Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory Syncytial Virus Maternal vaccine, Flu Quadrivalent influenza vaccine, Lot-to-lot consistency, Immunogenicity, Safety, Reactogenicity
Brief summary
The purpose of this study is to evaluate the clinical lot-to-lot consistency of the respiratory syncytial virus (RSV) maternal (RSV MAT) vaccine administered to healthy non-pregnant women 18-49 years of age (YOA). In addition, this study will evaluate immunogenicity, safety and reactogenicity from co-administration of RSV MAT vaccine and GSK's quadrivalent seasonal influenza (Flu D-QIV) vaccine.
Interventions
COMBINATION_PRODUCTRSVPreF3(120 μg)
A single dose of RSVPreF3(120 μg) combined with Sodium Chloride (NaCl) was administrated intramuscular (IM). There were used 3 different lots of RSVPreF3(120 μg), one for each individual group (RSV lot1 Group, RSV lot2 Group and RSV lot3 Group) considered under RSV pooled Group.
COMBINATION_PRODUCTFlu Quadrivalent influenza vaccine (15 μg HA)
A single dose of Flu Quadrivalent influenza (15 μg HA) vaccine was administrated intramuscular (IM).
COMBINATION_PRODUCTPlacebo
One dose of placebo, administered intramuscularly in the deltoid region of the right arm, at Day 1.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Observer-blind (lot-to-lot consistency) & single-blind (immunogenicity, safety and reactogenicity)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol. * Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study specific procedure. * Healthy female participants; as established by medical history and clinical examination, aged 18 to 49 years at the time of the first study intervention administration. * Female participants of childbearing potential may be enrolled in the study, if the participant: * has practiced adequate contraception for 1 month prior to study intervention administration, and * has a negative pregnancy test on the day of study intervention administration, and * has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration. * No local condition precluding injection in both left and right deltoid muscles.
Exclusion criteria
Medical conditions * History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions; * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination; * Current autoimmune disorder, for which the participant has received immune-modifying therapy within 6 months, before study vaccination; * Hypersensitivity to latex; * Acute or chronic clinically significant abnormality or poorly controlled pre-existent co-morbidities or any other clinical conditions, as determined by physical examination or medical history that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study; * Significant or uncontrolled psychiatric illness; * Recurrent history or uncontrolled neurological disorders or seizures; * Documented HIV-positive participant; * Body mass index \> 40 kg/m\^2; * Any clinically significant\* hematological parameter and/or biochemical laboratory abnormality. \*The investigator should use his/her clinical judgment to decide which abnormalities are clinically significant. * Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. Prior/Concomitant therapy * Use of any investigational or non-registered product other than the study intervention(s) during the period starting 30 days before study intervention (Day -29 to Day 1), or planned use during the study period; * Administration of long-acting immune-modifying drugs at any time during the study period; * Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the study intervention or planned administration during the study period; * Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first study intervention dose(s). For corticosteroids, this will mean prednisone 5 mg/day, or equivalent. Inhaled and topical steroids are allowed; * Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after the vaccination dose; * Administration of a seasonal influenza vaccine during the 6 months preceding entry into the study; * Previous experimental vaccination against RSV. 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; Other exclusions * Pregnant or lactating female; * Female planning to become pregnant or planning to discontinue contraceptive precautions; * Alcoholism or substance use disorder within the past 24 months based on the presence of two or more of the following abuse criteria: hazardous use, social/interpersonal problems related to use, neglected major roles to use, withdrawal tolerance, use of larger amounts or longer, repeated attempts to quit or control use, much time spent using, physical or psychological problems related to use, activities given up to use, craving; * Any study personnel or their immediate dependents, family, or household members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | From Day 1 to Day 7 (including Day 7) | Assessed solicited administration site events include pain, erythema and swelling. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | From Day 1 to Day 7 (including Day 7) | Assessed solicited systemic events include fatigue, headache, gastrointestinal (GI) symptoms (nausea, vomiting, diarrhea, abdominal pain) and fever. The preferred location for measuring temperature was the oral cavity. Fever was defined as temperature equal to or above (≥) 38.0 °C/ 100.4°F. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| Percentage of Participants Reporting Unsolicited Adverse Events (AEs) in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | From Day 1 to Day 30 (including Day 30) | An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| Percentage of Participants Reporting Serious Adverse Events (SAEs) in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | From Day 1 to Day 30 (including Day 30) | 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 or results i+F2n abnormal pregnancy outcomes. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| Percentage of Participants Reporting SAEs in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | From first vaccination up to study end (Day 1 to Day 181) | 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 or results in abnormal pregnancy outcomes.This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| RSV MAT Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 31 | At Day 31 | Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. RSV MAT IgG concentrations were expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EU/mL). As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze RSV MAT IgG ELISA concentrations, in order to demonstrate the lot-to-lot consistency of the vaccine lots. |
