<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/NCT02189603</url>
  </required_header>
  <id_info>
    <org_study_id>PRO-HE-05</org_study_id>
    <nct_id>NCT02189603</nct_id>
  </id_info>
  <brief_title>Phase Ⅳ Clinical Trial of Recombinant Hepatitis E Vaccine（Hecolin®）</brief_title>
  <official_title>Evaluation of Safety and Immunogenicity of Recombinant (E. Coli) Hepatitis E Vaccine（Hecolin®） in Seniors Aged Over 65 Years</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jun Zhang</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Xiamen Innovax Biotech Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Xiamen Center for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Xiamen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety and immunogenicity of the recombinant&#xD;
      hepatitis E vaccine in people older than 65 years, and evaluate the efficacy of hepatitis E&#xD;
      vaccine in this population.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">December 7, 2015</completion_date>
  <primary_completion_date type="Actual">December 7, 2015</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>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Serious and Non-Serious Adverse Events</measure>
    <time_frame>From month 0-7</time_frame>
    <description>Any adverse events reported within one month post each vaccination would be recorded, any serious adverse events reported throughout the study would be recorded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>anti-HEV IgG seropositive rate</measure>
    <time_frame>at month 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GMT of anti-HEV IgG</measure>
    <time_frame>7 month after first vaccination</time_frame>
    <description>Serum sample would be collected at month 7, and geometric mean titer of anti-HEV IgG would be tested</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">601</enrollment>
  <condition>Hepatitis E</condition>
  <arm_group>
    <arm_group_label>Senior group(over 65 years old)-HE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anti-HEV IgG seronegative participants over 65 years old were enrolled. Hepatitis E vaccine, containing 30mcg of HEV239 recombinant antigen adsorbed to alum adjuvant suspended in 0.5ml phosphate buffer, was given at 0, 1, 6m for three doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Younger groups(16-65 years old)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants aged 16-65 years old were enrolled. Hepatitis E vaccine, containing 30mcg of HEV239 recombinant antigen adsorbed to alum adjuvant suspended in 0.5ml phosphate buffer, was given at 0, 1, 6m for three doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Senior group(over 65 years old)-Cont</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Anti-HEV IgG seropositive participants over 65 years old were enrolled. This is the safety control group, without any intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Recombinant (E. Coli) Hepatitis E Vaccine</intervention_name>
    <arm_group_label>Senior group(over 65 years old)-HE</arm_group_label>
    <arm_group_label>Younger groups(16-65 years old)</arm_group_label>
    <other_name>Hecolin®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy people aged over 16 years old at the time of the first vaccination, normal&#xD;
             intelligence and agree to sign the informed consent form.&#xD;
&#xD;
          -  Healthy subjects as established by medical history and history-oriented clinical&#xD;
             examination before entering into the study.&#xD;
&#xD;
          -  Subjects will reside in the study region in the next 7 months.&#xD;
&#xD;
          -  Free of history of hepatitis E.&#xD;
&#xD;
          -  Can comply with the request of study.&#xD;
&#xD;
          -  Axillary temperature is below 37 degree centigrade.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        For dose 1:&#xD;
&#xD;
          -  receiving other vaccine or immunoglobulin within two weeks;&#xD;
&#xD;
          -  Having serious allergic history to vaccine and medicine&#xD;
&#xD;
          -  Eclampsia, epilepsy, encephalopathy and history of mental disease or family;&#xD;
&#xD;
          -  Thrombocytopenia or other disturbance of blood coagulation which would lead to muscle&#xD;
             injection taboo;&#xD;
&#xD;
          -  Fixed or suspected deficiency of immunologic function, containing immunosuppressant&#xD;
             treatment, genetic defect, HIV or other factors;&#xD;
&#xD;
