<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/NCT03784885</url>
  </required_header>
  <id_info>
    <org_study_id>1066021486</org_study_id>
    <nct_id>NCT03784885</nct_id>
  </id_info>
  <brief_title>A Phase 2, Double-blind Study to Evaluate Intranasal Trivalent Influenza Virus Vaccine in Healthy Adult</brief_title>
  <official_title>A Phase 2, Double-blind, Randomized Controlled Study to Evaluate Immunogenicity and Safety of Intranasal Trivalent Influenza Virus Vaccine in Healthy Adult V Olunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Advagene Biopharma Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Advagene Biopharma 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 objectives of this phase 2 study are to evaluate immunogenicity, safety and tolerability&#xD;
      of AD07030, a trivalent influenza virus antigens vaccine, given intranasally in 2 doses in&#xD;
      healthy adult volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2 prospective, randomized controlled, double-blind, multi-center study to&#xD;
      evaluate the immunogenicity, safety and tolerability of AD07030, a trivalent influenza virus&#xD;
      antigens vaccine, given intranasally in healthy adult volunteers.&#xD;
&#xD;
      About 358 healthy subjects, meeting all the eligibility criteria will be enrolled into the&#xD;
      study and randomized into 3 study groups (in 2:2:1 ratio) to receive either the study vaccine&#xD;
      at one of the dose levels of adjuvant AD07010 (30μg or 45μg LTh(αK)) in combination with&#xD;
      hemagglutinin (HA) antigens or to receive control vaccine consisting of HA antigens alone.&#xD;
      The 3 study groups are as follows:&#xD;
&#xD;
        -  Group 1: 22.5μg HA with 30μg AD07010&#xD;
&#xD;
        -  Group 2: 22.5μg HA with 45μg AD07010&#xD;
&#xD;
        -  Group 3: 22.5μg HA alone Each subject will receive intranasal administration of 2 doses&#xD;
           of IP (study or control vaccine) at same dosages, given 7 days apart on study Day 1 and&#xD;
           Day 8. Solicited local and general AEs will be recorded after each vaccination in the&#xD;
           subject's diary card for up to 7 days (the vaccine administration day and 6 days&#xD;
           following it). Subjects will be followed up for monitoring of safety and immunogenicity&#xD;
           for 180 days. AE and SAE and concomitant medication/vaccination will be collected&#xD;
           throughout the study. There will be total of 6 study visits and a telephone call.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">October 30, 2018</completion_date>
  <primary_completion_date type="Actual">January 7, 2018</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Geometric mean titer changes on Day 29</measure>
    <time_frame>29 days</time_frame>
    <description>Change from pre- to post-vaccination serum Geometric mean titers (GMT) of hemagglutinin inhibition (HI) antibody at Day 29(±2)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity (HI titers)</measure>
    <time_frame>29, 90 and 180 days</time_frame>
    <description>Derived variables: in terms of HI titers for: Seroconversion Rate (SCR), Seroconversion Factor (SCF), and Seroprotection Rate (SPR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity (IgA titers)</measure>
    <time_frame>29, 90 and 180 days</time_frame>
    <description>Change from pre- to post-vaccination GMT of mucosal anti-HA IgA antibody</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity (anti-LTh(αK) antibodies)</measure>
    <time_frame>29, 90 and 180 days</time_frame>
    <description>Change from pre- to post-vaccination GMT of anti- LTh(αK) antibodies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral neutralization</measure>
    <time_frame>29, 90 and 180 days</time_frame>
    <description>Change from pre- to post-vaccination GMT of virus neutralization titer</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">345</enrollment>
  <condition>Influenza Infection</condition>
  <arm_group>
    <arm_group_label>30 μg of AD07010</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects in this group received 2 doses of 22.2 μg HA antigens from inactivated trivalent influenza vaccine in 30 μg of AD07010</description>
  </arm_group>
  <arm_group>
    <arm_group_label>45 μg of AD07010</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects in this group received 2 doses of 22.2 μg HA antigens from inactivated trivalent influenza vaccine in 45 μg of AD07010</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AD07010</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>All subjects in this group received 2 doses of 22.2 μg HA antigens from inactivated trivalent influenza vaccine</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AD07010</intervention_name>
    <description>A protein based adjuvant</description>
    <arm_group_label>30 μg of AD07010</arm_group_label>
    <arm_group_label>45 μg of AD07010</arm_group_label>
    <other_name>LTh(αK)</other_name>
    <other_name>Escherichia coli heat-labile enterotoxin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Inactivated trivalent influenza vaccine</intervention_name>
    <description>Inactivated trivalent seasonal influenza vaccine</description>
    <arm_group_label>30 μg of AD07010</arm_group_label>
    <arm_group_label>45 μg of AD07010</arm_group_label>
    <arm_group_label>AD07010</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult male and female subjects aged between 20-70 (included) years.&#xD;
