<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/NCT02236052</url>
  </required_header>
  <id_info>
    <org_study_id>CP-Q13VLP-008</org_study_id>
    <nct_id>NCT02236052</nct_id>
  </id_info>
  <brief_title>Immunogenicity, Safety and Tolerability of a Plant-Derived Seasonal VLP Quadrivalent Influenza Vaccine in the Elderly Population</brief_title>
  <official_title>Immunogenicity, Safety and Tolerability of a Plant-Derived Seasonal Virus-Like Particles (VLP) Quadrivalent Influenza Vaccine in the Elderly Population</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medicago</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medicago</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multiple sites phase II trial, randomized, observer-blind, dose ranging,&#xD;
      placebo-controlled study to evaluate the immunogenicity, safety, and tolerability of a single&#xD;
      intramuscular injection of plant-based Seasonal VLP Quadrivalent Influenza Vaccine&#xD;
      administered in elderly subjects (50 years old and more).&#xD;
&#xD;
      A total of four hundred fifty (450) subjects will be randomized in six (6) groups of 75&#xD;
      subjects to receive one injection of either a non-adjuvanted low, medium or high dose level&#xD;
      of VLP, a low or high dose level of VLP of the quadrivalent VLP influenza vaccine combined&#xD;
      with Alhydrogel® as adjuvant or the placebo preparation (100 millimolar (mM) phosphate buffer&#xD;
      + 150 mM sodium chloride (NaCl) + 0.01% Tween 80)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will use cohort staggering (slow enrollment) for 3 non-adjuvanted dose levels&#xD;
      (low, medium, high dose level of VLP per strain), 2 adjuvanted dose levels (low or high dose&#xD;
      level of VLP per strain) and a placebo-controlled group divided in 3 cohorts:&#xD;
&#xD;
        -  Cohort 1: Approximately one hundred and thirty-eight (138) subjects will be randomized&#xD;
           and dosed as follows: seventy-five (75) subjects with the lowest non-adjuvanted dose of&#xD;
           the quadrivalent VLP vaccine, nineteen (19) subjects with the medium non-adjuvanted dose&#xD;
           of the quadrivalent VLP vaccine, nineteen (19) subjects with the lowest adjuvanted dose&#xD;
           of the quadrivalent VLP vaccine and twenty-five (25) subjects with a placebo. The 7-day&#xD;
           safety data after the immunization will be collected by the clinical staff and will be&#xD;
           reviewed by the Data and Safety Monitoring Board (DSMB). The DSMB consisting of the PIs,&#xD;
           the Sponsor's Medical Officer and 3 external medical advisors (voting members); the&#xD;
           members will determine if the clinical sites are allowed to continue with the&#xD;
           immunization of the second cohort.&#xD;
&#xD;
        -  Cohort 2: Approximately one hundred and seventy-five (175) subjects will be randomized&#xD;
           and dosed as follows: fifty-six (56) subjects with the medium non-adjuvanted dose&#xD;
           quadrivalent VLP vaccine, fifty-six (56) subjects with the lowest adjuvanted dose&#xD;
           quadrivalent VLP vaccine, nineteen (19) subjects with the highest adjuvanted dose&#xD;
           quadrivalent VLP vaccine, nineteen (19) subjects with the highest non-adjuvanted dose&#xD;
           quadrivalent VLP vaccine and twenty-five (25) subjects with a placebo. The 7-day safety&#xD;
           data after the immunization will be collected by the clinical staff and reviewed by the&#xD;
           DSMB prior to allowing immunization of the third cohort.&#xD;
&#xD;
        -  Cohort 3: Approximately one hundred and thirty-seven (137) subjects will be randomized&#xD;
           and dosed as follows: fifty-six (56) subjects with the highest adjuvanted dose,&#xD;
           fifty-six (56) subjects with the highest non-adjuvanted dose and twenty-five (25)&#xD;
           subjects with a placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 16, 2014</start_date>
  <completion_date type="Actual">June 17, 2015</completion_date>
  <primary_completion_date type="Actual">June 17, 2015</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>Immunogenicity</measure>
    <time_frame>21 days after injection</time_frame>
    <description>Immunogenicity will be assessed by Geometric mean titers (GMTs) of Hemagglutination Inhibition (HI) antibodies against the vaccine strains on Days 0 and 21 and assessed by measuring geometric mean fold rise, seroconversion rate and seroprotection rate. Follow-up serology samples for GMTs will be collected at Day 201.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Solicited systemic and local reactions</measure>
    <time_frame>21 days after injection</time_frame>
    <description>Safety and tolerability will be assessed by the rate, severity and relationship to vaccination of solicited and unsolicited adverse events post-vaccination. A 6-month follow-up period will be performed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity (against vaccine strains and heterologous strains)</measure>
    <time_frame>21 days after injection</time_frame>
    <description>Immunogenicity will be evaluated by Geometric mean titers (GMTs) of microneutralization (MN) antibodies (Days 0 and 21) against the vaccine strains and assessed by measuring Geometric mean fold rise ans seroconversion rate. Cross-reactivity of antibodies induced by a single dose of the quadrivalent VLP vaccine will also be assessed and measured by HI and microneutralization (MN) antibody titers for heterologous influenza strains. This will be assessed using the measure of Geometric mean fold rise, seroconversion rate and seroprotection rate (for HI only).</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">450</enrollment>
  <condition>Virus Diseases</condition>
  <condition>RNA Virus Infections</condition>
  <condition>Respiratory Tract Diseases</condition>
  <condition>Respiratory Tract Infections</condition>
  <arm_group>
    <arm_group_label>Non-adjuvanted low dose of quadrivalent VLP vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single non-adjuvanted low dose of quadrivalent VLP vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-adjuvanted medium dose of quadrivalent VLP vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single non-adjuvanted medium dose of quadrivalent VLP vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-adjuvanted high dose of quadrivalent VLP vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single non-adjuvanted high dose of quadrivalent VLP vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adjuvanted low dose of quadrivalent VLP vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single low dose of quadrivalent VLP vaccine mixed with Alhydrogel®</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adjuvanted high dose of quadrivalent VLP vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single high dose of quadrivalent VLP vaccine mixed with Alhydrogel®</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A single dose of Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Non-adjuvanted low dose of quadrivalent VLP vaccine</intervention_name>
    <description>A single non-adjuvanted low dose of quadrivalent VLP vaccine</description>
    <arm_group_label>Non-adjuvanted low dose of quadrivalent VLP vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Non-adjuvanted medium dose of quadrivalent VLP vaccine</intervention_name>
    <description>A single non-adjuvanted medium dose of quadrivalent VLP vaccine</description>
    <arm_group_label>Non-adjuvanted medium dose of quadrivalent VLP vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Non-adjuvanted high dose of quadrivalent VLP vaccine</intervention_name>
    <description>A single non-adjuvanted high dose of quadrivalent VLP vaccine</description>
    <arm_group_label>Non-adjuvanted high dose of quadrivalent VLP vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adjuvanted low dose of quadrivalent VLP vaccine</intervention_name>
    <description>A single low dose of quadrivalent VLP vaccine mixed with Alhydrogel®</description>
    <arm_group_label>Adjuvanted low dose of quadrivalent VLP vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adjuvanted high dose of quadrivalent VLP vaccine</intervention_name>
    <description>A single high dose of quadrivalent VLP vaccine mixed with Alhydrogel®</description>
    <arm_group_label>Adjuvanted high dose of quadrivalent VLP vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A single dose of placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female subjects, 50 years of age or older.&#xD;
&#xD;
          2. BMI of ≥18 and ≤32.&#xD;
&#xD;
          3. Give his/her consent to participate in this study (by signing the informed consent&#xD;
             form). In the opinion of the Investigator, competence and willingness to provide&#xD;
             written, informed consent for participation after reading the informed consent form.&#xD;
             The subject must have adequate opportunity to discuss the study with an Investigator&#xD;
             or qualified designee.&#xD;
&#xD;
          4. Healthy as judged by the Investigator or designee and determined by general physical&#xD;
             examination, vital signs, clinical laboratory tests, and medical history conducted no&#xD;
             more than 90 days prior to study vaccine administration. Subjects with a pre-existing&#xD;
             chronic disease will be allowed to participate if the disease is stable and, according&#xD;
