<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/NCT03307902</url>
  </required_header>
  <id_info>
    <org_study_id>UW 15-106</org_study_id>
    <nct_id>NCT03307902</nct_id>
  </id_info>
  <brief_title>ID HBV Vaccination With Imiquimod in OBI</brief_title>
  <official_title>Intradermal Hepatitis B Vaccination With Imiquimod in Occult Hepatitis B Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong</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>
      During the course of chronic hepatitis B infection, patients may undergo hepatitis B surface&#xD;
      antigen (HBsAg) seroclearance, resulting in undetectable circulating HBsAg. With the advance&#xD;
      of sensitive nucleic acid detection techniques, HBsAg-negative subjects with detectable HBV&#xD;
      DNA in sera or liver tissues can be identified. Patients who have undetectable HBsAg and yet&#xD;
      detectable HBV DNA in sera or liver tissues are defined as having occult HBV infection (OBI).&#xD;
      OBI as a cause of liver disease in HBsAg-negative patients remains clinically important&#xD;
      [1,2]. Studies conducted by our research group had demonstrated that patients with HBsAg&#xD;
      seroclearance could still develop flare of hepatitis B, advanced liver diseases and HCC&#xD;
      [3-6]. Prevention of these complications in OBI patients by conventional intramuscular&#xD;
      hepatitis B vaccination (HBVv) remains elusive with poor amnestic anti-HBs response [7].&#xD;
&#xD;
      The objective of this prospective double-blind randomized controlled trial is to evaluate the&#xD;
      effect and safety of topical treatment with imiquimod immediately before intradermal&#xD;
      vaccination with Sci-B-Vac™ in patients with OBI. Our a priori hypothesis is that imiquimod&#xD;
      pretreatment would improve immune responses to Sci-B-Vac™ further in OBI patients, resulting&#xD;
      in HBsAb conversion. Thereby preventing subsequent complications including flare of&#xD;
      hepatitis, cirrhosis and HCC in these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomized double-blind placebo-controlled trial will compare the safety, immunogenicity&#xD;
      and clinical efficacy of Sci-B-Vac™ with topical ointment pretreatment among 5 groups. Group&#xD;
      1: Intradermal Sci-B-Vac™ with topical imiquimod ointment pretreatment; Group 2: Intradermal&#xD;
      Sci-B-Vac™ with topical aqueous cream (placebo) pretreatment; Group 3: Intramuscular&#xD;
      Sci-B-Vac™ with topical imiquimod ointment pretreatment.&#xD;
&#xD;
      Vaccination Regimen and Data Collection Enrolled patients will be randomized into 3 groups&#xD;
      after written informed consent. Each patient will receive a 3 doses Sci-B-Vac™ regime at 0, 1&#xD;
      and 6 months. Group 1 will receive a total of 10μg intradermal HBsAg each time with topical&#xD;
      imiquimod ointment pretreatment; Group 2 will receive a total of 10μg intradermal HBsAg each&#xD;
      time with topical aqueous cream pretreatment. Group 3 will receive a total of 10μg&#xD;
      intramuscular HBsAg each time with topical imiquimod ointment pretreatment.&#xD;
&#xD;
      The primary outcome measurement will be the seroprotection rate of the HBVv at 12 months&#xD;
      after the first dose of vaccination and the secondary outcome measurements will include the&#xD;
      seroconversion rate, the GMT fold increase and the safety of the intradermal Sci-B-Vac™ with&#xD;
      topical imiquimod treatment at other time points.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2016</start_date>
  <completion_date type="Actual">July 31, 2019</completion_date>
  <primary_completion_date type="Actual">March 31, 2019</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Seroprotection rate to HBV at 12 month</measure>
    <time_frame>12 month</time_frame>
    <description>Percentage of recruited subjects with anti-HBs antibody titre &gt;10mIU/mL</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Seroprotection rate to HBV at 1 month</measure>
    <time_frame>1 month</time_frame>
    <description>Percentage of recruited subjects with anti-HBs antibody titre &gt;10mIU/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroprotection rate to HBV at 6 month</measure>
    <time_frame>6 month</time_frame>
    <description>Percentage of recruited subjects with anti-HBs antibody titre &gt;10mIU/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GMT of anti-HBs at 1 month</measure>
    <time_frame>1 month</time_frame>
    <description>Geometric mean titre of anti-HBs antibody at 1 month after vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GMT of anti-HBs at 6 month</measure>
    <time_frame>6 month</time_frame>
    <description>Geometric mean titre of anti-HBs antibody at 6 month after vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GMT of anti-HBs at 12 month</measure>
    <time_frame>12 month</time_frame>
    <description>Geometric mean titre of anti-HBs antibody at 12 month after vaccination</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Hepatitis B</condition>
  <arm_group>
