<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/NCT02195440</url>
  </required_header>
  <id_info>
    <org_study_id>PRI-724-1101</org_study_id>
    <secondary_id>UMIN000014395</secondary_id>
    <nct_id>NCT02195440</nct_id>
  </id_info>
  <brief_title>An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis</brief_title>
  <official_title>An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients With HCV-induced Cirrhosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Komagome Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Prism Pharma Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Japan Agency for Medical Research and Development</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Komagome Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the safety and tolerability of PRI-724 in&#xD;
      patients with HCV-induced cirrhosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, open-label, continuous i.v. administration, dose escalation Phase I&#xD;
      study in patients with hepatitis C cirrhosis.&#xD;
&#xD;
      One cycle consisted of one-week continuous i.v. administration of PRI-724 followed by a&#xD;
      one-week observation period. One cohort was a total of six cycles, a 12-week treatment&#xD;
      period.&#xD;
&#xD;
      PRI-724 was administered at a dose of 10 mg/m2/day in Cohort 1, 40 mg/m2/day in Cohort 2, and&#xD;
      160 mg/m2/day in Cohort 3 in a dose escalation manner. Each cohort was to include 6 subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">March 31, 2017</completion_date>
  <primary_completion_date type="Actual">March 31, 2017</primary_completion_date>
  <phase>Phase 1</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values)</measure>
    <time_frame>12 weeks after the initiation of PRI-724 administration</time_frame>
    <description>Items and ratio%</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Child-Pugh Score</measure>
    <time_frame>12 weeks after the initiation of PRI-724 administration</time_frame>
    <description>Changes of score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver biopsy: Histology Activity Index (HAI)</measure>
    <time_frame>12 weeks after the initiation of PRI-724 administration</time_frame>
    <description>Changes of index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum albumin level</measure>
    <time_frame>12 weeks after the initiation of PRI-724 administration</time_frame>
    <description>Changes of level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum fibrosis marker level(s)</measure>
    <time_frame>12 weeks after the initiation of PRI-724 administration</time_frame>
    <description>Changes of level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ascitic fluid level</measure>
    <time_frame>12 weeks after the initiation of PRI-724 administration</time_frame>
    <description>Changes of level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement rate of lower leg edema</measure>
    <time_frame>12 weeks after the initiation of PRI-724 administration</time_frame>
    <description>Changes of rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Area under the plasma concentration versus time curve (AUCinf) of PRI-724 through analysis of blood samples</measure>
    <time_frame>Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h</time_frame>
    <description>Comparison of AUC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Steady State Plasma Concentration (Css) of PRI-724 through analysis of blood samples</measure>
    <time_frame>Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h</time_frame>
    <description>Comparison of Css</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Hepatitis C Virus-infected Cirrhosis</condition>
  <arm_group>
    <arm_group_label>PRI-724</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 cohorts (PRI-724: 10, 40, 160 mg/m2/day), 6 cycles (1 cycle: 1-week continuous i.v. administration+1-week observation period)&#xD;
*Cycle 2 will not be started until plasma drug concentrations of PRI-724 and C-82 on Days 1 and 2 in Cycle 1 are confirmed.&#xD;
Cohort 1: 10 mg/m2/day (6 subjects) Cohort 2: 40 mg/m2/day (6 subjects) Cohort 3: 160 mg/m2/day (6 subjects) One cycle consists of 1-week continuous i.v. administration of PRI-724 followed by a 1-week observation period. The tolerability and safety after 6 cycles will be confirmed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PRI-724</intervention_name>
    <description>10 - 160 mg/m2, 7 days CIV (in the vein) with 7 days rest per one cycle. Number of Cycles: 6.</description>
    <arm_group_label>PRI-724</arm_group_label>
    <other_name>CBP-beta-catennin inhibitor</other_name>
    <other_name>OP-724</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Presence of cirrhosis due to hepatitis C virus. 1) Serum HCV-RNA test positive 2)&#xD;
             Definitive diagnosis of cirrhosis established by liver biopsy (HAI score: Grade IV-D).&#xD;
&#xD;
          2. Child-Pugh Class A or B at the time of informed consent, with no likelihood of&#xD;
             improvement with existing medical treatment.&#xD;
&#xD;
          3. Performance Status: 0 - 2.&#xD;
&#xD;
          4. Between =&gt;20 and &lt;75 years of age at the time of providing written consent.&#xD;
&#xD;
          5. Having provided voluntary written consent for participation in this study.&#xD;
&#xD;
          6. Esophageal and gastric varices are well controlled&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with cirrhosis due to causes other than hepatitis C virus; or patients with&#xD;
             cirrhosis due to unknown causes.&#xD;
&#xD;
          2. Patients with a history of primary liver cancer or a complication thereof.&#xD;
&#xD;
          3. Patients with a complication of malignant tumor or a history thereof (within 5 years&#xD;
             prior to screening).&#xD;
&#xD;
          4. Patients in whom such active viral infections as HBV, HIV or ATCL or syphilis&#xD;
             infection cannot be ruled out.&#xD;
&#xD;
          5. Patients with serum creatinine &gt;1.5 times over upper normal or creatinine clearance&#xD;
             =&lt;60 mL/min/1.73 m2.&#xD;
&#xD;
          6. Patients with hemoglobin &lt;8 g/dL.&#xD;
&#xD;
          7. Patients with platelet count &lt;50,000 /&amp;micro;L.&#xD;
&#xD;
          8. Patients with T.Bil =&gt;3.0 mg/dL.&#xD;
&#xD;
          9. Patients with a complication of poorly controlled diabetes, hypertension or heart&#xD;
             failure.&#xD;
&#xD;
         10. Patients with a complication of mental disorder requiring treatment.&#xD;
&#xD;
         11. Patients with serious allergy to contrast media or a history thereof.&#xD;
&#xD;
         12. Patients with allergy to inactive ingredients of the study drug.&#xD;
&#xD;
         13. Patients who have received interferon, ribavirin or anti-HCV agents within 12 weeks&#xD;
             before registration in this study.&#xD;
&#xD;
         14. When the medical treatment to a primary disease is carried out, Patient who was&#xD;
             changed the dosage and administration within the 12 weeks before registration.&#xD;
&#xD;
         15. Patients with a history of drug or alcohol addiction within five years at the time of&#xD;
             providing written consent or a history of drug or alcohol abuse within the past one&#xD;
             year.&#xD;
&#xD;
         16. The patient who received a liver transplant or other organ transplants (a bone marrow&#xD;
             transplantation is included), and the patient for whom intravenous administration and&#xD;
             venous access are difficult.&#xD;
&#xD;
         17. Patients contraindicated for liver biopsy.&#xD;
&#xD;
         18. Female patients who are pregnant or suspected to be pregnant; or those who desire to&#xD;
             get pregnant during the study period or those of childbearing potential.&#xD;
&#xD;
         19. Male patients who do not consent to practice birth control during the clinical study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kiminori Kimura, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Komagome Metropolitan Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tokyo metropolitan Komagome Hospital</name>
      <address>
        <city>Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <last_update_submitted>July 4, 2022</last_update_submitted>
  <last_update_submitted_qc>July 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Komagome Hospital</investigator_affiliation>
    <investigator_full_name>Kiminori Kimura, MD</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Hepatitis C virus, cirrhosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_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/NCT02195440
org study id: PRI-724-1101
secondary id: UMIN000014395
nct id: NCT02195440
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to investigate the safety and tolerability of PRI-724 in
      patients with HCV-induced cirrhosis.
This is a single-center, open-label, continuous i.v. administration, dose escalation Phase I
      study in patients with hepatitis C cirrhosis.

      One cycle consisted of one-week continuous i.v. administration of PRI-724 followed by a
      one-week observation period. One cohort was a total of six cycles, a 12-week treatment
      period.

      PRI-724 was administered at a dose of 10 mg/m2/day in Cohort 1, 40 mg/m2/day in Cohort 2, and
      160 mg/m2/day in Cohort 3 in a dose escalation manner. Each cohort was to include 6 subjects.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse events and adverse drug reactions (including subjective symptoms and abnormal laboratory values)
time frame: 12 weeks after the initiation of PRI-724 administration
description: Items and ratio%
measure: Child-Pugh Score
time frame: 12 weeks after the initiation of PRI-724 administration
description: Changes of score
measure: Liver biopsy: Histology Activity Index (HAI)
time frame: 12 weeks after the initiation of PRI-724 administration
description: Changes of index
measure: Serum albumin level
time frame: 12 weeks after the initiation of PRI-724 administration
description: Changes of level
measure: Serum fibrosis marker level(s)
time frame: 12 weeks after the initiation of PRI-724 administration
description: Changes of level
measure: Ascitic fluid level
time frame: 12 weeks after the initiation of PRI-724 administration
description: Changes of level
measure: Improvement rate of lower leg edema
time frame: 12 weeks after the initiation of PRI-724 administration
description: Changes of rate
measure: Assessment of Area under the plasma concentration versus time curve (AUCinf) of PRI-724 through analysis of blood samples
time frame: Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h
description: Comparison of AUC
measure: Assessment of Steady State Plasma Concentration (Css) of PRI-724 through analysis of blood samples
time frame: Days 1-2 for preinfusion, 0.5, 1.0, 2.0, 4.0, and 24h; Day 7-8 for prestopping, 0.5, 1.0, 2.0, 4.0, and 24h
description: Comparison of Css
arm group label: PRI-724
arm group type: Experimental
description: 3 cohorts (PRI-724: 10, 40, 160 mg/m2/day), 6 cycles (1 cycle: 1-week continuous i.v. administration+1-week observation period)
*Cycle 2 will not be started until plasma drug concentrations of PRI-724 and C-82 on Days 1 and 2 in Cycle 1 are confirmed.
Cohort 1: 10 mg/m2/day (6 subjects) Cohort 2: 40 mg/m2/day (6 subjects) Cohort 3: 160 mg/m2/day (6 subjects) One cycle consists of 1-week continuous i.v. administration of PRI-724 followed by a 1-week observation period. The tolerability and safety after 6 cycles will be confirmed.
intervention type: Drug
intervention name: PRI-724
description: 10 - 160 mg/m2, 7 days CIV (in the vein) with 7 days rest per one cycle. Number of Cycles: 6.
arm group label: PRI-724
other name: CBP-beta-catennin inhibitor
other name: OP-724
criteria: 
gender: All
minimum age: 20 Years
maximum age: 74 Years
healthy volunteers: No
last name: Kiminori Kimura, MD
role: Principal Investigator
affiliation: Komagome Metropolitan Hospital
facility: 
country: Japan
responsible party type: Principal Investigator
investigator affiliation: Komagome Hospital
investigator full name: Kiminori Kimura, MD
investigator title: MD
mesh term: Hepatitis C
mesh term: Hepatitis
mesh term: Liver Cirrhosis
mesh term: Fibrosis