<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/NCT03278132</url>
  </required_header>
  <id_info>
    <org_study_id>PRO-EV71-4011</org_study_id>
    <nct_id>NCT03278132</nct_id>
  </id_info>
  <brief_title>Phase IV Clinical Trial, Immunogenicity and Safety of EV71 Vaccine</brief_title>
  <official_title>A Phase IV Open-labelled, Single-centered, Stratified-randomized Clinical Trial in Zhejiang Province to Evaluate the Safety and Immunogenicity of EV71 Vaccine Developed by Sinovac Biotech Co., Ltd.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sinovac Biotech Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Zhejiang Provincial Center for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shangyu District Center for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sinovac Biotech Co., Ltd</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the immunogenicity and safety of EV71 vaccine in&#xD;
      infants aged 6 to 35 months old, by detecting the dynamic changes of neutralizing antibody at&#xD;
      different time after vaccination&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is an open-labelled, single-centered, stratified-randomized, phase IV clinical&#xD;
      trial. The purpose of this study is to evaluate the immunogenicity and safety of EV71 vaccine&#xD;
      (developed by Sinovac Biotech Co., Ltd.) in infants aged 6 to 35 months old, by detecting the&#xD;
      dynamic changes of neutralizing antibody at different times after vaccination. The enrolled&#xD;
      subjects in this study receive two doses of EV71 vaccine with 1-month interval between doses.&#xD;
      To evaluate safety of the vaccine, subjects will be observed for 30 days after the injection&#xD;
      for the potential adverse events. To evaluate the immunogenicity of the vaccine, venous blood&#xD;
      will be collected for the neutralizing antibody detection prior to vaccination, 10/20/30 days&#xD;
      after the 1st dose and 30 days after the 2nd dose vaccination. All subjects will receive&#xD;
      blood sampling for three times. Subjects will be randomly assigned to receive blood sampling&#xD;
      at 10/20/30 days after 1st dose injection, with a ratio of 1: 1: 1.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 16, 2017</start_date>
  <completion_date type="Actual">September 15, 2017</completion_date>
  <primary_completion_date type="Actual">September 15, 2017</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The seroconversion rate of EV71 neutralizing antibody 30 days after the two doses vaccination</measure>
    <time_frame>30 days</time_frame>
    <description>Immunogenicity indicator</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The seroconversion rate of EV71 neutralizing antibody 10, 20 and 30 days after the first dose vaccination</measure>
    <time_frame>10,20,and 30 days</time_frame>
    <description>Immunogenicity indicator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The seropositive rate of EV71 neutralizing antibody 10, 20, 30, and 60 days after the first dose vaccination</measure>
    <time_frame>10, 20,30,and 60 days</time_frame>
    <description>Immunogenicity indicator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GMT and GMT increase fold of EV71 neutralizing antibody 10,20,30,and 60 days after the first dose vaccination</measure>
    <time_frame>10,20，30，and 60 days</time_frame>
    <description>Immunogenicity indicator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of unsolicited local or systemic adverse events within 3 days after each dose</measure>
    <time_frame>3 days</time_frame>
    <description>Safety indicator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of unsolicited adverse events within 30 days after each dose</measure>
    <time_frame>30 days</time_frame>
    <description>Safety indicator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of the serious adverse events within 60 days after the first dose vaccination</measure>
    <time_frame>60 days</time_frame>
    <description>Safety indicator</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Hand, Foot and Mouth Disease</condition>
  <arm_group>
    <arm_group_label>EV71 vaccine &amp; blood sampling (0, 10,60)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group receive two doses injection of EV71 vaccine (0, 28 days), and three times of blood sampling on day of 0, 10, and 60 respectively for EV71 neutralizing antibody detection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EV71 vaccine &amp; blood sampling (0, 20,60)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group receive two doses injection of EV71 vaccine (0, 28 days), and three times of blood sampling on day of 0, 20, and 60 respectively for EV71 neutralizing antibody detection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EV71 vaccine&amp; blood sampling (0, 30, 60)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group receive two doses injection of EV71 vaccine (0, 28 days), and three times of blood sampling on day of 0, 30, and 60 respectively for EV71 neutralizing antibody detection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EV71 vaccine</intervention_name>
