Clinical trial NCT04735419: Development of a Serocorrelate of Protection Against Invasive Group B Streptococcus Disease
Official title: Development of a Serocorrelate of Protection Against Invasive Group B Streptococcus Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Streptococcus Agalactiae Infection
Keywords: Vaccine
Pregnancy
case control study
serocorrelate of protection
Lead sponsor: St George's, University of London
Sponsor class: OTHER
Collaborators: name: Medical Research Council
name: University of Nottingham
name: Public Health England
First posted: 2021-02-03
Enrollment: 400
Sex: ALL
Minimum age (years): 0
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Correlates objective
timeFrame: 36 months
measure: Kinetics objective
timeFrame: 12 months
Secondary outcomes:
measure: Correlates other than STIII
timeFrame: 36 months
measure: Kinetics other than STIII
timeFrame: 12 months
measure: Controls objective
timeFrame: 36 months
Other outcomes:
measure: Risk reduction objective
timeFrame: 36 months
measure: Other pathogens sub-study
timeFrame: 36 months
Locations:
city: London
country: United Kingdom
facility: St George's University of London
Study officials:
affiliation: St George's, University of London
name: Paul Heath
role: PRINCIPAL_INVESTIGATOR
References: