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/NCT06025552</url>
    </required_header>
    <id_info>
      <org_study_id>TUB4PI-01</org_study_id>
      <nct_id>NCT06025552</nct_id>
    </id_info>
    <brief_title>Study of TU7710 in Warfarin Anti-coagulated Healthy Male Subjects</brief_title>
    <official_title>A First-in-Human (FIH), Randomized, Double-Blind, Placebo-controlled, Phase 1a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of TU7710 Following Single, Ascending, Intravenous, Dose Administration in Warfarin Anti-coagulated Healthy Male Subjects</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>TiumBio Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>TiumBio Co., Ltd.</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>
        This is a Phase 1a, double-blind, randomized, placebo- controlled, SAD study to assess&#xD;
        safety, tolerability, PK, and PD of TU7710 in warfarin treated healthy male participants.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The 40 subjects will be divided into 5 cohorts, and the subjects assigned to each cohort will&#xD;
        be randomly assigned with 6 persons receiving TU7710 and 2 persons receiving a placebo for&#xD;
        TU7710. Each cohort will proceed in sequence and the next cohort study will be decided by the&#xD;
        Safety Monitoring Committee (SMC) .&#xD;
  &#xD;
        Subjects will be participated in the study after warfarin anti-coagulation to maintain the&#xD;
        INR between 2.00 and 3.00 as a preventive measure for potential thrombosis prior to the IP&#xD;
        administration.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 2, 2023</start_date>
    <completion_date type="Anticipated">February 2024</completion_date>
    <primary_completion_date type="Anticipated">February 2024</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>5 cohorts with 5 dose levels will sequentially be escalated after safety review.&#xD;
  8 subjects in each cohort who will be randomly assigned to placebo or TU7710 group in 2:6 ratio.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number and proportion of participants with adverse events</measure>
      <time_frame>30 days post-dose</time_frame>
      <description>Number and proportion of participants with adverse events/ adverse reaction /SAE overall and by treatment group</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of subjects with significant abnormal laboratory values</measure>
      <time_frame>30 days post-dose</time_frame>
      <description>Mean with standard deviation, median, maximum, minimum results of laboratory values in each treatment group. The laboratory parameters that will be assessed are clinical chemistry, hematology and urinalysis.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>ADA and Neutralizing antibody results</measure>
      <time_frame>30 days post-dose</time_frame>
      <description>Incidence of subjects with ADA and Nab positive results</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of subjects with significant abnormal Electrocardiography (ECG) findings</measure>
      <time_frame>30 days post-dose</time_frame>
      <description>Mean with standard deviation, median, maximum, minimum results of ECG results in each treatment group. The ECG parameters that will be assessed are heart rate, PR interval, QRS interval, QT interval, and QTcF interval.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of subjects With Significant Abnormal vital sign findings</measure>
      <time_frame>30 days post-dose</time_frame>
      <description>Mean with standard deviation, median, maximum, minimum results of vital sign values in each treatment group. The vital signs that will be assessed are body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics assessment_Maximum concentration</measure>
      <time_frame>4 days post-dose</time_frame>
      <description>Maximum plasma VIIa activity level in each dose level</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics assessment_AUC last</measure>
      <time_frame>4 days post-dose</time_frame>
      <description>Area under plasma activity-time curve after TU7710 single administration from time zero to last quantifiable concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics assessment_AUC inf</measure>
      <time_frame>4 days post-dose</time_frame>
      <description>Area Under the Plasma activity-time curve after TU7710 single administration From Time Zero Extrapolated to Infinity</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics assessment_Clearance</measure>
      <time_frame>4 days post-dose</time_frame>
      <description>Clearance after TU7710 single administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics assessment_Volume of distribution</measure>
      <time_frame>4 days post-dose</time_frame>
      <description>Volume of distribution after TU7710 single administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics assessment_Dose proportionality</measure>
      <time_frame>4 days post-dose</time_frame>
      <description>Regression analysis using the power model between the log-converted Cmax, AUClast, and the log-converted dose can be performed, and each parameter adjusted by dose can be calculated and compared between the dose groups</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics assessment_Tmax</measure>
      <time_frame>4 days post-dose</time_frame>
      <description>Time from administration to maximum plasma VIIa level in each dose level</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacodynamic assessment_INR change from baseline</measure>
      <time_frame>5 days post-dose</time_frame>
      <description>INR measurement change from baseline to day 5 in each treatment group and dose level</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacodynamic assessment_PT change from baseline</measure>