             to the Investigator's judgment, the condition is unlikely confound the results of the&#xD;
             study or pose additional risk to the subject by participating in the study. Stable&#xD;
             disease is defined as no new onset of exacerbation of pre-existing chronic disease 6&#xD;
             months prior to immunization. Based on Investigator's judgment, a subject with more&#xD;
             recent stabilisation of a disease may still be eligible.&#xD;
&#xD;
          5. Comprehension of the study requirements, expressed availability for the required study&#xD;
             period, ability to attend scheduled visits, accessible by phone on a consistent basis.&#xD;
&#xD;
          6. If female, have a negative serum pregnancy test result at screening and negative urine&#xD;
             pregnancy test on Day 0 prior to immunization.&#xD;
&#xD;
          7. Female of childbearing potential must use an effective method of contraception for 1&#xD;
             month prior to immunization and agrees to continue employing adequate birth control&#xD;
             measures for at least 60 days post-immunization. Moreover, she must have no plan to&#xD;
             become pregnant for at least 2 months post-immunization. Abstinent subjects should be&#xD;
             asked what method(s) they would use, should their circumstances change, and subjects&#xD;
             without a well-defined plan should be excluded.&#xD;
&#xD;
             The following relationship or methods of contraception are considered to be effective:&#xD;
&#xD;
               -  Hormonal contraceptives (e.g., injectable, topical [patch], estrogenic vaginal&#xD;
                  ring, etc.);&#xD;
&#xD;
               -  Intra-uterine device (IUD) with or without hormonal release;&#xD;
&#xD;
               -  Male partner using a condom plus spermicide or sterilized partner (at least 1&#xD;
                  year prior to immunization);&#xD;
&#xD;
               -  History of credible abstinence (self-reported);&#xD;
&#xD;
               -  Heterosexual abstinence at least 60 days post-immunization;&#xD;
&#xD;
               -  Female partner.&#xD;
&#xD;
          8. Non-childbearing females defines as:&#xD;
&#xD;
               -  Surgically-sterile (defined as bilateral tubal ligation or hysterectomy performed&#xD;
                  more than 1 month prior to immunization);&#xD;
&#xD;
               -  Post-menopausal (absence of menses for 24 consecutive months and age consistent&#xD;
                  with natural cessation of ovulation).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. According to Investigator's opinion, presence of significant acute or chronic,&#xD;
             uncontrolled medical or neuropsychiatric illness. &quot;Uncontrolled&quot; is defined as:&#xD;
&#xD;
               1. Requiring a new medical or surgical treatment within one month prior to study&#xD;
                  vaccine administration which would interfere with vaccine evaluation or study&#xD;
                  completion (subject requiring medical or surgical treatment that would not&#xD;
                  interfere with evaluation [e.g., minor knee surgery, cataracts, etc.] would be&#xD;
                  eligible);&#xD;
&#xD;
               2. Requiring a change in medication dosage in one month prior to study vaccine&#xD;
                  administration due to uncontrolled symptoms or drug toxicity (elective dosage&#xD;
                  adjustments in stable subjects are acceptable).&#xD;
&#xD;
          2. Any medical or neuropsychiatric condition or any history of excessive alcohol use or&#xD;
             drug abuse which, in the Investigator's opinion, would render the subject unable to&#xD;
             provide informed consent or unable to provide valid safety observations and reporting.&#xD;
&#xD;
          3. Any autoimmune disease or any confirmed or suspected immunosuppressive condition or&#xD;
             immunodeficiency including history of human immunodeficiency virus (HIV) infection,&#xD;
             Hepatitis B or C, or the presence of lymphoproliferative disease.&#xD;
&#xD;
          4. Administration of any vaccine (including any other influenza vaccine) within 30 days&#xD;
             prior to study enrolment or planned administration within the period from the&#xD;
             vaccination up to blood sampling at Day 21 or within 30 days prior to blood sampling&#xD;
             at Day 201. Immunization on an emergency basis will be evaluated in a case-by-case by&#xD;
             the Investigator.&#xD;
&#xD;
          5. Administration of any adjuvanted or investigational influenza vaccine within 1 year&#xD;
             prior to study enrolment or planned administration prior to the end of this trial (Day&#xD;
             201). Administration of any 'standard', not adjuvanted influenza vaccine (e.g., live&#xD;
             attenuated Trivalent Inactivated Influenza Vaccine (TIV) or Quadrivalent Inactivated&#xD;
             Vaccine (QIV) vaccine IN or split TIV or QIV vaccine by either intra-dermal or&#xD;
             intramuscular route) prior to the 30-day exclusion period mentioned above would be&#xD;
             acceptable.&#xD;
&#xD;
          6. Use of any investigational or non-registered product within 30 days prior to study&#xD;
             enrolment or planned use during the study period. Subjects may not participate in any&#xD;
             other investigational or marketed drug study while participating in this study&#xD;
             (approximately 7-12 months [depending when subjects undergo screening session and Day&#xD;
             201 visit]).&#xD;
&#xD;
          7. Treatment with systemic glucocorticoids at a dose exceeding 10 mg of prednisone per&#xD;
             day, or equivalent for more than 7 consecutive days or for 10 or more days in total,&#xD;
             within one month of study vaccine administration, any other cytotoxic or&#xD;
             immunosuppressant drug, or any immunoglobulin preparation within 3 months of&#xD;
             vaccination. Routine use of standard doses of nasal or inhaled glucocorticoids is&#xD;
             allowed.&#xD;
&#xD;
          8. Any significant disorder of coagulation or treatment with warfarin derivatives or&#xD;
             heparin. Persons receiving prophylactic anti-platelet medications, e.g., low-dose&#xD;
             aspirin (no more than 325 mg/day), and without a clinically apparent bleeding tendency&#xD;
             are eligible. Subjects treated with new generation drugs that will not increase risk&#xD;
             of intramuscular bleeding (such as clopidogrel) are also eligible.&#xD;
&#xD;
          9. History of allergy to any of the constituents of the VLP quadrivalent study vaccine,&#xD;
             Alhydrogel® (aluminum hydroxide) or to the phosphate buffered saline (PBS; used as&#xD;
             placebo), or tobacco allergy.&#xD;
&#xD;
         10. History of anaphylaxis reaction to any food, medication or bee sting.&#xD;
&#xD;
         11. Any history of severe asthma (e.g., status asthmatic, hospitalization for asthma&#xD;
             control) or recurrent asthma episodes requiring medical attention in the last 3 years&#xD;
             (≥ 1 episode/year).&#xD;
&#xD;
         12. Continuous use of anti-histamines in the last 4 weeks prior to immunization or use of&#xD;
             anti-histamines 48 hours prior to study immunization.&#xD;
&#xD;
         13. Have a rash, dermatological condition, tattoos, muscle mass, or any other&#xD;
             abnormalities at injection site which may interfere with injection site reaction&#xD;
             rating.&#xD;
&#xD;
         14. Have received a blood transfusion within 90 days prior to study vaccination.&#xD;
&#xD;
         15. If female, have a positive or doubtful pregnancy test prior to immunization or&#xD;
             lactating females.&#xD;
&#xD;
         16. Vital sign abnormalities (systolic blood pressure and/or diastolic blood pressure,&#xD;
             heart rate). Although a vital signs measurement is out of the acceptable ranges, a&#xD;
             subject may be included in the study based on Investigator's judgment. Presence of any&#xD;
             febrile illness (including oral temperature (OT) ≥38.0˚C within 24 hours prior to&#xD;
             immunization). Such subjects may be re-evaluated for enrolment after resolution of&#xD;
             illness.&#xD;
&#xD;
         17. Cancer or treatment for cancer within 3 years of study vaccine administration. Persons&#xD;
             with a history of cancer who are disease-free without treatment for 3 years or more&#xD;
             are eligible. Persons with treated and uncomplicated basal cell carcinoma of the skin&#xD;
             are eligible. Person with non-treated, non-disseminated local prostate cancer are&#xD;
             eligible.&#xD;
&#xD;
         18. Identified as an Investigator or employee of the Investigator or study center with&#xD;
             direct involvement in the proposed study, or identified as an immediate family member&#xD;
             (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with&#xD;
             direct involvement in the proposed study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Libman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MUHC-Vaccine Study Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Guy Boivin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre de recherche-CHU de Québec</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Richard Larouche, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>inVentiv Health Clinique</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MUHC-Vaccine Study Centre</name>
