Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory syncytial virus, High dose quadrivalent influenza vaccine, Immunogenicity, Safety, Reactogenicity, Adults aged 65 years and above
Brief summary
The purpose of this study is to assess the immunogenicity, safety and reactogenicity of the RSVPreF3 OA investigational vaccine when co-administered with the high dose quadrivalent influenza (FLU HD) vaccine in adults aged 65 years and above compared to separate administration of the vaccines.
Interventions
BIOLOGICALRSVPreF3 OA investigational vaccine
RSVPreF3 OA investigational vaccine administered intramuscularly in the deltoid region of the non-dominant arm.
BIOLOGICALFLU HD vaccine
FLU HD vaccine administered intramuscularly in the deltoid region of the dominant arm (Co-Ad Group) or the non-dominant arm (Control Group).
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol * A male or female ≥65 years of age at the time of the first study intervention administration. * Participants living in the general community or in an assisted-living facility that provides minimal assistance, such that the participant is primarily responsible for self-care and activities of daily living. * Written or witnessed informed consent obtained from the participant prior to performance of any study-specific procedure. * Participants who are medically stable in the opinion of the investigator at the time of first vaccination. Participants with chronic stable medical conditions with or without specific treatment are allowed to participate in this study if considered by the investigator as medically stable.
Exclusion criteria
Medical conditions * Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy, based on medical history and physical examination (no laboratory testing required). * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. * Hypersensitivity to latex. * History of Guillain Barré syndrome, or anaphylaxis. * Serious or unstable chronic illness. * Any history of dementia or any medical condition that moderately or severely impairs cognition. * Recurrent or un-controlled neurological disorders or seizures. Participants with medically-controlled active or chronic neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol (e.g. completion of diary cards, attend regular phone calls/study site visits). * Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study. * Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. Prior/Concomitant therapy * Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study interventions during the period beginning 30 days before the first study vaccine administration, or planned use during the study period. * Administration of an influenza vaccine during the 6 months preceding the study FLU vaccine administration. * Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first study intervention administration and ending 30 days after the last study intervention administration. Note: In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) is recommended and/or organized by the public health authorities, outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly. * Previous vaccination with an RSV vaccine. * Administration of long-acting immune-modifying drugs or planned administration at any time during the study period. * Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the first dose of study vaccine or planned administration during the study period. * Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the first study vaccination or planned administration during the study period. For corticosteroids, this will mean prednisone ≥20 mg/day, or equivalent. Inhaled and topical steroids are allowed. Prior/Concurrent clinical study experience • Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug/invasive medical device). Other exclusions * History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures. * Planned move during the study conduct that prohibits participation until 1 month post-last vaccine administration. * Bedridden participants. * Participation of any study personnel or their immediate dependents, family, or household members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RSV-A Neutralizing Titers Expressed as Group Geometric Mean Titers (GMTs) | At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) | RSV-A neutralizing titers were given as group GMTs and expressed as Estimated Dilution 60 (ED60). |
| Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs | At 1 month after the FLU vaccine dose (Day 31 for both groups) | HI titers were assessed against the Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata strains. |
| RSV-B Neutralizing Titers Expressed as Group GMTs | At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) | RSV-B neutralizing titers were given as group GMTs and expressed as Estimated Dilution 60 (ED60). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | At Day 1 and 1 month after FLU vaccine dose administration (Day 31 for both groups) | HI titers were assessed against the Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata strains. HI antibodies were expressed as GMTs, in titers. |
| HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | At Day 1 and 1 month after FLU vaccine dose administration (Day 31 for both groups) | SPR for HI titers was defined as the percentage of participants with a serum HI titer \>= 1:40. The assessed Flu strains were: The assessed Flu strains were: Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata. |
| HI Titers for 4 FLU Vaccine Strains, Expressed as MGI | At 1 month after the FLU vaccine dose administration (Day 31 for both groups) | MGI was defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer. |
| Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination (administered on Day 1 and 31) | The solicited administration site events after vaccination included erythema, pain and swelling. |
| HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | At 1 month after the FLU vaccine dose (Day 31 for both groups) | SCR for HI titers was defined as the percentage of participants who have either a HI predose titer less than (\<) 1:10 and a post-dose titer greater than or equal to (\>=) 1:40, or a pre-dose titer \>= 1:10 and at least a 4-fold increase in post-dose titer. The assessed Flu strains were: Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata. |
| Percentage of Participants Reporting Unsolicited Adverse Events (AEs) | Within 30 days after vaccine administration (the day of vaccination and 29 subsequent days after vaccination) | An unsolicited AEs is an AE that is not included in a list of solicited events using a participant diary. Unsolicited events must have been spontaneously communicated by a participant who signs the informed consent. Unsolicited AEs include both serious, non-serious AEs and potential immune-mediated diseases (pIMDs). |
| Percentage of Participants Reporting Serious Adverse Events (SAEs) | From Day 1 up to study end (6 months after last vaccination - Month 6 for Co-Ad Group and Month 7 for Control group) | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant. |
| Percentage of Participants Reporting Potential Immune-mediated Disease (pIMDs) | From Day 1 up to study end (6 months after last vaccination - Month 6 for Co-Ad Group and Month 7 for Control group) | pIMDs are a subset of AEs of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. The investigator must exercise his/her medical/scientific judgment to determine whether other diseases have an autoimmune origin (i.e. pathophysiology involving systemic or organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. |
| Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination (administered on Day 1 and 31) | The solicited systemic events after vaccination include arthralgia, fatigue, fever, headache and myalgia. |
| RSV-A Neutralizing Titers Expressed as Mean Geometric Increase (MGI) | At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) compared to pre-vaccination (Day 1 for Co-Ad group and Day 31 for Control group) | MGI was defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer. |
| RSV-B Neutralizing Titers Expressed as MGI | At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) compared to pre-vaccination (Day 1 for Co-Ad group and Day 31 for Control group) | MGI was defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer. |
Countries
United States
Participant flow
Recruitment details
1029 participants received at least one dose of the study intervention and were included in the exposed set.
Pre-assignment details
This study assessed the immunogenicity, safety and reactogenicity of the RSVPre3 OA vaccine when co-administered with Flu High-Dose vaccine (FLU-HD \[FLU\]), in adults aged 65 years old or above.
Participants by arm
| Arm | Count |
|---|---|
| Co-Ad Group Participants received one dose of FLU-HD vaccine and one dose of RSVPreF3 OA vaccine, both doses administered at Day 1, and were followed until end of study. | 516 |
| Control Group Participants received one dose of FLU-HD vaccine at Day 1, followed by one dose of RSVPreF3 OA vaccine at Day 31, and were followed until the study end. | 513 |
| Total | 1,029 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Consent withdrawal, not due to a (S)AE | 8 | 14 |
| Overall Study | Lost to Follow-up | 13 | 12 |
| Overall Study | Other | 0 | 2 |
Baseline characteristics
| Characteristic | Control Group | Total | Co-Ad Group |
|---|---|---|---|
| Age, Continuous | 71.1 YEARS STANDARD_DEVIATION 5.1 | 71.2 YEARS STANDARD_DEVIATION 5.2 | 71.3 YEARS STANDARD_DEVIATION 5.3 |
| Race/Ethnicity, Customized American Indian or Alasaka Native | 6 Participants | 10 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 68 Participants | 140 Participants | 72 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 82 Participants | 163 Participants | 81 Participants |
| Race/Ethnicity, Customized White | 352 Participants | 707 Participants | 355 Participants |
| Sex: Female, Male Female | 243 Participants | 510 Participants | 267 Participants |
| Sex: Female, Male Male | 270 Participants | 519 Participants | 249 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 516 | 0 / 513 |
| other Total, other adverse events | 339 / 516 | 319 / 513 |
| serious Total, serious adverse events | 12 / 516 | 15 / 513 |
Outcome results
Primary
Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs
HI titers were assessed against the Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata strains.
