<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/NCT02215863</url>
  </required_header>
  <id_info>
    <org_study_id>FLUPCV13</org_study_id>
    <nct_id>NCT02215863</nct_id>
  </id_info>
  <brief_title>Immunogenicity and Safety of PCV13 and Fluad in Adults Aged ≥60 Years</brief_title>
  <official_title>Immunogenicity and Safety of 13-valent Pneumococcal Conjugate Vaccine (PCV13) and MF59-adjuvanted Influenza Vaccine (Fluad) After Concomitant Vaccination in Adults Aged ≥60 Years</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Korea University Guro Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Korea University Guro Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recent reviews have highlighted the unpredictability and complexity of immune interference&#xD;
      when multivalent conjugate vaccines are co-administered with other pediatric vaccines. It has&#xD;
      become evident that the likelihood of immune interference (in response to conjugated- or&#xD;
      co-administered antigens) increases in proportional to the number of glyco-conjugates&#xD;
      (valencies) and dosages of carrier proteins. There are many kinds of carrier proteins:&#xD;
      tetanus toxoid (TT), diphtheria toxoid (DT), CRM197 (non-toxic variant of DT), OMP (complex&#xD;
      outer-membrane protein mixture from Neisseria meningitidis) and non-typeable Hemophilus&#xD;
      influenza-derived protein D. Among them, TT is a more potent inducer of T-helper immunity,&#xD;
      but carrier-induced-epitopic suppression (dose-dependent carrier antibody and carrier B cell&#xD;
      dominance) may occur with TT. In comparison, DT and CRM197 are weaker B-cell immunogens, but&#xD;
      apparently trigger more T-regulatory mechanism. Recent pediatric studies of PCV13&#xD;
      co-administered with DTaP vaccines showed 6B GMT (geometric mean titer) to be somewhat&#xD;
      reduced compared to the results with PCV13 alone.&#xD;
&#xD;
      Similar to children, adults frequently visit outpatient clinics to get two or more kinds of&#xD;
      vaccines at the same time: pneumococcal vaccine, influenza vaccine, Td (diphtheria and&#xD;
      tetanus) vaccine, HPV (human papilloma virus) vaccine, meningococcal vaccine, zoster vaccine,&#xD;
      etc. PCV13 has limited co-administration information for adjuvanted influenza vaccine.&#xD;
&#xD;
      This study is designed to evaluate the immunogenicity and safety of PCV13 and MF59-adjuvanted&#xD;
      influenza vaccine (Fluad) after concomitant administration in adults aged 60 years or older.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a multi-centered, randomized controlled clinical trial: Korea University Guro&#xD;
      Hospital, Korea University Ansan Hospital, Hallym University Gangnam Sacred Hospital and&#xD;
      Catholic University Medical College, St. Vincent's Hospital.&#xD;
&#xD;
      The primary objective is to evaluate the immunogenicity of Fluad after concomitant&#xD;
      administration of Fluad and PCV13 in adults aged 60 years or more. This study is designed to&#xD;
      demonstrate non-inferiority of sero-conversion rate after Fluad vaccination: Fluad-PCV13&#xD;
      co-administration group versus Fluad alone group&#xD;
&#xD;
      The secondary objective is to evaluate the immunogenicity of PCV13 after concomitant&#xD;
      administration in adults aged 60 years or more. This study is designed to demonstrate&#xD;
      non-inferiority of PCV13 when co-administered with Fluad compared with PCV13 alone.&#xD;
&#xD;
      This study is also designed to evaluate the safety of concomitant PCV13-Fluad administration&#xD;
      in adults aged 60 years or more. All the participants will be followed for the duration of an&#xD;
      expected average of 4 weeks after vaccination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Seroconversion rates (A/H1N1, A/H3N2, and B)</measure>
    <time_frame>Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination)</time_frame>
    <description>a post-vaccination titer ≥1:40 in subjects with a pre-vaccination titer of &lt;1:10 or a ≥4-fold titer increase in subjects with a pre-vaccination titer of ≥1:10</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Seroprotection rates and GMT folds (A/H1N1, A/H3N2, and B)</measure>
    <time_frame>Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination).</time_frame>
    <description>Seroprotection rate: percentage of subjects with a post-vaccination titer ≥1:40&#xD;
GMT-fold change: GMT ratio of the post-vaccination titer to pre-vaccination titer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Opsonophagocytic assay (OPA) titers for PCV13</measure>
    <time_frame>Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination).</time_frame>
