Clinical trial NCT06833957: Preparing for Maternal GBS Vaccine Trials in Africa
Official title: PReparing for OptimalPhase III/IV maTErnal Group B StreptococCal Vaccine Trials in Africa (PROTECT)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Group B Streptococcus
Invasive Bacterial Diseases (IBD)
Maternal Immunization
Keywords: Child health
Clinical research
Clinical trials
Infectious diseases
Group B Streptococcus
vaccines
maternal immunisation
maternal health
Lead sponsor: Barcelona Institute for Global Health
Sponsor class: OTHER
Collaborators: name: Fundação Manhiça
name: Universiteit Antwerpen
name: LINQ Management GMBH
name: Aga Khan University
name: University of Liverpool
name: Kamuzu University of Health Sciences
name: MU-JHU CARE
name: St George's, University of London
name: University of Oxford
First posted: 2025-02-19
Enrollment: 18100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: WP2 Pregnancy Exposure Registries study population:

Pregnant women and their infants up to hospital discharge at the chosen health facilities in Uganda, Malawi, Mozambique, and Kenya.

WP3 GBS surveillance study population:

All infants less than 90 days old admitted with GBS infection detected in blood or CSF by culture, or GBS detected in CSF by qPCR, at referral health facilities in the four countries during a period of at least 12 months.

WP4 study population:

All pregnant women attending the identified health facilities at the time of fieldwork and the health care workers who provide services to these women. It will also consist of stakeholders including, but not limited to, health workers from each country's Ministry of Health, head of facilities, community leaders (community gatekeepers and influencers), older women who give support in the community, male leaders, religious, political, administrative or cultural leaders.

Brief summary: Infections are one of the key causes of newborn deaths. Among them, Group B Streptococcus (GBS) is the leading cause of sepsis and bacterial meningitis in the first 90 days of life.

Fortunately, GBS vaccines for pregnant women, a powerful tool for fighting infections, are currently in development. Once vaccine trials are completed, these vaccines can stop preventable newborn deaths.

The PReparing for Optimal Phase III/IV maTErnal Group B StreptococCal vaccine Trials in Africa (PROTECT) project, funded by the European \& Developing Countries Clinical Trials Partnership (EDCTP) and European Commission, is supporting medical sites in Kenya, Malawi, Mozambique, and Uganda to establish uniform pregnancy and infant health data collection processes. It is also establishing surveillance of GBS in newborns to determine incidence rates and measure the burden of disease. With better reporting systems, medical sites can participate in vaccine trials and monitor vaccine safety. At the same time, the consortium is working to understand the drivers of vaccine hesitancy and to develop culturally appropriate communication tools to facilitate engagement with vaccines.

The end goal is to set up a network of sites that can monitor vaccine safety for current and future vaccines.

Detailed description: Two vaccines designed for pregnant women, to protect their unborn infant, are entering late phase development and will prevent infections from GBS and respiratory syncytial virus, respectively. For these vaccines to be approved, the vaccine must work effectively without causing any unwanted responses. To implement these vaccines in countries with low resources, healthcare systems must be strengthened by improving vaccine safety monitoring and surveillance of infection, and advancing vaccine delivery, vaccine confidence, and patient participation.

The PROTECT study, funded by the EU Commission EDCTP, is three-fold:

1. Establishment of pregnancy exposure registries:

   The rapid rollout of electronic health records (EHR) in some East African countries offers an opportunity to use routine data to strengthen reporting of rates of adverse pregnancy, neonatal and infant outcomes, and any adverse events following immunisation; this will be imperative in informing and preparing for future large scale vaccination rollout campaigns. The approach will develop pregnancy registries embedded within national reporting systems to establish this data, including baseline rates of pregnancy and infancy outcomes for Tetanus and COVID19 vaccines currently in use. These reporting systems will allow monitoring of potential safety signals once new vaccines are introduced.
2. Developing sentinel site GBS microbiological surveillance:

   The investigators will conduct a prospective observational GBS surveillance study among infants less than 90 days old who are admitted with laboratory confirmed GBS. The investigators will develop and strengthen invasive bacterial disease (IBD) surveillance, with a focus on GBS in Kenya, Malawi, Mozambique and Uganda. Each of the proposed lead sites has access to microbiological capacity that will be leveraged to monitor microbiologically confirmed neonatal sepsis burden. In doing so, the investigators will improve the nations' ability to participate in late phase clinical trials and post-licensure effectiveness studies.
3. Vaccine Confidence:

The aim of this study is evaluating the knowledge and practices of pregnant women and other key stakeholders around vaccination and factors influencing vaccine confidence during pregnancy. The investigators will also create tools and communication strategies to improve willingness of pregnant women to participate in vaccine trials and consequently increase confidence in vaccines and vaccine trials during pregnancy in Mozambique, Uganda, Malawi and Kenya.

