<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/NCT03268083</url>
  </required_header>
  <id_info>
    <org_study_id>EV-BR1501</org_study_id>
    <nct_id>NCT03268083</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Immunogenicity and Safety of EV71 Vaccine in Pediatric Subjects</brief_title>
  <official_title>An Open-Label, Dose-Finding, Phase II Study to Evaluate the Immunogenicity and Safety of the Bioreactor-generated EV71 Vaccine in Pediatric Subjects Aged 3 to 6 Years and 2 to 35 Months Old</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Enimmune Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Enimmune Corporation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objectives of this study are to evaluate the immune response and safety profiles of two&#xD;
      injections of EV71 vaccine administrated with or without adjuvant Al(OH)3 at 0.5-μg and 1-μg&#xD;
      dose in children aged 3 to 6 years old and 2 to 35 months old infants/toddlers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2016</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">August 2017</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Serum neutralizing antibody titers (NT) induced by the EV71 vaccine</measure>
    <time_frame>Day 56</time_frame>
    <description>Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 56</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Seroconversion rate (SCR) based on neutralizing antibody titers</measure>
    <time_frame>Day 56</time_frame>
    <description>Evaluate the immunogenicity change of SCR from baseline on Day 56</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum neutralizing antibody titers (NT) induced by the EV71 vaccine</measure>
    <time_frame>Day 28</time_frame>
    <description>Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 28</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum neutralizing antibody titers (NT) induced by the EV71 vaccine</measure>
    <time_frame>Day 196</time_frame>
    <description>Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 196</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Seroconversion rate (SCR) based on neutralizing antibody titers</measure>
    <time_frame>Day 28</time_frame>
    <description>Evaluate the immunogenicity change of SCR from baseline on Day 28</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Seroconversion rate (SCR) based on neutralizing antibody titers</measure>
    <time_frame>Day 196</time_frame>
    <description>Evaluate the immunogenicity change of SCR from baseline on Day 196</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Solicited adverse events</measure>
    <time_frame>7 days after each vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unsolicited adverse events</measure>
    <time_frame>28 days after each vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The occurrence of overall adverse events (AEs) and serious adverse event (SAEs)</measure>
    <time_frame>Day 0 to Day 196</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The occurrence of EV 71 breakthrough infection after Visit 3</measure>
    <time_frame>Day 57 to Day 364</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum neutralizing antibody titers (NT) induced by the EV71 vaccine</measure>
    <time_frame>Day 364</time_frame>
    <description>Evaluate the immunogenicity of serum neutralization antibody titer induced by the EV 71 vaccine on Day 364</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">140</enrollment>
  <condition>Enterovirus Infections</condition>
  <arm_group>
    <arm_group_label>Group A1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 to 6 years</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group A2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 to 6 years</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group A3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 to 6 years</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 to 35 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 to 35 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 to 35 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AI(OH)3] per dose)</intervention_name>
    <description>Two vaccinations at 28 days apart</description>
    <arm_group_label>Group A1</arm_group_label>
    <arm_group_label>Group B1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EV71 vaccine ([1 μg total protein + adjuvant 150 μg AI(OH)3] per dose)</intervention_name>
    <description>Two vaccinations at 28 days apart</description>
    <arm_group_label>Group A2</arm_group_label>
    <arm_group_label>Group B2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EV71 vaccine ([1 μg total protein ] per dose)</intervention_name>
    <description>Two vaccinations at 28 days apart</description>
    <arm_group_label>Group A3</arm_group_label>
    <arm_group_label>Group B3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy children aged from 3 to 6 years old (i.e. ≥ 3 years old and &lt; 7 years old) for&#xD;
             Part A,and from 2 to 35 months old (i.e. ≥ 2 months old and &lt; 36 months old) for Part&#xD;
             B at the time of first vaccination.&#xD;
&#xD;
          2. Subject's guardians are able and willing to comply with study procedures and provide&#xD;
             the signed informed consent.&#xD;
&#xD;
          3. Subject is able and can comply with the requirements of the protocol.&#xD;
&#xD;
          4. Subject with body temperature ≤38°C.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject with previous known exposure to Enterovirus 71 (EV71).&#xD;
&#xD;
          2. Subject with a history of herpangina, hand-foot-mouth disease,and acute hemorrhagic&#xD;
             conjunctivitis associated with enterovirus infection in the past 3 months.&#xD;
&#xD;
          3. Subject with gestation &lt; 37 weeks.&#xD;
&#xD;
          4. Subject with birth weight &lt;2.5 kg.&#xD;
&#xD;
          5. Subject with a history of hypersensitivity to vaccines, or a history of allergic&#xD;
             disease or reactions likely to be exacerbated by any component of the vaccine.&#xD;
&#xD;
          6. Family history of seizures or progressive neurological disease.&#xD;
&#xD;
          7. Family history of congenital or hereditary immunodeficiency.&#xD;
&#xD;
          8. Severe malnutrition or dysgenopathy.&#xD;
&#xD;
          9. Major congenital defects or serious chronic illness, including perinatal brain damage.&#xD;
&#xD;
         10. Subject diagnosed of having autoimmune disease (e.g., celiac disease, type I diabetes,&#xD;
             lupus (SLE), juvenile dermatomyositis, scleroderma, juvenile idiopathic arthritis&#xD;
             (JIA), immune (or idiopathic) thrombocytopenia purpura).&#xD;
&#xD;
         11. Bleeding disorder diagnosed by a doctor or significant bruising or hemostatic&#xD;
             difficulties with IM injections or blood draws.&#xD;
&#xD;
         12. Any acute infections 7 days prior to administrating the first vaccination.&#xD;
&#xD;
         13. Use of any investigational product (including drug, vaccine) within 30 days prior to&#xD;
             vaccination or planned use during the study period.&#xD;
&#xD;
         14. Administration of any vaccines within 14 days prior to randomization.&#xD;
&#xD;
         15. Use of immunoglobulins or any blood products within 3 months prior to vaccination or&#xD;
             planned use during the study period.&#xD;
&#xD;
         16. Chronic administration (defined as &gt; 14 days) of immunosuppressants or other&#xD;
             immunomodulators or systemic corticosteroids within 6 months prior to vaccination or&#xD;
             planned use during the study period.&#xD;
&#xD;
         17. Subjects who had ever received investigational EV-71 vaccine prior to randomization.&#xD;
&#xD;
         18. Under anti-tuberculosis prevention or therapy.&#xD;
&#xD;
         19. 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>2 Months</minimum_age>
    <maximum_age>6 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linkou Chang Gung Memorial Hospital</name>
      <address>
        <city>Taoyuan</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 4, 2016</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>October 18, 2021</last_update_submitted>
  <last_update_submitted_qc>October 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Foot-and-Mouth Disease</keyword>
  <keyword>Vaccines</keyword>
  <keyword>Hand, Foot and Mouth Disease</keyword>
  <keyword>EV71 vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enterovirus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</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/NCT03268083
org study id: EV-BR1501
nct id: NCT03268083
lead sponsor: 
has dmc: Yes
The objectives of this study are to evaluate the immune response and safety profiles of two
      injections of EV71 vaccine administrated with or without adjuvant Al(OH)3 at 0.5-μg and 1-μg
      dose in children aged 3 to 6 years old and 2 to 35 months old infants/toddlers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Serum neutralizing antibody titers (NT) induced by the EV71 vaccine
time frame: Day 56
description: Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 56
measure: Seroconversion rate (SCR) based on neutralizing antibody titers
time frame: Day 56
description: Evaluate the immunogenicity change of SCR from baseline on Day 56
measure: Serum neutralizing antibody titers (NT) induced by the EV71 vaccine
time frame: Day 28
description: Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 28
measure: Serum neutralizing antibody titers (NT) induced by the EV71 vaccine
time frame: Day 196
description: Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 196
measure: Seroconversion rate (SCR) based on neutralizing antibody titers
time frame: Day 28
description: Evaluate the immunogenicity change of SCR from baseline on Day 28
measure: Seroconversion rate (SCR) based on neutralizing antibody titers
time frame: Day 196
description: Evaluate the immunogenicity change of SCR from baseline on Day 196
measure: Solicited adverse events
time frame: 7 days after each vaccination
measure: Unsolicited adverse events
time frame: 28 days after each vaccination
measure: The occurrence of overall adverse events (AEs) and serious adverse event (SAEs)
time frame: Day 0 to Day 196
measure: The occurrence of EV 71 breakthrough infection after Visit 3
time frame: Day 57 to Day 364
measure: Serum neutralizing antibody titers (NT) induced by the EV71 vaccine
time frame: Day 364
description: Evaluate the immunogenicity of serum neutralization antibody titer induced by the EV 71 vaccine on Day 364
arm group label: Group A1
arm group type: Experimental
description: 3 to 6 years
arm group label: Group A2
arm group type: Experimental
description: 3 to 6 years
arm group label: Group A3
arm group type: Experimental
description: 3 to 6 years
arm group label: Group B1
arm group type: Experimental
description: 2 to 35 months
arm group label: Group B2
arm group type: Experimental
description: 2 to 35 months
arm group label: Group B3
arm group type: Experimental
description: 2 to 35 months
intervention type: Biological
intervention name: EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AI(OH)3] per dose)
description: Two vaccinations at 28 days apart
arm group label: Group A1
arm group label: Group B1
intervention type: Biological
intervention name: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AI(OH)3] per dose)
description: Two vaccinations at 28 days apart
arm group label: Group A2
arm group label: Group B2
intervention type: Biological
intervention name: EV71 vaccine ([1 μg total protein ] per dose)
description: Two vaccinations at 28 days apart
arm group label: Group A3
arm group label: Group B3
criteria: 
gender: All
minimum age: 2 Months
maximum age: 6 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Enterovirus Infections
mesh term: Vaccines
sharing ipd: No