<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/NCT03038776</url>
  </required_header>
  <id_info>
    <org_study_id>FLU007</org_study_id>
    <nct_id>NCT03038776</nct_id>
  </id_info>
  <brief_title>Recombinant H7 Hemagglutinin Influenza Vaccine Trial</brief_title>
  <acronym>FLU007</acronym>
  <official_title>A Randomised, Controlled, Phase 1 Study in Healthy Adults to Evaluate the Immunogenicity and Safety of a Recombinant H7 Hemagglutinin Influenza Vaccine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vaxine Pty Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Australian Respiratory and Sleep Medicine Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vaxine Pty Ltd</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recombinant H7 (rH7) vaccine has been shown to be poorly immunogenic in previous human&#xD;
      clinical trials. This study will test approaches to improve the immunogenicity of H7 vaccine,&#xD;
      namely use of a three dose regimen, use of a modified H7 HA sequence from which the Tregitope&#xD;
      has been removed (rH7m), and inclusion of delta inulin adjuvant adjuvant in the vaccine&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Because antibody responses to experimental H7 vaccine have been low even with high antigen&#xD;
      doses, there is a need to find ways to enhance the effectiveness of H7 vaccines. Protein&#xD;
      Sciences Corporation (PSC) produces an FDA approved seasonal recombinant trivalent influenza&#xD;
      vaccine consisting of influenza hemagglutinin proteins (HA) which are full length uncleaved&#xD;
      glycoproteins (rHA0) produced using baculovirus expression vectors in cultured insect cells&#xD;
      grown in serum-free media (FluBlok®). The mechanism of action of FluBlok is the same as that&#xD;
      of traditional inactivated seasonal influenza vaccines.&#xD;
&#xD;
      PanBlok H7 is a pandemic influenza vaccine produced by PSC in the same way as Flublok but it&#xD;
      is directed against H7 rather than seasonal influenza virus strains. The vaccine candidate&#xD;
      consists of a full-length recombinant monovalent hemagglutinin (rHA) derived from H7N9 virus,&#xD;
      in a sterile solution for intramuscular injection. PanBlok H7 rHA is manufactured using the&#xD;
      same production process as previously used for Panblok H1/2009pdm (&quot;swine flu&quot;) and Panblok&#xD;
      H5 pandemic vaccines, both of which vaccines have been previously successfully trialled by us&#xD;
      in clinical protocols, FLU005 and FLU003. In both these trials the Panblok antigen was&#xD;
      combined with Advax adjuvant formulations. In the FLU005 trial of Panblok H1N1/2009pdm&#xD;
      vaccine, the inclusion of Advax adjuvant doubled the seroconversion rate of the vaccine and&#xD;
      provided major antigen-sparing effects (Gordon et al, 2012). Whilst the FLU003 trial is&#xD;
      ongoing, preliminary data again shows the importance of the Advax adjuvants to vaccine&#xD;
      effectiveness. This provides a strong rationale for inclusion of Advax adjuvants in the&#xD;
      Panblok H7 vaccine.&#xD;
&#xD;
      It has also been recently recognised that at least one of the reasons for the low&#xD;
      immunogenicity of H7 vaccines in human trials to date is that the H7 antigen from this virus&#xD;
      contains a T-cell regulatory epitope (Tregitope) in the HA stem region which suppresses the&#xD;
      immune response to the vaccine. It was recently demonstrated in humanised animal studies&#xD;
      undertaken by collaborators in Japan that removing this Tregitope by modifying 3 amino acids&#xD;
      in the H7 stem was able to significantly increase the ability of the H7 vaccine to induce&#xD;
      antibody production by human immune cells. This trial will provide the first opportunity to&#xD;
      confirm this approach is able to enhance the immunogenicity of H7 in humans, which if&#xD;
      confirmed would represent a major breakthough in pandemic influenza vaccine design.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">May 2019</completion_date>
  <primary_completion_date type="Actual">November 2017</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>Seroconversion</measure>
    <time_frame>1 month post immunization</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Seroprotection</measure>
    <time_frame>1 month post immunization</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Fold rise in geometric mean titer</measure>
    <time_frame>1 month post immunization</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety: Frequency and severity of adverse events</measure>
    <time_frame>12 months post immunization</time_frame>
    <description>Frequency and severity of adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T cell response</measure>
    <time_frame>1 month post-immunization</time_frame>
    <description>Frequency of influenza specific T cells</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Influenza, Avian</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen) + Advax-1 adjuvant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen) + Advax-2 adjuvant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) antigen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) + Advax-1 adjuvant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) + Advax-2 adjuvant</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Recombinant influenza hemagglutinin</intervention_name>
    <description>Avian H7N9 influenza vaccine</description>
    <arm_group_label>1</arm_group_label>
    <arm_group_label>2</arm_group_label>
    <arm_group_label>3</arm_group_label>
    <arm_group_label>4</arm_group_label>
    <arm_group_label>5</arm_group_label>
    <arm_group_label>6</arm_group_label>
    <other_name>Panblok-H7</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female&#xD;
&#xD;
          -  Age 18 years or over&#xD;
&#xD;
          -  Able to provide written informed consent&#xD;
&#xD;
          -  Willing and able to comply with the protocol for the duration of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of serious vaccine allergy*&#xD;
&#xD;
          -  History of vasculitis, Wegener's granulomatosis, narcolepsy, Guillain Barre, SLE or&#xD;
             other systemic autoimmune disease that in the opinion of the investigator would make&#xD;
             the vaccine contraindicated&#xD;
&#xD;
          -  History of chronic liver disease or liver transaminases elevated more than 3xULN&#xD;
&#xD;
