xml: <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/NCT06001320</url>
    </required_header>
    <id_info>
      <org_study_id>HM20027540</org_study_id>
      <nct_id>NCT06001320</nct_id>
    </id_info>
    <brief_title>De-novo Initiation of Letermovir vs Valganciclovir for Cytomegalovirus Prophylaxis in AA Kidney Trans Recip</brief_title>
    <official_title>Historical Controlled, Single Center Open Label Pilot Comparing the Effectiveness and Tolerability of De-novo Initiation of Letermovir Versus Valganciclovir for Cytomegalovirus Prophylaxis in AA Kidney Transplant Recipients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Virginia Commonwealth University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Merck Sharp &amp; Dohme LLC</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </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>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        CMV viremia will be treated with either oral valganciclovir, intravenous ganciclovir or&#xD;
        alternative agents, according to AST ID COP (American Society of Transplantation Infectious&#xD;
        disease community of practice) guidelines.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Intervention: Letermovir prophylaxis. Prophylaxis is once daily dose of Letermovier starting&#xD;
        Day 1 of post-transplant up until 6 months post-transplant.&#xD;
  &#xD;
        Participants enrolled in this study will also receive prophylactic acyclovir 400mg twice&#xD;
        daily for the duration of their Letermovir treatment.&#xD;
  &#xD;
        Strategy for CMV Viremia: CMV viremia will be treated with either oral valganciclovir,&#xD;
        intravenous ganciclovir or alternative agents, according to AST ID COP (American Society of&#xD;
        Transplantation Infectious disease community of practice) guidelines.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2025</primary_completion_date>
    <phase>Early Phase 1</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>
      <intervention_model_description>Interventional, Historical Controlled, Single Center Open Label Pilot Study</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of cytomegalovirus viremia (defined as CMV PCR &gt; 137 units/ml) or symptomatic disease in AA kidney transplant recipients</measure>
      <time_frame>up to one year after transplantation</time_frame>
      <description>The incidence of cytomegalovirus viremia (defined as CMV PCR &gt; 137 units/ml) or symptomatic disease in AA kidney transplant recipients by one year post-transplantation</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Incidence of Leukopenia (defined as WBC &lt; 2.5 x 103 cells/mm3 beyond the first 2 weeks of transplantation, while on pharmacologic CMV prophylaxis)</measure>
      <time_frame>From 2 weeks up to 26 weeks post-transplant</time_frame>
      <description>The incidence of leukopenia (defined as WBC &lt; 2.5 x 103 cells/mm3 beyond the first 2 weeks of transplantation, while on pharmacologic CMV prophylaxis)- assessed from 2 weeks up to 26weeks post-transplant</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Impact of Pharmacological Prophylaxis on CMV T-Cell immunity up to 1 year post-transplant</measure>
      <time_frame>up to 1 Year post-transplant</time_frame>
      <description>CMV T-cell immunity assay, assessed up to 1 year post-transplant. At 12, 26 and 52 weeks post-transplant</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of acute kidney allograft rejection up to one year after transplantation</measure>
      <time_frame>up to 1 Year post-transplant</time_frame>
      <description>acute kidney allograft rejection up to one year after transplantation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Impact of Pharmacologic CMV Prophylaxis on Mycophenolate dosage up to 6 months post-transplant</measure>
      <time_frame>Up to 6 months post-transplant</time_frame>
      <description>Changes in mycophenolate dosage (assessed by review of patient's chart) up to 6 months post-transplant</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of de novo donor specific antibody formation up to 1 year after transplant</measure>
      <time_frame>up to 1 Year post-transplant</time_frame>
      <description>de novo donor specific antibody formation up to one year after transplantation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tolerability of Letermovir in AA kidney transplant recipients up to 6 months post-transplant, using a tolerability assessment questionnaire</measure>
      <time_frame>up to 6 months post-transplant</time_frame>
      <description>Tolerability of Letermovir in AA kidney transplant recipient up to 6 months post-transplant (assessed through patient observation, tolerability assessment questionnaire, obtaining medical history and conduction physical examination during visits, receiving an unsolicited complaint from the participant, and an abnormal value or result from a clinical or laboratory evaluation).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation between CYP3A5*1 and its impact on tacrolimus metabolism and incidence of kidney allograft rejection up to 1 year post-transplant</measure>
      <time_frame>up to 1 Year post-transplant</time_frame>
      <description>correlation between CYP3A5*1 and tacrolimus metabolism and incidence of kidney allograft rejection up to one year after transplantation</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Kidney Transplant; Complications</condition>
