<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/NCT03240744</url>
  </required_header>
  <id_info>
    <org_study_id>2017-003-02</org_study_id>
    <nct_id>NCT03240744</nct_id>
  </id_info>
  <brief_title>The Phase IVc of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell)</brief_title>
  <official_title>Study on Immunogenicity of Inactivated Enterovirus 71 (EV71) Vaccine (Human Diploid Cell, KMB-17) in Large-scale Healthy Children in China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hubei Provincial Center for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Enterovirus 71 (EV71), a major pathogen causing hand-foot-and-mouth disease (HFMD) worldwide,&#xD;
      is a member of the Human Enterovirus species A, family Picornaviridae. Its infection&#xD;
      occasionally leads to severe diseases and death, with central nervous system (CNS) damage.&#xD;
&#xD;
      Recently, except of inactivated vaccine, several EV71 vaccine candidates have been evaluated&#xD;
      in animals but no final results of clinical trials, such as attenuated vaccine, subunit&#xD;
      vaccine. A formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been&#xD;
      finished phase I, II and III clinical trials and licensed by SFDA in China at Dec. 3, 2015.&#xD;
      Based on the results of clinical trials, the protective efficacy of inactivated EV71 vaccine&#xD;
      is 97% against HFMD caused by EV71. The phase IV clinical trial has been carried out from&#xD;
      July 2016. The purpose of phase IVc is to evaluated the immunogenicity of the inactive EV71&#xD;
      vaccine in large scale population of Chinese children (from 6 to 71 months old) in Hubei&#xD;
      Province, China.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are two parts of phase IVc clinical trials have been performed. First, to evaluate the&#xD;
      immunogenicity of the inactive EV71 vaccine in large scale population of Chinese children&#xD;
      (from 6 to 71 months old), within 56-day-post-immunized.&#xD;
&#xD;
      Second, to long-term immunogenicity of the inactive EV71 vaccine in large scale population of&#xD;
      Chinese children (from 6 to 71 months old).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">June 22, 2017</start_date>
  <completion_date type="Anticipated">October 2020</completion_date>
  <primary_completion_date type="Anticipated">October 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Inactivated EV71 vaccine (KMB-17 cells)</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluate the seroconversion rate of anti-EV71 antibodies in serum of children</measure>
    <time_frame>at 28 days after finishing 2 doses immunization</time_frame>
    <description>Bloods were obtained at 0 and 56 days after first vaccination. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluate the antibody titers of anti-EV71 antibodies in serum of children</measure>
    <time_frame>at 28 days after finishing 2 doses immunization</time_frame>
    <description>Bloods were obtained at 0 and 56 days after first vaccination. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate long-term of the seroconversion rate of anti-EV71 antibodies in serum of children</measure>
    <time_frame>Up to 3 years after finishing 2 doses immunization</time_frame>
    <description>Bloods were obtained at 0, 28 and 56 days after first vaccination, and 180, 360 and 720 days after 2 doses immunization. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate long-term of the antibody titers of anti-EV71 antibodies in serum of children</measure>
    <time_frame>Up to 3 years after finishing 2 doses immunization</time_frame>
    <description>Bloods were obtained at 0, 28 and 56 days after first vaccination, and 180, 360 and 720 days after 2 doses immunization. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of treatment adverse events</measure>
    <time_frame>Up to 3 years after finishing 2 doses immunization</time_frame>
    <description>The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-1 days post immunization (d.p.i.), within 1-3 d.p.i. and within 3-7 d.p.i. after the 1st injection, as well as after the 2nd injection. And the adverse events were also observed and recorded following within 3 years after finishing 2 doses immunization.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">800</enrollment>
  <condition>Hand, Foot and Mouth Disease (HFMD)</condition>
  <arm_group>
    <arm_group_label>vaccine (3.0EU)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>healthy children (6-71 months old) have been injected by inactivated EV71 vaccine (KMB-17) of 3.0 EU (neutralization antibodies titer unit; 100 U in phase III clinical trials, or 320 EU (Elisa assay unit) in phase I and II clinical trials)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Inactivated EV71 vaccine (human diploid cell, KMB-17)</intervention_name>
    <description>3.0 EU of inactivated enterovirus 71 vaccine (KMB-17) on day 0, 28.</description>
    <arm_group_label>vaccine (3.0EU)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy subjects (6-71 months old children) as established by medical history and&#xD;
             clinical examination&#xD;
&#xD;
          -  The subjects' legal guardian must be aware of this vaccines&#xD;
&#xD;
          -  The subjects' legal guardian voluntarily participate in the study and signed Informed&#xD;
             Consent Form&#xD;
&#xD;
          -  Subjects with temperature ≤ 37.0 ℃&#xD;
&#xD;
          -  The subjects' legal guardian with the ability and objective to comply with the&#xD;
             requirements of the protocol&#xD;
&#xD;
          -  Persist for a 14-month visit (and receive blood, stool (or specimens by means of a&#xD;
             swab) tests according to program requirements in immunogenicity observation group)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy or serious side-effects to a vaccine or any ingredient of vaccine&#xD;
&#xD;
          -  Epilepsy, seizures, convulsions, neurological illness&#xD;
&#xD;
          -  Congenital or hereditary immunodeficiency&#xD;
&#xD;
          -  Autoimmune disease&#xD;
&#xD;
          -  Asthma, thyroidectomy, angioneurotic edema, diabetes or cancer&#xD;
&#xD;
          -  Asplenia, functional asplenia, and any circumstances leading to the asplenia or&#xD;
             splenectomy&#xD;
&#xD;
          -  Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation&#xD;
             disorders, platelet abnormalities), significant bruising or blood clotting disorder&#xD;
&#xD;
