<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/NCT03293732</url>
  </required_header>
  <id_info>
    <org_study_id>DCB07030-CT-01</org_study_id>
    <nct_id>NCT03293732</nct_id>
  </id_info>
  <brief_title>Study of the Safety, Tolerability and Immunogenicity of an Intranasal Influenza Vaccine Administered to Healthy Adults</brief_title>
  <official_title>A Randomized, Double-blind Phase I Trial to Evaluate the Safety, Tolerability, and Immunogenicity of DCB07010 Adjuvant Given Intranasally at Ascending Dose Levels and Co-administered With Trivalent Inactivated Influenza Virus Antigen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Advagene Biopharma Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Advagene Biopharma Co. Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</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 study were to assess the safety and tolerability of DCB07010 when&#xD;
      given intranasally at escalating dose levels of 7.5μg, 15μg, 30μg and 45μg, in combination&#xD;
      with 22.5μg of influenza HA antigen (7.5μg HA of each of three strains) and to generate&#xD;
      sufficient immunogenicity data to enable dose selection for larger and more definitive Phase&#xD;
      2 studies.&#xD;
&#xD;
      This was a single center, double-blind, randomized (2:1), dose-escalation study to assess the&#xD;
      safety, tolerability and immunogenicity of 4 different vaccine-adjuvant doses in comparison&#xD;
      to influenza HA alone. The 4 treatment cohorts were given DCB07010 in a dose- escalating&#xD;
      manner.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 28, 2012</start_date>
  <completion_date type="Actual">September 30, 2013</completion_date>
  <primary_completion_date type="Actual">March 30, 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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Geometric Mean Titers (GMT) against all three strains of viral antigen</measure>
    <time_frame>Day=0, 28</time_frame>
    <description>Geometric Mean Titers (GMT) against all three strains of viral antigen after 2 doses of DCB07010 adjuvanted egg-derived vaccines or egg-derived vaccine. The geometric mean titers against all three-vaccine strains were assessed by egg-derived antigen haemagglutination inhibition (HI) assay.&#xD;
Statistic tests were two-sided and were set for alpha = 0.05. The purpose of this study was exploratory in safety and the formal statistical analysis was not necessary.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Geometric Mean Ratio (GMR) after 2 dose of vaccines</measure>
    <time_frame>Day=0, 28</time_frame>
    <description>Geometric Mean Ratio (GMR) after 2 dose of egg-based vaccine and DCB07010-adjuvanted vaccines. Statistic tests were two-sided and were set for alpha = 0.05. The purpose of this study was exploratory in safety and the formal statistical analysis was not necessary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seroconversion Rates (SCR) measurements</measure>
    <time_frame>Day=0, 28</time_frame>
    <description>Seroconversion Rates (SCR) is defined the percentage of subjects with pre-vaccination HI titers &lt; 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer to each of the three vaccine components on Day 28.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Flu, Human</condition>
  <arm_group>
    <arm_group_label>HA antigen only</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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>7.5 μg of DCB07010</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects in this group received 7.5 μg of DCB07010 in 22.2 μg HA antigens twice.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>15 μg of DCB07010</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects in this group received 15 μg of DCB07010 in 22.2 μg HA antigens twice.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>30 μg of DCB07010</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects in this group received 30 μg of DCB07010 in 22.2 μg HA antigens twice.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>45 μg of DCB07010</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects in this group received 45 μg of DCB07010 in 22.2 μg HA antigens twice.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DCB07010</intervention_name>
    <description>A protein based adjuvant originated from prokaryotic organism.</description>
    <arm_group_label>15 μg of DCB07010</arm_group_label>
    <arm_group_label>30 μg of DCB07010</arm_group_label>
    <arm_group_label>45 μg of DCB07010</arm_group_label>
    <arm_group_label>7.5 μg of DCB07010</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>HA antigens</intervention_name>
    <description>HA antigens from three strains of influenza virus ( 7.5 μg of HA each strain).</description>
    <arm_group_label>15 μg of DCB07010</arm_group_label>
    <arm_group_label>30 μg of DCB07010</arm_group_label>
    <arm_group_label>45 μg of DCB07010</arm_group_label>
    <arm_group_label>7.5 μg of DCB07010</arm_group_label>
    <arm_group_label>HA antigen only</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Non-smoking adult aged between 20-40 years old;&#xD;
&#xD;
          2. Physically and mentally healthy subjects as confirmed by an interview, medical&#xD;
             history, clinical examination, chest X-rays, ophthalmoscopy, cardiac echo, and&#xD;
             electrocardiogram;&#xD;
&#xD;
          3. Body Mass Index (BMI) between 18.5 and 25, inclusive, (BMI will be calculated as&#xD;
             weight in kilogram [kg]/height in meters2 [m2]);&#xD;
&#xD;
          4. Normal hematology, biochemistry and urinalysis determinations;&#xD;
&#xD;
          5. Subject is willing and able to comply with study procedures and sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject with serious underlying chronic illness;&#xD;
&#xD;
          2. Documented evidence of allergic rhinitis;&#xD;
&#xD;
          3. Subject with acute sinusitis or chronic sinusitis accompanying acute symptoms within 3&#xD;
             days prior to enrollment;&#xD;