| Flu D-QIV Haemagglutinin Inhibition (HI) Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | At Day 31 | Flu D-QIV HI antibody titers against 3 influenza strains (A/Tasmania/503/2020 (H3N2) IVR-221; B/Washington/02/2019; B/Phuket/3073/2013) were expressed as geometric mean titers (GMTs), as assessed by HI assay. This objective analyzed the humoral immune response to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine in terms of antibody titers against 3 influenza strains. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu Group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RSV B Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | At Day 1 and Day 31 | Serological assays for the determination of antibodies against RSV B were performed by neutralization assay. RSV B neutralizing antibody titers were expressed as GMTs, in ED60. As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze the humoral immune response of RSV B neutralizing antibody titers, in order to demonstrate the lot-to-lot consistency of the vaccine lots. |
| RSV A Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | At Day 1 and Day 31 | Serological assays for the determilnation of antibodies against RSV A were performed by neutralization assay. RSV A neutralizing antibody titers were expressed as geometric mean titers (GMTs), in serum dilution inducing 60% inhibition in plaque forming units (ED60). This objective analyzed the humoral immune response of RSV MAT vaccine when given alone and co-administered with Flu D-QIV in terms of RSV A neutralizing antibody. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| RSV MAT IgG Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | At Day 1 and Day 31 | Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. RSV MAT IgG concentrations were expressed as GMCs, in EU/mL. As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze the RSV MAT IgG concentration, in order to demonstrate the lot-to-lot consistency of the vaccine lots. |
| Seroconversion Rate (SCR) to Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | At Day 31 | The SCR was defined as the percentage of participants with: a Day 1 (pre-vaccination) serum anti-HI titer \<1:10 and a Day 31 (post-vaccination) serum anti-HI titer ≥1:40, or a Day 1 (pre-vaccination) serum anti-HI titer ≥ 1:10 and a fold increase (post/pre) ≥ 4 at Day 31. The 3 influenza strains assessed were: A/Tasmania/503/2020 (H3N2) IVR-221; B/Washington/02/2019 and B/Phuket/3073/2013. This objective analyzed the seroconversion rate to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| RSV B Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | At Day 1 and Day 31 | Serological assays for the determination of antibodies against RSV B were performed by neutralization assay. RSV B neutralizing antibody titers were expressed as GMTs, in ED60. This objective analyzed the humoral immune response of RSV MAT vaccine when given alone and co-administered with Flu D-QIV in terms of RSV B neutralizing antibody. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| RSV MAT IgG Concentrations for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | At Day 1 and Day 31 | Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. RSV MAT IgG concentrations were expressed as GMCs, in EU/mL. This objective analyzed the humoral immune response of RSV MAT vaccine when given alone and co-administered with Flu D-QIV in terms of RSV MAT IgG concentrations. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | At Day 1 and Day 31 | Flu D-QIV HI antibody titers against 3 influenza strains (A/Tasmania/503/2020 (H3N2) IVR-221;B/Washington/02/2019; B/Phuket/3073/2013) were expressed as geometric mean titers (GMTs), as assessed by HI assay. This objective analyzed the humoral immune response to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine in terms of antibody titers against 3 influenza strains. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu Group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | At Day 1 and Day 31 | SPR was measured by the percentage of participants achieving an HI antibody titer ≥1:40. This objective analyzed the seroprotection rate to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu Group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. |
| RSV A Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | At Day 1 and Day 31 | Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. RSV A neutralizing antibody titers were expressed as GMTs, in ED60. As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze the humoral immune response of RSV A neutralizing antibody titers, in order to demonstrate the lot-to-lot consistency of the vaccine lots. |
Countries
Canada, Finland, South Korea, Spain, United States
Participant flow
Recruitment details
Out of 1586 participants enrolled,47 participants did not receive vaccination as they did not meet the eligibility criteria or they were lost to follow up, therefore only 1539 participants were included in the Exposed Set and started the study.
Pre-assignment details
As pre-specified in statistical plan, data reported in Participant Flow, Baseline Characteristics and Adverse Events were presented for individual RSV lot groups, pooled RSV+Flu group (since minimal differences were expected between participants who received different RSV lots of the vaccine) and Flu+Placebo Group. As pre-specified in protocol, immunogenicity outcome measures presented data for the pooled RSV and RSV+Flu groups, and individual RSV lot groups were used for lot-to-lot analyses.
Participants by arm
| Arm | Count |
|---|---|
| RSV lot1 Group Participants randomized to the RSV lot1 Group received one dose of RSV MAT Lot 1 vaccine intramuscularly at Day 1. Participants were also provided with an option of receiving Flu D-QIV vaccine at Day 31 to allow the participants receive the standard of care. | 220 |
| RSV lot2 Group Participants randomized to the RSV lot2 Group received one dose of RSV MAT Lot 2 vaccine intramuscularly at Day 1. Participants were also provided with an option of receiving Flu D-QIV vaccine at Day 31 to allow the participants receive the standard of care. | 223 |
| RSV lot3 Group Participants randomized to the RSV lot3 Group received one dose of RSV MAT Lot 3 vaccine intramuscularly at Day 1. Participants were also provided with an option of receiving Flu D-QIV vaccine at Day 31 to allow the participants receive the standard of care. | 218 |
| RSV+Flu Pooled Group Participants randomized in this group received one dose of RSVPreF3 vaccine (RSV MAT vaccine) from one of the three lots used (Lot 1, Lot 2 or Lot 3 of same formulation of RSVPreF3 vaccine) and one dose of the Flu D-QIV vaccine on Day 1, and were followed up until the end of the study (Day 181).
The participants in this group were considered for the immunogenicity and safety analyses of the RSV MAT and Flu D-QIV vaccines. | 438 |
| Flu+Placebo Group Participants randomized in this group received one dose of Flu D-QIV vaccine co-administered with one dose of placebo at Day 1, and were followed up until the end of the study (Day 181).
