<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/NCT01734408</url>
  </required_header>
  <id_info>
    <org_study_id>JSVCT005b</org_study_id>
    <nct_id>NCT01734408</nct_id>
  </id_info>
  <brief_title>A Booster Dose of Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children</brief_title>
  <official_title>A Booster Dose of Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu Province Centers for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bejing Vigoo Biological Co., LTD</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Jiangsu Province Centers for Disease Control and Prevention</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hand, foot, and mouth disease (HFMD) is a common viral illness in infants and children caused&#xD;
      by viruses that belong to the enterovirus genus of the picornavirus family. Although most&#xD;
      HFMD cases do not result in serious complications, outbreaks of HFMD caused by enterovirus 71&#xD;
      (EV71) can present with a high rate of neurological complications, including&#xD;
      meningoencephalitis, pulmonary complications, and can even cause infant death. HFMD caused by&#xD;
      EV71 has become a major emerging infectious disease in Asia and the highly pathogenic&#xD;
      potential of EV71 clearly requires the attention of world medical community.&#xD;
&#xD;
      The phase II study of inactivated vaccine (vero cell) against EV71 has completed last month&#xD;
      in Jiangsu Province in China. The data from the phase II study suggested that the inactivated&#xD;
      EV71 vaccine had a clinically acceptable safety and good immunogenicity for healthy Chinese&#xD;
      children and infants. But the antibody titer against EV71 was found decreased significantly&#xD;
      at month 8 compared to that at day 56. Considering the similar dynamic trend had also been&#xD;
      found in the antibody against poliovirus induced by polio vaccines, and whose immunization&#xD;
      schedule contains a booster dose administrated at 1 to 1.5 year after the first 3 doses of&#xD;
      fundamental immunity. In order to find a better immunization schedule for children, the&#xD;
      investigators decided to perform this booster immunity trial among these children who had&#xD;
      received two doses of EV71 vaccines (around one year after the fundamental immunity). The&#xD;
      investigators do the recruitment among these children who had participated in the previous&#xD;
      phase II trial and received EV71 vaccines, and randomize them in a ratio of 2:1 to receive&#xD;
      either a booster dose of EV71 vaccines or placebo.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">February 2013</completion_date>
  <primary_completion_date type="Actual">January 2013</primary_completion_date>
  <phase>Phase 2</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, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Geometric mean titer (GMT) of anti-EV71 antibodies</measure>
    <time_frame>28 days after vaccination</time_frame>
    <description>GMT of anti-EV71 antibodies in serum 28 days after booster dose injection</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of EV71 vaccine in healthy children</measure>
    <time_frame>28 days after vaccination</time_frame>
    <description>Frequency of systemic and local adverse reactions in healthy children following 28 days after the boosting dose of EV71 vaccine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean fold increase (GMFI) of anti-EV71 antibodies</measure>
    <time_frame>28 days after vaccination</time_frame>
    <description>GMFI of anti-EV71 antibodies in serum 28 days after vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroconversion of anti-EV71 antibodies</measure>
    <time_frame>28 days after vaccination</time_frame>
    <description>Seroconversion of anti-EV71 antibodies in serum 28 days after vaccination</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">773</enrollment>
  <condition>EV71-associated Disease</condition>
  <arm_group>
    <arm_group_label>alum-adjuvant 160U /0.5ml EV71 vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A booster dose of alum-adjuvant 160U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 160U/0.5ml EV71 vaccines one year before.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 160U/0.5ml EV71 vaccines one year before.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>alum-adjuvant 320U /0.5ml EV71 vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A booster dose of alum-adjuvant 320U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 320U/0.5ml EV71 vaccines one year before.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 320U/0.5ml EV71 vaccines one year before.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>alum-adjuvant 640U /0.5ml EV71 vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A booster dose of alum-adjuvant 640U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 640U/0.5ml EV71 vaccines one year before.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo C</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 640U/0.5ml EV71 vaccines one year before.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>adjuvant-free 640U /0.5ml EV71 vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A booster dose of adjuvant-free 640U /0.5ml EV71 vaccine in 160 children whom had received two doses of adjuvant-free 640U/0.5ml EV71 vaccines one year before.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo D</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A 0/0.5ml placebo in 80 children whom had received two doses of adjuvant-free 640U/0.5ml EV71 vaccines one year before.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>alum-adjuvant 160U /0.5ml</intervention_name>
    <description>inactivated vaccine (vero cell) alum-adjuvant 160U /0.5ml EV71 vaccine</description>
    <arm_group_label>alum-adjuvant 160U /0.5ml EV71 vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>alum-adjuvant 320U /0.5ml</intervention_name>
    <description>inactivated vaccine (vero cell) alum-adjuvant 320U /0.5ml EV71 vaccine</description>
    <arm_group_label>alum-adjuvant 320U /0.5ml EV71 vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>alum-adjuvant 640U /0.5ml</intervention_name>
    <description>inactivated vaccine (vero cell) alum-adjuvant 640U /0.5ml EV71 vaccine</description>
    <arm_group_label>alum-adjuvant 640U /0.5ml EV71 vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>adjuvant-free 640U /0.5ml</intervention_name>
    <description>inactivated vaccine (vero cell) adjuvant-free 640U /0.5ml EV71 vaccine</description>
    <arm_group_label>adjuvant-free 640U /0.5ml EV71 vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>0/0.5ml placebo</intervention_name>
    <description>0/0.5ml placebo</description>
    <arm_group_label>placebo A</arm_group_label>
    <arm_group_label>placebo B</arm_group_label>
    <arm_group_label>placebo C</arm_group_label>
    <arm_group_label>placebo D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Had participated in the previous phase II trial and received at least 1 dose of EV71&#xD;
             vaccine.&#xD;
&#xD;
          -  Healthy children as established by medical history and clinical examination&#xD;
&#xD;
          -  The subjects' guardians are able to understand and sign the informed consent&#xD;
&#xD;
          -  Subjects who can and will comply with the requirements of the protocol&#xD;
&#xD;
          -  Subjects with temperature &lt;=37.0°C on axillary setting&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Had participated in the previous phase II trial and received placebo.&#xD;
&#xD;
          -  Subject who has a medical history of EV71-associated disease with specific laboratory&#xD;
             evidence&#xD;
&#xD;
          -  &lt;= 37 weeks gestation&#xD;
&#xD;
          -  Subjects with a birth weight &lt;2.5 kg&#xD;
&#xD;
          -  Subject that has a medical history of any of the following: allergic history, or&#xD;
             allergic to any ingredient of vaccine&#xD;
&#xD;
          -  Family history of seizures or progressive neurological disease&#xD;
&#xD;
          -  Family history of congenital or hereditary immunodeficiency&#xD;
&#xD;
          -  Severe malnutrition or dysgenopathy&#xD;
&#xD;
          -  Major congenital defects or serious chronic illness, including perinatal brain damage&#xD;
&#xD;
          -  Autoimmune disease&#xD;
&#xD;
          -  Bleeding disorder diagnosed by a doctor or significant bruising or bleeding&#xD;
             difficulties with IM injections or blood draws&#xD;
&#xD;
          -  Any acute infections in last 7 days&#xD;
&#xD;
          -  Any prior administration of immunodepressant or corticosteroids in last 6month&#xD;
&#xD;
          -  Any prior administration of blood products in last 3 month&#xD;
&#xD;
          -  Any prior administration of other research medicines in last 1 month&#xD;
&#xD;
          -  Any prior administration of attenuated live vaccine in last 14 days&#xD;
&#xD;
          -  Any prior administration of subunit or inactivated vaccines in last 7 days, such as&#xD;
             pneumococcal vaccine&#xD;
&#xD;
          -  Under the anti-TB prevention or therapy&#xD;
&#xD;
          -  Any condition that in the opinion of the investigator, may interfere with the&#xD;
             evaluation of study objectives&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Months</minimum_age>
    <maximum_age>51 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Jiangsu Provincial Center for Diseases Control and Prevention</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210009</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2013</verification_date>
  <study_first_submitted>November 22, 2012</study_first_submitted>
  <study_first_submitted_qc>November 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>October 21, 2013</last_update_submitted>
  <last_update_submitted_qc>October 21, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 23, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Jiangsu Province Centers for Disease Control and Prevention</investigator_affiliation>
    <investigator_full_name>Fengcai Zhu</investigator_full_name>
    <investigator_title>vice director</investigator_title>
  </responsible_party>
  <keyword>immunogenicity</keyword>
  <keyword>safety</keyword>
  <keyword>inactivated EV71 vaccine</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aluminum Hydroxide</mesh_term>
    <mesh_term>Aluminum sulfate</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/NCT01734408
org study id: JSVCT005b
nct id: NCT01734408
lead sponsor: 
collaborator: 
has dmc: No
Hand, foot, and mouth disease (HFMD) is a common viral illness in infants and children caused
      by viruses that belong to the enterovirus genus of the picornavirus family. Although most
      HFMD cases do not result in serious complications, outbreaks of HFMD caused by enterovirus 71
      (EV71) can present with a high rate of neurological complications, including
      meningoencephalitis, pulmonary complications, and can even cause infant death. HFMD caused by
      EV71 has become a major emerging infectious disease in Asia and the highly pathogenic
      potential of EV71 clearly requires the attention of world medical community.

