<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/NCT04453852</url>
  </required_header>
  <id_info>
    <org_study_id>13110</org_study_id>
    <nct_id>NCT04453852</nct_id>
  </id_info>
  <brief_title>Monovalent Recombinant COVID19 Vaccine</brief_title>
  <acronym>COVAX19</acronym>
  <official_title>A Randomised, Controlled, Phase 1 Study to Evaluate the Safety and Immunogenicity of a Candidate Adjuvanted Recombinant Protein SARS-COV-2 Vaccine in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vaxine Pty Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Central Adelaide Local Health Network Incorporated</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vaxine Pty 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>
      This is a study to test a new vaccine (Covax-19) against COVID-19. COVID-19 is a potentially&#xD;
      deadly disease that is caused by a new strain of coronavirus called SARS-CoV-2. To date,&#xD;
      SARS-CoV-2 has infected over 4 million people worldwide resulted in the deaths of over three&#xD;
      hundred thousand people.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Human infections with zoonotic coronaviruses including severe acute respiratory syndrome&#xD;
      coronavirus (SARS CoV), Middle East respiratory syndrome-associated coronavirus (MERS CoV)&#xD;
      and now 2019 SARS-CoV-2, all pose major human public health threats with high case fatality&#xD;
      rates. The outbreak of SARS-CoV-2, which shares high similarity with SARS-CoV in its viral&#xD;
      genome, has so far caused more than 4,736,000 cases worldwide (as of May 17, 2020) with&#xD;
      3131,545 deaths, resulting in an estimated overall mortality rate of 4-5%. It has a&#xD;
      particularly high mortality rate in elderly people and those with chronic disease. To fight&#xD;
      the current outbreak and prepare for future human outbreaks of similar coronaviruses,&#xD;
      development of a safe and effective SARS-COV-2 vaccine remains a high priority. The fatality&#xD;
      rate in the elderly is very high, being 8% for those over 70 and over 20% for those over 80.&#xD;
      Notably, over 16% of the Australian population is aged 65 or older. Currently there is no way&#xD;
      to control infection with SARS-COV-2 other than minimise exposure by social isolation.&#xD;
&#xD;
      Development of a vaccine against COVID-19 would deliver major public health and economic&#xD;
      benefits for Australia, with potential to prevent numerous deaths, particularly among the&#xD;
      Australian elderly, reducing the burden on hospital ICUs, helping to alleviate public&#xD;
      concern, and ultimately allowing the Australian economy to return as fast as possible to&#xD;
      normal.&#xD;
&#xD;
      SARS-CoV and SARS-CoV-2 are both closely related enveloped, single positive-stranded RNA&#xD;
      viruses, with one genome encoding a non-structural replicase polyprotein and structural&#xD;
      proteins, including spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. SARS&#xD;
      virus neutralizing antibodies were shown to be directed against the S protein. S protein can&#xD;
      be cleaved into S1 and S2 subunits by proteases and within the S1 subunit there is a&#xD;
      receptor-binding domain (RBD), which was shown to bind angiotensin-converting enzyme 2&#xD;
      (ACE2), which mediates SARS virus entry into cells. SARS-CoV-2 spike protein similarly binds&#xD;
      ACE2 for cellular entry. Hence a recombinant SARS-CoV-2 spike protein vaccine that induces&#xD;
      neutralising antibody against the virus should be effective against SARS-CoV-2 infection just&#xD;
      as seen for SARS CoV.&#xD;
&#xD;
      SARS-COV-2 vaccine design is best informed by previous experience with closely related SARS&#xD;
      CoV vaccines. Antibodies against the coronavirus spike protein blocks infection. When&#xD;
      recombinant SARS spike protein vaccines produced in insect cells were formulated with Advax&#xD;
      adjuvant, this enhances neutralizing antibody and T cell responses which translate into rapid&#xD;
      lung viral clearance. Based on experience with developing successful and safe SARS and MERS&#xD;
      vaccines, Covax-19 vaccine design is based on recombinant insect cell- expressed SARS-COV-2&#xD;
      spike protein formulated with Advax-SM adjuvant. The vaccine is based on recombinant&#xD;
      expression of the ecto-domain of spike protein in insect cells. Insect cell expression of&#xD;
      recombinant protein is a well characterised platform, allowing standardised procedures to be&#xD;
      rapidly transferred to other facilities around the world. In response to the 2009 H1N1&#xD;
      influenza pandemic, roll-out of a pandemic vaccine based on hemagglutinin protein was&#xD;
      extremely fast, with the first cGMP batches of vaccine produced within 6 weeks of virus&#xD;
      discovery, and the first human trial subject dosed at Flinders just under 3 months after&#xD;
      virus discovery . The use of Advax adjuvant doubled the seroconversion and seroprotection&#xD;
      rates while maintaining vaccine tolerability and safety. Recombinant proteins manufactured&#xD;
      using this method and formulated with Advax adjuvants have been found to be effective and&#xD;
      safe in multiple human trials, including of H1N1/2009 and H5N1 (NCT02335164) and H7N9&#xD;
      (NCT03038776) influenza vaccines.&#xD;
&#xD;
      Covax-19 consists of highly purified recombinant SARS-COV-2 spike protein plus Advax-SM&#xD;
      adjuvant in a sterile solution for intramuscular injection. COVAX-19™ vaccine is manufactured&#xD;
      using a Sf9 platform. Advax-CpG adjuvant has previously been well tolerated and effective in&#xD;
      trials of hepatitis B, H5N1 (NCT02335164) and H7N9 (NCT03038776) influenza vaccines and has&#xD;
      recently been tested by the NIH in a US multicentre clinical trial with 2 quadrivalent&#xD;
      seasonal influenza vaccines (NCT03945825).&#xD;
&#xD;
      COVAX-19™ vaccine is designed to elicit an immune response against SARS-CoV-2 with generation&#xD;
      of neutralising antibodies against its spike protein that prevent the virus attaching to the&#xD;
      human ACE2 receptor in the respiratory epithelium. It is also designed to induce T cells&#xD;
      against the spike protein.&#xD;
&#xD;
      Study hypotheses&#xD;
&#xD;
        -  COVAX-19 vaccine is safe and well tolerated in adult human subjects&#xD;
&#xD;
        -  COVAX-19 vaccine will induce durable high titer neutralising antibodies and T cell&#xD;
           responses against SARS-COV-2 virus.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 30, 2020</start_date>
  <completion_date type="Actual">April 14, 2021</completion_date>
  <primary_completion_date type="Actual">February 1, 2021</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>
    <intervention_model_description>Randomised controlled study</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Non-blind Staff administering vaccine do not participate in any other aspects of the study. Remaining trial staff and participant are blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Adverse Events</measure>
    <time_frame>1 week post immunisation</time_frame>
    <description>Incidence of Adverse Events 1 week post immunisation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>COVID19 antibody titers</measure>
    <time_frame>3 weeks post second immunisation</time_frame>
    <description>COVID19 antibody titers post immunisation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>COVID19 T cell immunogenicity</measure>
    <time_frame>3 weeks post second immunisation</time_frame>
    <description>Frequency of COVID19 spike specific T cells 1-3 weeks post second immunisation</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Coronavirus Infection</condition>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Spike antigen (25ug) + 15 mg Advax-2 adjuvant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>COVID19 vaccine</intervention_name>
    <description>COVID19 recombinant spike protein with Advax-SM adjuvant</description>
    <arm_group_label>Group A</arm_group_label>
    <other_name>COVAX-19 vaccine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Saline control</description>
    <arm_group_label>Group B</arm_group_label>
    <other_name>Saline control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Subjects eligible to participate in this trial had to meet all of the following&#xD;
             inclusion criteria:&#xD;
&#xD;
          -  Provide written informed consent prior to initiation of any study procedures.&#xD;
&#xD;
          -  Healthy males or non-pregnant females, aged 18 years to 65 years inclusive.&#xD;
&#xD;
          -  Women of childbearing potential2 must use an acceptable contraception method3 from at&#xD;
             least 30 days before study vaccination until 90 days after study vaccination.&#xD;
&#xD;
             2Not sterilized via, bilateral oophorectomy, salpingectomy, hysterectomy, (permanent,&#xD;
             non-surgical, non-hormonal sterilization) with documented radiological confirmation&#xD;
             test at least 90 days after the procedure, and still menstruating or &lt;1 year has&#xD;
             passed since the last menses if menopausal.&#xD;
&#xD;
             3Includes full abstinence from sexual intercourse with a male partner, monogamous&#xD;
             relationship with vasectomized partner who has been vasectomized for 180 days or more&#xD;
             barrier methods such as condoms, effective intrauterine devices, tubal ligation, and&#xD;
             approved hormonal methods such as implants, injectables or oral contraceptives (&quot;the&#xD;
             pill&quot;).&#xD;
&#xD;
          -  Women of childbearing potential must have a negative urine or serum pregnancy test&#xD;
             within 24 hours prior to study vaccination&#xD;
&#xD;
          -  Are able to understand and comply with planned study procedures and be available for&#xD;
             all study visits.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  • Have an acute illness, as determined by the site Principal Investigator (PI) or&#xD;
             appropriate sub-investigator, within 72 hours prior to study vaccination.&#xD;
&#xD;
          -  Have a history of documented COVID-19 infection or a known positive COVID-19 antibody&#xD;
             test.&#xD;
&#xD;
          -  Liver function tests (ALT, AST or GGT) &gt; 2 times upper limit of normal&#xD;
&#xD;
          -  eGFR &lt;55 mL/min/1.73 m2&#xD;
&#xD;
          -  Have immunosuppression as a result of an underlying illness or treatment, a recent&#xD;
             history or current use of immunosuppressive or immunomodulating disease therapy.&#xD;
&#xD;
          -  Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior&#xD;
             to study vaccination.&#xD;
&#xD;
          -  Have known active or recently active (12 months) neoplastic disease or a history of&#xD;
             any hematologic malignancy.&#xD;
&#xD;
          -  Have known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection.&#xD;
&#xD;
          -  Have a history of severe systemic reactions following previous immunization with&#xD;
             licensed or unlicensed vaccines.&#xD;
&#xD;
          -  Have a history of Guillain-Barré Syndrome.&#xD;
&#xD;
          -  Have known hypersensitivity or allergy to insect stings or other components of the&#xD;
             study vaccine.&#xD;
&#xD;
          -  Have a history of epilepsy or febrile convulsions&#xD;
&#xD;
          -  Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).&#xD;
&#xD;
          -  Have a history of alcohol or drug abuse within 5 years prior to study vaccination.&#xD;
&#xD;
          -  Have any diagnosis, current or past, of schizophrenia, bipolar disease or other&#xD;
             psychiatric diagnosis that may interfere with subject compliance or safety evaluations&#xD;
             as determined by the site PI or appropriate sub-investigator.&#xD;
&#xD;
          -  Have been hospitalized for psychiatric illness, history of suicide attempt, or&#xD;
             confinement for danger to self or others within 5 years prior to study vaccination.&#xD;
&#xD;
          -  Have taken oral or parenteral (including intra-articular) corticosteroids of any dose&#xD;
             within 30 days prior to study vaccination.&#xD;
&#xD;
          -  Have taken high-dose inhaled corticosteroids within 30 days prior to study&#xD;
             vaccination.&#xD;
&#xD;
          -  Female participants who are breastfeeding or plan to breastfeed from the time of the&#xD;
             first study vaccination through 30 days after the last study vaccination.&#xD;
&#xD;
          -  Positive urine or serum pregnancy test within 24 hours prior to any study vaccination&#xD;
&#xD;
          -  Received an experimental agent within 30 days prior to the study vaccination or expect&#xD;
             to receive another experimental agent during the trial-reporting period.&#xD;
&#xD;
          -  Have any medical disease or condition that, in the opinion of the Investigator, is a&#xD;
             contraindication to study participation.&#xD;
&#xD;
          -  Have any medical disease or condition that, in the opinion of the site PI or&#xD;
             appropriate sub-investigator, is a contraindication to study participation. *Including&#xD;
             acute, subacute, intermittent or chronic medical disease or condition that would place&#xD;
             the subject at an unacceptable risk of injury, render the subject unable to meet the&#xD;
             requirements of the protocol, or may interfere with the evaluation of responses or the&#xD;
             subject's successful completion of this trial.&#xD;
&#xD;
          -  Any participant whose enrolment, in the opinion of the investigator, would be&#xD;
             detrimental to the participant or the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Gordon, MBBS, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>CALHN</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PARC,</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>February 12, 2022</last_update_submitted>
  <last_update_submitted_qc>February 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID19</keyword>
  <keyword>coronavirus</keyword>
  <keyword>vaccine</keyword>
  <keyword>adjuvant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronavirus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</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/NCT04453852
org study id: 13110
nct id: NCT04453852
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a study to test a new vaccine (Covax-19) against COVID-19. COVID-19 is a potentially
      deadly disease that is caused by a new strain of coronavirus called SARS-CoV-2. To date,
      SARS-CoV-2 has infected over 4 million people worldwide resulted in the deaths of over three
      hundred thousand people.
Human infections with zoonotic coronaviruses including severe acute respiratory syndrome
      coronavirus (SARS CoV), Middle East respiratory syndrome-associated coronavirus (MERS CoV)
      and now 2019 SARS-CoV-2, all pose major human public health threats with high case fatality
      rates. The outbreak of SARS-CoV-2, which shares high similarity with SARS-CoV in its viral
      genome, has so far caused more than 4,736,000 cases worldwide (as of May 17, 2020) with
      3131,545 deaths, resulting in an estimated overall mortality rate of 4-5%. It has a
      particularly high mortality rate in elderly people and those with chronic disease. To fight
      the current outbreak and prepare for future human outbreaks of similar coronaviruses,
      development of a safe and effective SARS-COV-2 vaccine remains a high priority. The fatality
      rate in the elderly is very high, being 8% for those over 70 and over 20% for those over 80.
      Notably, over 16% of the Australian population is aged 65 or older. Currently there is no way
      to control infection with SARS-COV-2 other than minimise exposure by social isolation.

