<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/NCT03032419</url>
  </required_header>
  <id_info>
    <org_study_id>VIPV-06</org_study_id>
    <nct_id>NCT03032419</nct_id>
  </id_info>
  <brief_title>Safety and Immunogenicity of Adjuvanted Reduced Dose Inactivated Polio Vaccine Given at 6, 10, 14 Weeks and 9 Months</brief_title>
  <acronym>VIPV-06</acronym>
  <official_title>Safety and Immunogenicity of Adjuvanted Reduced Dose Inactivated Polio Vaccine, IPV-Al SSI, in Comparison to Non-adjuvanted Full Dose IPV SSI, in Infants Vaccinated at 6, 10, 14 Weeks and 9 Months of Age</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Statens Serum Institut</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bill and Melinda Gates Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Larix A/S</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Syneos Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>AJ Vaccines A/S</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Statens Serum Institut</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial is a phase III, non-inferiority, observer-blind, randomised, controlled,&#xD;
      multicentre clinical trial with 2 parallel groups: IPV-Al SSI (investigational vaccine) and&#xD;
      IPV SSI (reference vaccine)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In addition to the trial vaccine (IPV-Al SSI or IPV SSI), the trial subjects will receive&#xD;
      vaccinations with the Philippine national childhood vaccination programme. The trial vaccine&#xD;
      (IPV-Al SSI or IPV SSI) is administered in the RIGHT thigh, where other injectable childhood&#xD;
      vaccines are administered in the opposite (LEFT) thigh. There are 6 trial visits:&#xD;
&#xD;
      Visit 1 (screening, 1st vaccination and blood sampling visit): written informed consent is&#xD;
      obtained. Information on medical history, demographics and concomitant medication is&#xD;
      collected, a physical examination is performed and the subject's eligibility is assessed&#xD;
      according to the pre-specified in-/exclusion criteria. A pre-vaccination blood sample is&#xD;
      taken for polio antibody measurements, and the subject is randomly allocated into one of the&#xD;
      2 groups and vaccinated. If it is not possible to draw a blood sample on Visit 1 the child&#xD;
      cannot continue in the trial. The subject is observed for immediate AEs ½ an hour after all&#xD;
      vaccinations. A diary, a ruler and a thermometer are handed out to the parents to record&#xD;
      daily the temperature and injection site reactions, during the first 3 days after the&#xD;
      vaccinations until resolved and to record any AEs as instructed by the trial staff. 2 days&#xD;
      after Visit 1 the trial staff will make a telephone call to the parent(s)/guardian(s) to&#xD;
      clarify any questions regarding the AE recording in the diary.&#xD;
&#xD;
      Visit 2 (2nd vaccination visit), 28-42 days after Visit 1: contraindications are reviewed,&#xD;
      the 2nd vaccination is given, the diary is collected and AEs and concomitant medications&#xD;
      (CMs) are recorded. A new diary is handed out.&#xD;
&#xD;
      2 days after Visit 2 the trial staff will make a telephone call to the parent(s)/guardian(s)&#xD;
      to clarify any questions regarding the AE recording in the diary.&#xD;
&#xD;
      Visit 3 (3rd vaccination visit), 28-42 days after Visit 2: contraindications are reviewed,&#xD;
      the 3rd vaccination is given, the diary is collected and AEs and CMs are recorded. A new&#xD;
      diary is handed out. 2 days after Visit 3 the trial staff will make a telephone call to the&#xD;
      parent(s)/guardian(s) to clarify any questions regarding the AE recording in the diary.&#xD;
&#xD;
      Visit 4 (blood sample visit), 28-42 days after Visit 3: a blood sample for polio antibody&#xD;
      measurements is taken, the diary is collected, and AEs and CMs are recorded.&#xD;
&#xD;
      Visit 5 (4th vaccination and blood sample visit), at 9 months of age (+14 days): a blood&#xD;
      sample is taken for polio antibody measurements, contraindications are reviewed, the 4th&#xD;
      vaccination is given, and AEs and CMs are recorded. A new diary is handed out. 2 days after&#xD;
      Visit 5 the trial staff will make a telephone call to the parent(s)/guardian(s) to clarify&#xD;
      any questions regarding the AE recording in the diary.&#xD;
&#xD;
      Visit 6 (blood sample and end of trial visit), 28-42 days after Visit 5: a blood sample for&#xD;
      polio antibody measurements is taken, the diary is collected, and AEs and CMs are recorded.&#xD;
      The end of trial form is completed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 6, 2017</start_date>
  <completion_date type="Actual">March 12, 2018</completion_date>
  <primary_completion_date type="Actual">September 21, 2017</primary_completion_date>
  <phase>Phase 3</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>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Seroconversion for poliovirus type 1, 2 and 3 for IPV-Al compared to IPV SSI</measure>
    <time_frame>Change from baseline to one month after 3rd vaccination</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse event following vaccinations (key secondary)</measure>
    <time_frame>After primary injections at 2, 4 and 6 months of age</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjects with seroprotection against poliovirus types 1, 2 and 3</measure>
    <time_frame>One months after 3rd vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjects with seroprotection against poliovirus types 1, 2 and 3</measure>
    <time_frame>Before and one month after the 4th vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjects with poliovirus types 1, 2 and 3 post-vaccination titres ≥ 4-fold above the estimated titre of maternal antibody</measure>
    <time_frame>One months after 3rd vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titres (GMTs) and medians for poliovirus types 1, 2 and 3</measure>
    <time_frame>One months after 3rd vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titres (GMTs) and medians for poliovirus types 1, 2 and 3</measure>
    <time_frame>Before and one month after the 4th vaccination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reverse cumulative titre distribution curves for poliovirus types 1, 2 and 3</measure>
