<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/NCT04471441</url>
  </required_header>
  <id_info>
    <org_study_id>B95-02LT1903</org_study_id>
    <nct_id>NCT04471441</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Everolimus Versus Mycophenolate Mofetil in Liver Transplant Recipients.</brief_title>
  <acronym>MONTBLANC</acronym>
  <official_title>Multi-center, Open-label, Randomized Controlled Phase 4 Study to Evaluate the Efficacy and Safety of CertiroBell® Compared With Mycophenolate Mofetil in Primary Living Donor Liver Transplant Recipients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chong Kun Dang Pharmaceutical</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chong Kun Dang Pharmaceutical</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</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 evaluate the efficacy and safety of CertiroBell® tablet&#xD;
      compared with mycophenolate mofetil in primary living donor liver transplant recipients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is multi-center, open-label, randomized controlled phase 4 study to evaluate the&#xD;
      efficacy and safety of certirobell® tablet compared with mycophenolate mofetil in primary&#xD;
      living donor liver transplant recipients.&#xD;
&#xD;
      On the first visit the patients scheduled to be operated liver transplant in 35 days will be&#xD;
      conducted screening. Patients who meet the criteria of this clinical trial will be randomized&#xD;
      to CertiroBell or mycophenolate mofetil on the second visit. Each group will take CertiroBell&#xD;
      or mycophenolate mofetil and will conduct scheduled tests with 5 additional visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 30, 2020</start_date>
  <completion_date type="Anticipated">November 17, 2022</completion_date>
  <primary_completion_date type="Anticipated">September 13, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of composite efficacy failure</measure>
    <time_frame>until 24 weeks after taking medicine</time_frame>
    <description>composite efficacy failure include biopsy-confirmed acute rejection, graft loss, death, or follow-up failure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of biopsy-confirmed acute rejection</measure>
    <time_frame>until 24weeks and 48weeks after taking medicine</time_frame>
    <description>acute rejection confirmed by result of biopsy(over 4 points of RAI score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The pathological results and time of occurrence and method of treatment, result of the treatment of acute rejection confirmed by biopsy(over 4 points of RAI score)</measure>
    <time_frame>until 24weeks and 48weeks after taking medicine</time_frame>
    <description>details of acute rejection confirmed by result of biopsy(over 4 points of RAI score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of composite efficacy failure</measure>
    <time_frame>until 48weeks after taking medicine</time_frame>
    <description>composite efficacy failure include biopsy-confirmed acute rejection, graft loss, death, or follow-up failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival rate of patients</measure>
    <time_frame>until 24weeks and 48weeks after taking medicine</time_frame>
    <description>Survival rate of patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival rate of transplanted organ</measure>
    <time_frame>until 24weeks and 48weeks after taking medicine</time_frame>
    <description>Survival rate of transplanted organ</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and recurrence rates of liver cancer</measure>
    <time_frame>until 24weeks and 48weeks after taking medicine</time_frame>
    <description>Incidence and recurrence rates of liver cancer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and recurrence rates of HCV infection</measure>
    <time_frame>until 24weeks and 48weeks after taking medicine</time_frame>
    <description>Incidence and recurrence rates of HCV infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of CMV infection</measure>
    <time_frame>until 24weeks and 48weeks after taking medicine</time_frame>
    <description>Incidence of CMV infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>variation of Serum creatinine, eGFR(estimated glomerular filtration rate) compared to the baseline</measure>
    <time_frame>at 24 weeks and 48weeks</time_frame>
    <description>eGFR using MDRD(Modification of Diet in Renal Disease) method</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Liver Transplant</condition>
  <arm_group>
    <arm_group_label>CertiroBell Tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>De novo liver transplant recipients will be randomized after liver transplant operation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mycophenolate mofetil Tablet/Capsule</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>De novo liver transplant recipients will be randomized after liver transplant operation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus Tab.</intervention_name>
    <description>After first dose 1mg BID(total 2mg daily PO), check the blood concentration of everolimus at each visit and adjust the dose to acheive the blood concentration maintaining at 3~8ng/mL.</description>
    <arm_group_label>CertiroBell Tablet</arm_group_label>
    <other_name>CertiroBell Tab.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate mofetil Tab./Cap.</intervention_name>
    <description>Up to 1.5g BID(total 3g daily), PO</description>
    <arm_group_label>Mycophenolate mofetil Tablet/Capsule</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        * Inclusion Criteria:&#xD;
&#xD;
        [Time of screening]&#xD;
&#xD;
          -  Patients who have transplanted in primary living donor liver in 35 days or who plan to&#xD;
             be transplanted in primary living donor liver.&#xD;
&#xD;
          -  Over 20 years old(male or female)&#xD;
&#xD;
          -  Agreement with written informed consent&#xD;
&#xD;
        [Time of randomization] - Patients who have transplanted liver within 4 weeks(25 days to 35&#xD;
        days)&#xD;
&#xD;
        * Exclusion Criteria&#xD;
&#xD;
        [Time of screening]&#xD;
&#xD;
          -  Patients who have transplanted non-liver organs or have plan to be transplanted&#xD;
             non-liver organs.&#xD;
&#xD;
          -  Patients with bioartificial liver (cell system)&#xD;
&#xD;
          -  Patients who diagnosed with malignant tumor within 5 years [however, who have&#xD;
             recovered from skin cancer (squamous cell/basal cell carcinoma) or thyroid cancer,&#xD;
             hepatocellular carcinoma without main vessel invasion or extrahepatic metastasis can&#xD;
             be enrolled]&#xD;
&#xD;
          -  Patients with severe systemic infection&#xD;
&#xD;
          -  Women who are pregnant or breast feeding or not agree to the proper use of&#xD;
             contraception during the trial&#xD;
&#xD;
          -  Participated in other trial within 4 weeks&#xD;
&#xD;
          -  In investigator's judgement&#xD;
&#xD;
        [Time of randomization]&#xD;
&#xD;
          -  Patients with acute rejection who have been clinically treated after liver&#xD;
             transplantation.&#xD;
&#xD;
          -  Patients with complication related to the hepatic artery such as hepatic artery&#xD;
             thrombosis at the time of randomization.&#xD;
&#xD;
          -  At screening&#xD;
&#xD;
               -  WBC &lt;1,500/mm^3 or PLT &lt;30,000/mm^3 or over 3 times upper than normal range of&#xD;
                  liver function tests(T-bilirubin, AST, ALT) levels&#xD;
&#xD;
               -  Protein/Creatinine ratio(urine test) &gt; 1 or eGFR by MDRD&lt; 30mL/min/1.73m^2 or&#xD;
                  Total cholesterol &gt; 350mg/dL or triglycerides &gt; 500mg/dL&#xD;
&#xD;
          -  Patients taking HCV(hepatitis C virus) Therapeutic Drugs&#xD;
&#xD;
          -  Patients who had plasmapheresis within 1 week.&#xD;
&#xD;
          -  Patents who had a record of taking mTOR inhibitor before.&#xD;
&#xD;
          -  In investigator's judgement&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Soon Il Kim, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Severance Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Soon Il Kim, M.D., Ph.D.</last_name>
    <phone>82-2-2228-2131</phone>
    <email>SOONKIM@YUHS.AC</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Soo J Myung</last_name>
    <phone>82-2-6373-0658</phone>
    <email>sjm9@ckdpharm.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>July 10, 2020</last_update_submitted>
  <last_update_submitted_qc>July 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 15, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Everolimus</keyword>
  <keyword>CertiroBell</keyword>
  <keyword>Mycophenolate mofetil</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Everolimus</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/NCT04471441
org study id: B95-02LT1903
nct id: NCT04471441
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of CertiroBell® tablet
      compared with mycophenolate mofetil in primary living donor liver transplant recipients.
This study is multi-center, open-label, randomized controlled phase 4 study to evaluate the
      efficacy and safety of certirobell® tablet compared with mycophenolate mofetil in primary
      living donor liver transplant recipients.

      On the first visit the patients scheduled to be operated liver transplant in 35 days will be
      conducted screening. Patients who meet the criteria of this clinical trial will be randomized
      to CertiroBell or mycophenolate mofetil on the second visit. Each group will take CertiroBell
      or mycophenolate mofetil and will conduct scheduled tests with 5 additional visits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of composite efficacy failure
time frame: until 24 weeks after taking medicine
description: composite efficacy failure include biopsy-confirmed acute rejection, graft loss, death, or follow-up failure
measure: Incidence of biopsy-confirmed acute rejection
time frame: until 24weeks and 48weeks after taking medicine
description: acute rejection confirmed by result of biopsy(over 4 points of RAI score)
measure: The pathological results and time of occurrence and method of treatment, result of the treatment of acute rejection confirmed by biopsy(over 4 points of RAI score)
time frame: until 24weeks and 48weeks after taking medicine
description: details of acute rejection confirmed by result of biopsy(over 4 points of RAI score)
measure: Incidence of composite efficacy failure
time frame: until 48weeks after taking medicine
description: composite efficacy failure include biopsy-confirmed acute rejection, graft loss, death, or follow-up failure
measure: Survival rate of patients
time frame: until 24weeks and 48weeks after taking medicine
description: Survival rate of patients
measure: Survival rate of transplanted organ
time frame: until 24weeks and 48weeks after taking medicine
description: Survival rate of transplanted organ
measure: Incidence and recurrence rates of liver cancer
time frame: until 24weeks and 48weeks after taking medicine
description: Incidence and recurrence rates of liver cancer
measure: Incidence and recurrence rates of HCV infection
time frame: until 24weeks and 48weeks after taking medicine
description: Incidence and recurrence rates of HCV infection
measure: Incidence of CMV infection
time frame: until 24weeks and 48weeks after taking medicine
description: Incidence of CMV infection
measure: variation of Serum creatinine, eGFR(estimated glomerular filtration rate) compared to the baseline
time frame: at 24 weeks and 48weeks
description: eGFR using MDRD(Modification of Diet in Renal Disease) method
arm group label: CertiroBell Tablet
arm group type: Experimental
description: De novo liver transplant recipients will be randomized after liver transplant operation.
arm group label: Mycophenolate mofetil Tablet/Capsule
arm group type: Active Comparator
description: De novo liver transplant recipients will be randomized after liver transplant operation.
intervention type: Drug
intervention name: Everolimus Tab.
description: After first dose 1mg BID(total 2mg daily PO), check the blood concentration of everolimus at each visit and adjust the dose to acheive the blood concentration maintaining at 3~8ng/mL.
arm group label: CertiroBell Tablet
other name: CertiroBell Tab.
intervention type: Drug
intervention name: Mycophenolate mofetil Tab./Cap.
description: Up to 1.5g BID(total 3g daily), PO
arm group label: Mycophenolate mofetil Tablet/Capsule
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Soon Il Kim, M.D., Ph.D.
role: Principal Investigator
affiliation: Severance Hospital
last name: Soon Il Kim, M.D., Ph.D.
phone: 82-2-2228-2131
email: SOONKIM@YUHS.AC
last name: Soo J Myung
phone: 82-2-6373-0658
email: sjm9@ckdpharm.com
facility: 
status: Recruiting
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Mycophenolic Acid
mesh term: Everolimus