          -  Congenital malformation, eccyliosis or severe chronic disease;&#xD;
&#xD;
          -  Fixed or suspected other disease including fever, active infection, liver and kidney&#xD;
             disease, angiocardiopathy, malignancy, acute and chronic disease;&#xD;
&#xD;
          -  joining other clinical study undergoing;&#xD;
&#xD;
          -  women pregnant or in lactation.&#xD;
&#xD;
        For dose 2 or 3:&#xD;
&#xD;
          -  Severe allergy for dose 1 or 2;&#xD;
&#xD;
          -  Severe adverse reaction associated with last vaccination;&#xD;
&#xD;
          -  New occurrence of symptoms meet dose 1 exclusion criteria after the first dose.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Center for disease control and prevention in Xiamen haicang district</name>
      <address>
        <city>Xiamen</city>
        <state>Fujian</state>
        <zip>361000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, Yang CL, Jiang HM, Cai JP, Wang YJ, Ai X, Hu YM, Tang Q, Yao X, Yan Q, Xian YL, Wu T, Li YM, Miao J, Ng MH, Shih JW, Xia NS. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010 Sep 11;376(9744):895-902. doi: 10.1016/S0140-6736(10)61030-6. Epub 2010 Aug 20.</citation>
    <PMID>20728932</PMID>
  </reference>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>July 9, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <last_update_submitted>August 15, 2018</last_update_submitted>
  <last_update_submitted_qc>August 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Xiamen University</investigator_affiliation>
    <investigator_full_name>Jun Zhang</investigator_full_name>
    <investigator_title>professor，Xiamen University</investigator_title>
  </responsible_party>
  <keyword>hepatitis E</keyword>
  <keyword>Immunogenicity</keyword>
  <keyword>vaccine</keyword>
  <keyword>safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis E</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_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/NCT02189603
org study id: PRO-HE-05
nct id: NCT02189603
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine the safety and immunogenicity of the recombinant
      hepatitis E vaccine in people older than 65 years, and evaluate the efficacy of hepatitis E
      vaccine in this population.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Number of Participants with Serious and Non-Serious Adverse Events
time frame: From month 0-7
description: Any adverse events reported within one month post each vaccination would be recorded, any serious adverse events reported throughout the study would be recorded.
measure: anti-HEV IgG seropositive rate
time frame: at month 7
measure: GMT of anti-HEV IgG
time frame: 7 month after first vaccination
description: Serum sample would be collected at month 7, and geometric mean titer of anti-HEV IgG would be tested
arm group label: Senior group(over 65 years old)-HE
arm group type: Experimental
description: Anti-HEV IgG seronegative participants over 65 years old were enrolled. Hepatitis E vaccine, containing 30mcg of HEV239 recombinant antigen adsorbed to alum adjuvant suspended in 0.5ml phosphate buffer, was given at 0, 1, 6m for three doses.
arm group label: Younger groups(16-65 years old)
arm group type: Active Comparator
description: Participants aged 16-65 years old were enrolled. Hepatitis E vaccine, containing 30mcg of HEV239 recombinant antigen adsorbed to alum adjuvant suspended in 0.5ml phosphate buffer, was given at 0, 1, 6m for three doses.
arm group label: Senior group(over 65 years old)-Cont
arm group type: No Intervention
description: Anti-HEV IgG seropositive participants over 65 years old were enrolled. This is the safety control group, without any intervention.
intervention type: Biological
intervention name: Recombinant (E. Coli) Hepatitis E Vaccine
arm group label: Senior group(over 65 years old)-HE
arm group label: Younger groups(16-65 years old)
other name: Hecolin®
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
citation: Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, Yang CL, Jiang HM, Cai JP, Wang YJ, Ai X, Hu YM, Tang Q, Yao X, Yan Q, Xian YL, Wu T, Li YM, Miao J, Ng MH, Shih JW, Xia NS. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010 Sep 11;376(9744):895-902. doi: 10.1016/S0140-6736(10)61030-6. Epub 2010 Aug 20.
PMID: 20728932
responsible party type: Sponsor-Investigator
investigator affiliation: Xiamen University
investigator full name: Jun Zhang
investigator title: professor，Xiamen University
mesh term: Hepatitis A
mesh term: Hepatitis E
mesh term: Hepatitis