<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/NCT03801538</url>
  </required_header>
  <id_info>
    <org_study_id>I-Cure-3X</org_study_id>
    <nct_id>NCT03801538</nct_id>
  </id_info>
  <brief_title>The Optimizing Treatment of Peginterferon Alpha in Chronic Hepatitis B Patients With Low Level HBsAg</brief_title>
  <official_title>The Optimizing Treatment of Peginterferon Alpha in Chronic Hepatitis B Patients With Low Level HBsAg(I-Cure-3X)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Third Affiliated Hospital, Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Wuhan Union Hospital, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Third Affiliated Hospital, Sun Yat-Sen University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      HBeAg-negative chronic hepatitis B (CHB) patients with low Level HBsAg were enrolled. After&#xD;
      giving informed consent, patients were treated with nucleoside analog(s) (NAs) once a day and&#xD;
      weekly subcutaneous injections of peginterferon alfa-2a 180 micrograms/week or peginterferon&#xD;
      alfa-2b 180 micrograms/week for 12 weeks. At week 12, the decrease of HBsAg was evaluated.&#xD;
&#xD;
      ①If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped,&#xD;
      patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or&#xD;
      peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(&lt;0.05 IU/ mL).&#xD;
      Depending on the decline of HBsAg level, treatment was either continued for a prolonged&#xD;
      period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.&#xD;
      After treatment, all patients were followed up for 48 weeks.&#xD;
&#xD;
      ②If the decrease of HBsAg is less than 50% compared to baseline level. The combination&#xD;
      therapy of NAs and peginterferon alfa was extended to week 24. Then, the decrease of HBsAg&#xD;
      was evaluated again.&#xD;
&#xD;
      If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped,&#xD;
      patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or&#xD;
      peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(&lt;0.05 IU/mL).&#xD;
      Depending on the decline of HBsAg level, treatment was either continued for a prolonged&#xD;
      period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.&#xD;
      After treatment, all patients were followed up for 48 weeks.&#xD;
&#xD;
      If the decrease of HBsAg is less than 50% compared to baseline level. Peginterferon alfa was&#xD;
      stopped, patients were treated with NAs once a day and then followed up for 48 weeks.&#xD;
&#xD;
      Patients who maintained the original NAs treatment served as a control group.&#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. HBeAg-negative CHB patients with low Level HBsAg were enrolled in the out-patient&#xD;
      department of Third Affiliated Hospital of Sun Yat-sen University and Wuhan Union Hospital.&#xD;
      All of them were HBsAg positive and anti-HBs negative for more than 6 months with HBV DNA&lt;100&#xD;
      IU/mL and HBsAg levels &lt;1000 IU/mL. All patients did not have other liver diseases and&#xD;
      contraindications for interferon therapy. After giving informed consent, patients were&#xD;
      treated with nucleoside analog(s) (NAs) once a day and weekly subcutaneous injections of&#xD;
      peginterferon alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week for 12&#xD;
      weeks. At week 12, the decrease of HBsAg was evaluated.&#xD;
&#xD;
      ①If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped,&#xD;
      patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or&#xD;
      peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(&lt;0.05 IU/ mL).&#xD;
      Depending on the decline of HBsAg level, treatment was either continued for a prolonged&#xD;
      period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.&#xD;
      After treatment, all patients were followed up for 48 weeks.&#xD;
&#xD;
      ②If the decrease of HBsAg is less than 50% compared to baseline level. The combination&#xD;
      therapy of NAs and peginterferon alfa was extended to week 24. Then, the decrease of HBsAg&#xD;
      was evaluated again.&#xD;
&#xD;
      If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped,&#xD;
      patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or&#xD;
      peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(&lt;0.05 IU/mL).&#xD;
      Depending on the decline of HBsAg level, treatment was either continued for a prolonged&#xD;
      period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.&#xD;
      After treatment, all patients were followed up for 48 weeks.&#xD;
&#xD;
      If the decrease of HBsAg is less than 50% compared to baseline level. Peginterferon alfa was&#xD;
      stopped, patients were treated with NAs once a day and then followed up for 48 weeks.&#xD;
&#xD;
      The use of other immune suppressive or regulatory drugs and other antiviral drugs was&#xD;