&#xD;
          -  Should be physically and mentally healthy and free of significant medical condition as&#xD;
             determined by Medical history, Physical examination and Clinical judgment of the&#xD;
             Investigator.&#xD;
&#xD;
          -  Negative urine β-human chorionic gonadotropin in women of childbearing potential&#xD;
             (WOCBP; defined as women ≤ 50 years old of age or history of amenorrhea for ≤12&#xD;
             months) prior to administration of first dose of Investigational Product.&#xD;
&#xD;
          -  WOCBP and male subjects having female partners, who are WOCBP, should be protected by&#xD;
             effective contraceptive method (e.g. oral contraceptive and condom, intra- uterine&#xD;
             device and condom, diaphragm with spermicide and condom) throughout the study period.&#xD;
&#xD;
          -  Willing and able to give written informed consent prior to Screening and comply with&#xD;
             study procedure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received vaccination against influenza within 6 months prior to Screening.&#xD;
&#xD;
          -  Received any vaccination (other than influenza) within 28 days prior to Screening.&#xD;
&#xD;
          -  Has previously experienced anaphylaxis or a life-threatening reaction; or has history&#xD;
             of allergy or hypersensitivity to egg proteins, chicken proteins, any of the&#xD;
             components of Investigational Product, or other vaccine containing same substances.&#xD;
&#xD;
          -  History of influenza infection (confirmed either clinically, serologically or&#xD;
             microbiologically) within the 6 months prior to administration of first dose of&#xD;
             Investigational Product.&#xD;
&#xD;
          -  Had active allergic rhinitis within 28 days prior to administration of first dose of&#xD;
             Investigational Product.&#xD;
&#xD;
          -  Has documented history of diarrhea within 28 days prior to administration of first&#xD;
             dose of Investigational Product.&#xD;
&#xD;
          -  Have used or been administered any intranasal medication or nasal topical treatment&#xD;
             within 7 days prior to Screening.&#xD;
&#xD;
          -  Acute respiratory illness within 7 days prior to administration of first dose of&#xD;
             Investigational Product.&#xD;
&#xD;
          -  Had administration of systemic antibiotics or antivirals within 7 days prior to&#xD;
             Screening (excluding topical/external use of antibiotics).&#xD;
&#xD;
          -  Acute sinusitis or chronic sinusitis accompanying acute symptoms within 3 days prior&#xD;
             to administration of first dose of Investigational Product.&#xD;
&#xD;
          -  With acute disease (defined as fever with body temperature &gt;38.0°C), within 3 days&#xD;
             prior to administration of first dose of Investigational Product.&#xD;
&#xD;
          -  Having any serious chronic illness, including but not limited to, cardiovascular,&#xD;
             pulmonary, hepatic, metabolic, renal or any auto-immune disorders, at a stage that&#xD;
             could interfere with trial conduct or completion.&#xD;
&#xD;
          -  Any confirmed or suspected immunosuppressive or immune-deficient condition, based on&#xD;
             medical history and physical examination.&#xD;
&#xD;
          -  Documented history of Bell's palsy or neurological disorder.&#xD;
&#xD;
          -  Receive aspirin (Salicylate) anytime in the study from screening (Visit 1)&#xD;
&#xD;
          -  A positive test for HIV antibody&#xD;
&#xD;
          -  Receipt of any immunoglobulins and/or blood products within 3 months of study&#xD;
             Screening.&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Require extended long-term use of steroids including parenteral steroids or high dose&#xD;
             inhaled steroids or have used within 28 days prior to Screening&#xD;
&#xD;
          -  Participated in any other clinical investigation or use of any investigational therapy&#xD;
             other than AD07030, within 4 weeks (28 days) or 5 half-lives, whichever is longer,&#xD;
             before Screening.&#xD;
&#xD;
          -  Unable to communicate reliably with the Investigator or unlikely to cooperate with the&#xD;
             requirements of the study procedures or schedule, or other cases judged by the&#xD;
             Investigator to be ineligible for participation in the study.&#xD;
&#xD;
          -  Other cases judged by the Investigator to be ineligible for participation in the&#xD;
             study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Advagene Biopharma</name>
      <address>
        <city>Taipei</city>
        <zip>104</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>December 21, 2018</last_update_submitted>
  <last_update_submitted_qc>December 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>adjuvant</keyword>
  <keyword>vaccine</keyword>
  <keyword>mucosa</keyword>
  <keyword>IgA</keyword>
  <keyword>Escherichia coli Enterotoxin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03784885
org study id: 1066021486
nct id: NCT03784885
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objectives of this phase 2 study are to evaluate immunogenicity, safety and tolerability
      of AD07030, a trivalent influenza virus antigens vaccine, given intranasally in 2 doses in
      healthy adult volunteers.
