Respiratory Syncytial Virus Infections
Conditions
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 seasonal quadrivalent influenza vaccine (FLU-QIV) in adults aged 60 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-QIV
FLU-QIV administered intramuscularly in the deltoid region of the dominant (Co-Ad Group) arm or the non-dominant (Control Group) arm.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 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 ≥60 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 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. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. * Hypersensitivity to latex. * History of GBS, anaphylaxis, febrile seizures, Bell's palsy and narcolepsy. * 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 dose of study vaccines and ending 30 days after the last vaccine administration, or planned use during the study period. * Administration of an influenza vaccine during the 6 months preceding the study FLU-QIV 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 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 Neutralization Antibody Titers Expressed as Geometric Mean Titers (GMTs) | At 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group) | The serum neutralization assay is a functional assay that measures the ability of serum antibodies to neutralize RSV-A entry and replication in a host cell line. The serum neutralizing antibody titer is expressed in ED60 (Estimated Dilution 60) and corresponds to the inverse of the interpolated serum dilution that yields a 60% reduction of the signal compared to a control without serum. |
| Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs | 1 month after the FLU vaccine dose (at Day 31) | HI antibody titers were assessed for each of the Flu vaccine strains, namely Flu A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). The serum HI antibody titers are expressed in 1/Dilution (DIL) where DIL corresponds to the highest dilution that shows complete HI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RSV-B Neutralization Antibody Titers Expressed as Geometric Mean Titers (GMT) | 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group) | The serum neutralization assay is a functional assay that measures the ability of serum antibodies to neutralize RSV-B entry and replication in a host cell line. The serum neutralizing antibody titer is expressed in ED60 (Estimated Dilution 60) and corresponds to the inverse of the interpolated serum dilution that yields a 60% reduction of the signal compared to a control without serum. |
| RSV-B Neutralization Antibody Titers Expressed as MGI | 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group) | MGI was defined as the geometric mean of the within participant ratios of the post-dose titer over the pre-dose titer. |
| HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | At baseline (at Day 1) and 1 month after the FLU vaccine dose (at Day 31) | HI antibody titers were assessed for each of the Flu vaccine strains, namely A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). The serum HI antibody titers are expressed in 1/DIL where DIL corresponds to the highest dilution that shows complete HI. |
| HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | At baseline (at Day 1) and 1 month after the FLU vaccine dose (at Day 31) | SPR for HI antibody response was defined as percentage of vaccinees with a serum HI titer \>= 1:40 that usually is accepted as indicating protection. HI antibody titers were assessed for each of the Flu vaccine strains, namely A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). |
| HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as MGI | 1 month after the FLU vaccine dose (at Day 31) | MGI was defined as the geometric mean of the within participant ratios of the post-dose titer over the pre-dose titer. HI antibody were assessed for each of the FLUvaccine strain, namely A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). |
| Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR) | 1 month after the FLU vaccine dose (at Day 31) | SCR for HI antibody response was defined as the percentage of vaccinees who have either a HI pre-dose titer \< 1:10 and a post-dose titer \>= 1:40 or a pre-dose titer \>= 1:10 and at least a four-fold increase in post-dose titer. HI antibody titers were assessed for each of the Flu vaccine strains, namely Flu A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). |
| Percentage of Participants With Solicited Systemic Events | Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination | Solicited systemic events assessed were arthralgia, fatigue, fever \[defined as temperature equal to or above (\>=) 38 degrees Celsius (C)/100.4 degrees Fahrenheit (F)\], headache and myalgia. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. |
| Percentage of Participants Reporting at Least One Unsolicited Adverse Event | Within 30 days (the day of vaccination and 29 subsequent days) after each vaccination | An unsolicited AEs is any AE reported in addition to those solicited during the clinical study and that was not included in a list of solicited events using a Participant Diary. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event. Unsolicited AEs include serious, non-serious AEs and potential immune-mediated diseases (pIMDs). Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. |
| Percentage of Participants Reporting at Least One Serious Adverse Event (SAE) | From Day 1 up to study end (6 months after last vaccination) | 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. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. |
| Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMD) | From Day 1 up to study end (6 months after last vaccination) | 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. |
| Percentage of Participants With Solicited Administration Site Events | Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination | Solicited administration site adverse events(AEs) assessed were erythema, pain and swelling. Any = occurrence of the adverse event regardless of intensity grade. |
| RSV-A Neutralization Antibody Titers Expressed as Mean Geometric Increase (MGI) | 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the 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
New Zealand, Panama, South Africa
Participant flow
Pre-assignment details
Out of 976 participants enrolled in the study, 86 participants were not assigned to any study group and 5 participants did not receive any study treatment. 885 participants were vaccinated and included in the Exposed Set.
