<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/NCT02251288</url>
  </required_header>
  <id_info>
    <org_study_id>13-0087</org_study_id>
    <nct_id>NCT02251288</nct_id>
  </id_info>
  <brief_title>A Phase I Study Priming With an Inactivated A/H7N9 Influenza Virus Vaccine With or Without MF59 Adjuvant Followed by Live Attenuated A/H7N9 Influenza Virus Vaccine</brief_title>
  <official_title>A Phase I Randomized Study in Healthy Adults to Assess the Safety, Reactogenicity and Immunogenicity of Priming With an Inactivated A/H7N9 Influenza Virus Vaccine With or Without MF59 Adjuvant Followed by Live Attenuated A/H7N9 Influenza Virus Vaccine</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>
      A phase I prospective, randomized study in healthy adult subjects at a single center. Adult&#xD;
      subjects age 18 to 47 years and meeting all enrollment criteria will choose to participate as&#xD;
      subjects who receive inactivated vaccine followed by a live vaccine boost at 4 weeks (Group&#xD;
      1), 12 weeks (Group 2), or 24 weeks (Group 3), or to be in an observational group (Group 4)&#xD;
      which will not be scheduled for a booster dose but may serve as a roll-over group for&#xD;
      subjects who withdraw prior to the second vaccination but agree to remain in follow-up. A&#xD;
      fifth group will receive two intramuscular doses of adjuvanted H7N9 pIIV separated by four&#xD;
      weeks. The primary objectives of this study are to (1) assess the safety of H7N9 pLAIV&#xD;
      administered to individuals who have previously received MF59-adjuvanted or unadjuvanted H7N9&#xD;
      pIIV, (2) evaluate the ability of a single dose of unadjuvanted H7N9 pIIV to prime for&#xD;
      enhanced immunogenicity (booster response) to subsequent administration of&#xD;
      antigenically-matched H7N9 pLAIV vaccine, and to (3) evaluate the ability of a single dose of&#xD;
      MF59-adjuvanted H7N9 pIIV to prime for enhanced immunogenicity (booster response) to&#xD;
      subsequent administration of antigenically-matched H7N9 pLAIV vaccine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be conducted as a Phase I prospective, randomized study in healthy adult&#xD;
      subjects at a single center. Adult subjects age 18 to 47 years and meeting all enrollment&#xD;
      criteria will choose to participate as subjects who receive unadjuvanted or adjuvanted H7H9&#xD;
      pIIV vaccine followed by a live vaccine boost at 4 weeks (Group 1, n=24), 12 weeks (Group 2,&#xD;
      n=24), or 24 weeks (Group 3, n=24), or to be in an observational group (Group 4, n=16) which&#xD;
      will not be scheduled for a booster dose but may serve as a roll-over group for subjects who&#xD;
      withdraw prior to the second vaccination but agree to remain in follow-up. Within each group,&#xD;
      subjects will be randomized at a 1:1 ratio to receive a single dose of either unadjuvanted&#xD;
      H7N9 pIIV at 15 mcg (Subgroup A), or the same vaccine adjuvanted with the oil-in-water&#xD;
      emulsion, MF59, (Subgroup B) delivered intramuscularly. Finally, a fifth group (Group 5,&#xD;
      n=12) will receive two intramuscular doses of adjuvanted H7N9 pIIV separated by four weeks.&#xD;
      The total duration of study participation for all subjects will be approximately 13 months.&#xD;
      Recruitment, enrollment and administration of study product will be suspended when one of the&#xD;
      following occurs in the clinical or research laboratory at the clinical site: at least two&#xD;
      respiratory cultures or PCR assays are determined to be positive for influenza or at least&#xD;
      10% diagnostic tests (rapid tests, respiratory cultures or PCR assays) performed for&#xD;
      influenza as positive during two consecutive weeks in the clinical or research laboratory at&#xD;
      the clinical site. Recruitment, enrollment and administration of study product may be resumed&#xD;
      after 2 weeks without a signal that influenza is still circulating in the community, as&#xD;
      defined by the same measures that indicate the start of influenza season (i.e., less than 2&#xD;
      respiratory cultures or PCR assays are determined to positive for influenza or less than 10%&#xD;
      of diagnostic tests performed or influenza with positive results). The primary objectives of&#xD;
      this study are to (1) assess the safety of H7N9 pLAIV administered to individuals who have&#xD;
      previously received MF59-adjuvanted or unadjuvanted H7N9 pIIV, (2) evaluate the ability of a&#xD;
      single dose of unadjuvanted H7N9 pIIV to prime for enhanced immunogenicity (booster response)&#xD;
      to subsequent administration of antigenically-matched H7N9 pLAIV vaccine, and to (3) evaluate&#xD;
      the ability of a single dose of MF59-adjuvanted H7N9 pIIV to prime for enhanced&#xD;
      immunogenicity (booster response) to subsequent administration of antigenically-matched H7N9&#xD;
      pLAIV vaccine. The secondary objectives of this study are to (1) assess the safety of priming&#xD;
      with MF59-adjuvanted H7N9 pIIV or unadjuvanted H7N9 pIIV, (2) assess the immune response in&#xD;
      subjects vaccinated with a single dose of MF59-adjuvanted H7N9 pIIV or a single dose of&#xD;
      unadjuvanted H7N9 pIIV, and to (3) compare the booster effect seen after intervals of 4&#xD;
      weeks, 12 weeks, or 24 weeks within each priming group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 18, 2015</start_date>
  <completion_date type="Actual">August 17, 2018</completion_date>
  <primary_completion_date type="Actual">August 17, 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>Factorial Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA)</measure>
    <time_frame>Day 29</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA) for Group 2</measure>
    <time_frame>Day 113</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA) for Group 3</measure>
    <time_frame>Day 197</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA) for Groups 1, 5</measure>
    <time_frame>Day 57</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of respiratory reactogenicity following pLAIV vaccination for Group 1</measure>
    <time_frame>Day 29 through Day 39</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of respiratory reactogenicity following pLAIV vaccination for Group 2</measure>
    <time_frame>Day 85 through Day 95</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of respiratory reactogenicity following pLAIV vaccination for Group 3</measure>
    <time_frame>Day 169 through Day 179</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of solicited systemic reactogenicity following pLAIV vaccination for Group 1</measure>
    <time_frame>Day 29 through Day 39</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of solicited systemic reactogenicity following pLAIV vaccination for Group 2</measure>
    <time_frame>Day 85 through Day 95</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of solicited systemic reactogenicity following pLAIV vaccination for Group 3</measure>
    <time_frame>Day 169 through Day 179</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of study vaccine-related serious adverse events following pLAIV vaccination for Group 1</measure>
    <time_frame>Day 29 through Day 209</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of study vaccine-related serious adverse events following pLAIV vaccination for Group 2</measure>
    <time_frame>Day 85 through Day 265</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of study vaccine-related serious adverse events following pLAIV vaccination for Group 3</measure>
    <time_frame>Day 169 through Day 349</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of study vaccine-related unsolicited non-serious adverse events following pLAIV vaccination for Group 1</measure>
    <time_frame>Day 29 through Day 57</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of study vaccine-related unsolicited non-serious adverse events following pLAIV vaccination for Group 2</measure>
    <time_frame>Day 85 through 113</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of study vaccine-related unsolicited non-serious adverse events following pLAIV vaccination for Group 3</measure>
    <time_frame>Day 169 through 197</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 2</measure>
    <time_frame>Day 113</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 3</measure>
    <time_frame>Day 197</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Groups 1, 5</measure>
    <time_frame>Day 57</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer &lt;1:10 and a post-vaccination HAI titer = / &gt; 1:40 or a pre-vaccination HAI titer = / &gt; 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) for Group 2</measure>
    <time_frame>Day 113</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer &lt;1:10 and a post-vaccination HAI titer = / &gt; 1:40 or a pre-vaccination HAI titer = / &gt; 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) for Group 3</measure>
    <time_frame>Day 197</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer &lt;1:10 and a post-vaccination HAI titer = / &gt; 1:40 or a pre-vaccination HAI titer = / &gt; 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) for Groups 1,5</measure>
    <time_frame>Day 57</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects shedding vaccine virus as detected by rRT-PCR following pLAIV vaccination for Group 1</measure>
    <time_frame>Day 29 through Day 36</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects shedding vaccine virus as detected by rRT-PCR following pLAIV vaccination for Group 2</measure>
    <time_frame>Day 85 through Day 92</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects shedding vaccine virus as detected by rRT-PCR following pLAIV vaccination for Group 3</measure>
    <time_frame>Day 169 through Day 176</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells</measure>
    <time_frame>Day 29</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 2</measure>
    <time_frame>Day 113</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 2</measure>
    <time_frame>Day 141</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 2</measure>
    <time_frame>Day 265</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 3</measure>
    <time_frame>Day 197</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 3</measure>
    <time_frame>Day 225</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 3</measure>
    <time_frame>Day 349</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Groups 1, 5</measure>
    <time_frame>Day 209</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Groups 1, 5</measure>
    <time_frame>Day 57</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Groups 1, 5</measure>
    <time_frame>Day 85</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody for Group 2</measure>
    <time_frame>Day 113</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody for Group 2</measure>
    <time_frame>Day 141</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody for Group 2</measure>
    <time_frame>Day 265</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody for Group 3</measure>
    <time_frame>Day 197</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody for Group 3</measure>
    <time_frame>Day 225</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody for Group 3</measure>
    <time_frame>Day 349</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody for Groups 1, 5</measure>
    <time_frame>Day 209</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody for Groups 1, 5</measure>
    <time_frame>Day 57</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum HAI antibody for Groups 1, 5</measure>
    <time_frame>Day 85</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody for Group 2</measure>
    <time_frame>Day 113</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody for Group 2</measure>
    <time_frame>Day 141</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody for Group 2</measure>
    <time_frame>Day 265</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody for Group 3</measure>
    <time_frame>Day 197</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody for Group 3</measure>
    <time_frame>Day 225</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody for Group 3</measure>
    <time_frame>Day 349</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody for Groups 1, 5</measure>
    <time_frame>Day 209</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody for Groups 1, 5</measure>
    <time_frame>Day 57</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titers of serum NtAb antibody for Groups 1, 5</measure>
    <time_frame>Day 85</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of adverse events of special interest following pIIV vaccination</measure>
    <time_frame>Day 1 through Day 366</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of adverse events of special interest following pIIV vaccination for Group 5</measure>
    <time_frame>Day 1 through Day 394</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of local reactogenicity following pIIV vaccination</measure>
    <time_frame>Day 1 through Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of local reactogenicity following pIIV vaccination for Group 5</measure>
    <time_frame>Day 29 through Day 36</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of new-onset chronic medical conditions for Group 2</measure>
    <time_frame>Day 1 through Day 265</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of new-onset chronic medical conditions for Group 3</measure>
