<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/NCT01728935</url>
  </required_header>
  <id_info>
    <org_study_id>TDF-HKU</org_study_id>
    <secondary_id>UW 11-241</secondary_id>
    <nct_id>NCT01728935</nct_id>
  </id_info>
  <brief_title>Tenofovir in Asian Chronic Hepatitis B Patients</brief_title>
  <official_title>Serologic and Virologic Outcomes of Tenofovir in Asian Chronic Hepatitis B Patients With Prior Nucleoside Analogue Exposure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Hong Kong</source>
  <brief_summary>
    <textblock>
      Tenofovir (TDF) has been demonstrated to have potency antiviral against the hepatitis B virus&#xD;
      (HBV) in various multiple-centre trials, with no cases of resistance encountered. However,&#xD;
      its efficacy and resistance profile in the Asian population, which constitute the majority of&#xD;
      chronic hepatitis B (CHB) patients, is unknown. Compared to other nucleoside analogues, TDF&#xD;
      has been associated with relatively high rates of hepatitis B surface antigen (HBsAg)&#xD;
      seroclearance. It would be interested to see if this could be reproduced. The investigators&#xD;
      plan to report the serologic and virologic results of our 140 nucleoside analogue-experienced&#xD;
      patients who were commenced on TDF.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recent multi-center trials have shown tenofovir disoprovil fumarate (TDF) demonstrating&#xD;
      potent antiviral efficacy in both nucleoside-naive and -experienced chronic hepatitis B (CHB)&#xD;
      patients. At present, there has been no identifiable amino acid substitutions associated with&#xD;
      resistance to TDF.&#xD;
&#xD;
      Since TDF and adefovir (ADV), another licensed drug for CHB, belong to same molecular group,&#xD;
      acyclic phosphonate, there had been various studies investigating the efficacy of TDF in&#xD;
      ADV-resistant patients. The efficacy of tenofovir in this group of patients is conflicting.&#xD;
      While several studies have shown TDF achieving similar viral suppression when compared to CHB&#xD;
      patients without ADV-resistance , another study found that patients with the signature ADV&#xD;
      mutations of rtA181V/T and /or rtN236T responded suboptimally to TDF. For all published&#xD;
      studies, the number of patients with documented genotypic resistance to adefovir is actually&#xD;
      small (n = 17-40), and therefore, further studies in this area are required.&#xD;
&#xD;
      Another interesting point to note was the relatively high rate of hepatitis B surface antigen&#xD;
      (HBsAg) seroclearance found in patients taking TDF. The cumulative rate of HBsAg&#xD;
      seroclearance up in hepatitis B e antigen (HBeAg)-positive was 10% after 4 years . However,&#xD;
      the same study did not find any HBeAg-negative patients achieving HBsAg seroclearance. In&#xD;
      addition, studies on TDF were mainly performed in Caucasian patients, the majority being&#xD;
      genotypes A and D. A preliminary study performed in Asian patients, predominantly genotypes B&#xD;
      and C, did not discover any cases of HBsAg seroclearance . Given the majority of the CHB&#xD;
      population is found in Asia, further studies are needed to clarify if HBsAg seroclearance by&#xD;
      nucleoside / nucleotide analogues is potentially achievable using TDF.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2008</start_date>
  <completion_date type="Actual">March 2013</completion_date>
  <primary_completion_date type="Actual">November 2012</primary_completion_date>
  <phase>N/A</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>Serum HBV DNA levels</measure>
    <time_frame>3 Years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Resistance Profile</measure>
    <time_frame>3 Years</time_frame>
    <description>Performed using a Line Probe Assay (LiPA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HBsAg levels</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">141</enrollment>
  <condition>Chronic Hepatitis B</condition>
  <arm_group>
    <arm_group_label>Tenofovir disoproxil</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Tenofovir disoproxil 300mg daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir disoproxil</intervention_name>
    <description>Tenofovir disoproxil 300mg daily</description>
    <arm_group_label>Tenofovir disoproxil</arm_group_label>
    <other_name>Viread</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. HBsAg-positivity for at least 6 months at presentation&#xD;
&#xD;
          2. Commenced on tenofovir for chronic hepatitis B&#xD;
&#xD;
          3. Exposure to other nucleoside analogues before starting TDF&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concomitant liver diseases including chronic hepatitis C and/ or D infection, Wilson's&#xD;
             disease, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing&#xD;
             cholangitis.&#xD;
&#xD;
          2. Significant alcohol intake (&gt; 20 grams per day)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Man-Fung Yuen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Hong Kong</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Medicine, The University of Hong Kong, Queen Mary Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <last_update_submitted>December 29, 2014</last_update_submitted>
  <last_update_submitted_qc>December 29, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 30, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HBV</keyword>
  <keyword>Tenofovir</keyword>
  <keyword>HBV DNA</keyword>
  <keyword>HBsAg</keyword>
  <keyword>Resistance</keyword>
  <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>
    <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/NCT01728935
org study id: TDF-HKU
secondary id: UW 11-241
nct id: NCT01728935
lead sponsor: 
collaborator: 
Tenofovir (TDF) has been demonstrated to have potency antiviral against the hepatitis B virus
      (HBV) in various multiple-centre trials, with no cases of resistance encountered. However,
      its efficacy and resistance profile in the Asian population, which constitute the majority of
      chronic hepatitis B (CHB) patients, is unknown. Compared to other nucleoside analogues, TDF
      has been associated with relatively high rates of hepatitis B surface antigen (HBsAg)
      seroclearance. It would be interested to see if this could be reproduced. The investigators
      plan to report the serologic and virologic results of our 140 nucleoside analogue-experienced
      patients who were commenced on TDF.
Recent multi-center trials have shown tenofovir disoprovil fumarate (TDF) demonstrating
      potent antiviral efficacy in both nucleoside-naive and -experienced chronic hepatitis B (CHB)
      patients. At present, there has been no identifiable amino acid substitutions associated with
      resistance to TDF.

      Since TDF and adefovir (ADV), another licensed drug for CHB, belong to same molecular group,
      acyclic phosphonate, there had been various studies investigating the efficacy of TDF in
      ADV-resistant patients. The efficacy of tenofovir in this group of patients is conflicting.
      While several studies have shown TDF achieving similar viral suppression when compared to CHB
      patients without ADV-resistance , another study found that patients with the signature ADV
      mutations of rtA181V/T and /or rtN236T responded suboptimally to TDF. For all published
      studies, the number of patients with documented genotypic resistance to adefovir is actually
      small (n = 17-40), and therefore, further studies in this area are required.

      Another interesting point to note was the relatively high rate of hepatitis B surface antigen
      (HBsAg) seroclearance found in patients taking TDF. The cumulative rate of HBsAg
      seroclearance up in hepatitis B e antigen (HBeAg)-positive was 10% after 4 years . However,
      the same study did not find any HBeAg-negative patients achieving HBsAg seroclearance. In
      addition, studies on TDF were mainly performed in Caucasian patients, the majority being
      genotypes A and D. A preliminary study performed in Asian patients, predominantly genotypes B
      and C, did not discover any cases of HBsAg seroclearance . Given the majority of the CHB
      population is found in Asia, further studies are needed to clarify if HBsAg seroclearance by
      nucleoside / nucleotide analogues is potentially achievable using TDF.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Serum HBV DNA levels
time frame: 3 Years
measure: Resistance Profile
time frame: 3 Years
description: Performed using a Line Probe Assay (LiPA)
measure: HBsAg levels
time frame: 3 years
arm group label: Tenofovir disoproxil
arm group type: Other
description: Tenofovir disoproxil 300mg daily
intervention type: Drug
intervention name: Tenofovir disoproxil
description: Tenofovir disoproxil 300mg daily
arm group label: Tenofovir disoproxil
other name: Viread
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Man-Fung Yuen, MD
role: Principal Investigator
affiliation: The University of Hong Kong
facility: 
country: Hong Kong
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
mesh term: Tenofovir