GBS Sero-correlate of Protection

Invasive Group B Streptococcus Disease Clinical Trial

— V98_28OBTP  

Official title:

Establishing a Sero-correlate of Protection Against Invasive Group B Streptococcus Disease in Newborns and Young Infants Aged <=90 Days

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02215226
• Other study ID #: V98_28OBTP
• Status: Completed
• Start date: July 2014
• Est. completion date: December 31, 2016

Study information

• Verified date: September 2018
• Source: University of Witwatersrand, South Africa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35274
• Est. completion date: December 31, 2016
• Est. primary completion date: December 9, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• (i) Pregnant women attending participating community/hospital antenatal clinics and/or delivering at participating delivery centers.

(ii) Subjects aged =18 years. (iii) Able to understand and comply with planned study procedures. (iv) Provides written informed consent.

Exclusion Criteria:

• (i) Refuses to consent to study participation.

Related Conditions & MeSH terms

• Invasive Group B Streptococcus Disease

Locations

Country	Name	City	State
South Africa	Respiratory and Meningeal Pathogen Research Unit	Soweto, Johannesburg	Gauteng

Sponsors (2)

Lead Sponsor	Collaborator
University of Witwatersrand, South Africa	Novartis Vaccines

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Birth to 6 days of age
Secondary	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	7 to 90 days