Respiratory Syncytial Virus Infections
Conditions
Keywords
RSV, Respiratory Syncytial Virus, COVID-19 mRNA vaccine, Immunogenicity, Safety, Reactogenicity, Older Adults
Brief summary
This study is assessing the immunogenicity, safety and reactogenicity of the RSVPreF3 OA investigational vaccine when it is co-administered with a COVID-19 messenger ribonucleic acid (mRNA) vaccine (Omicron XBB.1.5), compared to administration of the vaccines separately in adults aged 50 years and above.
Interventions
BIOLOGICALRSVPreF3 OA investigational vaccine
1 dose of RSVPreF3 OA investigational vaccine is administered intramuscularly on Day 1 to participants in the Co-ad Group and on Day 31 to participants in the Control Group.
BIOLOGICALCOVID-19 mRNA vaccine
1 dose of COVID-19 mRNA vaccine is administered intramuscularly on Day 1 to participants in the Co-ad and Control Groups.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
This is an open-label study.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
• Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits). Note: In case of physical incapacity that would preclude the self-completion of the diary cards, either site staff can assist the participant (for activities performed during site visits) or the participant may assign a caregiver to assist him/her with this activity (for activities performed at home). However, at no time will the site staff or caregiver evaluate the participant's health status while answering diaries or make decisions on behalf of the participant. * Written or witnessed informed consent obtained from the participant (participant must be able to understand the informed consent) prior to performance of any study-specific procedure. * A male/female of ≥50 Years of age (YOA) at the time of the first study intervention administration. * 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, such as diabetes, hypertension or cardiac disease, are allowed to participate in this study if considered by the investigator as medically stable. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment. • 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. Participants who have received previously a SARS-CoV-2 vaccine, being administered at least 3 months prior to study vaccination. * Female participants of non-childbearing potential may be enrolled in the study. Non childbearing potential is defined as hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and post-menopause. * Female participants of childbearing potential may be enrolled in the study if the participant. * has practiced adequate contraception from 1 month prior to study intervention administration and agreed to continue adequate contraception for at least 1 month after the last vaccination. * has a negative pregnancy test on the day of and prior to study intervention administration.
Exclusion criteria
Medical Conditions * History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions, including a known history of severe allergic reaction (e.g., anaphylaxis). * Any confirmed or suspected immunosuppressive or immunodeficient condition, resulting from disease (e.g., current malignancy, human immunodeficiency virus) or immunosuppressive/cytotoxic therapy (e.g., medication used during cancer chemotherapy, organ transplantation, or to treat autoimmune disorders), based on medical history and physical examination (no laboratory testing required). * Any history of myocarditis or pericarditis. * Recurrent history or uncontrolled neurological disorders or seizures. Participants with medically-controlled active or chronic neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol (e.g. completion of diary cards, attend regular phone calls/study site visits). * Serious or unstable chronic illness. * Any history of dementia or any medical condition that moderately or severely impairs cognition. * Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival up to study end). * Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. * Any SAE attributed to a previous dose of the SARS-CoV-2 mRNA vaccine. * Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. * Recent SARS-CoV-2 infection within 3 months prior to the COVID-19 vaccine dose administration. Timelines to be determined from symptoms onset or positive COVID-19 test (if infection was asymptomatic). Prior/Concomitant Therapy Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study interventions during the period beginning 30 days before the first dose of study interventions and ending 30 days after the last vaccine administration, or their planned use during the study period. * Planned administration of a vaccine in the period starting 30 days before the first dose and ending 30 days after the last dose of study intervention(s) administration\*, with the exception of inactivated and subunit influenza vaccines which can be administered up to 14 days before or from 14 days after the study vaccination. \*If emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is recommended and/or organized by 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 Sponsor is notified. * Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the last blood sampling visit. * Up to 3 months prior to the study intervention administration: * For corticosteroids, this will mean prednisone equivalent ≥ 20 mg/day. Inhaled and topical steroids are allowed. * Administration of immunoglobulins and/or any blood products or plasma derivatives. * Up to 6 months prior to study intervention administration: long-acting immune modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies and antitumoral medication. * Administration of any SARS-CoV-2 vaccine during the 3 months preceding the study COVID-19 mRNA vaccine administration. * Previous vaccination with licensed or investigational RSV vaccine. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Geometric Mean Titers (GMT) of Respiratory Syncytial Virus-A (RSV-A) Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) | RSV-A neutralizing titers were provided as group GMTs and expressed as estimated dilution 60 (ED60) titers. Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model adjusted for baseline differences (in the pre-dose titers) includes treatment group and age category (age at vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-transformed titers as a covariate. |
