<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/NCT03014310</url>
  </required_header>
  <id_info>
    <org_study_id>15-0066</org_study_id>
    <secondary_id>HHSN272201300015I</secondary_id>
    <nct_id>NCT03014310</nct_id>
  </id_info>
  <brief_title>H5N8 Mix and Match With or Without AS03 or MF59 in Healthy Adults: Immunology</brief_title>
  <official_title>A Phase I Cohort-Randomized, Double-Blind, Controlled Trial in Healthy Adults to Assess the Safety, Reactogenicity, and Immunogenicity of a Monovalent Inactivated Influenza A/H5N8 Virus Vaccine Administered Intramuscularly at Different Dosages Given With or Without AS03 or MF59 Adjuvants: Assessment of Immunological Responses and Lymphocyte Interplay</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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase I cohort-randomized, double-blind, controlled trial designed to assess the&#xD;
      safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H5N8 virus&#xD;
      vaccine administered at different dosages (3.75 and 15 mcg of HA per dose) given with or&#xD;
      without AS03 or MF59 adjuvants. This study will be conducted at 6 sites and enroll 150 (up to&#xD;
      380) males and non-pregnant females, 19 to 64 years old, inclusive who are in good health and&#xD;
      meet all eligibility criteria. The entire study duration is approximately 24 months and each&#xD;
      subject participation duration is approximately 13 months. The primary objectives are: 1) To&#xD;
      assess the safety and reactogenicity of a monovalent inactivated influenza A/H5N8 virus&#xD;
      vaccine following receipt of two doses administered intramuscularly at different dosages&#xD;
      (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants approximately&#xD;
      21 days apart. 2) To assess the serum HAI and Neut antibody responses to a monovalent&#xD;
      inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered&#xD;
      intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without&#xD;
      AS03 or MF59 adjuvants approximately 21 days apart.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I cohort-randomized, double-blind, controlled trial designed to assess the&#xD;
      safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H5N8 virus&#xD;
      vaccine manufactured by bioCSL administered at different dosages (3.75 and 15 mcg of HA per&#xD;
      dose) given with or without AS03 or MF59 adjuvants manufactured by GlaxoSmithKline&#xD;
      Biologicals (GSK) and Novartis Vaccines and Diagnostics (NVD), respectively. This study will&#xD;
      be conducted at 6 VTEU sites and enroll 150 (up to 380) males and non-pregnant females, 19 to&#xD;
      64 years old, inclusive who are in good health and meet all eligibility criteria. The entire&#xD;
      study duration is approximately 24 months and subject participation duration is approximately&#xD;
      13 months. Subjects will be enrolled in one of two cohorts, and within each cohort subjects&#xD;
      will be randomized in a 2:2:1 ratio. Subjects in Cohort 1 will be randomly assigned to 1 of 3&#xD;
      treatment arms to receive two doses of the A/H5N8 vaccine at varying antigen dosages (3.75 or&#xD;
      15 mcg HA) with AS03 (30-76 subjects per treatment arm), or to a comparator arm receiving two&#xD;
      doses of the A/H5N8 vaccine (15 mcg HA) without adjuvant (15-38 subjects). Subjects in Cohort&#xD;
      2 will be randomly assigned to 1 of 3 treatment arms to receive two doses of the A/H5N8&#xD;
      vaccine at varying antigen dosages (3.75 or 15 mcg HA) with MF59 (30-76 subjects per&#xD;
      treatment arm), or to a comparator arm receiving two doses of the A/H5N8 vaccine (15 mcg HA)&#xD;
      without adjuvant (15-38 subjects). All subjects will receive the same dosage of vaccine with&#xD;
      or without the same adjuvant at both of their first and second study vaccinations, with the&#xD;
      exception that subjects in Cohort 1 who do not receive Vaccination 2 prior to February 28,&#xD;
      2017 will receive a second unadjuvanted vaccination with the same antigen dosage as their&#xD;
      randomized assignment. All doses will be administered intramuscularly approximately 21 days&#xD;
      apart. Primary objectives are: 1) To assess the safety and reactogenicity of a monovalent&#xD;
      inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered&#xD;
      intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without&#xD;
      AS03 or MF59 adjuvants approximately 21 days apart. 2) To assess the serum HAI and Neut&#xD;
      antibody responses to a monovalent inactivated influenza A/H5N8 virus vaccine following&#xD;
      receipt of two doses administered intramuscularly at different dosages (3.75 and 15 mcg of HA&#xD;
      per dose) given with or without AS03 or MF59 adjuvants approximately 21 days apart. Secondary&#xD;
      objectives are: 1) To assess study unsolicited non-serious AEs following receipt of two doses&#xD;
      of a monovalent inactivated influenza A/H5N8 virus vaccine administered intramuscularly at&#xD;
      different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59&#xD;
      adjuvants approximately 21 days apart. 2) To assess medically-attended adverse events&#xD;
