Preparing for Maternal GBS Vaccine Trials in Africa (PROTECT)

Barcelona Institute for Global Health

Status: Enrolling

Conditions: Invasive Bacterial Diseases (IBD); Maternal Immunization; Group B Streptococcus

Study type: Observational

Funder types: Other

Identifiers

NCT06833957

101145724

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18,100 estimated patients

Sex: All

Volunteers: Accepts Healthy Volunteers

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.

Trial design

18,100 participants in 3 patient groups

WP2: Pregnancy Episode Registries

Description:

This work package (WP2) will develop systems to determine background pregnancy and infancy outcomes, as defined by Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA), in preparation for maternal vaccine clinical trials and post-implementation studies. WP2 will assess the utility of existing medical records data to accurately determine pregnancy events following immunisation and, using patient data related to atleast 4000 pregnancies in each country, to establish an easy to use pregnancy episodes registry (PER) that can be used for future Phase III/IV trials. The PER will be developed using freely available code developed under EDCTP2 so that it can be used in other African settings in the future. The WP2 group consists of pregnant women and their infants up to hospital discharge at the chosen health facilities in Uganda, Malawi, Mozambique, and Kenya.

WP3: GBS disease sentinel site surveillance

Description:

WP3 will conduct a prospective observational GBS surveillance study among infants less than 90 days old who are admitted with laboratory confirmed GBS at sentinel sites in Kenya, Uganda, Malawi and Mozambique. The WP3 study team will develop and strengthen IBD surveillance, with a focus on GBS in each site. All of the proposed sites have access to microbiological capacity that will be leveraged to monitor microbiologically confirmed neonatal sepsis burden. In doing so, WP3 will improve the nations' ability to participate in late phase clinical trials and post-licensure effectiveness studies in preparation for phase III/IV GBS maternal vaccine clinical trials and vaccine decision making. The WP3 group consists of all infants less than 90 days old admitted with GBS infection detected in blood or cerebrospinal fluid (CSF) by culture, or GBS detected in CSF by quantitative polymerase chain reaction, at the health facilities in the four countries during a period of at least 12 months.

WP4: Vaccine confidence

Description:

Many low- and middle-income countries face significant challenges regarding vaccine implementation including vaccine confidence and participation in vaccine clinical trials, especially for vaccines targeting pregnant women. Through a mixed-methods study, WP4 will assess the knowledge, attitudes and practices of pregnant women, health care providers, community members and other relevant stakeholders towards maternal vaccines, and assess the understanding and willingness to participate in maternal vaccine trials in Kenya, Malawi, Mozambique and Uganda. WP4 will also co-create a communication/education toolkit to enhance understanding of the importance of maternal vaccines and participation in maternal vaccine trials. The WP4 group therefore consists of pregnant women and health care workers at the identified health facilities at the time of fieldwork. It will also consist of stakeholders such as Ministries of Health, community leaders, religious, political, or cultural leaders.