<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/NCT03816878</url>
  </required_header>
  <id_info>
    <org_study_id>CIR 327</org_study_id>
    <nct_id>NCT03816878</nct_id>
  </id_info>
  <brief_title>Immunogenicity and Safety Study of Inactivated Subunit H5N1 Influenza Vaccine in Prior Recipients of Live Attenuated H2N2, H6N1 and H9N2 Influenza Vaccines and in H5N1 and Live Attenuated Vaccine Naïve Individuals</brief_title>
  <official_title>An Exploration of a Prime-Boost Approach for Universal Influenza Vaccination: Immunogenicity and Safety Study of Inactivated Subunit H5N1 Influenza Vaccine in Prior Recipients of Live Attenuated H2N2, H6N1 and H9N2 Influenza Vaccines and in H5N1 and Live Attenuated Vaccine Naïve Individuals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the immunogenicity and safety of inactivated subunit&#xD;
      H5N1 influenza vaccine in individuals who have previously received live attenuated H2N2,&#xD;
      H6N1, or H9N2 influenza vaccine, as well as in individuals who have never previously received&#xD;
      H5N1 or other pandemic live attenuated influenza vaccines.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will evaluate the immunogenicity and safety of inactivated subunit H5N1 influenza&#xD;
      vaccine in individuals who have previously received live attenuated H2N2, H6N1, or H9N2&#xD;
      influenza vaccine, as well as in individuals who have never previously received H5N1 or other&#xD;
      pandemic live attenuated influenza vaccines (pLAIVs).&#xD;
&#xD;
      Participants will be enrolled in two cohorts. Cohort 1 will include participants who received&#xD;
      two doses of live attenuated H2N2, H6N1, or H9N2 influenza vaccine during a prior Center for&#xD;
      Immunization Research (CIR) study; Cohort 2 will include participants who have never&#xD;
      previously received a pLAIV. Participants in both cohorts will receive one dose of H5N1 pISV&#xD;
      vaccine by injection at Day 0.&#xD;
&#xD;
      Participants will attend study visits on Days 0, 7, 14, 28, 56, 90, and 360. Study visits may&#xD;
      include a physical examination, medical history, and blood and urine collection. All&#xD;
      participants will be followed for approximately 360 days after receiving the H5N1 pISV&#xD;
      vaccine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 8, 2019</start_date>
  <completion_date type="Actual">March 17, 2020</completion_date>
  <primary_completion_date type="Actual">April 18, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fold rise in titer of anti-group 1 stalk-antibodies in recipients of the pandemic live attenuated influenza vaccines (pLAIVs) (H2N2, H6N1 and H9N2) compared to the control pLAIV-naïve cohort</measure>
    <time_frame>Measured through Day 360</time_frame>
    <description>As measured by enzyme-linked immunosorbent assay (ELISA) and microneutralization assay (MN) using the chimeric cH6/N1 probe</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of vaccine-related adverse events in the recipients of the pLAIV compared to the control cohort</measure>
    <time_frame>Measured through Day 90</time_frame>
    <description>Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>Cohort 1: pLAIV Recipients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have received the pandemic live attenuated influenza vaccines (pLAIVs) H2N2, H6N1, or H9N2 during a previous CIR study will receive a single dose of 0.5 mL H5N1 pISV vaccine at Day 0.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: pLAIV Naive</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have never previously received a pLAIV will receive one dose of 0.5 mL H5N1 pISV vaccine at Day 0.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>H5N1 pISV</intervention_name>
    <description>Administered as an intramuscular (IM) injection</description>
    <arm_group_label>Cohort 1: pLAIV Recipients</arm_group_label>
    <arm_group_label>Cohort 2: pLAIV Naive</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult males and non-pregnant females between 18 years and 60 years of age inclusive.&#xD;
&#xD;
          -  General good health, without significant medical illness, physical examination&#xD;
             findings, or significant laboratory abnormalities as determined by the investigator.&#xD;
&#xD;
          -  Available for the duration of the trial.&#xD;
&#xD;
          -  Able to demonstrate understanding of key study concepts, study rationale, and study&#xD;
             participation requirements by scoring greater than or equal to 70% on a written&#xD;
             comprehension assessment in 3 or fewer attempts.&#xD;
&#xD;
          -  Willingness to participate in the study as evidenced by signing the informed consent&#xD;
             document.&#xD;
&#xD;
          -  Willingness to allow storage and testing of laboratory samples for future research.&#xD;
&#xD;
          -  Received 2 doses of live attenuated H2N2, H6N1, or H9N2 vaccine in a prior trial&#xD;
             (Cohort 1) or H2N2, H6N1 and H9N2 naïve (Cohort 2)&#xD;
&#xD;
          -  Willingness to forego seasonal influenza virus vaccination from 1 month before&#xD;
             vaccination until 3 months after vaccination.&#xD;
&#xD;
          -  Female subjects of childbearing potential must agree to have used effective birth&#xD;
             control methods beginning at least one month prior to vaccination, and continuing with&#xD;
             'per label/fully effective use' for the chosen method for duration of the study, from&#xD;
             amongst these:&#xD;
&#xD;
               -  pharmacologic/hormonal contraceptives, including oral, parenteral, subcutaneous,&#xD;
                  and transcutaneous delivery;&#xD;
&#xD;
               -  condoms with spermicide;&#xD;
&#xD;
               -  diaphragm with spermicide;&#xD;
&#xD;
               -  intrauterine device;&#xD;
&#xD;
               -  absolute abstinence from heterosexual intercourse as a matter of normal preferred&#xD;
                  lifestyle;&#xD;
&#xD;
               -  or must be surgically sterile or must be age 50 AND have had no menses at all for&#xD;
                  at least one full year.&#xD;
&#xD;
               -  All females must provide urine for pregnancy testing prior to enrollment&#xD;
                  (immediately prior vaccination), as well as a statement of menstrual history and&#xD;
                  a summary of all potentially reproductive sexual activity for the month prior to&#xD;
                  vaccination, and at each study contact throughout the study, and report known or&#xD;
                  suspected pregnancy immediately.&#xD;
&#xD;
          -  Willingness to refrain from blood donation during the course of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy as determined by a positive test for human choriogonadotropin (beta-HCG), an&#xD;
             indicator of pregnancy or history of recent unprotected intercourse in a woman of&#xD;
             reproductive capacity.&#xD;
&#xD;
          -  Currently breast-feeding.&#xD;
&#xD;
          -  Evidence of clinically significant neurologic, cardiac, pulmonary, hematologic,&#xD;
             hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination,&#xD;
             and/or laboratory studies.&#xD;
&#xD;
          -  Behavioral or cognitive impairment or psychiatric disease that in the opinion of the&#xD;
             investigator affects the ability of the subject to understand and cooperate with the&#xD;
             study protocol.&#xD;
&#xD;
          -  Have medical, occupational, or family problems as a result of alcohol or illicit drug&#xD;
             use during the past 12 months.&#xD;
&#xD;
          -  Other condition that in the opinion of the investigator would jeopardize the safety or&#xD;
             rights of a subject participating in the trial or would render the subject unable to&#xD;
             comply with the protocol.&#xD;
&#xD;
          -  History of anaphylaxis in response to any vaccine or vaccine component.&#xD;
&#xD;
          -  History of life-threatening reaction to prior influenza vaccine.&#xD;
&#xD;
          -  Positive enzyme-linked immunosorbent assay (ELISA) and confirmatory test for human&#xD;
             immunodeficiency virus type 1 (HIV-1).&#xD;
&#xD;
          -  Positive ELISA and confirmatory test (e.g., HCV RNA PCR) for hepatitis C virus (HCV).&#xD;
&#xD;
          -  Positive hepatitis B virus surface antigen (HBsAg) by ELISA.&#xD;
&#xD;
          -  Known immunodeficiency syndrome or history suggestive of impaired immune function.&#xD;
&#xD;
          -  History of Guillain-Barré syndrome.&#xD;
&#xD;
          -  Use of chronic oral or intravenous administration (greater than or equal to 14 days)&#xD;
             of immunosuppressive doses of steroids, i.e., prednisone greater than 10 mg per day,&#xD;
             immunosuppressants or other immune-modifying drugs within 30 days of starting this&#xD;
             study.&#xD;
&#xD;
          -  Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to&#xD;
             study vaccination.&#xD;
