<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/NCT02213354</url>
  </required_header>
  <id_info>
    <org_study_id>13-0034</org_study_id>
    <secondary_id>HHSN272201300016I</secondary_id>
    <nct_id>NCT02213354</nct_id>
  </id_info>
  <brief_title>H7N9 Mix and Match With MF59 in Healthy Elderly Persons</brief_title>
  <official_title>A Phase II Randomized, Partially-Blinded, Controlled Trial in Healthy Adults Aged 65 Years and Older to Assess the Safety, Reactogenicity, and Immunogenicity of an MF59-Adjuvanted, Monovalent Inactivated Influenza A/H7N9 Virus Vaccine Administered Intramuscularly at Different Intervals and Dosages</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>
  <brief_summary>
    <textblock>
      This is a Phase II randomized, partially-blinded, controlled trial in 360 (up to 600) males&#xD;
      and females, 65 years of age and older, who are in good health and meet all eligibility&#xD;
      criteria. This clinical trial is designed to assess the safety, reactogenicity, and&#xD;
      immunogenicity of a monovalent inactivated influenza A/H7N9 virus vaccine manufactured by&#xD;
      Sanofi Pasteur administered intramuscularly at different intervals and dosages (3.75, 7.5, or&#xD;
      15 mcg of HA/0.5 mL dose) given with MF59 adjuvant manufactured by Novartis Vaccines and&#xD;
      Diagnostics. Subjects will receive three doses of the vaccine. Safety, reactogenicity, and&#xD;
      immunogenicity data will be collected at standard time points with safety follow-up to&#xD;
      continue through one year post dose 2. Study Duration is approximately 30 months and Subject&#xD;
      Participation is approximately 18 months. The primary objectives are to (1) assess the safety&#xD;
      and reactogenicity of different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL dose) of an&#xD;
      MF59-adjuv&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase II randomized, partially-blinded, controlled trial in males and females, 65&#xD;
      years of age and older, who are in good health and meet all eligibility criteria. This&#xD;
      clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a&#xD;
      monovalent inactivated influenza A/H7N9 virus vaccine, derived from the influenza&#xD;
      A/Shanghai/2/2013 virus, manufactured by Sanofi Pasteur administered intramuscularly at&#xD;
      different intervals and dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with MF59&#xD;
      adjuvant manufactured by Novartis Vaccines and Diagnostics. Subjects will be assigned&#xD;
      randomly to 1 of 6 groups (60 to 100 subjects per group) to receive three doses&#xD;
      intramuscularly of the inactivated A/H7N9 vaccine at dosages (3.75, 7.5, or 15 mcg of HA/0.5&#xD;
      mL dose) given with MF59 adjuvant using two different study vaccination schedules. The first&#xD;
      and third study vaccinations will be administered to all subjects on Day 1 and approximately&#xD;
      Day 169. The second study vaccination will be administered either on approximately Day 29 for&#xD;
      Groups 1, 3, and 5 or approximately Day 57 for Groups 2, 4, and 6. Reactogenicity will be&#xD;
      measured from the time of each study vaccination through 8 days after each study vaccination&#xD;
      by the occurrence of solicited injection site and systemic reactions. Unsolicited non-serious&#xD;
      adverse events (AEs) will be collected from the time of each study vaccination through&#xD;
      approximately 28 days after each study vaccination. Serious adverse events (SAEs) and&#xD;
      new-onset chronic medical conditions will be collected from the time of the first study&#xD;
      vaccination through approximately 12 months after the last study vaccination.&#xD;
&#xD;
      Immunogenicity testing will include performing hemagglutination inhibition (HAI) and&#xD;
      neutralizing (Neut) antibody assays on serum obtained immediately prior to the first study&#xD;
      vaccination (Day 1), approximately 28 days after the second study vaccination (approximately&#xD;
      Day 57 for Groups 1, 3, and 5; approximately Day 85 for Groups 2, 4, and 6), immediately&#xD;
      prior to the third study vaccination (approximately Day 169), and approximately 28 days after&#xD;
      the third study vaccination (approximately Day 197). Subjects in Groups 1, 3, and 5 will also&#xD;
      have immunogenicity testing for HAI and Neut antibody assays performed on serum obtained at&#xD;
      approximately 56 days after the second study vaccination (approximately Day 85). Between 360&#xD;
      and 600 subjects will be enrolled in this trial. Study Duration is approximately 30 months&#xD;
      and Subject Participation is approximately 18 months. The primary objectives are to (1)&#xD;
