A Clinical Trial on Safety in Pregnant Women and How Well the Infant is Protected Against RSV-associated Lower Respiratory Tract Infection When the Pregnant Woman Receives the Approved RSV Vaccine Compared to a Placebo.

Summary

Respiratory syncytial virus (RSV) is a virus that often affects children during childhood. Even though most cases of RSV are mild, it can cause serious disease and even death - especially in very young babies, babies born too early and those born with heart and lung problems. It is the most common cause for children under 5 years old to be hospitalised. In 2019, there were about 33 million RSV-infections in the lower respiratory tract (in the lungs and below the voice box) of which 3,6 million people were hospitalised and 26,300 passed away in hospital due to RSV. Almost half (50%) of deaths that are caused by RSV, happen in children younger than 6 months old and the majority (more than 95%) of these deaths happen to infants and children in low- and middle-income countries.

A way that can help protect babies from becoming infected is through giving vaccines against the germ (RSV) that is targeted for prevention. There are currently no registered vaccines that can be given directly to babies however there is a lot of information available that shows that a vaccine can be safely giving to a mother while she is still pregnant. The mother then produces antibodies (protection cells) that is transferred to the baby before the baby is born, and the baby is protected from getting sick during the first few months of life.

One of the vaccines that has been developed (ABRYSVO) has been used in many clinical trials in pregnant moms (and older people) to test if it is safe and will protect young babies and much older people who are all at the highest risk for a severe RSV disease. The vaccine was given to more than 4,000 pregnant women. The results from the study and previous studies showed that the vaccine was safe and the babies had a lower chance of getting severe RSV disease and going to hospital. It showed that the vaccine prevented severe RSV infection in around 80% of babies younger than 90 days, and 70% of babies younger than 6 months. Therefore, the vaccine has been licensed in a few countries around the world (including the United States of America and other high-income countries) which means that pregnant women can receive this vaccine during their pregnancy if they wish to (without being on a clinical trial). It has also been licensed in South Africa but is not yet available in the country for pregnant women to receive. The licensure is also underway in other African countries.

However, the results of the previous studies of this vaccine also showed that a slightly higher number of premature babies were born to women who received the vaccine compared to women who did not receive the vaccine. The information received from these studies was however not enough to decide if the earlier births were related to the vaccine or not, and more information is needed - which is one of the main reasons for this study. Importantly, all of the babies who were born earlier were only born a few weeks earlier than expected (around 35 weeks of pregnancy), and all the babies were well and survived. The previous studies on this vaccine happened during the COVID-19 pandemic at which time people were wearing masks and contacting other people less therefore not spreading RSV around as we would normally expect. By doing this study, it will assist the investigators to determine if the vaccine is really as good as it is perceived to be for preventing serious RSV illness in the babies.

This RSV vaccine is a very important medical intervention, and it is as important that the effect that this vaccine will have on pregnant women and on the infants born to mothers who receive the vaccine can be measured. It is especially important in African and lower-middle income countries as the vaccine was not tested as much in people living in Africa compared to others. Therefore, the main reason for doing this trial is to see how much value the vaccine can bring to these countries in terms of protecting young babies and infants where many may get a severe infection and be hospitalised. It will also measure if the vaccine does increase the chances of a baby being born earlier than expected. It will only be carried out in the countries after the vaccine has been approved for use by pregnant women (at the right time) as part of their pregnancy care.

Conditions

• RSV Infections
• RSV Immunisation
• Preterm Labour

Interventions

DRUG

Vaccine

The active ingredients in RSVpreF are 2 stabilized RSV prefusion F antigens, in equal amounts from virus subgroups A and B, in a lyophilized dosage form for reconstitution.

OTHER

Placebo

Placebo matched to vaccine but not containing any active ingredients

Sponsors & Collaborators

• World Health Organization

  collaborator OTHER

• Bill and Melinda Gates Foundation

  collaborator OTHER

• University of Witwatersrand, South Africa

  lead OTHER

Principal Investigators

• Shabir Madhi · Wits Vaccines & Infectious Diseases Analytics Research Unit

• Ziyaad Dangor · Wits Vaccines & Infectious Diseases Analytics Research Unit

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

14 Years

Max Age

55 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-09-03

Primary Completion

2028-02-29

Completion

2028-02-29

FDA Drug

Yes

Countries

• Ghana
• Kenya
• South Africa
• The Gambia

Study Locations