Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory syncytial virus, Adjuvanted quadrivalent influenza vaccine, Immunogenicity, Safety, Reactogenicity, Adults aged 65 years and above
Brief summary
The aim of this study is to assess the immunogenicity, safety and reactogenicity of the RSV PreFusion protein 3 older adult (RSVPreF3 OA) investigational vaccine when co-administered with an adjuvanted quadrivalent influenza (FLU aQIV) vaccine, in adults aged 65 years of age (YOA).
Interventions
BIOLOGICALRSVPreF3 OA vaccine
One dose of RSVPreF3 OA vaccine administered intramuscularly.
BIOLOGICALFLU vaccine
One dose of FLU vaccine administered intramuscularly.
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 (e.g., completion of the electronic diary cards \[eDiaries\], return for follow-up visits, ability to access and utilize a phone or other electronic communications). * A male or female ≥ 65 YOA 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 study intervention administration. Participants with chronic stable medical conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease, 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 study interventions, in particular any history of severe allergic reaction to egg protein or to a previous influenza vaccine. * Hypersensitivity to latex. * Guillain-Barré syndrome that occurred within 6 weeks of receipt of prior influenza vaccine. * Serious or unstable chronic illness. * Any history of dementia or any medical condition that moderately or severely impairs cognition. * Recurrent or uncontrolled 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. * 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 dose of study interventions, 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. In the case of COVID-19 vaccines, this time window can be decreased to 14 days before and after each study intervention administration provided this COVID-19 vaccine use is in line with local governmental recommendations. * 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 administration of first dose of study interventions 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 intervention dose 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 vaccine/product (drug or 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. * Bedridden participants. * Planned move during the study conduct that prohibits participation until study end. * Participation of any study personnel or their immediate dependents, family, or household members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose | At 1 month after the FLU vaccine dose (Day 31 for both groups) | HI antibodies assessed were antibodies 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 flu strains. |
| RSV-A Neutralizing Antibody Titers Expressed as GMTs | At 1 month after the RSVPreF3 OA dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group) | RSV-A neutralizing antibodies were given as GMTs and expressed as Estimated Dilution 60 (ED60). |
| RSV-B Neutralizing Antibody Titers Expressed as GMTs | At 1 month after the RSVPreF3 OA dose (Day 31 for the CoAd Group and Day 61 for the Control Group) | RSV B neutralizing antibodies are given as GMTs and expressed as Estimated Dilution 60 (ED60). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Titers for HI Antibodies Against 4 FLU Vaccine Strains | At Day 1 (Baseline) and Day 31 | HI antibodies assessed were antibodies 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 flu strains. HI antibodies were expressed as GMT, in titers. |
| HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | At Day 1 (Baseline) and Day 31 | SPR for HI antibody was defined as the percentage of participants with a serum HI titer \>= 1:40. 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 Antibody Titers for 4 FLU Vaccine Strains Expressed as MGI | At 1 month after the FLU dose (Day 31 for both groups) compared to pre-vaccination (Day 1 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. 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 Each Solicited Administration Site Event After Each Vaccine Dose Administration | Within 7 days (the day of vaccination and 6 subsequent days) after each vaccine administration (vaccines administered at Day 1 for CoAd Group and at Day 1 and Day 31 for Control group) | The solicited administration site events after vaccination include 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 antibody is 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 (the day of vaccination and 29 subsequent days) after each vaccine administration | An unsolicited AEs is an AE that is not included in a list of solicited events using a Participant Electronic Diary. Unsolicited events must be 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 at Least One Serious Adverse Event (SAEs) | From Day 1 until 6 months after last vaccination (Month 6 for the Co-Ad Group, Month 7 for the Control group) | An 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 participant. |
| Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMDs) | From Day 1 until 6 months after last vaccination (Month 6 for the Co-Ad Group, Month 7 for the 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 Dose Administration | Within 7 days (the day of vaccination and 6 subsequent days) after each vaccine administration (vaccines administered at Day 1 and Day 31 for C-oAd Group and at Day 1 and Day 31 for Control group) | The solicited systemic events after vaccination include fever, headache, fatigue, myalgia and arthralgia. |
| RSV-A Neutralization Antibody 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 Neutralization Antibody 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
Belgium, Finland, France, Spain, United Kingdom
Participant flow
Recruitment details
All 1045 enrolled participants were randomized to Co-Ad and Control Groups and received at least 1 dose of 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 an adjuvanted quadrivalent influenza (FLU-aQIV \[FLU\]) vaccine, in adults aged 65 years old or above.