The investigators will work closely with the World Health Organization (WHO), African Medicines Agency and Country Stakeholders. This programme of work culminates in a network of maternal vaccine trial sites that can rapidly evaluate vaccines in pregnancy from late-stage trials through to introduction on a national level.

Eligibility criteria: Inclusion Criteria:

* WP2 Pregnancy Exposure Registries inclusion criteria:

All women and their infants attending for antenatal and/or delivery and postpartum services at the study sites in Uganda, Malawi, Mozambique, and Kenya.

WP3 GBS Surveillance inclusion criteria:

* Infants aged less than 90 days old with laboratory-confirmed GBS infection admitted at participating health facilities in Uganda, Malawi, Mozambique, and Kenya.
* Infants whose parents or guardians provided written informed consent for their participation.
* Residents in the catchment area of participating health facilities.

WP4 Vaccine Confidence inclusion criteria:

* In Uganda, Kenya and Mozambique, pregnant women at any gestation period aged 18 years and above (reproductive age).
* In Malawi, pregnant women aged 16 years are eligible to be included in the study because they are considered emancipated minors.
* Pregnant women who consent to the study and give written consent.
* Stakeholders who include pregnant women, health workers, women leaders, community leaders, national stakeholders, cultural and religious leaders who are willing to take part and can give written informed consent.

Exclusion Criteria:

WP4 Vaccine Confidence exclusion criteria:

* Pregnant women who are visiting/non-resident in the research area.
* Those who may be unwell and unable to consent to take part in the study.

Primary outcomes:
measure: Pregnancy exposure registries outcome 1.1
timeFrame: 01.03.2026 - 28.02.2027
measure: Pregnancy exposure registries outcome 1.2
timeFrame: 01.03.2026 - 28.02.2027
measure: Pregnancy exposure registries outcomes 1.3
timeFrame: 01.03.2026 - 28.02.2027
measure: Sentinel site GBS disease surveillance outcome 2.1
timeFrame: 01.01.2025 - 01.09.2025
measure: Sentinel site GBS disease surveillance outcome 2.2
timeFrame: 01.03.2026 - 28.02.2027
measure: Vaccine confidence outcome 3.1
timeFrame: 01.03.2025 - 28.02.2027
measure: Vaccine confidence outcome 3.2
timeFrame: 01.03.2025 - 28.02.2027
measure: Vaccine confidence outcome 3.3
timeFrame: 01.11.2025 - 20.08.2026
Secondary outcomes:
measure: Sentinel site GBS disease surveillance outcome 2.3
timeFrame: 01.09.2025 - 28.02.2027
measure: Sentinel site GBS disease surveillance outcome 2.4
timeFrame: 01.09.2025 - 28.02.2027
Other outcomes:
Locations:
city: Mariakani
country: Kenya
facility: Mariakani Sub-County Hospital
state: Coast
city: Rabai
country: Kenya
facility: Rabai Sub County Hospital
state: Kilifi
city: Blantyre
country: Malawi
facility: Queen Elizabeth Central Hospital
state: Blantyre District
city: Blantyre
country: Malawi
facility: Lirangwe Health Centre
state: Blantyre District
city: Blantyre
country: Malawi
facility: Ndirande Health Centre
city: Manhiça
country: Mozambique
facility: Manhiça District Hospital
city: Maputo
country: Mozambique
facility: Hospital Geral De Mavalane
city: Maputo
country: Mozambique
facility: Jose Macamo General hospital
city: Kampala
country: Uganda
facility: Kawempe National Referral Hospital
Study officials:
affiliation: MU-JHU CARE
name: Eve Nakabembe
role: STUDY_DIRECTOR
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