<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/NCT02188810</url>
  </required_header>
  <id_info>
    <org_study_id>PE1202</org_study_id>
    <nct_id>NCT02188810</nct_id>
  </id_info>
  <brief_title>Safety and Reactogenicity of a PAL Combined With Seasonal Flu Vaccine in Healthy Adults</brief_title>
  <official_title>A Phase I Randomized, Observer-blind, Controlled, Dose Escalation Trial of the Safety and Tolerability of a Single Intramuscular Dose of a PAL Adjuvant (FB-631) Co-administered With Seasonal TIV (2013-2014) in Healthy Adults.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Folia Biotech Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Folia Biotech Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 1, research study is looking at the safety and acceptability of a new vaccine&#xD;
      adjuvant (immune booster) called PAL when combined with the seasonal flu vaccine (Fluviral)&#xD;
      to test the safety and effectiveness of new vaccines and medications on healthy volunteers.&#xD;
&#xD;
      The study will enroll approximately 48 healthy adult participants, and occur over 3 years. In&#xD;
      the first six months/180 days of the study participants will have visits to the study site&#xD;
      during which safety and immunogenicity outcomes will be measured. From Day 181 to Year 3,&#xD;
      participants will be contacted by telephone or email to collect information on any adverse&#xD;
      events.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 1, dose-ranging, randomized (5:1), observer-blind, controlled study of the&#xD;
      safety and immune response to intramuscular injection of PapMV (Papaya Mosaic Virus) rVLP&#xD;
      (Recombinant Virus-Like Particles) which is PAL adjuvant, or &quot;PAL&quot; combined with Trivalent&#xD;
      Influenza Vaccines (TIV) at one of four dose levels of PAL, combined with one of two dose&#xD;
      levels of TIV, or active control (TIV). The study will enroll approximately 48 healthy adult&#xD;
      participants, and occur over 3 years. In the first six months/180 days (Epoch 1) of the study&#xD;
      participants will have visits to the study site during which safety and immunogenicity&#xD;
      outcomes will be measured. In Epoch 2 (Day 181 to Year 3) participants will be contacted by&#xD;
      telephone or email to collect unsolicited adverse events.&#xD;
&#xD;
      This is a controlled clinical trial. The control group will receive the standard dose of TIV,&#xD;
      0.5 mL, which consists of 15 μg haemagglutinin (HA) of each influenza strain recommended by&#xD;
      the World Health Organization (WHO) for the 2013-2014 influenza season in the northern&#xD;
      hemisphere. An active control is used so that the attributable risk of adverse events can be&#xD;
      estimated, and so that outcome measures can be assessed in a blinded fashion. Only adults in&#xD;
      stable health will be eligible in order to minimize participant risk. Only non-pregnant&#xD;
      females of childbearing age are eligible, and they must agree to continue adequate&#xD;
      contraception for 180 days after injection. Study holding rules and a safety evaluation by a&#xD;
      Safety Review Committee (SRC) will be in place. The study will follow a staggered&#xD;
      dose-escalation design, with each of four steps introducing a new dose of the adjuvant (30,&#xD;
      60, 120 and 240 μg respectively).&#xD;
&#xD;
      The first dose level of PAL adjuvant FB-631 is 0.5 X 60 µg (i.e., 30 µg), which is half the&#xD;
      dose that was found to be most immunogenic in animal studies. The adjuvant is co-administered&#xD;
      with 0.25 mL of TIV, which is half the dose of TIV that is routinely administered to adults&#xD;
      (i.e. 7.5 μg of each of the three influenza subtypes contained in the vaccine). The next dose&#xD;
      level is 60µg of FB-631 combined with 0.25 mL TIV. The third dose level is 120 μg of FB-631&#xD;
      with 0.25 mL TIV. In the fourth and final step the dose of adjuvant is 240 μg of PAL adjuvant&#xD;
      combined with 0.25 mL TIV (8 participants) or 0.125 mL TIV (i.e. 3.75 μg HA of each influenza&#xD;
      subtype contained in the vaccine) (8 participants).&#xD;
&#xD;
      Any safety signal observed in the study will lead to a hold until the decision of Safety&#xD;
      Review Committee to continue, modify or suspend the conduct of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>April 2014</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">December 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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety</measure>
    <time_frame>3 years</time_frame>
    <description>The occurrence of adverse events from injection to Day 1095 (36 months/three years, in all participants, in all groups:</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>6 months</time_frame>
    <description>Evaluate the immunogenicity of influenza antigens contained in TIV when combined with PAL adjuvant as measured by haemagglutination inhibition (HAI) titres, pre-injection (Day 0) and post-injection (Days 28, 120 and 180).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity of TIV combined with PAL</measure>
    <time_frame>6 months</time_frame>
    <description>Immunogenicity of the influenza antigens contained in TIV when combined with PAL adjuvant as measured by IgG and IgG1 antibody directed to influenza A viral nucleoproteins on Days 0, 28, 120 and 180.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune responses</measure>
    <time_frame>6 months</time_frame>
    <description>Describe cellular immune responses to the investigational products as assessed by antigen-secreted interferon-gamma secretion, and interferon-gamma to IL-10 ratio, pre-injection (Day 0) and post-injection (Day 28, Day 120 and Day 180).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Induced immune responses</measure>
    <time_frame>6 months</time_frame>
    <description>Describe immune responses induced by PAL adjuvant combined with TIV as measured by Granzyme B levels in Peripheral Blood Mononuclear Cells (PBMC), pre-injection (Day 0) and post-injection (Day 28, Day 120 and Day 180).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Solicited and General Adverse Events</measure>
    <time_frame>up to 6 months</time_frame>
    <description>The occurrence of each solicited local and general AE (adverse event), during a 7-day follow-up period after injection (i.e. the day of injection and 6 subsequent days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematological laboratory values</measure>
    <time_frame>up to 6 months</time_frame>
    <description>The occurrence of any hematological (hemoglobin level, WBC (white blood cells), lymphocyte, neutrophil, eosinophil and platelet count) and biochemical (ALT, AST(angiotensin sensitivity test) and creatinine) laboratory abnormality at Day 0 and at Day 7.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unsolicited Adverse Events</measure>
    <time_frame>3 years</time_frame>
    <description>The occurrence of any unsolicited AE, during a 28-day follow-up period after injection (i.e. the day of injection and 27 subsequent days), and through to Day 1095. The occurrence of any SAE through to Day 1095.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Flu</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single dose of control vaccine (a single dose of 0.5 mL TIV).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of the test article (0.25 mL TIV, which is 7.5 μg of each influenza strain with 0.5x PAL, i.e. 30 μg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of the test article (0.25 mL TIV, which is 7.5 μg of each influenza strain with 1x PAL, i.e. 60 μg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of the test article (0.25 mL of TIV which is 7.5 μg of each influenza strain with 2x PAL (i.e., 120 μg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of the test article (0.25 mL of TIV which is 7.5 μg of each influenza strain with 4x PAL (i.e., 240 μg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of the test article (0.125 mL of TIV with 4x PAL i.e., 240 μg).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PAL</intervention_name>
    <description>Single dose administered intramuscularly.</description>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_label>Group 6</arm_group_label>
    <other_name>PapMV Adjuvant Long lasting immune response</other_name>
    <other_name>FB-631</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TIV</intervention_name>
    <description>Single dose administered intramuscularly .</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_label>Group 6</arm_group_label>
    <other_name>Trivalent Influenza Vaccines</other_name>
    <other_name>Fluviral</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Good general health status, as determined by history and physical examination no&#xD;
             greater than 30 days prior to administration of the first test article.&#xD;
&#xD;
          -  Participants who, in the opinion of the investigator, can and will comply with the&#xD;
             requirements of the protocol (e.g. completion of Diary Cards, return for follow-up&#xD;
             visits).&#xD;
&#xD;
          -  If female of child-bearing potential and heterosexually active, has practiced adequate&#xD;
             contraception for 30 days prior to injection and has a negative pregnancy test on the&#xD;
             day of injection and has agreed to continue adequate contraception until 180 days&#xD;
             after injection. (Please refer to the glossary for the definition of child-bearing&#xD;
             potential and adequate contraception).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of any investigational or non-registered product (drug or vaccine) other than the&#xD;
             study product within 28 days preceding the dose of study product, or planned use&#xD;
             during the study period.&#xD;
&#xD;
          -  Planned administration/ administration of a vaccine/product not foreseen by the study&#xD;
             protocol within the period starting 28 days before injection and ending 28 days after.&#xD;
&#xD;
          -  Planned administration/ administration of the seasonal influenza vaccine recommended&#xD;
             by local public health authorities within the period starting 120 days before&#xD;
             injection and ending 121 days after. (Note: enrolment should be completed 120 days&#xD;
             before the annual seasonal influenza vaccine campaigns in October and December)&#xD;
&#xD;
          -  Administration of immunoglobulins and/or any blood products within the 3 months&#xD;
             preceding the dose of study product or planned administration during the study period.&#xD;
&#xD;
          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on&#xD;
             medical history and physical examination. (Laboratory testing for HIV, Hepatitis C and&#xD;
             Hepatitis B will be performed during the screening visit).&#xD;
&#xD;
          -  Chronic administration (defined as more than 14 days in total) of immunosuppressants&#xD;
             or other immune-modifying drug within 6 months prior to the product dose&#xD;
&#xD;
          -  Family history of congenital or hereditary immunodeficiency.&#xD;
&#xD;
          -  History of or current autoimmune disease.&#xD;
&#xD;
          -  Known or suspected hypersensitivity to Fluviral, to thimerosal, or to any other&#xD;
             ingredient in the formulation or component of the container.&#xD;
&#xD;
          -  Pregnant or lactating female.&#xD;
&#xD;
          -  Any hematological (hemoglobin level, white blood cell [WBC], and platelet count) and&#xD;
             biochemical (alanine aminotransferase [ALT], aspartate aminotransferase [AST], blood&#xD;
             urea nitrogen [BUN] and creatinine) abnormality as per local laboratory normal values&#xD;
             considered clinically significant by the investigator.&#xD;
&#xD;
          -  Any acute or chronic, clinically significant disease, as determined by physical&#xD;
             examination or laboratory screening tests.&#xD;
&#xD;
          -  Any other condition that the investigator judges may interfere with study procedures&#xD;
             (e.g. drawing blood) or findings (e.g. immune response).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joanne Langley, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Canadian Center for Vaccinology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Canadian Center for Vaccinology</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3K 6R8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>July 1, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <last_update_submitted>February 11, 2016</last_update_submitted>
  <last_update_submitted_qc>February 11, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 12, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PAL</keyword>
  <keyword>fluviral</keyword>
  <keyword>healthy volunteer</keyword>
  <keyword>adjuvant</keyword>
  <keyword>TH1 immune response</keyword>
  <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/NCT02188810
org study id: PE1202
nct id: NCT02188810
lead sponsor: 
has dmc: Yes
This is a phase 1, research study is looking at the safety and acceptability of a new vaccine
      adjuvant (immune booster) called PAL when combined with the seasonal flu vaccine (Fluviral)
      to test the safety and effectiveness of new vaccines and medications on healthy volunteers.

      The study will enroll approximately 48 healthy adult participants, and occur over 3 years. In
      the first six months/180 days of the study participants will have visits to the study site
      during which safety and immunogenicity outcomes will be measured. From Day 181 to Year 3,
      participants will be contacted by telephone or email to collect information on any adverse
      events.
This is a phase 1, dose-ranging, randomized (5:1), observer-blind, controlled study of the
      safety and immune response to intramuscular injection of PapMV (Papaya Mosaic Virus) rVLP
      (Recombinant Virus-Like Particles) which is PAL adjuvant, or "PAL" combined with Trivalent
      Influenza Vaccines (TIV) at one of four dose levels of PAL, combined with one of two dose
      levels of TIV, or active control (TIV). The study will enroll approximately 48 healthy adult
      participants, and occur over 3 years. In the first six months/180 days (Epoch 1) of the study
      participants will have visits to the study site during which safety and immunogenicity
      outcomes will be measured. In Epoch 2 (Day 181 to Year 3) participants will be contacted by
      telephone or email to collect unsolicited adverse events.

      This is a controlled clinical trial. The control group will receive the standard dose of TIV,
      0.5 mL, which consists of 15 μg haemagglutinin (HA) of each influenza strain recommended by
      the World Health Organization (WHO) for the 2013-2014 influenza season in the northern
      hemisphere. An active control is used so that the attributable risk of adverse events can be
      estimated, and so that outcome measures can be assessed in a blinded fashion. Only adults in
      stable health will be eligible in order to minimize participant risk. Only non-pregnant
      females of childbearing age are eligible, and they must agree to continue adequate
      contraception for 180 days after injection. Study holding rules and a safety evaluation by a
      Safety Review Committee (SRC) will be in place. The study will follow a staggered
      dose-escalation design, with each of four steps introducing a new dose of the adjuvant (30,
      60, 120 and 240 μg respectively).

      The first dose level of PAL adjuvant FB-631 is 0.5 X 60 µg (i.e., 30 µg), which is half the
      dose that was found to be most immunogenic in animal studies. The adjuvant is co-administered
      with 0.25 mL of TIV, which is half the dose of TIV that is routinely administered to adults
      (i.e. 7.5 μg of each of the three influenza subtypes contained in the vaccine). The next dose
      level is 60µg of FB-631 combined with 0.25 mL TIV. The third dose level is 120 μg of FB-631
      with 0.25 mL TIV. In the fourth and final step the dose of adjuvant is 240 μg of PAL adjuvant
      combined with 0.25 mL TIV (8 participants) or 0.125 mL TIV (i.e. 3.75 μg HA of each influenza
      subtype contained in the vaccine) (8 participants).

      Any safety signal observed in the study will lead to a hold until the decision of Safety
      Review Committee to continue, modify or suspend the conduct of the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Investigator)
measure: Safety
time frame: 3 years
description: The occurrence of adverse events from injection to Day 1095 (36 months/three years, in all participants, in all groups:
measure: Immunogenicity
time frame: 6 months
description: Evaluate the immunogenicity of influenza antigens contained in TIV when combined with PAL adjuvant as measured by haemagglutination inhibition (HAI) titres, pre-injection (Day 0) and post-injection (Days 28, 120 and 180).
measure: Immunogenicity of TIV combined with PAL
time frame: 6 months
description: Immunogenicity of the influenza antigens contained in TIV when combined with PAL adjuvant as measured by IgG and IgG1 antibody directed to influenza A viral nucleoproteins on Days 0, 28, 120 and 180.
measure: Immune responses
time frame: 6 months
description: Describe cellular immune responses to the investigational products as assessed by antigen-secreted interferon-gamma secretion, and interferon-gamma to IL-10 ratio, pre-injection (Day 0) and post-injection (Day 28, Day 120 and Day 180).
measure: Induced immune responses
time frame: 6 months
description: Describe immune responses induced by PAL adjuvant combined with TIV as measured by Granzyme B levels in Peripheral Blood Mononuclear Cells (PBMC), pre-injection (Day 0) and post-injection (Day 28, Day 120 and Day 180).
measure: Solicited and General Adverse Events
time frame: up to 6 months
description: The occurrence of each solicited local and general AE (adverse event), during a 7-day follow-up period after injection (i.e. the day of injection and 6 subsequent days).
measure: Hematological laboratory values
time frame: up to 6 months
description: The occurrence of any hematological (hemoglobin level, WBC (white blood cells), lymphocyte, neutrophil, eosinophil and platelet count) and biochemical (ALT, AST(angiotensin sensitivity test) and creatinine) laboratory abnormality at Day 0 and at Day 7.
measure: Unsolicited Adverse Events
time frame: 3 years
description: The occurrence of any unsolicited AE, during a 28-day follow-up period after injection (i.e. the day of injection and 27 subsequent days), and through to Day 1095. The occurrence of any SAE through to Day 1095.
arm group label: Group 1
arm group type: Active Comparator
description: Single dose of control vaccine (a single dose of 0.5 mL TIV).
arm group label: Group 2
arm group type: Experimental
description: Single dose of the test article (0.25 mL TIV, which is 7.5 μg of each influenza strain with 0.5x PAL, i.e. 30 μg).
arm group label: Group 3
arm group type: Experimental
description: Single dose of the test article (0.25 mL TIV, which is 7.5 μg of each influenza strain with 1x PAL, i.e. 60 μg).
arm group label: Group 4
arm group type: Experimental
description: Single dose of the test article (0.25 mL of TIV which is 7.5 μg of each influenza strain with 2x PAL (i.e., 120 μg).
arm group label: Group 5
arm group type: Experimental
description: Single dose of the test article (0.25 mL of TIV which is 7.5 μg of each influenza strain with 4x PAL (i.e., 240 μg).
arm group label: Group 6
arm group type: Experimental
description: Single dose of the test article (0.125 mL of TIV with 4x PAL i.e., 240 μg).
intervention type: Biological
intervention name: PAL
description: Single dose administered intramuscularly.
arm group label: Group 2
arm group label: Group 3
arm group label: Group 4
arm group label: Group 5
arm group label: Group 6
other name: PapMV Adjuvant Long lasting immune response
other name: FB-631
intervention type: Biological
intervention name: TIV
description: Single dose administered intramuscularly .
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
arm group label: Group 4
arm group label: Group 5
arm group label: Group 6
other name: Trivalent Influenza Vaccines
other name: Fluviral
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Joanne Langley, M.D.
role: Principal Investigator
affiliation: Canadian Center for Vaccinology
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Vaccines