Clinical trial NCT04732026: Serocorrelate of Protection Against GBS (PREPARE WP3)
Official title: PREPARE Work Package 3 -Development of a Serocorrelate of Protection Against GBS - Protocol Harmonisation.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Group B Streptococcus Carrier in Childbirth
Group B Streptococcal Infection, Late-Onset
Group B Streptococcal Infection, Early-Onset
Group B Streptococcus Neonatal Sepsis
Group B Strep Infection
Lead sponsor: St George's, University of London
Sponsor class: OTHER
Collaborators: name: MU-JHU CARE
name: MRC/UVRI and LSHTM Uganda Research Unit
name: University of Liverpool
name: Assistance Publique - Hôpitaux de Paris
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Azienda Ospedaliero-Universitaria di Modena
First posted: 2021-02-01
Enrollment: 600
Sex: ALL
Maximum age (years): 90
Standard ages: CHILD
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will enroll infant subjects from the general population who are delivered at one of the six hospital sites.

Brief summary: A multicentre, international case-control study to develop a biobank of sera from 150 cases of serotype III GBS disease and associated clinical information from seven countries (Malawi, Uganda, UK, the Netherlands, Italy and France), with 3:1 (450) serotype matched healthy controls.

Detailed description: Group B Streptococcus (GBS) causes severe infections in young infants across the world. In 2015 it was estimated that there were at least 319,000 infants under three 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. Given the complexity, size and costs associated with a phase III trial, it is generally agreed that indirect evidence (correlates) of protection (CoP), based on immunologic data from vaccine and seroepidemiological studies, opsonophagocytic assays and supported by animal models, could be pivotal for vaccine licensure, with effectiveness subsequently confirmed in post-licensure evaluations.

This study aims to develop a biobank of sera from 150 cases of serotype III GBS disease and associated clinical information from seven countries (Malawi, Uganda, UK, the Netherlands, Italy and France) with 3:1 (450) serotype matched healthy controls.

GBS cases will be identified through active surveillance of GBS disease in infants, as part of ongoing epidemiological studies in Uganda, the UK, Italy, France, the Netherlands and Malawi. Upon identification of cases, consent will be requested to obtain a serum sample (1-2 mL of blood collected from infant), the GBS isolate and to collect brief clinical and demographic details. Each site will aim to collect around 50 cases of invasive GBS disease cases (with all samples) over the course of 2 years.

Each site will also recruit approximately 1000 women to have a rectovaginal swab at 35-37 weeks gestation and cord and maternal blood samples at delivery. These women and their infants will be followed up to 90 days of age and considered appropriate controls if the infants are exposed to the same serotype/strain of GBS at delivery as the case - but do not develop GBS the first 90 days of life. We will select 3 controls for every case.

The biorepository will be established at the St George's University of London for all samples from the European Union and Malawi and the MRC/UVRI \& LSHTM Uganda Research Unit for Ugandan samples.

Eligibility criteria: Inclusion Criteria:

Cases:

Infant 0-90 days of life with GBS identified from a normally sterile site.

Controls:

Healthy infant born to a GBS colonised woman that does not develop GBS disease between birth and 90 days of life.

Exclusion Criteria An infant is not eligible unless a parent/person with parental responsibility gives informed consent.

Primary outcomes:
measure: To establish a biobank of at least 150 GBS serotype III cases including both the isolate and associated maternal and infant serum.
timeFrame: Over the course of 2 years
Secondary outcomes:
measure: To determine the quantity of antibody associated with protection against GBS disease
timeFrame: Over the course of 2 years
measure: To determine the functional antibody associated with protection against GBS disease.
timeFrame: Over the course of 2 years
measure: To demonstrate the relationship between antibody quantity and function in protection against GBS disease
timeFrame: Over the course of 2 years
measure: To refine estimates for serocorrelates of protection against GBS disease.
timeFrame: Over the course of 2 years
measure: To provide training to participating African laboratories to assure the quality of sample collection and data curation.
timeFrame: Over the course of 2 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Assistance Publique Hopitaux de Paris (AP-HP)
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena (AOU)
city: Blantyre
country: Malawi
facility: Queen Elizabeth Central Hospital College of Medicine, P.O. Box 30096 Chichiri,
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum,Universiteit van Amsterdam
city: Kampala
country: Uganda
facility: MUJHU - Makerere University Johns Hopkins University Research Collaboration/MUJHU Care Ltd
city: London
country: United Kingdom
facility: St George's, University of London
Study officials:
affiliation: St George's, University of London
name: Kirsty Le Doare, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine
name: Stephen Cose, Dr
role: PRINCIPAL_INVESTIGATOR
References: