<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/NCT03752658</url>
  </required_header>
  <id_info>
    <org_study_id>IN-US-320-4669</org_study_id>
    <nct_id>NCT03752658</nct_id>
  </id_info>
  <brief_title>TAF Real World Study for Universal Effectiveness</brief_title>
  <acronym>TRUE</acronym>
  <official_title>A Real-world Clinical Study on Effectiveness and Safety of Long-term TAF Treatment in Chronic Hepatitis B Patients in China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tongji Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Tongji Hospital</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>
      This study is a multi-center, prospective, real-world study, males and non-pregnant,&#xD;
      non-lactating female HBeAg positive or negative patients (above 18 years of age) who were&#xD;
      mono-infected with HBV, either NA treatment-naïve or treatment-experienced, but TAF naïve&#xD;
      will be enrolled in this study, and they will be treated with TAF, alone or in combination&#xD;
      with other HBV antivirals. During 36 months of treatment, efficacy and safety will be&#xD;
      evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a multi-center, prospective, real-world study, aiming to investigate the use of&#xD;
      TAF in routine clinical management of chronic hepatitis B patients and evaluate its&#xD;
      effectiveness and safety across a heterogeneous population in China. Approximately 500&#xD;
      patients will take part in this study, 10 sites will be included which distribute in China's&#xD;
      major cities, thus each site will enroll 50 patients. Male or female HBeAg positive or&#xD;
      negative patients (above 18 years of age) who were mono-infected with HBV, either NA&#xD;
      treatment-naïve or treatment-experienced, but TAF naïve will be enrolled in this study, and&#xD;
      they will be treated with TAF, alone or in combination with other HBV antivirals. During 36&#xD;
      months of treatment, efficacy and safety will be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 25, 2019</start_date>
  <completion_date type="Anticipated">September 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>proportion of participants with HBV DNA &lt; 20 IU/mL</measure>
    <time_frame>36 months</time_frame>
    <description>proportion of participants with HBV DNA &lt; 20 IU/mL as measured by the COBAS TaqMan HBV Test (Roche Molecular Diagnostics, Pleasanton, CA, USA), with taken at 36 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with HBV DNA &lt; 20 IU/mL</measure>
    <time_frame>12 months</time_frame>
    <description>The proportion of patients with HBV DNA &lt; 20 IU/mL at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with HBV DNA &lt;300 copies/mL</measure>
    <time_frame>12 months</time_frame>
    <description>The proportion of patients with HBV DNA &lt;300 copies/mL at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with HBV DNA &lt; 20 IU/mL</measure>
    <time_frame>24 months</time_frame>
    <description>The proportion of patients with HBV DNA &lt; 20 IU/mL at 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with HBV DNA &lt;300 copies/mL IU/mL</measure>
    <time_frame>24 months</time_frame>
    <description>The proportion of patients with HBV DNA &lt;300 copies/mL at 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with HBV DNA &lt;300 copies/mL IU/mL</measure>
    <time_frame>36 months</time_frame>
    <description>The proportion of patients with HBV DNA &lt;300 copies/mL at 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with Hepatitis B e Antigen (HBeAg) Loss</measure>
    <time_frame>36 months</time_frame>
    <description>Proportion of participants with Hepatitis B e Antigen (HBeAg) Loss at 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with seroconversion to Anti-Hepatitis B e-Antigen (Anti-HBe)</measure>
    <time_frame>36 months</time_frame>
    <description>Proportion of participants with seroconversion to Anti-Hepatitis B e-Antigen (Anti-HBe) at 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with Normal Alanine Aminotransferase (ALT)</measure>
    <time_frame>36 months</time_frame>
    <description>Proportion of participants with Normal Alanine Aminotransferase (ALT) at 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in fibrosis as assessed by Fibroscan®</measure>
    <time_frame>36 months</time_frame>
