<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/NCT04501224</url>
  </required_header>
  <id_info>
    <org_study_id>TAF</org_study_id>
    <nct_id>NCT04501224</nct_id>
  </id_info>
  <brief_title>The Efficacy and Safety of TAF vs Other NAs in Patients With LVL</brief_title>
  <official_title>The Efficacy and Safety of Tenofovir Alafenamide Fumarate Compared With Other Nucleoside Analogues (Acid) to Treat Patients With Low-level Viremia of HBV</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Third Affiliated Hospital, Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Third Affiliated Hospital, Sun Yat-Sen University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with chronic hepatitis B should maximize the inhibition of HBV replication, which&#xD;
      could reduce the incidence of liver cancer and liver disease-related complications. However,&#xD;
      after 96 weeks of treatment with the first-line drugs, entecavir or tenofovir disoproxil&#xD;
      fumarate, a certain proportion of patients still had low levels of HBV replication. Tenofovir&#xD;
      alafenamide fumarate is a newly marketed anti-hepatitis B drug that is currently considered&#xD;
      to be non-inferior to tenofovir disoproxil fumarate and safer bone and renal effects.&#xD;
      Therefore, this research was put forward to investigate whether tenofovir alafenamide&#xD;
      fumarate replacement for hepatitis B had a higher virological response rate and safety in&#xD;
      patients with low levels of virus after 48 weeks of treatment with entecavir and tenofovir&#xD;
      disoproxil fumarate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients who meet the inclusion and exclusion criteria will be enrolled into the research.&#xD;
      The participants will voluntarily choose to enter the experimental group or the control group&#xD;
      with full informed consent. The control group will continue with the original regimen, while&#xD;
      the study group will switch to tenofovir alafenamide fumarate antiviral therapy. Each group&#xD;
      will enroll 100 participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 3, 2020</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2021</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ratio of patients with undetectable hepatitis b virus DNA after treatment</measure>
    <time_frame>24 week</time_frame>
    <description>Hepatitis b virus DNA would be tested to know the ratio of patients with undetectable hepatitis b virus DNA at 24 week after treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The changes of glomerular filtration rate</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>Glomerular filtration rate will be tested to know the changes after treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The changes of bone mineral density in lumbar spine and hip</measure>
    <time_frame>0 week, 48 week, 96 week, 144 week.</time_frame>
    <description>Bone mineral density in lumbar spine and hip were tested after treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ratio of patients with undetectable hepatitis b virus DNA after treatment</measure>
    <time_frame>12 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>Hepatitis b virus DNA would be tested at 6 time points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The changes of HBsAg</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>The levels of HBsAg were tested at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The changes of the degree of liver fibrosis</measure>
    <time_frame>0 week, 48 week, 96 week, 144 week.</time_frame>
    <description>Fibroscan would be conducted once every 48 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in symptoms</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>Symptoms would be evaluated at each time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The changes of HBeAg</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>The levels of HBeAg were tested at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The changes of alanine aminotransferase</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>The levels of alanine aminotransferase were tested at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in body weight</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>Body weight would be evaluated at each time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in proteinuria, albuminuria and urinary β2-microglobulin</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>Proteinuria, albuminuria and urinary β2-microglobulin would be evaluated at each time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in osmotic pressure</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>The levels of osmotic pressure would be evaluated at each time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in blood calcium and phosphorus</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>The levels of blood calcium and phosphorus would be evaluated at each time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in blood lipid</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>The levels of blood lipid would be evaluated at each time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in serum creatine kinase</measure>
    <time_frame>0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week</time_frame>
    <description>The levels of creatine kinase would be evaluated at each time point</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Chronic Hepatitis b</condition>
  <condition>Cirrhosis Due to Hepatitis B</condition>
  <arm_group>
    <arm_group_label>switch to tenofovir alafenamide fumarate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will switch to tenofovir alafenamide fumarate treatment, 25mg，once a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continue with the original regimen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will continue with the original regimen treatment, entecavir, 0.5mg once a day, or tenofovir disoproxil fumarate 300mg once a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir alafenamide fumarate</intervention_name>
    <description>Patients would take tenofovir alafenamide fumarate, 25mg，once per day</description>
    <arm_group_label>switch to tenofovir alafenamide fumarate</arm_group_label>
    <other_name>Vemlidy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entecavir or Tenofovir disoproxil fumarate</intervention_name>
    <description>Patients would take entecavir 0.5 mg once per day, or tenofovir disoproxil fumarate 300 mg once per day</description>
    <arm_group_label>Continue with the original regimen</arm_group_label>
    <other_name>Baraclude or Viread</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HBsAg positive for over half a year;&#xD;
&#xD;
          -  Age from 18 to 80 years old;&#xD;
&#xD;
          -  Entecavir (0.5mg qd) or Tenofovir disoproxil fumarate (300mg qd) for 48 weeks or more;&#xD;
&#xD;
          -  HBV DNA level was between 20IU/ ml-2000 IU /mL (COBAS, Taqman).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Low-level viremia of HBV caused by non-standard medication;&#xD;
&#xD;
          -  serum total bilirubin is more than 2 times the upper limit of normal (ULN), or ALT or&#xD;
             AST is more than 5ULN, or serum albumin is less than 30g/L;&#xD;
&#xD;
          -  Overlap with HAV, HCV, HDV, HEV or HIV infection;&#xD;
&#xD;
          -  Other liver disease: drug liver disease, alcoholic liver disease, autoimmune liver&#xD;
             disease, genetic metabolic liver disease, etc.;&#xD;
