<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/NCT02189811</url>
  </required_header>
  <id_info>
    <org_study_id>PEGS</org_study_id>
    <nct_id>NCT02189811</nct_id>
  </id_info>
  <brief_title>Polio End-game Strategies - Poliovirus Type 2 Challenge Study</brief_title>
  <official_title>Polio End-game Strategies - Poliovirus Type 2 Challenge Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aga Khan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>World Health Organization</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Aga Khan University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Poliomyelitis eradication has entered its last phase with only three remaining endemic&#xD;
      countries, of which Pakistan is one. There hasn't been a case of wild type poliovirus 2 since&#xD;
      1999, and no case of wild type poliovirus 3 since November 2012. However, paralytic polio&#xD;
      resulting from circulating strains of Sabin poliovirus type 2 have become a challenge, and&#xD;
      reported from several areas with low population immunity to polio, including in Pakistan.&#xD;
      This study will provide data to National Immunization Authorities in order to make strategic&#xD;
      decisions about their polio vaccination schedules in anticipation of the global tOPV to bOPV&#xD;
      switch and will provide data on the proposed responses to type 2 poliovirus outbreaks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The &quot;Polio Endgame Strategy&quot; consists of set of tasks and activities that will be implemented&#xD;
      in the next five years. It includes gradual withdrawal of the widely used oral poliomyelitis&#xD;
      vaccine (OPV) containing live poliovirus, and will eventually lead to complete eradication&#xD;
      and containment of all wild, vaccine-related (VDPV) and Sabin polioviruses. The withdrawal of&#xD;
      the type 2 components of trivalent OPV (tOPV) is the key component in the elimination of&#xD;
      cVDPVs. This entails strengthening of the immunization system by introducing at least one&#xD;
      dose of affordable IPV into the routine immunization schedule globally and then replacing the&#xD;
      trivalent OPV with bivalent OPV in all OPV-using countries - setting the stage for eventually&#xD;
      ending bOPV use in 2019-2020. Most of the developing countries have an OPV schedule however&#xD;
      many developed and European countries follow the IPV only schedule. The current&#xD;
      recommendations for polio eradication and endgame is IPV vaccine to be administered together&#xD;
      with third OPV dose, which in most countries occurs at 14 weeks of age.&#xD;
&#xD;
      This study will assess the protection to type 2 poliovirus achieved after completion of the&#xD;
      recommended schedule with bOPV and IPV; it will compare immunogenicity of bOPV + IPV schedule&#xD;
      with tOPV only schedule; and will quantify the cross-reactivity of bOPV on inducing type 2&#xD;
      immunological reaction. In addition, it will also provide first data on the proposed outbreak&#xD;
      response to type 2 (either with mOPV 2 or with a combination of mOPV 2 and IPV 2).&#xD;
&#xD;
      This study will provide data to National Immunization Authorities in order to make strategic&#xD;
      decisions about their polio vaccination schedules in anticipation of the global tOPV to bOPV&#xD;
      switch and will provide data on the proposed responses to type 2 poliovirus outbreaks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">April 2016</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>Difference in seroprevalence of neutralizing antibodies for type 2 in 19 weeks of age between arms</measure>
    <time_frame>19 weeks of age</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Seroprevalence of neutralizing antibodies at 18 weeks of age</measure>
    <time_frame>18 weeks of age</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Difference in shedding of poliovirus type 2 in stool in 19 weeks of age between arms</measure>
    <time_frame>19 weeks of age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Difference in seroprevalence of neutralizing antibodies at 22 weeks of age between arms</measure>
    <time_frame>22 weeks of age</time_frame>
  </other_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">900</enrollment>
  <condition>Poliomyelitis</condition>
  <arm_group>
    <arm_group_label>IPV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IPV at birth, 6 weeks, 10 weeks, 14 weeks, followed by tOPV at 18 and 22 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bOPV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>bOPV at birth, 6, 10, and 14 weeks. followed by tOPV at 18 and 22 weeks of age</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bOPV and IPV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>bOPV at birth, 6, 10 weeks, and IPV+bOPV at 14 weeks, and tOPV at 18 and 22 weeks of age</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bOPV and IPV and IPV2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>bOPV at birth, 6, 10 weeks and bOPV+IPV at 14 weeks and tOPV+IPV2 at 18 weeks and tOPV alone at 22 weeks of age</description>
