<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/NCT02999828</url>
  </required_header>
  <id_info>
    <org_study_id>CY2016KMEV</org_study_id>
    <nct_id>NCT02999828</nct_id>
  </id_info>
  <brief_title>The Phase IVa of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell, KMB-17)</brief_title>
  <official_title>The Safety, Immune Persistence and Consistency of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell, KMB-17)</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>Beijing Chaoyang District Centre for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Neimenggu Province Centre 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>
    <has_dmc>Yes</has_dmc>
  </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.&#xD;
&#xD;
      A formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been finished phase&#xD;
      I, II and III clinical trials and licensed by SFDA in China at Dec. 3, 2015. Based on the&#xD;
      results of clinical trials, the protective efficacy of inactivated EV71 vaccine is 97%&#xD;
      against HFMD caused by EV71. The phase IV clinical trial has been carried out from July 2016.&#xD;
      The purpose of phase IV is to evaluated the safety and efficacy of the inactive EV71 vaccine&#xD;
      in large scale population of Chinese children (from 6 to 71 months old).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <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.&#xD;
&#xD;
      A formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been finished phase&#xD;
      I, II and III clinical trials and licensed by SFDA in China at Dec. 3, 2015. Based on the&#xD;
      results of clinical trials, the protective efficacy of inactivated EV71 vaccine is 97%&#xD;
      against HFMD caused by EV71. The phase IV clinical trial has been carried out from July 2016.&#xD;
      The purpose of phase IV is to evaluated the safety and efficacy of the inactive EV71 vaccine&#xD;
      in large scale population of Chinese children (from 6 to 71 months old).&#xD;
&#xD;
      There are three parts of phase IV clinical trials have been performed. First, to evaluate the&#xD;
      safety of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to&#xD;
      71 months old).&#xD;
&#xD;
      Second, to evaluate the immune persistence of the inactive EV71 vaccine in large scale&#xD;
      population of Chinese children (from 6 to 71 months old).&#xD;
&#xD;
      Third, to evaluate the efficacy 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">September 2016</start_date>
  <completion_date type="Anticipated">February 2019</completion_date>
  <primary_completion_date type="Anticipated">February 2019</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of treatment adverse events</measure>
    <time_frame>Up to 24 months after finishing 2 doses immunization</time_frame>
    <description>The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-7 days post immunization (d.p.i.) and within 8-28 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 24 months after finishing 2 doses immunization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The incidence rates of HFMD</measure>
    <time_frame>Up to 24 months after finishing 2 doses immunization</time_frame>
    <description>All hand, foot and mouth disease (HFMD) cases from the subjects were observed and recorded, including common cases, severe cases, dead cases, the cases caused by enterovirus 71, the severe cases caused by enterovirus 71, the dead cases caused by enterovirus 71. The incidence rates of the subjects from this clinical trial were calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>immune response of inactivated EV71 vaccine (KMB-17) in a large crowd</measure>
    <time_frame>Up to 24 months after finishing 2 doses immunization</time_frame>
    <description>The blood specimens were obtained at 0, 28, 56, 180, 360 and 720 days post the 1st immunization (p.i.). The levels of neutralization antibodies and cytokines were tested at each time point. The seroconversion rate of anti-EV71 antibodies was evaluated in serum of children. And the specific IFN-γ in subjects were tested and evaluated at 0, 180 and 360 d.p.i..</description>
  </secondary_outcome>
  <other_outcome>
    <measure>The level of anti-EV71 antibodies was evaluated in serum of children</measure>
    <time_frame>Up to 24 months after finishing 2 doses immunization</time_frame>
    <description>The blood specimens were obtained at 0, 28, 56, 180, 360 and 720 days post the 1st immunization (p.i.). The levels of neutralization antibodies were tested at each time point. The level of anti-EV71 antibodies was evaluated in serum of children.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20770</enrollment>
  <condition>Safety of Inactivated EV71 Vaccine</condition>
  <condition>Immunization of Inactivated EV71 Vaccine</condition>
  <arm_group>
    <arm_group_label>3.0 EU in Children</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 (KMB-17)</intervention_name>
    <description>3.0EU of inactivated enterovirus 71 vaccine (KMB-17) on day 0, 28.</description>
    <arm_group_label>3.0 EU in Children</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 24-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;
          -  report the HFMD cases&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD)&#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;
          -  Severe malnutrition or dysgenopathy&#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 ﹥90mmHg; systolic blood pressure ﹤90 mmHg and/or diastolic blood pressure ﹤60&#xD;
             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>Nianmin Shi, M.S.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chaoyang Provincial Center for Diseases Control and Prevention in Beijing</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shaohong Yan, M.S.</last_name>
    <role>Study Chair</role>
    <affiliation>Neimenggu Provincial Center for Diseases Control and Prevention</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chaoyang of Provincial Center for Diseases Control and Prevention in Beijing</name>
      <address>
        <city>Beijing</city>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>September 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 18, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>January 18, 2018</last_update_submitted>
  <last_update_submitted_qc>January 18, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2018</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>safety</keyword>
  <keyword>immune persistence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enterovirus Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Participants do not agree to share individual data.</ipd_description>
  </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/NCT02999828
org study id: CY2016KMEV
nct id: NCT02999828
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
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 IV is to evaluated the safety and efficacy of the inactive EV71 vaccine
      in large scale population of Chinese children (from 6 to 71 months old).
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 IV is to evaluated the safety and efficacy of the inactive EV71 vaccine
      in large scale population of Chinese children (from 6 to 71 months old).