    <time_frame>Day 1 through Day 349</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of new-onset chronic medical conditions for Group 4</measure>
    <time_frame>Day 1 through Day 181</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of new-onset chronic medical conditions for Groups 1, 5</measure>
    <time_frame>Day 1 through Day 209</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of study vaccine-related serious adverse events following pIIV vaccination</measure>
    <time_frame>Day 1 through Day 366</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of study vaccine-related serious adverse events following pIIV vaccination for Group 5</measure>
    <time_frame>Day 29 through Day 394</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of study vaccine-related unsolicited non-serious adverse events following pIIV vaccination</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of study vaccine-related unsolicited non-serious adverse events following pIIV vaccination for Group 5</measure>
    <time_frame>Day 57</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of systemic reactogenicity following pIIV vaccination</measure>
    <time_frame>Day 1 through Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of systemic reactogenicity following pIIV vaccination for Group 5</measure>
    <time_frame>Day 29 through Day 36</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 1, 5</measure>
    <time_frame>Day 209</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 1, 5</measure>
    <time_frame>Day 85</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 2</measure>
    <time_frame>Day 141</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 2</measure>
    <time_frame>Day 265</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 3</measure>
    <time_frame>Day 225</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 3</measure>
    <time_frame>Day 349</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 2</measure>
    <time_frame>Day 113</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 2</measure>
    <time_frame>Day 141</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 2</measure>
    <time_frame>Day 265</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 3</measure>
    <time_frame>Day 197</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 3</measure>
    <time_frame>Day 225</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 3</measure>
    <time_frame>Day 349</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Groups 1, 5</measure>
    <time_frame>Day 209</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Groups 1, 5</measure>
    <time_frame>Day 57</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Groups 1, 5</measure>
    <time_frame>Day 85</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer &lt;1:10 and a post-vaccination HAI titer = / &gt; 1:40 or a pre-vaccination HAI titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer)</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer &lt;1:10 and a post-vaccination HAI titer = / &gt; 1:40 or a pre-vaccination HAI titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Group 2</measure>
    <time_frame>Day 141</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer &lt;1:10 and a post-vaccination HAI titer = / &gt; 1:40 or a pre-vaccination HAI titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Group 2</measure>
    <time_frame>Day 265</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer &lt;1:10 and a post-vaccination HAI titer = / &gt; 1:40 or a pre-vaccination HAI titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Group 3</measure>
    <time_frame>Day 225</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer &lt;1:10 and a post-vaccination HAI titer = / &gt; 1:40 or a pre-vaccination HAI titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Group 3</measure>
    <time_frame>Day 349</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer &lt;1:10 and a post-vaccination HAI titer = / &gt; 1:40 or a pre-vaccination HAI titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Groups 1, 5</measure>
    <time_frame>Day 209</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer &lt;1:10 and a post-vaccination HAI titer = / &gt; 1:40 or a pre-vaccination HAI titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Groups 1, 5</measure>
    <time_frame>Day 85</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer &lt;1:10 and a post-vaccination NtAb titer = / &gt; 1:40 or a pre-vaccination NtAb titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer)</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer &lt;1:10 and a post-vaccination NtAb titer = / &gt; 1:40 or a pre-vaccination NtAb titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 2</measure>
    <time_frame>Day 113</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer &lt;1:10 and a post-vaccination NtAb titer = / &gt; 1:40 or a pre-vaccination NtAb titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 2</measure>
    <time_frame>Day 141</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer &lt;1:10 and a post-vaccination NtAb titer = / &gt; 1:40 or a pre-vaccination NtAb titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 2</measure>
    <time_frame>Day 265</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer &lt;1:10 and a post-vaccination NtAb titer = / &gt; 1:40 or a pre-vaccination NtAb titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 3</measure>
    <time_frame>Day 197</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer &lt;1:10 and a post-vaccination NtAb titer = / &gt; 1:40 or a pre-vaccination NtAb titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 3</measure>
    <time_frame>Day 225</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer &lt;1:10 and a post-vaccination NtAb titer = / &gt; 1:40 or a pre-vaccination NtAb titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 3</measure>
    <time_frame>Day 349</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer &lt;1:10 and a post-vaccination NtAb titer = / &gt; 1:40 or a pre-vaccination NtAb titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Groups 1, 5</measure>
    <time_frame>Day 209</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer &lt;1:10 and a post-vaccination NtAb titer = / &gt; 1:40 or a pre-vaccination NtAb titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Groups 1, 5</measure>
    <time_frame>Day 57</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer &lt;1:10 and a post-vaccination NtAb titer = / &gt; 1:40 or a pre-vaccination NtAb titer = / &gt; 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Groups 1, 5</measure>
    <time_frame>Day 85</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Avian Influenza</condition>
