<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/NCT01676675</url>
  </required_header>
  <id_info>
    <org_study_id>JSVCT011</org_study_id>
    <nct_id>NCT01676675</nct_id>
  </id_info>
  <brief_title>A Phase I Clinical Trial With Whole Virus Inactivated Influenza H5N1 Vaccine in Healthy Adolescents and Adults</brief_title>
  <official_title>A Single Center, Randomized, Double-blind, Placebo-controlled, Dose-escalation Phase I Clinical Trial for Safety and Preliminary Immunogenicity of a Whole Virus Inactivated Influenza H5N1 Vaccine in Healthy Adolescents and Adults, on Day 0 and 21 Intramuscularly</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu Province Centers for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Wuhan Institute of Biological Products 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>
      Influenza is an acute respiratory infection caused by influenza virus with high incidence and&#xD;
      serious complications even causing death. According to the announcement released by the World&#xD;
      Health Organization (WHO), the number of global annual influenza case was 0.6 to 1.2 billion&#xD;
      and 0.5 to 1 million people died. The emergence of a new subtype of influenza virus may cause&#xD;
      an influenza pandemic with occurence once every 10 to 50 years which cause serious adverse&#xD;
      consequences for human health and social welfare worldwide.&#xD;
&#xD;
      From 1997 to 2003，the H5N1 virus infection has increased highly and gradually spreaded to&#xD;
      Europe, Africa and other countries and regions. High mortality caused by H5N1 virus has&#xD;
      attracted the WHO and national government great attention. So it is meaningful to develop&#xD;
      vaccine to provide effective antibody to reduce the number of infections.&#xD;
&#xD;
      The objective of this study is to evaluate the safety and preliminary immunogenicity of a&#xD;
      whole virus inactivated influenza H5N1 vaccine.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">March 2013</completion_date>
  <primary_completion_date type="Anticipated">January 2013</primary_completion_date>
  <phase>Phase 1</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>the safety of whole virus inactivated influenza H5N1 vaccine in healthy adolescents aged from 12-17 years and adults aged from 18-60 years</measure>
    <time_frame>21 days after the first dose</time_frame>
    <description>Frequency of systemic and local adverse reactions within 21 days after the first doses of whole virus inactivated influenza H5N1 vaccine in healthy adolescents aged from 12-17 years and adults aged from 18-60 years</description>
  </primary_outcome>
  <primary_outcome>
    <measure>the safety of whole virus inactivated influenza H5N1 vaccine in healthy adolescents aged from 12-17 years and adults aged from 18-60 years</measure>
    <time_frame>21 days after the second dose</time_frame>
    <description>Frequency of systemic and local adverse reactions within 21 days after the second doses of whole virus inactivated influenza H5N1 vaccine in healthy adolescents aged from 12-17 years and adults aged from 18-60 years</description>
  </primary_outcome>
  <primary_outcome>
    <measure>the immunogenicity of the vaccine after first dose</measure>
    <time_frame>on day 21±3 days</time_frame>
    <description>the seroconversion rate and GMFI of antibodies on day 21 after first dose with different formulation vaccines in healthy adolescents aged from 12-17 years and adults aged from 18-60 years</description>
  </primary_outcome>
  <primary_outcome>
    <measure>the immunogenicity of the vaccine after second dose</measure>
    <time_frame>on day 42±7 days</time_frame>
    <description>the seroconversion rate and GMFI of antibodies on day 21 after second dose with different formulation vaccines in healthy adolescents aged from 12-17 years and adults aged from 18-60 years</description>
  </primary_outcome>
  <primary_outcome>
    <measure>the immunogenicity of the vaccine after whole immunization</measure>
    <time_frame>3 months after second dose (±14 days)</time_frame>
    <description>the seroconversion rate and GMFI of antibodies 3 months after the second dose with different formulation vaccines in healthy adolescents aged from 12-17 years and adults aged from 18-60 years</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>abnormal change of hematological examination and the function of liver and kidney after first dose</measure>
    <time_frame>3 days after first dose</time_frame>
    <description>abnormal change of hematological examination and the function of liver and kidney 3 days after first dose with different formulation vaccines in healthy adolescents aged from 12-17 years and adults aged from 18-60 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>abnormal change of hematological examination and the function of liver and kidney after second dose</measure>
    <time_frame>3 days after second dose</time_frame>