      <time_frame>5 days post-dose</time_frame>
      <description>PT measurement change from baseline to day 5 in each treatment group and dose level</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacodynamic assessment_aPTT change from baseline</measure>
      <time_frame>5 days post-dose</time_frame>
      <description>aPTT measurement change from baseline to day 5 in each treatment group and dose level</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics assessment_incremental recovery</measure>
      <time_frame>4 days post-dose</time_frame>
      <description>Incremental recovery after TU7710 single administration expressed as the ratio of measured peak level against dose per bodyweight</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Hemophilia A</condition>
    <condition>Hemophilia B</condition>
    <condition>Blood Coagulation Disorders</condition>
    <arm_group>
      <arm_group_label>TU7710</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>TU7710 of escalating 5 doses</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Normal Saline (placebo of TU7710)</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo of TU7710 at corresponding TU7710 dose level</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>TU7710</intervention_name>
      <description>In each dose level, 6 subjects will be assigned to TU7710. Anticipated escalating dose levels are 100mcg/kg, 200mcg/kg, 400mcg/kg, 800mcg/kg and the last dose will be decided after assessing cohort 1~4 PK, PD, safety, and exploratory efficacy data.</description>
      <arm_group_label>TU7710</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Normal saline</intervention_name>
      <description>Placebo of TU7710 at corresponding TU7710 dose level. In each dose level, 2 subjects will be assigned to placebo group.</description>
      <arm_group_label>Normal Saline (placebo of TU7710)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age ≥19 and ≤45&#xD;
  &#xD;
            -  BMI of ≥18.0 kg/m2 and ≤30.0 kg/m2&#xD;
  &#xD;
            -  Body weight of ≥55.0 kg and ≤90.0 kg&#xD;
  &#xD;
            -  Provide informed consent and willing to comply with study requirements.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History or at risk of developing diseases related to venous thromboembolic events or&#xD;
               has family history of such disease&#xD;
  &#xD;
            -  History of major bleeding/traumatic event or major surgery within 6 month&#xD;
  &#xD;
            -  History of any other clinically relevant coagulation disorder (such as&#xD;
               gastrointestinal bleeding, hemorrhoid hemorrhage)&#xD;
  &#xD;
            -  Abnormal coagulation related laboratory abnormal test results, including protein C,&#xD;
               protein S, PT, aPTT&#xD;
  &#xD;
            -  history or current symptoms of gastrointestinal, liver, or renal disease that may&#xD;
               affect the pharmacokinetics of the IP&#xD;
  &#xD;
            -  History of or are currently with hepatitis B or C (active or carrier state) or human&#xD;
               immunodeficiency virus (HIV) or syphilis infection.&#xD;
  &#xD;
            -  Currently smoking or have smoked within 1 month before IP or positive cotinine results&#xD;
  &#xD;
            -  History of alcohol abuse or positive alcohol breath test&#xD;
  &#xD;
            -  Excessive caffeine intake within 7 days before IP&#xD;
  &#xD;
            -  INR results not between 2.0~3.0 range after warfarin treatment&#xD;
  &#xD;
            -  History of hypersensitivity to medicinal product similar to TU7710 active ingredient&#xD;
               or excipient&#xD;
  &#xD;
            -  Laboratory abnormal test results, such as QTcF &lt;340msec or &gt;450msec (or family history&#xD;
               of long QT syndrome), LDL &gt;190mg/dl , Total cholesterol &gt;300mg/dl, triglycerides &gt;&#xD;
               350mg/dl, ALT &gt;1.5*ULN, AST &gt;1.5*ULN, bilirubin &gt;1.5*ULN&#xD;
  &#xD;
            -  Abnormal vital sign SBP &gt;140mmHG, DBP &lt;90mmHg, heart rate &lt;40bpm or &gt;85bpm&#xD;
  &#xD;
            -  Any medical history that may increase the risk or affect the evaluation of study&#xD;
               objectives by participating in this study at the discretion of the investigator.&#xD;
               (e.g., neurology or psychiatric history)&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Heeyeon Jung</last_name>
      <phone>031-600-1500</phone>
      <phone_ext>1513</phone_ext>
      <email>tiumbio@tiumbio.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Seoul National University Hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <investigator>
        <last_name>Kyung Sang Yoo, M.D, Ph.D</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Korea, Republic of</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hemostatic Disorders</mesh_term>
      <mesh_term>Hemophilia A</mesh_term>
      <mesh_term>Hemophilia B</mesh_term>
      <mesh_term>Blood Coagulation Disorders</mesh_term>
    </condition_browse>
    <!-- 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/NCT06025552
  org study id: TUB4PI-01
  nct id: NCT06025552
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a Phase 1a, double-blind, randomized, placebo- controlled, SAD study to assess
        safety, tolerability, PK, and PD of TU7710 in warfarin treated healthy male participants.
  The 40 subjects will be divided into 5 cohorts, and the subjects assigned to each cohort will
        be randomly assigned with 6 persons receiving TU7710 and 2 persons receiving a placebo for
        TU7710. Each cohort will proceed in sequence and the next cohort study will be decided by the
        Safety Monitoring Committee (SMC) .