    <description>Two doses vaccination of EV71vaccine (Intramuscular injection, 0.5ml) with a schedule of 0, 28 days.</description>
    <arm_group_label>EV71 vaccine &amp; blood sampling (0, 10,60)</arm_group_label>
    <arm_group_label>EV71 vaccine &amp; blood sampling (0, 20,60)</arm_group_label>
    <arm_group_label>EV71 vaccine&amp; blood sampling (0, 30, 60)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers aged 6-35 months old&#xD;
&#xD;
          -  Guardian(s) of the volunteer should be capable of understanding the written consent&#xD;
             form, and such form should be signed before the infant being included into this study&#xD;
&#xD;
          -  Proven legal identity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        For subjects with any of the following conditions, vaccination should not be administrated:&#xD;
&#xD;
          -  History of hand foot and mouth disease&#xD;
&#xD;
          -  Allergy to gentamicin; history of allergy to any vaccine or vaccine ingredient, or&#xD;
             serious adverse reaction(s) to vaccination, such as urticaria, difficulty in&#xD;
             breathing, angioneurotic edema, pain, etc&#xD;
&#xD;
          -  Severe chronic diseases&#xD;
&#xD;
          -  Thrombocytopenia or hemorrhagic disease&#xD;
&#xD;
          -  Immunodeficiency disease or receipt of immunosuppressant treatment&#xD;
&#xD;
          -  Uncontrolled epilepsy or progressive neurological disorders(e.g. Guillain-Barre&#xD;
             syndrome)&#xD;
&#xD;
          -  Acute disease or acute stage of chronic disease prior to the study entry&#xD;
&#xD;
          -  History of thyroidectomy, thyroid disease within 12 months prior to the study entry&#xD;
&#xD;
          -  Asplenia or functional asplenia&#xD;
&#xD;
          -  Axillary temperature &gt;37.0 ℃&#xD;
&#xD;
          -  Any other factor that suggesting the volunteer is unsuitable for this study based on&#xD;
             the judgment of investigators&#xD;
&#xD;
        Exclusion Criteria of the Second Injection:&#xD;
&#xD;
          -  Subjects with any of the following conditions are forbidden to continue the 2nd dose&#xD;
             of vaccination:&#xD;
&#xD;
               1. Any serious adverse event that has a causal relationship with the investigated&#xD;
                  vaccine&#xD;
&#xD;
               2. Severe allergic reactions or hypersensitivity after vaccination (including&#xD;
                  urticaria / rash appear within 30 minutes after vaccination&#xD;
&#xD;
               3. Any confirmed or suspected autoimmune disease or immunodeficiency disease (e.g.,&#xD;
                  HIV infection)&#xD;
&#xD;
               4. Other reactions (including severe pain, severe swelling, severe activity&#xD;
                  limitation, persistent hyperthermia, severe headache or other systemic or local&#xD;
                  reactions)determined by the investigators&#xD;
&#xD;
          -  For subjects suffering from acute disease or acute stage of chronic disease , whether&#xD;
             to continue vaccination depends on themselves&#xD;
&#xD;
          -  Subjects with the following conditions may receive vaccination in delayed time or&#xD;
             withdraw from the study depending on the judgment of investigator&#xD;
&#xD;
               1. Acute disease (moderate or severe disease with or without fever) in case of&#xD;
                  vaccination&#xD;
&#xD;
               2. Axillary temperature &gt; 37.0 °C&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>35 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Huakun Lv</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zhejiang Provincial Center for Disease Control and Prevention</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Shangyu District Center for Disease Control and Prevention</name>
      <address>
        <city>Shaoxing</city>
        <state>Zhejiang</state>
        <zip>312300</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>December 28, 2018</last_update_submitted>
  <last_update_submitted_qc>December 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Inactivated Enterovirus Type 71 (EV71) Vaccine</keyword>
  <keyword>Safety</keyword>
  <keyword>Immunogenicity</keyword>
  <keyword>Infant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Foot-and-Mouth Disease</mesh_term>
    <mesh_term>Hand, Foot and Mouth Disease</mesh_term>
    <mesh_term>Mouth Diseases</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/NCT03278132
org study id: PRO-EV71-4011
nct id: NCT03278132
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the immunogenicity and safety of EV71 vaccine in
      infants aged 6 to 35 months old, by detecting the dynamic changes of neutralizing antibody at
      different time after vaccination
This study is an open-labelled, single-centered, stratified-randomized, phase IV clinical
      trial. The purpose of this study is to evaluate the immunogenicity and safety of EV71 vaccine
      (developed by Sinovac Biotech Co., Ltd.) in infants aged 6 to 35 months old, by detecting the
      dynamic changes of neutralizing antibody at different times after vaccination. The enrolled
      subjects in this study receive two doses of EV71 vaccine with 1-month interval between doses.
