Prevention of RSV Infection in Infants by Administering Nirsevimab to Infants, With or Without Maternal RSV Vaccination

Prevention of RSV Infection in Infants by Administering Nirsevimab to Infants, With or Without Maternal RSV Vaccination: a Randomised Controlled Trial in France as Part of the Pregnancy and Infant PrEparedness pLatform IN Europe - PIPELINE

RSV (which stands for Respiratory Syncytial Virus) is an infection that causes cold-like symptoms and is most common during winter months. Most people with RSV infection get better by themselves but babies and younger children can become very poorly. About 1 in 15 infants with confirmed RSV within the first 12 months of life will be hospitalised, and a very small proportion will be seriously ill and may die.

Currently there are two different prevention options that can be used to prevent RSV infection in babies. One is a vaccine given to the mother during pregnancy, and the other is a monoclonal antibody given by injection to the baby. Although both prevention options work well on their own and are safe, neither provides 100% protection to the infant. It is not known whether giving both medicines, one to the mother in pregnancy and one to the infant, would provide better protection than giving only one medicine - this is what the PIPELINE-RSV study will look at.

PIPELINE-RSV-France will recruit about 1000 pregnant women in France. A parallel trial, running across Europe (PIPELINE-RSV-International) will recruit about 1500 pregnant women in UK, Switzerland, the Netherlands and Belgium. The protocols will align on key aspects and the data will be analysed together. The study will include two study groups with different prevention options used in each: (1) an injection given to the baby at the beginning of RSV season, or (2) both a vaccine given to the mother in pregnancy and an injection given to the baby at around 4 months of age. Each mother-baby pair will be randomly allocated to group by a computer. The numbers of babies in each of these groups who acquire RSV will be compared. In some countries participating to the International trial, an other study groups may be available : (3) a vaccine given to the mother in pregnancy.

Pregnant women and their babies will be followed until the baby reaches 12 months of age. Information will be collected about medically-important side effects either the mother or the baby had from their medicine(s) and any symptoms of RSV the baby had. Visits with the mother and baby will occur at birth and 12 months later. The mother will complete questionnaires via a Web-based platform to report any non-routine in-person visits, once in pregnancy and after the baby is born twice a month or monthly (more often in the winter), to also report baby's symptoms, to report their trial experience when the baby is 4 and 12 months' old, and to provide their views on vaccination at birth, and when the baby is 4 and 12 months' old. If the baby develops symptoms that might be RSV, their mother or another caregiver will be asked to take a sample using a swab from the baby's nose or mouth, and to send it by post for testing to find out if the baby has RSV.

As well as the main research study, there are also some substudies. A questionnaire will be given to women who consent to take part, to find out their motivations for joining the study and how they prefer to receive information about taking part in studies. A small number of women will be asked to take part in a study to look at how mothers' and babies' immune systems respond to the two different study prevention options , and to investigate different ways of collecting samples from their babies. In addition, researchers will use data from the study to see whether giving both medicines is cost-effective compared with giving just one medicine.

Inclusion Criteria:

1. Pregnant women
2. Provide informed consent prior to study enrolment
3. Willing and able (in the site investigator's opinion) to comply with all study requirements
4. More than 18 years of age
5. Between 32 and 36 weeks of gestation
6. Able to read and complete the eHealth questionnaire in French or English
7. Willing to receive maternal vaccine in pregnancy, if allocated
8. Willing for the baby to receive infant nirsevimab
9. Willing for their data to be re-used as part of the joint analysis with PIPELINE-RSV-International trial
10. Affiliated to social security regime or an equivalent system

Inclusion Criteria - Infants:

1. Live-birth to mother enrolled in the study
2. Informed consent from the mother, and the other legal representative (partner / co-parent) when applicable

Exclusion Criteria:

1. Major illness of the maternal participant or conditions of the foetus that, in the investigator's judgment, would substantially increase the risk associated with the maternal or infant participant's participation in and completion of the study
2. Any suspected or confirmed condition in the foetus that in the opinion of the site investigator would contraindicate participation of the future newborn/infant in the study
3. High risk of prematurity as judged by treating clinician
4. Multiple pregnancy (i.e. twins, triplets or more)
5. Previous participation in the PIPELINE-RSV trial
6. Receipt of any previous RSV prevention product in this pregnancy or currently participating in another interventional RSV prevention trial
7. Any contraindication for receipt of intramuscular injection (bleeding diathesis or a condition associated with prolonged bleeding) or of vaccine (history of severe allergic reaction (e.g. anaphylaxis) to any component of the vaccine)
8. History of Guillain Barré Syndrome (GBS)