  
        Subjects will be participated in the study after warfarin anti-coagulation to maintain the
        INR between 2.00 and 3.00 as a preventive measure for potential thrombosis prior to the IP
        administration.
  allocation: Randomized
  intervention model: Sequential Assignment
  intervention model description: 5 cohorts with 5 dose levels will sequentially be escalated after safety review.
  8 subjects in each cohort who will be randomly assigned to placebo or TU7710 group in 2:6 ratio.
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Number and proportion of participants with adverse events
  time frame: 30 days post-dose
  description: Number and proportion of participants with adverse events/ adverse reaction /SAE overall and by treatment group
  measure: Number of subjects with significant abnormal laboratory values
  time frame: 30 days post-dose
  description: Mean with standard deviation, median, maximum, minimum results of laboratory values in each treatment group. The laboratory parameters that will be assessed are clinical chemistry, hematology and urinalysis.
  measure: ADA and Neutralizing antibody results
  time frame: 30 days post-dose
  description: Incidence of subjects with ADA and Nab positive results
  measure: Number of subjects with significant abnormal Electrocardiography (ECG) findings
  time frame: 30 days post-dose
  description: Mean with standard deviation, median, maximum, minimum results of ECG results in each treatment group. The ECG parameters that will be assessed are heart rate, PR interval, QRS interval, QT interval, and QTcF interval.
  measure: Number of subjects With Significant Abnormal vital sign findings
  time frame: 30 days post-dose
  description: Mean with standard deviation, median, maximum, minimum results of vital sign values in each treatment group. The vital signs that will be assessed are body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
  measure: Pharmacokinetics assessment_Maximum concentration
  time frame: 4 days post-dose
  description: Maximum plasma VIIa activity level in each dose level
  measure: Pharmacokinetics assessment_AUC last
  time frame: 4 days post-dose
  description: Area under plasma activity-time curve after TU7710 single administration from time zero to last quantifiable concentration
  measure: Pharmacokinetics assessment_AUC inf
  time frame: 4 days post-dose
  description: Area Under the Plasma activity-time curve after TU7710 single administration From Time Zero Extrapolated to Infinity
  measure: Pharmacokinetics assessment_Clearance
  time frame: 4 days post-dose
  description: Clearance after TU7710 single administration
  measure: Pharmacokinetics assessment_Volume of distribution
  time frame: 4 days post-dose
  description: Volume of distribution after TU7710 single administration
  measure: Pharmacokinetics assessment_Dose proportionality
  time frame: 4 days post-dose
  description: Regression analysis using the power model between the log-converted Cmax, AUClast, and the log-converted dose can be performed, and each parameter adjusted by dose can be calculated and compared between the dose groups
  measure: Pharmacokinetics assessment_Tmax
  time frame: 4 days post-dose
  description: Time from administration to maximum plasma VIIa level in each dose level
  measure: Pharmacodynamic assessment_INR change from baseline
  time frame: 5 days post-dose
  description: INR measurement change from baseline to day 5 in each treatment group and dose level
  measure: Pharmacodynamic assessment_PT change from baseline
  time frame: 5 days post-dose
  description: PT measurement change from baseline to day 5 in each treatment group and dose level
  measure: Pharmacodynamic assessment_aPTT change from baseline
  time frame: 5 days post-dose
  description: aPTT measurement change from baseline to day 5 in each treatment group and dose level
  measure: Pharmacokinetics assessment_incremental recovery
  time frame: 4 days post-dose
  description: Incremental recovery after TU7710 single administration expressed as the ratio of measured peak level against dose per bodyweight
  arm group label: TU7710
  arm group type: Experimental
  description: TU7710 of escalating 5 doses
  arm group label: Normal Saline (placebo of TU7710)
  arm group type: Placebo Comparator
  description: Placebo of TU7710 at corresponding TU7710 dose level
  intervention type: Drug
  intervention name: TU7710
  description: In each dose level, 6 subjects will be assigned to TU7710. Anticipated escalating dose levels are 100mcg/kg, 200mcg/kg, 400mcg/kg, 800mcg/kg and the last dose will be decided after assessing cohort 1~4 PK, PD, safety, and exploratory efficacy data.
  arm group label: TU7710
  intervention type: Drug
  intervention name: Normal saline
  description: Placebo of TU7710 at corresponding TU7710 dose level. In each dose level, 2 subjects will be assigned to placebo group.
  arm group label: Normal Saline (placebo of TU7710)
  criteria: 
  gender: Male
  minimum age: 19 Years
  maximum age: 45 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Heeyeon Jung
  phone: 031-600-1500
  phone ext: 1513
  email: tiumbio@tiumbio.com
  facility: 
  status: Recruiting
  investigator: 
  country: Korea, Republic of
  responsible party type: Sponsor
  mesh term: Hemostatic Disorders
  mesh term: Hemophilia A
  mesh term: Hemophilia B
  mesh term: Blood Coagulation Disorders