      To evaluate safety of the vaccine, subjects will be observed for 30 days after the injection
      for the potential adverse events. To evaluate the immunogenicity of the vaccine, venous blood
      will be collected for the neutralizing antibody detection prior to vaccination, 10/20/30 days
      after the 1st dose and 30 days after the 2nd dose vaccination. All subjects will receive
      blood sampling for three times. Subjects will be randomly assigned to receive blood sampling
      at 10/20/30 days after 1st dose injection, with a ratio of 1: 1: 1.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: The seroconversion rate of EV71 neutralizing antibody 30 days after the two doses vaccination
time frame: 30 days
description: Immunogenicity indicator
measure: The seroconversion rate of EV71 neutralizing antibody 10, 20 and 30 days after the first dose vaccination
time frame: 10,20,and 30 days
description: Immunogenicity indicator
measure: The seropositive rate of EV71 neutralizing antibody 10, 20, 30, and 60 days after the first dose vaccination
time frame: 10, 20,30,and 60 days
description: Immunogenicity indicator
measure: GMT and GMT increase fold of EV71 neutralizing antibody 10,20,30,and 60 days after the first dose vaccination
time frame: 10,20，30，and 60 days
description: Immunogenicity indicator
measure: Incidence of unsolicited local or systemic adverse events within 3 days after each dose
time frame: 3 days
description: Safety indicator
measure: Incidence of unsolicited adverse events within 30 days after each dose
time frame: 30 days
description: Safety indicator
measure: Incidence of the serious adverse events within 60 days after the first dose vaccination
time frame: 60 days
description: Safety indicator
arm group label: EV71 vaccine & blood sampling (0, 10,60)
arm group type: Experimental
description: This group receive two doses injection of EV71 vaccine (0, 28 days), and three times of blood sampling on day of 0, 10, and 60 respectively for EV71 neutralizing antibody detection.
arm group label: EV71 vaccine & blood sampling (0, 20,60)
arm group type: Experimental
description: This group receive two doses injection of EV71 vaccine (0, 28 days), and three times of blood sampling on day of 0, 20, and 60 respectively for EV71 neutralizing antibody detection.
arm group label: EV71 vaccine& blood sampling (0, 30, 60)
arm group type: Experimental
description: This group receive two doses injection of EV71 vaccine (0, 28 days), and three times of blood sampling on day of 0, 30, and 60 respectively for EV71 neutralizing antibody detection.
intervention type: Biological
intervention name: EV71 vaccine
description: Two doses vaccination of EV71vaccine (Intramuscular injection, 0.5ml) with a schedule of 0, 28 days.
arm group label: EV71 vaccine & blood sampling (0, 10,60)
arm group label: EV71 vaccine & blood sampling (0, 20,60)
arm group label: EV71 vaccine& blood sampling (0, 30, 60)
criteria: 
gender: All
minimum age: 6 Months
maximum age: 35 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Huakun Lv
role: Principal Investigator
affiliation: Zhejiang Provincial Center for Disease Control and Prevention
facility: 
country: China
responsible party type: Sponsor
mesh term: Foot-and-Mouth Disease
mesh term: Hand, Foot and Mouth Disease
mesh term: Mouth Diseases