          -  Acute illness or acute exacerbation of chronic disease in last 7 days&#xD;
&#xD;
          -  Any prior administration of immunodepressant or corticosteroids in last 6 months&#xD;
&#xD;
          -  Any prior administration of blood products in last 3 months&#xD;
&#xD;
          -  Any prior administration of live-attenuated vaccine in last 15 days&#xD;
&#xD;
          -  Any prior administration of subunit or inactivated vaccines in last 7 days&#xD;
&#xD;
          -  Fever before vaccination, axillary temperature ﹥37.0 ℃&#xD;
&#xD;
          -  The laboratory test abnormalities before vaccination, including blood tests&#xD;
             (hemoglobin, total white blood cells, WBC, platelets), blood biochemistry tests (ALT,&#xD;
             total bilirubin, direct bilirubin, Cr, BUN) and urine tests (urine protein, urine&#xD;
             sugar, blood cells), etc.&#xD;
&#xD;
          -  Hypertension or hypotension. Systolic blood pressure ﹥140 mmHg and/ or diastolic blood&#xD;
             pressure ﹥90 mmHg; systolic blood pressure ﹤90 mmHg and/or diastolic blood pressure&#xD;
             ﹤60 mmHg&#xD;
&#xD;
          -  Any condition that in the opinion of the investigator, may interfere with the&#xD;
             evaluation of study objectives&#xD;
&#xD;
          -  take part into other vaccine or drug clinical trials in last half year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>71 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xuhua Guan, M.S.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hubei Province Center for Diseases Control and Prevention</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hubei Province Center for Diseases Control and Prevention</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>June 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>September 1, 2017</last_update_submitted>
  <last_update_submitted_qc>September 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Qihan Li</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>immunogenicity</keyword>
  <keyword>safety</keyword>
  <keyword>Hand, Foot and Mouth Disease (HFMD)</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/NCT03240744
org study id: 2017-003-02
nct id: NCT03240744
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Enterovirus 71 (EV71), a major pathogen causing hand-foot-and-mouth disease (HFMD) worldwide,
      is a member of the Human Enterovirus species A, family Picornaviridae. Its infection
      occasionally leads to severe diseases and death, with central nervous system (CNS) damage.

      Recently, except of inactivated vaccine, several EV71 vaccine candidates have been evaluated
      in animals but no final results of clinical trials, such as attenuated vaccine, subunit
      vaccine. A formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been
      finished phase I, II and III clinical trials and licensed by SFDA in China at Dec. 3, 2015.
      Based on the results of clinical trials, the protective efficacy of inactivated EV71 vaccine
      is 97% against HFMD caused by EV71. The phase IV clinical trial has been carried out from
      July 2016. The purpose of phase IVc is to evaluated the immunogenicity of the inactive EV71
      vaccine in large scale population of Chinese children (from 6 to 71 months old) in Hubei
      Province, China.
There are two parts of phase IVc clinical trials have been performed. First, to evaluate the
      immunogenicity of the inactive EV71 vaccine in large scale population of Chinese children
      (from 6 to 71 months old), within 56-day-post-immunized.

      Second, to long-term immunogenicity of the inactive EV71 vaccine in large scale population of
      Chinese children (from 6 to 71 months old).
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Inactivated EV71 vaccine (KMB-17 cells)
primary purpose: Prevention
masking: None (Open Label)
measure: Evaluate the seroconversion rate of anti-EV71 antibodies in serum of children
time frame: at 28 days after finishing 2 doses immunization
description: Bloods were obtained at 0 and 56 days after first vaccination. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.
measure: Evaluate the antibody titers of anti-EV71 antibodies in serum of children
time frame: at 28 days after finishing 2 doses immunization
description: Bloods were obtained at 0 and 56 days after first vaccination. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.
measure: Evaluate long-term of the seroconversion rate of anti-EV71 antibodies in serum of children
time frame: Up to 3 years after finishing 2 doses immunization
description: Bloods were obtained at 0, 28 and 56 days after first vaccination, and 180, 360 and 720 days after 2 doses immunization. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.
measure: Evaluate long-term of the antibody titers of anti-EV71 antibodies in serum of children
time frame: Up to 3 years after finishing 2 doses immunization
description: Bloods were obtained at 0, 28 and 56 days after first vaccination, and 180, 360 and 720 days after 2 doses immunization. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.
measure: Incidence of treatment adverse events
time frame: Up to 3 years after finishing 2 doses immunization
description: The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-1 days post immunization (d.p.i.), within 1-3 d.p.i. and within 3-7 d.p.i. after the 1st injection, as well as after the 2nd injection. And the adverse events were also observed and recorded following within 3 years after finishing 2 doses immunization.
arm group label: vaccine (3.0EU)
arm group type: Experimental
description: healthy children (6-71 months old) have been injected by inactivated EV71 vaccine (KMB-17) of 3.0 EU (neutralization antibodies titer unit; 100 U in phase III clinical trials, or 320 EU (Elisa assay unit) in phase I and II clinical trials)
intervention type: Biological
intervention name: Inactivated EV71 vaccine (human diploid cell, KMB-17)
description: 3.0 EU of inactivated enterovirus 71 vaccine (KMB-17) on day 0, 28.
arm group label: vaccine (3.0EU)
criteria: 
gender: All
minimum age: 6 Months
maximum age: 71 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Xuhua Guan, M.S.
role: Principal Investigator
affiliation: Hubei Province Center for Diseases Control and Prevention
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
investigator full name: Qihan Li
investigator title: Professor
mesh term: Foot-and-Mouth Disease
mesh term: Hand, Foot and Mouth Disease
mesh term: Mouth Diseases