Participants by arm
| Arm | Count |
|---|---|
| Co-Ad Group Participants received 1 dose of RSV\_PreF3 Older Adult (OA) investigational vaccine and 1 dose of FLU-QIV at Day 1 and were followed up until the study end. | 442 |
| Control Group Participants received 1 dose of FLU-QIV at Day 1 and 1 dose of RSV\_PreF3 OA investigational vaccine at Day 31 and were followed up until the study end. | 443 |
| Total | 885 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 10 |
| Overall Study | CONSENT WITHDRAWAL, NOT DUE TO A (S)AE | 0 | 8 |
| Overall Study | Lost to Follow-up | 8 | 7 |
| Overall Study | Other | 0 | 1 |
Baseline characteristics
| Characteristic | Co-Ad Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 68.4 Years STANDARD_DEVIATION 6.9 | 68.6 Years STANDARD_DEVIATION 6.9 | 68.5 Years STANDARD_DEVIATION 6.9 |
| Race/Ethnicity, Customized Asian | 4 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Black Or African American | 72 Participants | 70 Participants | 142 Participants |
| Race/Ethnicity, Customized Maori | 7 Participants | 5 Participants | 12 Participants |
| Race/Ethnicity, Customized Mixed Race | 218 Participants | 227 Participants | 445 Participants |
| Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 137 Participants | 135 Participants | 272 Participants |
| Sex: Female, Male Female | 228 Participants | 228 Participants | 456 Participants |
| Sex: Female, Male Male | 214 Participants | 215 Participants | 429 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 442 | 8 / 443 |
| other Total, other adverse events | 290 / 442 | 276 / 443 |
| serious Total, serious adverse events | 15 / 442 | 20 / 443 |
Outcome results
Primary
Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs
HI antibody titers were assessed for each of the Flu vaccine strains, namely Flu A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). The serum HI antibody titers are expressed in 1/Dilution (DIL) where DIL corresponds to the highest dilution that shows complete HI.
