<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/NCT03771677</url>
  </required_header>
  <id_info>
    <org_study_id>XC1</org_study_id>
    <nct_id>NCT03771677</nct_id>
  </id_info>
  <brief_title>To Optimize the Therapeutic Pathway of Peginterferon Treatment in Patients With CHB Based on IFNA2p.Ala120Thr /ISGs.</brief_title>
  <acronym>IFNA2/ISGs</acronym>
  <official_title>A Clinical Controlled Study to Optimize the Therapeutic Pathway of Peginterferon Alfa-2b Treatment in Patients With Chronic Hepatitis B Based on IFNA2p.Ala120Thr /ISGs Gene Spectrum.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>First People's Hospital of Foshan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eighth Affiliated Hospital, Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The study is to guide clinical cure of peginterferon alfa-2a treatment in patients with&#xD;
      chronic hepatitis B based on the detection of interferon gene mutation (IFNA2p.Ala120Thr) and&#xD;
      interferon-stimulated genes (ISGs) detection gene spectrum.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is estimated that more than 400 million people are infected with hepatitis B virus (HBV)&#xD;
      globally.How to make more patients with chronic hepatitis B get clinical treatment through&#xD;
      the existing anti-viral treatment is an urgent problem to be solved.This study is a random,&#xD;
      multi-center and open experiment,the collaborators includes the second people's hospital of&#xD;
      zhongshan city, the eighth people's hospital of guangzhou city, and the first people's&#xD;
      hospital of foshan city.&#xD;
&#xD;
      Patients with chronic hepatitis B who were treated with NAs for over 1 year,HBsAg&#xD;
      quantification≤1500 IU/mL, HBeAg negative and serum HBV DNA quantification &lt;100 IU/mL were&#xD;
      enrolled in this study. In our study, the enrolled patient's IFNA2p.Ala120Thr without&#xD;
      variation and ISGs&gt;0.05 were divided into two groups. After informed consent , patients were&#xD;
      grouped according to their treatment intentions,in one group, patients continued NAs for&#xD;
      another 48 weeks. In another group , patients were treated with peg-interferon-2a and NAs for&#xD;
      48 weeks.Patient's BMI, genotype, family history, smoking history, drinking history, other&#xD;
      medical history, suspected transmission channels, types and time of use were recorded in this&#xD;
      study.Moreover, Patients were assessed every 12 weeks,included liver and kidney function,&#xD;
      blood routine, HBV cccDNA, HBeAg quantification, HBsAg quantification, pgRNA and so on.In&#xD;
      addition,liver imaging examination and liver hardness test were assessed every six months.&#xD;
&#xD;
      In this study, we will analyze whether clinical cure rates differed between patients with&#xD;
      chronic hepatitis B treated with peginterferon alfa-2a and NAs;Bisedes,the baseline&#xD;
      interferon variant site variants and changes in interferon-stimulated gene profile expression&#xD;
      were analyzed to determine whether they could be used as molecular markers to predict&#xD;
      clinical cure with interferon.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Anticipated">December 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2023</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>
    <intervention_model_description>Drug: nucleotide analogues(NAs)&#xD;
Drug: Peginterferon alfa-2a and nucleotide analogues(NAs)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Active Comparator:nucleotide analogues(NAs) patients continue to use NAs&#xD;
Experimental: peg-interferon alfa-2a patients switch to sequential peg-interferon α-2a</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>HBsAg clearance rate</measure>
    <time_frame>48 weeks</time_frame>
    <description>Whether the HBsAg clearance rate of patients who received interferon treatment was higher than those treated with nucleoside drugs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HBV cccDNA and pgRNA quantification dynamic change</measure>
    <time_frame>48 weeks</time_frame>
    <description>The difference in cccDNA and pgRNA clearance rate between the two groups after 48 weeks of treatment in immune-controlled patients.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Hepatitis B</condition>
  <arm_group>
    <arm_group_label>Active Comparator:NAs group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Active Comparator:nucleotide analogues(NAs)&#xD;
patients continue to use NAs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental:PEG-IFN group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental: peg-interferon alfa-2a&#xD;
patients use peg-interferon α-2a and nucleotide analogues(NAs)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nucleotide Analog</intervention_name>
    <description>such as Entecavir,entecavir 0.5mg per day</description>
    <arm_group_label>Active Comparator:NAs group</arm_group_label>
    <arm_group_label>Experimental:PEG-IFN group</arm_group_label>
    <other_name>Nucleotide Analogs</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Interferon Alfa-2A</intervention_name>
    <description>Peginterferon alfa-2a 180ug per week</description>
    <arm_group_label>Experimental:PEG-IFN group</arm_group_label>
    <other_name>Pegasys</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 18 and 60 years old;&#xD;
&#xD;
          -  HBsAg positive, HBsAg quantification≤1500 IU/mL;&#xD;
&#xD;
          -  Serum HBV DNA quantification &lt;100 IU/mL;&#xD;
&#xD;
          -  HBeAg negative.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treated with interferon in the past six months;&#xD;
&#xD;
          -  Liver cirrhosis or HCC and other associated tumors;&#xD;
&#xD;
          -  Women during pregnancy or lactation;&#xD;
&#xD;
          -  With liver disease caused by other causes;&#xD;
&#xD;
          -  Combination infection of HIV or other immunodeficiency diseases;&#xD;
&#xD;
          -  With diabetes, autoimmune diseases and other organ dysfunction or failure;&#xD;