      (MAAEs), including new-onset chronic medical conditions (NOCMCs), potentially immune-mediated&#xD;
      medical conditions (PIMMCs), and all serious adverse events (SAEs) following receipt of two&#xD;
      doses of a monovalent inactivated influenza A/H5N8 virus vaccine administered intramuscularly&#xD;
      at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59&#xD;
      adjuvants approximately 21 days apart. 3) To assess the serum HAI and Neut antibody responses&#xD;
      to a monovalent inactivated influenza A/H5N8 virus vaccine following receipt of one dose&#xD;
      administered intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with&#xD;
      or without AS03 or MF59 adjuvants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 9, 2017</start_date>
  <completion_date type="Actual">December 19, 2018</completion_date>
  <primary_completion_date type="Actual">December 19, 2018</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Geometric Mean Titers of Neut antibodies against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 43</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric Mean Titers of serum HAI antibodies against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 43</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of clinical safety laboratory AEs</measure>
    <time_frame>Day 1-9</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of clinical safety laboratory AEs</measure>
    <time_frame>Day 22-30</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of solicited injection site and systemic reactogenicity events</measure>
    <time_frame>Day 1-9</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of solicited injection site and systemic reactogenicity events</measure>
    <time_frame>Day 22-30</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of study vaccine-related SAEs</measure>
    <time_frame>Day 1-387</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects achieving HAI seroconversion against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 43</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects achieving Neut seroconversion against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 43</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects achieving serum HAI antibody titer of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 43</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects achieving serum Neut antibody titer of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 43</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Geometric Mean Titers of Neut antibodies against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 1, 8, 22, 29, 43, 202, and 387</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric Mean Titers of serum HAI antibodies against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 1, 8, 22, 29, 43, 202, and 387</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of all serious adverse events (SAEs), regardless of the assessment of relatedness</measure>
    <time_frame>Day 1-387</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness</measure>
    <time_frame>Day 1-22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness</measure>
    <time_frame>Day 22-43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of MAAEs, including NOCMCs, and PIMMCs</measure>
    <time_frame>Day 1-387</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of study vaccine-related unsolicited non-serious AEs</measure>
    <time_frame>Day 1-22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of study vaccine-related unsolicited non-serious AEs</measure>
    <time_frame>Day 22-43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving HAI seroconversion against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 8, 22, 29, 43, 202, and 387</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving Neut antibody titers of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 1, 8, 22, 29, 43, 202, and 387</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving Neut seroconversion against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 8, 22, 29, 43, 202, and 387</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving serum HAI antibody titers of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine</measure>
    <time_frame>Day 1, 8, 22, 29, 43, 202, and 387</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">388</enrollment>
  <condition>Avian Influenza</condition>
  <arm_group>
    <arm_group_label>Arm 1: 3.75 mcg A/H5N8 + AS03</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3.75 mcg A/H5N8 + AS03 given IM on Day 1 and 22, n=30</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: 15 mcg A/H5N8 + AS03</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>15 mcg A/H5N8 + AS03 given IM on Day 1 and 22, n=30</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3: 15 mcg A/H5N8 unadjuvanted</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>15 mcg A/H5N8 unadjuvanted given IM on Day 1 and 22, n=15</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 4: 3.75 mcg A/H5N8 + MF59</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3.75 mcg A/H5N8 + MF59 given IM on Day 1 and 22, n=30</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 5: 15 mcg A/H5N8 + MF59</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>15 mcg A/H5N8 + MF59 given IM on Day 1 and 22, n=30</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 6: 15 mcg A/H5N8 unadjuvanted</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>15 mcg A/H5N8 unadjuvanted given IM on Day and 22, n=15</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AS03</intervention_name>