| Adjusted GMTs of RSV-B Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) | RSV-B neutralizing titers were provided as group GMTs and expressed as estimated dilution 60 (ED60) titers. Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model adjusted for baseline differences (in the pre-dose titers) includes treatment group and age category (age at vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-transformed titers as a covariate. |
| Adjusted GMTs of SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers at 1 Month After the COVID-19 mRNA Vaccination | At 1 month post-COVID-19 mRNA vaccine dose administration (at Day 31 for both groups) | SARS-CoV-2 Omicron XBB.1.5 neutralizing titers against the pseudovirus bearing S protein were provided as group GMTs and expressed as titers. The neutralizing titer was calculated as the reciprocal serum dilution corresponding to the 50% signal reduction (NT50). Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model adjusted for baseline differences (in the pre-dose titers) includes treatment group and age category (age at vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-transformed titers as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RSV-A Neutralizing Titers Expressed as GMT at 1 Month After RSVPreF3 OA Vaccination | At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) | Neutralizing titers for RSV-A were measured with neutralizing assay and the results were expressed as GMT. GMT is a descriptive statistic calculated directly from the observed titer values at the 1-month post-vaccination timepoint for all participants in the analysis set, without any statistical modelling or adjustment for covariates. |
| Mean Geometric Increase (MGI) of RSV-A Neutralizing Titers at 1 Month After RSVPreF3 OA Vaccination | At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) compared to pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group) | The MGI was defined as the geometric mean of the within participant ratios of the post-vaccination titer over the pre-vaccination titer. |
| RSV-A Neutralizing Titers Expressed as Seroresponse Rate (SRR) at 1 Month After RSVPreF3 OA Vaccination | At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) compared to pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group) | The SRR was defined as the percentage of participants having a fold increase in neutralizing titers (1 month post-study intervention administration over pre-study intervention administration) greater than or equal to (\>=) 4. |
| Percentage of Participants Having RSV-A Neutralizing Titers Greater or Equal to the Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination | At pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group) and at 1 month post-RSVPreF3 OA vaccine dose administration (Day 31 for Co-Ad Group and Day 61 for Control Group) | Percentage of participants with RSV-A neutralizing titers \>= to the assay cut-off value (i.e. lower limit of quantification \[LLOQ\]) are presented. |
| RSV-B Neutralizing Titers Expressed as GMT at 1 Month After RSVPreF3 OA Vaccination | At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) | Neutralizing titers for RSV-B were measured with neutralizing assay and the results were expressed as GMT. GMT is a descriptive statistic calculated directly from the observed titer values at the 1-month post-vaccination timepoint for all participants in the analysis set, without any statistical modelling or adjustment for covariates. |
| MGI of RSV-B Neutralizing Titers at 1 Month After RSVPreF3 OA Vaccination | At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) compared to pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group) | The MGI was defined as the geometric mean of the within participant ratios of the post-vaccination titer over the pre-vaccination titer. |
| RSV-B Neutralizing Titers Expressed as SRR at 1 Month After RSVPreF3 OA Vaccination | At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) compared to pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group) | The SRR was defined as the percentage of participants having a fold increase in neutralizing titers (1 month post-study intervention administration over pre-study intervention administration) \>= 4. |
| Percentage of Participants Having RSV-B Neutralizing Titers Greater or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination | At pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group) and at 1 month post-RSVPreF3 OA vaccine dose administration (Day 31 for Co-Ad Group and Day 61 for Control Group) | Percentage of participants with RSV-B neutralizing titers \>= to the assay cut-off value (i.e. LLOQ) are presented. |
| SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers Expressed as GMT at 1 Month After COVID-19 mRNA Vaccination | At 1 month post-COVID-19 mRNA vaccine dose administration (Day 31 for both groups) | The SARS-CoV-2 Omicron XBB.1.5 neutralizing titers against the pseudovirus bearing S protein were measured with neutralizing assay and the results were expressed as GMT. GMT is a descriptive statistic calculated directly from the observed titer values at the 1-month post-vaccination timepoint for all participants in the analysis set, without any statistical modelling or adjustment for covariates. |
| MGI of SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers at 1 Month After COVID-19 mRNA Vaccination | At 1 month post-COVID-19 mRNA vaccine dose administration (Day 31 for both groups) compared to pre-vaccination (at Day 1 for both groups) | The MGI was defined as the geometric mean of the within participant ratios of the post-vaccination titer over the pre-vaccination titer. |
| Percentage of Participants Having SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers Greater Than or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After COVID-19 mRNA Vaccination | At pre-vaccination (Day 1 for both groups) and at 1 month post-COVID-19 mRNA vaccine dose administration (Day 31 for both groups) | Percentage of participants with SARS-CoV-2 Omicron XBB.1.5 neutralizing titers \>= to the assay cut-off value (i.e. LLOQ) are presented. |
| Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Within 4 days (the day of administration and 3 subsequent days) after each type of vaccine (RSVPreF3 OA vaccine administered at Day 1 for Co-Ad Group and at Day 31 for Control Group, COVID-19 mRNA vaccine administered at Day 1 for both groups) | The solicited administration site events after vaccination included pain, erythema/redness, and swelling. Any = occurrence of the events regardless of the intensity grade. |
| Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Within 4 days (the day of dose administered and 3 subsequent days) after each dose (administered at Day 1 for Co-Ad Group and at Days 1 and 31 for Control Group) | The solicited systemic events after vaccination included arthralgia, fatigue, fever (pyrexia), headache and myalgia. Fever was defined as body temperature equal or greater than 38 degrees Celsius (°C). Any = occurrence of the events regardless of the intensity grade. |
| Number of Participants Reporting Unsolicited Adverse Events (AEs), for Each Day of Dose Administered | Within 30 days (the day of vaccination and 29 subsequent days) after each dose (dose administered at Day 1 for Co-Ad Group and at Days 1 and 31 for Control Group) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study vaccine, which does not necessarily have a causal relationship with study vaccine. An unsolicited AE was an AE that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs must had been communicated by participant/participant's caregiver(s) who had signed the informed consent. Unsolicited AEs included both serious and non-serious AEs. Any = occurrence of the events regardless of the intensity grade or relation to study dose administration. |
| Number of Participants Reporting Any Serious Adverse Events (SAEs) | Throughout the study period (from Day 1 up to 6 months after the last dose administration [last dose given at Day 1 for Co-Ad Group and Day 31 for Control Group]) | An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. Any = occurrence of the events regardless of the intensity grade or relation to study dose administration. |
| Number of Participants Reporting Any Potential Immune-mediated Diseases (pIMDs) | Throughout the study period (from Day 1 up to 6 months after the last dose administration [last dose given at Day 1 for Co-Ad Group and Day 31 for Control Group]) | The pIMD was defined as a subset of adverse events of special interest that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. Any = occurrence of the events regardless of the intensity grade or relation to study dose administration. |
Countries
Belgium, Netherlands, Spain, United States
Participant flow
Pre-assignment details
Out of 841 enrolled participants, 833 participants were randomized in a 1:1 ratio to either Co-Ad Group or Control Group at Day 1 and started the study. These participants were included in the Exposed Set.
Participants by arm
| Arm | Count |
|---|---|
| Co-Ad Group Participants received a single dose of RSVPreF3 OA vaccine and a single dose of COVID-19 mRNA vaccine at Day 1, in different arms. | 417 |
| Control Group Participants received a single dose of COVID-19 mRNA vaccine at Day 1, followed by a single dose of RSVPreF3 OA vaccine at Day 31. | 416 |
| Total | 833 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lost to Follow-up | 6 | 9 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 7 |
Baseline characteristics
| Characteristic | Co-Ad Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 63.7 YEARS STANDARD_DEVIATION 8.4 | 63.5 YEARS STANDARD_DEVIATION 8.4 | 63.6 YEARS STANDARD_DEVIATION 8.4 |
| Race/Ethnicity, Customized Black or African American | 31 Participants | 32 Participants | 63 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Not reported | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Other Races | 5 Participants | 7 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 378 Participants | 375 Participants | 753 Participants |
| Sex: Female, Male Female | 216 Participants | 223 Participants | 439 Participants |
| Sex: Female, Male Male | 201 Participants | 193 Participants | 394 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 417 | 0 / 416 |
| other Total, other adverse events | 365 / 417 | 337 / 416 |
| serious Total, serious adverse events | 16 / 417 | 14 / 416 |
Outcome results
Primary
Adjusted Geometric Mean Titers (GMT) of Respiratory Syncytial Virus-A (RSV-A) Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination
RSV-A neutralizing titers were provided as group GMTs and expressed as estimated dilution 60 (ED60) titers. Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model adjusted for baseline differences (in the pre-dose titers) includes treatment group and age category (age at vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-transformed titers as a covariate.
Time frame: At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group)
Population: Per protocol set (PPS) for RSVPreF3 OA included participants who: received RSVPreF3 OA, had immunogenicity results for RSV titers, complied with the blood draw interval, without intercurrent medical conditions, without prohibited concomitant medication/vaccination, did not meet criteria for elimination. Only participants included in both pre-vaccination and 1-month post vaccination timepoints and with results for adjusted GMTs for RSV-A at 1-month post dose were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | Adjusted Geometric Mean Titers (GMT) of Respiratory Syncytial Virus-A (RSV-A) Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | 7885.8 Titers |
| Control Group | Adjusted Geometric Mean Titers (GMT) of Respiratory Syncytial Virus-A (RSV-A) Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | 8803.4 Titers |
Comparison: To demonstrate non-inferiority of humoral immune response to RSVPreF3 OA vaccine when co-administered with a COVID-19 mRNA vaccine compared to RSVPreF3 OA vaccine administered alone.95% CI: [0.97, 1.28]ANCOVA
Primary
Adjusted GMTs of RSV-B Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination
RSV-B neutralizing titers were provided as group GMTs and expressed as estimated dilution 60 (ED60) titers. Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model adjusted for baseline differences (in the pre-dose titers) includes treatment group and age category (age at vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-transformed titers as a covariate.
Time frame: At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group)
Population: Analysis was performed on PPS for RSVPreF3 OA. Only participants included in both pre-vaccination and 1-month post vaccination timepoints and with results for adjusted GMTs for RSV-B at 1-month post dose were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | Adjusted GMTs of RSV-B Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | 7333.3 Titers |
| Control Group | Adjusted GMTs of RSV-B Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | 7903.1 Titers |
Comparison: To demonstrate non-inferiority of humoral immune response to RSVPreF3 OA vaccine when co-administered with a COVID-19 mRNA vaccine compared to RSVPreF3 OA vaccine administered alone.95% CI: [0.94, 1.23]ANCOVA
Primary
Adjusted GMTs of SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers at 1 Month After the COVID-19 mRNA Vaccination
SARS-CoV-2 Omicron XBB.1.5 neutralizing titers against the pseudovirus bearing S protein were provided as group GMTs and expressed as titers. The neutralizing titer was calculated as the reciprocal serum dilution corresponding to the 50% signal reduction (NT50). Adjusted GMTs are derived using an ANCOVA model on log10-transformed titers for the neutralization assay. The final ANCOVA model adjusted for baseline differences (in the pre-dose titers) includes treatment group and age category (age at vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-transformed titers as a covariate.
Time frame: At 1 month post-COVID-19 mRNA vaccine dose administration (at Day 31 for both groups)
Population: The PPS for COVID-19 mRNA included participants who:received COVID-19 mRNA, had immunogenicity results for SARS-CoV-2 titers, complied with the blood draw interval, without intercurrent medical conditions, without prohibited concomitant medication/vaccination, did not meet criteria for elimination. Only participants included in both pre-vaccination and 1-month post vaccination timepoints and with results for adjusted GMTs for SARS-CoV-2 titers at 1-month post dose were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | Adjusted GMTs of SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers at 1 Month After the COVID-19 mRNA Vaccination | 1063.6 Titers |
| Control Group | Adjusted GMTs of SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers at 1 Month After the COVID-19 mRNA Vaccination | 1392.0 Titers |
Comparison: To demonstrate non-inferiority of humoral immune response to a COVID-19 mRNA vaccine when co-administered with the RSVPreF3 OA vaccine compared to COVID-19 mRNA vaccine administered alone.95% CI: [1.13, 1.51]ANCOVA
Secondary
Mean Geometric Increase (MGI) of RSV-A Neutralizing Titers at 1 Month After RSVPreF3 OA Vaccination
The MGI was defined as the geometric mean of the within participant ratios of the post-vaccination titer over the pre-vaccination titer.
