatment with another investigational drug or other intervention at the time of&#xD;
             transplant (excluding device or intervention mechanical support or investigational&#xD;
             drug trials where the intervention ends at the time of transplant)&#xD;
&#xD;
         22. Potential candidates for whom a calcineurin inhibitor other than tacrolimus (Prograf®)&#xD;
             is anticipated after transplant. If during the course of the study, a participant is&#xD;
             transitioned to another calcineurin inhibitor due to side effects or inability to&#xD;
             achieve stable therapeutic trough levels, they may continue in the study at the&#xD;
             discretion of the investigator&#xD;
&#xD;
         23. Any potential participant who remains on mechanical circulatory support for &gt; 72 hours&#xD;
             post-transplant will be excluded from the study&#xD;
&#xD;
         24. The need for ongoing high dose vasopressor support &gt; 72 hours post-transplant&#xD;
&#xD;
         25. The need or anticipated need for post-transplant dialysis&#xD;
&#xD;
         26. Platelet count &lt;75,000/mm (within 24 hours prior to transplant)&#xD;
&#xD;
         27. Absolute neutrophil count (ANC) of less than 2000/mm3 within 24 hours prior to&#xD;
             transplant&#xD;
&#xD;
         28. Any past or current medical problems or findings on history, physical examination, or&#xD;
             laboratory testing, not listed above, that in the opinion of the investigator, may&#xD;
             pose additional risk to participation, may interfere with the participant's ability to&#xD;
             comply with study requirements, or that may impact the quality or interpretation of&#xD;
             study results&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marlena V. Habal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU Langone Health</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Andrea Kim</last_name>
    <phone>646-457-0987</phone>
    <email>Andrea.Kim@nyulangone.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Steven R. Russum</last_name>
    <email>Steven.Russum@nyulangone.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>NYU Langone Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrea Kim</last_name>
      <email>Andrea.Kim@nyulangone.org</email>
    </contact>
    <investigator>
      <last_name>Marlena Habal, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>April 3, 2023</last_update_submitted>
  <last_update_submitted_qc>April 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Heart Transplant</keyword>
  <keyword>Nulojix</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Abatacept</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04477629
org study id: 22-01135
nct id: NCT04477629
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine if Belatacept is safe to give to adult heart
      transplant recipients. Belatacept (NULOJIX) is an anti-rejection medication that is available
      through a prescription from a doctor. In this research study, belatacept is being used in an
      investigational manner (not for the purpose that it is approved for).
Long-term outcomes after heart transplant remain suboptimal with renal failure and cardiac
      allograft vasculopathy contributing to morbidity and mortality. Belatacept is Food and Drug
      Administration (FDA) approved for use in kidney transplant recipients on the basis of two
      randomized controlled trials, which demonstrated important renal sparing benefits, a
      reduction in de novo donor-specific antibodies (DSA), and improved long-term outcomes. In
      this study, ten (10) primary heart transplant recipients will receive belatacept in addition
      to mycophenolate mofetil, corticosteroids, and a tacrolimus tapering regimen.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Study population includes first-time Epstein-Barr virus (EBV) seropositive, male and non-pregnant female heart transplant recipients 18 years of age or older, who are able to provide written informed consent for the study.
primary purpose: Prevention
masking: None (Open Label)
measure: Number of Major Graft-Related Adverse Events
time frame: Up to 18 months after transplantation
description: Adverse events that will be counted in the total number include: Episodes of acute cellular rejection ≥ 2R/3A, antibody mediated rejection (AMR) ≥ International Society of Heart and Lung Transplantation (ISHLT) AMR 1, hemodynamically compromised rejection, development of cardiac allograft vasculopathy, graft failure occurring ≥ 14 days post-transplant, the need for re-transplant, serious infection requiring inpatient intravenous therapies, post-transplant lymphoproliferative disorder (PTLD), or death.
measure: Change in Estimated Glomerular Filtration Rate (eGFR)
time frame: Baseline and 18 months
measure: Percentage of Individuals with Development of De Novo Donor Specific Antibodies (DSA)
time frame: 18 months
arm group label: Belatacept
arm group type: Experimental
description: Participants will receive Belatacept along with an upfront tacrolimus taper Participants will also receive mycophenolate mofetil and corticosteroids are part of standard of care after heart transplant and will follow dosing recommendations as per standard clinical practice.
intervention type: Drug
intervention name: Belatacept
description: Belatacept will be given in the following way - 10mg/kg IV day 1, 5, end of weeks 2, 4, 8, 12 then 5mg/kg every 4 weeks.
arm group label: Belatacept
other name: Nulojix
intervention type: Drug
intervention name: Tacrolimus
description: Non-experimental: Tacrolimus will be given in the following way - trough level at month 1, 10-12ng/mL; month 2-3, 6-10ng/mL; month 4-6, 4-6ng/mL; months 7-9 taper off.
arm group label: Belatacept
other name: Tacrolimus taper
intervention type: Drug
intervention name: Mycophenolate Mofetil
description: Non-experimental: MMF is part of standard of care after heart transplant and will follow dosing recommendations as per standard clinical practice at 500-1500mg twice a day (BID) (dosed to tolerance and effect).
arm group label: Belatacept
other name: MMF
intervention type: Drug
intervention name: Corticosteroid
description: Non-experimental: CS is part of standard of care after heart transplant and will follow dosing recommendations as per standard clinical practice at a dose no less than 5mg/d.
arm group label: Belatacept
other name: CS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Marlena V. Habal, MD
role: Principal Investigator
affiliation: NYU Langone Health
last name: Andrea Kim
phone: 646-457-0987
email: Andrea.Kim@nyulangone.org
last name: Steven R. Russum
email: Steven.Russum@nyulangone.org
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
country: United States
responsible party type: Sponsor
mesh term: Mycophenolic Acid
mesh term: Abatacept
mesh term: Tacrolimus
sharing ipd: Undecided