  <condition>Immunisation</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>12 patients receive Intramuscular (IM) A/H7N9 15 mcg on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of Intranasal (IN) sprayer 10^7 FFU H7 N9 pLAIV on Day 29</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>12 patients receive A/H7N9 15 mcg IM on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of IN sprayer10^7 FFU H7 N9 pLAIV on Day 85</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>12 patients receive S A/H7N9 15 mcg IM on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of IN sprayer 10^7 FFU H7 N9 pLAIV on Day 169</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 patients receive A/H7N9 15 mcg IM on Day 1, 8 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>12 patients receive A/H7N9 15 mcg plus MF59 adjuvant on Day 1 and Day 29</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca</intervention_name>
    <description>MedImmune supplies pLAIV vaccines as a colorless to pale yellow and clear to slightly cloudy suspension in single, unit-dose, Becton-Dickinson Accuspray™ Nasal Spray Systems sprayer devices. Each filled sprayer device contains a 0.5 mL dose of 10^7FFU of H7N9 Anhui 2013/AA ca vaccine. Group I receives the IN dose on Day 29, Group 2 on Day 85, and Group 3 on Day 169.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013</intervention_name>
    <description>Sanofi supplies the monovalent influenza A/H7N9 virus vaccine as a sterile, clear, and slightly opalescent suspension in single-dose vials containing 15 mcg HA per 0.5 mL. Group 1 through Group5 will receive the IM vaccine on Day 1</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_label>Group 5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MF59 adjuvant</intervention_name>
    <description>Novartis supplies the MF59 adjuvant as an oil-in-water milky emulsion in single-use vials containing a fill volume of 0.7 mL. Group 1 through Group 5 will receive MF59 IM on Day 1.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_label>Group 5</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provide written informed consent prior to initiation of any study procedures,&#xD;
             including future use of specimens.&#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, non-breastfeeding females, 18 to 47 years old, inclusive.&#xD;
&#xD;
          4. Are in good health, as determined by medical history, and targeted physical&#xD;
             examination to ensure any existing medical diagnoses or conditions (except those&#xD;
             exclusionary) are stable* **.&#xD;
&#xD;
             *Stable chronic medical condition - no change in prescription medication, dose, or&#xD;
             frequency of medication in the last 3 months (defined as 90 days) and health outcomes&#xD;
             of the specific disease are considered to be within acceptable limits in the last 6&#xD;
             months (defined as 180 days). Any change that is due to change of health care&#xD;
             provider, insurance company etc., or that is done for financial reasons, as long as in&#xD;
             the same class of medication, will not be considered a violation of this inclusion&#xD;
             criterion. Any change in prescription medication due to improvement of a disease&#xD;
             outcome, as determined by the site principal investigator or appropriate&#xD;
             sub-investigator, will not be considered a violation of this inclusion criterion.&#xD;
&#xD;
             **Subjects may be on chronic or as needed (prn) medications if, in the opinion of the&#xD;
             site principal investigator or appropriate sub-investigator, they pose no additional&#xD;
             risk to subject safety or assessment of reactogenicity and immunogenicity. Note:&#xD;
             Topical, nasal, and inhaled medications (with the exception of steroids as outlined in&#xD;
             the Subject Exclusion Criteria), vitamins, and contraceptives are permitted.&#xD;
&#xD;
          5. Oral temperature is less than 100.4 degrees Fahrenheit.&#xD;
&#xD;
          6. Pulse is 55 to 100 bpm, inclusive.&#xD;
&#xD;
          7. Systolic blood pressure is 90 to 140 mmHg, inclusive.&#xD;
&#xD;
          8. Diastolic blood pressure is 55 to 90 mmHg, inclusive.&#xD;
&#xD;
          9. Women of childbearing potential* in sexual relationships with men must use an&#xD;
             acceptable method of contraception** from 30 days prior to pIIV administration until&#xD;
             90 days after last study vaccination.&#xD;
&#xD;
             *Not sterilized via tubal ligation, bilateral oophorectomy or hysterectomy and still&#xD;
             menstruating or &lt; 1 year of the last menses if menopausal).&#xD;
&#xD;
             **Includes, but is not limited to, abstinence from intercourse with a male partner,&#xD;
             monogamous relationship with a vasectomized partner, male condoms with the use of&#xD;
             applied spermicide, intrauterine devices, and licensed hormonal methods, with use of a&#xD;
             highly effective method of contraception for a minimum of 30 days prior to study&#xD;
             product exposure and agree to practice highly effective contraception for the duration&#xD;
             of study product exposure, including 3 months (defined as 90 days) after the last&#xD;
             study vaccination. A highly effective method of contraception is defined as one which&#xD;
             results in a low failure rate (i.e., less than 1% per year) when used consistently and&#xD;
             correctly.&#xD;
&#xD;
         10. Female subjects of childbearing potential must have a negative urine or serum&#xD;
             pregnancy test within 24 hours prior to study vaccination.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have an acute illness within 72 hours prior to study vaccination.&#xD;
&#xD;
          2. Any medical disease or condition that, in the opinion of the investigator, is a&#xD;
             contraindication to study participation*.&#xD;
&#xD;
             *Includes medical disease or condition that would place the subject at an unacceptable&#xD;
             risk of injury, render them unable to meet the requirements of the protocol, or may&#xD;
             interfere with the evaluation of responses or their successful completion of the&#xD;
             study.&#xD;
&#xD;
          3. Have history of any significant acute or chronic medical conditions* or need for&#xD;
             chronic medications that, in the opinion of the investigator, will interfere with&#xD;
             immunogenicity or affect safety.&#xD;
&#xD;
             *Chronic medical condition - a medical condition persisting 3 months (defined as 90&#xD;
             days) or longer&#xD;
&#xD;
          4. Have immunosuppression or are taking systemic immunosuppressants as a result of an&#xD;
             underlying illness or treatment.&#xD;
&#xD;
          5. Diagnosis of asthma or reactive airway disease within the past 2 years.&#xD;