      Development of a vaccine against COVID-19 would deliver major public health and economic
      benefits for Australia, with potential to prevent numerous deaths, particularly among the
      Australian elderly, reducing the burden on hospital ICUs, helping to alleviate public
      concern, and ultimately allowing the Australian economy to return as fast as possible to
      normal.

      SARS-CoV and SARS-CoV-2 are both closely related enveloped, single positive-stranded RNA
      viruses, with one genome encoding a non-structural replicase polyprotein and structural
      proteins, including spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. SARS
      virus neutralizing antibodies were shown to be directed against the S protein. S protein can
      be cleaved into S1 and S2 subunits by proteases and within the S1 subunit there is a
      receptor-binding domain (RBD), which was shown to bind angiotensin-converting enzyme 2
      (ACE2), which mediates SARS virus entry into cells. SARS-CoV-2 spike protein similarly binds
      ACE2 for cellular entry. Hence a recombinant SARS-CoV-2 spike protein vaccine that induces
      neutralising antibody against the virus should be effective against SARS-CoV-2 infection just
      as seen for SARS CoV.

      SARS-COV-2 vaccine design is best informed by previous experience with closely related SARS
      CoV vaccines. Antibodies against the coronavirus spike protein blocks infection. When
      recombinant SARS spike protein vaccines produced in insect cells were formulated with Advax
      adjuvant, this enhances neutralizing antibody and T cell responses which translate into rapid
      lung viral clearance. Based on experience with developing successful and safe SARS and MERS
      vaccines, Covax-19 vaccine design is based on recombinant insect cell- expressed SARS-COV-2
      spike protein formulated with Advax-SM adjuvant. The vaccine is based on recombinant
      expression of the ecto-domain of spike protein in insect cells. Insect cell expression of
      recombinant protein is a well characterised platform, allowing standardised procedures to be
      rapidly transferred to other facilities around the world. In response to the 2009 H1N1
      influenza pandemic, roll-out of a pandemic vaccine based on hemagglutinin protein was
      extremely fast, with the first cGMP batches of vaccine produced within 6 weeks of virus
      discovery, and the first human trial subject dosed at Flinders just under 3 months after
      virus discovery . The use of Advax adjuvant doubled the seroconversion and seroprotection
      rates while maintaining vaccine tolerability and safety. Recombinant proteins manufactured
      using this method and formulated with Advax adjuvants have been found to be effective and
      safe in multiple human trials, including of H1N1/2009 and H5N1 (NCT02335164) and H7N9
      (NCT03038776) influenza vaccines.

      Covax-19 consists of highly purified recombinant SARS-COV-2 spike protein plus Advax-SM
      adjuvant in a sterile solution for intramuscular injection. COVAX-19™ vaccine is manufactured
      using a Sf9 platform. Advax-CpG adjuvant has previously been well tolerated and effective in
      trials of hepatitis B, H5N1 (NCT02335164) and H7N9 (NCT03038776) influenza vaccines and has
      recently been tested by the NIH in a US multicentre clinical trial with 2 quadrivalent
      seasonal influenza vaccines (NCT03945825).

      COVAX-19™ vaccine is designed to elicit an immune response against SARS-CoV-2 with generation
      of neutralising antibodies against its spike protein that prevent the virus attaching to the
      human ACE2 receptor in the respiratory epithelium. It is also designed to induce T cells
      against the spike protein.

      Study hypotheses

        -  COVAX-19 vaccine is safe and well tolerated in adult human subjects

        -  COVAX-19 vaccine will induce durable high titer neutralising antibodies and T cell
           responses against SARS-COV-2 virus.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomised controlled study
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Non-blind Staff administering vaccine do not participate in any other aspects of the study. Remaining trial staff and participant are blinded
measure: Incidence of Adverse Events
time frame: 1 week post immunisation
description: Incidence of Adverse Events 1 week post immunisation
measure: COVID19 antibody titers
time frame: 3 weeks post second immunisation
description: COVID19 antibody titers post immunisation
measure: COVID19 T cell immunogenicity
time frame: 3 weeks post second immunisation
description: Frequency of COVID19 spike specific T cells 1-3 weeks post second immunisation
arm group label: Group A
arm group type: Experimental
description: Spike antigen (25ug) + 15 mg Advax-2 adjuvant
arm group label: Group B
arm group type: Placebo Comparator
description: Saline
intervention type: Biological
intervention name: COVID19 vaccine
description: COVID19 recombinant spike protein with Advax-SM adjuvant
arm group label: Group A
other name: COVAX-19 vaccine
intervention type: Biological
intervention name: Saline
description: Saline control
arm group label: Group B
other name: Saline control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David Gordon, MBBS, Ph.D
role: Principal Investigator
affiliation: CALHN
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Coronavirus Infections
mesh term: Vaccines
sharing ipd: No