Efficacy Study of GSK's Investigational Respiratory Syncytial Virus (RSV) Vaccine in Adults Aged 60 Years and Above

Dose 1 Period will be conducted in 2 parts: Part 1: Participants in RSVPreF3 groups will receive lots 1, 2 and 3 of the investigational vaccine before Season 1. Part 2: Will be initiated when the vaccine lots in part 1 are exhausted at the study sites and participants in RSVPreF3 group will receive lot 4 of the investigational vaccine before Season 1.

Primary Outcome Measures

1. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated Lower Respiratory Tract Disease (LRTD) During the First Season Following a Single Dose of the RSVPreF3 OA Vaccine
   First episode of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated LRTD during the first season was assessed. The case definition for RSV-confirmed LRTD is as follows: Presence of at least one RSV-positive swab detected by RT-PCR.

Secondary Outcome Measures

1. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated LRTD Over Several Seasons Following a Single Dose of the RSVPreF3 OA Vaccine
   Efficacy of a single dose of the RSVPreF3 OA vaccine was assessed against RSV A and/or B confirmed LRTD over several seasons according to the case definition.
2. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated LRTD Over Several Seasons Following Annual Revaccination Doses of the RSVPreF3 OA Vaccine
   Efficacy of annual revaccination doses of the RSVPreF3 OA vaccine was assessed against RSV A and/or B confirmed LRTD over several seasons according to the case definition.
3. Number of Participants With First Episode of RT-PCR Confirmed RSV Subtype A and Subtype B LRTD Over 3 Seasons Following a Single Dose of the RSVPreF3 OA Vaccine
   Efficacy of a single dose of the RSVPreF3 OA vaccine was assessed against LRTD episode caused by RSV A and B subtype over 3 seasons according to the case definition.
4. Number of Participants With First Episode of RT-PCR Confirmed RSV Subtype A and Subtype B LRTD Over 3 Seasons Following a Single Dose of the RSVPreF3 OA Vaccine and Following 1 Annual Revaccination Dose
   Efficacy of a single dose and 1 annual revaccination dose of the RSVPreF3 OA vaccine was assessed against LRTD episode caused by RSV A and B subtype over 3 seasons according to the case definition.
5. Number of Participants With First Episode of RT-PCR Confirmed LRTD Caused by Human Metapneumovirus (hMPV) up to the End of Season 1 Following a Single Dose of the RSVPreF3 OA Vaccine
6. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated LRTD, by Age Categories Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
   Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses was assessed against RSV A and/or B confirmed LRTD episode according to the case definition, in the following age categories: greater than or equal to (≥) 65 years of age (YOA), ≥70 YOA and ≥80 YOA.
7. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated LRTD by RSV Season Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
   Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses was assessed against RSV A and/or B confirmed LRTD episode according to the case definition, by RSV season as follows: VE after each season includes the first occurrence of episodes reported from Day 15 post vaccination at first season, and for the next seasons, excluding analysis of participants who already reported a case in the previous season. The RSV season may be extended based on epidemiology data.
8. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated LRTD by Year Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
   Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses was assessed against RSV A and/or B confirmed LRTD episode according to the case definition, by years after vaccination as follows: VE at each year includes the first occurrence of episodes reported from Day 14 post vaccination at first year, and for the next years, excluding analysis of participants who already reported a case in the previous year.
9. Number of Participants With First Episode of RT-PCR Confirmed RSV A and /or B Associated LRTD, Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
10. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated LRTD by Baseline Comorbidities Using Charlson Comorbidity Index Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
    Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against RSV A and/or B associated LRTD episode by baseline comorbidities using Charlson Comorbidity Index. Low/medium Risk = Participants with co-morbidity score at baseline less than or equal to 3 (Charlson Index); High Risk = Participants with co-morbidity score at baseline greater than 3 (Charlson Index).
11. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated LRTD by Baseline Comorbidities According to Comorbidities of Interest Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
    Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against RSV A and/or B associated LRTD episode by baseline comorbidities of interest divided into 2: cardiorespiratory conditions such as chronic obstructive pulmonary disease (COPD), asthma, any chronic respiratory or pulmonary disease, and endocrinometabolic conditions such as diabetes mellitus type 1 or 2, chronic heart failure and advanced liver or renal disease.
12. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated LRTD by Baseline Frailty Status Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
    Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against RSV A and /or B associated LRTD episode according to the case definition, by baseline frailty status of frail, pre-frail and fit. Frail = Participants with a walking speed of less than (\<) 0.4 meters per second (m/s) or who were not able to perform the test; Pre-Frail = Participants with a walking speed between 0.4-0.99 m/s; Fit = Participants with a walking speed of ≥1 m/s.
13. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated Severe LRTD Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
    Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against RSV A and/or B associated severe LRTD episode. Case definition for RSV-confirmed severe LRTD: An RT-PCR confirmed case of RSV-associated severe LRTD is characterized by presence of lower respiratory signs or an LRTD episode assessed as severe by the investigator (Severe LRTD case definition 1) or presence of an LRTD with need for oxygen supplementation or need for positive airway pressure therapy or need for other types of mechanical ventilation (Severe LRTD case definition 2) and with at least one RSV positive swab detected by RT-PCR.
14. Number of Participants With First Episode of RT-PCR Confirmed RSV A and/or B Associated ARI Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
    Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against RSV confirmed A and/or B associated ARI episode. A case of RT-PCR confirmed RSV-associated ARI is characterized by the presence of respiratory symptoms/signs for at least 24 hours OR respiratory symptom/sign + systemic symptom/sign for at least 24 hours with at least one RSV-positive swab detected by RT-PCR.
15. Number of Participants With First Episode of Any ARI or Any LRTD Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
    Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against any ARI and any LRTD.
16. Number of Hospitalizations Due to RSV-confirmed Respiratory Diseases or Due to Complication Related to RSV-confirmed Respiratory Diseases, Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses up to End of Study
    RSV infection was confirmed by RT-PCR.
17. Number of Hospitalizations Due to Any Respiratory Diseases or Due to a Complication Related to Any Respiratory Diseases, During the RSV Seasons Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses up to End of Study
    A diagnosis of respiratory disease included: acute respiratory infections, other diseases of upper respiratory tract, pneumonia and influenza, chronic obstructive pulmonary disease and allied conditions, pneumoconioses and other lung diseases due to external agents, other diseases of respiratory system.
18. Number of Complications Related to RSV-confirmed ARI During the RSV Seasons Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses up to End of Study
    RSV infection was confirmed by RT-PCR.
19. Number of Complications Related to Any ARI During the RSV Seasons Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses up to End of Study
    RSV infection was confirmed by RT-PCR.
20. Maximum Influenza Patient-Reported Outcome (Flu-PRO) Chest Score for the Participants With RT-PCR-confirmed RSV A and/or B-associated ARI Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
    For this outcome measure, the Health Related -Quality of life (HR-QOL) score is measured by Flu-PRO questionnaire version 2.0. The Flu-PRO is a 32 items daily diary, which assesses influenza signs across 6 body systems- nose, throat, eyes, chest/respiratory, gastrointestinal and body/systemic. The objective of this outcome measure was to present data only for chest/respiratory system after a single dose and after annual revaccination. The FLU-PRO score was computed as the mean score across questionaire items for chest/respiratory body system, with the scores ranging from 0 (symptom free) to 4 (very severe symptoms).
21. Least Square Mean Flu-PRO Total Score for the Participants With RT-PCR-confirmed RSV A and/or B-associated ARI Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
    The Flu-PRO questionnaire version 2.0 is a 32 items daily diary, which assesses influenza signs across 6 body systems- nose, throat, eyes, chest/respiratory, gastrointestinal and body/systemic. The FLU-PRO total score was computed as the mean score across all 32 items of the questionaire for all 6 body systems, with the total scores ranging from 0 (symptom free) to 4 (very severe symptoms).
22. EuroQol 5-dimension Health Questionnaire (EQ-5D) Utility Score for Participants With RT-PCR-confirmed RSV A and/or B-associated ARI Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
    The EQ-5D is a general health utility questionnaire with health states, defined through 5 dimensions- mobility, self-care, usual activities, pain/ discomfort and anxiety/ depression. A participant who responds 1 (no problem/no symptom) to all 5 items has a profile "11111" and similarly a participant who responds 3 (the highest level of difficulty or symptom) to all items has a profile "33333". The health states indicated in these 5 dimensions are converted and presented as a single mean index value as recommended by EuroQol group, where values range from 0 (worst) to 1 (full health).
23. Least Square Mean of Short Form-12 (SF-12) Health Survey for Participants With RT-PCR Confirmed RSV A and/or B-associated ARI Following a Single Dose of the RSVPreF3 OA Vaccine and Following Annual Revaccination Doses
    SF-12 is a health survey with 12 questions, covering 8 domains- physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. Summary scores are computed from these domains for the physical and mental component. The total score of the SF-12 questionnaire is evaluated on a scale from 0 to 100, with a higher score indicating a better perceived health-related quality of life.
24. Duration in Days of RT-PCR Confirmed RSV A and/or B ARI and LRTD Episodes
    The duration in days of RT-PCR confirmed RSV A and/or B ARI and LRTD episodes are described.
25. Number of Participants With Each Reported Symptom/Sign and Supportive Therapy Use Associated With of RT-PCR Confirmed RSV A and/or B ARI Episodes During Season 1
    RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B ARI episodes were reported. Fever was defined as a temperature ≥38.0 degrees Celsius (°C) by any route.
26. Number of Participants With Each Reported Symptom/Sign and Supportive Therapy Use Associated With of RT-PCR Confirmed RSV A and/or B ARI Episodes During Season 2
    RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B ARI episodes were reported. Fever was defined as a temperature ≥38.0 degrees Celsius (°C) by any route.
27. Number of Participants With Each Reported Symptom/Sign and Supportive Therapy Use Associated With of RT-PCR Confirmed RSV A and/or B ARI Episodes During Season 3
    RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B ARI episodes were reported. Fever was defined as a temperature ≥38.0 degrees Celsius (°C) by any route.
28. Number of Participants With Each Reported Symptom/Sign and Supportive Therapy Use Associated With of RT-PCR Confirmed RSV A and/or B LRTD Episodes During Season 1
    RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B LRTD episodes were reported. Fever was defined as a temperature ≥38.0°C by any route.
29. Number of Participants With Each Reported Symptom/Sign and Supportive Therapy Use Associated With of RT-PCR Confirmed RSV A and/or B LRTD Episodes During Season 2
    RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B LRTD episodes were reported. Fever was defined as a temperature ≥38.0°C by any route.
30. Number of Participants With Each Reported Symptom/Sign and Supportive Therapy Use Associated With of RT-PCR Confirmed RSV A and/or B LRTD Episodes During Season 3
    RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B LRTD episodes were reported. Fever was defined as a temperature ≥38.0°C by any route.
31. Number of Participants With RT-PCR Confirmed RSV A and/or B ARI and LRTD Episodes According to Severity
    RSV A and/or B ARI and LRTD episodes were assessed as "mild", "moderate" or "severe" by the investigator after the single dose and after annual revaccination. Mild = an ARI/LRTD episode which is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. Moderate = an ARI/LRTD episode which is sufficiently discomforting to interfere with normal everyday activities. Severe = an ARI/LRTD episode which prevents normal, everyday activities.
32. RSVPreF3 Specific Immunoglobulin G(IgG) Antibody Concentrations
    The RSVPreF3 IgG antibody concentrations are expressed as geometric mean concentrations (GMCs) in ELISA units per milliliter (EU/mL).
33. RSV A Neutralizing Antibody Titers
    The RSV A neutralizing antibody titers are expressed as geometric mean titers (GMTs).
34. RSV B Neutralizing Antibody Titers
    RSV B neutralizing antibodies are expressed as GMTs.
35. Number of Participants With Any and Grade 3 Solicited Administration Site Adverse Events
    Any solicited event is defined as the occurrence of any solicited adverse event (AE) regardless of intensity grade or relation to study vaccination. Grade 3 = an event which prevented normal, everyday activities. The assessed administration site events include pain, erythema and swelling.
36. Number of Participants With Any and Grade 3 Solicited Systemic Adverse Events
    Any solicited event is defined as the occurrence of any solicited adverse event (AE) regardless of intensity grade or relation to study vaccination. Grade 3 = an event which prevented normal, everyday activities. The assessed solicited systemic events include arthralgia, fatigue, fever, headache and myalgia. Fever is defined as a temperature ≥ 38.0°C by any route. Grade 3 fever is defined as temperature \>39°C by any route.
37. Number of Days With Solicited Administration Site Adverse Events
38. Number of Days With Solicited Systemic Adverse Events
39. Number of Participants With Any Unsolicited AEs
    An unsolicited AE is defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside of the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Any= occurrence of the event regardless of intensity grade or relation to the study vaccination.
40. Number of Participants With Serious Adverse Events (SAEs)
    An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or in other situations that were considered serious per medical or scientific judgment. Any = occurrence of any SAE regardless of intensity grade or relation to study vaccination.
41. Number of Participants With Potential Immune Mediated Diseases (pIMDs)
    pIMDs aredefined as a subset of Adverse Events of Specific Interest (AESIs) that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Any= occurrence of any pIMD regardless of intensity grade or relation to the study vaccination.
42. Number of Participants With Related SAEs
    Related SAEs that occur throughout the study are assessed. Related SAEs= Any SAE related to investigational vaccine or related to study participation or to a GSK concomitant medication/vaccine as assessed by the investigator.
43. Number of Participants With Fatal SAEs
    Fatal SAEs that occur throughout the study are assessed. Fatal SAEs= Any SAEs leading to deaths.
44. Number of Participants With Related pIMDs
    Related pIMD = pIMD assessed by the investigator as related to the study vaccination.