      prohibited during the course of the study. In this study, HBsAg loss(&lt;0.05 IU/mL) was defined&#xD;
      as treatment endpoint. Anti-HBs positive(&gt;10 milli-International unit)(mIU/mL) was defined as&#xD;
      seroconversion.&#xD;
&#xD;
      Patients who maintained the original NAs treatment served as a control group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Phase 4</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>HBsAg Clearance</measure>
    <time_frame>96 weeks</time_frame>
    <description>Participants with HBsAg &lt;0.05 IU/mL.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HBsAg Seroconversion</measure>
    <time_frame>96 weeks</time_frame>
    <description>Participants with HBsAg &lt;0.05 IU/mL and anti-HBsAg positive</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Chronic Hepatitis B</condition>
  <arm_group>
    <arm_group_label>PEG-IFN group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients were treated with NAs once a day and PEG-IFN once a week for 12 weeks. At week 12, the decrease of HBsAg was evaluated.&#xD;
①If the decrease of HBsAg is more than 50%. NAs was stopped. PEG-IFN Treatment was continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.&#xD;
②If the decrease of HBsAg is less than 50%.NAs and PEG-IFN was extended to week 24. Then, If the decrease of HBsAg is more than 50%. NAs was stopped, PEG-IFN Treatment was continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96. If the decrease of HBsAg is less than 50%. PEG-IFN was stopped, patients were treated with NAs once a day and then followed up for 48 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NAs group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>CHB patients do not need to change their NAs treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Peginterferon Alfa</intervention_name>
    <description>Peginterferon Alfa-2A 180 micrograms/week or Peginterferon Alfa-2B 180 micrograms/week, for at most 96 weeks.</description>
    <arm_group_label>PEG-IFN group</arm_group_label>
    <other_name>PEG-IFN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nucleoside Analog (Substance)</intervention_name>
    <description>Patients do not need to change their NAs treatment.</description>
    <arm_group_label>NAs group</arm_group_label>
    <other_name>NAs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. CHB patients who had received NAs for more than 12 months.&#xD;
&#xD;
          2. Hepatitis B e antigen (HBeAg)-negative.&#xD;
&#xD;
          3. Hepatitis B surface antigen (HBsAg) positive and &lt;1000 IU/mL.&#xD;
&#xD;
          4. Hepatitis B virus DNA &lt;100 IU/mL.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with liver cirrhosis, Hepatocellular Carcinoma or alpha feto protein (AFP) &gt;2&#xD;
             upper limit of normal(ULN) or other malignancies.&#xD;
&#xD;
          2. Patients with other factors causing liver diseases.&#xD;
&#xD;
          3. Pregnant and lactating women.&#xD;
&#xD;
          4. Patients with concomitant HIV infection or congenital immune deficiency diseases.&#xD;
&#xD;
          5. Patients with diabetes, autoimmune diseases.&#xD;
&#xD;
          6. Patients with important organ dysfunctions.&#xD;
&#xD;
          7. Patients with serious complications (e.g., infection, hepatic encephalopathy,&#xD;
             hepatorenal syndrome, gastrointestinal bleeding.)&#xD;
&#xD;
          8. Patients who receive antineoplastic or immunomodulatory therapy in the past 12 months.&#xD;
&#xD;
          9. Patients who can't come back to clinic for follow-up on schedule.&#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>Zhiliang Gao</last_name>
    <role>Principal Investigator</role>
    <affiliation>Third Affiliated Hospital, Sun Yat-Sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Infectious Diseases, The Third Affliated Hospital of Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510630</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>January 12, 2019</last_update_submitted>
  <last_update_submitted_qc>January 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2019</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>Zhiliang Gao</investigator_full_name>
    <investigator_title>Professor</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>
    <mesh_term>Hepatitis, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03801538
org study id: I-Cure-3X
nct id: NCT03801538
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
HBeAg-negative chronic hepatitis B (CHB) patients with low Level HBsAg were enrolled. After
      giving informed consent, patients were treated with nucleoside analog(s) (NAs) once a day and
      weekly subcutaneous injections of peginterferon alfa-2a 180 micrograms/week or peginterferon
      alfa-2b 180 micrograms/week for 12 weeks. At week 12, the decrease of HBsAg was evaluated.