Time frame: At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) compared to pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group)
Population: Analysis was performed on PPS for RSVPreF3 OA. Only participants with data available for RSV-A titers at the specified timepoints were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | Mean Geometric Increase (MGI) of RSV-A Neutralizing Titers at 1 Month After RSVPreF3 OA Vaccination | 8.31 Ratio |
| Control Group | Mean Geometric Increase (MGI) of RSV-A Neutralizing Titers at 1 Month After RSVPreF3 OA Vaccination | 10.21 Ratio |
Secondary
MGI of RSV-B Neutralizing Titers at 1 Month After RSVPreF3 OA Vaccination
The MGI was defined as the geometric mean of the within participant ratios of the post-vaccination titer over the pre-vaccination titer.
Time frame: At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) compared to pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group)
Population: Analysis was performed on PPS for RSVPreF3 OA. Only participants with data available for RSV-B titers at the specified timepoints were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | MGI of RSV-B Neutralizing Titers at 1 Month After RSVPreF3 OA Vaccination | 6.79 Ratio |
| Control Group | MGI of RSV-B Neutralizing Titers at 1 Month After RSVPreF3 OA Vaccination | 8.19 Ratio |
Secondary
MGI of SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers at 1 Month After COVID-19 mRNA Vaccination
The MGI was defined as the geometric mean of the within participant ratios of the post-vaccination titer over the pre-vaccination titer.
Time frame: At 1 month post-COVID-19 mRNA vaccine dose administration (Day 31 for both groups) compared to pre-vaccination (at Day 1 for both groups)
Population: Analysis was performed on PPS for COVID-19 mRNA. Only participants with data available for SARS-CoV-2 Omicron XBB.1.5 neutralizing titers against the pseudovirus bearing S protein at the specified timepoints were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | MGI of SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers at 1 Month After COVID-19 mRNA Vaccination | 4.25 Ratio |
| Control Group | MGI of SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers at 1 Month After COVID-19 mRNA Vaccination | 5.46 Ratio |
Secondary
Number of Participants Reporting Any Potential Immune-mediated Diseases (pIMDs)
The pIMD was defined as a subset of adverse events of special interest that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. Any = occurrence of the events regardless of the intensity grade or relation to study dose administration.
Time frame: Throughout the study period (from Day 1 up to 6 months after the last dose administration [last dose given at Day 1 for Co-Ad Group and Day 31 for Control Group])
Population: Analysis was performed on Exposed set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Co-Ad Group | Number of Participants Reporting Any Potential Immune-mediated Diseases (pIMDs) | 0 Participants |
| Control Group | Number of Participants Reporting Any Potential Immune-mediated Diseases (pIMDs) | 1 Participants |
Secondary
Number of Participants Reporting Any Serious Adverse Events (SAEs)
An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. Any = occurrence of the events regardless of the intensity grade or relation to study dose administration.
Time frame: Throughout the study period (from Day 1 up to 6 months after the last dose administration [last dose given at Day 1 for Co-Ad Group and Day 31 for Control Group])
Population: Analysis was performed on Exposed set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Co-Ad Group | Number of Participants Reporting Any Serious Adverse Events (SAEs) | 16 Participants |
| Control Group | Number of Participants Reporting Any Serious Adverse Events (SAEs) | 14 Participants |
Secondary
Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered
The solicited administration site events after vaccination included pain, erythema/redness, and swelling. Any = occurrence of the events regardless of the intensity grade.
