A Study of a Vaccine Against Respiratory Syncytial Virus (RSV) When Given Alone and Together With a Vaccine Against Diphtheria, Pertussis and Tetanus (Tdap) Viruses Followed by a 2nd Dose of the RSV Vaccine to Healthy Non-Pregnant Women

Phase 2

Completed

Conditions: Respiratory Syncytial Virus Infections

Interventions: Biological: RSVPreF3 formulation 3
Drug: Placebo
Biological: Boostrix-ex-US
Biological: RSVPreF3 formulation 2
Biological: Boostrix-US

Registration Number: NCT04138056

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study is to evaluate the safety, ability of GSK Biologicals' investigational RSV maternal vaccine (RSVPreF3) to generate an immune response and the degree to which the vaccine can cause side effects, when administered alone and in combination with Boostrix vaccine in healthy non-pregnant women 18-45 years of age. Two dose levels of RSVPreF3 and 2 Boostrix \[Diphtheria, Tetanus and acellular Pertussis (dTpa) vaccine\] formulations (US and ex-US) will be evaluated. A 2nd dose of RSVPreF3 will be administered in an extension of the study to assess the durability of the immune response after the first dose vaccination, and to assess the safety and immunogenicity following a second dose vaccination of the RSVPreF3 maternal vaccine.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 509

Inclusion Criteria

Primary study

Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
Written or witnessed/thumb printed informed consent obtained from the subject prior to performance of any study specific procedure.
Healthy female subjects; as established by medical history and clinical examination, aged 18 to 45 years at the time of the 1st vaccination;
Female subjects of childbearing potential may be enrolled in the study, if the subject:
- has practiced adequate contraception for 30 days prior to primary vaccination, and
- has a negative pregnancy test on the day of primary vaccination, and
- has agreed to continue adequate contraception for 90 days after completion of the vaccination.
No local condition precluding injection in both left and right deltoid muscles.

Extension study

Completed primary study and received 1st dose of a study vaccine.
Written or witnessed/thumb printed informed consent obtained from the subject prior to performance of any study specific procedure to the study extension.

All subjects must satisfy ALL the following criteria:

Subjects who can and will comply with the requirements of the protocol.
Female subjects remain healthy; as established by medical history and clinical examination, aged 18 to 45 years at the time of the 1st vaccination;
Female subjects of childbearing potential are eligible for the extension, if the subject:
- has practiced adequate contraception for 30 days prior to 2nd vaccination
- has a negative pregnancy test with results available on the day of 2nd vaccination
- has agreed to continue adequate contraception for 90 days after completion of the 2nd vaccination.

Exclusion Criteria

Primary study

Medical conditions

History of any reaction/hypersensitivity likely to be exacerbated by any vaccines' component;
Any confirmed/suspected immunosuppressive/immunodeficient condition, based on medical history and physical examination;
Hypersensitivity to latex;
Major congenital defects;
Acute/chronic clinically significant pulmonary, cardiovascular, hepatic/renal functional abnormality;
Significant/uncontrolled psychiatric illness;
Recurrent history/uncontrolled neurological disorders/seizures;
Documented HIV-positive subject;
History of/current autoimmune disease;
Body mass index (BMI)>40 kg/m^2;
Any clinically significant hematological parameter and/or biochemical laboratory abnormality.
Any other clinical condition that might pose additional risk to the subject due to participation in the study.

Prior/Concomitant therapy

Use of any investigational/non-registered product other than the study vaccines during the period starting 30 days before 1st vaccination, or planned use during the study;
Administration of long-acting immune-modifying drugs at any time during the study;
Administration of immunoglobulins and/or any blood products/plasma derivatives during the period starting 3 months before the 1st vaccination or planned administration during the study;
Chronic administration of immunosuppressants/other immune-modifying drugs during the period starting 3 months prior to 1st vaccine dose(s). For corticosteroids, this will mean prednisone ≥5 mg/day, or equivalent. Inhaled and topical steroids are allowed;
Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after study 1st vaccination, with the exception of any licensed influenza vaccine which may be administered ≥ 15 days before/after study vaccination;
Administration of a vaccine containing diphtheria, tetanus/pertussis antigens/diphtheria and tetanus toxoids within the previous 5 years;
Previous experimental vaccination against RSV;

Prior/Concurrent clinical study experience • Concurrently participating in another clinical study, at any time during the study, in which the subject has been/will be exposed to an investigational/a non-investigational vaccine/product;

Other exclusions

Pregnant/lactating female;
Female planning to become pregnant/planning to discontinue contraceptive precautions;
History of alcoholism, drug abuse and/or use disorder within the past 2 years;
Any study personnel/their immediate dependents, family/household members.