&#xD;
          4. Immunosuppressed subjects as result of illness or treatment;&#xD;
&#xD;
          5. Female subject of childbearing potential who:&#xD;
&#xD;
               -  is lactating; or&#xD;
&#xD;
               -  has positive urine pregnancy test at Visit 2 or Visit 3; or&#xD;
&#xD;
               -  refuse to adopt reliable method of contraception during the study;&#xD;
&#xD;
          6. Subject received blood products or immunoglobulin within 3 months prior enrollment;&#xD;
&#xD;
          7. Subjects with long-term use of steroids, including parenteral steroids or high dose&#xD;
             inhaled steroids within 28 days prior to enrollment;&#xD;
&#xD;
          8. Subject has received any intranasal medication or nasal topical treatment within 7&#xD;
             days prior to enrollment;&#xD;
&#xD;
          9. Subject has received any investigational agent within 28 days or 5 half- lives,&#xD;
             whichever is longer, prior to the first dose of investigational product;&#xD;
&#xD;
         10. Subject has previously experienced anaphylaxis;&#xD;
&#xD;
         11. Subject has allergy to eggs or prior influenza vaccine;&#xD;
&#xD;
         12. Subject with laboratory-confirmed influenza or has been vaccinated against influenza&#xD;
             within 6 months prior to enrollment;&#xD;
&#xD;
         13. Subject with acute respiratory illness or administered antibiotics or antivirals&#xD;
             within 7 days prior to enrollment;&#xD;
&#xD;
         14. Subject with body temperature high than 38°C within 3 days prior to enrollment;&#xD;
&#xD;
         15. Subject with documented history of Bell's palsy or neurological disorder.&#xD;
&#xD;
         16. Subject with documented history of diarrhea within one month prior to study enrollment&#xD;
&#xD;
         17. A positive test for HIV antibody.&#xD;
&#xD;
         18. Subject has received Chinese medication or herbal medication within 28 days prior to&#xD;
             enrollment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shaun-Chwen Chang, Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Taiwan Univserity Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>January 6, 2020</last_update_submitted>
  <last_update_submitted_qc>January 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>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/NCT03293732
org study id: DCB07030-CT-01
nct id: NCT03293732
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The objectives of this study were to assess the safety and tolerability of DCB07010 when
      given intranasally at escalating dose levels of 7.5μg, 15μg, 30μg and 45μg, in combination
      with 22.5μg of influenza HA antigen (7.5μg HA of each of three strains) and to generate
      sufficient immunogenicity data to enable dose selection for larger and more definitive Phase
      2 studies.

      This was a single center, double-blind, randomized (2:1), dose-escalation study to assess the
      safety, tolerability and immunogenicity of 4 different vaccine-adjuvant doses in comparison
      to influenza HA alone. The 4 treatment cohorts were given DCB07010 in a dose- escalating
      manner.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Geometric Mean Titers (GMT) against all three strains of viral antigen
time frame: Day=0, 28
description: Geometric Mean Titers (GMT) against all three strains of viral antigen after 2 doses of DCB07010 adjuvanted egg-derived vaccines or egg-derived vaccine. The geometric mean titers against all three-vaccine strains were assessed by egg-derived antigen haemagglutination inhibition (HI) assay.
Statistic tests were two-sided and were set for alpha = 0.05. The purpose of this study was exploratory in safety and the formal statistical analysis was not necessary.
measure: Geometric Mean Ratio (GMR) after 2 dose of vaccines
time frame: Day=0, 28
description: Geometric Mean Ratio (GMR) after 2 dose of egg-based vaccine and DCB07010-adjuvanted vaccines. Statistic tests were two-sided and were set for alpha = 0.05. The purpose of this study was exploratory in safety and the formal statistical analysis was not necessary.
measure: Seroconversion Rates (SCR) measurements
time frame: Day=0, 28
description: Seroconversion Rates (SCR) is defined the percentage of subjects with pre-vaccination HI titers < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer to each of the three vaccine components on Day 28.
arm group label: HA antigen only
arm group type: Active Comparator
description: All subjects in this group received 2 doses of 22.2 μg HA antigens
arm group label: 7.5 μg of DCB07010
arm group type: Experimental
description: All subjects in this group received 7.5 μg of DCB07010 in 22.2 μg HA antigens twice.
arm group label: 15 μg of DCB07010
arm group type: Experimental
description: All subjects in this group received 15 μg of DCB07010 in 22.2 μg HA antigens twice.
arm group label: 30 μg of DCB07010
arm group type: Experimental
description: All subjects in this group received 30 μg of DCB07010 in 22.2 μg HA antigens twice.
arm group label: 45 μg of DCB07010
arm group type: Experimental
description: All subjects in this group received 45 μg of DCB07010 in 22.2 μg HA antigens twice.
intervention type: Biological
intervention name: DCB07010
description: A protein based adjuvant originated from prokaryotic organism.
arm group label: 15 μg of DCB07010
arm group label: 30 μg of DCB07010
arm group label: 45 μg of DCB07010
arm group label: 7.5 μg of DCB07010
intervention type: Biological
intervention name: HA antigens
description: HA antigens from three strains of influenza virus ( 7.5 μg of HA each strain).
arm group label: 15 μg of DCB07010
arm group label: 30 μg of DCB07010
arm group label: 45 μg of DCB07010
arm group label: 7.5 μg of DCB07010
arm group label: HA antigen only
criteria: 
gender: All
minimum age: 20 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Shaun-Chwen Chang, Ph.D.
role: Study Chair
affiliation: National Taiwan University Hospital
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Influenza, Human
sharing ipd: No