Time frame: Within 4 days (the day of administration and 3 subsequent days) after each type of vaccine (RSVPreF3 OA vaccine administered at Day 1 for Co-Ad Group and at Day 31 for Control Group, COVID-19 mRNA vaccine administered at Day 1 for both groups)
Population: Exposed set included all participants in the enrolled set who received at least 1 study intervention. Only those participants with solicited administration site AEs were included in this analysis. Analysis was reported based on each type of vaccine administered (RSVPreF3 OA vaccine and COVID-19 mRNA vaccine).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Co-Ad Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Erythema, within 4 days from COVID-19 mRNA Dosing | 19 Participants |
| Co-Ad Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Erythema, within 4 days from RSVPreF3 OA Dosing | 34 Participants |
| Co-Ad Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Pain, within 4 days from COVID-19 mRNA Dosing | 297 Participants |
| Co-Ad Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Pain, within 4 days from RSVPreF3 OA Dosing | 302 Participants |
| Co-Ad Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Swelling, within 4 days from COVID-19 mRNA Dosing | 10 Participants |
| Co-Ad Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Swelling, within 4 days from RSVPreF3 OA Dosing | 20 Participants |
| Control Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Swelling, within 4 days from COVID-19 mRNA Dosing | 13 Participants |
| Control Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Erythema, within 4 days from COVID-19 mRNA Dosing | 20 Participants |
| Control Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Pain, within 4 days from RSVPreF3 OA Dosing | 235 Participants |
| Control Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Erythema, within 4 days from RSVPreF3 OA Dosing | 26 Participants |
| Control Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Swelling, within 4 days from RSVPreF3 OA Dosing | 9 Participants |
| Control Group | Number of Participants Reporting Each Solicited Administration Site Event, for Each Type of Vaccine Administered | Pain, within 4 days from COVID-19 mRNA Dosing | 264 Participants |
Secondary
Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered
The solicited systemic events after vaccination included arthralgia, fatigue, fever (pyrexia), headache and myalgia. Fever was defined as body temperature equal or greater than 38 degrees Celsius (°C). Any = occurrence of the events regardless of the intensity grade.
Time frame: Within 4 days (the day of dose administered and 3 subsequent days) after each dose (administered at Day 1 for Co-Ad Group and at Days 1 and 31 for Control Group)
Population: Analysis was performed on the Exposed set. Only those participants with solicited systemic AEs were included in this analysis. Analysis was reported based on the day of study dose administration.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Co-Ad Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Fatigue, within 4 days from dosing at Day 1 | 166 Participants |
| Co-Ad Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Fever, within 4 days from dosing at Day 1 | 26 Participants |
| Co-Ad Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Myalgia, within 4 days from dosing at Day 1 | 170 Participants |
| Co-Ad Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Headache, within 4 days from dosing at Day 1 | 120 Participants |
| Co-Ad Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Arthralgia, within 4 days from dosing at Day 1 | 81 Participants |
| Control Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Fever, within 4 days from dosing at Day 1 | 7 Participants |
| Control Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Fever, within 4 days from dosing at Day 31 | 9 Participants |
| Control Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Headache, within 4 days from dosing at Day 1 | 98 Participants |
| Control Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Headache, within 4 days from dosing at Day 31 | 83 Participants |
| Control Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Myalgia, within 4 days from dosing at Day 1 | 117 Participants |
| Control Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Myalgia, within 4 days from dosing at Day 31 | 91 Participants |
| Control Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Arthralgia, within 4 days from dosing at Day 1 | 47 Participants |
| Control Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Arthralgia, within 4 days from dosing at Day 31 | 36 Participants |
| Control Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Fatigue, within 4 days from dosing at Day 1 | 115 Participants |
| Control Group | Number of Participants Reporting Each Solicited Systemic Event, for Each Day of Dose Administered | Fatigue, within 4 days from dosing at Day 31 | 95 Participants |
Secondary
Number of Participants Reporting Unsolicited Adverse Events (AEs), for Each Day of Dose Administered
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study vaccine, which does not necessarily have a causal relationship with study vaccine. An unsolicited AE was an AE that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs must had been communicated by participant/participant's caregiver(s) who had signed the informed consent. Unsolicited AEs included both serious and non-serious AEs. Any = occurrence of the events regardless of the intensity grade or relation to study dose administration.
Time frame: Within 30 days (the day of vaccination and 29 subsequent days) after each dose (dose administered at Day 1 for Co-Ad Group and at Days 1 and 31 for Control Group)
Population: Analysis was performed on Exposed set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Co-Ad Group | Number of Participants Reporting Unsolicited Adverse Events (AEs), for Each Day of Dose Administered | Within 30 days after dosing at at Day 1 | 87 Participants |
| Control Group | Number of Participants Reporting Unsolicited Adverse Events (AEs), for Each Day of Dose Administered | Within 30 days after dosing at at Day 1 | 71 Participants |
| Control Group | Number of Participants Reporting Unsolicited Adverse Events (AEs), for Each Day of Dose Administered | Within 30 days after dosing at at Day 31 | 57 Participants |
Secondary
Percentage of Participants Having RSV-A Neutralizing Titers Greater or Equal to the Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination
Percentage of participants with RSV-A neutralizing titers \>= to the assay cut-off value (i.e. lower limit of quantification \[LLOQ\]) are presented.