&#xD;
          -  Decompensated cirrhosis or liver cancer;&#xD;
&#xD;
          -  Kidney damage, or autoimmune disease, or other organ failure;&#xD;
&#xD;
          -  Combination of Entecavir or Tenofovir disoproxil fumarate ;&#xD;
&#xD;
          -  Interferon therapy within half a year;&#xD;
&#xD;
          -  Entecavir (0.5mg qd) or Tenofovir disoproxil fumarate;&#xD;
&#xD;
          -  Investigator considering inappropriate.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yuehua Huang, doctorate</last_name>
    <role>Principal Investigator</role>
    <affiliation>Third Affiliated Hospital, Sun Yat-Sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yuehua Huang, doctorate</last_name>
    <phone>0086-13822232795</phone>
    <email>huangyh53@mail.sysu.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Guofen Zeng, masterate</last_name>
    <phone>0086-13570305907</phone>
    <email>zengguofen06@126.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Third Affiliated Hospital of Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510630</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guofen Zeng, Master</last_name>
      <phone>86-13570305907</phone>
      <email>zenggfen@mail.sysu.edu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 19, 2020</study_first_submitted>
  <study_first_submitted_qc>August 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>October 28, 2020</last_update_submitted>
  <last_update_submitted_qc>October 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Third Affiliated Hospital, Sun Yat-Sen University</investigator_affiliation>
    <investigator_full_name>Yuehua Huang</investigator_full_name>
    <investigator_title>Laboratory director of hepatology#Deputy director of infection</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Entecavir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04501224
org study id: TAF
nct id: NCT04501224
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Patients with chronic hepatitis B should maximize the inhibition of HBV replication, which
      could reduce the incidence of liver cancer and liver disease-related complications. However,
      after 96 weeks of treatment with the first-line drugs, entecavir or tenofovir disoproxil
      fumarate, a certain proportion of patients still had low levels of HBV replication. Tenofovir
      alafenamide fumarate is a newly marketed anti-hepatitis B drug that is currently considered
      to be non-inferior to tenofovir disoproxil fumarate and safer bone and renal effects.
      Therefore, this research was put forward to investigate whether tenofovir alafenamide
      fumarate replacement for hepatitis B had a higher virological response rate and safety in
      patients with low levels of virus after 48 weeks of treatment with entecavir and tenofovir
      disoproxil fumarate.
Patients who meet the inclusion and exclusion criteria will be enrolled into the research.
      The participants will voluntarily choose to enter the experimental group or the control group
      with full informed consent. The control group will continue with the original regimen, while
      the study group will switch to tenofovir alafenamide fumarate antiviral therapy. Each group
      will enroll 100 participants.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Ratio of patients with undetectable hepatitis b virus DNA after treatment
time frame: 24 week
description: Hepatitis b virus DNA would be tested to know the ratio of patients with undetectable hepatitis b virus DNA at 24 week after treatment.
measure: The changes of glomerular filtration rate
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: Glomerular filtration rate will be tested to know the changes after treatment
measure: The changes of bone mineral density in lumbar spine and hip
time frame: 0 week, 48 week, 96 week, 144 week.
description: Bone mineral density in lumbar spine and hip were tested after treatment
measure: Ratio of patients with undetectable hepatitis b virus DNA after treatment
time frame: 12 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: Hepatitis b virus DNA would be tested at 6 time points.
measure: The changes of HBsAg
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: The levels of HBsAg were tested at each time point.
measure: The changes of the degree of liver fibrosis
time frame: 0 week, 48 week, 96 week, 144 week.
description: Fibroscan would be conducted once every 48 weeks
measure: Differences in symptoms
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: Symptoms would be evaluated at each time point
measure: The changes of HBeAg
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: The levels of HBeAg were tested at each time point.
measure: The changes of alanine aminotransferase
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: The levels of alanine aminotransferase were tested at each time point.
measure: Differences in body weight
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: Body weight would be evaluated at each time point
measure: Differences in proteinuria, albuminuria and urinary β2-microglobulin
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: Proteinuria, albuminuria and urinary β2-microglobulin would be evaluated at each time point
measure: Differences in osmotic pressure
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: The levels of osmotic pressure would be evaluated at each time point
measure: Differences in blood calcium and phosphorus
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: The levels of blood calcium and phosphorus would be evaluated at each time point
measure: Differences in blood lipid
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: The levels of blood lipid would be evaluated at each time point
measure: Differences in serum creatine kinase
time frame: 0 week, 12 week, 24 week, 48 week, 72 week, 96 week, 120 week, 144 week
description: The levels of creatine kinase would be evaluated at each time point
arm group label: switch to tenofovir alafenamide fumarate
arm group type: Experimental
description: Patients will switch to tenofovir alafenamide fumarate treatment, 25mg，once a day
arm group label: Continue with the original regimen
arm group type: Active Comparator
description: Patients will continue with the original regimen treatment, entecavir, 0.5mg once a day, or tenofovir disoproxil fumarate 300mg once a day
intervention type: Drug
intervention name: Tenofovir alafenamide fumarate
description: Patients would take tenofovir alafenamide fumarate, 25mg，once per day
arm group label: switch to tenofovir alafenamide fumarate
other name: Vemlidy
intervention type: Drug
intervention name: Entecavir or Tenofovir disoproxil fumarate
description: Patients would take entecavir 0.5 mg once per day, or tenofovir disoproxil fumarate 300 mg once per day
arm group label: Continue with the original regimen
other name: Baraclude or Viread
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Yuehua Huang, doctorate
role: Principal Investigator
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
last name: Yuehua Huang, doctorate
phone: 0086-13822232795
email: huangyh53@mail.sysu.edu.cn
last name: Guofen Zeng, masterate
phone: 0086-13570305907
email: zengguofen06@126.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Third Affiliated Hospital, Sun Yat-Sen University
investigator full name: Yuehua Huang
investigator title: Laboratory director of hepatology#Deputy director of infection
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Tenofovir
mesh term: Entecavir
sharing ipd: No