&#xD;
          6. History of surgical splenectomy.&#xD;
&#xD;
          7. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 36 months prior&#xD;
             to vaccination.&#xD;
&#xD;
          8. Have known active neoplastic disease or a history of any hematologic malignancy.&#xD;
&#xD;
          9. Have known hepatitis B or hepatitis C infection.&#xD;
&#xD;
         10. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based&#xD;
             adjuvants, or other components of the study vaccine.&#xD;
&#xD;
         11. Known allergy or intolerance to oseltamivir.&#xD;
&#xD;
         12. Have a history of severe reactions following previous immunization with licensed or&#xD;
             unlicensed influenza virus vaccines.&#xD;
&#xD;
         13. Have a history of Guillain-Barré Syndrome.&#xD;
&#xD;
         14. Have a history of neuralgia, paresthesia, neuritis, convulsions, or encephalomyelitis&#xD;
             within 90 days prior to study vaccination.&#xD;
&#xD;
         15. Have a history of autoimmune disease*.&#xD;
&#xD;
             *Including, but not limited to, neuroinflammatory diseases, vasculitis, clotting&#xD;
             disorders, dermatitis, arthritis, thyroiditis, or muscle, liver, or kidney disease.&#xD;
&#xD;
         16. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.&#xD;
&#xD;
         17. 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;
         18. 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;
         19. Have taken oral or parenteral corticosteroids of any dose within 30 days prior to&#xD;
             study vaccination.&#xD;
&#xD;
         20. Chronic use (defined as daily use for &gt; 7days within the 30 days prior to study&#xD;
             vaccination) of any inhaled medication, including inhaled corticosteroids.&#xD;
&#xD;
         21. Received any licensed live vaccine within 30 days prior to pIIV vaccination. This is&#xD;
             inclusive of licensed seasonal influenza vaccines.&#xD;
&#xD;
         22. Received any licensed inactivated vaccine within 14 days prior to pIIV vaccination.&#xD;
             This is inclusive of licensed seasonal influenza vaccines.&#xD;
&#xD;
         23. Planned receipt of any vaccine from the first study vaccination through the follow-up&#xD;
             visit at approximately 56 days after the second study vaccination. This is inclusive&#xD;
             of licensed seasonal influenza vaccines&#xD;
&#xD;
         24. Received immunoglobulin or other blood products (with exception of Rho D&#xD;
             immunoglobulin) within 90 days prior to study vaccination.&#xD;
&#xD;
         25. Received an experimental agent* within 30 days prior to pIIV administration or planned&#xD;
             receipt of an experimental agent to within 90 days after pLAIV administration.&#xD;
&#xD;
             *Includes vaccine, drug, biologic, device, blood product, or medication.&#xD;
&#xD;
         26. Plans to enroll in another clinical trial* that could interfere with safety assessment&#xD;
             of the investigational product at any time during the study period.&#xD;
&#xD;
             *Includes trials that have a study intervention such as a drug, biologic, or device&#xD;
&#xD;
         27. Prior participation in a clinical trial of influenza A/H7 vaccine* or have a history&#xD;
             of A/H7 actual or potential exposure or infection prior to the first study&#xD;
             vaccination.&#xD;
&#xD;
             *Documented receipt of placebo in such a trial is not exclusionary&#xD;
&#xD;
         28. Plan to travel outside the U.S. (continental U.S., Hawaii and Alaska) in the time&#xD;
             between the first study vaccination and 56 days after the second study vaccination.&#xD;
&#xD;
         29. Positive screening pregnancy test or other evidence of pregnancy.&#xD;
&#xD;
         30. Female subjects who are breastfeeding or plan to breastfeed at any given time from the&#xD;
             first study vaccination until 30 days after their last study vaccination.&#xD;
&#xD;
         31. Seropositive to the H7N9 influenza A virus (serum HAI titer &gt; 1:8) during the&#xD;
             screening period prior to the first study vaccination.&#xD;
&#xD;
         32. Positive urine drug screen for opiates and cocaine at the time of check-in for the&#xD;
             period of confinement.&#xD;
&#xD;
         33. Positive ELISA and confirmatory Western blot tests for human immunodeficiency virus-1&#xD;
             (HIV-1) during the screening period prior to vaccination.&#xD;
&#xD;
         34. Current smoker unwilling to stop smoking for the period of confinement. A nicotine&#xD;
             patch during the period of confinement may be offered.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>47 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Rochester Medical Center - Vaccine Research Unit</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642-0001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 1, 2018</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <last_update_submitted>January 23, 2020</last_update_submitted>
  <last_update_submitted_qc>January 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>H7N9 pandemic</keyword>
  <keyword>inactivated influenza vaccine (pIIV)</keyword>
  <keyword>live attenuated influenza vaccine (pLAIV)</keyword>
  <keyword>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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02251288
org study id: 13-0087
nct id: NCT02251288
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
A phase I prospective, randomized study in healthy adult subjects at a single center. Adult
      subjects age 18 to 47 years and meeting all enrollment criteria will choose to participate as
      subjects who receive inactivated vaccine followed by a live vaccine boost at 4 weeks (Group
      1), 12 weeks (Group 2), or 24 weeks (Group 3), or to be in an observational group (Group 4)
      which will not be scheduled for a booster dose but may serve as a roll-over group for
      subjects who withdraw prior to the second vaccination but agree to remain in follow-up. A
      fifth group will receive two intramuscular doses of adjuvanted H7N9 pIIV separated by four
      weeks. The primary objectives of this study are to (1) assess the safety of H7N9 pLAIV
      administered to individuals who have previously received MF59-adjuvanted or unadjuvanted H7N9
      pIIV, (2) evaluate the ability of a single dose of unadjuvanted H7N9 pIIV to prime for
      enhanced immunogenicity (booster response) to subsequent administration of
      antigenically-matched H7N9 pLAIV vaccine, and to (3) evaluate the ability of a single dose of
      MF59-adjuvanted H7N9 pIIV to prime for enhanced immunogenicity (booster response) to
      subsequent administration of antigenically-matched H7N9 pLAIV vaccine.