    <description>abnormal change of hematological examination and the function of liver and kidney 3 days after second dose with different formulation vaccines in healthy adolescents aged from 12-17 years and adults aged from 18-60 years</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>7.5μg/0.5ml in subjects(12-17 years old)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>whole virus inactivated influenza H5N1 vaccine of 7.5μg /0.5ml in 30 adolescents aged 12-17 years old on day 0, 21</description>
  </arm_group>
  <arm_group>
    <arm_group_label>15μg/0.5ml in subjects(12-17 years old)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>whole virus inactivated influenza H5N1 vaccine of 15.0μg /0.5ml in 30 adolescents aged 12-17 years old on day0,21</description>
  </arm_group>
  <arm_group>
    <arm_group_label>30μg/0.5ml in subjects(12-17 years old)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>whole virus inactivated influenza H5N1 vaccine of 30.0μg /0.5ml in 30 adolescents aged 12-17 years old on day0,21</description>
  </arm_group>
  <arm_group>
    <arm_group_label>7.5μg/0.5ml in subjects(18-60 years old)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>whole virus inactivated influenza H5N1 vaccine of 7.5μg /0.5ml in 30 adults aged 18-60 years old on day 0, 21</description>
  </arm_group>
  <arm_group>
    <arm_group_label>15μg/0.5ml in subjects(18-60 years old)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>whole virus inactivated influenza H5N1 vaccine of 15.0μg /0.5ml in 30 adults aged 18-60 years old on day 0, 21</description>
  </arm_group>
  <arm_group>
    <arm_group_label>30μg/0.5ml in subjects(18-60 years old)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>whole virus inactivated influenza H5N1 vaccine of 30.0μg /0.5ml in 30 adults aged 18-60 years old on day 0, 21</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0/0.5ml in adolescents (12-17 years old)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0/0.5ml placebo in 30 adolescents aged 12-17 years old on day 0, 21</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0/0.5ml in adults(18-60 years old)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0/0.5ml placebo in 30 adults aged 18-60 years old on day 0, 21</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>7.5μg /0.5ml</intervention_name>
    <description>whole virus inactivated influenza H5N1 vaccine of 7.5μg /0.5ml, two doses, 21 days interval</description>
    <arm_group_label>7.5μg/0.5ml in subjects(12-17 years old)</arm_group_label>
    <arm_group_label>7.5μg/0.5ml in subjects(18-60 years old)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>15.0μg /0.5ml</intervention_name>
    <description>whole virus inactivated influenza H5N1 vaccine of 15.0μg /0.5ml, two doses, 21 days interval</description>
    <arm_group_label>15μg/0.5ml in subjects(12-17 years old)</arm_group_label>
    <arm_group_label>15μg/0.5ml in subjects(18-60 years old)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>30.0μg /0.5ml</intervention_name>
    <description>whole virus inactivated influenza H5N1 vaccine of 30.0μg /0.5ml, two doses, 21 days interval</description>
    <arm_group_label>30μg/0.5ml in subjects(12-17 years old)</arm_group_label>
    <arm_group_label>30μg/0.5ml in subjects(18-60 years old)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>0/0.5ml placebo</intervention_name>
    <description>0/0.5ml placebo, two doses, 21 days interval</description>
    <arm_group_label>0/0.5ml in adolescents (12-17 years old)</arm_group_label>
    <arm_group_label>0/0.5ml in adults(18-60 years old)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy subjects aged from 12 to 60 years old of normal intelligence;&#xD;
&#xD;
          -  The subjects' guardians are able to understand and sign the informed consent;&#xD;
&#xD;
          -  Subjects established as healthy after medical history questioning, physical&#xD;
             examination and clinical decision;&#xD;
&#xD;
          -  Subjects who can comply with the requirements of the clinical trial protocol;&#xD;
&#xD;
          -  Subjects who have never received influenza H5N1 vaccine and other preventive products;&#xD;
&#xD;
          -  Subjects with temperature ≤37°C on axillary setting.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Exclusion Criteria for the first dose:&#xD;
&#xD;
          -  Women in pregnancy / lactation or plan to be pregnant during the study;&#xD;
&#xD;
          -  The subject has a history of allergy or is allergic with any Ingredient of vaccine,&#xD;
             such as egg, ovalbumin;&#xD;
&#xD;
          -  Had serious adverse reactions in previous vaccination, such as allergies, hives,&#xD;
             difficult breath, angioneurotic edema or abdominal pain;&#xD;
&#xD;
          -  Autoimmune diseases or immune deficiency;&#xD;
&#xD;
          -  Had asthma, over the past two years, the condition is unstable in need of emergency&#xD;
             treatment, hospitalization and oral or intravenous corticosteroids;&#xD;
&#xD;