Participants by arm
| Arm | Count |
|---|---|
| Co-Ad Group Participants received one dose of FLU-aQIV vaccine and one dose of RSVPreF3 OA vaccine, both doses administered at Day 1, and were followed until end of study. | 523 |
| Control Group Participants received one dose of FLU-aQIV vaccine at Day 1, followed by one dose of RSVPreF3 OA vaccine at Day 31, and were followed until end of study. | 522 |
| Total | 1,045 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 8 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 10 |
Baseline characteristics
| Characteristic | Control Group | Total | Co-Ad Group |
|---|---|---|---|
| Age, Continuous | 72.2 YEARS STANDARD_DEVIATION 5.2 | 72.2 YEARS STANDARD_DEVIATION 5.3 | 72.1 YEARS STANDARD_DEVIATION 5.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other - Unspecified | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 516 Participants | 1038 Participants | 522 Participants |
| Sex: Female, Male Female | 275 Participants | 530 Participants | 255 Participants |
| Sex: Female, Male Male | 247 Participants | 515 Participants | 268 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 523 | 6 / 522 |
| other Total, other adverse events | 427 / 523 | 428 / 522 |
| serious Total, serious adverse events | 21 / 523 | 36 / 522 |
Outcome results
Primary
RSV-A Neutralizing Antibody Titers Expressed as GMTs
RSV-A neutralizing antibodies were given as GMTs and expressed as Estimated Dilution 60 (ED60).
Time frame: At 1 month after the RSVPreF3 OA dose (Day 31 for the Co-Ad Group and Day 61 for the Control Group)
Population: Analysis was performed on Per Protocol Set for RSV OA analysis which included eligible participants who: received at least one control group intervention or all Co-Ad group interventions, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, with immunogenicity data available for the specified analysis at the specified time point post-RSVPreF3 OA vaccine dose, who lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-A Neutralizing Antibody Titers Expressed as GMTs | 6673.4 Titers |
| Control Group | RSV-A Neutralizing Antibody Titers Expressed as GMTs | 6591.8 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).0.95% CI: [0.87, 1.12]
Primary
RSV-B Neutralizing Antibody Titers Expressed as GMTs
RSV B neutralizing antibodies are given as GMTs and expressed as Estimated Dilution 60 (ED60).
Time frame: At 1 month after the RSVPreF3 OA dose (Day 31 for the CoAd Group and Day 61 for the Control Group)
Population: Analysis was performed on Per Protocol Set for RSV OA analysis which included eligible participants who: received at least one control group intervention or all Co-Ad group interventions, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, with immunogenicity data available for the specified analysis at the specified time point post-RSVPreF3 OA vaccine dose, who lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-B Neutralizing Antibody Titers Expressed as GMTs | 7880.1 Titers |
| Control Group | RSV-B Neutralizing Antibody Titers Expressed as GMTs | 9134.1 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 CoAd Group and Day 61 for the Control Group).0.95% CI: [1.03, 1.3]
Primary
Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose
HI antibodies assessed were antibodies 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 flu strains.