Time frame: 1 month after the FLU vaccine dose (at Day 31)
Population: The analysis was performed on the PPS which consisted of all eligible participants who received at least 1 study intervention as per protocol, had immunogenicity results pre-post-dose for at least 1 antigen, complied with blood draw intervals and contribution of participants to PPS at specific timepoint will be defined by timepoint, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-Ad Group | Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs | Flu A/Hong Kong/2671/2019 H3N2 | 295.2 Titers (1/DIL) |
| Co-Ad Group | Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs | Flu A/Victoria/2570/2019 H1N1 | 267.1 Titers (1/DIL) |
| Co-Ad Group | Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs | Flu B/Phuket/3073/2013 Yamagata | 28.9 Titers (1/DIL) |
| Co-Ad Group | Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs | Flu B/Washington/02/2019 Victoria | 41.6 Titers (1/DIL) |
| Control Group | Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs | Flu B/Washington/02/2019 Victoria | 47.9 Titers (1/DIL) |
| Control Group | Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs | Flu A/Hong Kong/2671/2019 H3N2 | 346.8 Titers (1/DIL) |
| Control Group | Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs | Flu B/Phuket/3073/2013 Yamagata | 34.8 Titers (1/DIL) |
| Control Group | Hemagglutinin Inhibition (HI) Antibody Titers for Each of the FLU Vaccine Strains Expressed as Group GMTs | Flu A/Victoria/2570/2019 H1N1 | 325.4 Titers (1/DIL) |
Comparison: For the Flu A/Hong Kong/2671/2019 (H3N2) strain, an ANCOVA model was used to analyze post-vaccination log-transformed titers. The ANCOVA model included the treatment group, the age category (age at vaccination: 60-69, 70-79 or \>=80 years), country and sex as fixed effects and the pre-dose log-10 transformed titer as covariate.95% CI: [1.02, 1.35]
Comparison: For the Flu A/Victoria/2570/2019 (H1N1) strain, an ANCOVA model was used to analyze post-vaccination log-transformed titers. The ANCOVA model included the treatment group, the age category (age at vaccination: 60-69, 70-79 or \>=80 years), country and sex as fixed effects and the pre-dose log-10 transformed titer as covariate.95% CI: [1.03, 1.44]
Comparison: For the Flu B/Phuket/3073/2013 (Yamagata) strain, an ANCOVA model was used to analyze post-vaccination log-transformed titers. The ANCOVA model included the treatment group, the age category (age at vaccination: 60-69, 70-79 or \>=80 years), country and sex as fixed effects and the pre-dose log-10 transformed titer as covariate.95% CI: [1.04, 1.32]
Comparison: For the Flu B/Washington/02/2019 (Victoria) strain, an ANOVA model was used to analyze post-vaccination log-transformed titers. The ANCOVA model included the treatment group, the age category (age at vaccination: 60-69, 70-79 or \>=80 years), country and sex as fixed effects and the pre-dose log-10 transformed titer as covariate.95% CI: [0.95, 1.26]
Primary
RSV-A Neutralization Antibody Titers Expressed as Geometric Mean Titers (GMTs)
The serum neutralization assay is a functional assay that measures the ability of serum antibodies to neutralize RSV-A entry and replication in a host cell line. The serum neutralizing antibody titer is expressed in ED60 (Estimated Dilution 60) and corresponds to the inverse of the interpolated serum dilution that yields a 60% reduction of the signal compared to a control without serum.
Time frame: At 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group)
Population: The analysis was performed on the Per Protocol set (PPS) which consisted of all eligible participants who received at least 1 study intervention as per protocol, had immunogenicity results pre-post-dose for at least 1 antigen, complied with blood draw intervals and contribution of participants to PPS at specific timepoint will be defined by timepoint, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-A Neutralization Antibody Titers Expressed as Geometric Mean Titers (GMTs) | 10060.5 Titers (ED 60) |
| Control Group | RSV-A Neutralization Antibody Titers Expressed as Geometric Mean Titers (GMTs) | 12255 Titers (ED 60) |
Comparison: Adjusted ratios of Control group over Co-Ad Group in RSV-A Neutralizing antibody GMTs at one month after RSV\_PreF3 OA investigational vaccination. An Analysis of Covariance (ANCOVA) model was used to analyse post-vaccination log-transformed titers of RSV-A neutralizing antibodies The ANCOVA model included the treatment group, the age category (age at vaccination: 60-69, 70-79 or \>=80 years), country and sex as fixed effects and the pre-dose log-10 titer as covariate.95% CI: [1.12, 1.44]
Secondary
HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs
HI antibody titers were assessed for each of the Flu vaccine strains, namely A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria). The serum HI antibody titers are expressed in 1/DIL where DIL corresponds to the highest dilution that shows complete HI.
Time frame: At baseline (at Day 1) and 1 month after the FLU vaccine dose (at Day 31)
Population: The analysis was performed on the PPS which consisted of all eligible participants who received at least 1 study intervention as per protocol, had immunogenicity results pre-post-dose for at least 1 antigen, complied with blood draw intervals and contribution of participants to PPS at specific timepoint will be defined by timepoint, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu A/Hong Kong/2671/2019 H3N2, Day 1 | 61.4 Titers (1/DIL) |
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu A/Hong Kong/2671/2019 H3N2, Day 31 | 295.2 Titers (1/DIL) |
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu A/Victoria/2570/2019 H1N1, Day 1 | 20 Titers (1/DIL) |
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu A/Victoria/2570/2019 H1N1, Day 31 | 267.1 Titers (1/DIL) |
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 10.4 Titers (1/DIL) |
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu B/Phuket/3073/2013 Yamagata, Day 31 | 28.9 Titers (1/DIL) |
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu B/Washington/02/2019 Victoria, Day 1 | 12.2 Titers (1/DIL) |
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu B/Washington/02/2019 Victoria, Day 31 | 41.6 Titers (1/DIL) |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu B/Washington/02/2019 Victoria, Day 31 | 47.9 Titers (1/DIL) |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu A/Hong Kong/2671/2019 H3N2, Day 1 | 63.3 Titers (1/DIL) |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 10.8 Titers (1/DIL) |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu A/Hong Kong/2671/2019 H3N2, Day 31 | 346.8 Titers (1/DIL) |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu B/Washington/02/2019 Victoria, Day 1 | 13.5 Titers (1/DIL) |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu A/Victoria/2570/2019 H1N1, Day 1 | 19.9 Titers (1/DIL) |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu B/Phuket/3073/2013 Yamagata, Day 31 | 34.8 Titers (1/DIL) |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as GMTs | Flu A/Victoria/2570/2019 H1N1, Day 31 | 325.4 Titers (1/DIL) |
Secondary
HI Antibody Titers for Each of the 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. HI antibody were assessed for each of the FLUvaccine strain, namely A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria).
Time frame: 1 month after the FLU vaccine dose (at Day 31)
Population: The analysis was performed on the PPS which consisted of all eligible participants who received at least 1 study intervention as per protocol, had immunogenicity results pre-post-dose for at least 1 antigen, complied with blood draw intervals and contribution of participants to PPS at specific timepoint will be defined by timepoint, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as MGI | Flu B/Washington/02/2019 Victoria | 3.43 Ratio |
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as MGI | Flu A/Hong Kong/2671/2019 H3N2 | 4.81 Ratio |
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as MGI | Flu A/Victoria/2570/2019 H1N1 | 13.36 Ratio |
| Co-Ad Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as MGI | Flu B/Phuket/3073/2013 Yamagata HI | 2.82 Ratio |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as MGI | Flu B/Phuket/3073/2013 Yamagata HI | 3.22 Ratio |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as MGI | Flu B/Washington/02/2019 Victoria | 3.60 Ratio |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as MGI | Flu A/Victoria/2570/2019 H1N1 | 16.25 Ratio |
| Control Group | HI Antibody Titers for Each of the FLU Vaccine Strains Expressed as MGI | Flu A/Hong Kong/2671/2019 H3N2 | 5.50 Ratio |
Secondary
HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR)
SPR for HI antibody response was defined as percentage of vaccinees with a serum HI titer \>= 1:40 that usually is accepted as indicating protection. HI antibody titers were assessed for each of the Flu vaccine strains, namely A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria).
Time frame: At baseline (at Day 1) and 1 month after the FLU vaccine dose (at Day 31)
Population: The analysis was performed on the PPS which consisted of all eligible participants who received at least 1 study intervention as per protocol, had immunogenicity results pre-post-dose for at least 1 antigen, complied with blood draw intervals and contribution of participants to PPS at specific timepoint will be defined by timepoint, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu A/Hong Kong/2671/2019 H3N2, Day 1 | 70.8 Percentage of participants |
| Co-Ad Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu A/Hong Kong/2671/2019 H3N2, Day 31 | 97.4 Percentage of participants |
| Co-Ad Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu A/Victoria/2570/2019 H1N1, Day 1 | 35.4 Percentage of participants |
| Co-Ad Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu A/Victoria/2570/2019 H1N1, Day 31 | 94.6 Percentage of participants |
| Co-Ad Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 14.3 Percentage of participants |
| Co-Ad Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu B/Phuket/3073/2013 Yamagata, Day 31 | 47.8 Percentage of participants |
| Co-Ad Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu B/Washington/02/2019 Victoria, Day 1 | 20 Percentage of participants |
| Co-Ad Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu B/Washington/02/2019 Victoria, Day 31 | 59.3 Percentage of participants |
| Control Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu B/Washington/02/2019 Victoria, Day 31 | 61.3 Percentage of participants |
| Control Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu A/Hong Kong/2671/2019 H3N2, Day 1 | 70.3 Percentage of participants |
| Control Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu B/Phuket/3073/2013 Yamagata, Day 1 | 14.9 Percentage of participants |
| Control Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu A/Hong Kong/2671/2019 H3N2, Day 31 | 97.1 Percentage of participants |
| Control Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu B/Washington/02/2019 Victoria, Day 1 | 23.6 Percentage of participants |
| Control Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu A/Victoria/2570/2019 H1N1, Day 1 | 34.6 Percentage of participants |
| Control Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu B/Phuket/3073/2013 Yamagata, Day 31 | 54.3 Percentage of participants |
| Control Group | HI Seroprotection Status for Each of the FLU Vaccine Strains Expressed as Seroprotection Rate (SPR) | Flu A/Victoria/2570/2019 H1N1, Day 31 | 93.4 Percentage of participants |
Secondary
Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMD)
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.
Time frame: From Day 1 up to study end (6 months after last vaccination)
Population: The analysis was performed on the Exposed set, which included All participants who received a study intervention. Analysis per group is based on the study intervention administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMD) | 1.1 Percentage of participants |
| Control Group | Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMD) | 0.2 Percentage of participants |
Secondary
Percentage of Participants Reporting at Least One Serious Adverse Event (SAE)
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. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.
Time frame: From Day 1 up to study end (6 months after last vaccination)
Population: The analysis was performed on the Exposed set, which included All participants who received a study intervention. Analysis per group is based on the study intervention administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting at Least One Serious Adverse Event (SAE) | 3.4 Percentage of Participants |
| Control Group | Percentage of Participants Reporting at Least One Serious Adverse Event (SAE) | 4.5 Percentage of Participants |
Secondary
Percentage of Participants Reporting at Least One Unsolicited Adverse Event
An unsolicited AEs is any AE reported in addition to those solicited during the clinical study and that was not included in a list of solicited events using a Participant Diary. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event. Unsolicited AEs include serious, non-serious AEs and potential immune-mediated diseases (pIMDs). Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time frame: Within 30 days (the day of vaccination and 29 subsequent days) after each vaccination
Population: The analysis was performed on the Exposed set, which included All participants who received a study intervention. Analysis per group is based on the study intervention administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | Percentage of Participants Reporting at Least One Unsolicited Adverse Event | 18.8 Percentage of participants |
| Control Group | Percentage of Participants Reporting at Least One Unsolicited Adverse Event | 23.7 Percentage of participants |
Secondary
Percentage of Participants With Solicited Administration Site Events
Solicited administration site adverse events(AEs) assessed were erythema, pain and swelling. Any = occurrence of the adverse event regardless of intensity grade.