This group was considered comparator for immunogenicity and safety analyses for RSV+ Flu Pooled group. | 440 |
| Total | 1,539 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 | 3 | 5 | 13 |
| Overall Study | MIGRATED / MOVED FROM THE STUDY AREA | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | RSV lot1 Group | Total | Flu+Placebo Group | RSV+Flu Pooled Group | RSV lot3 Group | RSV lot2 Group |
|---|---|---|---|---|---|---|
| Age, Continuous | 32.0 YEARS STANDARD_DEVIATION 9.6 | 31.9 YEARS STANDARD_DEVIATION 9.1 | 32.1 YEARS STANDARD_DEVIATION 8.9 | 32.0 YEARS STANDARD_DEVIATION 8.9 | 31.9 YEARS STANDARD_DEVIATION 9.3 | 31.4 YEARS STANDARD_DEVIATION 9.4 |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE | 2 Participants | 26 Participants | 7 Participants | 10 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized ASIAN | 22 Participants | 149 Participants | 43 Participants | 38 Participants | 21 Participants | 25 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 12 Participants | 55 Participants | 17 Participants | 17 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized OTHER | 1 Participants | 18 Participants | 7 Participants | 3 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized WHITE | 183 Participants | 1290 Participants | 366 Participants | 369 Participants | 185 Participants | 187 Participants |
| Sex: Female, Male Female | 220 Participants | 1539 Participants | 440 Participants | 438 Participants | 218 Participants | 223 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 220 | 0 / 223 | 0 / 218 | 0 / 438 | 0 / 440 |
| other Total, other adverse events | 182 / 220 | 193 / 223 | 194 / 218 | 409 / 438 | 396 / 440 |
| serious Total, serious adverse events | 2 / 220 | 1 / 223 | 2 / 218 | 4 / 438 | 4 / 440 |
Outcome results
Primary
Flu D-QIV Haemagglutinin Inhibition (HI) Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31
Flu D-QIV HI antibody titers against 3 influenza strains (A/Tasmania/503/2020 (H3N2) IVR-221; B/Washington/02/2019; B/Phuket/3073/2013) were expressed as geometric mean titers (GMTs), as assessed by HI assay. This objective analyzed the humoral immune response to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine in terms of antibody titers against 3 influenza strains. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu Group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: At Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of Flu D-QIV vaccine and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RSV Pooled Group | Flu D-QIV Haemagglutinin Inhibition (HI) Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | A/Tasmania/503/2020 (H3N2) | 301.6 Titers |
| RSV Pooled Group | Flu D-QIV Haemagglutinin Inhibition (HI) Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | B/Washington/02/2019 | 30.7 Titers |
| RSV Pooled Group | Flu D-QIV Haemagglutinin Inhibition (HI) Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | B/Phuket/3073/2013 | 56.2 Titers |
| RSV+Flu Pooled Group | Flu D-QIV Haemagglutinin Inhibition (HI) Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | A/Tasmania/503/2020 (H3N2) | 421.3 Titers |
| RSV+Flu Pooled Group | Flu D-QIV Haemagglutinin Inhibition (HI) Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | B/Washington/02/2019 | 33.0 Titers |
| RSV+Flu Pooled Group | Flu D-QIV Haemagglutinin Inhibition (HI) Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | B/Phuket/3073/2013 | 69.9 Titers |
Comparison: To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the ratio of HI GMTs of Flu D-QIV antibody titers against A/Tasmania/503/2020 (H3N2) IVR-221 strain at 30 days post administration (Day 31).95% CI: [0.63, 0.82]GMC ratio
Comparison: To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the ratio of HI GMTs of Flu D-QIV antibody titers against B/Washington/02/2019 strain at 30 days post administration (Day 31).95% CI: [0.79, 1.1]GMC ratio
Comparison: To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the ratio of HI GMTs of Flu D-QIV antibody titers against B/Phuket/3073/2013 strain at 30 days post administration (Day 31).95% CI: [0.69, 0.93]GMC ratio
Primary
Percentage of Participants Reporting SAEs in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results in abnormal pregnancy outcomes.This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: From first vaccination up to study end (Day 1 to Day 181)
Population: Analysis is performed on the ES, which includes all participants who received at least 1 dose of the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV Pooled Group | Percentage of Participants Reporting SAEs in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | 0.8 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting SAEs in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | 0.9 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting SAEs in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | 0.9 Percentage of participants |
Primary
Percentage of Participants Reporting Serious Adverse Events (SAEs) in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results i+F2n abnormal pregnancy outcomes. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: From Day 1 to Day 30 (including Day 30)
