Respiratory Syncytial Viruses, Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory syncytial virus, Infection, Vaccine, Older adult, Immunogenicity, Safety
Brief summary
To assess the ability of RSVPreF3 OA investigational vaccine to generate an immune response when given in combination with HZ/su vaccine and its safety in older adults, aged \>=50 years of age.
Interventions
BIOLOGICALRSVPreF3 OA investigational vaccine
One dose of RSVPreF3 OA investigational vaccine given intramuscularly on Day 1 (Coadministration group) or Day 31 (Control group).
BIOLOGICALHZ/su vaccine
Two doses of HZ/su vaccine given intramuscularly on Day 1 and Day 61.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* A male or female participant ≥50 YOA at the time of the first study intervention administration. * Female participants of non-childbearing potential may be enrolled in the study. * 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. * has a negative pregnancy test on the day of and prior to study intervention administration. * has agreed to continue effective contraception until the end of the study. * Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Written or witnessed informed consent obtained from the participant prior to any study specific procedure being performed. * 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 are medically stable in the opinion of the investigator at the time of first study intervention administration. Participants with chronic stable medical conditions with or without specific treatment, such as diabetes mellitus, hypertension, or cardiac disease, are allowed to participate in this study if considered by the investigator as medically stable.
Exclusion criteria
* Pregnant or lactating female. * Female planning to become pregnant or planning to discontinue contraceptive precautions. * Any confirmed or suspected autoimmune disorders, immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy, based on medical history and physical examination. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions, in particular any history of severe allergic reaction to any vaccine component. * History of Guillain-Barré syndrome. * Any history of dementia or any medical condition that moderately or severely impairs cognition. * Recurrent or uncontrolled neurological disorders or seizures. Participants with medically controlled chronic neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol. * Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study. * Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. * Clinically suspected or polymerase chain reaction (PCR)-confirmed ongoing episode of herpes zoster. * History of previous vaccination with any licensed or investigational recombinant adjuvanted zoster vaccine (HZ/su vaccine; Shingrix) before the study start or planned receipt through study participation. * History of previous vaccination with any licensed or investigational live herpes zoster vaccine (Zostavax) in the last 2 years from enrollment, or planned receipt through study participation. * Previous vaccination with licensed or investigational RSV vaccine. * Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study interventions during the period beginning 30 days before the first dose of study interventions, or their planned use during the study period. * Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first study intervention administration and ending 30 days after the last study intervention administration. o In the case of COVID-19 and inactivated/subunit/split influenza vaccines, this time window can be decreased to 14 days before and after each study intervention administration provided COVID-19 vaccine use is in line with local governmental recommendations. * Planned or actual administration of adjuvanted quadrivalent influenza vaccine influenza vaccine not foreseen by the study protocol in the period starting 30 days before the first study intervention administration and ending 30 days after the last study intervention administration. * Administration of long-acting immune-modifying drugs during the period starting 180 days before the administration of first dose of study interventions or planned administration at any time during the study period (e.g., infliximab). * Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the administration of first dose of study interventions or planned administration during the study period. * Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune modifying drugs during the period starting 90 days prior to the first study intervention dose or planned administration during the study period. For corticosteroids, this will mean prednisone ≥20 mg/day, or equivalent. Inhaled, topical or intra-articular steroids are allowed. * 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 (IMP) (drug or invasive medical device). * History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.Bedridden participants. * Planned move during the study conduct that prohibits participation until study end. * Participation of any study personnel or their immediate dependents, family, or household members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Geometric Mean Concentration (GMC) of Anti-glycoprotein E (gE) Antibodies at 1 Month Post-second Dose of HZ/su Vaccination | At 1 month post-second dose of HZ/su vaccination (Day 91) | Anti-gE antibodies were measured with enzyme linked immunosorbent assay (ELISA) and the results were expressed as GMC, in milli international units per milliliter (mIU/mL). |
| Adjusted Geometric Mean Titers (GMT) of Respiratory Syncytial Virus-A (RSV-A) Neutralizing Titers [Estimated Dilution 60 (ED60)] at 1 Month After the RSVPreF3 OA Vaccination | At Day 31 for Co-administration Group and at Day 61 for Control Group | Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. The ED60 was defined as the dose that produced an effect in 60% of the population. |
| Adjusted GMTs of RSV-B Neutralizing Titers (ED60) at 1 Month After the RSVPreF3 OA Vaccination | At Day 31 for Co-administration Group and at Day 61 for Control Group | Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. The ED60 was defined as the dose that produced an effect in 60% of the population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vaccine Response Rate (VRR) at 1 Month Post-second Dose of HZ/su Vaccination | At 1 month post-second dose of HZ/su vaccination (Day 91) | The VRR was defined as the percentage of participants who had at least: a 4-fold increase post-vaccination anti-gE antibody concentration as compared to (over) the pre-vaccination anti-gE antibody concentration (for participants who were seropositive at pre-vaccination); or, a 4-fold increase post-vaccination anti-gE antibody concentration as compared to (over) the anti-gE antibody cut-off value for seropositivity (97 mIU/mL) (for participants who were seronegative at pre-vaccination). |
