Study of Safety, Reactogenicity and Immunogenicity of GlaxoSmithKline's (GSK)Respiratory Syncytial Virus (RSV)Maternal Unadjuvanted Vaccine in Healthy Pregnant Women (Aged 18 to 40 Years) and Their Infants

The placental transfer ratio of IgG specific antibody concentration was determined from cord blood (or blood sample collected within 3 days after birth from infants if cord blood was not collected) over that of the blood sample from mother at delivery if blood sample was not collected during delivery). Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA.

Time frame: At delivery (for maternal subjects) or within 3 days after birth (for infants)

Population: The analysis was performed on all pairs of maternal subjects (from PPSM) and their infants (from PPSI) with available results for this outcome measure at the specified time point.

Biochemical parameters assessed were Alanine Amino-Transferase (ALT), Aspartate Amino-Transferase (AST), Creatinine (CRE) and Urea nitrogen (URN). The increase was evaluated only for AST and ALT parameters at Day 8. Abnormal laboratory values refer to range indicator at Day 8 (D8) categorized as Missing, Below, Within and Above normal values and compared to the baseline (B) range indicator of the same parameter, at Screening (up to 15 days before vaccination) i.e. Missing, Below, Within and Above. E.g. 'AST increase Below (B) - Within (D8)' = AST increase in subjects with below normal values at baseline and within normal values at Day 8.

Time frame: At Day 8

Population: The analysis was performed on the ESM, which included all the maternal subjects who received at least 1 dose of study intervention.

Hematological parameters assessed were Eosinophils (EOS), Erythrocytes (ERY), Hematocrit (HEM), Lymphocytes (LYMP), Mean Corpuscular Volume (MCV), Neutrophils (NEU), Platelets (PLA), and White Blood Cells (WBC) count. The increase and/or decrease of these parameters were evaluated at Day 8. Abnormal laboratory values refer to range indicator at Day 8 (D8) categorized as Missing, Below, Within and Above normal values and compared to the baseline (B) range indicator of the same parameter, at Screening (up to 15 days before vaccination) i.e. Missing, Below, Within and Above. E.g. 'WBC decrease Below (B) - Within (D8)' = WBC decrease in subjects with below normal values at baseline and within normal values at Day 8.

Time frame: At Day 8

Population: The analysis was performed on the Exposed Set-Maternal (ESM), which included all the maternal subjects who received at least 1 dose of study intervention.

An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs leading to study withdrawal = AEs identified by investigators to cause subject(s) withdrawal until the resolution of the event. These subject withdrawals were considered different from subject withdrawals for other reasons.

Time frame: From birth to Day 43 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Also, for instances where, due to the special circumstances, the subject could not seek medical advice for symptoms/an illness by visiting a medical facility or arranging for a home visit, the subject sought this advice instead via telephone, SMS, email, videotelephony or telemedicine, or other means. Any = occurrence of the symptom regardless of intensity grade.

Time frame: From birth to Day 43 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

SAEs assessed included any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity or is a congenital anomaly/birth defect, other situations (medical events that might jeopardize the participant or required medical/surgical intervention to prevent one of the other SAEs listed above: e.g. invasive/malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization). Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

Time frame: From birth to Day 43 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

Neonatal AESIs, reported up to 6 weeks after birth were: Respiratory Distress In The Neonate, Macrosomia, Low Birth Weight, Small For Gestational Age, Preterm Birth, Large For Gestational Age, Neonatal Invasive Blood Stream Infections (NIBSI) and Congenital Anomalies (CA).

Time frame: From birth to Day 43 post-birth

Population: The analysis was performed on the Exposed Set-Infant (ESI), which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs leading to study withdrawal = AEs identified by investigators to cause subject(s) withdrawal until the resolution of the event. These subject withdrawals were considered different from subject withdrawals for other reasons.

Time frame: From Day 1 to Day 43 post-delivery

Population: The analysis was performed on the ESM, which included all the maternal subjects who received at least 1 dose of study intervention.

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Also, for instances where, due to the special circumstances, the subject could not seek medical advice for symptoms/an illness by visiting a medical facility or arranging for a home visit, the subject sought this advice instead via telephone, SMS, email, videotelephony or telemedicine, or other means. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

Time frame: From Day 1 to Day 43 post-delivery

Population: The analysis was performed on the ESM, which included all the maternal subjects who received at least 1 dose of study intervention.