    <description>AS03 oil-in-water emulsion adjuvant.</description>
    <arm_group_label>Arm 1: 3.75 mcg A/H5N8 + AS03</arm_group_label>
    <arm_group_label>Arm 2: 15 mcg A/H5N8 + AS03</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MF59 adjuvant</intervention_name>
    <description>Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion.</description>
    <arm_group_label>Arm 4: 3.75 mcg A/H5N8 + MF59</arm_group_label>
    <arm_group_label>Arm 5: 15 mcg A/H5N8 + MF59</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Monovalent Influenza A/H5N8 vaccine</intervention_name>
    <description>Monovalent inactivated influenza A/H5N8 virus vaccine for IM injection. prepared from influenza virus propagated in chicken egg fluid using seed virus prepared from the candidate vaccine virus (CVV), influenza virus A/gyrfalcon/Washington/41088-6/2014(H5N8)-PR8-IDCDC-RG43A (abbreviated as IDCDC-RG43A).</description>
    <arm_group_label>Arm 1: 3.75 mcg A/H5N8 + AS03</arm_group_label>
    <arm_group_label>Arm 2: 15 mcg A/H5N8 + AS03</arm_group_label>
    <arm_group_label>Arm 3: 15 mcg A/H5N8 unadjuvanted</arm_group_label>
    <arm_group_label>Arm 4: 3.75 mcg A/H5N8 + MF59</arm_group_label>
    <arm_group_label>Arm 5: 15 mcg A/H5N8 + MF59</arm_group_label>
    <arm_group_label>Arm 6: 15 mcg A/H5N8 unadjuvanted</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provide written informed consent prior to initiation of any study procedures.&#xD;
&#xD;
          2. Are able to understand and comply with planned study procedures and be available for&#xD;
             all study visits.&#xD;
&#xD;
          3. Are males or non-pregnant females, 19 to 64 years old, inclusive.&#xD;
&#xD;
          4. Are in good health.&#xD;
&#xD;
             -As determined by medical history and physical examination to evaluate acute or&#xD;
             currently ongoing chronic medical diagnoses or conditions, defined as those that have&#xD;
             been present for at least 90 days, that would affect the assessment of the safety of&#xD;
             subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or&#xD;
             conditions should be stable for the last 60 days. This includes no change in chronic&#xD;
             prescription medication, dose, or frequency as a result of deterioration of the&#xD;
             chronic medical diagnosis or condition in the 60 days prior to enrollment. Any&#xD;
             prescription change that is due to change of health care provider, insurance company,&#xD;
             etc., or that is done for financial reasons, as long as in the same class of&#xD;
             medication, will not be considered a deviation of this inclusion criterion. Any change&#xD;
             in prescription medication due to improvement of a disease outcome, as determined by&#xD;
             the site principal investigator or appropriate sub-investigator, will not be&#xD;
             considered a deviation of this inclusion criterion. Subjects may be on chronic or as&#xD;
             needed (prn) medications if, in the opinion of the site principal investigator or&#xD;
             appropriate sub-investigator, they pose no additional risk to subject safety or&#xD;
             assessment of reactogenicity and immunogenicity and do not indicate a worsening of&#xD;
             medical diagnosis or condition. Similarly, medication changes subsequent to enrollment&#xD;
             and study vaccination are acceptable provided there was no deterioration in the&#xD;
             subject's chronic medical condition that necessitated a medication change, and there&#xD;
             is no additional risk to the subject or interference with the evaluation of responses&#xD;
             to study vaccination. Note: Topical, nasal, and inhaled medications (with the&#xD;
             exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria&#xD;
             (see Section 5.1.2), herbals, vitamins, and supplements are permitted.&#xD;
&#xD;
          5. Oral temperature is less than 100.0°F.&#xD;
&#xD;
          6. Pulse is 50 to 115 bpm, inclusive.&#xD;
&#xD;
          7. Systolic blood pressure is 85 to 150 mmHg, inclusive.&#xD;
&#xD;
          8. Diastolic blood pressure is 55 to 95 mmHg, inclusive.&#xD;
&#xD;
          9. Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour.&#xD;
&#xD;
         10. Alanine aminotransferase (ALT) is less than 44 IU/L for females or is less than 61&#xD;
             IU/L for males.&#xD;
&#xD;
         11. Creatinine is less than 1.11 mg/dL for females or is less than 1.38 mg/dL for males.&#xD;
&#xD;
         12. White blood cells (WBC) are greater than 3.9 x10^3/µL and less than 10.6 x10^3/µL.&#xD;
&#xD;
         13. Hemoglobin (Hgb) is greater than 11.4 g/dL for females or is greater than 12.4 g/dL&#xD;