Time frame: At pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group) and at 1 month post-RSVPreF3 OA vaccine dose administration (Day 31 for Co-Ad Group and Day 61 for Control Group)
Population: Analysis was performed on PPS for RSVPreF3 OA. Only participants with data available for RSV-A titers at the specified timepoints were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | Percentage of Participants Having RSV-A Neutralizing Titers Greater or Equal to the Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination | At pre-vaccination | 100 Percentage of participants |
| Co-Ad Group | Percentage of Participants Having RSV-A Neutralizing Titers Greater or Equal to the Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination | 1 month post RSVPreF3 administration | 100 Percentage of participants |
| Control Group | Percentage of Participants Having RSV-A Neutralizing Titers Greater or Equal to the Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination | At pre-vaccination | 100 Percentage of participants |
| Control Group | Percentage of Participants Having RSV-A Neutralizing Titers Greater or Equal to the Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination | 1 month post RSVPreF3 administration | 100 Percentage of participants |
Secondary
Percentage of Participants Having RSV-B Neutralizing Titers Greater or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination
Percentage of participants with RSV-B neutralizing titers \>= to the assay cut-off value (i.e. LLOQ) are presented.
Time frame: At pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group) and at 1 month post-RSVPreF3 OA vaccine dose administration (Day 31 for Co-Ad Group and Day 61 for Control Group)
Population: Analysis was performed on PPS for RSVPreF3 OA. Only participants with data available for RSV-B titers at the specified timepoints were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | Percentage of Participants Having RSV-B Neutralizing Titers Greater or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination | At pre-vaccination | 100 Percentage of participants |
| Co-Ad Group | Percentage of Participants Having RSV-B Neutralizing Titers Greater or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination | 1 month post RSVPreF3 administration | 100 Percentage of participants |
| Control Group | Percentage of Participants Having RSV-B Neutralizing Titers Greater or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination | At pre-vaccination | 100 Percentage of participants |
| Control Group | Percentage of Participants Having RSV-B Neutralizing Titers Greater or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After RSVPreF3 OA Vaccination | 1 month post RSVPreF3 administration | 100 Percentage of participants |
Secondary
Percentage of Participants Having SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers Greater Than or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After COVID-19 mRNA Vaccination
Percentage of participants with SARS-CoV-2 Omicron XBB.1.5 neutralizing titers \>= to the assay cut-off value (i.e. LLOQ) are presented.
Time frame: At pre-vaccination (Day 1 for both groups) and at 1 month post-COVID-19 mRNA vaccine dose administration (Day 31 for both groups)
Population: Analysis was performed on PPS for COVID-19 mRNA. Only participants with data available for SARS-CoV-2 Omicron XBB.1.5 neutralizing titers against the pseudovirus bearing S protein at the specified timepoints were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-Ad Group | Percentage of Participants Having SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers Greater Than or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After COVID-19 mRNA Vaccination | At pre-dose administration | 95.1 Percentage of participants |
| Co-Ad Group | Percentage of Participants Having SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers Greater Than or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After COVID-19 mRNA Vaccination | 1 month after COVID-19 mRNA vaccination | 99.7 Percentage of participants |
| Control Group | Percentage of Participants Having SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers Greater Than or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After COVID-19 mRNA Vaccination | At pre-dose administration | 94.3 Percentage of participants |
| Control Group | Percentage of Participants Having SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers Greater Than or Equal to Assay Cut-off Value at Pre-vaccination and at 1 Month After COVID-19 mRNA Vaccination | 1 month after COVID-19 mRNA vaccination | 99.7 Percentage of participants |
Secondary
RSV-A Neutralizing Titers Expressed as GMT at 1 Month After RSVPreF3 OA Vaccination
Neutralizing titers for RSV-A were measured with neutralizing assay and the results were expressed as GMT. GMT is a descriptive statistic calculated directly from the observed titer values at the 1-month post-vaccination timepoint for all participants in the analysis set, without any statistical modelling or adjustment for covariates.