      assess the safety and reactogenicity of different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL&#xD;
      dose) of an MF59-adjuvanted, monovalent inactivated influenza A/H7N9 virus vaccine using two&#xD;
      different study vaccination schedules and (2) assess the serum hemagglutination inhibition&#xD;
      (HAI) antibody responses to different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL dose) of an&#xD;
      MF59-adjuvanted, monovalent inactivated influenza A/H7N9 virus vaccine using two different&#xD;
      study vaccination schedules following receipt of the second study vaccination. The secondary&#xD;
      obectives are to (1) assess study vaccine-related unsolicited non-serious adverse events&#xD;
      following receipt of different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL dose) of an&#xD;
      MF59-adjuvanted, monovalent inactivated influenza A/H7N9 virus vaccine using two different&#xD;
      study vaccination schedules, (2) assess new-onset chronic medical conditions following&#xD;
      receipt of different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL dose) of an MF59-adjuvanted,&#xD;
      monovalent inactivated influenza A/H7N9 virus vaccine using two different study vaccination&#xD;
      sched&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine</measure>
    <time_frame>28 days after the second study vaccination</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent of subjects achieving HAI seroconversion against the A/H7N9 antigen contained in the study vaccine (either a pre-vaccine HAI titer &lt; 1:10 and a post-vaccine HAI titer &gt; /= 1:40 or a pre-vaccine HAI titer &gt; /=1:10 and a min 4-fold rise in post-vac</measure>
    <time_frame>28 days after the second study vaccination</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of study vaccine-related serious adverse events</measure>
    <time_frame>Through Day 1 to 12 months after the last study vaccination</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of solicited injection site and systemic reactogenicity events</measure>
    <time_frame>Through 8 days after each study vaccination</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Occurrence of study vaccine-related unsolicited non-serious adverse events</measure>
    <time_frame>28 days after each study vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of new-onset chronic medical conditions</measure>
    <time_frame>Through Day 1 to 12 months after the last study vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving Neut seroconversion against A/H7N9 antigen (either prevaccination Neut titer &lt; 1:10 and postvaccination Neut titer &gt; /=1:40 or prevaccination Neut titer &gt; /=1:10 and minimum fourfold rise in post-vaccination Neut</measure>
    <time_frame>28 days after the second and third study vaccinations</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric Mean Titers of serum HAI and Neut antibodies against the A/H7N9 antigen</measure>
    <time_frame>Baseline and 28 days after the second and third study vaccinations</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine</measure>
    <time_frame>Baseline and 28 days after the third study vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum Neut antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine</measure>
    <time_frame>Baseline and 28 days after the second and third study vaccinations</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving HAI seroconversion against the A/H7N9 antigen</measure>
    <time_frame>28 days after the third study vaccination</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">479</enrollment>
  <condition>Avian Influenza</condition>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 subjects receive Sanofi A/H7N9 antigen 3.75 mcg plus Novartis MF59 adjuvant IM on Day 1, Day 57, and Day 169</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 subjects receive Sanofi A/H7N9 antigen 15 mcg plus Novartis MF59 adjuvant IM on Day 1, Day 57, and Day 169</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 subjects receive Sanofi A/H7N9 antigen 15 mcg plus Novartis MF59 adjuvant IM on Day 1, Day 29 and Day 169</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 subjects receive Sanofi A/H7N9 antigen 7.5 mcg plus Novartis MF59 adjuvant IM on Day 1, Day 57, and Day 169</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group I</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 subjects receive Sanofi A/H7N9 antigen 3.75 mcg plus Novartis MF59 adjuvant intramuscularly (IM) on Day 1, Day 29 and Day 169</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 subjects receive Sanofi A/H7N9 antigen 7.5 mcg plus Novartis MF59 adjuvant IM on Day 1, Day 29 and Day 169</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MF59</intervention_name>
