<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/NCT02215226</url>
  </required_header>
  <id_info>
    <org_study_id>V98_28OBTP</org_study_id>
    <nct_id>NCT02215226</nct_id>
  </id_info>
  <brief_title>GBS Sero-correlate of Protection</brief_title>
  <acronym>V98_28OBTP</acronym>
  <official_title>Establishing a Sero-correlate of Protection Against Invasive Group B Streptococcus Disease in Newborns and Young Infants Aged &lt;=90 Days</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Witwatersrand, South Africa</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Vaccines</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Witwatersrand, South Africa</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Compare anticapsular antibody levels against Group B Streptococcus at delivery in mothers and&#xD;
      their infants who develop disease versus those who do not. Use this comparison to establish&#xD;
      antibody levels associated with reductions in risk of GBS disease in infants aged less than&#xD;
      90 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Group B Streptococcus (GBS) is a leading cause of invasive disease during the neonatal period&#xD;
      in developed and developing countries. The global incidence of disease is 0.53 per 1000 live&#xD;
      births, though a substantially higher incidence has been reported from South Africa (3 per&#xD;
      1000 live births). Of the disease-causing serotypes, types Ia and III account for over 70% of&#xD;
      invasive disease in young infants. The introduction of screening for maternal rectovaginal&#xD;
      GBS colonization, with subsequent treatment of colonized women with intrapartum antibiotic&#xD;
      prophylaxis (IAP) at delivery, has led to a &gt;80% reduction in the incidence of disease in&#xD;
      some settings (Schrag, 2012). However, the residual burden of early-onset disease (EOD) in&#xD;
      countries which have implemented universal screening and IAP remains similar to the incidence&#xD;
      of late-onset disease (LOD), which has not declined over time. The resources necessary to&#xD;
      implement a screening and IAP program has limited the establishment of this intervention in&#xD;
      other developed and most developing countries.&#xD;
&#xD;
      GBS capsular polysaccharide-protein conjugate vaccines (GBS-CV) aimed at the immunization of&#xD;
      pregnant women, with protection of the newborn expected from trans-placental acquisition of&#xD;
      the induced antibodies in utero have been developed.&#xD;
&#xD;
      There are a number of challenges to undertaking a large efficacy trial of GBS-CV aimed at&#xD;
      licensure of this vaccine. Consequently, licensure of GBS-CV may depend on establishing an&#xD;
      immunologic/serologic correlate of protection against invasive disease in newborns, as has&#xD;
      been successfully motivated for and adopted in the licensure pathway of meningococcal&#xD;
      vaccines. Although previous studies have aimed to identify serotype-specific correlates of&#xD;
      anticapsular antibody protection against invasive GBS disease during early-infancy;&#xD;
      differences in study-design, age-range of invasive-cases, antibody assay methods and a lack&#xD;
      of standardized reference serum between tests mean a robust sero-correlate of protection&#xD;
      against GBS has yet to be identified.&#xD;
&#xD;
      We propose to conduct a case control study nested within a prospective, longitudinal cohort&#xD;
      of mothers and their infants &lt;=90 days of age, at one academic hospital center in South&#xD;
      Africa. The limited intrapartum antibiotic exposure (10-12% deliveries), relatively high&#xD;
      incidence of both EOD and LOD (2 per 1000 live births and 1 per 1000 live births&#xD;
      respectively) and standardized laboratory surveillance (for case identification) offers an&#xD;
      optimal setting in which to establish correlates of protection against the GBS serotypes that&#xD;
      predominate in this setting (serotypes Ia and III for EOD and serotype III for LOD).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 31, 2016</completion_date>
  <primary_completion_date type="Actual">December 9, 2016</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>3 Months</target_duration>
  <primary_outcome>
    <measure>Risk of early onset Group B Steptococcus disease (due to serotypes Ia or III) with respect to maternal or newborn anticapsular antibody levels at delivery.</measure>
    <time_frame>Birth to 6 days of age</time_frame>
    <description>Early onset Group B Streptococcus disease due to serotypes Ia &amp; III</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Risk of late onset Group B Streptococcus disease (due to serotypes III) with respect to maternal or newborn anticapsular antibody levels at delivery</measure>
    <time_frame>7 to 90 days</time_frame>
    <description>Late onset Group B Streptococcus disease due to serotype III</description>
  </secondary_outcome>
  <enrollment type="Actual">35274</enrollment>
  <condition>Invasive Group B Streptococcus Disease</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Cord blood and maternal blood (serum samples) Vaginal swab samples from mothers Invasive GBS&#xD;
      isolates from cases&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Pregnant women aged 18 years or older attending for antenatal care or delivery at Chris&#xD;
        Hani Baragwanath Academic hospital, and infants who develop GBS disease at the other 2&#xD;
        hospitals in the Johannesburg area&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  (i) Pregnant women attending participating community/hospital antenatal clinics and/or&#xD;
             delivering at participating delivery centers.&#xD;
&#xD;
        (ii) Subjects aged ≥18 years. (iii) Able to understand and comply with planned study&#xD;
        procedures. (iv) Provides written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  (i) Refuses to consent to study participation.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Respiratory and Meningeal Pathogen Research Unit</name>
      <address>
        <city>Soweto, Johannesburg</city>
        <state>Gauteng</state>
        <zip>2013</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>September 2018</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>September 12, 2018</last_update_submitted>
  <last_update_submitted_qc>September 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Witwatersrand, South Africa</investigator_affiliation>
    <investigator_full_name>Shabir Madhi</investigator_full_name>
    <investigator_title>Medical officer</investigator_title>
  </responsible_party>
  <keyword>Group B Streptococcus, early onset disease, late onset disease, anticapsular antibodies, serotype specific</keyword>
  <!-- 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/NCT02215226
org study id: V98_28OBTP
nct id: NCT02215226
lead sponsor: 
collaborator: 
has dmc: No
Compare anticapsular antibody levels against Group B Streptococcus at delivery in mothers and
      their infants who develop disease versus those who do not. Use this comparison to establish
      antibody levels associated with reductions in risk of GBS disease in infants aged less than
      90 days.
Group B Streptococcus (GBS) is a leading cause of invasive disease during the neonatal period
      in developed and developing countries. The global incidence of disease is 0.53 per 1000 live
      births, though a substantially higher incidence has been reported from South Africa (3 per
      1000 live births). Of the disease-causing serotypes, types Ia and III account for over 70% of
      invasive disease in young infants. The introduction of screening for maternal rectovaginal
      GBS colonization, with subsequent treatment of colonized women with intrapartum antibiotic
      prophylaxis (IAP) at delivery, has led to a >80% reduction in the incidence of disease in
      some settings (Schrag, 2012). However, the residual burden of early-onset disease (EOD) in
      countries which have implemented universal screening and IAP remains similar to the incidence
      of late-onset disease (LOD), which has not declined over time. The resources necessary to
      implement a screening and IAP program has limited the establishment of this intervention in
      other developed and most developing countries.

