<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/NCT03274102</url>
  </required_header>
  <id_info>
    <org_study_id>PRO-EV71-4003</org_study_id>
    <nct_id>NCT03274102</nct_id>
  </id_info>
  <brief_title>Safety and Immunogenicity of Concomitant Administration of EV71 Vaccine With EPI Vaccines</brief_title>
  <official_title>A Randomized, Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of Concomitant Administration of EV71 Vaccine With Recombinant Hepatitis B Vaccine/Group A Meningococcal Polysaccharide Vaccine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sinovac Biotech Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Guangdong Center for Disease Prevention and Control</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 safety and immunogenicity of concomitant&#xD;
      administration of EV71 vaccine with recombinant hepatitis B vaccine/Group A meningococcal&#xD;
      polysaccharide vaccine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is an open-label, single-center, randomized, comparative phase IV clinical trial.&#xD;
      The purpose of this study is to evaluate the safety and immunogenicity of concomitant&#xD;
      administration of EV71 vaccine manufactured by Sinovac (Beijing) Vaccine Technology Co., Ltd.&#xD;
      with recombinant hepatitis B vaccine/Group A meningococcal polysaccharide vaccine. 780&#xD;
      healthy infants of 6 months old as participants are randomly assigned into three experimental&#xD;
      groups in the ratio 1:1:1. The group I receive EV71 Vaccine (first dose)&amp; recombinant&#xD;
      hepatitis B vaccine on day 0 and EV71 vaccine (second dose)&amp; Group A meningococcal&#xD;
      polysaccharide vaccine on day 30. The group II receive recombinant hepatitis B vaccine on day&#xD;
      0 and Group A meningococcal polysaccharide vaccine on day 30. The group III receive the first&#xD;
      and second dose of EV71 Vaccine on day 0 and day 30 respectively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 22, 2017</start_date>
  <completion_date type="Actual">November 1, 2017</completion_date>
  <primary_completion_date type="Actual">November 1, 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>
    <masking_description>open-labelled</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The seropositive rate of EV71 neutralizing antibody, anti-HBs and serum bactericidal antibody 1 month after 2 doses of vaccination</measure>
    <time_frame>30 days after 2 doses of injection</time_frame>
    <description>Immunogenicity indicator</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of solicited local or systemic adverse events within 7 days after each dose</measure>
    <time_frame>7 days after each dose of injection</time_frame>
    <description>Safety indicator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of unsolicited local or systemic adverse events within 30 days after each dose</measure>
    <time_frame>30 days after each dose of injection</time_frame>
    <description>Safety indicator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of serious adverse events during the period of safety monitoring</measure>
    <time_frame>60 days after the first dose injection</time_frame>
    <description>Safety indicator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The seroconversion rate of EV71 neutralizing antibody, anti-HBs and serum bactericidal antibody(SBA) 1 month after 2 doses of vaccination</measure>
    <time_frame>30 days after 2 doses of injection</time_frame>
    <description>Immunogenicity indicator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EV71 neutralizing antibody GMT, anti-HBs GMC and SBA antibody GMT 1 month after 2 doses of vaccination</measure>
    <time_frame>30 days after 2 doses of injection</time_frame>
    <description>Immunogenicity indicator</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">780</enrollment>
  <condition>Hand, Foot and Mouth Disease</condition>
  <arm_group>
    <arm_group_label>Group I-EV71 vaccine and EPI vaccines</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Concomitant administration of EV71 vaccine with EPI vaccines: EV71 Vaccine (intramuscular injection,0.5ml,first dose)/recombinant hepatitis B vaccine（intramuscular injection,0.5ml）on day 0 and EV71 Vaccine (injection, 0.5ml,second dose)/ Group A meningococcal polysaccharide vaccine(subcutaneous injection, 150ug) on day 30.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group II-EPI vaccine only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single injection of EPI vaccine: recombinant hepatitis B vaccine (intramuscular injection, 0.5ml) on day 0 and Group A meningococcal polysaccharide vaccine (subcutaneous injection,150ug) on day 30.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group III-EV71 vaccine only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>EV71 Vaccine only: the first and second dose of EV71 Vaccine (intramuscular injection,0.5ml) on day 0 and day 30 respectively.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Concomitant administration of EV71 vaccine with EPI vaccines</intervention_name>
    <description>The investigated EV17 vaccine was manufactured by Sinovac Biotech Co., Ltd.； the recombinant hepatitis B vaccine was manufactured by Shenzhen Kangtai Biological Products Co., Ltd; the Group A meningococcal polysaccharide vaccine was manufactured by Wuhan Institute of Biological Products Co., Ltd.&#xD;
The primary vaccination schedule of hepatitis B vaccine includes 3 doses with a schedule of 0,1,6 month, and subjects only receive 3rd vaccination in this study; the primary vaccination schedule of Group A meningococcal polysaccharide vaccine includes 2 doses with 3 months interval between doses, and subjects only receive 1st vaccination in this study</description>
    <arm_group_label>Group I-EV71 vaccine and EPI vaccines</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Single injection of EPI vaccine</intervention_name>
    <description>The recombinant hepatitis B vaccine was manufactured by Shenzhen Kangtai Biological Products Co., Ltd; the Group A meningococcal polysaccharide vaccine was manufactured by Wuhan Institute of Biological Products Co., Ltd.&#xD;
The primary vaccination schedule of hepatitis B vaccine includes 3 doses with a schedule of 0,1,6 month, and subjects only receive 3rd vaccination in this study; the primary vaccination schedule of Group A meningococcal polysaccharide vaccine includes 2 doses with 3 months interval between doses, and subjects only receive 1st vaccination in this study</description>
    <arm_group_label>Group II-EPI vaccine only</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EV71 Vaccine only</intervention_name>
    <description>The investigated EV17 vaccine was manufactured by Sinovac Biotech Co., Ltd.</description>
    <arm_group_label>Group III-EV71 vaccine only</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers aged 6 months&#xD;
&#xD;
          -  Finished two doses of vaccination (0,1 month) of hepatitis B vaccine prior to study&#xD;
             entry&#xD;
&#xD;
          -  Proven legal identity&#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;
        Exclusion Criteria:&#xD;
&#xD;
          -  Finished all the three doses vaccination (0,1,6 month) of hepatitis B vaccine prior to&#xD;
             study entry&#xD;
&#xD;
          -  Prior vaccination of meningococcal polysaccharide vaccine&#xD;
&#xD;
          -  Prior vaccination of EV71 vaccine&#xD;
&#xD;
          -  Unable to receive vaccination on both arms&#xD;
&#xD;
          -  History of hand foot and mouth disease&#xD;
&#xD;
          -  Previously tested HBsAg positive&#xD;
&#xD;
          -  Mother of the subject had been previously tested HBsAg positive&#xD;
&#xD;
          -  History of asthma; history of allergy to any vaccine or vaccine ingredient, or serious&#xD;
             adverse reaction(s) to vaccination, such as urticaria, difficulty in breathing,&#xD;
             angioneurotic edema, abdominal pain, etc&#xD;
&#xD;
          -  Congenital malformation, developmental disorders, genetic defects&#xD;
&#xD;
          -  Autoimmune disease or immunodeficiency/immunosuppressive&#xD;
&#xD;