    <description>Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion. Group 1-6 receive 3.75 mcg, 7.5 mcg and 15 mcg.</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>
    <arm_group_label>Group I</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013</intervention_name>
    <description>Monovalent inactivated split influenza virus vaccine made with HA antigen derived from the influenza A/Shanghai/2/2013 virus. Monovalent influenza A/H7N9 virus vaccine. Group 1-6 receive 3.75 mcg, 7.5 mcg and 15 mcg.</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>
    <arm_group_label>Group I</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 females, 65 years of age and older.&#xD;
&#xD;
          4. Are in good health1. 1As determined by medical history and targeted physical&#xD;
             examination, if indicated based on medical history, to evaluate acute or currently&#xD;
             ongoing chronic medical diagnoses or conditions that would affect the assessment of&#xD;
             eligibility and safety of subjects. Chronic medical diagnoses or conditions being&#xD;
             actively managed must be within acceptable limits in the last 180 days. Good health in&#xD;
             the elderly is also defined as no change in chronic prescription medication, dose, or&#xD;
             frequency of medication in the 90 days prior to enrollment. Any prescription change&#xD;
             that is due to change of health care provider, insurance company, etc., or that is&#xD;
             done for financial reasons, as long as in the same class of medication, will not be&#xD;
             considered a deviation of this inclusion criterion. Any change in prescription&#xD;
             medication due to improvement of a disease outcome, as determined by the site&#xD;
             principal investigator or appropriate sub-investigator, will not be considered a&#xD;
             deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn)&#xD;
             medications if, in the opinion of the site principal investigator or appropriate&#xD;
             sub-investigator, they pose no additional risk to subject safety or assessment of&#xD;
             reactogenicity and immunogenicity and does not indicate a worsening of medical&#xD;
             diagnosis or condition. Similarly, medication changes subsequent to enrollment and&#xD;
             first study vaccination are acceptable provided the subject is asymptomatic, condition&#xD;
             stable, and there is no additional risk to the subject or interference with the&#xD;
             evaluation of responses to study vaccination. Note: Topical, nasal, and inhaled&#xD;
             medications (with the exception of steroids as outlined in the Subject Exclusion&#xD;
             Criteria (see Section 5.2)), herbals, vitamins, and supplements are permitted&#xD;
&#xD;
          5. Oral temperature is less than 100.0 degrees F.&#xD;
&#xD;
          6. Pulse is 50 to 115 bpm, inclusive.&#xD;
&#xD;
          7. Systolic blood pressure is 85 to 160 mm Hg, inclusive.&#xD;
&#xD;
          8. Diastolic blood pressure is 55 to 95 mm Hg, inclusive&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Have an acute illness2, as determined by the site principal investigator or appropriate&#xD;
        sub-investigator, within 72 hours prior to study vaccination.&#xD;
&#xD;
        2An acute illness which is nearly resolved with only minor residual symptoms remaining is&#xD;
        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;
        participation3.&#xD;
&#xD;
        3Including acute or chronic medical disease or condition, defined as persisting 3 months&#xD;
        (defined as 90 days) or longer, that would place the subject at an unacceptable risk of&#xD;
        injury, render the subject unable to meet the requirements of the protocol, or may&#xD;
        interfere with the evaluation of responses or the subject's successful completion of this&#xD;
        study.&#xD;
&#xD;
        3. Reside in a nursing home4 or other skilled nursing facility or have a requirement for&#xD;
        skilled nursing care.&#xD;
&#xD;
        4An ambulatory subject who does not require skilled nursing care and is a resident of a&#xD;
        retirement home or community is eligible for this clinical trial.&#xD;
&#xD;
        4. Inability to provide informed consent or complete study activities, for example, due to&#xD;
        dementia or other impairment.&#xD;
&#xD;
        5. 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;
        6. Have known active neoplastic disease or a history of any hematologic malignancy.&#xD;
