Invasive Group B Streptococcus DiseaseV98_28OBTPNCT02215226
GBS Sero-correlate of Protection
An observational study of Invasive Group B Streptococcus Disease, run by University of Witwatersrand, South Africa at 1 site in South Africa.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Invasive Group B Streptococcus Disease
- How many people
- 35,274 participants
- Where
- 1 siteSouth Africa
- Study dates
- Jul 2014to 31 Dec 2016
- How long will I take part?
- 3 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Pregnant women aged 18 years or older attending for antenatal care or delivery at Chris Hani Baragwanath Academic hospital, and infants who develop GBS disease at the other 2 hospitals in the Johannesburg area
Who may be able to join
- (i) Pregnant women attending participating community/hospital antenatal clinics and/or delivering at participating delivery centers.
- Subjects aged ≥18 years. (iii) Able to understand and comply with planned study procedures. (iv) Provides written informed consent.
Who cannot join
- (i) Refuses to consent to study participation.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Respiratory and Meningeal Pathogen Research Unit
Soweto, Johannesburg, Gauteng, 2013
About this study
Official title: Establishing a Sero-correlate of Protection Against Invasive Group B Streptococcus Disease in Newborns and Young Infants Aged <=90 Days
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.
Read the detailed description
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).
- Conditions
- Invasive Group B Streptococcus Disease
- Keywords
- Group B Streptococcus, early onset disease, late onset disease, anticapsular antibodies, serotype specific
- Medical subject headings
- Late Onset Disorders
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Early onset Group B Streptococcus disease due to serotypes Ia \& III
Measured: Birth to 6 days of age
Secondary outcomes (1)
Risk of late onset Group B Streptococcus disease (due to serotypes III) with respect to maternal or newborn anticapsular antibody levels at delivery
Late onset Group B Streptococcus disease due to serotype III
Measured: 7 to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2014 (estimated)
- Study startJul 2014
- Primary completion9 Dec 2016
- Study completion31 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Invasive Group B Streptococcus DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 35,274 participants (actual)
- Target duration
- 3 Months
Sponsor and investigators
- Lead sponsor
- University of Witwatersrand, South Africa
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Vaccines
- Responsible party
- Principal investigator, Shabir Madhi, University of Witwatersrand, South Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02215226
- Sponsor's protocol ID
- V98_28OBTP
- Acronym
- V98_28OBTP
- Status last verified
- Sep 2018
- First submitted
- 11 Aug 2014
- Last updated
- 13 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Gent V, Dhar N, Izu A, Jones S, Dangor Z, Briner C, Hosken N, Kwatra G, Madhi SA. Association of serum anti-gbs2106 protein immunoglobulin G (IgG) in newborns and risk reduction of invasive group B streptococcus disease during early infancy. Vaccine. 2025 Apr 30;54:127016. doi: 10.1016/j.vaccine.2025.127016. Epub 2025 Mar 14.
PubMed 40088514Madhi SA, Izu A, Kwatra G, Jones S, Dangor Z, Wadula J, Moultrie A, Adam Y, Pu W, Henry O, Briner C, Cutland CL. Association of Group B Streptococcus (GBS) Serum Serotype-Specific Anticapsular Immunoglobulin G Concentration and Risk Reduction for Invasive GBS Disease in South African Infants: An Observational Birth-Cohort, Matched Case-Control Study. Clin Infect Dis. 2021 Sep 7;73(5):e1170-e1180. doi: 10.1093/cid/ciaa1873.
PubMed 33341870Jallow S, Agosti Y, Kgagudi P, Vandecar M, Cutland CL, Simoes EAF, Nunes MC, Suchard MS, Madhi SA. Impaired Transplacental Transfer of Respiratory Syncytial Virus-neutralizing Antibodies in Human Immunodeficiency Virus-infected Versus -uninfected Pregnant Women. Clin Infect Dis. 2019 Jun 18;69(1):151-154. doi: 10.1093/cid/ciy1071.
PubMed 30561563
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Establishing a Sero-correlate of Protection Against Invasive Group B Streptococcus Disease in Newborns and Young Infants Aged <=90 Days
- ClinicalTrials.gov ID
- NCT02215226
- Acronym / sponsor ID
- V98_28OBTP / V98_28OBTP
- Conditions
- Invasive Group B Streptococcus Disease
- Keywords
- Group B Streptococcus, early onset disease, late onset disease, anticapsular antibodies, serotype specific
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 35,274 participants (actual)
- Lead sponsor
- University of Witwatersrand, South AfricaUniversity, hospital or other
- Collaborators
- Novartis Vaccines
- Study start
- Jul 2014
- Primary completion
- 9 Dec 2016 (actual)
- Study completion
- 31 Dec 2016 (actual)
- First posted
- 13 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 3 Months
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Pregnant women aged 18 years or older attending for antenatal care or delivery at Chris Hani Baragwanath Academic hospital, and infants who develop GBS disease at the other 2 hospitals in the Johannesburg area
Key inclusion criteria (2 listed)
- (i) Pregnant women attending participating community/hospital antenatal clinics and/or delivering at participating delivery centers.
- Subjects aged ≥18 years. (iii) Able to understand and comply with planned study procedures. (iv) Provides written informed consent.
Key exclusion criteria (1 listed)
- (i) Refuses to consent to study participation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Early onset Group B Streptococcus disease due to serotypes Ia \& III
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2018.
- Derived from this study: PubMed 40088514Gent V, Dhar N, Izu A, Jones S, Dangor Z, Briner C, Hosken N, Kwatra G, Madhi SA. Association of serum anti-gbs2106 protein immunoglobulin G (IgG) in newborns and risk reduction of invasive group B streptococcus disease during early infancy. Vaccine. 2025 Apr 30;54:127016. doi: 10.1016/j.vaccine.2025.127016. Epub 2025 Mar 14.
- Derived from this study: PubMed 33341870Madhi SA, Izu A, Kwatra G, Jones S, Dangor Z, Wadula J, Moultrie A, Adam Y, Pu W, Henry O, Briner C, Cutland CL. Association of Group B Streptococcus (GBS) Serum Serotype-Specific Anticapsular Immunoglobulin G Concentration and Risk Reduction for Invasive GBS Disease in South African Infants: An Observational Birth-Cohort, Matched Case-Control Study. Clin Infect Dis. 2021 Sep 7;73(5):e1170-e1180. doi: 10.1093/cid/ciaa1873.
- Derived from this study: PubMed 30561563Jallow S, Agosti Y, Kgagudi P, Vandecar M, Cutland CL, Simoes EAF, Nunes MC, Suchard MS, Madhi SA. Impaired Transplacental Transfer of Respiratory Syncytial Virus-neutralizing Antibodies in Human Immunodeficiency Virus-infected Versus -uninfected Pregnant Women. Clin Infect Dis. 2019 Jun 18;69(1):151-154. doi: 10.1093/cid/ciy1071.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Invasive Group B Streptococcus Disease, run by University of Witwatersrand, South Africa at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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. (time frame: Birth to 6 days of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02215226, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2018.