Population: Analysis was performed on the ES, which includes all participants who received at least 1 dose of the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV Pooled Group | Percentage of Participants Reporting Serious Adverse Events (SAEs) in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | 0.2 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Serious Adverse Events (SAEs) in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | 0 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Serious Adverse Events (SAEs) in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | 0.2 Percentage of participants |
Primary
Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group
Assessed solicited administration site events include pain, erythema and swelling. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: From Day 1 to Day 7 (including Day 7)
Population: Analysis was performed on the Solicited Safety Set (SSS), which includes all participants who received at least 1 dose of the study intervention (Exposed Set \[ES\]) and who have solicited safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RSV Pooled Group | Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Erythema | 4.4 Percentage of participants |
| RSV Pooled Group | Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Pain | 53.6 Percentage of participants |
| RSV Pooled Group | Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Swelling | 4.5 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Erythema | 3.7 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Pain | 51.1 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Swelling | 4.6 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Pain | 34.4 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Swelling | 0.9 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Solicited Administration Site Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Erythema | 0.5 Percentage of participants |
Primary
Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group
Assessed solicited systemic events include fatigue, headache, gastrointestinal (GI) symptoms (nausea, vomiting, diarrhea, abdominal pain) and fever. The preferred location for measuring temperature was the oral cavity. Fever was defined as temperature equal to or above (≥) 38.0 °C/ 100.4°F. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: From Day 1 to Day 7 (including Day 7)
Population: Analysis was performed on the Solicited Safety Set (SSS), which includes all participants who received at least 1 dose of the study intervention (Exposed Set \[ES\]) and who have solicited safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RSV Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Headache | 47.6 Percentage of participants |
| RSV Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Diarrhea | 12.1 Percentage of participants |
| RSV Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Vomiting | 2.3 Percentage of participants |
| RSV Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Fatigue | 52 Percentage of participants |
| RSV Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Temperature | 2.4 Percentage of participants |
| RSV Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Abdominal pain | 12 Percentage of participants |
| RSV Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Nausea | 14.5 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Vomiting | 1.8 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Fatigue | 59.8 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Headache | 51.4 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Nausea | 15.3 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Diarrhea | 13 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Abdominal pain | 13.5 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Temperature | 3 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Diarrhea | 17.1 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Headache | 43.1 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Temperature | 0.7 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Abdominal pain | 14.1 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Vomiting | 2.3 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Nausea | 12.3 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Solicited Systemic Events in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | Fatigue | 51.9 Percentage of participants |
Primary
Percentage of Participants Reporting Unsolicited Adverse Events (AEs) in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group
An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: From Day 1 to Day 30 (including Day 30)
Population: Analysis was performed on the ES (Exposed Set), which includes all participants who received at least 1 dose of the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV Pooled Group | Percentage of Participants Reporting Unsolicited Adverse Events (AEs) in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | 26.6 Percentage of participants |
| RSV+Flu Pooled Group | Percentage of Participants Reporting Unsolicited Adverse Events (AEs) in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | 30.1 Percentage of participants |
| Flu+Placebo Group | Percentage of Participants Reporting Unsolicited Adverse Events (AEs) in RSV Pooled Group, RSV+Flu Pooled Group and Flu+Placebo Group | 25.7 Percentage of participants |
Primary
RSV MAT Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 31
Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. RSV MAT IgG concentrations were expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EU/mL). As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze RSV MAT IgG ELISA concentrations, in order to demonstrate the lot-to-lot consistency of the vaccine lots.