&#xD;
        7. Have known HIV, hepatitis B, or hepatitis C infection. 8. Have known hypersensitivity or&#xD;
        allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of&#xD;
        the study vaccine.&#xD;
&#xD;
        9. Have a history of severe reactions following previous immunization with licensed or&#xD;
        unlicensed influenza virus vaccines.&#xD;
&#xD;
        10. Have a history of Guillain-Barré Syndrome. 11. Have a history of neuralgia,&#xD;
        paresthesia, neuritis, convulsions, or encephalomyelitis within 90 days prior to study&#xD;
        vaccination.&#xD;
&#xD;
        12. Have a history of autoimmune disease5. 5Including, but not limited to, autoimmune&#xD;
        processes resulting in neuroinflammatory diseases, vasculitis, clotting disorders,&#xD;
        dermatitis, arthritis, thyroiditis, or muscle, liver, or kidney disease.&#xD;
&#xD;
        13. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.&#xD;
&#xD;
        14. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other&#xD;
        psychiatric diagnosis that may interfere with subject compliance or safety evaluations.&#xD;
&#xD;
        15. 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;
        16. Have taken oral or parenteral corticosteroids of any dose within 30 days prior to study&#xD;
        vaccination.&#xD;
&#xD;
        17. Have taken high-dose inhaled corticosteroidswithin 30 days prior to study vaccination.&#xD;
        High-dose defined as &gt;800 mcg/day of beclomethasone dipropionate CFC or equivalent.&#xD;
&#xD;
        18. Received a licensed live vaccine within 30 days prior to enrollment in this study, or&#xD;
        plans to receive a licensed live vaccine within 30 days before or after each study vaccine.&#xD;
&#xD;
        19. Received a licensed inactivated vaccine within 14 days prior to enrollment in this&#xD;
        study, or plans to receive a licensed inactivated vaccine within 14 days before or after&#xD;
        each study vaccine.&#xD;
&#xD;
        20. Received immunoglobulin or other blood products within 90 days prior to study&#xD;
        vaccination.&#xD;
&#xD;
        21. Received an experimental agent6 within 30 days prior to the first study vaccination, or&#xD;
        expects to receive an experimental agent7 during the 18-month study period.&#xD;
&#xD;
        6Including vaccine, drug, biologic, device, blood product, or medication. 7Other than from&#xD;
        participation in this study. 22. Are participating or plan to participate in another&#xD;
        clinical trial with an interventional agent8 during the 18-month study period.&#xD;
&#xD;
        8 Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or&#xD;
        medication.&#xD;
&#xD;
        23. Prior participation in a clinical trial of influenza A/H7 vaccine9 or have a history of&#xD;
        A/H7 actual or potential exposure or infection prior to the first study vaccination.&#xD;
&#xD;
        9And assigned to a group receiving influenza A/H7 vaccine, does not apply to documented&#xD;
        placebo recipients.&#xD;
&#xD;
        24. Plan to travel outside the US (continental US, Hawaii, and Alaska) within the 28 days&#xD;
        following each study vaccination.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Emory Vaccine Center - The Hope Clinic</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030-1705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa - Vaccine Research and Education Unit</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242-2600</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland School of Medicine - Center for Vaccine Development - Baltimore</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 Clinical Vaccine 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>45229-3026</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center - Vanderbilt Institute for Clinical and Translational Research - Clinical Research Center (VICTR-CRC)</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232-0011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Medical Branch - Sealy Center for Vaccine Development - Clinical Trials Group</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555-1119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine - Molecular Virology and Microbiology</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030-3411</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Group Health Research Institute - Seattle - Vaccines and Infectious Diseases</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98101-1466</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 11, 2014</study_first_posted>