SAEs assessed included any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study subject or abnormal pregnancy outcomes (spontaneous abortion, foetal death, stillbirth, congenital anomalies, ectopic pregnancy), other situations (medical events that might jeopardize the participant or required medical/surgical intervention to prevent one of the other SAEs listed above: e.g. invasive/malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization). Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

Time frame: From Day 1 to Day 43 post-delivery

Population: The analysis was performed on the ESM, which included all the maternal subjects who received at least 1 dose of study intervention.

Assessed solicited administration site events were pain, erythema and swelling. Any = occurrence of the symptom regardless of intensity grade. Any erythema and swelling symptom = symptom reported with a surface diameter greater than 0 millimeters.

Time frame: During the 7-day follow-up period after vaccination (i.e. day of vaccination and 6 subsequent days)

Population: The analysis was performed on the Solicited Safety Set (SSS), which included all the maternal subjects who received at least 1 dose of the study intervention and who had solicited safety data.

Assessed solicited systemic events were fatigue, headache, nausea, vomiting, diarrhea, abdominal pain and fever \[temperature equal to or above (≥) 38 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade or relation to study intervention.

Time frame: During the 7-day follow-up period after vaccination (i.e. day of vaccination and 6 subsequent days)

Population: The analysis was performed on the SSS, which included all the maternal subjects who received at least 1 dose of the study intervention and who had solicited safety data.

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Unsolicited AE is any AE reported in addition to those solicited during the clinical study and that was spontaneously communicated by a maternal subject. Also, any solicited symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

Time frame: During 30-day follow-up period after vaccination (i.e. the day of vaccination and 29 subsequent days)

Population: The analysis was performed on the Unsolicited Safety Set-Maternal, which included maternal subjects who received at least 1 dose of the study intervention (ESM) that reported unsolicited AEs/reported not having unsolicited AEs.

Pregnancy outcomes were: live birth with no congenital anomalies, live birth with congenital anomalies, Fetal death/still birth with no Congenital Anomalies (CA) - Antepartum and Unknown (Subjects withdrew from the study before delivery and pregnancy outcome information was not available for them).

Time frame: From Day 1 to Day 43 post-delivery

Population: The analysis was performed on the ESM, which included all the maternal subjects who received at least 1 dose of study intervention.

Pregnancy-related AESIs were: Non-Reassuring Fetal Status, Hypertensive Disorders of Pregnancy (HDP), Oligohydramnios, Pathways to Preterm Birth (PPB), Chorioamnionitis, Fetal Growth Restriction, Gestational Liver Disease (GLD), Postpartum Haemorrhage and Gestational Diabetes Mellitus.

Time frame: From Day 1 to Day 43 post-delivery

Population: The analysis was performed on the ESM, which included all the maternal subjects who received at least 1 dose of study intervention.

Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were expressed in Estimated Dilution 60 (ED60) and were measured on blood samples collected from vaccinated maternal subjects.

Time frame: At Day 1 (before vaccination), Day 31 and at delivery

Population: The analysis was performed on the PPSM for immunogenicity which included all the maternal subjects who received at least 1 dose of the study intervention to which they were randomized and had post-vaccination data minus those subjects with protocol deviations that lead to exclusion.

Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were presented as GMTs, expressed in ED60. The antibodies were measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 3 days after birth (if no cord blood sample could be obtained).

Time frame: At delivery or within 3 days after birth

Population: The analysis was performed on the PPSI, which included all infant subjects in the ESI who have post-delivery/birth immunogenicity data minus those who (a) were born less than 4 weeks post-maternal subject vaccination and/ or (b) have protocol deviations that lead to exclusion and for whom blood samples were collected at relevant time points.

Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. The corresponding antibody concentrations were expressed in EU/mL. The antibodies were measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 3 days after birth (if no cord blood sample could be obtained).

Time frame: At delivery or within 3 days after birth

Population: The analysis was performed on the Per Protocol Set-Infants (PPSI), which included all infant subjects in the ESI who have post-delivery/birth immunogenicity data minus those who (a) were born less than 4 weeks post-maternal subject vaccination and/ or (b) have protocol deviations that lead to exclusion and for whom blood samples were collected at relevant time points.