  </arm_group>
  <arm_group>
    <arm_group_label>tOPV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>tOPV at birth, 6, 10, 14, 18 and 22 weeks of age</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IPV</intervention_name>
    <description>IPV at birth, 6, 10, 14 weeks of age and tOPV at 18 and 22 weeks of age</description>
    <arm_group_label>IPV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>bOPV</intervention_name>
    <description>bOPV at birth, 6, 10, 14 weeks and tOPV at 18 and 22 weeks of age</description>
    <arm_group_label>bOPV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>bOPV and IPV</intervention_name>
    <description>bOPV till week 10, bOPV+IPV at 14 and tOPV at 18 and 22 weeks of age</description>
    <arm_group_label>bOPV and IPV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>bOPV and IPV and IPV2</intervention_name>
    <description>bOPV till week 10, bOPV+IPV at 14, tOPV+IPV2 at 18 and tOPV at 22 weeks of age</description>
    <arm_group_label>bOPV and IPV and IPV2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>tOPV</intervention_name>
    <description>tOPV till 22 weeks of age</description>
    <arm_group_label>tOPV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newborn of either gender born healthy with birth weight 2.0 kg or more, with immediate&#xD;
             cry, at the study sites (home or health facility births)&#xD;
&#xD;
          -  Not planning to travel away during entire the study period (birth-154 days; birth 22&#xD;
             weeks).&#xD;
&#xD;
          -  Parents resident of the study area for last 3 month at the time of enrolment&#xD;
&#xD;
          -  Parent/guardian provides informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Newborns found acutely ill at the time of enrolment and requiring emergent medical&#xD;
             care/hospitalization, birth weight below 2.0 kg, cry &gt;2 minutes after birth, or family&#xD;
             is planning to be absent during the birth - 154 days study period&#xD;
&#xD;
          -  Refusal of blood testing and cord blood testing&#xD;
&#xD;
          -  Receipt of OPV after birth before eligibility screen&#xD;
&#xD;
          -  Newborns with certain medical conditions i.e., syndromic infants, neonate with&#xD;
             petechial or purpura (contraindication of intramuscular injections)&#xD;
&#xD;
          -  A diagnosis or suspicion of immunodeficiency disorder (either in the participant or in&#xD;
             a member of the immediate family - e.g. several early infant deaths, household member&#xD;
             on chemotherapy) will render the newborn ineligible for the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>1 Day</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ali F Saleem, MBBS,FCPS,MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aga Khan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rehri goth, Ibrahim Hyderi, Ali Akbar Shah, and Bhens Colony</name>
      <address>
        <city>Karachi</city>
        <state>Sindh</state>
        <country>Pakistan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>July 9, 2014</study_first_submitted>
  <study_first_submitted_qc>July 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 15, 2014</study_first_posted>
  <last_update_submitted>May 2, 2016</last_update_submitted>
  <last_update_submitted_qc>May 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 3, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aga Khan University</investigator_affiliation>
    <investigator_full_name>Ali Faisal Saleem</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>IPV</keyword>
  <keyword>OPV</keyword>
  <keyword>tOPV</keyword>
  <keyword>bOPV</keyword>
  <keyword>Polio</keyword>
  <keyword>Endgame</keyword>
  <keyword>Pakistan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Poliomyelitis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02189811
org study id: PEGS
nct id: NCT02189811
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Poliomyelitis eradication has entered its last phase with only three remaining endemic
      countries, of which Pakistan is one. There hasn't been a case of wild type poliovirus 2 since
      1999, and no case of wild type poliovirus 3 since November 2012. However, paralytic polio
      resulting from circulating strains of Sabin poliovirus type 2 have become a challenge, and
      reported from several areas with low population immunity to polio, including in Pakistan.
      This study will provide data to National Immunization Authorities in order to make strategic
      decisions about their polio vaccination schedules in anticipation of the global tOPV to bOPV
      switch and will provide data on the proposed responses to type 2 poliovirus outbreaks.