The study will be conducted as a Phase I prospective, randomized study in healthy adult
      subjects at a single center. Adult subjects age 18 to 47 years and meeting all enrollment
      criteria will choose to participate as subjects who receive unadjuvanted or adjuvanted H7H9
      pIIV vaccine followed by a live vaccine boost at 4 weeks (Group 1, n=24), 12 weeks (Group 2,
      n=24), or 24 weeks (Group 3, n=24), or to be in an observational group (Group 4, n=16) which
      will not be scheduled for a booster dose but may serve as a roll-over group for subjects who
      withdraw prior to the second vaccination but agree to remain in follow-up. Within each group,
      subjects will be randomized at a 1:1 ratio to receive a single dose of either unadjuvanted
      H7N9 pIIV at 15 mcg (Subgroup A), or the same vaccine adjuvanted with the oil-in-water
      emulsion, MF59, (Subgroup B) delivered intramuscularly. Finally, a fifth group (Group 5,
      n=12) will receive two intramuscular doses of adjuvanted H7N9 pIIV separated by four weeks.
      The total duration of study participation for all subjects will be approximately 13 months.
      Recruitment, enrollment and administration of study product will be suspended when one of the
      following occurs in the clinical or research laboratory at the clinical site: at least two
      respiratory cultures or PCR assays are determined to be positive for influenza or at least
      10% diagnostic tests (rapid tests, respiratory cultures or PCR assays) performed for
      influenza as positive during two consecutive weeks in the clinical or research laboratory at
      the clinical site. Recruitment, enrollment and administration of study product may be resumed
      after 2 weeks without a signal that influenza is still circulating in the community, as
      defined by the same measures that indicate the start of influenza season (i.e., less than 2
      respiratory cultures or PCR assays are determined to positive for influenza or less than 10%
      of diagnostic tests performed or influenza with positive results). The primary objectives of
      this study are to (1) assess the safety of H7N9 pLAIV administered to individuals who have
      previously received MF59-adjuvanted or unadjuvanted H7N9 pIIV, (2) evaluate the ability of a
      single dose of unadjuvanted H7N9 pIIV to prime for enhanced immunogenicity (booster response)
      to subsequent administration of antigenically-matched H7N9 pLAIV vaccine, and to (3) evaluate
      the ability of a single dose of MF59-adjuvanted H7N9 pIIV to prime for enhanced
      immunogenicity (booster response) to subsequent administration of antigenically-matched H7N9
      pLAIV vaccine. The secondary objectives of this study are to (1) assess the safety of priming
      with MF59-adjuvanted H7N9 pIIV or unadjuvanted H7N9 pIIV, (2) assess the immune response in
      subjects vaccinated with a single dose of MF59-adjuvanted H7N9 pIIV or a single dose of
      unadjuvanted H7N9 pIIV, and to (3) compare the booster effect seen after intervals of 4
      weeks, 12 weeks, or 24 weeks within each priming group.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA)
time frame: Day 29
measure: Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA) for Group 2
time frame: Day 113
measure: Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA) for Group 3
time frame: Day 197
measure: Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA) for Groups 1, 5
time frame: Day 57
measure: Occurrence of respiratory reactogenicity following pLAIV vaccination for Group 1
time frame: Day 29 through Day 39
measure: Occurrence of respiratory reactogenicity following pLAIV vaccination for Group 2
time frame: Day 85 through Day 95
measure: Occurrence of respiratory reactogenicity following pLAIV vaccination for Group 3
time frame: Day 169 through Day 179
measure: Occurrence of solicited systemic reactogenicity following pLAIV vaccination for Group 1
time frame: Day 29 through Day 39
measure: Occurrence of solicited systemic reactogenicity following pLAIV vaccination for Group 2
time frame: Day 85 through Day 95
measure: Occurrence of solicited systemic reactogenicity following pLAIV vaccination for Group 3
time frame: Day 169 through Day 179
measure: Occurrence of study vaccine-related serious adverse events following pLAIV vaccination for Group 1
time frame: Day 29 through Day 209
measure: Occurrence of study vaccine-related serious adverse events following pLAIV vaccination for Group 2
time frame: Day 85 through Day 265
measure: Occurrence of study vaccine-related serious adverse events following pLAIV vaccination for Group 3
time frame: Day 169 through Day 349
measure: Occurrence of study vaccine-related unsolicited non-serious adverse events following pLAIV vaccination for Group 1
time frame: Day 29 through Day 57
measure: Occurrence of study vaccine-related unsolicited non-serious adverse events following pLAIV vaccination for Group 2
time frame: Day 85 through 113
measure: Occurrence of study vaccine-related unsolicited non-serious adverse events following pLAIV vaccination for Group 3
time frame: Day 169 through 197
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 2
time frame: Day 113
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 3
time frame: Day 197
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Groups 1, 5
time frame: Day 57
measure: Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) for Group 2
time frame: Day 113
measure: Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) for Group 3
time frame: Day 197
measure: Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) for Groups 1,5
time frame: Day 57
measure: Percentage of subjects shedding vaccine virus as detected by rRT-PCR following pLAIV vaccination for Group 1