          -  Severe nervous system disease or mental illness&#xD;
&#xD;
          -  Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency,&#xD;
             coagulation disorder, or platelet abnormalities) , or obvious bruising or coagulation&#xD;
             disorders&#xD;
&#xD;
          -  Any immunosuppressant, cytotoxic medicine, or inhaled corticosteroids (except&#xD;
             corticosteroid spray for treatment of allergic rhinitis or corticosteroid treatment on&#xD;
             surface for acute non-complicated dermatitis) within 6 month prior to study entry&#xD;
&#xD;
          -  Receipt of blood product (e.g., immunoglobulin) within 3 months prior to study entry&#xD;
&#xD;
          -  Receipt of any other investigational medicine(s) within 30 days prior to study entry&#xD;
&#xD;
          -  Receipt of any live attenuated vaccine within 14 days prior to study entry&#xD;
&#xD;
          -  Receipt of any subunit vaccine or inactivated vaccine within 7 days prior to study&#xD;
             entry&#xD;
&#xD;
          -  Acute disease or acute stage of chronic disease within 7 days prior to study entry&#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 judgement of investigators&#xD;
&#xD;
        Exclusion Criteria of the Second Injection:&#xD;
&#xD;
          -  Subjects with one of the following 1 to 3 conditions are forbidden to continue&#xD;
             vaccination, while the other study steps could be carried out based on the judgement&#xD;
             of investigator; for subjects with one of the following 4 to 5 conditions, whether to&#xD;
             continue vaccination are determined by the investigator; for subjects with one of the&#xD;
             following 6 to 7 conditions, vaccination may be delayed in the time window specified&#xD;
             in the study:&#xD;
&#xD;
               1. Any serious adverse event that has a causal relationship with the investigated&#xD;
                  vaccine (except the group II)&#xD;
&#xD;
               2. Severe allergic reactions or hypersensitivity after vaccination (including&#xD;
                  urticaria / rash appear within 30 minutes after vaccination, except the group II&#xD;
                  )&#xD;
&#xD;
               3. Any confirmed or suspected autoimmune disease or immunodeficiency disease (e.g.,&#xD;
                  HIV infection)&#xD;
&#xD;
               4. New chronic diseases or acute stage of chronic diseases&#xD;
&#xD;
               5. 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;
               6. Acute diseases (moderate or severe diseases with or without fever)&#xD;
&#xD;
               7. Axillary temperature&gt; 37.0 ℃&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>6 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Huizhen Zheng</last_name>
    <role>Principal Investigator</role>
    <affiliation>Guangdong Center for Disease Prevention and Control</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dongguan Municipal Center for Disease Control and Prevention</name>
      <address>
        <city>Dongguan</city>
        <state>Guangdong</state>
        <zip>523129</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <last_update_submitted>July 26, 2021</last_update_submitted>
  <last_update_submitted_qc>July 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Inactivated Enterovirus Type 71 (EV71) Vaccine</keyword>
  <keyword>Concomitant vaccination</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</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/NCT03274102
org study id: PRO-EV71-4003
nct id: NCT03274102
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the safety and immunogenicity of concomitant
      administration of EV71 vaccine with recombinant hepatitis B vaccine/Group A meningococcal
      polysaccharide vaccine.
This study is an open-label, single-center, randomized, comparative phase IV clinical trial.
      The purpose of this study is to evaluate the safety and immunogenicity of concomitant
      administration of EV71 vaccine manufactured by Sinovac (Beijing) Vaccine Technology Co., Ltd.