      <address>
        <city>Pierrefonds</city>
        <state>Quebec</state>
        <zip>H9H 4Y6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre de recherche-CHU de Québec</name>
      <address>
        <city>Québec</city>
        <zip>G1E 7G9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>inVentiv Health Clinique</name>
      <address>
        <city>Québec</city>
        <zip>G1P 0A2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <results_reference>
    <citation>Pillet S, Couillard J, Trepanier S, Poulin JF, Yassine-Diab B, Guy B, Ward BJ, Landry N. Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate-Two randomized Phase II clinical trials in 18 to 49 and &gt;/=50 years old adults. PLoS One. 2019 Jun 5;14(6):e0216533. doi: 10.1371/journal.pone.0216533. eCollection 2019.</citation>
    <PMID>31166987</PMID>
  </results_reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <last_update_submitted>October 31, 2019</last_update_submitted>
  <last_update_submitted_qc>October 31, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Influenza</keyword>
  <keyword>Human</keyword>
  <keyword>RNA Virus Infections</keyword>
  <keyword>Immunologic</keyword>
  <keyword>Immunogenic Factors</keyword>
  <keyword>Physiological Effects of Drugs</keyword>
  <keyword>Virus diseases</keyword>
  <keyword>Orthomyxoviridae Infections</keyword>
  <keyword>Infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Influenza, Human</mesh_term>
    <mesh_term>Respiratory Tract Infections</mesh_term>
    <mesh_term>RNA Virus Infections</mesh_term>
    <mesh_term>Respiratory Tract Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_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/NCT02236052
org study id: CP-Q13VLP-008
nct id: NCT02236052
lead sponsor: 
has dmc: Yes
This is a multiple sites phase II trial, randomized, observer-blind, dose ranging,
      placebo-controlled study to evaluate the immunogenicity, safety, and tolerability of a single
      intramuscular injection of plant-based Seasonal VLP Quadrivalent Influenza Vaccine
      administered in elderly subjects (50 years old and more).

      A total of four hundred fifty (450) subjects will be randomized in six (6) groups of 75
      subjects to receive one injection of either a non-adjuvanted low, medium or high dose level
      of VLP, a low or high dose level of VLP of the quadrivalent VLP influenza vaccine combined
      with Alhydrogel® as adjuvant or the placebo preparation (100 millimolar (mM) phosphate buffer
      + 150 mM sodium chloride (NaCl) + 0.01% Tween 80)
This study will use cohort staggering (slow enrollment) for 3 non-adjuvanted dose levels
      (low, medium, high dose level of VLP per strain), 2 adjuvanted dose levels (low or high dose
      level of VLP per strain) and a placebo-controlled group divided in 3 cohorts:

        -  Cohort 1: Approximately one hundred and thirty-eight (138) subjects will be randomized
           and dosed as follows: seventy-five (75) subjects with the lowest non-adjuvanted dose of
           the quadrivalent VLP vaccine, nineteen (19) subjects with the medium non-adjuvanted dose
           of the quadrivalent VLP vaccine, nineteen (19) subjects with the lowest adjuvanted dose
           of the quadrivalent VLP vaccine and twenty-five (25) subjects with a placebo. The 7-day
           safety data after the immunization will be collected by the clinical staff and will be
           reviewed by the Data and Safety Monitoring Board (DSMB). The DSMB consisting of the PIs,
           the Sponsor's Medical Officer and 3 external medical advisors (voting members); the
           members will determine if the clinical sites are allowed to continue with the
           immunization of the second cohort.

        -  Cohort 2: Approximately one hundred and seventy-five (175) subjects will be randomized
           and dosed as follows: fifty-six (56) subjects with the medium non-adjuvanted dose
           quadrivalent VLP vaccine, fifty-six (56) subjects with the lowest adjuvanted dose
           quadrivalent VLP vaccine, nineteen (19) subjects with the highest adjuvanted dose
           quadrivalent VLP vaccine, nineteen (19) subjects with the highest non-adjuvanted dose
           quadrivalent VLP vaccine and twenty-five (25) subjects with a placebo. The 7-day safety
           data after the immunization will be collected by the clinical staff and reviewed by the
           DSMB prior to allowing immunization of the third cohort.