Time frame: At 1 month after the FLU vaccine dose (Day 31 for both groups)
Population: Analysis was performed on Per Protocol Set for FLU analysis which included eligible participants who: received at least one control group intervention or all Co-Ad group interventions, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, with immunogenicity data available for the specified analysis at the specified time point post-FLU vaccine dose, who lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-Ad Group | Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose | Flu A/Darwin/6/2021 H3N2 | 43.8 Titers |
| Co-Ad Group | Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose | Flu A/Victoria/2570/2019 H1N1 | 143.0 Titers |
| Co-Ad Group | Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose | Flu B/Austria/1359417/2021 Victoria | 613.9 Titers |
| Co-Ad Group | Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose | Flu B/Phuket/3073/2013 Yamagata | 406.2 Titers |
| Control Group | Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose | Flu B/Phuket/3073/2013 Yamagata | 421.0 Titers |
| Control Group | Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose | Flu A/Darwin/6/2021 H3N2 | 57.7 Titers |
| Control Group | Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose | Flu B/Austria/1359417/2021 Victoria | 597.5 Titers |
| Control Group | Titers for Hemagglutination Inhibition (HI) Antibodies Against 4 FLU Vaccine Strains Expressed as Group Geometric Mean Titers (GMTs) at 1 Month After FLU Vaccine Dose | Flu A/Victoria/2570/2019 H1N1 | 148.5 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 strain, at 1 month post-FLU vaccine dose administration (Day 31 for both groups).0.95% CI: [1.13, 1.53]
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 included in the FLU vaccine, at 1 month post-FLU vaccine dose administration (Day 31 for both groups).0.95% CI: [0.91, 1.18]
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 included in the FLU vaccine, at 1 month post-FLU vaccine dose administration (Day 31 for both groups).0.95% CI: [0.9, 1.06]
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 included in the FLU vaccine, at 1 month post-FLU vaccine dose administration (Day 31 for both groups).0.95% CI: [0.95, 1.13]
Secondary
HI Antibody 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. 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 dose (Day 31 for both groups) compared to pre-vaccination (Day 1 for both groups)
Population: Analysis was performed on Per Protocol Set for FLU analysis which included eligible participants who: received at least one control group intervention or all Co-Ad group interventions, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, with immunogenicity data available for the specified analysis at the specified time point post-FLU vaccine dose, who lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-Ad Group | HI Antibody Titers for 4 FLU Vaccine Strains Expressed as MGI | Flu B/Phuket/3073/2013 Yamagata HI | 1.94 Ratio |
| Co-Ad Group | HI Antibody Titers for 4 FLU Vaccine Strains Expressed as MGI | Flu A/Victoria/2570/2019 H1N1 HI | 3.85 Ratio |
| Co-Ad Group | HI Antibody Titers for 4 FLU Vaccine Strains Expressed as MGI | Flu B/Austria/1359417/2021 Victoria HI | 1.89 Ratio |
| Co-Ad Group | HI Antibody Titers for 4 FLU Vaccine Strains Expressed as MGI | Flu A/Darwin/6/2021 H3N2 HI | 5.10 Ratio |
| Control Group | HI Antibody Titers for 4 FLU Vaccine Strains Expressed as MGI | Flu B/Austria/1359417/2021 Victoria HI | 1.84 Ratio |
| Control Group | HI Antibody Titers for 4 FLU Vaccine Strains Expressed as MGI | Flu A/Darwin/6/2021 H3N2 HI | 6.87 Ratio |
| Control Group | HI Antibody Titers for 4 FLU Vaccine Strains Expressed as MGI | Flu B/Phuket/3073/2013 Yamagata HI | 2.11 Ratio |
| Control Group | HI Antibody Titers for 4 FLU Vaccine Strains Expressed as MGI | Flu A/Victoria/2570/2019 H1N1 HI | 3.79 Ratio |
Secondary
HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains
SCR for HI antibody is 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 Per Protocol Set for FLU analysis which included eligible participants who: received at least one control group intervention or all Co-Ad group interventions, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, with immunogenicity data available for the specified analysis at the specified time point post-FLU vaccine dose, who 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 A/Darwin/6/2021 H3N2 | 51.7 Percentage of participants |
| Co-Ad Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1 | 44.0 Percentage of participants |
| Co-Ad Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria | 17.2 Percentage of participants |
| Co-Ad Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata | 18.5 Percentage of participants |
| Control Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata | 19.3 Percentage of participants |
| Control Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2 | 62.0 Percentage of participants |
| Control Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria | 17.5 Percentage of participants |
| Control Group | HI Seroconversion Rate (SCR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1 | 45.7 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).0.95% CI: [3.5, 16.9]