Extension study

Medical conditions

History of any reaction/hypersensitivity likely to be exacerbated by any component of the vaccines;
Any confirmed/suspected immunosuppressive/immunodeficient condition, based on medical history and physical examination;
Hypersensitivity to latex;
Acute/chronic clinically significant pulmonary, cardiovascular, hepatic/renal functional abnormality;
Significant/uncontrolled psychiatric illness;
Recurrent history/uncontrolled neurological disorders/seizures;
Documented HIV-positive subject;
History of/current autoimmune disease;
BMI>40 kg/m^2;
Participants who experienced any SAE judged to be possibly or probably related to 1st dose of RSVPreF3, including hypersensitivity reactions.
Any other clinical condition that might pose additional risk to the subject due to participation in the study.

Prior/Concomitant therapy

Use of any investigational/non-registered product other than the study vaccines during the period starting 30 days before the 2nd vaccination, or planned use during the 6-month study extension;
Administration of long-acting immune-modifying drugs at any time during the study;
Administration of immunoglobulins and/or any blood products/plasma derivatives during the period starting 3 months before the 1st dose of study vaccines/planned administration during the study;
Chronic administration of immunosuppressants or other immune-modifying drugs during the starting 3 months prior to the 1st vaccine dose(s). For corticosteroids, this will mean prednisone ≥5 mg/day, or equivalent. Inhaled and topical steroids are allowed;
Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after study 2nd vaccination, with the exception of any licensed influenza vaccine which may be administered ≥ 15 days before/after study vaccination.

Prior/Concurrent clinical study experience

• Concurrently participating in another clinical study, at any time during the study, in which the subject has been/will be exposed to an investigational/a non-investigational vaccine/product;