      with recombinant hepatitis B vaccine/Group A meningococcal polysaccharide vaccine. 780
      healthy infants of 6 months old as participants are randomly assigned into three experimental
      groups in the ratio 1:1:1. The group I receive EV71 Vaccine (first dose)& recombinant
      hepatitis B vaccine on day 0 and EV71 vaccine (second dose)& Group A meningococcal
      polysaccharide vaccine on day 30. The group II receive recombinant hepatitis B vaccine on day
      0 and Group A meningococcal polysaccharide vaccine on day 30. The group III receive the first
      and second dose of EV71 Vaccine on day 0 and day 30 respectively.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
masking description: open-labelled
measure: The seropositive rate of EV71 neutralizing antibody, anti-HBs and serum bactericidal antibody 1 month after 2 doses of vaccination
time frame: 30 days after 2 doses of injection
description: Immunogenicity indicator
measure: Incidence of solicited local or systemic adverse events within 7 days after each dose
time frame: 7 days after each dose of injection
description: Safety indicator
measure: Incidence of unsolicited local or systemic adverse events within 30 days after each dose
time frame: 30 days after each dose of injection
description: Safety indicator
measure: Incidence of serious adverse events during the period of safety monitoring
time frame: 60 days after the first dose injection
description: Safety indicator
measure: The seroconversion rate of EV71 neutralizing antibody, anti-HBs and serum bactericidal antibody(SBA) 1 month after 2 doses of vaccination
time frame: 30 days after 2 doses of injection
description: Immunogenicity indicator
measure: EV71 neutralizing antibody GMT, anti-HBs GMC and SBA antibody GMT 1 month after 2 doses of vaccination
time frame: 30 days after 2 doses of injection
description: Immunogenicity indicator
arm group label: Group I-EV71 vaccine and EPI vaccines
arm group type: Experimental
description: Concomitant administration of EV71 vaccine with EPI vaccines: EV71 Vaccine (intramuscular injection,0.5ml,first dose)/recombinant hepatitis B vaccine（intramuscular injection,0.5ml）on day 0 and EV71 Vaccine (injection, 0.5ml,second dose)/ Group A meningococcal polysaccharide vaccine(subcutaneous injection, 150ug) on day 30.
arm group label: Group II-EPI vaccine only
arm group type: Active Comparator
description: Single injection of EPI vaccine: recombinant hepatitis B vaccine (intramuscular injection, 0.5ml) on day 0 and Group A meningococcal polysaccharide vaccine (subcutaneous injection,150ug) on day 30.
arm group label: Group III-EV71 vaccine only
arm group type: Active Comparator
description: EV71 Vaccine only: the first and second dose of EV71 Vaccine (intramuscular injection,0.5ml) on day 0 and day 30 respectively.
intervention type: Biological
intervention name: Concomitant administration of EV71 vaccine with EPI vaccines
description: The investigated EV17 vaccine was manufactured by Sinovac Biotech Co., Ltd.； the recombinant hepatitis B vaccine was manufactured by Shenzhen Kangtai Biological Products Co., Ltd; the Group A meningococcal polysaccharide vaccine was manufactured by Wuhan Institute of Biological Products Co., Ltd.
The primary vaccination schedule of hepatitis B vaccine includes 3 doses with a schedule of 0,1,6 month, and subjects only receive 3rd vaccination in this study; the primary vaccination schedule of Group A meningococcal polysaccharide vaccine includes 2 doses with 3 months interval between doses, and subjects only receive 1st vaccination in this study
arm group label: Group I-EV71 vaccine and EPI vaccines
intervention type: Biological
intervention name: Single injection of EPI vaccine
description: The recombinant hepatitis B vaccine was manufactured by Shenzhen Kangtai Biological Products Co., Ltd; the Group A meningococcal polysaccharide vaccine was manufactured by Wuhan Institute of Biological Products Co., Ltd.
The primary vaccination schedule of hepatitis B vaccine includes 3 doses with a schedule of 0,1,6 month, and subjects only receive 3rd vaccination in this study; the primary vaccination schedule of Group A meningococcal polysaccharide vaccine includes 2 doses with 3 months interval between doses, and subjects only receive 1st vaccination in this study
arm group label: Group II-EPI vaccine only
intervention type: Biological
intervention name: EV71 Vaccine only
description: The investigated EV17 vaccine was manufactured by Sinovac Biotech Co., Ltd.
arm group label: Group III-EV71 vaccine only
criteria: 
gender: All
minimum age: 6 Months
maximum age: 6 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Huizhen Zheng
role: Principal Investigator
affiliation: Guangdong Center for Disease Prevention and Control
facility: 
country: China
responsible party type: Sponsor
mesh term: Foot-and-Mouth Disease
mesh term: Hand, Foot and Mouth Disease
mesh term: Mouth Diseases
mesh term: Vaccines