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).0.95% CI: [-5.16, 8.47]
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).0.95% CI: [-4.92, 5.46]
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).0.95% CI: [-4.54, 6.17]
Secondary
HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains
SPR for HI antibody was defined as the percentage of participants with a serum HI titer \>= 1:40. 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 (Baseline) and Day 31
Population: Analysis was performed on Per Protocol Set for FLU analysis which included eligible participants who: received at least one control group intervention or all Co-Ad group interventions, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, with immunogenicity data available for the specified analysis at the specified time point post-FLU vaccine dose, who 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 | 10.4 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2, Day 31 | 63.6 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 1 | 60.0 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 31 | 92.0 Percentage of participants |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria, Day 1 | 99.6 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 |
| Co-Ad Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 99.8 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 |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, 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 | 10.7 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria, Day 1 | 100 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2, Day 31 | 71.0 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 98.9 Percentage of participants |
| Control Group | HI Seroprotection Rate (SPR) for 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 1 | 64.3 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 31 | 95.2 Percentage of participants |
Secondary
Percentage of Participants Reporting at Least One 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 until 6 months after last vaccination (Month 6 for the Co-Ad Group, Month 7 for the Control group)
Population: Analysis was performed on Exposed set which included participants who received at least a study intervention and had data for the assessed timepoint and analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMDs) | 0 Percentage of participants |
| Control Group | Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMDs) | 0.6 Percentage of participants |
Secondary
Percentage of Participants Reporting at Least One Serious Adverse Event (SAEs)
An 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 participant.
Time frame: From Day 1 until 6 months after last vaccination (Month 6 for the Co-Ad Group, Month 7 for the Control group)
Population: Analysis was performed on Exposed set which included participants who received at least a study intervention and had data for the assessed timepoint and analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting at Least One Serious Adverse Event (SAEs) | 4.0 Percentage of participants |
| Control Group | Percentage of Participants Reporting at Least One Serious Adverse Event (SAEs) | 6.9 Percentage of participants |
Secondary
Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration
The solicited administration site events after vaccination include erythema, pain and swelling.
Time frame: Within 7 days (the day of vaccination and 6 subsequent days) after each vaccine administration (vaccines administered at Day 1 for CoAd Group and at Day 1 and Day 31 for Control group)
Population: Analysis was performed on Exposed set which included participants who received a study intervention and with the electronic diary completed post-each vaccination and for whom solicited administration event data was available for 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. Analysis per group is based on the study intervention administered on specific visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Erythema, FLU dose given at Day 1 | 6.6 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Erythema, RSV dose given at Day 1 | 14.1 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Pain, FLU dose given at Day 1 | 51.7 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Pain, RSV dose given at Day 1 | 66.1 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Swelling, RSV dose given at Day 1 | 10.5 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Swelling, FLU dose given at Day 1 | 5.2 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Swelling, RSV dose given at Day 31 | 8.4 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Erythema, FLU dose given at Day 1 | 5.3 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Pain, RSV dose given at Day 31 | 58.8 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Erythema, RSV dose given at Day 31 | 12.4 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Swelling, FLU dose given at Day 1 | 6.0 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Administration Site Event After Each Vaccine Dose Administration | Pain, FLU dose given at Day 1 | 44.8 Percentage of participants |
Secondary
Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration
The solicited systemic events after vaccination include fever, headache, fatigue, myalgia and arthralgia.