    <time_frame>From baseline, one month after 3rd vaccination, and before and one month after 4th vaccination</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Sensitivity analysis: subjects with ≥ 4-fold increases in poliovirus types 1, 2 and 3 titres</measure>
    <time_frame>From baseline to one month after 3rd vaccination</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - seroprotection against poliovirus types 1, 2 and 3</measure>
    <time_frame>One month after 3rd vaccinations</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - seroprotection against poliovirus types 1, 2 and 3</measure>
    <time_frame>Before and one month after 4th vaccination</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - post-vaccination titre ≥ 4-fold above maternal titre against poliovirus types 1, 2 and 3</measure>
    <time_frame>One month after 3th vaccination</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - geometric mean titres and median for poliovirus types 1, 2 and 3</measure>
    <time_frame>One month after 3th vaccination</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - geometric mean titres and median for poliovirus types 1, 2 and 3</measure>
    <time_frame>Before and one month after 4th vaccination</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - reverse cumulative titre distribution curves for poliovirus types 1, 2 and 3</measure>
    <time_frame>From baseline to one month after 4th vaccination</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1002</enrollment>
  <condition>Poliomyelitis</condition>
  <arm_group>
    <arm_group_label>IPV-Al SSI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IPV-Al contains the reduced dose of IPV to be administered intramuscularly to the anterolateral aspect of the right thigh. Each subject randomised to this group will receive three primary injection at 6, 10, and 14 weeks of age and one booster injection at 9 months of age</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IPV SSI</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>IPV SSI contains the full dose of IPV to be administered intramuscularly to the anterolateral aspect of the right thigh. Each subject randomised to this group will receive three primary injection at 6, 10, and 14 weeks of age and one booster injection at 9 months of age</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IPV-Al SSI</intervention_name>
    <description>3 primary injections of IPV-Al SSI at 6, 10, and 14 weeks of age and 1 booster at 9 months of age</description>
    <arm_group_label>IPV-Al SSI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IPV SSI</intervention_name>
    <description>3 primary injections of IPV SSI at 6, 10, and 14 weeks of age and 1 booster at 9 months of age</description>
    <arm_group_label>IPV SSI</arm_group_label>
    <other_name>IPV Vaccine SSI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Infants of 6 weeks of age (-3 to +14 days) on the date of the 1st vaccination&#xD;
&#xD;
          2. Healthy assessed from medical history and physical examination&#xD;
&#xD;
          3. Parent(s)/guardian(s) willing to let their infant follow the national Philippine&#xD;
             childhood vaccination programme and schedule, in addition to let their infant receive&#xD;
             the trial vaccine&#xD;
&#xD;
          4. Parent(s)/guardian(s) properly informed about the trial and has signed the informed&#xD;
             consent form&#xD;
&#xD;
          5. Parent(s)/guardian(s) granting access to the infant's trial related medical records&#xD;
&#xD;
          6. Parent(s)/guardian(s) likely to comply with the trial procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Vaccinated with any polio vaccine other than the trial vaccines, prior to inclusion or&#xD;
             planned during the trial&#xD;
&#xD;
          2. OPV vaccination or known exposure to poliovirus (wild or vaccine derived) in household&#xD;
             (living together) within 3 months prior to inclusion or planned during the trial&#xD;
&#xD;
          3. Low birth weight (&lt; 2,500 g)&#xD;
&#xD;
          4. Known or suspected immunodeficiency (e.g. leukaemia, lymphoma) or family history of&#xD;
             congenital or hereditary immunodeficiency. HIV infection is not an exclusion criteria&#xD;
&#xD;
          5. Severe uncontrolled chronic (e.g. neurologic, pulmonary, gastrointestinal, hepatic,&#xD;
             renal or endocrine) disease&#xD;
&#xD;
          6. Known or suspected allergy to vaccine constituents (e.g. hypersensitivity to&#xD;
             formaldehyde, aluminium or 2-phenoxyethanol)&#xD;
&#xD;
          7. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections&#xD;
             or blood sampling&#xD;
&#xD;
          8. Treatment with a product which is likely to modify the immune response (e.g. blood&#xD;
             products and immunoglobulins) prior to inclusion or planned during the trial&#xD;
&#xD;
          9. Participating in another clinical trial&#xD;
&#xD;
         10. Not suitable for inclusion in the opinion of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Weeks</minimum_age>
    <maximum_age>9 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ingrid Kromann</last_name>
    <role>Study Director</role>
    <affiliation>Statens Serum Institut</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>5 sites in Philippines</name>
      <address>
        <city>Manila</city>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Philippines</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>January 16, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>November 12, 2018</last_update_submitted>
  <last_update_submitted_qc>November 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Poliomyelitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03032419
org study id: VIPV-06
nct id: NCT03032419
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The trial is a phase III, non-inferiority, observer-blind, randomised, controlled,
      multicentre clinical trial with 2 parallel groups: IPV-Al SSI (investigational vaccine) and
      IPV SSI (reference vaccine)
In addition to the trial vaccine (IPV-Al SSI or IPV SSI), the trial subjects will receive
      vaccinations with the Philippine national childhood vaccination programme. The trial vaccine
      (IPV-Al SSI or IPV SSI) is administered in the RIGHT thigh, where other injectable childhood
      vaccines are administered in the opposite (LEFT) thigh. There are 6 trial visits:

      Visit 1 (screening, 1st vaccination and blood sampling visit): written informed consent is
      obtained. Information on medical history, demographics and concomitant medication is
      collected, a physical examination is performed and the subject's eligibility is assessed
      according to the pre-specified in-/exclusion criteria. A pre-vaccination blood sample is
      taken for polio antibody measurements, and the subject is randomly allocated into one of the
      2 groups and vaccinated. If it is not possible to draw a blood sample on Visit 1 the child
      cannot continue in the trial. The subject is observed for immediate AEs ½ an hour after all
      vaccinations. A diary, a ruler and a thermometer are handed out to the parents to record
      daily the temperature and injection site reactions, during the first 3 days after the
      vaccinations until resolved and to record any AEs as instructed by the trial staff. 2 days
      after Visit 1 the trial staff will make a telephone call to the parent(s)/guardian(s) to
      clarify any questions regarding the AE recording in the diary.

      Visit 2 (2nd vaccination visit), 28-42 days after Visit 1: contraindications are reviewed,
      the 2nd vaccination is given, the diary is collected and AEs and concomitant medications
      (CMs) are recorded. A new diary is handed out.

      2 days after Visit 2 the trial staff will make a telephone call to the parent(s)/guardian(s)
      to clarify any questions regarding the AE recording in the diary.

      Visit 3 (3rd vaccination visit), 28-42 days after Visit 2: contraindications are reviewed,
      the 3rd vaccination is given, the diary is collected and AEs and CMs are recorded. A new
      diary is handed out. 2 days after Visit 3 the trial staff will make a telephone call to the
      parent(s)/guardian(s) to clarify any questions regarding the AE recording in the diary.

