<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/NCT04420195</url>
  </required_header>
  <id_info>
    <org_study_id>19-01247</org_study_id>
    <nct_id>NCT04420195</nct_id>
  </id_info>
  <brief_title>Envarsus XR in Lung Transplant</brief_title>
  <official_title>Pilot Study Comparing Early Conversion to Extended-Release Tacrolimus (ENVARSUS XR) to Immediate-Release Tacrolimus in Lung Transplant Recipients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
      Patients undergoing a lung transplant will be enrolled. All patients will undergo lung&#xD;
      transplantation with standard post-operative management, including triple immunosuppression.&#xD;
      As soon as the patient is deemed appropriate to take medications via the oral route, they&#xD;
      will be converted from IR tacrolimus to Envarsus XR. Patients will be followed per site's&#xD;
      standard of care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lung transplantation will be performed per standard-of-care techniques. All post-transplant&#xD;
      management, including initial triple immunosuppression, will be carried out per standard of&#xD;
      care. Once the patient is able to take medications via the oral route, they will be converted&#xD;
      to Envarsus XR, which will be maintained for the first year post-lung transplant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 23, 2020</start_date>
  <completion_date type="Actual">November 30, 2022</completion_date>
  <primary_completion_date type="Actual">November 30, 2022</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>Percentage of Patients Remaining on Envarsus XR at 1 Year</measure>
    <time_frame>1 Year Post-Transplant</time_frame>
    <description>The primary endpoint is the percentage of patients remaining on Envarsus XR at the 1-year follow-up visit.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Freedom from Acute Cellular Rejection (ACR) at 1 Year</measure>
    <time_frame>Up to 1 Year Post-Transplant</time_frame>
    <description>Percentage of participants who did not experience ACR as of the 1-year follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite Rejection Standardized Score (CRSS)</measure>
    <time_frame>1 Year Post-Transplant</time_frame>
    <description>The CRSS is a novel measure of burden of ACR. The score ranges from 0-6; higher scores indicate greater severity of burden of ACR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Treated Episodes of ACR</measure>
    <time_frame>Up to 1 Year Post-Transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Chronic Lung Allograft Dysfunction (CLAD)</measure>
    <time_frame>Up to 1 Year Post-Transplant</time_frame>
    <description>Number of instances of CLAD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of De Novo Donor-Specific Antibody (DSA)</measure>
    <time_frame>Up to 1 Year Post-Transplant</time_frame>
    <description>Number of instances in which an antibody is detected within a participant only after transplantation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Estimated Glomerular Filtration Rate (eGFR)</measure>
    <time_frame>Baseline, 1 Year Post-Transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival at 1 Year</measure>
    <time_frame>1 Year Post-Transplant</time_frame>
    <description>The percentage of participants who are alive at 1 year post-transplant.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Lung Transplant</condition>
  <arm_group>
    <arm_group_label>Envarsus XR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Envarsus XR to be initiated once patient is tolerating oral medications</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IR tacrolimus (historical control)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Historical cohort of patients maintained on IR tacrolimus following transplant</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Extended-Release Tacrolimus</intervention_name>
    <description>Envarsus XR is an FDA-approved drug for the prophylaxis of organ rejection in de novo kidney transplant patients or in kidney transplant patients converted from IR tacrolimus when used with other immunosuppressants. Envarsus XR is a novel extended-release formulation of tacrolimus created using MeltDose technology. Envarsus XR is available in tablet form. It is available in 0.75, 1, and 4 mg tablets.</description>
    <arm_group_label>Envarsus XR</arm_group_label>
    <other_name>Envarsus XR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Immediate-Release Tacrolimus</intervention_name>
    <description>Historical cohort of 20 subjects who will be maintained on IR tacrolimus following transplant. Dosing will be converted on an individual basis (Capsules: 0.5 mg, 1 mg and 5 mg or Injection: 5 mg) . All patients will be initiated on IR tacrolimus either under the tongue (sublingual) or as a solution given through a tube placed through the nose into the stomach, which is standard of care for all lung transplant recipients.</description>
    <arm_group_label>IR tacrolimus (historical control)</arm_group_label>
    <other_name>Prograf</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Prospective arm:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Received a lung transplant at NYU Langone Health&#xD;
&#xD;
          -  Be able to convert to Envarsus XR within the first month post-transplant&#xD;
&#xD;
          -  Able and willing to provide informed consent&#xD;
&#xD;
        Historical control:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Received a lung transplant at NYU Langone Health&#xD;
&#xD;
          -  Completed one year from transplant on IR tacrolimus&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Prospective arm:&#xD;
&#xD;
          -  Contraindication to tacrolimus due to allergic or adverse reactions&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Multi-organ transplant recipient&#xD;
&#xD;
        Historical control:&#xD;
&#xD;
          -  Contraindication to tacrolimus due to allergic or adverse reactions (not including&#xD;
             chronic kidney disease)&#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>Luis Angel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU Langone Health</affiliation>
  </overall_official>
  <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>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>May 30, 2023</last_update_submitted>
  <last_update_submitted_qc>May 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>IPD collected for this study will be used for the sole purpose of this study.</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/NCT04420195
org study id: 19-01247
nct id: NCT04420195
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Patients undergoing a lung transplant will be enrolled. All patients will undergo lung
      transplantation with standard post-operative management, including triple immunosuppression.