    <condition>CMV</condition>
    <arm_group>
      <arm_group_label>Letermovir group (study group)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Letermovir 480 mg once daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Historically matched AA kidney transplant recipients who received valganciclovir</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Compare outcomes to a historical group of 50 AA kidney transplant recipients who have received valganciclovir prophylaxis</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Letermovir 480 mg once daily</intervention_name>
      <description>We will test the study hypothesis in a single center, matched (1:1 fashion) pilot study of Letermovir 480 mg once daily versus historically matched AA kidney transplant recipients who received valganciclovir. We will enroll 50 AA patients over a 12-month period into the Letermovir group and compare outcomes to a historical group of 50 AA kidney transplant recipients who have received valganciclovir prophylaxis (1:1 fashion), for a total of 100 patients. We will attempt to match patients on Letermovir to the historical patients who received valganciclovir, based on age, kidney Donor profile index and the presence of panel of reactive antibodies.</description>
      <arm_group_label>Letermovir group (study group)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Historical/Control</intervention_name>
      <description>The control study group will include high-risk African American kidney transplant recipients cared for with Valganciclovir in the 5 years prior to the enrollment start for the study group. This time frame is based upon the current volume of transplants done at VCU. On average 30 liver and/or kidney transplants are done per month. Thus, 5 years should be an adequate time frame to mine enough number of participants to answer our primary research hypothesis.</description>
      <arm_group_label>Historically matched AA kidney transplant recipients who received valganciclovir</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Historical Control group:&#xD;
  &#xD;
          Inclusion Criteria&#xD;
  &#xD;
            1. Kidney transplant recipients&#xD;
  &#xD;
            2. Male or female age ≥ 18 years old&#xD;
  &#xD;
            3. African American race&#xD;
  &#xD;
            4. CMV high risk (D+/R-)&#xD;
  &#xD;
            5. received valganciclovir for CMV prophylaxis&#xD;
  &#xD;
          Historical Control group:&#xD;
  &#xD;
          Exclusion&#xD;
  &#xD;
            1. Re-transplantation&#xD;
  &#xD;
            2. Panel of reactive antibody ≥80% at the time of transplant&#xD;
  &#xD;
            3. Positive cytotoxic cross match at the time of transplant&#xD;
  &#xD;
          Experimental Group Inclusion Criteria&#xD;
  &#xD;
            1. Kidney transplant recipients&#xD;
  &#xD;
            2. Male or female age ≥ 18 years old&#xD;
  &#xD;
            3. African American race&#xD;
  &#xD;
            4. CMV high risk (D+/R-)&#xD;
  &#xD;
            5. Ability to provide informed consent before any trial related activities&#xD;
  &#xD;
          Exclusion Criteria&#xD;
  &#xD;
            1. Re-transplantation&#xD;
  &#xD;
            2. Panel of reactive antibody ≥80% at the time of transplant&#xD;
  &#xD;
            3. Positive cytotoxic cross match at the time of transplant&#xD;
  &#xD;
            4. Pregnancy and Breastfeeding&#xD;
  &#xD;
            5. Prisoners&#xD;
  &#xD;
            6. Patients with hypersensitivity to acyclovir, valacyclovir or any of its components&#xD;
  &#xD;
            7. Patients with hypersensitivity to Letermovir or any of its components&#xD;
  &#xD;
            8. If Patients are taking any of these medications: pimozide, ergot alkaloids&#xD;
               (ergotamine, dihydroergotamine), or pitavastatin/simvastatin co-administered with&#xD;
               cyclosporine, we will work with the prescribing physician to find an appropriate&#xD;
               replacement therapy which will not interfere with any study-related interventions.&#xD;
               Otherwise, participants will be excluded from the study.&#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>Gaurav Gupta, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Virginia Commonwealth University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Idris Yakubu, PharmD</last_name>
      <phone>804-828-6286</phone>
      <email>idris.yakubu@vcuhealth.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Gelila Abebe</last_name>
      <email>gelila.abebe@vcuhealth.org</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 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>Letermovir</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06001320
  org study id: HM20027540
  nct id: NCT06001320
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  CMV viremia will be treated with either oral valganciclovir, intravenous ganciclovir or
        alternative agents, according to AST ID COP (American Society of Transplantation Infectious
        disease community of practice) guidelines.
  Intervention: Letermovir prophylaxis. Prophylaxis is once daily dose of Letermovier starting
        Day 1 of post-transplant up until 6 months post-transplant.
  
        Participants enrolled in this study will also receive prophylactic acyclovir 400mg twice
        daily for the duration of their Letermovir treatment.