Time frame: At 1 month after the FLU vaccine dose (Day 31 for both groups)
Population: Analysis was performed on PPS for FLU analysis which included eligible participants who: received FLU vaccine dose in Control group and all study doses in Co-Ad group, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, had immunogenicity data available for the specified analysis at the specified time point post-FLU vaccine dose, lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-Ad Group | Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs | Flu A/Darwin/6/2021 H3N2 | 72.7 Titers |
| Co-Ad Group | Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs | Flu A/Victoria/2570/2019 H1N1 | 189.9 Titers |
| Co-Ad Group | Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs | Flu B/Austria/1359417/2021 Victoria | 859.8 Titers |
| Co-Ad Group | Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs | Flu B/Phuket/3073/2013 Yamagata | 758.7 Titers |
| Control Group | Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs | Flu B/Phuket/3073/2013 Yamagata | 703.4 Titers |
| Control Group | Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs | Flu A/Darwin/6/2021 H3N2 | 72.3 Titers |
| Control Group | Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs | Flu B/Austria/1359417/2021 Victoria | 820.9 Titers |
| Control Group | Hemagglutinin Inhibition (HI) Titers for 4 FLU Vaccine Strains Expressed as Group GMTs | Flu A/Victoria/2570/2019 H1N1 | 177.3 Titers |
Comparison: To demonstrate the non-inferiority of the FLU vaccine when co-administered with the RSVPreF3 OA vaccine compared to the FLU vaccine administered alone, in terms of HI GMTs against the Flu A/Darwin/6/2021 H3N2 influenza strain, at 1 month post-FLU vaccine dose administration (Day 31 for both groups).95% CI: [0.85, 1.16]
Comparison: To demonstrate the non-inferiority of the FLU vaccine when co-administered with the RSVPreF3 OA vaccine compared to the FLU vaccine administered alone, in terms of HI GMTs against the Flu A/Victoria/2570/2019 H1N1 influenza strain, at 1 month post-FLU vaccine dose administration (Day 31 for both groups).95% CI: [0.8, 1.09]
Comparison: To demonstrate the non-inferiority of the FLU vaccine when co administered with the RSVPreF3 OA vaccine compared to the FLU vaccine administered alone, in terms of HI GMTs against the Flu B/Austria/1359417/2021 influenza strain, at 1 month post-FLU vaccine dose administration (Day 31 for both groups).95% CI: [0.88, 1.03]
Comparison: To demonstrate the non-inferiority of the FLU vaccine when co administered with the RSVPreF3 OA vaccine compared to the FLU vaccine administered alone, in terms of HI GMTs against the Flu B/Phuket/3073/2013 Yamagata influenza strain, at 1 month post-FLU vaccine dose administration (Day 31 for both groups).95% CI: [0.84, 1.02]
Primary
RSV-A Neutralizing Titers Expressed as Group Geometric Mean Titers (GMTs)
RSV-A neutralizing titers were given as group GMTs and expressed as Estimated Dilution 60 (ED60).
Time frame: At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group)
Population: Analysis was performed on Per Protocol Set (PPS) for RSV analysis which included eligible participants who: received RSVPreF3 OA vaccine dose in Control group and all study doses in Co-Ad group, had pre and post-dose immunogenicity results, adhered to specified blood draw intervals, had immunogenicity data available for the specified analysis at the specified time point post-RSVPreF3 OA vaccine dose, lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-A Neutralizing Titers Expressed as Group Geometric Mean Titers (GMTs) | 5876.3 Titers |
| Control Group | RSV-A Neutralizing Titers Expressed as Group Geometric Mean Titers (GMTs) | 6935.3 Titers |
Comparison: To demonstrate the non-inferiority of the RSVPreF3 OA vaccine when co-administered with the FLU vaccine compared to the RSVPreF3 OA vaccine administered alone, in terms of RSV-A neutralizing antibody titers, at 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group).95% CI: [1.03, 1.35]
Primary
RSV-B Neutralizing Titers Expressed as Group GMTs
RSV-B neutralizing titers were given as group GMTs and expressed as Estimated Dilution 60 (ED60).
Time frame: At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group)
Population: Analysis was performed on PPS for RSV analysis which included eligible participants who: received RSVPreF3 OA vaccine dose in Control group and all study doses in Co-Ad group, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, had immunogenicity data available for the specified analysis at the specified time point post- RSVPreF3 OA vaccine dose, lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-B Neutralizing Titers Expressed as Group GMTs | 8251.5 Titers |
| Control Group | RSV-B Neutralizing Titers Expressed as Group GMTs | 8359.0 Titers |
Comparison: To demonstrate the non-inferiority of the RSVPreF3 OA vaccine when co-administered with the FLU vaccine compared to the RSVPreF3 OA vaccine administered alone, in terms of RSV-B neutralizing antibody titers, at 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group).95% CI: [0.89, 1.15]
Secondary
HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains
SCR for HI titers was defined as the percentage of participants who have either a HI predose titer less than (\<) 1:10 and a post-dose titer greater than or equal to (\>=) 1:40, or a pre-dose titer \>= 1:10 and at least a 4-fold increase in post-dose titer. The assessed Flu strains were: Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata.