    <arm_group_label>Imiquimod + ID HBVv</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>topical imiquimod + intradermal hepatitis B vaccination</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aqueous + ID HBVv</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>topical aqueous + intradermal hepatitis B vaccination</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Imiquimod + IM HBVv</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>topical imiquimod + intramuscular hepatitis B vaccination</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Imiquimod + ID HBVv</intervention_name>
    <description>Imiquimod ointment + intradermal 10μg Sci-B-Vac vaccine</description>
    <arm_group_label>Imiquimod + ID HBVv</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Aqueous + ID HBVv</intervention_name>
    <description>Aqueous ointment + intradermal 10μg Sci-B-Vac vaccine</description>
    <arm_group_label>Aqueous + ID HBVv</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Imiquimod + IM HBVv</intervention_name>
    <description>Imiquimod ointment + intramuscular 10μg Sci-B-Vac vaccine</description>
    <arm_group_label>Imiquimod + IM HBVv</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects recruited have to be aged ≥27 years (born before the universal hepatitis B&#xD;
             immunization program for newborns introduced in Hong Kong in 1988), with documentation&#xD;
             of loss of HBsAg without anti-HBs production during follow-up of the chronic hepatitis&#xD;
             B infection in our clinics in Queen Mary Hospital. These patients should have normal&#xD;
             liver function tests.&#xD;
&#xD;
          -  Subjects have to give written informed consent.&#xD;
&#xD;
          -  Subjects must be available to complete the study and comply with study procedures.&#xD;
&#xD;
          -  Subjects are willing to allow for serum samples to be stored beyond the study period,&#xD;
             for potential additional future testing to better characterize immune response.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history or any illness that might interfere with the results of the&#xD;
             study or participation in the study may pose additional risk to the subjects.&#xD;
&#xD;
          -  Subjects have a recent history (documented, confirmed or suspected) of a flu-like&#xD;
             disease within a week of vaccination.&#xD;
&#xD;
          -  Subjects have a known allergy to components of the study vaccine Sci-B-Vac™.&#xD;
&#xD;
          -  Subjects have a positive urine or serum pregnancy test within 24 hours prior to&#xD;
             vaccination, or women who are breastfeeding.&#xD;
&#xD;
          -  Subjects have an active neoplastic disease or a history of any hematologic malignancy.&#xD;
&#xD;
          -  Subjects have known chronic active hepatitis C (anti-HCV+ve), autoimmune hepatitis or&#xD;
             cirrhosis.&#xD;
&#xD;
          -  Subjects have known active human immunodeficiency virus infection (anti-HIV+ve).&#xD;
&#xD;
          -  Subjects have known chronic liver disease due to primary biliary cirrhosis, metabolic&#xD;
             or hereditary causes.&#xD;
&#xD;
          -  Subjects have received an experimental agent (vaccine, drug, biologic, device, blood&#xD;
             product, or medication) within 1 month prior to vaccination in this study or expect to&#xD;
             receive an experimental agent during this study.&#xD;
&#xD;
          -  Subjects participate in another clinical study during the current study.&#xD;
&#xD;
          -  Subjects have axillary temperature ≥38°C or oral temperature ≥38.5°C within 3 days of&#xD;
             intended study vaccination&#xD;
&#xD;
          -  Subjects have a history of alcohol or drug abuse in the last 5 years.&#xD;
&#xD;
          -  Subjects have any condition that the investigator believes may interfere with&#xD;
             successful completion of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>27 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Hong Kong</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>October 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 12, 2017</study_first_posted>
  <last_update_submitted>October 21, 2019</last_update_submitted>
  <last_update_submitted_qc>October 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vaccination</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>Imiquimod</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/NCT03307902
org study id: UW 15-106
nct id: NCT03307902
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
During the course of chronic hepatitis B infection, patients may undergo hepatitis B surface
      antigen (HBsAg) seroclearance, resulting in undetectable circulating HBsAg. With the advance
      of sensitive nucleic acid detection techniques, HBsAg-negative subjects with detectable HBV
      DNA in sera or liver tissues can be identified. Patients who have undetectable HBsAg and yet
      detectable HBV DNA in sera or liver tissues are defined as having occult HBV infection (OBI).