Time frame: Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination
Population: The analysis was performed on the Exposed set, which included All participants who received a study intervention. Analysis per group is based on the study intervention administered. RSV vaccine was administered at day 1 for the control group and at day 31 for the Co-Ad group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events | Erythema against Flu Dose given at Day 1 | 1.1 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events | Erythema against RSV Dose given at Day 1 | 4.1 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events | Pain against Flu Dose given at Day 1 | 28.3 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events | Pain against RSV Dose given at Day 1 | 47.9 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events | Swelling against Flu Dose given at Day 1 | 1.4 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Administration Site Events | Swelling against RSV Dose given at Day 1 | 3.2 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events | Swelling against Flu Dose given at Day 1 | 0.7 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events | Erythema against Flu Dose given at Day 1 | 0.5 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events | Pain against RSV Dose give at Day 31 | 39.1 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events | Erythema against RSV Dose given at Day 31 | 2.1 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events | Swelling against RSV Dose given at Day 31 | 1 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Events | Pain against Flu Dose given at Day 1 | 20.5 Percentage of participants |
Secondary
Percentage of Participants With Solicited Systemic Events
Solicited systemic events assessed were arthralgia, fatigue, fever \[defined as temperature equal to or above (\>=) 38 degrees Celsius (C)/100.4 degrees Fahrenheit (F)\], headache and myalgia. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination.
Time frame: Within 4 days (the day of vaccination and 3 subsequent days) after each vaccination
Population: The analysis was performed on the Exposed set, which included All participants who received a study intervention. Analysis per group is based on the study intervention administered. The Co-Ad group only received vaccination at Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | Percentage of Participants With Solicited Systemic Events | Fatigue, Dosing at Day 1 | 22.4 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Systemic Events | Fever, Dosing at Day 1 | 2.5 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Systemic Events | Myalgia, Dosing at Day 1 | 22.1 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Systemic Events | Headache, Dosing at Day 1 | 21.7 Percentage of participants |
| Co-Ad Group | Percentage of Participants With Solicited Systemic Events | Arthralgia, Dosing at Day 1 | 16.2 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic Events | Fever, Dosing at Day 1 | 0.7 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic Events | Fever, Dosing at Day 31 | 1 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic Events | Headache, Dosing at Day 1 | 12.8 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic Events | Headache, Dosing at Day 31 | 16.2 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic Events | Myalgia, Dosing at Day 1 | 9.4 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic Events | Myalgia, Dosing at Day 31 | 19.6 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic Events | Arthralgia, Dosing at Day 1 | 4.8 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic Events | Arthralgia, Dosing at Day 31 | 11.2 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic Events | Fatigue, Dosing at Day 1 | 12.8 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic Events | Fatigue, Dosing at Day 31 | 17.9 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: 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group)
Population: The analysis was performed on the PPS which consisted of all eligible participants who received at least 1 study intervention as per protocol, had immunogenicity results pre-post-dose for at least 1 antigen, complied with blood draw intervals and contribution of participants to PPS at specific timepoint will be defined by timepoint, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-A Neutralization Antibody Titers Expressed as Mean Geometric Increase (MGI) | 9.61 Ratio |
| Control Group | RSV-A Neutralization Antibody Titers Expressed as Mean Geometric Increase (MGI) | 12.95 Ratio |
Secondary
RSV-B Neutralization Antibody Titers Expressed as Geometric Mean Titers (GMT)
The serum neutralization assay is a functional assay that measures the ability of serum antibodies to neutralize RSV-B entry and replication in a host cell line. The serum neutralizing antibody titer is expressed in ED60 (Estimated Dilution 60) and corresponds to the inverse of the interpolated serum dilution that yields a 60% reduction of the signal compared to a control without serum.