      ①If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped,
      patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or
      peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(<0.05 IU/ mL).
      Depending on the decline of HBsAg level, treatment was either continued for a prolonged
      period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.
      After treatment, all patients were followed up for 48 weeks.

      ②If the decrease of HBsAg is less than 50% compared to baseline level. The combination
      therapy of NAs and peginterferon alfa was extended to week 24. Then, the decrease of HBsAg
      was evaluated again.

      If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped,
      patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or
      peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(<0.05 IU/mL).
      Depending on the decline of HBsAg level, treatment was either continued for a prolonged
      period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.
      After treatment, all patients were followed up for 48 weeks.

      If the decrease of HBsAg is less than 50% compared to baseline level. Peginterferon alfa was
      stopped, patients were treated with NAs once a day and then followed up for 48 weeks.

      Patients who maintained the original NAs treatment served as a control group.
It is estimated that more than 400 million people are infected with hepatitis B virus (HBV)
      globally. HBeAg-negative CHB patients with low Level HBsAg were enrolled in the out-patient
      department of Third Affiliated Hospital of Sun Yat-sen University and Wuhan Union Hospital.
      All of them were HBsAg positive and anti-HBs negative for more than 6 months with HBV DNA<100
      IU/mL and HBsAg levels <1000 IU/mL. All patients did not have other liver diseases and
      contraindications for interferon therapy. After giving informed consent, patients were
      treated with nucleoside analog(s) (NAs) once a day and weekly subcutaneous injections of
      peginterferon alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week for 12
      weeks. At week 12, the decrease of HBsAg was evaluated.

      ①If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped,
      patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or
      peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(<0.05 IU/ mL).
      Depending on the decline of HBsAg level, treatment was either continued for a prolonged
      period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.
      After treatment, all patients were followed up for 48 weeks.

      ②If the decrease of HBsAg is less than 50% compared to baseline level. The combination
      therapy of NAs and peginterferon alfa was extended to week 24. Then, the decrease of HBsAg
      was evaluated again.

      If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped,
      patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or
      peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(<0.05 IU/mL).
      Depending on the decline of HBsAg level, treatment was either continued for a prolonged
      period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.
      After treatment, all patients were followed up for 48 weeks.

      If the decrease of HBsAg is less than 50% compared to baseline level. Peginterferon alfa was
      stopped, patients were treated with NAs once a day and then followed up for 48 weeks.

      The use of other immune suppressive or regulatory drugs and other antiviral drugs was
      prohibited during the course of the study. In this study, HBsAg loss(<0.05 IU/mL) was defined
      as treatment endpoint. Anti-HBs positive(>10 milli-International unit)(mIU/mL) was defined as
      seroconversion.

      Patients who maintained the original NAs treatment served as a control group.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: HBsAg Clearance
time frame: 96 weeks
description: Participants with HBsAg <0.05 IU/mL.
measure: HBsAg Seroconversion
time frame: 96 weeks
description: Participants with HBsAg <0.05 IU/mL and anti-HBsAg positive
arm group label: PEG-IFN group
arm group type: Experimental
description: patients were treated with NAs once a day and PEG-IFN once a week for 12 weeks. At week 12, the decrease of HBsAg was evaluated.
①If the decrease of HBsAg is more than 50%. NAs was stopped. PEG-IFN Treatment was continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.
②If the decrease of HBsAg is less than 50%.NAs and PEG-IFN was extended to week 24. Then, If the decrease of HBsAg is more than 50%. NAs was stopped, PEG-IFN Treatment was continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96. If the decrease of HBsAg is less than 50%. PEG-IFN was stopped, patients were treated with NAs once a day and then followed up for 48 weeks.
arm group label: NAs group
arm group type: Other
description: CHB patients do not need to change their NAs treatment.
intervention type: Drug
intervention name: Peginterferon Alfa
description: Peginterferon Alfa-2A 180 micrograms/week or Peginterferon Alfa-2B 180 micrograms/week, for at most 96 weeks.
arm group label: PEG-IFN group
other name: PEG-IFN
intervention type: Drug
intervention name: Nucleoside Analog (Substance)
description: Patients do not need to change their NAs treatment.
arm group label: NAs group
other name: NAs
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Zhiliang Gao
role: Principal Investigator
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Third Affiliated Hospital, Sun Yat-Sen University
investigator full name: Zhiliang Gao
investigator title: Professor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
sharing ipd: Undecided