        -  Cohort 3: Approximately one hundred and thirty-seven (137) subjects will be randomized
           and dosed as follows: fifty-six (56) subjects with the highest adjuvanted dose,
           fifty-six (56) subjects with the highest non-adjuvanted dose and twenty-five (25)
           subjects with a placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Immunogenicity
time frame: 21 days after injection
description: Immunogenicity will be assessed by Geometric mean titers (GMTs) of Hemagglutination Inhibition (HI) antibodies against the vaccine strains on Days 0 and 21 and assessed by measuring geometric mean fold rise, seroconversion rate and seroprotection rate. Follow-up serology samples for GMTs will be collected at Day 201.
measure: Solicited systemic and local reactions
time frame: 21 days after injection
description: Safety and tolerability will be assessed by the rate, severity and relationship to vaccination of solicited and unsolicited adverse events post-vaccination. A 6-month follow-up period will be performed.
measure: Immunogenicity (against vaccine strains and heterologous strains)
time frame: 21 days after injection
description: Immunogenicity will be evaluated by Geometric mean titers (GMTs) of microneutralization (MN) antibodies (Days 0 and 21) against the vaccine strains and assessed by measuring Geometric mean fold rise ans seroconversion rate. Cross-reactivity of antibodies induced by a single dose of the quadrivalent VLP vaccine will also be assessed and measured by HI and microneutralization (MN) antibody titers for heterologous influenza strains. This will be assessed using the measure of Geometric mean fold rise, seroconversion rate and seroprotection rate (for HI only).
arm group label: Non-adjuvanted low dose of quadrivalent VLP vaccine
arm group type: Experimental
description: A single non-adjuvanted low dose of quadrivalent VLP vaccine
arm group label: Non-adjuvanted medium dose of quadrivalent VLP vaccine
arm group type: Experimental
description: A single non-adjuvanted medium dose of quadrivalent VLP vaccine
arm group label: Non-adjuvanted high dose of quadrivalent VLP vaccine
arm group type: Experimental
description: A single non-adjuvanted high dose of quadrivalent VLP vaccine
arm group label: Adjuvanted low dose of quadrivalent VLP vaccine
arm group type: Experimental
description: A single low dose of quadrivalent VLP vaccine mixed with Alhydrogel®
arm group label: Adjuvanted high dose of quadrivalent VLP vaccine
arm group type: Experimental
description: A single high dose of quadrivalent VLP vaccine mixed with Alhydrogel®
arm group label: Placebo
arm group type: Placebo Comparator
description: A single dose of Placebo
intervention type: Biological
intervention name: Non-adjuvanted low dose of quadrivalent VLP vaccine
description: A single non-adjuvanted low dose of quadrivalent VLP vaccine
arm group label: Non-adjuvanted low dose of quadrivalent VLP vaccine
intervention type: Biological
intervention name: Non-adjuvanted medium dose of quadrivalent VLP vaccine
description: A single non-adjuvanted medium dose of quadrivalent VLP vaccine
arm group label: Non-adjuvanted medium dose of quadrivalent VLP vaccine
intervention type: Biological
intervention name: Non-adjuvanted high dose of quadrivalent VLP vaccine
description: A single non-adjuvanted high dose of quadrivalent VLP vaccine
arm group label: Non-adjuvanted high dose of quadrivalent VLP vaccine
intervention type: Biological
intervention name: Adjuvanted low dose of quadrivalent VLP vaccine
description: A single low dose of quadrivalent VLP vaccine mixed with Alhydrogel®
arm group label: Adjuvanted low dose of quadrivalent VLP vaccine
intervention type: Biological
intervention name: Adjuvanted high dose of quadrivalent VLP vaccine
description: A single high dose of quadrivalent VLP vaccine mixed with Alhydrogel®
arm group label: Adjuvanted high dose of quadrivalent VLP vaccine
intervention type: Biological
intervention name: Placebo
description: A single dose of placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Michael Libman, MD
role: Principal Investigator
affiliation: MUHC-Vaccine Study Centre
last name: Guy Boivin, MD
role: Principal Investigator
affiliation: Centre de recherche-CHU de Québec
last name: Richard Larouche, MD
role: Principal Investigator
affiliation: inVentiv Health Clinique
facility: 
facility: 
facility: 
country: Canada
citation: Pillet S, Couillard J, Trepanier S, Poulin JF, Yassine-Diab B, Guy B, Ward BJ, Landry N. Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate-Two randomized Phase II clinical trials in 18 to 49 and >/=50 years old adults. PLoS One. 2019 Jun 5;14(6):e0216533. doi: 10.1371/journal.pone.0216533. eCollection 2019.
PMID: 31166987
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Virus Diseases
mesh term: Influenza, Human
mesh term: Respiratory Tract Infections
mesh term: RNA Virus Infections
mesh term: Respiratory Tract Diseases
mesh term: Vaccines