Other exclusions

Pregnant/lactating female at the time of Visit 4;
Female planning to become pregnant/planning to discontinue contraceptive precautions;
History of alcoholism, drug abuse and/or use disorder within the past 2 years;
Any study personnel/their immediate dependents, family/household members.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RSV120_Placebo_RSV120(Pooled)	Placebo	Subjects received one dose of 120 μg RSVPreF3 formulation 3 vaccine and one dose of Placebo on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received a second dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV120_Placebo_RSV120(Pooled)	RSVPreF3 formulation 3	Subjects received one dose of 120 μg RSVPreF3 formulation 3 vaccine and one dose of Placebo on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received a second dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV120_dTpa_RSV120(Pooled)	RSVPreF3 formulation 3	Subjects received one dose of 120 μg RSVPreF3 formulation 3 vaccine and either one dose of 300 μg or 500 μg dTpa (Boostrix) vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received a second dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV120_dTpa_RSV120(Pooled)	Boostrix-ex-US	Subjects received one dose of 120 μg RSVPreF3 formulation 3 vaccine and either one dose of 300 μg or 500 μg dTpa (Boostrix) vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received a second dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV120_dTpa_RSV120(Pooled)	Boostrix-US	Subjects received one dose of 120 μg RSVPreF3 formulation 3 vaccine and either one dose of 300 μg or 500 μg dTpa (Boostrix) vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received a second dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV60_dTpa_RSV120(Pooled)	RSVPreF3 formulation 3	Subjects received one dose of 60 μg RSVPreF3 formulation 2 vaccine and either one dose of 300 μg or 500 μg dTpa vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV60_dTpa_RSV120(Pooled)	RSVPreF3 formulation 2	Subjects received one dose of 60 μg RSVPreF3 formulation 2 vaccine and either one dose of 300 μg or 500 μg dTpa vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV60_dTpa_RSV120(Pooled)	Boostrix-ex-US	Subjects received one dose of 60 μg RSVPreF3 formulation 2 vaccine and either one dose of 300 μg or 500 μg dTpa vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV60_dTpa_RSV120(Pooled)	Boostrix-US	Subjects received one dose of 60 μg RSVPreF3 formulation 2 vaccine and either one dose of 300 μg or 500 μg dTpa vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV60_Placebo_RSV120(Pooled)	RSVPreF3 formulation 3	Subjects received one dose of 60 μg RSVPreF3 formulation 2 vaccine and one dose of Placebo on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV60_Placebo_RSV120(Pooled)	RSVPreF3 formulation 2	Subjects received one dose of 60 μg RSVPreF3 formulation 2 vaccine and one dose of Placebo on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
RSV60_Placebo_RSV120(Pooled)	Placebo	Subjects received one dose of 60 μg RSVPreF3 formulation 2 vaccine and one dose of Placebo on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
dTpa_Placebo_RSV120(Pooled)	RSVPreF3 formulation 3	Subjects received one dose of Placebo and either one dose of 300 μg or 500 μg dTpa vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
dTpa_Placebo_RSV120(Pooled)	Boostrix-ex-US	Subjects received one dose of Placebo and either one dose of 300 μg or 500 μg dTpa vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
dTpa_Placebo_RSV120(Pooled)	Boostrix-US	Subjects received one dose of Placebo and either one dose of 300 μg or 500 μg dTpa vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.
dTpa_Placebo_RSV120(Pooled)	Placebo	Subjects received one dose of Placebo and either one dose of 300 μg or 500 μg dTpa vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Any SAEs [Extension Period]	From the Day of 2nd vaccination to Day 31 post 2nd vaccination	A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any is defined as any occurrence of SAE regardless of intensity grade or relation to study vaccination. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the safety response to RSVPreF3.
RSV A Neutralizing Antibody GMTs at Day 8 [Primary Study]	At Day 8	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay and titers are expressed in ED60. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the immunogenicity response to RSVPreF3.
RSV PreF3 IgG GMCs at Day 8 [Primary Study]	At Day 8	Serological assays for the determination of IgG antibodies against RSV PreF3 were performed by Enzyme-linked immunosorbent assay (ELISA). The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the immunogenicity response to RSVPreF3.
Percentage of Subjects With Any Solicited Local Adverse Event (AEs) [Primary Study]	From Day 1 to Day 8	Assessed solicited local AEs are: erythema, pain and swelling. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the safety response to RSVPreF3.
Percentage of Subjects With Any Solicited General AEs [Primary Study]	From Day 1 to Day 8	Assessed solicited general AEs are: fatigue, gastrointestinal symptoms, headache and fever (body temperature ≥ 38 degree celcius/100.4 degree Farenhit). Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the safety response to RSVPreF3.
Percentage of Subjects With Any Unsolicited AEs [Primary Study]	From Day 1 to Day 31	An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the safety response to RSVPreF3.
Number of Subjects With Any SAEs [Primary Study]	From Day 1 to Day 31	A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any is defined as any occurrence of SAE regardless of intensity grade or relation to study vaccination. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the safety response to RSVPreF3.
Percentage of Subjects With Any Solicited Local AEs [Extension Study]	From the Day of 2nd vaccination to Day 8 post 2nd vaccination	Assessed solicited local AEs are: erythema, pain and swelling. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies.The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the safety response to RSVPreF3.
Percentage of Subjects Any Solicited General AEs [Extension Period]	From the Day of 2nd vaccination to Day 8 post 2nd vaccination	Assessed solicited general AEs are: fatigue, gastrointestinal symptoms, headache and fever(body temperature ≥ 38 degree celcius/100.4 degree Farenhit). Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the safety response to RSVPreF3.
Percentage of Subjects With Any Unsolicited AEs [Extension Period]	From the Day of 2nd vaccination to Day 31 post 2nd vaccination	An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the safety response to RSVPreF3.
RSV A Neutralizing Antibody GMTs at Day 31 [Primary Study]	At Day 31	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay and titers are expressed in ED60. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the immunogenicity response to RSVPreF3.
RSV PreF3 IgG Antibody Geometric Mean Concentration (GMCs) at Screening [Primary Study]	At Screening (Day -7 to Day 1)	Serological assays for the determination of IgG antibodies against RSV PreF3 were performed by Enzyme-linked immunosorbent assay (ELISA ). The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the immunogenicity response to RSVPreF3.
RSV A Neutralizing Antibody Geometric Mean Titers (GMTs) at Screening [Primary Study]	At Screening (Day -7 to Day 1)	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay and titers are expressed in ED60 (Estimated Dilution 60). The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the immunogenicity response to RSVPreF3.
RSV PreF3 IgG GMCs at Day 31 [Primary Study]	At Day 31	Serological assays for the determination of IgG antibodies against RSV PreF3 were performed by Enzyme-linked immunosorbent assay (ELISA). Analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the immunogenicity response to RSVPreF3.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Any SAEs by Each Boostrix Formulation [Primary Study]	From Day 1 to Day 31	A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any is defined as any occurrence of SAE regardless of intensity grade or relation to study vaccination. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the safety response to RSVPreF3.
Percentage of Subjects With Any Solicited General AEs by Each Boostrix Formulation [Primary Study]	From Day 1 to Day 8	Assessed solicited general AEs are: fatigue, gastrointestinal symptoms, headache and fever(body temperature ≥ 38 degree celcius/100.4 degree Farenhit). Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the safety response to RSVPreF3.
Number of Subjects With Any SAEs From 1st Vaccination to Day 181 [Primary Study]	From Day 1 to Day 181	A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any is defined as any occurrence of SAE regardless of intensity grade or relation to study vaccination. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the safety response to RSVPreF3.
Number of Subjects With Any SAEs From 1st Vaccination to Day 181 by Each Boostrix Formulation [Primary Study]	From Day 1 to Day 181	A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any is defined as any occurrence of SAE regardless of intensity grade or relation to study vaccination. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the safety response to RSVPreF3.
Number of Subjects With Any SAEs From 2nd Vaccination to Day 181 Post 2nd Vaccination [Extension Period]	From the Day of 2nd vaccination to Day 181 post 2nd vaccination	A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. Any is defined as any occurrence of SAE regardless of intensity grade or relation to study vaccination. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies, as the objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the safety response to RSVPreF3.
RSV A Neutralizing GMTs at Single Time Point Between 12 to 18 Months Post 1st Vaccination by Each Boostrix Formulation [Primary Study]	At a single timepoint between 12 to 18 months post 1st vaccination	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay and titers are expressed in ED60. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the immunogenicity response to RSVPreF3.
Percentage of Subjects With Any Solicited Local Adverse Event (AEs) by Each Boostrix Formulation [Primary Study]	From Day 1 to Day 8	Assessed solicited local AEs are: erythema, pain and swelling. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the safety response to RSVPreF3.
Percentage of Subjects With Any Unsolicited AEs by Each Boostrix Formulation [Primary Study]	From Day 1 to Day 31	An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the safety response to RSVPreF3.
RSV A Neutralizing GMTs at Screening by Each Boostrix Formulation [Primary Study]	At Screening (Day -7 to Day 1)	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay and titers are expressed in ED60. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the immunogenicity response to RSVPreF3.
RSV A Neutralizing GMTs at Day 8 by Each Boostrix Formulation [Primary Study]	At Day 8	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay and titers are expressed in ED60. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the immunogenicity response to RSVPreF3.
RSV PreF3 IgG GMCs at Day 8 by Each Boostrix Formulation [Primary Study]	At Day 8	Serological assays for the determination of IgG antibodies against RSV PreF3 were performed by ELISA. The corresponding antibody concentration is expressed in EU/mL. The cut-off value for the assay is 25 EU/mL. The analysis of this outcome measure was reported for each formulation of the Boostrix (300 μg or 500 μg of aluminum). The objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of Boostrix formulation on the immunogenicity response to RSVPreF3.
Diphtheria (Anti-D) GMC at Screening by Each Boostrix Formulation [Primary Study]	At Screening (Day -7 to Day 1)	Serological assays for the determination of IgG antibodies against anti-D were performed by ELISA. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum).
Diphtheria (Anti-D) GMCs at Day 31 by Each Boostrix Formulation [Primary Study]	At Day 31	Serological assays for the determination of IgG antibodies against anti-D were performed by ELISA. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum).
Tetanus (Anti-T) GMCs at Screening by Each Boostrix Formulation [Primary Study]	At Screening (Day -7 to Day 1)	Serological assays for the determination of IgG antibodies against anti-T were performed by ELISA. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum).