Time frame: At 1 month after the FLU vaccine dose (Day 31 for both groups)
Population: Analysis was performed on PPS for FLU analysis which included eligible participants who: received FLU vaccine dose in Control group and all study doses in Co-Ad group, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, had immunogenicity data available for the specified analysis at the specified time point post-FLU vaccine dose, lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata | 43.6 Percentage of participants |
| Co-Ad Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1 | 50.9 Percentage of participants |
| Co-Ad Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria | 39.7 Percentage of participants |
| Co-Ad Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2 | 59.2 Percentage of participants |
| Control Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria | 31.1 Percentage of participants |
| Control Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2 | 57.5 Percentage of participants |
| Control Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata | 37.7 Percentage of participants |
| Control Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1 | 46.8 Percentage of participants |
Comparison: To evaluate the non-inferiority of the FLU vaccine when co-administered with the RSVPreF3 OA vaccine compared to the FLU vaccine administered alone as measured by the difference of percentage of participants achieving seroconversion for HI antibody titers against Flu A/Darwin/6/2021 H3N2 strain at 1 month post-FLU vaccine dose administration (Day 31 for both groups).95% CI: [-8.15, 4.74]
Comparison: To evaluate the non-inferiority of the FLU vaccine when co administered with the RSVPreF3 OA vaccine compared to the FLU vaccine administered alone as measured by the difference of percentage of participants achieving seroconversion for HI antibody titers against Flu A/Victoria/2570/2019 H1N1 strain at 1 month post-FLU vaccine dose administration (Day 31 for both groups).95% CI: [-10.67, 2.48]
Comparison: To evaluate the non-inferiority of the FLU vaccine when co-administered with the RSVPreF3 OA vaccine compared to the FLU vaccine administered alone as measured by the difference of percentage of participants achieving seroconversion for HI antibody titers against Flu B/Austria/1359417/2021 Victoria at 1 month post-FLU vaccine dose administration (Day 31 for both groups).95% CI: [-14.75, -2.29]
Comparison: To evaluate the non-inferiority of the FLU vaccine when co-administered with the RSVPreF3 OA vaccine compared to the FLU vaccine administered alone as measured by the difference of percentage of participants achieving seroconversion for HI antibody titers against Flu B/Phuket/3073/2013 Yamagata strain at 1 month post-FLU vaccine dose administration (Day 31 for both groups).95% CI: [-12.28, 0.56]
Secondary
HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains
SPR for HI titers was defined as the percentage of participants with a serum HI titer \>= 1:40. The assessed Flu strains were: The assessed Flu strains were: Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata.
Time frame: At Day 1 and 1 month after FLU vaccine dose administration (Day 31 for both groups)
Population: Analysis was performed on PPS for FLU analysis which included eligible participants who: received FLU vaccine dose in Control group and all study doses in Co-Ad group, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, had immunogenicity data available for the specified analysis at the specified time point post-FLU vaccine dose, lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2, Day 1 | 17.9 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2, Day 31 | 75.3 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 96.8 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, Day 31 | 100 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 1 | 53.4 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 31 | 92.3 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria, Day 1 | 98.8 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria, Day 31 | 100 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2, Day 1 | 21.9 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 31 | 94.5 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2, Day 31 | 76.6 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria, Day 31 | 100 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 1 | 61.0 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 98.2 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria, Day 1 | 99.6 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, Day 31 | 100 Percentage of participants |
Secondary
HI Titers for 4 FLU Vaccine Strains, Expressed as MGI
MGI was defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer.
Time frame: At 1 month after the FLU vaccine dose administration (Day 31 for both groups)
Population: Analysis was performed on PPS for FLU analysis which included eligible participants who: received FLU vaccine dose in Control group and all study doses in Co-Ad group, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, had immunogenicity data available for the specified analysis at the specified time point post-FLU vaccine dose, lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-Ad Group | HI Titers for 4 FLU Vaccine Strains, Expressed as MGI | Flu A/Darwin/6/2021 H3N2 | 6.20 Ratio |
| Co-Ad Group | HI Titers for 4 FLU Vaccine Strains, Expressed as MGI | Flu A/Victoria/2570/2019 H1N1 | 5.57 Ratio |
| Co-Ad Group | HI Titers for 4 FLU Vaccine Strains, Expressed as MGI | Flu B/Austria/1359417/2021 Victoria | 2.92 Ratio |
| Co-Ad Group | HI Titers for 4 FLU Vaccine Strains, Expressed as MGI | Flu B/Phuket/3073/2013 Yamagata | 3.13 Ratio |
| Control Group | HI Titers for 4 FLU Vaccine Strains, Expressed as MGI | Flu B/Phuket/3073/2013 Yamagata | 2.87 Ratio |
| Control Group | HI Titers for 4 FLU Vaccine Strains, Expressed as MGI | Flu A/Darwin/6/2021 H3N2 | 5.87 Ratio |
| Control Group | HI Titers for 4 FLU Vaccine Strains, Expressed as MGI | Flu B/Austria/1359417/2021 Victoria | 2.71 Ratio |
| Control Group | HI Titers for 4 FLU Vaccine Strains, Expressed as MGI | Flu A/Victoria/2570/2019 H1N1 | 4.53 Ratio |
Secondary
HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT
HI titers were assessed against the Flu A/Darwin/6/2021 H3N2, Flu A/Victoria/2570/2019 H1N1, Flu B/Austria/1359417/2021 Victoria, and Flu B/Phuket/3073/2013 Yamagata strains. HI antibodies were expressed as GMTs, in titers.