Time frame: At Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received only 1 dose of RSV MAT vaccine (from RSV MAT vaccine Lot 1, Lot 2 or Lot 3), and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| RSV Pooled Group | RSV MAT Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 31 | 102811.0 EU/mL |
| RSV+Flu Pooled Group | RSV MAT Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 31 | 100635.8 EU/mL |
| Flu+Placebo Group | RSV MAT Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 31 | 108709.3 EU/mL |
Comparison: To demonstrate lot-to-lot consistency of the immune responses of Lot 1 and Lot 2 of the RSV MAT vaccine, as measured by ELISA in terms of IgG GMCs at Day 31.95% CI: [0.92, 1.13]GMC ratio
Comparison: To demonstrate lot-to-lot consistency of the immune responses of Lot 1 and Lot 3 of the RSV MAT vaccine, as measured by ELISA in terms of IgG GMCs at Day 31.95% CI: [0.85, 1.05]GMC ratio
Comparison: To demonstrate lot-to-lot consistency of the immune responses of Lot 2 and Lot 3 of the RSV MAT vaccine, as measured by ELISA in terms of IgG GMCs at Day 31.95% CI: [0.83, 1.03]GMC ratio
Secondary
Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31
Flu D-QIV HI antibody titers against 3 influenza strains (A/Tasmania/503/2020 (H3N2) IVR-221;B/Washington/02/2019; B/Phuket/3073/2013) were expressed as geometric mean titers (GMTs), as assessed by HI assay. This objective analyzed the humoral immune response to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine in terms of antibody titers against 3 influenza strains. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu Group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: At Day 1 and Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of Flu D-QIV vaccine and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RSV Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | A/Tasmania/503/2020 (H3N2) , Day 1 | 92.2 Titers |
| RSV Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | A/Tasmania/503/2020 (H3N2) , Day 31 | 301.6 Titers |
| RSV Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Washington/02/2019 , Day 1 | 11.7 Titers |
| RSV Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Washington/02/2019 , Day 31 | 30.7 Titers |
| RSV Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Phuket/3073/2013 , Day 1 | 21.2 Titers |
| RSV Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Phuket/3073/2013 , Day 31 | 56.2 Titers |
| RSV+Flu Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Phuket/3073/2013 , Day 1 | 21.9 Titers |
| RSV+Flu Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | A/Tasmania/503/2020 (H3N2) , Day 1 | 110.3 Titers |
| RSV+Flu Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Washington/02/2019 , Day 31 | 33 Titers |
| RSV+Flu Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | A/Tasmania/503/2020 (H3N2) , Day 31 | 421.3 Titers |
| RSV+Flu Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Phuket/3073/2013 , Day 31 | 69.9 Titers |
| RSV+Flu Pooled Group | Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Washington/02/2019 , Day 1 | 10.3 Titers |
Secondary
RSV A Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31
Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. RSV A neutralizing antibody titers were expressed as GMTs, in ED60. As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze the humoral immune response of RSV A neutralizing antibody titers, in order to demonstrate the lot-to-lot consistency of the vaccine lots.
Time frame: At Day 1 and Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received only 1 dose of RSV MAT vaccine (from RSV MAT vaccine Lot 1, Lot 2 or Lot 3), and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RSV Pooled Group | RSV A Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 1 | 727.5 Titers |
| RSV Pooled Group | RSV A Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 31 | 8545.5 Titers |
| RSV+Flu Pooled Group | RSV A Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 1 | 758.4 Titers |
| RSV+Flu Pooled Group | RSV A Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 31 | 8760.3 Titers |
| Flu+Placebo Group | RSV A Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 1 | 680.2 Titers |
| Flu+Placebo Group | RSV A Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 31 | 9409.2 Titers |
Secondary
RSV A Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31
Serological assays for the determilnation of antibodies against RSV A were performed by neutralization assay. RSV A neutralizing antibody titers were expressed as geometric mean titers (GMTs), in serum dilution inducing 60% inhibition in plaque forming units (ED60). This objective analyzed the humoral immune response of RSV MAT vaccine when given alone and co-administered with Flu D-QIV in terms of RSV A neutralizing antibody. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: At Day 1 and Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of RSV MAT vaccine (from one of the 3 lots used) and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RSV Pooled Group | RSV A Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 1 | 721.6 Titers |
| RSV Pooled Group | RSV A Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 31 | 8900.9 Titers |
| RSV+Flu Pooled Group | RSV A Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 1 | 707.2 Titers |
| RSV+Flu Pooled Group | RSV A Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 31 | 7761.6 Titers |
Comparison: To demonstrate the immunological non-inferiority of the RSV MAT vaccine when co-administered with Flu D-QIV vaccine, compared to RSV MAT vaccine given alone as measured by the ratio of GMTs of RSV A neutralizing antibody titers at 30 days post administration (Day 31).95% CI: [0.78, 0.97]GMC ratio
Secondary
RSV B Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31
Serological assays for the determination of antibodies against RSV B were performed by neutralization assay. RSV B neutralizing antibody titers were expressed as GMTs, in ED60. As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze the humoral immune response of RSV B neutralizing antibody titers, in order to demonstrate the lot-to-lot consistency of the vaccine lots.