      The phase II study of inactivated vaccine (vero cell) against EV71 has completed last month
      in Jiangsu Province in China. The data from the phase II study suggested that the inactivated
      EV71 vaccine had a clinically acceptable safety and good immunogenicity for healthy Chinese
      children and infants. But the antibody titer against EV71 was found decreased significantly
      at month 8 compared to that at day 56. Considering the similar dynamic trend had also been
      found in the antibody against poliovirus induced by polio vaccines, and whose immunization
      schedule contains a booster dose administrated at 1 to 1.5 year after the first 3 doses of
      fundamental immunity. In order to find a better immunization schedule for children, the
      investigators decided to perform this booster immunity trial among these children who had
      received two doses of EV71 vaccines (around one year after the fundamental immunity). The
      investigators do the recruitment among these children who had participated in the previous
      phase II trial and received EV71 vaccines, and randomize them in a ratio of 2:1 to receive
      either a booster dose of EV71 vaccines or placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: Geometric mean titer (GMT) of anti-EV71 antibodies
time frame: 28 days after vaccination
description: GMT of anti-EV71 antibodies in serum 28 days after booster dose injection
measure: Safety of EV71 vaccine in healthy children
time frame: 28 days after vaccination
description: Frequency of systemic and local adverse reactions in healthy children following 28 days after the boosting dose of EV71 vaccine
measure: Geometric mean fold increase (GMFI) of anti-EV71 antibodies
time frame: 28 days after vaccination
description: GMFI of anti-EV71 antibodies in serum 28 days after vaccination
measure: Seroconversion of anti-EV71 antibodies
time frame: 28 days after vaccination
description: Seroconversion of anti-EV71 antibodies in serum 28 days after vaccination
arm group label: alum-adjuvant 160U /0.5ml EV71 vaccine
arm group type: Experimental
description: A booster dose of alum-adjuvant 160U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 160U/0.5ml EV71 vaccines one year before.
arm group label: placebo A
arm group type: Placebo Comparator
description: A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 160U/0.5ml EV71 vaccines one year before.
arm group label: alum-adjuvant 320U /0.5ml EV71 vaccine
arm group type: Experimental
description: A booster dose of alum-adjuvant 320U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 320U/0.5ml EV71 vaccines one year before.
arm group label: placebo B
arm group type: Placebo Comparator
description: A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 320U/0.5ml EV71 vaccines one year before.
arm group label: alum-adjuvant 640U /0.5ml EV71 vaccine
arm group type: Experimental
description: A booster dose of alum-adjuvant 640U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 640U/0.5ml EV71 vaccines one year before.
arm group label: placebo C
arm group type: Placebo Comparator
description: A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 640U/0.5ml EV71 vaccines one year before.
arm group label: adjuvant-free 640U /0.5ml EV71 vaccine
arm group type: Experimental
description: A booster dose of adjuvant-free 640U /0.5ml EV71 vaccine in 160 children whom had received two doses of adjuvant-free 640U/0.5ml EV71 vaccines one year before.
arm group label: placebo D
arm group type: Placebo Comparator
description: A 0/0.5ml placebo in 80 children whom had received two doses of adjuvant-free 640U/0.5ml EV71 vaccines one year before.
intervention type: Biological
intervention name: alum-adjuvant 160U /0.5ml
description: inactivated vaccine (vero cell) alum-adjuvant 160U /0.5ml EV71 vaccine
arm group label: alum-adjuvant 160U /0.5ml EV71 vaccine
intervention type: Biological
intervention name: alum-adjuvant 320U /0.5ml
description: inactivated vaccine (vero cell) alum-adjuvant 320U /0.5ml EV71 vaccine
arm group label: alum-adjuvant 320U /0.5ml EV71 vaccine
intervention type: Biological
intervention name: alum-adjuvant 640U /0.5ml
description: inactivated vaccine (vero cell) alum-adjuvant 640U /0.5ml EV71 vaccine
arm group label: alum-adjuvant 640U /0.5ml EV71 vaccine
intervention type: Biological
intervention name: adjuvant-free 640U /0.5ml
description: inactivated vaccine (vero cell) adjuvant-free 640U /0.5ml EV71 vaccine
arm group label: adjuvant-free 640U /0.5ml EV71 vaccine
intervention type: Biological
intervention name: 0/0.5ml placebo
description: 0/0.5ml placebo
arm group label: placebo A
arm group label: placebo B
arm group label: placebo C
arm group label: placebo D
criteria: 
gender: All
minimum age: 21 Months
maximum age: 51 Months
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Jiangsu Province Centers for Disease Control and Prevention
investigator full name: Fengcai Zhu
investigator title: vice director
mesh term: Aluminum Hydroxide
mesh term: Aluminum sulfate