      There are three parts of phase IV clinical trials have been performed. First, to evaluate the
      safety of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to
      71 months old).

      Second, to evaluate the immune persistence of the inactive EV71 vaccine in large scale
      population of Chinese children (from 6 to 71 months old).

      Third, to evaluate the efficacy 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
primary purpose: Prevention
masking: None (Open Label)
measure: Incidence of treatment adverse events
time frame: Up to 24 months after finishing 2 doses immunization
description: The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-7 days post immunization (d.p.i.) and within 8-28 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 24 months after finishing 2 doses immunization.
measure: The incidence rates of HFMD
time frame: Up to 24 months after finishing 2 doses immunization
description: All hand, foot and mouth disease (HFMD) cases from the subjects were observed and recorded, including common cases, severe cases, dead cases, the cases caused by enterovirus 71, the severe cases caused by enterovirus 71, the dead cases caused by enterovirus 71. The incidence rates of the subjects from this clinical trial were calculated.
measure: immune response of inactivated EV71 vaccine (KMB-17) in a large crowd
time frame: Up to 24 months after finishing 2 doses immunization
description: The blood specimens were obtained at 0, 28, 56, 180, 360 and 720 days post the 1st immunization (p.i.). The levels of neutralization antibodies and cytokines were tested at each time point. The seroconversion rate of anti-EV71 antibodies was evaluated in serum of children. And the specific IFN-γ in subjects were tested and evaluated at 0, 180 and 360 d.p.i..
measure: The level of anti-EV71 antibodies was evaluated in serum of children
time frame: Up to 24 months after finishing 2 doses immunization
description: The blood specimens were obtained at 0, 28, 56, 180, 360 and 720 days post the 1st immunization (p.i.). The levels of neutralization antibodies were tested at each time point. The level of anti-EV71 antibodies was evaluated in serum of children.
arm group label: 3.0 EU in Children
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 (KMB-17)
description: 3.0EU of inactivated enterovirus 71 vaccine (KMB-17) on day 0, 28.
arm group label: 3.0 EU in Children
criteria: 
gender: All
minimum age: 6 Months
maximum age: 71 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Nianmin Shi, M.S.
role: Principal Investigator
affiliation: Chaoyang Provincial Center for Diseases Control and Prevention in Beijing
last name: Shaohong Yan, M.S.
role: Study Chair
affiliation: Neimenggu Provincial 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: Enterovirus Infections
sharing ipd: No
ipd description: Participants do not agree to share individual data.