Serological assays for the determination of IgG antibodies against RSV MAT were performed by Enzyme-linked immunosorbent assay (ELISA). The corresponding antibody concentrations were expressed in ELISA units per milliliter (EU/mL) and were measured on blood samples collected from vaccinated maternal subjects.

Time frame: At Day 1 (before vaccination), Day 31 and at delivery

Population: The analysis was performed on the Per Protocol Set-Maternal (PPSM) for immunogenicity which included all the maternal subjects who received at least 1 dose of the study intervention to which they were randomized and had post-vaccination data minus those subjects with protocol deviations that lead to exclusion.

An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs leading to study withdrawal = AEs identified by investigators to cause subject(s) withdrawal until the resolution of the event. These subject withdrawals were considered different from subject withdrawals for other reasons.

Time frame: From birth to Day 181 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

An AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs leading to study withdrawal = AEs identified by investigators to cause subject(s) withdrawal until the resolution of the event. These subject withdrawals were considered different from subject withdrawals for other reasons.

Time frame: From birth to Month 12 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Also, for instances where, due to the special circumstances, the subject could not seek medical advice for symptoms/an illness by visiting a medical facility or arranging for a home visit, the subject sought this advice instead via telephone, SMS, email, videotelephony or telemedicine, or other means. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

Time frame: From birth to Day 181 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Also, for instances where, due to the special circumstances, the subject could not seek medical advice for symptoms/an illness by visiting a medical facility or arranging for a home visit, the subject sought this advice instead via telephone, SMS, email, videotelephony or telemedicine, or other means. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

Time frame: From birth to Month 12 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

SAEs assessed included any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject, other situations (medical events that might jeopardize the participant or required medical/surgical intervention to prevent one of the other SAEs listed above: e.g. invasive/malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization). Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

Time frame: From birth to Day 181 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

SAEs assessed included any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject, other situations (medical events that might jeopardize the participant or required medical/surgical intervention to prevent one of the other SAEs listed above: e.g. invasive/malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization). Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

Time frame: From birth to Month 12 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

An RSV-associated hospitalisation is characterised by a confirmed RSV infection and a hospitalisation for an acute medical condition.

Time frame: From birth to Day 181 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

An RSV-associated LRTI is characterised by a history of cough or difficulty in breathing, a blood oxygen saturation by pulse oximetry (SpO2) lesser than (\<) 95% or respiratory rate increase and a confirmed RSV infection.

Time frame: From birth to Day 181 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

A RSV-associated severe LRTI is characterised by a history of cough or difficulty in breathing, a SpO2 \< 93% or lower chest wall in-drawing and a confirmed RSV infection.

Time frame: From birth to Day 181 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

A RSV-associated very severe LRTI is characterised by a history of cough or difficulty in breathing, a SpO2 \< 90% or inability to feed or failure to respond/unconscious and a confirmed RSV infection.

Time frame: From birth to Day 181 post-birth

Population: The analysis was performed on the ESI, which included all the infants live-born to exposed maternal subjects, whose parents/LARs completed the informed consent process and signed the informed consent form.

An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs leading to study withdrawal = AEs identified by investigators to cause subject(s) withdrawal until the resolution of the event. These subject withdrawals were considered different from subject withdrawals for other reasons.

Time frame: From Day 1 to Day 181 post-delivery

Population: The analysis was performed on the ESM, which included all the maternal subjects who received at least 1 dose of study intervention.

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Also, for instances where, due to the special circumstances, the subject could not seek medical advice for symptoms/an illness by visiting a medical facility or arranging for a home visit, the subject sought this advice instead via telephone, SMS, email, videotelephony or telemedicine, or other means. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

Time frame: From Day 1 to Day 181 post-delivery

Population: The analysis was performed on the ESM, which included all the maternal subjects who received at least 1 dose of study intervention.

SAEs assessed included any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study subject or abnormal pregnancy outcomes (spontaneous abortion, foetal death, stillbirth, congenital anomalies, ectopic pregnancy), other situations (medical events that might jeopardize the participant or required medical/surgical intervention to prevent one of the other SAEs listed above: e.g. invasive/malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization). Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.

Time frame: From Day 1 to Day 181 post-delivery

Population: The analysis was performed on the ESM, which included all the maternal subjects who received at least 1 dose of study intervention.