time frame: Day 29 through Day 36
measure: Percentage of subjects shedding vaccine virus as detected by rRT-PCR following pLAIV vaccination for Group 2
time frame: Day 85 through Day 92
measure: Percentage of subjects shedding vaccine virus as detected by rRT-PCR following pLAIV vaccination for Group 3
time frame: Day 169 through Day 176
measure: Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells
time frame: Day 29
measure: Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 2
time frame: Day 113
measure: Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 2
time frame: Day 141
measure: Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 2
time frame: Day 265
measure: Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 3
time frame: Day 197
measure: Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 3
time frame: Day 225
measure: Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 3
time frame: Day 349
measure: Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Groups 1, 5
time frame: Day 209
measure: Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Groups 1, 5
time frame: Day 57
measure: Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Groups 1, 5
time frame: Day 85
measure: Geometric mean titers of serum HAI antibody
time frame: Day 1
measure: Geometric mean titers of serum HAI antibody
time frame: Day 29
measure: Geometric mean titers of serum HAI antibody for Group 2
time frame: Day 113
measure: Geometric mean titers of serum HAI antibody for Group 2
time frame: Day 141
measure: Geometric mean titers of serum HAI antibody for Group 2
time frame: Day 265
measure: Geometric mean titers of serum HAI antibody for Group 3
time frame: Day 197
measure: Geometric mean titers of serum HAI antibody for Group 3
time frame: Day 225
measure: Geometric mean titers of serum HAI antibody for Group 3
time frame: Day 349
measure: Geometric mean titers of serum HAI antibody for Groups 1, 5
time frame: Day 209
measure: Geometric mean titers of serum HAI antibody for Groups 1, 5
time frame: Day 57
measure: Geometric mean titers of serum HAI antibody for Groups 1, 5
time frame: Day 85
measure: Geometric mean titers of serum NtAb antibody
time frame: Day 1
measure: Geometric mean titers of serum NtAb antibody
time frame: Day 29
measure: Geometric mean titers of serum NtAb antibody for Group 2
time frame: Day 113
measure: Geometric mean titers of serum NtAb antibody for Group 2
time frame: Day 141
measure: Geometric mean titers of serum NtAb antibody for Group 2
time frame: Day 265
measure: Geometric mean titers of serum NtAb antibody for Group 3
time frame: Day 197
measure: Geometric mean titers of serum NtAb antibody for Group 3
time frame: Day 225
measure: Geometric mean titers of serum NtAb antibody for Group 3
time frame: Day 349
measure: Geometric mean titers of serum NtAb antibody for Groups 1, 5
time frame: Day 209
measure: Geometric mean titers of serum NtAb antibody for Groups 1, 5
time frame: Day 57
measure: Geometric mean titers of serum NtAb antibody for Groups 1, 5
time frame: Day 85
measure: Occurrence of adverse events of special interest following pIIV vaccination
time frame: Day 1 through Day 366
measure: Occurrence of adverse events of special interest following pIIV vaccination for Group 5
time frame: Day 1 through Day 394
measure: Occurrence of local reactogenicity following pIIV vaccination
time frame: Day 1 through Day 8
measure: Occurrence of local reactogenicity following pIIV vaccination for Group 5
time frame: Day 29 through Day 36
measure: Occurrence of new-onset chronic medical conditions for Group 2
time frame: Day 1 through Day 265
measure: Occurrence of new-onset chronic medical conditions for Group 3
time frame: Day 1 through Day 349
measure: Occurrence of new-onset chronic medical conditions for Group 4
time frame: Day 1 through Day 181
measure: Occurrence of new-onset chronic medical conditions for Groups 1, 5
time frame: Day 1 through Day 209
measure: Occurrence of study vaccine-related serious adverse events following pIIV vaccination
time frame: Day 1 through Day 366
measure: Occurrence of study vaccine-related serious adverse events following pIIV vaccination for Group 5
time frame: Day 29 through Day 394
measure: Occurrence of study vaccine-related unsolicited non-serious adverse events following pIIV vaccination
time frame: Day 29
measure: Occurrence of study vaccine-related unsolicited non-serious adverse events following pIIV vaccination for Group 5
time frame: Day 57
measure: Occurrence of systemic reactogenicity following pIIV vaccination
time frame: Day 1 through Day 8
measure: Occurrence of systemic reactogenicity following pIIV vaccination for Group 5
time frame: Day 29 through Day 36
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine
time frame: Day 1
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine
time frame: Day 29
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 1, 5
time frame: Day 209
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 1, 5
time frame: Day 85
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 2
time frame: Day 141
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 2
time frame: Day 265
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 3
time frame: Day 225
measure: Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine for Group 3
time frame: Day 349
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines
time frame: Day 1
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines
time frame: Day 29
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 2
time frame: Day 113
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 2
time frame: Day 141
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 2
time frame: Day 265
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 3
time frame: Day 197
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 3