      GBS capsular polysaccharide-protein conjugate vaccines (GBS-CV) aimed at the immunization of
      pregnant women, with protection of the newborn expected from trans-placental acquisition of
      the induced antibodies in utero have been developed.

      There are a number of challenges to undertaking a large efficacy trial of GBS-CV aimed at
      licensure of this vaccine. Consequently, licensure of GBS-CV may depend on establishing an
      immunologic/serologic correlate of protection against invasive disease in newborns, as has
      been successfully motivated for and adopted in the licensure pathway of meningococcal
      vaccines. Although previous studies have aimed to identify serotype-specific correlates of
      anticapsular antibody protection against invasive GBS disease during early-infancy;
      differences in study-design, age-range of invasive-cases, antibody assay methods and a lack
      of standardized reference serum between tests mean a robust sero-correlate of protection
      against GBS has yet to be identified.

      We propose to conduct a case control study nested within a prospective, longitudinal cohort
      of mothers and their infants <=90 days of age, at one academic hospital center in South
      Africa. The limited intrapartum antibiotic exposure (10-12% deliveries), relatively high
      incidence of both EOD and LOD (2 per 1000 live births and 1 per 1000 live births
      respectively) and standardized laboratory surveillance (for case identification) offers an
      optimal setting in which to establish correlates of protection against the GBS serotypes that
      predominate in this setting (serotypes Ia and III for EOD and serotype III for LOD).
observational model: Case-Control
time perspective: Prospective
measure: Risk of early onset Group B Steptococcus disease (due to serotypes Ia or III) with respect to maternal or newborn anticapsular antibody levels at delivery.
time frame: Birth to 6 days of age
description: Early onset Group B Streptococcus disease due to serotypes Ia & III
measure: Risk of late onset Group B Streptococcus disease (due to serotypes III) with respect to maternal or newborn anticapsular antibody levels at delivery
time frame: 7 to 90 days
description: Late onset Group B Streptococcus disease due to serotype III
Cord blood and maternal blood (serum samples) Vaginal swab samples from mothers Invasive GBS
      isolates from cases
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: South Africa
responsible party type: Principal Investigator
investigator affiliation: University of Witwatersrand, South Africa
investigator full name: Shabir Madhi
investigator title: Medical officer