    <description>OPA geometric mean titers for 13 PCV13 serotypes with corresponding 2-sided 95% confidence intervals between groups receiving PCV 13 and then compare the results</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Frequency and duration of local and systemic adverse events</measure>
    <time_frame>All participants will be followed until 4 weeks after vaccination)</time_frame>
    <description>The safety profiles of co-administration of Fluad and PCV13 will be compared to those of single vaccination.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">1195</enrollment>
  <condition>Influenza</condition>
  <condition>Streptococcus Pneumoniae</condition>
  <arm_group>
    <arm_group_label>PCV13 and Fluad</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>437 concomitant Fluad-PCV13 recipients: one dose of each vaccine administered on Day 0</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fluad alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>437 Fluad recipients: one vaccine injection administered on Day 0</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PCV13 alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>437 PCV13 recipients: one vaccine injection administered on Day 0</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fluad and Prevenar13</intervention_name>
    <arm_group_label>PCV13 and Fluad</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fluad</intervention_name>
    <arm_group_label>Fluad alone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Prevenar13</intervention_name>
    <arm_group_label>PCV13 alone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults aged ≥60 years who signed the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous pneumococcal vaccine recipients&#xD;
&#xD;
          -  Egg allergy&#xD;
&#xD;
          -  History of serious adverse event after vaccination,&#xD;
&#xD;
          -  any acute disease or infection&#xD;
&#xD;
          -  History of neurological symptoms or signs&#xD;
&#xD;
          -  Impairment of immune function or immunosuppressant use&#xD;
&#xD;
          -  Bleeding diathesis&#xD;
&#xD;
          -  Fever (defined as axillary temperature ³38.0°C) within 3 days (prior to Visit 1)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hee Jin Cheong, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Korea University Guro Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Joon Young Song, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Korea University Guro Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Korea University Ansan Hospital</name>
      <address>
        <city>Ansan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hallym University Gangnam Sacred Hospita</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Catholic University Medical College, St. Vincent's Hospital</name>
      <address>
        <city>Suwon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>March 31, 2015</last_update_submitted>
  <last_update_submitted_qc>March 31, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 1, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Korea University Guro Hospital</investigator_affiliation>
    <investigator_full_name>Hee Jin Cheong</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Immunogenicity, Safety, MF59, Influenza vaccine, Pneumococcal vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
    <mesh_term>Pneumonia, Pneumococcal</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heptavalent Pneumococcal Conjugate Vaccine</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/NCT02215863
org study id: FLUPCV13
nct id: NCT02215863
lead sponsor: 
collaborator: 
has dmc: Yes
Recent reviews have highlighted the unpredictability and complexity of immune interference
      when multivalent conjugate vaccines are co-administered with other pediatric vaccines. It has
      become evident that the likelihood of immune interference (in response to conjugated- or
      co-administered antigens) increases in proportional to the number of glyco-conjugates
      (valencies) and dosages of carrier proteins. There are many kinds of carrier proteins:
      tetanus toxoid (TT), diphtheria toxoid (DT), CRM197 (non-toxic variant of DT), OMP (complex
      outer-membrane protein mixture from Neisseria meningitidis) and non-typeable Hemophilus
      influenza-derived protein D. Among them, TT is a more potent inducer of T-helper immunity,
      but carrier-induced-epitopic suppression (dose-dependent carrier antibody and carrier B cell
      dominance) may occur with TT. In comparison, DT and CRM197 are weaker B-cell immunogens, but
      apparently trigger more T-regulatory mechanism. Recent pediatric studies of PCV13
      co-administered with DTaP vaccines showed 6B GMT (geometric mean titer) to be somewhat
      reduced compared to the results with PCV13 alone.