&#xD;
          -  Receipt of blood or blood-derived products (including immunoglobulin) within 6 months&#xD;
             prior to study vaccination.&#xD;
&#xD;
          -  Receipt of another investigational vaccine or drug within 30 days prior to study&#xD;
             vaccination.&#xD;
&#xD;
          -  In addition to the above, participants in Cohort 1 (pandemic live attenuated influenza&#xD;
             vaccine [pLAIV] recipients) and Cohort 2 (naïve cohort) must also not experience any&#xD;
             of the following:&#xD;
&#xD;
               -  Previous enrollment in an H5N1 influenza vaccine trial.&#xD;
&#xD;
          -  Participants in Cohort 2 (naïve cohort) will be excluded if they are:&#xD;
&#xD;
               -  Seropositive to the H5N1 influenza A virus (serum hemagglutination inhibition&#xD;
                  assay (HAI) titer greater than 1:8).&#xD;
&#xD;
               -  Have previously received an investigational live attenuated influenza vaccine&#xD;
                  (LAIV) in another study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kawsar R. Talaat, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>February 15, 2022</last_update_submitted>
  <last_update_submitted_qc>February 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
    <mesh_term>Influenza in Birds</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/78/NCT03816878/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03816878
org study id: CIR 327
nct id: NCT03816878
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the immunogenicity and safety of inactivated subunit
      H5N1 influenza vaccine in individuals who have previously received live attenuated H2N2,
      H6N1, or H9N2 influenza vaccine, as well as in individuals who have never previously received
      H5N1 or other pandemic live attenuated influenza vaccines.
This study will evaluate the immunogenicity and safety of inactivated subunit H5N1 influenza
      vaccine in individuals who have previously received live attenuated H2N2, H6N1, or H9N2
      influenza vaccine, as well as in individuals who have never previously received H5N1 or other
      pandemic live attenuated influenza vaccines (pLAIVs).

      Participants will be enrolled in two cohorts. Cohort 1 will include participants who received
      two doses of live attenuated H2N2, H6N1, or H9N2 influenza vaccine during a prior Center for
      Immunization Research (CIR) study; Cohort 2 will include participants who have never
      previously received a pLAIV. Participants in both cohorts will receive one dose of H5N1 pISV
      vaccine by injection at Day 0.

      Participants will attend study visits on Days 0, 7, 14, 28, 56, 90, and 360. Study visits may
      include a physical examination, medical history, and blood and urine collection. All
      participants will be followed for approximately 360 days after receiving the H5N1 pISV
      vaccine.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Fold rise in titer of anti-group 1 stalk-antibodies in recipients of the pandemic live attenuated influenza vaccines (pLAIVs) (H2N2, H6N1 and H9N2) compared to the control pLAIV-naïve cohort
time frame: Measured through Day 360
description: As measured by enzyme-linked immunosorbent assay (ELISA) and microneutralization assay (MN) using the chimeric cH6/N1 probe
measure: Number of vaccine-related adverse events in the recipients of the pLAIV compared to the control cohort
time frame: Measured through Day 90
description: Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017
arm group label: Cohort 1: pLAIV Recipients
arm group type: Experimental
description: Participants who have received the pandemic live attenuated influenza vaccines (pLAIVs) H2N2, H6N1, or H9N2 during a previous CIR study will receive a single dose of 0.5 mL H5N1 pISV vaccine at Day 0.
arm group label: Cohort 2: pLAIV Naive
arm group type: Experimental
description: Participants who have never previously received a pLAIV will receive one dose of 0.5 mL H5N1 pISV vaccine at Day 0.
intervention type: Biological
intervention name: H5N1 pISV
description: Administered as an intramuscular (IM) injection
arm group label: Cohort 1: pLAIV Recipients
arm group label: Cohort 2: pLAIV Naive
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kawsar R. Talaat, MD
role: Principal Investigator
affiliation: Johns Hopkins Bloomberg School of Public Health
facility: 
country: United States
responsible party type: Sponsor
mesh term: Influenza, Human
mesh term: Influenza in Birds
provided document: 