This is a Phase 2 prospective, randomized controlled, double-blind, multi-center study to
      evaluate the immunogenicity, safety and tolerability of AD07030, a trivalent influenza virus
      antigens vaccine, given intranasally in healthy adult volunteers.

      About 358 healthy subjects, meeting all the eligibility criteria will be enrolled into the
      study and randomized into 3 study groups (in 2:2:1 ratio) to receive either the study vaccine
      at one of the dose levels of adjuvant AD07010 (30μg or 45μg LTh(αK)) in combination with
      hemagglutinin (HA) antigens or to receive control vaccine consisting of HA antigens alone.
      The 3 study groups are as follows:

        -  Group 1: 22.5μg HA with 30μg AD07010

        -  Group 2: 22.5μg HA with 45μg AD07010

        -  Group 3: 22.5μg HA alone Each subject will receive intranasal administration of 2 doses
           of IP (study or control vaccine) at same dosages, given 7 days apart on study Day 1 and
           Day 8. Solicited local and general AEs will be recorded after each vaccination in the
           subject's diary card for up to 7 days (the vaccine administration day and 6 days
           following it). Subjects will be followed up for monitoring of safety and immunogenicity
           for 180 days. AE and SAE and concomitant medication/vaccination will be collected
           throughout the study. There will be total of 6 study visits and a telephone call.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Geometric mean titer changes on Day 29
time frame: 29 days
description: Change from pre- to post-vaccination serum Geometric mean titers (GMT) of hemagglutinin inhibition (HI) antibody at Day 29(±2)
measure: Immunogenicity (HI titers)
time frame: 29, 90 and 180 days
description: Derived variables: in terms of HI titers for: Seroconversion Rate (SCR), Seroconversion Factor (SCF), and Seroprotection Rate (SPR)
measure: Immunogenicity (IgA titers)
time frame: 29, 90 and 180 days
description: Change from pre- to post-vaccination GMT of mucosal anti-HA IgA antibody
measure: Immunogenicity (anti-LTh(αK) antibodies)
time frame: 29, 90 and 180 days
description: Change from pre- to post-vaccination GMT of anti- LTh(αK) antibodies
measure: Viral neutralization
time frame: 29, 90 and 180 days
description: Change from pre- to post-vaccination GMT of virus neutralization titer
arm group label: 30 μg of AD07010
arm group type: Experimental
description: All subjects in this group received 2 doses of 22.2 μg HA antigens from inactivated trivalent influenza vaccine in 30 μg of AD07010
arm group label: 45 μg of AD07010
arm group type: Experimental
description: All subjects in this group received 2 doses of 22.2 μg HA antigens from inactivated trivalent influenza vaccine in 45 μg of AD07010
arm group label: AD07010
arm group type: Active Comparator
description: All subjects in this group received 2 doses of 22.2 μg HA antigens from inactivated trivalent influenza vaccine
intervention type: Biological
intervention name: AD07010
description: A protein based adjuvant
arm group label: 30 μg of AD07010
arm group label: 45 μg of AD07010
other name: LTh(αK)
other name: Escherichia coli heat-labile enterotoxin
intervention type: Biological
intervention name: Inactivated trivalent influenza vaccine
description: Inactivated trivalent seasonal influenza vaccine
arm group label: 30 μg of AD07010
arm group label: 45 μg of AD07010
arm group label: AD07010
criteria: 
gender: All
minimum age: 20 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Influenza, Human
sharing ipd: Undecided