Time frame: At Day 1 and Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received only 1 dose of RSV MAT vaccine (from RSV MAT vaccine Lot 1, Lot 2 or Lot 3), and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RSV Pooled Group | RSV B Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 1 | 895 Titers |
| RSV Pooled Group | RSV B Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 31 | 10457 Titers |
| RSV+Flu Pooled Group | RSV B Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 1 | 1030.3 Titers |
| RSV+Flu Pooled Group | RSV B Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 31 | 11107.2 Titers |
| Flu+Placebo Group | RSV B Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 1 | 979.7 Titers |
| Flu+Placebo Group | RSV B Neutralizing Antibody Titers for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 31 | 11543.3 Titers |
Secondary
RSV B Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31
Serological assays for the determination of antibodies against RSV B were performed by neutralization assay. RSV B neutralizing antibody titers were expressed as GMTs, in ED60. This objective analyzed the humoral immune response of RSV MAT vaccine when given alone and co-administered with Flu D-QIV in terms of RSV B neutralizing antibody. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: At Day 1 and Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of RSV MAT vaccine (from one of the 3 lots used) and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RSV Pooled Group | RSV B Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 1 | 967.4 Titers |
| RSV Pooled Group | RSV B Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 31 | 11030.5 Titers |
| RSV+Flu Pooled Group | RSV B Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 1 | 940.1 Titers |
| RSV+Flu Pooled Group | RSV B Neutralizing Antibody Titers for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 31 | 9162.3 Titers |
Secondary
RSV MAT IgG Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31
Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. RSV MAT IgG concentrations were expressed as GMCs, in EU/mL. As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze the RSV MAT IgG concentration, in order to demonstrate the lot-to-lot consistency of the vaccine lots.
Time frame: At Day 1 and Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received only 1 dose of RSV MAT vaccine (from RSV MAT vaccine Lot 1, Lot 2 or Lot 3), and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RSV Pooled Group | RSV MAT IgG Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 1 | 5691.9 EU/mL |
| RSV Pooled Group | RSV MAT IgG Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 31 | 102811 EU/mL |
| RSV+Flu Pooled Group | RSV MAT IgG Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 1 | 5613 EU/mL |
| RSV+Flu Pooled Group | RSV MAT IgG Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 31 | 100635.8 EU/mL |
| Flu+Placebo Group | RSV MAT IgG Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 1 | 5270.1 EU/mL |
| Flu+Placebo Group | RSV MAT IgG Concentrations for Participants in RSV lot1, RSV lot2 and RSV lot3 Groups at Day 1 and Day 31 | Day 31 | 108709.3 EU/mL |
Secondary
RSV MAT IgG Concentrations for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31
Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. RSV MAT IgG concentrations were expressed as GMCs, in EU/mL. This objective analyzed the humoral immune response of RSV MAT vaccine when given alone and co-administered with Flu D-QIV in terms of RSV MAT IgG concentrations. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: At Day 1 and Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of RSV MAT vaccine (from one of the 3 lots used) and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RSV Pooled Group | RSV MAT IgG Concentrations for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 1 | 5522.7 EU/mL |
| RSV Pooled Group | RSV MAT IgG Concentrations for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 31 | 104025.1 EU/mL |
| RSV+Flu Pooled Group | RSV MAT IgG Concentrations for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 1 | 5772 EU/mL |
| RSV+Flu Pooled Group | RSV MAT IgG Concentrations for Participants in RSV Pooled Group and RSV+Flu Pooled Group at Day 1 and Day 31 | Day 31 | 83937 EU/mL |
Secondary
Seroconversion Rate (SCR) to Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31