      As soon as the patient is deemed appropriate to take medications via the oral route, they
      will be converted from IR tacrolimus to Envarsus XR. Patients will be followed per site's
      standard of care.
Lung transplantation will be performed per standard-of-care techniques. All post-transplant
      management, including initial triple immunosuppression, will be carried out per standard of
      care. Once the patient is able to take medications via the oral route, they will be converted
      to Envarsus XR, which will be maintained for the first year post-lung transplant.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Patients Remaining on Envarsus XR at 1 Year
time frame: 1 Year Post-Transplant
description: The primary endpoint is the percentage of patients remaining on Envarsus XR at the 1-year follow-up visit.
measure: Freedom from Acute Cellular Rejection (ACR) at 1 Year
time frame: Up to 1 Year Post-Transplant
description: Percentage of participants who did not experience ACR as of the 1-year follow-up.
measure: Composite Rejection Standardized Score (CRSS)
time frame: 1 Year Post-Transplant
description: The CRSS is a novel measure of burden of ACR. The score ranges from 0-6; higher scores indicate greater severity of burden of ACR.
measure: Number of Treated Episodes of ACR
time frame: Up to 1 Year Post-Transplant
measure: Incidence of Chronic Lung Allograft Dysfunction (CLAD)
time frame: Up to 1 Year Post-Transplant
description: Number of instances of CLAD.
measure: Incidence of De Novo Donor-Specific Antibody (DSA)
time frame: Up to 1 Year Post-Transplant
description: Number of instances in which an antibody is detected within a participant only after transplantation.
measure: Change in Estimated Glomerular Filtration Rate (eGFR)
time frame: Baseline, 1 Year Post-Transplant
measure: Overall Survival at 1 Year
time frame: 1 Year Post-Transplant
description: The percentage of participants who are alive at 1 year post-transplant.
arm group label: Envarsus XR
arm group type: Experimental
description: Envarsus XR to be initiated once patient is tolerating oral medications
arm group label: IR tacrolimus (historical control)
arm group type: Experimental
description: Historical cohort of patients maintained on IR tacrolimus following transplant
intervention type: Drug
intervention name: Extended-Release Tacrolimus
description: Envarsus XR is an FDA-approved drug for the prophylaxis of organ rejection in de novo kidney transplant patients or in kidney transplant patients converted from IR tacrolimus when used with other immunosuppressants. Envarsus XR is a novel extended-release formulation of tacrolimus created using MeltDose technology. Envarsus XR is available in tablet form. It is available in 0.75, 1, and 4 mg tablets.
arm group label: Envarsus XR
other name: Envarsus XR
intervention type: Drug
intervention name: Immediate-Release Tacrolimus
description: Historical cohort of 20 subjects who will be maintained on IR tacrolimus following transplant. Dosing will be converted on an individual basis (Capsules: 0.5 mg, 1 mg and 5 mg or Injection: 5 mg) . All patients will be initiated on IR tacrolimus either under the tongue (sublingual) or as a solution given through a tube placed through the nose into the stomach, which is standard of care for all lung transplant recipients.
arm group label: IR tacrolimus (historical control)
other name: Prograf
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Luis Angel, MD
role: Principal Investigator
affiliation: NYU Langone Health
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tacrolimus
sharing ipd: No
ipd description: IPD collected for this study will be used for the sole purpose of this study.