A maternal MA-RTI occurs when the maternal subject visits a healthcare professional for any respiratory symptom, including cough, sputum production and difficulty breathing. An RSV associated MA-RTI is characterised by a medically attended visit for RTI symptoms (runny nose or blocked nose or cough) and a confirmed RSV infection.

Time frame: From delivery to Day 181 post-delivery

Population: The analysis was performed on the ESM, which included all the maternal subjects who received at least 1 dose of study intervention.

Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were expressed in ED60.

Time frame: At Day 121 after birth

Population: The analysis was performed on a subcohort (subcohort V2-New borns) from PPSI, for the subjects who provided sample for this outcome measure at the specified time point.

Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were expressed in ED60.

Time frame: At Day 181 after birth

Population: The analysis was performed on a subcohort (subcohort V2-New borns) from PPSI, for the subjects who provided sample for this outcome measure at the specified time point.

Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were expressed in ED60.

Time frame: At Day 43 after birth

Population: The analysis was performed on a subcohort (subcohort V2-New borns) from PPSI, for the subjects who provided sample for this outcome measure at the specified time point.

Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were expressed in ED60.

Time frame: At Day 43 post-delivery

Population: The analysis was performed on the PPSM for immunogenicity which included all the maternal subjects who received at least 1 dose of the study intervention to which they were randomized and have post-vaccination data minus those subjects with protocol deviations that lead to exclusion.

Serological assays for the determination of antibodies against RSV-B were performed by neutralization assay. The corresponding antibody titers were expressed in ED60. The antibodies were measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 3 days after birth (if no cord blood sample could be obtained).

Time frame: At delivery or within 3 days after birth

Population: The analysis was performed on the Per Protocol Set-Infants (PPSI), which included all infant subjects in the ESI who have post-delivery/birth immunogenicity data minus those who (a) were born less than 4 weeks post- maternal subject vaccination and/ or (b) have protocol deviations that lead to exclusion and for whom blood samples were collected at relevant time points.

Serological assays for the determination of antibodies against RSV-B were performed by neutralization assay. The corresponding antibody titers were expressed in ED60.

Time frame: At Day 121 after birth

Population: The analysis was performed on a subcohort (subcohort V2-New borns) from PPSI, for the subjects who provided sample for this outcome measure at the specified time point.

Serological assays for the determination of antibodies against RSV-B were performed by neutralization assay. The corresponding antibody titers were expressed in ED60.

Time frame: At Day 181 after birth

Population: The analysis was performed on a subcohort (subcohort V2-New borns) from PPSI, for the subjects who provided sample for this outcome measure at the specified time point.

Serological assays for the determination of antibodies against RSV-B were performed by neutralization assay. The corresponding antibody titers were expressed in ED60.

Time frame: At Day 43 after birth

Population: The analysis was performed on a subcohort (subcohort V2-New borns) from PPSI, for the subjects who provided sample for this outcome measure at the specified time point.

Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers were expressed in ED60.

Time frame: At Day 1 (before vaccination), Day 31, at delivery and Day 43 post-delivery

Population: The analysis was performed on the PPSM for immunogenicity which included all the maternal subjects who received at least 1 dose of the study intervention to which they were randomized and have post-vaccination data minus those subjects with protocol deviations that lead to exclusion.

Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. The corresponding antibody concentration were expressed in EU/mL.

Time frame: At Day 121 after birth

Population: The analysis was performed on a subcohort (subcohort V2-New borns) from PPSI, for the subjects who provided sample for this outcome measure at the specified time point.

Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. The corresponding antibody concentration were expressed in EU/mL.

Time frame: At Day 181 after birth

Population: The analysis was performed on a subcohort (subcohort V2-New borns) from PPSI, for the subjects who provided sample for this outcome measure at the specified time point.

Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. The corresponding antibody concentration were expressed in EU/mL.

Time frame: At Day 43 after birth

Population: The analysis was performed on a subcohort (subcohort V2-New borns) from PPSI, for the subjects who provided sample for this outcome measure at the specified time point.

Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. The corresponding antibody concentration were expressed in EU/mL.

Time frame: At Day 43 post-delivery

Population: The analysis was performed on the PPSM for immunogenicity which included all the maternal subjects who received at least 1 dose of the study intervention to which they were randomized and have post-vaccination data minus those subjects with protocol deviations that lead to exclusion.