    <description>Change from baseline in fibrosis as assessed by Fibroscan® at 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change from baseline in Bone Mineral Density (BMD)</measure>
    <time_frame>36 months</time_frame>
    <description>Percent Change from baseline in Bone Mineral Density (BMD) at 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)</measure>
    <time_frame>36 months</time_frame>
    <description>Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the rate of mother-to-child transmission of HBV</measure>
    <time_frame>at postpartum 6 months</time_frame>
    <description>For unplanned pregnant subjects, if not withdrawn, mother-to-child transmission (MTCT) rate</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Chronic Hepatitis b</condition>
  <arm_group>
    <arm_group_label>Tenofovir alafenamide (TAF)</arm_group_label>
    <description>Male or female HBeAg positive or negative patients (above 18 years of age) who were mono-infected with HBV, either NA treatment-naïve or treatment-experienced, but TAF naïve will be enrolled in this study, and they will be treated with TAF, alone or in combination with anti-HBV agents.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir Alafenamide</intervention_name>
    <description>The dose of tenofovir alafenamide (TAF) will be 25mg tablet taken orally once daily with food for 36 months, patients will be treated with TAF alone or in combination with anti-HBV agents</description>
    <arm_group_label>Tenofovir alafenamide (TAF)</arm_group_label>
    <other_name>Vemlidy®</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum, urine and whole blood will be restored in central lab&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Males and non-pregnant, non-lactating female patients with HBsAg positive &gt; 6 months above&#xD;
        18 years of age; Documented evidence of chronic HBV infection previously; HBV mono-infected&#xD;
        HBeAg positive or negative; NA treatment-naive and treatment-experienced; TAF naive; Agree&#xD;
        to participate in the study and sign the patient informed consent.&#xD;
&#xD;
        Subjects coinfected with HCV, hepatitis D virus (HDV), human immunodeficiency virus (HIV)&#xD;
        or who have received TAF or who haveChild-Pugh C decompensated liver disease or HCC will be&#xD;
        excluded.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Must have the ability to understand and sign a written informed consent form, consent&#xD;
             must be obtained prior to initiation of study procedures&#xD;
&#xD;
          2. Adult males and nonpregnant, nonlactating females&#xD;
&#xD;
          3. Documented evidence of chronic HBV infection previously&#xD;
&#xD;
          4. TAF naive&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patents who were TAF experienced&#xD;
&#xD;
          2. Women who are breastfeeding&#xD;
&#xD;
          3. Pregnant females&#xD;
&#xD;
          4. Co-infection with hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus&#xD;
             (HDV), or HIV&#xD;
&#xD;
          5. Evidence of hepatocellular carcinoma (Note: if screening alpha-fetoprotein (AFP) is &lt;&#xD;
             50 ng/mL no imaging study is needed; however, if the screening AFP is &gt; 50 ng/mL an&#xD;
             imaging study is required)&#xD;
&#xD;
          6. Chronic liver disease of non-HBV etiology (e.g., hemochromatosis, fatty liver disease,&#xD;
             cholangitis)&#xD;
&#xD;
          7. Current evidence of Child-Pugh Score C decompensated liver disease,or moderate to&#xD;
             severe ascites, Grade III-IV hepatic encephalopathy&#xD;
&#xD;
          8. Abnormal hematological and biochemical parameters, including:&#xD;
&#xD;
          9. Albumin &lt; 2.8 mg/ dL&#xD;
&#xD;
         10. International normalized ratio (INR) &gt; 2.3 X ULN (unless stable on anticoagulant&#xD;
             regimen)&#xD;
&#xD;
         11. Total bilirubin &gt; 3 X ULN&#xD;
&#xD;
         12. Patient develops clinical or laboratory findings suggestive of lactic acidosis or&#xD;
             pronounced hepatotoxicity&#xD;
&#xD;
         13. Received solid organ or bone marrow transplant, except patients who underwent liver or&#xD;
             kidney transplantation&#xD;
&#xD;
         14. Malignancy within 5 years prior to screening, with the exception of specific cancers&#xD;
             that are cured by surgical resection (e.g., basal cell skin cancer). Individuals under&#xD;
             evaluation for possible malignancy are not eligible.&#xD;
&#xD;
         15. Individuals receiving ongoing therapy with drugs not to be used with TAF or&#xD;
             individuals with a known hypersensitivity to study drugs, metabolites, or formulation&#xD;
             excipients&#xD;
&#xD;
         16. Any other clinical condition or prior therapy that, in the opinion of the&#xD;
             investigator, would make the individual unsuitable for the study or unable to comply&#xD;
             with dosing requirements&#xD;
&#xD;
         17. Use of investigational agents within 3 months of screening, unless allowed by the&#xD;
             sponsor&#xD;
&#xD;
         18. Patients included in another trial or having been given investigational drugs within&#xD;
             12 weeks prior to screening&#xD;
&#xD;
         19. Current alcohol or substance abuse judged by the investigator to potentially interfere&#xD;
             with compliance&#xD;
&#xD;
         20. Inability or unwillingness to provide informed consent or abide by the requirements of&#xD;
             the study&#xD;
&#xD;
         21. In addition to the above exclusion criteria, patients who meet any of the&#xD;
             contraindications for TAF&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Qin Ning, MD., Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Qin Ning, MD., Ph.D.</last_name>
    <phone>+86 278366 2391</phone>
    <email>qning@vip.sina.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Di Wu, MD., Ph.D.</last_name>
    <phone>+86 278366 2391</phone>
    <email>woody_1984@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Qin Ning, Prof.</last_name>
      <phone>862883662391</phone>
      <email>qning@vip.sina.com</email>
    </contact>
    <investigator>
      <last_name>Qin Ning, Doctor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Di Wu, Doctor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Shulan(Hangzhou) hospitai</name>
      <address>
        <city>Hangzhou</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhe Yu</last_name>
    </contact>
    <investigator>
      <last_name>Zhe Yu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>First Affiliated Hospital of Nanchang University</name>
      <address>
        <city>Nanchang</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiaoping Wu, Doctor</last_name>
    </contact>
    <investigator>
      <last_name>Xiaoping Wu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Shanghai public health clinic</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Liang Chen</last_name>
    </contact>
    <investigator>
      <last_name>Liang Chen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>General Hospital of The Yangtze River Shipping</name>
      <address>
        <city>Wuhan</city>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lvye Xu</last_name>
    </contact>
    <investigator>
      <last_name>Lvye Xu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Seventh Hospital of Wuhan</name>
      <address>
        <city>Wuhan</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Youqin Yan</last_name>
    </contact>
    <investigator>
      <last_name>Youqin Yan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Xiangya Hospital of Central South University</name>
      <address>
        <city>Xiangya</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yan Huang</last_name>
    </contact>
    <investigator>
      <last_name>Yan Huang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 26, 2018</study_first_posted>
  <last_update_submitted>November 25, 2019</last_update_submitted>
  <last_update_submitted_qc>November 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tongji Hospital</investigator_affiliation>
    <investigator_full_name>Qin Ning</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</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/NCT03752658
org study id: IN-US-320-4669
nct id: NCT03752658
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is a multi-center, prospective, real-world study, males and non-pregnant,
      non-lactating female HBeAg positive or negative patients (above 18 years of age) who were
      mono-infected with HBV, either NA treatment-naïve or treatment-experienced, but TAF naïve
      will be enrolled in this study, and they will be treated with TAF, alone or in combination
      with other HBV antivirals. During 36 months of treatment, efficacy and safety will be
      evaluated.