      Visit 4 (blood sample visit), 28-42 days after Visit 3: a blood sample for polio antibody
      measurements is taken, the diary is collected, and AEs and CMs are recorded.

      Visit 5 (4th vaccination and blood sample visit), at 9 months of age (+14 days): a blood
      sample is taken for polio antibody measurements, contraindications are reviewed, the 4th
      vaccination is given, and AEs and CMs are recorded. A new diary is handed out. 2 days after
      Visit 5 the trial staff will make a telephone call to the parent(s)/guardian(s) to clarify
      any questions regarding the AE recording in the diary.

      Visit 6 (blood sample and end of trial visit), 28-42 days after Visit 5: a blood sample for
      polio antibody measurements is taken, the diary is collected, and AEs and CMs are recorded.
      The end of trial form is completed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Seroconversion for poliovirus type 1, 2 and 3 for IPV-Al compared to IPV SSI
time frame: Change from baseline to one month after 3rd vaccination
measure: Adverse event following vaccinations (key secondary)
time frame: After primary injections at 2, 4 and 6 months of age
measure: Subjects with seroprotection against poliovirus types 1, 2 and 3
time frame: One months after 3rd vaccination
measure: Subjects with seroprotection against poliovirus types 1, 2 and 3
time frame: Before and one month after the 4th vaccination
measure: Subjects with poliovirus types 1, 2 and 3 post-vaccination titres ≥ 4-fold above the estimated titre of maternal antibody
time frame: One months after 3rd vaccination
measure: Geometric mean titres (GMTs) and medians for poliovirus types 1, 2 and 3
time frame: One months after 3rd vaccination
measure: Geometric mean titres (GMTs) and medians for poliovirus types 1, 2 and 3
time frame: Before and one month after the 4th vaccination
measure: Reverse cumulative titre distribution curves for poliovirus types 1, 2 and 3
time frame: From baseline, one month after 3rd vaccination, and before and one month after 4th vaccination
measure: Sensitivity analysis: subjects with ≥ 4-fold increases in poliovirus types 1, 2 and 3 titres
time frame: From baseline to one month after 3rd vaccination
measure: Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - seroprotection against poliovirus types 1, 2 and 3
time frame: One month after 3rd vaccinations
measure: Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - seroprotection against poliovirus types 1, 2 and 3
time frame: Before and one month after 4th vaccination
measure: Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - post-vaccination titre ≥ 4-fold above maternal titre against poliovirus types 1, 2 and 3
time frame: One month after 3th vaccination
measure: Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - geometric mean titres and median for poliovirus types 1, 2 and 3
time frame: One month after 3th vaccination
measure: Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - geometric mean titres and median for poliovirus types 1, 2 and 3
time frame: Before and one month after 4th vaccination
measure: Sensitivity analysis: sub-groups of infants with and without seroprotection at baseline - reverse cumulative titre distribution curves for poliovirus types 1, 2 and 3
time frame: From baseline to one month after 4th vaccination
arm group label: IPV-Al SSI
arm group type: Experimental
description: IPV-Al contains the reduced dose of IPV to be administered intramuscularly to the anterolateral aspect of the right thigh. Each subject randomised to this group will receive three primary injection at 6, 10, and 14 weeks of age and one booster injection at 9 months of age
arm group label: IPV SSI
arm group type: Active Comparator
description: IPV SSI contains the full dose of IPV to be administered intramuscularly to the anterolateral aspect of the right thigh. Each subject randomised to this group will receive three primary injection at 6, 10, and 14 weeks of age and one booster injection at 9 months of age
intervention type: Biological
intervention name: IPV-Al SSI
description: 3 primary injections of IPV-Al SSI at 6, 10, and 14 weeks of age and 1 booster at 9 months of age
arm group label: IPV-Al SSI
intervention type: Biological
intervention name: IPV SSI
description: 3 primary injections of IPV SSI at 6, 10, and 14 weeks of age and 1 booster at 9 months of age
arm group label: IPV SSI
other name: IPV Vaccine SSI
criteria: 
gender: All
minimum age: 6 Weeks
maximum age: 9 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Ingrid Kromann
role: Study Director
affiliation: Statens Serum Institut
facility: 
country: Philippines
responsible party type: Sponsor
mesh term: Poliomyelitis
mesh term: Vaccines
sharing ipd: Yes