Time frame: At Day 1 and 1 month after FLU vaccine dose administration (Day 31 for both groups)
Population: Analysis was performed on PPS for FLU analysis which included eligible participants who: received FLU vaccine dose in Control group and all study doses in Co-Ad group, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, had immunogenicity data available for the specified analysis at the specified time point post-FLU vaccine dose, lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-Ad Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 239.2 Titers |
| Co-Ad Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu A/Victoria/2570/2019 H1N1, Day 1 | 35.3 Titers |
| Co-Ad Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu A/Victoria/2570/2019 H1N1, Day 31 | 200.0 Titers |
| Co-Ad Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu B/Austria/1359417/2021 Victoria, Day 1 | 292.6 Titers |
| Co-Ad Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu B/Phuket/3073/2013 Yamagata, Day 31 | 751.1 Titers |
| Co-Ad Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu A/Darwin/6/2021 H3N2, Day 1 | 11.5 Titers |
| Co-Ad Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu B/Austria/1359417/2021 Victoria, Day 31 | 848.0 Titers |
| Co-Ad Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu A/Darwin/6/2021 H3N2, Day 31 | 71.8 Titers |
| Control Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu B/Austria/1359417/2021 Victoria, Day 1 | 308.5 Titers |
| Control Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu A/Darwin/6/2021 H3N2, Day 31 | 75.1 Titers |
| Control Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu B/Phuket/3073/2013 Yamagata, Day 31 | 699.6 Titers |
| Control Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu A/Victoria/2570/2019 H1N1, Day 1 | 41.9 Titers |
| Control Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu B/Austria/1359417/2021 Victoria, Day 31 | 818.3 Titers |
| Control Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu A/Victoria/2570/2019 H1N1, Day 31 | 194.7 Titers |
| Control Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu A/Darwin/6/2021 H3N2, Day 1 | 12.6 Titers |
| Control Group | HI Titers for Each of the 4 FLU Vaccine Strains Expressed as GMT | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 245.5 Titers |
Secondary
Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration
The solicited systemic events after vaccination include arthralgia, fatigue, fever, headache and myalgia.
Time frame: Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination (administered on Day 1 and 31)
Population: Analysis was performed on Modified Safety Set, which included participants who received a study intervention, with the electronic diary completed post-each vaccination by the participant or authorized caregiver, and for whom solicited administration event data was available for the specific visit. The Control group received FLU vaccination at Day 1 and RSVPreF3 OA vaccination at Day 31; Co-Ad group received co-administered vaccine (RSVPreF3 OA + FLU) on Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Fatigue, Dosing at Day 1 | 30.5 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Headache, Dosing at Day 1 | 24.3 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Fever, Dosing at Day 1 | 2.1 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Arthralgia, Dosing at Day 1 | 16.1 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Myalgia, Dosing at Day 1 | 40.2 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Myalgia, Dosing at Day 1 | 34.1 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Fever, Dosing at Day 1 | 0.7 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Fever, Dosing at Day 31 | 2.0 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Headache, Dosing at Day 1 | 17.1 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Headache, Dosing at Day 31 | 19.0 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Fatigue, Dosing at Day 31 | 23.5 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Myalgia, Dosing at Day 31 | 31.3 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Arthralgia, Dosing at Day 1 | 13.8 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Arthralgia, Dosing at Day 31 | 13.0 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Vaccine Dose Administration | Fatigue, Dosing at Day 1 | 22.0 Percentage of participants |
Secondary
Percentage of Participants Reporting Potential Immune-mediated Disease (pIMDs)
pIMDs are a subset of AEs of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. The investigator must exercise his/her medical/scientific judgment to determine whether other diseases have an autoimmune origin (i.e. pathophysiology involving systemic or organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD.