The "Polio Endgame Strategy" consists of set of tasks and activities that will be implemented
      in the next five years. It includes gradual withdrawal of the widely used oral poliomyelitis
      vaccine (OPV) containing live poliovirus, and will eventually lead to complete eradication
      and containment of all wild, vaccine-related (VDPV) and Sabin polioviruses. The withdrawal of
      the type 2 components of trivalent OPV (tOPV) is the key component in the elimination of
      cVDPVs. This entails strengthening of the immunization system by introducing at least one
      dose of affordable IPV into the routine immunization schedule globally and then replacing the
      trivalent OPV with bivalent OPV in all OPV-using countries - setting the stage for eventually
      ending bOPV use in 2019-2020. Most of the developing countries have an OPV schedule however
      many developed and European countries follow the IPV only schedule. The current
      recommendations for polio eradication and endgame is IPV vaccine to be administered together
      with third OPV dose, which in most countries occurs at 14 weeks of age.

      This study will assess the protection to type 2 poliovirus achieved after completion of the
      recommended schedule with bOPV and IPV; it will compare immunogenicity of bOPV + IPV schedule
      with tOPV only schedule; and will quantify the cross-reactivity of bOPV on inducing type 2
      immunological reaction. In addition, it will also provide first data on the proposed outbreak
      response to type 2 (either with mOPV 2 or with a combination of mOPV 2 and IPV 2).

      This study will provide data to National Immunization Authorities in order to make strategic
      decisions about their polio vaccination schedules in anticipation of the global tOPV to bOPV
      switch and will provide data on the proposed responses to type 2 poliovirus outbreaks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Difference in seroprevalence of neutralizing antibodies for type 2 in 19 weeks of age between arms
time frame: 19 weeks of age
measure: Seroprevalence of neutralizing antibodies at 18 weeks of age
time frame: 18 weeks of age
measure: Difference in shedding of poliovirus type 2 in stool in 19 weeks of age between arms
time frame: 19 weeks of age
measure: Difference in seroprevalence of neutralizing antibodies at 22 weeks of age between arms
time frame: 22 weeks of age
arm group label: IPV
arm group type: Experimental
description: IPV at birth, 6 weeks, 10 weeks, 14 weeks, followed by tOPV at 18 and 22 weeks
arm group label: bOPV
arm group type: Experimental
description: bOPV at birth, 6, 10, and 14 weeks. followed by tOPV at 18 and 22 weeks of age
arm group label: bOPV and IPV
arm group type: Experimental
description: bOPV at birth, 6, 10 weeks, and IPV+bOPV at 14 weeks, and tOPV at 18 and 22 weeks of age
arm group label: bOPV and IPV and IPV2
arm group type: Experimental
description: bOPV at birth, 6, 10 weeks and bOPV+IPV at 14 weeks and tOPV+IPV2 at 18 weeks and tOPV alone at 22 weeks of age
arm group label: tOPV
arm group type: Active Comparator
description: tOPV at birth, 6, 10, 14, 18 and 22 weeks of age
intervention type: Biological
intervention name: IPV
description: IPV at birth, 6, 10, 14 weeks of age and tOPV at 18 and 22 weeks of age
arm group label: IPV
intervention type: Biological
intervention name: bOPV
description: bOPV at birth, 6, 10, 14 weeks and tOPV at 18 and 22 weeks of age
arm group label: bOPV
intervention type: Biological
intervention name: bOPV and IPV
description: bOPV till week 10, bOPV+IPV at 14 and tOPV at 18 and 22 weeks of age
arm group label: bOPV and IPV
intervention type: Biological
intervention name: bOPV and IPV and IPV2
description: bOPV till week 10, bOPV+IPV at 14, tOPV+IPV2 at 18 and tOPV at 22 weeks of age
arm group label: bOPV and IPV and IPV2
intervention type: Biological
intervention name: tOPV
description: tOPV till 22 weeks of age
arm group label: tOPV
criteria: 
gender: All
minimum age: N/A
maximum age: 1 Day
healthy volunteers: No
last name: Ali F Saleem, MBBS,FCPS,MSc
role: Principal Investigator
affiliation: Aga Khan University
facility: 
country: Pakistan
responsible party type: Principal Investigator
investigator affiliation: Aga Khan University
investigator full name: Ali Faisal Saleem
investigator title: Assistant Professor
mesh term: Poliomyelitis