Time frame: At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group)
Population: Analysis was performed on PPS for RSVPreF3 OA. Only participants included in 1-month post vaccination timepoint and with data available for RSV-A titers at the specified timepoint were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-A Neutralizing Titers Expressed as GMT at 1 Month After RSVPreF3 OA Vaccination | 8119.1 Titers |
| Control Group | RSV-A Neutralizing Titers Expressed as GMT at 1 Month After RSVPreF3 OA Vaccination | 8407.1 Titers |
Secondary
RSV-A Neutralizing Titers Expressed as Seroresponse Rate (SRR) at 1 Month After RSVPreF3 OA Vaccination
The SRR was defined as the percentage of participants having a fold increase in neutralizing titers (1 month post-study intervention administration over pre-study intervention administration) greater than or equal to (\>=) 4.
Time frame: At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) compared to pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group)
Population: Analysis was performed on PPS for RSVPreF3 OA. Only participants with data available for RSV-A titers at the specified timepoints were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | RSV-A Neutralizing Titers Expressed as Seroresponse Rate (SRR) at 1 Month After RSVPreF3 OA Vaccination | 73.8 Percentage of participants |
| Control Group | RSV-A Neutralizing Titers Expressed as Seroresponse Rate (SRR) at 1 Month After RSVPreF3 OA Vaccination | 81.3 Percentage of participants |
Secondary
RSV-B Neutralizing Titers Expressed as GMT at 1 Month After RSVPreF3 OA Vaccination
Neutralizing titers for RSV-B were measured with neutralizing assay and the results were expressed as GMT. GMT is a descriptive statistic calculated directly from the observed titer values at the 1-month post-vaccination timepoint for all participants in the analysis set, without any statistical modelling or adjustment for covariates.
Time frame: At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group)
Population: Analysis was performed on PPS for RSVPreF3 OA. Only participants included in 1-month post vaccination timepoint and with data available for RSV-B titers at the specified timepoint were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | RSV-B Neutralizing Titers Expressed as GMT at 1 Month After RSVPreF3 OA Vaccination | 7537.1 Titers |
| Control Group | RSV-B Neutralizing Titers Expressed as GMT at 1 Month After RSVPreF3 OA Vaccination | 7588.9 Titers |
Secondary
RSV-B Neutralizing Titers Expressed as SRR at 1 Month After RSVPreF3 OA Vaccination
The SRR was defined as the percentage of participants having a fold increase in neutralizing titers (1 month post-study intervention administration over pre-study intervention administration) \>= 4.
Time frame: At 1 month post-RSVPreF3 OA vaccine dose administration (at Day 31 for Co-Ad Group and Day 61 for Control Group) compared to pre-vaccination (Day 1 for Co-Ad Group and Day 31 for Control Group)
Population: Analysis was performed on PPS for RSVPreF3 OA. Only participants with data available for RSV-B titers at the specified timepoints were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-Ad Group | RSV-B Neutralizing Titers Expressed as SRR at 1 Month After RSVPreF3 OA Vaccination | 66.8 Percentage of participants |
| Control Group | RSV-B Neutralizing Titers Expressed as SRR at 1 Month After RSVPreF3 OA Vaccination | 75.5 Percentage of participants |
Secondary
SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers Expressed as GMT at 1 Month After COVID-19 mRNA Vaccination
The SARS-CoV-2 Omicron XBB.1.5 neutralizing titers against the pseudovirus bearing S protein were measured with neutralizing assay and the results were expressed as GMT. GMT is a descriptive statistic calculated directly from the observed titer values at the 1-month post-vaccination timepoint for all participants in the analysis set, without any statistical modelling or adjustment for covariates.
Time frame: At 1 month post-COVID-19 mRNA vaccine dose administration (Day 31 for both groups)
Population: Analysis was performed on PPS for COVID-19 mRNA. Only participants included in 1-month post vaccination timepoint and with data available for SARS-CoV-2 titers at the specified timepoint were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-Ad Group | SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers Expressed as GMT at 1 Month After COVID-19 mRNA Vaccination | 1030.4 Titers |
| Control Group | SARS-CoV-2 Omicron XBB.1.5 Neutralizing Titers Expressed as GMT at 1 Month After COVID-19 mRNA Vaccination | 1407.3 Titers |