Time frame: 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group)
Population: The analysis was performed on the PPS which consisted of all eligible participants who received at least 1 study intervention as per protocol, had immunogenicity results pre-post-dose for at least 1 antigen, complied with blood draw intervals and contribution of participants to PPS at specific timepoint will be defined by timepoint, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-B Neutralization Antibody Titers Expressed as Geometric Mean Titers (GMT) | 10518.6 Titers (ED 60) |
| Control Group | RSV-B Neutralization Antibody Titers Expressed as Geometric Mean Titers (GMT) | 14349.7 Titers (ED 60) |
Comparison: Adjusted ratios of Control group over Co-Ad Group in RSV-B Neutralizing antibody GMTs at one month after RSV\_PreF3 OA investigational vaccination. An Analysis of Covariance (ANCOVA) model was used to analyse post-vaccination log-transformed titers of RSV-B neutralizing antibodies. The ANCOVA model included the treatment group, the age category (age at vaccination: 60-69, 70-79 or \>=80 years), country and sex as fixed effects and the pre-dose log-10 titer as covariate.95% CI: [1.09, 1.51]
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: 1 month after the RSV_PreF3 OA investigational vaccine dose (at Day 31 for the Co-Ad Group and at Day 61 for the Control Group)
Population: The analysis was performed on a subset of the PPS which consisted of all eligible participants who received at least 1 study intervention as per protocol, had immunogenicity results pre-post-dose for at least 1 antigen, complied with blood draw intervals and contribution of participants to PPS at specific timepoint will be defined by timepoint, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-B Neutralization Antibody Titers Expressed as MGI | 7.67 Ratio |
| Control Group | RSV-B Neutralization Antibody Titers Expressed as MGI | 9.28 Ratio |
Secondary
Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR)
SCR for HI antibody response was defined as the percentage of vaccinees who have either a HI pre-dose titer \< 1:10 and a post-dose titer \>= 1:40 or a pre-dose titer \>= 1:10 and at least a four-fold increase in post-dose titer. HI antibody titers were assessed for each of the Flu vaccine strains, namely Flu A/Hong Kong/2671/2019 (H3N2), Flu A/Victoria/2570/2019 (H1N1), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Washington/02/2019 (Victoria).
Time frame: 1 month after the FLU vaccine dose (at Day 31)
Population: The analysis was performed on the PPS which consisted of all eligible participants who received at least 1 study intervention as per protocol, had immunogenicity results pre-post-dose for at least 1 antigen, complied with blood draw intervals and contribution of participants to PPS at specific timepoint will be defined by timepoint, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR) | Flu A/Hong Kong/2671/2019 H3N2 | 54.3 Percentage of participants |
| Co-Ad Group | Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR) | Flu A/Victoria/2570/2019 H1N1 | 78.9 Percentage of participants |
| Co-Ad Group | Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR) | Flu B/Phuket/3073/2013 Yamagata | 28.8 Percentage of participants |
| Co-Ad Group | Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR) | Flu B/Washington/02/2019 Victoria | 35.6 Percentage of participants |
| Control Group | Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR) | Flu B/Washington/02/2019 Victoria | 36 Percentage of participants |
| Control Group | Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR) | Flu A/Hong Kong/2671/2019 H3N2 | 56.9 Percentage of participants |
| Control Group | Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR) | Flu B/Phuket/3073/2013 Yamagata | 32.8 Percentage of participants |
| Control Group | Secondary: HI Seroconversion Status for Each of the Flu Vaccine Strains Expressed as Seroconversion Rate (SCR) | Flu A/Victoria/2570/2019 H1N1 | 83.5 Percentage of participants |
Comparison: For the Flu A/Hong Kong/2671/2019 (H3N2) strain, the 2-sided 95% CI on group difference in seroconversion rate (Control group minus Co-Ad group).95% CI: [-4.13, 9.3]Miettinen and Nurminen
Comparison: For the Flu A/Victoria/2570/2019 (H1N1) strain, the 2-sided 95% CI on group difference in seroconversion rate (Control group minus Co-Ad group).95% CI: [-0.77, 9.83]Miettinen and Nurminen
Comparison: For the Flu B/Phuket/3073/2013 (Yamagata) strain, the 2-sided 95% CI on group difference in seroconversion rate (Control group minus Co-Ad group).95% CI: [-2.21, 10.28]Miettinen and Nurminen
Comparison: For the Flu B/Washington/02/2019 (Victoria) strain, the 2-sided 95% CI on group difference in seroconversion rate (Control group minus Co-Ad group).95% CI: [-6.07, 6.9]Miettinen and Nurminen