time frame: Day 225
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 3
time frame: Day 349
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Groups 1, 5
time frame: Day 209
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Groups 1, 5
time frame: Day 57
measure: Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Groups 1, 5
time frame: Day 85
measure: Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer)
time frame: Day 29
measure: Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Group 2
time frame: Day 141
measure: Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Group 2
time frame: Day 265
measure: Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Group 3
time frame: Day 225
measure: Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Group 3
time frame: Day 349
measure: Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Groups 1, 5
time frame: Day 209
measure: Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer) for Groups 1, 5
time frame: Day 85
measure: Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer <1:10 and a post-vaccination NtAb titer = / > 1:40 or a pre-vaccination NtAb titer = / > 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer)
time frame: Day 29
measure: Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer <1:10 and a post-vaccination NtAb titer = / > 1:40 or a pre-vaccination NtAb titer = / > 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 2
time frame: Day 113
measure: Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer <1:10 and a post-vaccination NtAb titer = / > 1:40 or a pre-vaccination NtAb titer = / > 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 2
time frame: Day 141
measure: Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer <1:10 and a post-vaccination NtAb titer = / > 1:40 or a pre-vaccination NtAb titer = / > 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 2
time frame: Day 265
measure: Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer <1:10 and a post-vaccination NtAb titer = / > 1:40 or a pre-vaccination NtAb titer = / > 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 3
time frame: Day 197
measure: Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer <1:10 and a post-vaccination NtAb titer = / > 1:40 or a pre-vaccination NtAb titer = / > 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 3
time frame: Day 225
measure: Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer <1:10 and a post-vaccination NtAb titer = / > 1:40 or a pre-vaccination NtAb titer = / > 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Group 3
time frame: Day 349
measure: Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer <1:10 and a post-vaccination NtAb titer = / > 1:40 or a pre-vaccination NtAb titer = / > 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Groups 1, 5
time frame: Day 209
measure: Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer <1:10 and a post-vaccination NtAb titer = / > 1:40 or a pre-vaccination NtAb titer = / > 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Groups 1, 5
time frame: Day 57
measure: Percentage of subjects achieving seroconversion (a pre-vaccination NtAb titer <1:10 and a post-vaccination NtAb titer = / > 1:40 or a pre-vaccination NtAb titer = / > 1:10 and a minimum 4-fold rise in post-vaccination NtAb titer) for Groups 1, 5
time frame: Day 85
arm group label: Group 1
arm group type: Experimental
description: 12 patients receive Intramuscular (IM) A/H7N9 15 mcg on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of Intranasal (IN) sprayer 10^7 FFU H7 N9 pLAIV on Day 29
arm group label: Group 2
arm group type: Experimental
description: 12 patients receive A/H7N9 15 mcg IM on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of IN sprayer10^7 FFU H7 N9 pLAIV on Day 85
arm group label: Group 3
arm group type: Experimental
description: 12 patients receive S A/H7N9 15 mcg IM on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of IN sprayer 10^7 FFU H7 N9 pLAIV on Day 169
arm group label: Group 4
arm group type: Experimental
description: 8 patients receive A/H7N9 15 mcg IM on Day 1, 8 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1
arm group label: Group 5
arm group type: Experimental
description: 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant on Day 1 and Day 29
intervention type: Biological
intervention name: Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca
description: MedImmune supplies pLAIV vaccines as a colorless to pale yellow and clear to slightly cloudy suspension in single, unit-dose, Becton-Dickinson Accuspray™ Nasal Spray Systems sprayer devices. Each filled sprayer device contains a 0.5 mL dose of 10^7FFU of H7N9 Anhui 2013/AA ca vaccine. Group I receives the IN dose on Day 29, Group 2 on Day 85, and Group 3 on Day 169.
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
intervention type: Biological
intervention name: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
description: Sanofi supplies the monovalent influenza A/H7N9 virus vaccine as a sterile, clear, and slightly opalescent suspension in single-dose vials containing 15 mcg HA per 0.5 mL. Group 1 through Group5 will receive the IM vaccine on Day 1
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
arm group label: Group 4
arm group label: Group 5
intervention type: Drug
intervention name: MF59 adjuvant
description: Novartis supplies the MF59 adjuvant as an oil-in-water milky emulsion in single-use vials containing a fill volume of 0.7 mL. Group 1 through Group 5 will receive MF59 IM on Day 1.
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
arm group label: Group 4
arm group label: Group 5
criteria: 
gender: All
minimum age: 18 Years
maximum age: 47 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Influenza, Human
mesh term: Influenza in Birds
mesh term: Vaccines