          -  Diabete (type I or type II) not including gestational diabete;&#xD;
&#xD;
          -  Thyroidectomy history, or treatment because of thyroid diseases in the past 12 months;&#xD;
&#xD;
          -  Over the past 3 years, severe angioneurotic edema, or need treatment in the past 2&#xD;
             years;&#xD;
&#xD;
          -  Severe hypertension and blood pressure is still more than 150/100 mmHg after drug&#xD;
             maintenance therapy;&#xD;
&#xD;
          -  coagulation abnormalities diagnosed by doctor (such as lack of coagulation factors,&#xD;
             coagulation disorder diseases, platelet abnormality) or coagulation disorder;&#xD;
&#xD;
          -  Malignancy, active or treated tumor without explicitly been cured, or the possibility&#xD;
             of a recurrence during the study period;&#xD;
&#xD;
          -  Epilepsy not including alcohol epilepsy of stop drinking in the first 3 years or the&#xD;
             simplicity not requiring treatment in the past 3 years;&#xD;
&#xD;
          -  Asplenia, functional asplenia, and any circumstances leading to asplenia or&#xD;
             splenectomy;&#xD;
&#xD;
          -  Guillain-Barre syndrome;&#xD;
&#xD;
          -  Had immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids (excluding&#xD;
             corticosteroid spray to treat allergic rhinitis and corticosteroid treatment of the&#xD;
             acute uncomplicated dermatitis) within the past six months;&#xD;
&#xD;
          -  Received immune globulin in three months before study;&#xD;
&#xD;
          -  Received other experimental drugs in 30 days before study;&#xD;
&#xD;
          -  Received live attenuated vaccine in 30 days before study;&#xD;
&#xD;
          -  Receiving subunit or inactivated vaccines in 14days before study, such as pneumococcal&#xD;
             vaccine or allergy treatment;&#xD;
&#xD;
          -  In prevention or treatment of the anti-TB (antituberculosis) now;&#xD;
&#xD;
          -  Had fever (axillary temperature ≥ 38.0℃) 3 days before vaccination or had any acute&#xD;
             illness in the past five days requiring systemic antibiotics or antiviral therapy);&#xD;
&#xD;
          -  The subject is unable to comply with the study requirements because of psychology, or&#xD;
             had mental illness or dual-stage affective psychosis not well controlled within the&#xD;
             past two years or had psychology in medication and suicidal tendency in the past five&#xD;
             years;&#xD;
&#xD;
          -  According to the researcher, contrary to the study protocol or effect signed informed&#xD;
             consent due to a variety of medical, psychological, social conditions, occupational&#xD;
             factors or other conditions.&#xD;
&#xD;
        Exclusion Criteria for the second dose:&#xD;
&#xD;
          -  Had any vaccination-related Grade 3 or more adverse reactions in 72 hours after first&#xD;
             vaccination;&#xD;
&#xD;
          -  Any situation meets the exclusion criteria stated in the exclusion criteria for first&#xD;
             dose;&#xD;
&#xD;
          -  Had serious adverse reactions caused by the study vaccination.&#xD;
&#xD;
          -  Acute infection;&#xD;
&#xD;
          -  Any condition the investigator believed may affect the evaluation of the vaccine.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>60 Years</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>March 2013</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <last_update_submitted>March 14, 2013</last_update_submitted>
  <last_update_submitted_qc>March 14, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 15, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>whole virus</keyword>
  <keyword>inactivated</keyword>
  <keyword>influenza</keyword>
  <keyword>H5N1 vaccine</keyword>
  <keyword>safety</keyword>
  <keyword>immunogenicity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
    <mesh_term>Influenza in Birds</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/NCT01676675
org study id: JSVCT011
nct id: NCT01676675
lead sponsor: 
collaborator: 
has dmc: No
Influenza is an acute respiratory infection caused by influenza virus with high incidence and
      serious complications even causing death. According to the announcement released by the World
      Health Organization (WHO), the number of global annual influenza case was 0.6 to 1.2 billion
      and 0.5 to 1 million people died. The emergence of a new subtype of influenza virus may cause
      an influenza pandemic with occurence once every 10 to 50 years which cause serious adverse
      consequences for human health and social welfare worldwide.

      From 1997 to 2003，the H5N1 virus infection has increased highly and gradually spreaded to
      Europe, Africa and other countries and regions. High mortality caused by H5N1 virus has
      attracted the WHO and national government great attention. So it is meaningful to develop
      vaccine to provide effective antibody to reduce the number of infections.