The SCR was defined as the percentage of participants with: a Day 1 (pre-vaccination) serum anti-HI titer \<1:10 and a Day 31 (post-vaccination) serum anti-HI titer ≥1:40, or a Day 1 (pre-vaccination) serum anti-HI titer ≥ 1:10 and a fold increase (post/pre) ≥ 4 at Day 31. The 3 influenza strains assessed were: A/Tasmania/503/2020 (H3N2) IVR-221; B/Washington/02/2019 and B/Phuket/3073/2013. This objective analyzed the seroconversion rate to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: At Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of Flu D-QIV vaccine and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RSV Pooled Group | Seroconversion Rate (SCR) to Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | A/Tasmania/503/2020 (H3N2) | 42.5 Percentage of participants |
| RSV Pooled Group | Seroconversion Rate (SCR) to Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | B/Washington/02/2019 | 25.4 Percentage of participants |
| RSV Pooled Group | Seroconversion Rate (SCR) to Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | B/Phuket/3073/2013 | 31.4 Percentage of participants |
| RSV+Flu Pooled Group | Seroconversion Rate (SCR) to Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | A/Tasmania/503/2020 (H3N2) | 45.9 Percentage of participants |
| RSV+Flu Pooled Group | Seroconversion Rate (SCR) to Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | B/Washington/02/2019 | 29.5 Percentage of participants |
| RSV+Flu Pooled Group | Seroconversion Rate (SCR) to Flu D-QIV HI Antibody Titers Against 3 Influenza Strains for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 31 | B/Phuket/3073/2013 | 35.5 Percentage of participants |
Comparison: To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the difference of proportion of participants achieving seroconversion for HI antibody titers against A/Tasmania/503/2020 (H3N2) IVR-221 strain at 30 days post administration (Day 31).95% CI: [-3.44, 10.29]Miettinen and Nurminen
Comparison: To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the difference of proportion of participants achieving seroconversion for HI antibody titers against B/Washington/02/2019 strain at 30 days post administration (Day 31).95% CI: [-2.04, 10.32]Miettinen and Nurminen
Comparison: To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the difference of proportion of participants achieving seroconversion for HI antibody titers against B/Phuket/3073/2013 strain at 30 days post administration (Day 31).95% CI: [-2.46, 10.58]Miettinen and Nurminen
Secondary
Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31
SPR was measured by the percentage of participants achieving an HI antibody titer ≥1:40. This objective analyzed the seroprotection rate to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu Group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine.
Time frame: At Day 1 and Day 31
Population: Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of Flu D-QIV vaccine and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RSV Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | A/Tasmania/503/2020 (H3N2) , Day 1 | 78.7 Percentage of participants |
| RSV Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | A/Tasmania/503/2020 (H3N2) , Day 31 | 98 Percentage of participants |
| RSV Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Washington/02/2019 , Day 1 | 19.7 Percentage of participants |
| RSV Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Washington/02/2019 , Day 31 | 48 Percentage of participants |
| RSV Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Phuket/3073/2013 , Day 1 | 36.7 Percentage of participants |
| RSV Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Phuket/3073/2013 , Day 31 | 74.4 Percentage of participants |
| RSV+Flu Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Phuket/3073/2013 , Day 1 | 39.8 Percentage of participants |
| RSV+Flu Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | A/Tasmania/503/2020 (H3N2) , Day 1 | 82.8 Percentage of participants |
| RSV+Flu Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Washington/02/2019 , Day 31 | 48.8 Percentage of participants |
| RSV+Flu Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | A/Tasmania/503/2020 (H3N2) , Day 31 | 98.5 Percentage of participants |
| RSV+Flu Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Phuket/3073/2013 , Day 31 | 77.2 Percentage of participants |
| RSV+Flu Pooled Group | Seroprotection Rate (SPR) to Flu D-QIV HI Antibody Titers for Participants in Flu+Placebo Group and RSV+Flu Pooled Group at Day 1 and Day 31 | B/Washington/02/2019 , Day 1 | 16.9 Percentage of participants |