Time frame: From Day 1 up to study end (6 months after last vaccination - Month 6 for Co-Ad Group and Month 7 for Control group)
Population: Analysis was performed on Exposed set which included participants who received a study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting Potential Immune-mediated Disease (pIMDs) | 0 Percentage of participants |
| Control Group | Percentage of Participants Reporting Potential Immune-mediated Disease (pIMDs) | 0.4 Percentage of participants |
Secondary
Percentage of Participants Reporting Serious Adverse Events (SAEs)
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant.
Time frame: From Day 1 up to study end (6 months after last vaccination - Month 6 for Co-Ad Group and Month 7 for Control group)
Population: Analysis was performed on Exposed set which included participants who received a study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting Serious Adverse Events (SAEs) | 2.3 Percentage of participants |
| Control Group | Percentage of Participants Reporting Serious Adverse Events (SAEs) | 2.9 Percentage of participants |
Secondary
Percentage of Participants Reporting Unsolicited Adverse Events (AEs)
An unsolicited AEs is an AE that is not included in a list of solicited events using a participant diary. Unsolicited events must have been spontaneously communicated by a participant who signs the informed consent. Unsolicited AEs include both serious, non-serious AEs and potential immune-mediated diseases (pIMDs).
Time frame: Within 30 days after vaccine administration (the day of vaccination and 29 subsequent days after vaccination)
Population: Analysis was performed on Exposed set which included participants who received a study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting Unsolicited Adverse Events (AEs) | 12.2 Percentage of participants |
| Control Group | Percentage of Participants Reporting Unsolicited Adverse Events (AEs) | 13.5 Percentage of participants |
Secondary
Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration
The solicited administration site events after vaccination included erythema, pain and swelling.
Time frame: Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination (administered on Day 1 and 31)
Population: Analysis was performed on Modified Safety Set, which included participants who received a study intervention, with the electronic diary completed post-each vaccination by the participant or authorized caregiver, and for whom solicited administration event data was available for the specific visit. The Control group received FLU vaccination at Day 1 and RSVPreF3 OA vaccination at Day 31; Co-Ad group received co-administered vaccine (RSVPreF3 OA + FLU) on Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Erythema, Flu administration at Day 1 | 4.0 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Erythema, RSV administration at Day 1 | 4.3 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Pain, Flu administration at Day 1 | 47.0 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Pain, RSV administration at Day 1 | 55.6 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Swelling, Flu administration at Day 1 | 4.5 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Swelling, RSV administration at Day 1 | 4.0 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Swelling, Flu administration at Day 1 | 5.6 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Erythema, Flu administration at Day 1 | 4.6 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Pain, RSV administration at Day 31 | 45.8 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Erythema, RSV administration at Day 31 | 4.3 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Swelling, RSV administration at Day 31 | 4.3 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events After Each Vaccine Dose Administration | Pain, Flu administration at Day 1 | 43.5 Percentage of participants |
Secondary
RSV-A Neutralizing Titers Expressed as Mean Geometric Increase (MGI)
MGI was defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer.
Time frame: At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) compared to pre-vaccination (Day 1 for Co-Ad group and Day 31 for Control group)
Population: Analysis was performed on PPS for RSV analysis which included eligible participants who: received RSVPreF3 OA vaccine dose in Control group and all study doses in Co-Ad group, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, had immunogenicity data available for the specified analysis at the specified time point post- RSVPreF3 OA vaccine dose, lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-A Neutralizing Titers Expressed as Mean Geometric Increase (MGI) | 5.59 Ratio |
| Control Group | RSV-A Neutralizing Titers Expressed as Mean Geometric Increase (MGI) | 6.75 Ratio |
Secondary
RSV-B Neutralizing Titers Expressed as MGI
MGI was defined as the geometric mean of the within-participant ratios of the post-dose titer over the pre-dose titer.
Time frame: At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) compared to pre-vaccination (Day 1 for Co-Ad group and Day 31 for Control group)
Population: Analysis was performed on PPS for RSV analysis which included eligible participants who: received RSVPreF3 OA vaccine dose in Control group and all study doses in Co-Ad group, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, had immunogenicity data available for the specified analysis at the specified time point post- RSVPreF3 OA vaccine dose, lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-B Neutralizing Titers Expressed as MGI | 5.19 Ratio |
| Control Group | RSV-B Neutralizing Titers Expressed as MGI | 5.29 Ratio |