             for males.&#xD;
&#xD;
         14. Platelets are greater than 139 x10^3/µL and less than 416 x10^3/µL.&#xD;
&#xD;
         15. Total bilirubin is less than 1.3 mg/dL.&#xD;
&#xD;
         16. Women of childbearing potential must use an acceptable contraception method from 30&#xD;
             days before first study vaccination until 60 days after last study vaccination.&#xD;
&#xD;
               -  Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or&#xD;
                  successful Essure® placement (permanent, non-surgical, non-hormonal&#xD;
                  sterilization) with documented radiological confirmation test at least 90 days&#xD;
                  after the procedure, and still menstruating or &lt; 1 year of the last menses if&#xD;
                  menopausal.&#xD;
&#xD;
                    -  Includes, but is not limited to, non-male sexual relationships, abstinence&#xD;
                       from sexual intercourse with a male partner, monogamous relationship with&#xD;
                       vasectomized partner who has been vasectomized for 180 days or more prior to&#xD;
                       the subject receiving the first study vaccination, barrier methods such as&#xD;
                       condoms or diaphragms with spermicide or foam, effective intrauterine&#xD;
                       devices, NuvaRing®, and licensed hormonal methods such as implants,&#xD;
                       injectables, or oral contraceptives (&quot;the pill).&#xD;
&#xD;
         17. Women of childbearing potential must have a negative urine or serum pregnancy test&#xD;
             within 24 hours prior to study vaccination.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have an acute illness, as determined by the site principal investigator or appropriate&#xD;
             sub-investigator, within 72 hours prior to study vaccination.&#xD;
&#xD;
             -An acute illness which is nearly resolved with only minor residual symptoms remaining&#xD;
             is allowable if, in the opinion of the site principal investigator or appropriate&#xD;
             sub-investigator, the residual symptoms will not interfere with the ability to assess&#xD;
             safety parameters as required by the protocol.&#xD;
&#xD;
          2. Have any medical disease or condition that, in the opinion of the site principal&#xD;
             investigator or appropriate sub-investigator, is a contraindication to study&#xD;
             participation.&#xD;
&#xD;
             -Including acute or chronic medical disease or condition, defined as persisting for at&#xD;
             least 90 days, that would place the subject at an unacceptable risk of injury, render&#xD;
             the subject unable to meet the requirements of the protocol, or may interfere with the&#xD;
             evaluation of responses or the subject's successful completion of this trial.&#xD;
&#xD;
          3. Have immunosuppression as a result of an underlying illness or treatment, or use of&#xD;
             anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study&#xD;
             vaccination.&#xD;
&#xD;
          4. Have known active neoplastic disease or a history of any hematologic malignancy.&#xD;
             Non-melanoma skin cancers are permitted.&#xD;
&#xD;
          5. Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.&#xD;
&#xD;
          6. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based&#xD;
             adjuvants, or other components of the study vaccine.&#xD;
&#xD;
          7. Have a history of severe reactions following previous immunization with licensed or&#xD;
             unlicensed influenza vaccines.&#xD;
&#xD;
          8. Have a personal or family history of narcolepsy.&#xD;
&#xD;
          9. Have a history of Guillain-Barré syndrome.&#xD;
&#xD;
         10. Have a history of convulsions or encephalomyelitis within 90 days prior to study&#xD;
             vaccination.&#xD;
&#xD;
         11. Have a history of PIMMCs.&#xD;
&#xD;
             -Refer to Appendix B: List of Potentially Immune-Mediated Medical Conditions.&#xD;
&#xD;
         12. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.&#xD;
&#xD;
         13. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other&#xD;
             psychiatric diagnosis that may interfere with subject compliance or safety&#xD;
             evaluations.&#xD;
&#xD;
         14. Have been hospitalized for psychiatric illness, history of suicide attempt, or&#xD;
             confinement for danger to self or others within 10 years prior to study vaccination.&#xD;
&#xD;
         15. Have taken oral or parenteral (including intraarticular) corticosteroids of any dose&#xD;
             within 30 days prior to study vaccination.&#xD;
&#xD;
         16. Have taken high-dose inhaled corticosteroids within 30 days prior to study&#xD;
             vaccination. High-dose defined as &gt; 840 mcg/day of beclomethasone dipropionate CFC or&#xD;
             equivalent.&#xD;
&#xD;
         17. Received a licensed live vaccine within 30 days prior to the first study vaccination,&#xD;
             or plan to receive a licensed live vaccine within 30 days before or after each study&#xD;
             vaccination.&#xD;
&#xD;
         18. Received a licensed inactivated vaccine within 14 days prior to the first study&#xD;
             vaccination, or plan to receive a licensed inactivated vaccine within 14 days before&#xD;
             or after each study vaccination.&#xD;
&#xD;
         19. Received immunoglobulin or other blood products (with exception of Rho D&#xD;
             immunoglobulin) within 90 days prior to study vaccination.&#xD;
&#xD;
         20. Received an experimental agent within 30 days prior to the first study vaccination, or&#xD;
             expect to receive an experimental agent during the 13-month trial-reporting period.&#xD;
&#xD;
             -Including vaccine, drug, biologic, device, blood product, or medication.&#xD;
&#xD;
             --Other than from participation in this trial.&#xD;
&#xD;
         21. Are participating or plan to participate in another clinical trial with an&#xD;
             interventional agent that will be received during the 13-month trial-reporting period.&#xD;
&#xD;
             -Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or&#xD;
             medication.&#xD;
&#xD;
         22. Received or plan to receive an influenza A/H5 vaccine* or have a history of influenza&#xD;
             A/H5 virus actual or potential exposure or infection prior to the first study&#xD;
             vaccination.&#xD;
&#xD;
             *And assigned to a group receiving influenza A/H5 vaccine, does not apply to&#xD;
             documented placebo recipients.&#xD;
&#xD;
         23. Occupational exposure to or substantial direct physical contact with birds in the past&#xD;
             year and through the 21 days after the second study vaccination.&#xD;
&#xD;
             -Exposure to free range chickens in the yard does warrant exclusion. Casual contact&#xD;
             with birds at petting zoos or county or state fairs or having pet birds does not&#xD;
             exclude subjects from study participation.&#xD;
&#xD;
         24. Female subjects who are breastfeeding or plan to breastfeed at any given time from the&#xD;
             first study vaccination until 30 days after the last study vaccination.&#xD;
&#xD;
         25. Plan to travel outside the US (continental US, Hawaii, and Alaska) from enrollment&#xD;
             through 21 days after the second study vaccination.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Emory Children's Center - Pediatric Infectious Diseases</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322-1014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Baltimore - School of Medicine - Medicine</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201-1509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Louis University - Center for Vaccine Development</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63104-1015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Human Vaccine Institute - Duke Vaccine and Trials Unit</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center - Infectious Diseases</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229-3039</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232-2573</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Medical Branch - Sealy Center for Vaccine Development (SCVD)</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555-1121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>March 19, 2020</last_update_submitted>
  <last_update_submitted_qc>March 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>A/H5N8</keyword>
  <keyword>Adjuvants</keyword>
  <keyword>AS03</keyword>
  <keyword>Inactivated</keyword>
  <keyword>Influenza</keyword>
  <keyword>MF59</keyword>
  <keyword>Monovalent</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
    <mesh_term>Influenza in Birds</mesh_term>
  </condition_browse>
  <!-- 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/NCT03014310
org study id: 15-0066
secondary id: HHSN272201300015I
nct id: NCT03014310
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a Phase I cohort-randomized, double-blind, controlled trial designed to assess the
      safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H5N8 virus
      vaccine administered at different dosages (3.75 and 15 mcg of HA per dose) given with or
      without AS03 or MF59 adjuvants. This study will be conducted at 6 sites and enroll 150 (up to
      380) males and non-pregnant females, 19 to 64 years old, inclusive who are in good health and
      meet all eligibility criteria. The entire study duration is approximately 24 months and each
      subject participation duration is approximately 13 months. The primary objectives are: 1) To
      assess the safety and reactogenicity of a monovalent inactivated influenza A/H5N8 virus
      vaccine following receipt of two doses administered intramuscularly at different dosages
      (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants approximately
      21 days apart. 2) To assess the serum HAI and Neut antibody responses to a monovalent
      inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered
      intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without
      AS03 or MF59 adjuvants approximately 21 days apart.