      OBI as a cause of liver disease in HBsAg-negative patients remains clinically important
      [1,2]. Studies conducted by our research group had demonstrated that patients with HBsAg
      seroclearance could still develop flare of hepatitis B, advanced liver diseases and HCC
      [3-6]. Prevention of these complications in OBI patients by conventional intramuscular
      hepatitis B vaccination (HBVv) remains elusive with poor amnestic anti-HBs response [7].

      The objective of this prospective double-blind randomized controlled trial is to evaluate the
      effect and safety of topical treatment with imiquimod immediately before intradermal
      vaccination with Sci-B-Vac™ in patients with OBI. Our a priori hypothesis is that imiquimod
      pretreatment would improve immune responses to Sci-B-Vac™ further in OBI patients, resulting
      in HBsAb conversion. Thereby preventing subsequent complications including flare of
      hepatitis, cirrhosis and HCC in these patients.
This randomized double-blind placebo-controlled trial will compare the safety, immunogenicity
      and clinical efficacy of Sci-B-Vac™ with topical ointment pretreatment among 5 groups. Group
      1: Intradermal Sci-B-Vac™ with topical imiquimod ointment pretreatment; Group 2: Intradermal
      Sci-B-Vac™ with topical aqueous cream (placebo) pretreatment; Group 3: Intramuscular
      Sci-B-Vac™ with topical imiquimod ointment pretreatment.

      Vaccination Regimen and Data Collection Enrolled patients will be randomized into 3 groups
      after written informed consent. Each patient will receive a 3 doses Sci-B-Vac™ regime at 0, 1
      and 6 months. Group 1 will receive a total of 10μg intradermal HBsAg each time with topical
      imiquimod ointment pretreatment; Group 2 will receive a total of 10μg intradermal HBsAg each
      time with topical aqueous cream pretreatment. Group 3 will receive a total of 10μg
      intramuscular HBsAg each time with topical imiquimod ointment pretreatment.

      The primary outcome measurement will be the seroprotection rate of the HBVv at 12 months
      after the first dose of vaccination and the secondary outcome measurements will include the
      seroconversion rate, the GMT fold increase and the safety of the intradermal Sci-B-Vac™ with
      topical imiquimod treatment at other time points.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Double blind
measure: Seroprotection rate to HBV at 12 month
time frame: 12 month
description: Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL
measure: Seroprotection rate to HBV at 1 month
time frame: 1 month
description: Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL
measure: Seroprotection rate to HBV at 6 month
time frame: 6 month
description: Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL
measure: GMT of anti-HBs at 1 month
time frame: 1 month
description: Geometric mean titre of anti-HBs antibody at 1 month after vaccination
measure: GMT of anti-HBs at 6 month
time frame: 6 month
description: Geometric mean titre of anti-HBs antibody at 6 month after vaccination
measure: GMT of anti-HBs at 12 month
time frame: 12 month
description: Geometric mean titre of anti-HBs antibody at 12 month after vaccination
arm group label: Imiquimod + ID HBVv
arm group type: Experimental
description: topical imiquimod + intradermal hepatitis B vaccination
arm group label: Aqueous + ID HBVv
arm group type: Active Comparator
description: topical aqueous + intradermal hepatitis B vaccination
arm group label: Imiquimod + IM HBVv
arm group type: Active Comparator
description: topical imiquimod + intramuscular hepatitis B vaccination
intervention type: Biological
intervention name: Imiquimod + ID HBVv
description: Imiquimod ointment + intradermal 10μg Sci-B-Vac vaccine
arm group label: Imiquimod + ID HBVv
intervention type: Biological
intervention name: Aqueous + ID HBVv
description: Aqueous ointment + intradermal 10μg Sci-B-Vac vaccine
arm group label: Aqueous + ID HBVv
intervention type: Biological
intervention name: Imiquimod + IM HBVv
description: Imiquimod ointment + intramuscular 10μg Sci-B-Vac vaccine
arm group label: Imiquimod + IM HBVv
criteria: 
gender: All
minimum age: 27 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Hong Kong
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis
mesh term: Imiquimod
sharing ipd: No