&#xD;
          -  Combination of other serious complications (infection, hepatic&#xD;
             encephalopathy,gastrointestinal bleeding, hepatorenal syndrome, etc.);&#xD;
&#xD;
          -  Others who cannot be treated with interferon;&#xD;
&#xD;
          -  Anyone cannot return to the hospital for follow-up and follow-up visits regularly as&#xD;
             planned&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chan Xie</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Third Affliated Hospital of Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chan Xie, Professor</last_name>
    <phone>862085252043</phone>
    <email>happyxiechan@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Chan Xie</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chan Xie, Professor</last_name>
      <phone>862085252043</phone>
      <email>happyxiechan@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 8, 2018</study_first_submitted>
  <study_first_submitted_qc>December 8, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>May 4, 2023</last_update_submitted>
  <last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Chan Xie</investigator_full_name>
    <investigator_title>Professor of department of infectious disease Third Affiliated Hospital,Sun Yat-Sen University</investigator_title>
  </responsible_party>
  <keyword>Chronic Hepatitis B</keyword>
  <keyword>IFNA2p.Ala120Thr /ISGs</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</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
    <mesh_term>Interferon-alpha</mesh_term>
    <mesh_term>Interferon alpha-2</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/NCT03771677
org study id: XC1
nct id: NCT03771677
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The study is to guide clinical cure of peginterferon alfa-2a treatment in patients with
      chronic hepatitis B based on the detection of interferon gene mutation (IFNA2p.Ala120Thr) and
      interferon-stimulated genes (ISGs) detection gene spectrum.
It is estimated that more than 400 million people are infected with hepatitis B virus (HBV)
      globally.How to make more patients with chronic hepatitis B get clinical treatment through
      the existing anti-viral treatment is an urgent problem to be solved.This study is a random,
      multi-center and open experiment,the collaborators includes the second people's hospital of
      zhongshan city, the eighth people's hospital of guangzhou city, and the first people's
      hospital of foshan city.

      Patients with chronic hepatitis B who were treated with NAs for over 1 year,HBsAg
      quantification≤1500 IU/mL, HBeAg negative and serum HBV DNA quantification <100 IU/mL were
      enrolled in this study. In our study, the enrolled patient's IFNA2p.Ala120Thr without
      variation and ISGs>0.05 were divided into two groups. After informed consent , patients were
      grouped according to their treatment intentions,in one group, patients continued NAs for
      another 48 weeks. In another group , patients were treated with peg-interferon-2a and NAs for
      48 weeks.Patient's BMI, genotype, family history, smoking history, drinking history, other
      medical history, suspected transmission channels, types and time of use were recorded in this
      study.Moreover, Patients were assessed every 12 weeks,included liver and kidney function,
      blood routine, HBV cccDNA, HBeAg quantification, HBsAg quantification, pgRNA and so on.In
      addition,liver imaging examination and liver hardness test were assessed every six months.

      In this study, we will analyze whether clinical cure rates differed between patients with
      chronic hepatitis B treated with peginterferon alfa-2a and NAs;Bisedes,the baseline
      interferon variant site variants and changes in interferon-stimulated gene profile expression
      were analyzed to determine whether they could be used as molecular markers to predict
      clinical cure with interferon.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Drug: nucleotide analogues(NAs)
Drug: Peginterferon alfa-2a and nucleotide analogues(NAs)
primary purpose: Treatment
masking: None (Open Label)
masking description: Active Comparator:nucleotide analogues(NAs) patients continue to use NAs
Experimental: peg-interferon alfa-2a patients switch to sequential peg-interferon α-2a
measure: HBsAg clearance rate
time frame: 48 weeks
description: Whether the HBsAg clearance rate of patients who received interferon treatment was higher than those treated with nucleoside drugs.
measure: HBV cccDNA and pgRNA quantification dynamic change
time frame: 48 weeks
description: The difference in cccDNA and pgRNA clearance rate between the two groups after 48 weeks of treatment in immune-controlled patients.
arm group label: Active Comparator:NAs group
arm group type: Active Comparator
description: Active Comparator:nucleotide analogues(NAs)
patients continue to use NAs
arm group label: Experimental:PEG-IFN group
arm group type: Experimental
description: Experimental: peg-interferon alfa-2a
patients use peg-interferon α-2a and nucleotide analogues(NAs)
intervention type: Drug
intervention name: Nucleotide Analog
description: such as Entecavir,entecavir 0.5mg per day
arm group label: Active Comparator:NAs group
arm group label: Experimental:PEG-IFN group
other name: Nucleotide Analogs
intervention type: Drug
intervention name: Interferon Alfa-2A
description: Peginterferon alfa-2a 180ug per week
arm group label: Experimental:PEG-IFN group
other name: Pegasys
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Chan Xie
role: Principal Investigator
affiliation: The Third Affliated Hospital of Sun Yat-sen University
last name: Chan Xie, Professor
phone: 862085252043
email: happyxiechan@hotmail.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Chan Xie
investigator title: Professor of department of infectious disease Third Affiliated Hospital,Sun Yat-Sen University
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis
mesh term: Interferons
mesh term: Interferon-alpha
mesh term: Interferon alpha-2