This is a Phase I cohort-randomized, double-blind, controlled trial designed to assess the
      safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H5N8 virus
      vaccine manufactured by bioCSL administered at different dosages (3.75 and 15 mcg of HA per
      dose) given with or without AS03 or MF59 adjuvants manufactured by GlaxoSmithKline
      Biologicals (GSK) and Novartis Vaccines and Diagnostics (NVD), respectively. This study will
      be conducted at 6 VTEU sites and enroll 150 (up to 380) males and non-pregnant females, 19 to
      64 years old, inclusive who are in good health and meet all eligibility criteria. The entire
      study duration is approximately 24 months and subject participation duration is approximately
      13 months. Subjects will be enrolled in one of two cohorts, and within each cohort subjects
      will be randomized in a 2:2:1 ratio. Subjects in Cohort 1 will be randomly assigned to 1 of 3
      treatment arms to receive two doses of the A/H5N8 vaccine at varying antigen dosages (3.75 or
      15 mcg HA) with AS03 (30-76 subjects per treatment arm), or to a comparator arm receiving two
      doses of the A/H5N8 vaccine (15 mcg HA) without adjuvant (15-38 subjects). Subjects in Cohort
      2 will be randomly assigned to 1 of 3 treatment arms to receive two doses of the A/H5N8
      vaccine at varying antigen dosages (3.75 or 15 mcg HA) with MF59 (30-76 subjects per
      treatment arm), or to a comparator arm receiving two doses of the A/H5N8 vaccine (15 mcg HA)
      without adjuvant (15-38 subjects). All subjects will receive the same dosage of vaccine with
      or without the same adjuvant at both of their first and second study vaccinations, with the
      exception that subjects in Cohort 1 who do not receive Vaccination 2 prior to February 28,
      2017 will receive a second unadjuvanted vaccination with the same antigen dosage as their
      randomized assignment. All doses will be administered intramuscularly approximately 21 days
      apart. Primary objectives are: 1) To assess the safety and reactogenicity of a monovalent
      inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered
      intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without
      AS03 or MF59 adjuvants approximately 21 days apart. 2) To assess the serum HAI and Neut
      antibody responses to a monovalent inactivated influenza A/H5N8 virus vaccine following
      receipt of two doses administered intramuscularly at different dosages (3.75 and 15 mcg of HA
      per dose) given with or without AS03 or MF59 adjuvants approximately 21 days apart. Secondary
      objectives are: 1) To assess study unsolicited non-serious AEs following receipt of two doses
      of a monovalent inactivated influenza A/H5N8 virus vaccine administered intramuscularly at
      different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59
      adjuvants approximately 21 days apart. 2) To assess medically-attended adverse events
      (MAAEs), including new-onset chronic medical conditions (NOCMCs), potentially immune-mediated
      medical conditions (PIMMCs), and all serious adverse events (SAEs) following receipt of two
      doses of a monovalent inactivated influenza A/H5N8 virus vaccine administered intramuscularly
      at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59
      adjuvants approximately 21 days apart. 3) To assess the serum HAI and Neut antibody responses
      to a monovalent inactivated influenza A/H5N8 virus vaccine following receipt of one dose
      administered intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with
      or without AS03 or MF59 adjuvants.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Geometric Mean Titers of Neut antibodies against the A/H5N8 antigen contained in the study vaccine
time frame: Day 43
measure: Geometric Mean Titers of serum HAI antibodies against the A/H5N8 antigen contained in the study vaccine
time frame: Day 43
measure: Occurrence of clinical safety laboratory AEs
time frame: Day 1-9
measure: Occurrence of clinical safety laboratory AEs
time frame: Day 22-30
measure: Occurrence of solicited injection site and systemic reactogenicity events
time frame: Day 1-9
measure: Occurrence of solicited injection site and systemic reactogenicity events
time frame: Day 22-30
measure: Occurrence of study vaccine-related SAEs
time frame: Day 1-387
measure: Percentage of subjects achieving HAI seroconversion against the A/H5N8 antigen contained in the study vaccine
time frame: Day 43
measure: Percentage of subjects achieving Neut seroconversion against the A/H5N8 antigen contained in the study vaccine
time frame: Day 43
measure: Percentage of subjects achieving serum HAI antibody titer of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine
time frame: Day 43
measure: Percentage of subjects achieving serum Neut antibody titer of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine
time frame: Day 43
measure: Geometric Mean Titers of Neut antibodies against the A/H5N8 antigen contained in the study vaccine
time frame: Day 1, 8, 22, 29, 43, 202, and 387
measure: Geometric Mean Titers of serum HAI antibodies against the A/H5N8 antigen contained in the study vaccine
time frame: Day 1, 8, 22, 29, 43, 202, and 387
measure: Occurrence of all serious adverse events (SAEs), regardless of the assessment of relatedness
time frame: Day 1-387
measure: Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness
time frame: Day 1-22
measure: Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness
time frame: Day 22-43
measure: Occurrence of MAAEs, including NOCMCs, and PIMMCs
time frame: Day 1-387
measure: Occurrence of study vaccine-related unsolicited non-serious AEs
time frame: Day 1-22
measure: Occurrence of study vaccine-related unsolicited non-serious AEs
time frame: Day 22-43
measure: Percentage of subjects achieving HAI seroconversion against the A/H5N8 antigen contained in the study vaccine
time frame: Day 8, 22, 29, 43, 202, and 387
measure: Percentage of subjects achieving Neut antibody titers of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine
time frame: Day 1, 8, 22, 29, 43, 202, and 387
measure: Percentage of subjects achieving Neut seroconversion against the A/H5N8 antigen contained in the study vaccine
time frame: Day 8, 22, 29, 43, 202, and 387
measure: Percentage of subjects achieving serum HAI antibody titers of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine
time frame: Day 1, 8, 22, 29, 43, 202, and 387
arm group label: Arm 1: 3.75 mcg A/H5N8 + AS03
arm group type: Experimental
description: 3.75 mcg A/H5N8 + AS03 given IM on Day 1 and 22, n=30
arm group label: Arm 2: 15 mcg A/H5N8 + AS03
arm group type: Experimental
description: 15 mcg A/H5N8 + AS03 given IM on Day 1 and 22, n=30
arm group label: Arm 3: 15 mcg A/H5N8 unadjuvanted
arm group type: Active Comparator
description: 15 mcg A/H5N8 unadjuvanted given IM on Day 1 and 22, n=15
arm group label: Arm 4: 3.75 mcg A/H5N8 + MF59
arm group type: Experimental
description: 3.75 mcg A/H5N8 + MF59 given IM on Day 1 and 22, n=30
arm group label: Arm 5: 15 mcg A/H5N8 + MF59
arm group type: Experimental
description: 15 mcg A/H5N8 + MF59 given IM on Day 1 and 22, n=30
arm group label: Arm 6: 15 mcg A/H5N8 unadjuvanted
arm group type: Active Comparator
description: 15 mcg A/H5N8 unadjuvanted given IM on Day and 22, n=15
intervention type: Drug
intervention name: AS03
description: AS03 oil-in-water emulsion adjuvant.
arm group label: Arm 1: 3.75 mcg A/H5N8 + AS03
arm group label: Arm 2: 15 mcg A/H5N8 + AS03
intervention type: Drug
intervention name: MF59 adjuvant
description: Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion.
arm group label: Arm 4: 3.75 mcg A/H5N8 + MF59
arm group label: Arm 5: 15 mcg A/H5N8 + MF59
intervention type: Biological
intervention name: Monovalent Influenza A/H5N8 vaccine
description: Monovalent inactivated influenza A/H5N8 virus vaccine for IM injection. prepared from influenza virus propagated in chicken egg fluid using seed virus prepared from the candidate vaccine virus (CVV), influenza virus A/gyrfalcon/Washington/41088-6/2014(H5N8)-PR8-IDCDC-RG43A (abbreviated as IDCDC-RG43A).
arm group label: Arm 1: 3.75 mcg A/H5N8 + AS03
arm group label: Arm 2: 15 mcg A/H5N8 + AS03
arm group label: Arm 3: 15 mcg A/H5N8 unadjuvanted
arm group label: Arm 4: 3.75 mcg A/H5N8 + MF59
arm group label: Arm 5: 15 mcg A/H5N8 + MF59
arm group label: Arm 6: 15 mcg A/H5N8 unadjuvanted
criteria: 
gender: All
minimum age: 19 Years
maximum age: 64 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Influenza, Human
mesh term: Influenza in Birds