Tetanus (Anti-T) GMCs at Day 31 by Each Boostrix Formulation [Primary Study]	At Day 31	Serological assays for the determination of IgG antibodies against anti-T were performed by ELISA. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum).
Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) GMCs at Screening [Primary Study]	At Screening (Day -7 to Day 1)	Serological assays for the determination of IgG antibodies against Bordetella pertussis: anti-PT, anti-FHA and anti-PRN were performed by ELISA. Analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies.
Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) GMCs at Day 31 [Primary Study]	At Day 31	Serological assays for the determination of IgG antibodies against Bordetella pertussis: anti-PT, anti-FHA and anti-PRN were performed by ELISA. Analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies.
RSV A Neutralizing GMTs at Day 31 by Each Boostrix Formulation [Primary Study]	At Day 31	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay and titers are expressed in ED60. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the immunogenicity response to RSVPreF3.
RSV A Neutralizing GMTs at Single Time Point Between 12 to 18 Months Post 1st Vaccination [Primary Study]	At a single timepoint between 12 to 18 months post 1st vaccination	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay and titers are expressed in ED60. Analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the immunogenicity response to RSVPreF3.
Tetanus (Anti-T) GMCs at Screening [Primary Study]	At Screening (Day -7 to Day 1)	Serological assays for the determination of IgG antibodies against anti-T were performed by ELISA. Analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies.
Tetanus (Anti-T) GMCs at Day 31 [Primary Study]	At Day 31	Serological assays for the determination of IgG antibodies against anti-T were performed by ELISA. Analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies.
RSV A Neutralizing GMTs at Day 31 Post 2nd Vaccination [Extension Study]	At Day 31 post 2nd vaccination	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay and titers are expressed in ED60. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies, as the objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the immunogenicity response to RSVPreF3.
RSV PreF3 IgG GMCs at Screening by Each Boostrix Formulation [Primary Study]	At Screening (Day -7 to Day 1)	Serological assays for the determination of IgG antibodies against RSV PreF3 were performed by ELISA. The corresponding antibody concentration is expressed in EU/mL. The cut-off value for the assay is 25 EU/mL. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the immunogenicity response to RSVPreF3.
RSV PreF3 IgG GMCs at Day 31 by Each Boostrix Formulation [Primary Study]	At Day 31	Serological assays for the determination of IgG antibodies against RSV PreF3 were performed by ELISA. The corresponding antibody concentration is expressed in EU/mL. The cut-off value for the assay is 25 EU/mL. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum), as the objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of dTpa (Boostrix) formulation on the immunogenicity response to RSVPreF3.
RSV PreF3 IgG GMCs at Single Time Point Between 12 to 18 Months Post 1st Vaccination by Each Boostrix Formulation [Primary Study]	At a single timepoint between 12 to 18 months post 1st vaccination	Serological assays for the determination of IgG antibodies against RSV PreF3 were performed by ELISA. The corresponding antibody concentration is expressed in EU/mL. The cut-off value for the assay is 25 EU/mL. The analysis of this outcome measure was reported for each formulation of the Boostrix (300 μg or 500 μg of aluminum). The objective of this endpoint was to analyze the impact of co-administration of RSVPreF3 with either 300 μg or 500 μg of Boostrix formulation on the immunogenicity response to RSVPreF3.
RSV PreF3 IgG GMCs at Single Time Point Between 12 to 18 Months Post 1st Vaccination [Primary Study]	At a single timepoint between 12 to 18 months post 1st vaccination	Serological assays for the determination of IgG antibodies against RSV PreF3 were performed by ELISA. The corresponding antibody concentration is expressed in EU/mL. The cut-off value for the assay is 25 EU/mL. Analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies. The objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the immunogenicity response to RSVPreF3.
RSV PreF3 IgG GMCs at Day 31 Post 2nd Vaccination [Extension Study]	At Day 31 post 2nd vaccination	Serological assays for the determination of IgG antibodies against RSV PreF3 were performed by ELISA. The analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled), RSV120_Placebo_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies, as the objective of this endpoint was to analyze the impact of the co-administration of RSVPreF3 with dTpa (Boostrix) (both formulations together) on the immunogenicity response to RSVPreF3.
Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) GMCs at Screening by Each Boostrix Formulation [Primary Study]	At Screening (Day -7 to Day 1)	Serological assays for the determination of IgG antibodies against Bordetella pertussis: anti-PT, anti-FHA and anti-PRN were performed by ELISA. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum).
Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) GMCs at Day 31 by Each Boostrix Formulation [Primary Study]	At Day 31	Serological assays for the determination of IgG antibodies against Bordetella pertussis: anti-PT, anti-FHA and anti-PRN were performed by ELISA. The analysis of this outcome measure was reported for each formulation of the dTpa (Boostrix) vaccine (300 μg or 500 μg of aluminum).
Diphtheria (Anti-D) GMCs at Screening [Primary Study]	At Screening (Day -7 to Day 1)	Serological assays for the determination of IgG antibodies against anti-D were performed by ELISA. Analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies.
Diphtheria (Anti-D) GMCs at Day 31 [Primary Study]	At Day 31	Serological assays for the determination of IgG antibodies against anti-D were performed by ELISA. Analysis of this outcome measure was reported for the Pooled groups \[RSV120_dTpa_RSV120(Pooled), RSV60_dTpa_RSV120(Pooled) and dTpa_Placebo_RSV120(Pooled)\] as the two formulations of the dTpa vaccine (containing 300 μg or 500 μg of aluminum) showed similar immunogenicity and safety profiles in previous studies.