      Similar to children, adults frequently visit outpatient clinics to get two or more kinds of
      vaccines at the same time: pneumococcal vaccine, influenza vaccine, Td (diphtheria and
      tetanus) vaccine, HPV (human papilloma virus) vaccine, meningococcal vaccine, zoster vaccine,
      etc. PCV13 has limited co-administration information for adjuvanted influenza vaccine.

      This study is designed to evaluate the immunogenicity and safety of PCV13 and MF59-adjuvanted
      influenza vaccine (Fluad) after concomitant administration in adults aged 60 years or older.
This study is a multi-centered, randomized controlled clinical trial: Korea University Guro
      Hospital, Korea University Ansan Hospital, Hallym University Gangnam Sacred Hospital and
      Catholic University Medical College, St. Vincent's Hospital.

      The primary objective is to evaluate the immunogenicity of Fluad after concomitant
      administration of Fluad and PCV13 in adults aged 60 years or more. This study is designed to
      demonstrate non-inferiority of sero-conversion rate after Fluad vaccination: Fluad-PCV13
      co-administration group versus Fluad alone group

      The secondary objective is to evaluate the immunogenicity of PCV13 after concomitant
      administration in adults aged 60 years or more. This study is designed to demonstrate
      non-inferiority of PCV13 when co-administered with Fluad compared with PCV13 alone.

      This study is also designed to evaluate the safety of concomitant PCV13-Fluad administration
      in adults aged 60 years or more. All the participants will be followed for the duration of an
      expected average of 4 weeks after vaccination.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Seroconversion rates (A/H1N1, A/H3N2, and B)
time frame: Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination)
description: a post-vaccination titer ≥1:40 in subjects with a pre-vaccination titer of <1:10 or a ≥4-fold titer increase in subjects with a pre-vaccination titer of ≥1:10
measure: Seroprotection rates and GMT folds (A/H1N1, A/H3N2, and B)
time frame: Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination).
description: Seroprotection rate: percentage of subjects with a post-vaccination titer ≥1:40
GMT-fold change: GMT ratio of the post-vaccination titer to pre-vaccination titer
measure: Opsonophagocytic assay (OPA) titers for PCV13
time frame: Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination).
description: OPA geometric mean titers for 13 PCV13 serotypes with corresponding 2-sided 95% confidence intervals between groups receiving PCV 13 and then compare the results
measure: Frequency and duration of local and systemic adverse events
time frame: All participants will be followed until 4 weeks after vaccination)
description: The safety profiles of co-administration of Fluad and PCV13 will be compared to those of single vaccination.
arm group label: PCV13 and Fluad
arm group type: Active Comparator
description: 437 concomitant Fluad-PCV13 recipients: one dose of each vaccine administered on Day 0
arm group label: Fluad alone
arm group type: Active Comparator
description: 437 Fluad recipients: one vaccine injection administered on Day 0
arm group label: PCV13 alone
arm group type: Active Comparator
description: 437 PCV13 recipients: one vaccine injection administered on Day 0
intervention type: Biological
intervention name: Fluad and Prevenar13
arm group label: PCV13 and Fluad
intervention type: Biological
intervention name: Fluad
arm group label: Fluad alone
intervention type: Biological
intervention name: Prevenar13
arm group label: PCV13 alone
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Hee Jin Cheong, MD, PhD
role: Principal Investigator
affiliation: Korea University Guro Hospital
last name: Joon Young Song, MD, PhD
role: Principal Investigator
affiliation: Korea University Guro Hospital
facility: 
facility: 
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Korea University Guro Hospital
investigator full name: Hee Jin Cheong
investigator title: Professor
mesh term: Influenza, Human
mesh term: Pneumonia, Pneumococcal
mesh term: Heptavalent Pneumococcal Conjugate Vaccine