Time frame: Within 7 days (the day of vaccination and 6 subsequent days) after each vaccine administration (vaccines administered at Day 1 and Day 31 for C-oAd Group and at Day 1 and Day 31 for Control group)
Population: Analysis was performed on Exposed set which included participants who received a study intervention and with the electronic diary completed post-each vaccination and for whom solicited administration event data was available for 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. Analysis per group is based on the study intervention administered on specific visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Fatigue, Dosing at Day 1 | 45.7 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each 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 Dose Administration | Myalgia, Dosing at Day 1 | 39.0 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Headache, Dosing at Day 1 | 32.2 Percentage of participants |
| Co-Ad Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Arthralgia, Dosing at Day 1 | 25.8 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Fever, Dosing at Day 1 | 0.6 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Fever, Dosing at Day 31 | 1.1 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Headache, Dosing at Day 1 | 19.3 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Headache, Dosing at Day 31 | 23.9 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Myalgia, Dosing at Day 1 | 23.0 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Myalgia, Dosing at Day 31 | 31.9 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Arthralgia, Dosing at Day 1 | 15.6 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Arthralgia, Dosing at Day 31 | 17.1 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Fatigue, Dosing at Day 1 | 28.5 Percentage of participants |
| Control Group | Percentage of Participants Reporting Each Solicited Systemic Event After Each Dose Administration | Fatigue, Dosing at Day 31 | 30.4 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 Electronic Diary. Unsolicited events must be 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 (the day of vaccination and 29 subsequent days) after each vaccine administration
Population: Analysis was performed on Exposed set which included participants who received at least a study intervention and had data for the assessed timepoint and analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting Unsolicited Adverse Events (AEs) | 13.6 Percentage of participants |
| Control Group | Percentage of Participants Reporting Unsolicited Adverse Events (AEs) | 24.5 Percentage of participants |
Secondary
RSV-A Neutralization Antibody 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 Per Protocol Set for RSV OA analysis which included eligible participants who: received at least one control group intervention or all Co-Ad group interventions, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, with immunogenicity data available for the specified analysis at the specified time point post-RSVPreF3 OA vaccine dose, who lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-A Neutralization Antibody Titers Expressed as Mean Geometric Increase (MGI) | 8.50 Ratio |
| Control Group | RSV-A Neutralization Antibody Titers Expressed as Mean Geometric Increase (MGI) | 7.58 Ratio |
Secondary
RSV-B Neutralization Antibody 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 Per Protocol Set for RSV OA analysis which included eligible participants who: received at least one control group intervention or all Co-Ad group interventions, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, with immunogenicity data available for the specified analysis at the specified time point post-RSVPreF3 OA vaccine dose, who lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-B Neutralization Antibody Titers Expressed as MGI | 7.11 Ratio |
| Control Group | RSV-B Neutralization Antibody Titers Expressed as MGI | 7.46 Ratio |
Secondary
Titers for HI Antibodies Against 4 FLU Vaccine Strains
HI antibodies assessed were antibodies 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 flu strains. HI antibodies were expressed as GMT, in titers.
Time frame: At Day 1 (Baseline) and Day 31
Population: Analysis was performed on Per Protocol Set for FLU analysis which included eligible participants who: received at least one control group intervention or all Co-Ad group interventions, had pre- and post-dose immunogenicity results, adhered to specified blood draw intervals, with immunogenicity data available for the specified analysis at the specified time point post-FLU vaccine dose, who lacked interfering medical conditions and avoided prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-Ad Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2, Day 1 | 9.1 Titers |
| Co-Ad Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria, Day 1 | 323.6 Titers |
| Co-Ad Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 1 | 40.0 Titers |
| Co-Ad Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria, Day 31 | 614.9 Titers |
| Co-Ad Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2 , Day 31 | 45.3 Titers |
| Co-Ad Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 213.1 Titers |
| Co-Ad Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, Day 31 | 423.0 Titers |
| Co-Ad Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 31 | 151.0 Titers |
| Control Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, Day 31 | 417.5 Titers |
| Control Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2, Day 1 | 8.7 Titers |
| Control Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu A/Darwin/6/2021 H3N2 , Day 31 | 58.3 Titers |
| Control Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 1 | 43.2 Titers |
| Control Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu A/Victoria/2570/2019 H1N1, Day 31 | 163.8 Titers |
| Control Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria, Day 1 | 327.2 Titers |
| Control Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu B/Austria/1359417/2021 Victoria, Day 31 | 608.1 Titers |
| Control Group | Titers for HI Antibodies Against 4 FLU Vaccine Strains | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 193.2 Titers |