      The objective of this study is to evaluate the safety and preliminary immunogenicity of a
      whole virus inactivated influenza H5N1 vaccine.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: the safety of whole virus inactivated influenza H5N1 vaccine in healthy adolescents aged from 12-17 years and adults aged from 18-60 years
time frame: 21 days after the first dose
description: Frequency of systemic and local adverse reactions within 21 days after the first doses of whole virus inactivated influenza H5N1 vaccine in healthy adolescents aged from 12-17 years and adults aged from 18-60 years
measure: the safety of whole virus inactivated influenza H5N1 vaccine in healthy adolescents aged from 12-17 years and adults aged from 18-60 years
time frame: 21 days after the second dose
description: Frequency of systemic and local adverse reactions within 21 days after the second doses of whole virus inactivated influenza H5N1 vaccine in healthy adolescents aged from 12-17 years and adults aged from 18-60 years
measure: the immunogenicity of the vaccine after first dose
time frame: on day 21±3 days
description: the seroconversion rate and GMFI of antibodies on day 21 after first dose with different formulation vaccines in healthy adolescents aged from 12-17 years and adults aged from 18-60 years
measure: the immunogenicity of the vaccine after second dose
time frame: on day 42±7 days
description: the seroconversion rate and GMFI of antibodies on day 21 after second dose with different formulation vaccines in healthy adolescents aged from 12-17 years and adults aged from 18-60 years
measure: the immunogenicity of the vaccine after whole immunization
time frame: 3 months after second dose (±14 days)
description: the seroconversion rate and GMFI of antibodies 3 months after the second dose with different formulation vaccines in healthy adolescents aged from 12-17 years and adults aged from 18-60 years
measure: abnormal change of hematological examination and the function of liver and kidney after first dose
time frame: 3 days after first dose
description: abnormal change of hematological examination and the function of liver and kidney 3 days after first dose with different formulation vaccines in healthy adolescents aged from 12-17 years and adults aged from 18-60 years
measure: abnormal change of hematological examination and the function of liver and kidney after second dose
time frame: 3 days after second dose
description: abnormal change of hematological examination and the function of liver and kidney 3 days after second dose with different formulation vaccines in healthy adolescents aged from 12-17 years and adults aged from 18-60 years
arm group label: 7.5μg/0.5ml in subjects(12-17 years old)
arm group type: Experimental
description: whole virus inactivated influenza H5N1 vaccine of 7.5μg /0.5ml in 30 adolescents aged 12-17 years old on day 0, 21
arm group label: 15μg/0.5ml in subjects(12-17 years old)
arm group type: Experimental
description: whole virus inactivated influenza H5N1 vaccine of 15.0μg /0.5ml in 30 adolescents aged 12-17 years old on day0,21
arm group label: 30μg/0.5ml in subjects(12-17 years old)
arm group type: Experimental
description: whole virus inactivated influenza H5N1 vaccine of 30.0μg /0.5ml in 30 adolescents aged 12-17 years old on day0,21
arm group label: 7.5μg/0.5ml in subjects(18-60 years old)
arm group type: Experimental
description: whole virus inactivated influenza H5N1 vaccine of 7.5μg /0.5ml in 30 adults aged 18-60 years old on day 0, 21
arm group label: 15μg/0.5ml in subjects(18-60 years old)
arm group type: Experimental
description: whole virus inactivated influenza H5N1 vaccine of 15.0μg /0.5ml in 30 adults aged 18-60 years old on day 0, 21
arm group label: 30μg/0.5ml in subjects(18-60 years old)
arm group type: Experimental
description: whole virus inactivated influenza H5N1 vaccine of 30.0μg /0.5ml in 30 adults aged 18-60 years old on day 0, 21
arm group label: 0/0.5ml in adolescents (12-17 years old)
arm group type: Placebo Comparator
description: 0/0.5ml placebo in 30 adolescents aged 12-17 years old on day 0, 21
arm group label: 0/0.5ml in adults(18-60 years old)
arm group type: Placebo Comparator
description: 0/0.5ml placebo in 30 adults aged 18-60 years old on day 0, 21
intervention type: Biological
intervention name: 7.5μg /0.5ml
description: whole virus inactivated influenza H5N1 vaccine of 7.5μg /0.5ml, two doses, 21 days interval
arm group label: 7.5μg/0.5ml in subjects(12-17 years old)
arm group label: 7.5μg/0.5ml in subjects(18-60 years old)
intervention type: Biological
intervention name: 15.0μg /0.5ml
description: whole virus inactivated influenza H5N1 vaccine of 15.0μg /0.5ml, two doses, 21 days interval
arm group label: 15μg/0.5ml in subjects(12-17 years old)
arm group label: 15μg/0.5ml in subjects(18-60 years old)
intervention type: Biological
intervention name: 30.0μg /0.5ml
description: whole virus inactivated influenza H5N1 vaccine of 30.0μg /0.5ml, two doses, 21 days interval
arm group label: 30μg/0.5ml in subjects(12-17 years old)
arm group label: 30μg/0.5ml in subjects(18-60 years old)
intervention type: Biological
intervention name: 0/0.5ml placebo
description: 0/0.5ml placebo, two doses, 21 days interval
arm group label: 0/0.5ml in adolescents (12-17 years old)
arm group label: 0/0.5ml in adults(18-60 years old)
criteria: 
gender: All
minimum age: 12 Years
maximum age: 60 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Influenza, Human
mesh term: Influenza in Birds