          -  Women of childbearing potential, unless using a reliable and appropriate contraceptive&#xD;
             method, specifically oral contraceptive pill, IUD or mechanical barrier device.&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
&#xD;
          -  Any serious medical, social or mental condition which, in the opinion of the&#xD;
             investigator, would be detrimental to the subjects or the study.&#xD;
&#xD;
          -  Receipt of another investigational agent within 28 days preceding initiation of&#xD;
             treatment.&#xD;
&#xD;
               -  Individuals who have a past history of potential vaccine reactions will be&#xD;
                  assessed by the investigator, who will decide whether any past potential&#xD;
                  vaccine-related side are sufficiently minimal to allow vaccine administration to&#xD;
                  proceed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dimitar Sajkov, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Flinders University/ARASMI</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Flinders University</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5042</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <last_update_submitted>May 6, 2019</last_update_submitted>
  <last_update_submitted_qc>May 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>vaccine</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemagglutinins</mesh_term>
  </intervention_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/NCT03038776
org study id: FLU007
nct id: NCT03038776
lead sponsor: 
collaborator: 
has dmc: No
Recombinant H7 (rH7) vaccine has been shown to be poorly immunogenic in previous human
      clinical trials. This study will test approaches to improve the immunogenicity of H7 vaccine,
      namely use of a three dose regimen, use of a modified H7 HA sequence from which the Tregitope
      has been removed (rH7m), and inclusion of delta inulin adjuvant adjuvant in the vaccine
Because antibody responses to experimental H7 vaccine have been low even with high antigen
      doses, there is a need to find ways to enhance the effectiveness of H7 vaccines. Protein
      Sciences Corporation (PSC) produces an FDA approved seasonal recombinant trivalent influenza
      vaccine consisting of influenza hemagglutinin proteins (HA) which are full length uncleaved
      glycoproteins (rHA0) produced using baculovirus expression vectors in cultured insect cells
      grown in serum-free media (FluBlok®). The mechanism of action of FluBlok is the same as that
      of traditional inactivated seasonal influenza vaccines.

      PanBlok H7 is a pandemic influenza vaccine produced by PSC in the same way as Flublok but it
      is directed against H7 rather than seasonal influenza virus strains. The vaccine candidate
      consists of a full-length recombinant monovalent hemagglutinin (rHA) derived from H7N9 virus,
      in a sterile solution for intramuscular injection. PanBlok H7 rHA is manufactured using the
      same production process as previously used for Panblok H1/2009pdm ("swine flu") and Panblok
      H5 pandemic vaccines, both of which vaccines have been previously successfully trialled by us
      in clinical protocols, FLU005 and FLU003. In both these trials the Panblok antigen was
      combined with Advax adjuvant formulations. In the FLU005 trial of Panblok H1N1/2009pdm
      vaccine, the inclusion of Advax adjuvant doubled the seroconversion rate of the vaccine and
      provided major antigen-sparing effects (Gordon et al, 2012). Whilst the FLU003 trial is
      ongoing, preliminary data again shows the importance of the Advax adjuvants to vaccine
      effectiveness. This provides a strong rationale for inclusion of Advax adjuvants in the
      Panblok H7 vaccine.

      It has also been recently recognised that at least one of the reasons for the low
      immunogenicity of H7 vaccines in human trials to date is that the H7 antigen from this virus
      contains a T-cell regulatory epitope (Tregitope) in the HA stem region which suppresses the
      immune response to the vaccine. It was recently demonstrated in humanised animal studies
      undertaken by collaborators in Japan that removing this Tregitope by modifying 3 amino acids
      in the H7 stem was able to significantly increase the ability of the H7 vaccine to induce
      antibody production by human immune cells. This trial will provide the first opportunity to
      confirm this approach is able to enhance the immunogenicity of H7 in humans, which if
      confirmed would represent a major breakthough in pandemic influenza vaccine design.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Seroconversion
time frame: 1 month post immunization
measure: Seroprotection
time frame: 1 month post immunization
measure: Fold rise in geometric mean titer
time frame: 1 month post immunization
measure: Safety: Frequency and severity of adverse events
time frame: 12 months post immunization
description: Frequency and severity of adverse events
measure: T cell response
time frame: 1 month post-immunization
description: Frequency of influenza specific T cells
arm group label: 1
arm group type: Experimental
description: Two i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen)
arm group label: 2
arm group type: Experimental
description: Two i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen) + Advax-1 adjuvant
arm group label: 3
arm group type: Experimental
description: Two i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen) + Advax-2 adjuvant
arm group label: 4
arm group type: Experimental
description: Two i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) antigen
arm group label: 5
arm group type: Experimental
description: Two i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) + Advax-1 adjuvant
arm group label: 6
arm group type: Experimental
description: Two i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) + Advax-2 adjuvant
intervention type: Biological
intervention name: Recombinant influenza hemagglutinin
description: Avian H7N9 influenza vaccine
arm group label: 1
arm group label: 2
arm group label: 3
arm group label: 4
arm group label: 5
arm group label: 6
other name: Panblok-H7
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Dimitar Sajkov, MD, PhD
role: Principal Investigator
affiliation: Flinders University/ARASMI
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Influenza, Human
mesh term: Influenza in Birds
mesh term: Hemagglutinins
sharing ipd: No