  
        Strategy for CMV Viremia: CMV viremia will be treated with either oral valganciclovir,
        intravenous ganciclovir or alternative agents, according to AST ID COP (American Society of
        Transplantation Infectious disease community of practice) guidelines.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  intervention model description: Interventional, Historical Controlled, Single Center Open Label Pilot Study
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of cytomegalovirus viremia (defined as CMV PCR > 137 units/ml) or symptomatic disease in AA kidney transplant recipients
  time frame: up to one year after transplantation
  description: The incidence of cytomegalovirus viremia (defined as CMV PCR > 137 units/ml) or symptomatic disease in AA kidney transplant recipients by one year post-transplantation
  measure: Incidence of Leukopenia (defined as WBC < 2.5 x 103 cells/mm3 beyond the first 2 weeks of transplantation, while on pharmacologic CMV prophylaxis)
  time frame: From 2 weeks up to 26 weeks post-transplant
  description: The incidence of leukopenia (defined as WBC < 2.5 x 103 cells/mm3 beyond the first 2 weeks of transplantation, while on pharmacologic CMV prophylaxis)- assessed from 2 weeks up to 26weeks post-transplant
  measure: Impact of Pharmacological Prophylaxis on CMV T-Cell immunity up to 1 year post-transplant
  time frame: up to 1 Year post-transplant
  description: CMV T-cell immunity assay, assessed up to 1 year post-transplant. At 12, 26 and 52 weeks post-transplant
  measure: Incidence of acute kidney allograft rejection up to one year after transplantation
  time frame: up to 1 Year post-transplant
  description: acute kidney allograft rejection up to one year after transplantation
  measure: Impact of Pharmacologic CMV Prophylaxis on Mycophenolate dosage up to 6 months post-transplant
  time frame: Up to 6 months post-transplant
  description: Changes in mycophenolate dosage (assessed by review of patient's chart) up to 6 months post-transplant
  measure: Incidence of de novo donor specific antibody formation up to 1 year after transplant
  time frame: up to 1 Year post-transplant
  description: de novo donor specific antibody formation up to one year after transplantation
  measure: Tolerability of Letermovir in AA kidney transplant recipients up to 6 months post-transplant, using a tolerability assessment questionnaire
  time frame: up to 6 months post-transplant
  description: Tolerability of Letermovir in AA kidney transplant recipient up to 6 months post-transplant (assessed through patient observation, tolerability assessment questionnaire, obtaining medical history and conduction physical examination during visits, receiving an unsolicited complaint from the participant, and an abnormal value or result from a clinical or laboratory evaluation).
  measure: Correlation between CYP3A5*1 and its impact on tacrolimus metabolism and incidence of kidney allograft rejection up to 1 year post-transplant
  time frame: up to 1 Year post-transplant
  description: correlation between CYP3A5*1 and tacrolimus metabolism and incidence of kidney allograft rejection up to one year after transplantation
  arm group label: Letermovir group (study group)
  arm group type: Experimental
  description: Letermovir 480 mg once daily
  arm group label: Historically matched AA kidney transplant recipients who received valganciclovir
  arm group type: Other
  description: Compare outcomes to a historical group of 50 AA kidney transplant recipients who have received valganciclovir prophylaxis
  intervention type: Drug
  intervention name: Letermovir 480 mg once daily
  description: We will test the study hypothesis in a single center, matched (1:1 fashion) pilot study of Letermovir 480 mg once daily versus historically matched AA kidney transplant recipients who received valganciclovir. We will enroll 50 AA patients over a 12-month period into the Letermovir group and compare outcomes to a historical group of 50 AA kidney transplant recipients who have received valganciclovir prophylaxis (1:1 fashion), for a total of 100 patients. We will attempt to match patients on Letermovir to the historical patients who received valganciclovir, based on age, kidney Donor profile index and the presence of panel of reactive antibodies.
  arm group label: Letermovir group (study group)
  intervention type: Other
  intervention name: Historical/Control
  description: The control study group will include high-risk African American kidney transplant recipients cared for with Valganciclovir in the 5 years prior to the enrollment start for the study group. This time frame is based upon the current volume of transplants done at VCU. On average 30 liver and/or kidney transplants are done per month. Thus, 5 years should be an adequate time frame to mine enough number of participants to answer our primary research hypothesis.
  arm group label: Historically matched AA kidney transplant recipients who received valganciclovir
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Gaurav Gupta, MD
  role: Principal Investigator
  affiliation: Virginia Commonwealth University
  last name: Idris Yakubu, PharmD
  phone: 804-828-6286
  email: idris.yakubu@vcuhealth.org
  last name: Gelila Abebe
  email: gelila.abebe@vcuhealth.org
  responsible party type: Sponsor
  mesh term: Letermovir
  sharing ipd: No