  <disposition_first_submitted>July 3, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>July 3, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">July 6, 2017</disposition_first_posted>
  <last_update_submitted>July 3, 2017</last_update_submitted>
  <last_update_submitted_qc>July 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Influenza, H7N9, Elderly, Vaccine, MF59 Adjuvant</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, but a results disposition has been submitted           -->
</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/NCT02213354
org study id: 13-0034
secondary id: HHSN272201300016I
nct id: NCT02213354
lead sponsor: 
This is a Phase II randomized, partially-blinded, controlled trial in 360 (up to 600) males
      and females, 65 years of age and older, who are in good health and meet all eligibility
      criteria. This clinical trial is designed to assess the safety, reactogenicity, and
      immunogenicity of a monovalent inactivated influenza A/H7N9 virus vaccine manufactured by
      Sanofi Pasteur administered intramuscularly at different intervals and dosages (3.75, 7.5, or
      15 mcg of HA/0.5 mL dose) given with MF59 adjuvant manufactured by Novartis Vaccines and
      Diagnostics. Subjects will receive three doses of the vaccine. Safety, reactogenicity, and
      immunogenicity data will be collected at standard time points with safety follow-up to
      continue through one year post dose 2. Study Duration is approximately 30 months and Subject
      Participation is approximately 18 months. The primary objectives are to (1) assess the safety
      and reactogenicity of different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL dose) of an
      MF59-adjuv
This is a Phase II randomized, partially-blinded, controlled trial in males and females, 65
      years of age and older, who are in good health and meet all eligibility criteria. This
      clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a
      monovalent inactivated influenza A/H7N9 virus vaccine, derived from the influenza
      A/Shanghai/2/2013 virus, manufactured by Sanofi Pasteur administered intramuscularly at
      different intervals and dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with MF59
      adjuvant manufactured by Novartis Vaccines and Diagnostics. Subjects will be assigned
      randomly to 1 of 6 groups (60 to 100 subjects per group) to receive three doses
      intramuscularly of the inactivated A/H7N9 vaccine at dosages (3.75, 7.5, or 15 mcg of HA/0.5
      mL dose) given with MF59 adjuvant using two different study vaccination schedules. The first
      and third study vaccinations will be administered to all subjects on Day 1 and approximately
      Day 169. The second study vaccination will be administered either on approximately Day 29 for
      Groups 1, 3, and 5 or approximately Day 57 for Groups 2, 4, and 6. Reactogenicity will be
      measured from the time of each study vaccination through 8 days after each study vaccination
      by the occurrence of solicited injection site and systemic reactions. Unsolicited non-serious
      adverse events (AEs) will be collected from the time of each study vaccination through
      approximately 28 days after each study vaccination. Serious adverse events (SAEs) and
      new-onset chronic medical conditions will be collected from the time of the first study
      vaccination through approximately 12 months after the last study vaccination.

      Immunogenicity testing will include performing hemagglutination inhibition (HAI) and
      neutralizing (Neut) antibody assays on serum obtained immediately prior to the first study
      vaccination (Day 1), approximately 28 days after the second study vaccination (approximately
      Day 57 for Groups 1, 3, and 5; approximately Day 85 for Groups 2, 4, and 6), immediately
      prior to the third study vaccination (approximately Day 169), and approximately 28 days after
      the third study vaccination (approximately Day 197). Subjects in Groups 1, 3, and 5 will also
      have immunogenicity testing for HAI and Neut antibody assays performed on serum obtained at
      approximately 56 days after the second study vaccination (approximately Day 85). Between 360
      and 600 subjects will be enrolled in this trial. Study Duration is approximately 30 months
      and Subject Participation is approximately 18 months. The primary objectives are to (1)
      assess the safety and reactogenicity of different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL
      dose) of an MF59-adjuvanted, monovalent inactivated influenza A/H7N9 virus vaccine using two
      different study vaccination schedules and (2) assess the serum hemagglutination inhibition
      (HAI) antibody responses to different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL dose) of an
      MF59-adjuvanted, monovalent inactivated influenza A/H7N9 virus vaccine using two different
      study vaccination schedules following receipt of the second study vaccination. The secondary
      obectives are to (1) assess study vaccine-related unsolicited non-serious adverse events
      following receipt of different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL dose) of an
      MF59-adjuvanted, monovalent inactivated influenza A/H7N9 virus vaccine using two different
      study vaccination schedules, (2) assess new-onset chronic medical conditions following
      receipt of different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL dose) of an MF59-adjuvanted,
      monovalent inactivated influenza A/H7N9 virus vaccine using two different study vaccination
      sched
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine
time frame: 28 days after the second study vaccination
measure: Percent of subjects achieving HAI seroconversion against the A/H7N9 antigen contained in the study vaccine (either a pre-vaccine HAI titer < 1:10 and a post-vaccine HAI titer > /= 1:40 or a pre-vaccine HAI titer > /=1:10 and a min 4-fold rise in post-vac
time frame: 28 days after the second study vaccination
measure: Occurrence of study vaccine-related serious adverse events
time frame: Through Day 1 to 12 months after the last study vaccination
measure: Occurrence of solicited injection site and systemic reactogenicity events
time frame: Through 8 days after each study vaccination
measure: Occurrence of study vaccine-related unsolicited non-serious adverse events
time frame: 28 days after each study vaccination
measure: Occurrence of new-onset chronic medical conditions
time frame: Through Day 1 to 12 months after the last study vaccination
measure: Percentage of subjects achieving Neut seroconversion against A/H7N9 antigen (either prevaccination Neut titer < 1:10 and postvaccination Neut titer > /=1:40 or prevaccination Neut titer > /=1:10 and minimum fourfold rise in post-vaccination Neut
time frame: 28 days after the second and third study vaccinations
measure: Geometric Mean Titers of serum HAI and Neut antibodies against the A/H7N9 antigen
time frame: Baseline and 28 days after the second and third study vaccinations
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine
time frame: Baseline and 28 days after the third study vaccination
measure: Percentage of subjects achieving a serum Neut antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine
time frame: Baseline and 28 days after the second and third study vaccinations
measure: Percentage of subjects achieving HAI seroconversion against the A/H7N9 antigen
time frame: 28 days after the third study vaccination
arm group label: Group 2
arm group type: Experimental
description: 60 subjects receive Sanofi A/H7N9 antigen 3.75 mcg plus Novartis MF59 adjuvant IM on Day 1, Day 57, and Day 169
arm group label: Group 6
arm group type: Experimental
description: 60 subjects receive Sanofi A/H7N9 antigen 15 mcg plus Novartis MF59 adjuvant IM on Day 1, Day 57, and Day 169
arm group label: Group 5
arm group type: Experimental
description: 60 subjects receive Sanofi A/H7N9 antigen 15 mcg plus Novartis MF59 adjuvant IM on Day 1, Day 29 and Day 169
arm group label: Group 4
arm group type: Experimental
description: 60 subjects receive Sanofi A/H7N9 antigen 7.5 mcg plus Novartis MF59 adjuvant IM on Day 1, Day 57, and Day 169
arm group label: Group I
arm group type: Experimental
description: 60 subjects receive Sanofi A/H7N9 antigen 3.75 mcg plus Novartis MF59 adjuvant intramuscularly (IM) on Day 1, Day 29 and Day 169
arm group label: Group 3
arm group type: Experimental
description: 60 subjects receive Sanofi A/H7N9 antigen 7.5 mcg plus Novartis MF59 adjuvant IM on Day 1, Day 29 and Day 169
intervention type: Drug
intervention name: MF59
description: Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion. Group 1-6 receive 3.75 mcg, 7.5 mcg and 15 mcg.
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
arm group label: Group I
intervention type: Biological
intervention name: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
description: Monovalent inactivated split influenza virus vaccine made with HA antigen derived from the influenza A/Shanghai/2/2013 virus. Monovalent influenza A/H7N9 virus vaccine. Group 1-6 receive 3.75 mcg, 7.5 mcg and 15 mcg.
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
arm group label: Group I
criteria: 
gender: All
minimum age: 65 Years
maximum age: 99 Years
healthy volunteers: Accepts Healthy Volunteers
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country: United States
responsible party type: Sponsor
mesh term: Influenza, Human
mesh term: Influenza in Birds