Development of a Serocorrelate of Protection Against Invasive Group B Streptococcus Disease (iGBS3)

A multicentre study to provide evidence that the relationship between an immune marker value (anti-GBS IgG concentration) and the probability of invasive GBS (iGBS) disease in infants less than 90 days of age is sufficiently strong that a vaccine able to induce an immune response will lead to a meaningful decrease in the probability of iGBS disease.

Study Overview

• Status: Recruiting
• Conditions: Streptococcus Agalactiae Infection
• Intervention / Treatment: Other: No intervention

Detailed Description

Group B Streptococcus (GBS) is a bacterium (a bug) that causes serious infections in young infants across the world. In 2015 it was estimated that there were at least 319,000 infants under 3 months of age with GBS disease worldwide, resulting in 90,000 deaths and at least 10,000 children with long term disabilities. Around 20% of all pregnant women carry GBS in their vagina and bowel and babies are exposed to GBS bacteria around the time of birth. The options for prevention are currently limited to offering antibiotics during labour.

A vaccine that could be given to pregnant women has the greatest potential to benefit mothers and babies worldwide. There are vaccines currently being tested in clinical trials, including in pregnant women. The iGBS3 study aims to find out what levels of immunity (usually measured as antibody) a woman needs to pass to her baby to protect the baby from getting GBS disease. This will allow us to predict what antibody level a vaccine has to achieve to be effective and then to get those vaccines licensed and implemented as quickly as possible.

To do this, the study need to take a small sample of cord blood from a very large number of women just after delivering their baby. The study will need to follow around 180 000 babies in order to find at least 170 babies with GBS disease (of which 100 will have disease with the most common type) and compare their levels of antibody in cord blood with 300 healthy babies exposed to the same GBS type. To achieve this, SGUL will work with the Nottingham Clinical Trials Unit to embed this study in their existing GBS3 Trial, in which 80 hospitals across England, Scotland and Wales will be involved for 2 years.

Study Design iGBS3 is a large, multicentre, prospective, unmatched case control study in the UK designed to compare levels of antibody in cord blood in mothers whose infants develop GBS disease (iGBS) and colonised mothers whose infants do not develop GBS disease. To achieve this, the project aim to recruit at least 170 babies with GBS disease (of which 100 will have disease with the most common type) and 300 healthy babies exposed to the same GBS type. An exploratory substudy will look into levels of antibody in cord blood in mothers whose infants develop severe bacterial or viral infections caused by pathogens other than GBS.

Duration The overall duration of the project is planned for 36 months. This includes 2 months set-up, 12 months recruitment for Phase 1, 4 months for interval analysis, 12 months recruitment for Phase 2, 6 months for final retrieval of data, analysis and write-up.

Two phases

1. Phase 1 - cord blood collection and blood from an infant at time of GBS disease to establish the correlation between antibody at time of disease and cord blood
2. Phase 2 - if Phase 1 demonstrates that the correlation is strong, then in Phase 2 collection of blood from disease cases is required only; if Phase 2 shows a weak correlation, then in Phase 2 prospective collection of cord blood will continue.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Nadia Azzouzi; Phone Number: 02082666488; Email: nazzouzi@sgul.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SW17 ORE
    • Recruiting
    • St George's University of London
    • Principal Investigator: Paul Heath, PhD
    • Contact: Sam Hollingworth; Phone Number: 02082666488; Email: shollin@sgul.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women giving birth in maternity units in England, Scotland and Wales participating in the GBS3 study and their infants in the first 3 month of life

Description

Inclusion Criteria:

-

Exclusion Criteria:

For iGBS disease case recruitment, an infant is not eligible unless a parent/person with parental responsibility gives informed consent For iGBS disease control recruitment, a mother is not eligible unless she gives informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases; Cases are defined as infants who develop invasive GBS disease (iGBS disease= isolation of GBS from a normally sterile site, i.e. blood or CSF) in the first 90 days of life.	Other: No intervention; No intervention
Controls; Controls are defined as infants who are exposed to the same serotype of GBS at birth as the case - but who do not develop iGBS disease in the first 90 days of life.	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlates objective	• To provide initial data on the relationship between antibody and iGBS disease risk by estimating the odds ratio of iGBS disease for antibody concentrations above various thresholds for STIII	36 months
Kinetics objective	• To determine whether antibody concentrations obtained at the time of disease (acute disease sample) can be used to predict cord antibody concentrations at birth in cases of iGBS STIII disease	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlates other than STIII	• To provide data on the relationship between antibody and iGBS disease risk by estimating the odds ratio of iGBS disease for antibody concentrations above various thresholds for serotypes other than STIII as well as all serotypes combined	36 months
Kinetics other than STIII	• To determine whether antibody concentrations obtained at the time of disease (acute disease sample) can be used to predict cord antibody concentrations in cases for serotypes others than STIII and to see if any declines differ by serotype	12 months
Controls objective	• To generate sufficient controls of women colonised with STIII and other serotypes	36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk reduction objective	• To combine case-control study results (odds ratios and antibody RCD curves at different cut-offs) with other data on antibody distribution in the population and iGBS disease risk to determine absolute risk reduction. This could then be combined with vaccine immunologic trial data when available to allow prediction of vaccine efficacy (the decrease in probability of iGBS disease in infants of vaccinated compared to unvaccinated mothers).	36 months
Other pathogens sub-study	• To provide data on the relationship between antibody and infant infections caused by pathogens other than GBS	36 months

Collaborators and Investigators

• Sponsor: St George's, University of London
• Collaborators: University of Nottingham; Medical Research Council; Public Health England
• Investigators: Principal Investigator: Paul Heath, St George's, University of London

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Estimated): March 30, 2024
• Study Completion (Estimated): March 30, 2024

Study Registration Dates

• First Submitted: January 28, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Pregnancy; Vaccine; case control study; serocorrelate of protection
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections
• Other Study ID Numbers: 2020.0176

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No