This study is a multi-center, prospective, real-world study, aiming to investigate the use of
      TAF in routine clinical management of chronic hepatitis B patients and evaluate its
      effectiveness and safety across a heterogeneous population in China. Approximately 500
      patients will take part in this study, 10 sites will be included which distribute in China's
      major cities, thus each site will enroll 50 patients. Male or female HBeAg positive or
      negative patients (above 18 years of age) who were mono-infected with HBV, either NA
      treatment-naïve or treatment-experienced, but TAF naïve will be enrolled in this study, and
      they will be treated with TAF, alone or in combination with other HBV antivirals. During 36
      months of treatment, efficacy and safety will be evaluated.
observational model: Cohort
time perspective: Prospective
measure: proportion of participants with HBV DNA < 20 IU/mL
time frame: 36 months
description: proportion of participants with HBV DNA < 20 IU/mL as measured by the COBAS TaqMan HBV Test (Roche Molecular Diagnostics, Pleasanton, CA, USA), with taken at 36 months
measure: The proportion of patients with HBV DNA < 20 IU/mL
time frame: 12 months
description: The proportion of patients with HBV DNA < 20 IU/mL at 12 months
measure: The proportion of patients with HBV DNA <300 copies/mL
time frame: 12 months
description: The proportion of patients with HBV DNA <300 copies/mL at 12 months
measure: The proportion of patients with HBV DNA < 20 IU/mL
time frame: 24 months
description: The proportion of patients with HBV DNA < 20 IU/mL at 24 months
measure: The proportion of patients with HBV DNA <300 copies/mL IU/mL
time frame: 24 months
description: The proportion of patients with HBV DNA <300 copies/mL at 24 months
measure: The proportion of patients with HBV DNA <300 copies/mL IU/mL
time frame: 36 months
description: The proportion of patients with HBV DNA <300 copies/mL at 36 months
measure: Proportion of participants with Hepatitis B e Antigen (HBeAg) Loss
time frame: 36 months
description: Proportion of participants with Hepatitis B e Antigen (HBeAg) Loss at 36 months
measure: Proportion of participants with seroconversion to Anti-Hepatitis B e-Antigen (Anti-HBe)
time frame: 36 months
description: Proportion of participants with seroconversion to Anti-Hepatitis B e-Antigen (Anti-HBe) at 36 months
measure: Proportion of participants with Normal Alanine Aminotransferase (ALT)
time frame: 36 months
description: Proportion of participants with Normal Alanine Aminotransferase (ALT) at 36 months
measure: Change from baseline in fibrosis as assessed by Fibroscan®
time frame: 36 months
description: Change from baseline in fibrosis as assessed by Fibroscan® at 36 months
measure: Percent Change from baseline in Bone Mineral Density (BMD)
time frame: 36 months
description: Percent Change from baseline in Bone Mineral Density (BMD) at 36 months
measure: Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
time frame: 36 months
description: Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at 36 months
measure: the rate of mother-to-child transmission of HBV
time frame: at postpartum 6 months
description: For unplanned pregnant subjects, if not withdrawn, mother-to-child transmission (MTCT) rate
arm group label: Tenofovir alafenamide (TAF)
description: Male or female HBeAg positive or negative patients (above 18 years of age) who were mono-infected with HBV, either NA treatment-naïve or treatment-experienced, but TAF naïve will be enrolled in this study, and they will be treated with TAF, alone or in combination with anti-HBV agents.
intervention type: Drug
intervention name: Tenofovir Alafenamide
description: The dose of tenofovir alafenamide (TAF) will be 25mg tablet taken orally once daily with food for 36 months, patients will be treated with TAF alone or in combination with anti-HBV agents
arm group label: Tenofovir alafenamide (TAF)
other name: Vemlidy®
Serum, urine and whole blood will be restored in central lab
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Qin Ning, MD., Ph.D.
role: Study Chair
affiliation: Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
last name: Qin Ning, MD., Ph.D.
phone: +86 278366 2391
email: qning@vip.sina.com
last name: Di Wu, MD., Ph.D.
phone: +86 278366 2391
email: woody_1984@163.com
facility: 
status: Not yet recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Tongji Hospital
investigator full name: Qin Ning
investigator title: Director
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
mesh term: Tenofovir