| GMT of RSV-A Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination | At pre-vaccination (Day 1) and Day 31 for Co-administration Group and at pre-vaccination (Day 1) and Day 61 for Control Group | Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. The ED60 was defined as the dose that produced an effect in 60% of the population. |
| MGI of Respiratory Syncytial Virus-A Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for Co-administration Group and Day 61 for Control Group) compared to Pre-vaccination (Day 1 for Co-administration Group and 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. Neutralizing titers were measured with neutralization assay. |
| GMT of RSV-B Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination | At pre-vaccination (Day 1) and Day 31 for Co-administration Group and at pre-vaccination (Day 1) and Day 61 for Control Group | Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. The ED60 was defined as the dose that produced an effect in 60% of the population. |
| MGI of RSV-B Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for Co-administration Group and Day 61 for Control Group) compared to Pre-vaccination (Day 1 for Co-administration Group and 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. Neutralizing titers were measured with neutralization assay. |
| Percentage of Participants With Seropositivity at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | Pre-vaccination (Day 1) and 1 month post-second dose of HZ/su vaccination (Day 91) | Seropositivity was defined as the percentage of participants whose antibody concentration was greater than or equal to the assay cut-off value (97 mIU/mL). |
| Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Within 7 days (the day of vaccination and 6 subsequent days) after each vaccine administration (vaccines administered at Days 1 and 61 for Co-Administration Group and at Days 1, 31 and 61 for Control group) | The solicited systemic events after vaccination included arthralgia, fatigue, fever (pyrexia), headache, myalgia, shivering/chills, and gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain). |
| Percentage of Participants With Unsolicited Adverse Events | Within 30 days (the day of vaccination and 29 subsequent days) after vaccine administration | 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. |
| Percentage of Participants With Serious Adverse Events (SAEs) | From first dose of study vaccine administration (Day 1) up to 6 months after last dose of study vaccine administration, approximately 241 days | 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. |
| Percentage of Participants With Potential Immune-mediated Diseases (pIMDs) | From first dose of study vaccine administration (Day 1) up to 6 months after last dose of study vaccine administration, approximately 241 days | The pIMD was 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. |
| Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Within 7 days (the day of vaccination and 6 subsequent days) after each vaccine administration (vaccines administered at Days 1 and 61 for Co-Administration Group and at Days 1, 31 and 61 for Control group) | The solicited administration site events after vaccination included pain, erythema/redness, and swelling. |
| GMC of Anti-glycoprotein Antibodies at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | Pre-vaccination (Day 1) and 1 month post-second dose of HZ/su vaccination (Day 91) | Anti-gE antibodies were measured with ELISA and the results were expressed as GMC. |
| Mean Geometric Increase (MGI) of Anti-glycoprotein Antibodies at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | At 1 month post-second dose of HZ/su vaccination (Day 91) compared to Pre-vaccination (Day 1) | The MGI was defined as the geometric mean of the within participant ratios of the post-vaccination titer over the pre-vaccination titer. Anti-gE antibodies were measured with ELISA. |
Countries
Canada, United States
Participant flow
Recruitment details
This study was conducted in adult participants aged 50 years and older, in 20 study sites.
Pre-assignment details
A total of 530 eligible participants were randomized in a 1:1 ratio to either co-administration group or control group at Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Co-administration Group Participants received both HZ/su vaccine and RSVPreF3 OA vaccine on Day 1 followed by second dose of HZ/su vaccine on Day 61. | 265 |
| Control Group Participants received HZ/su vaccine on Day 1 and RSVPreF3 OA vaccine on Day 31 followed by second dose of HZ/su vaccine on Day 61. | 265 |
| Total | 530 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 6 | 6 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Protocol-Specified Withdrawal Criterion Met | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Co-administration Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 8.56 | 63.9 years STANDARD_DEVIATION 8.73 | 63.9 years STANDARD_DEVIATION 8.64 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants | 30 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 237 Participants | 235 Participants | 472 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 146 Participants | 146 Participants | 292 Participants |
| Sex: Female, Male Male | 119 Participants | 119 Participants | 238 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 265 | 0 / 265 |
| other Total, other adverse events | 240 / 265 | 235 / 265 |
| serious Total, serious adverse events | 13 / 265 | 6 / 265 |
Outcome results
Primary
Adjusted Geometric Mean Concentration (GMC) of Anti-glycoprotein E (gE) Antibodies at 1 Month Post-second Dose of HZ/su Vaccination
Anti-gE antibodies were measured with enzyme linked immunosorbent assay (ELISA) and the results were expressed as GMC, in milli international units per milliliter (mIU/mL).
Time frame: At 1 month post-second dose of HZ/su vaccination (Day 91)
Population: Per protocol set for HZ/su included all eligible participants in the exposed set who: received 2 doses of HZ/su vaccine, had immunogenicity results for anti-gE antibody concentrations, complied with the blood draw interval, without intercurrent medical conditions and without prohibited concomitant medication/vaccination, did not met any of the criteria for elimination up to blood sample collection. Participants with data available at the time of analysis were reported in this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-administration Group | Adjusted Geometric Mean Concentration (GMC) of Anti-glycoprotein E (gE) Antibodies at 1 Month Post-second Dose of HZ/su Vaccination | 49326.9 mIU/mL |
| Control Group | Adjusted Geometric Mean Concentration (GMC) of Anti-glycoprotein E (gE) Antibodies at 1 Month Post-second Dose of HZ/su Vaccination | 61192.7 mIU/mL |
Comparison: To demonstrate non-inferiority of the humoral immune response to 2 doses of HZ/su vaccine when the first dose of HZ/su vaccine was co-administered with RSVPreF3 OA investigational vaccine, compared to 2 doses of HZ/su vaccine administered alone.95% CI: [1.08, 1.42]
Primary
Adjusted Geometric Mean Titers (GMT) of Respiratory Syncytial Virus-A (RSV-A) Neutralizing Titers [Estimated Dilution 60 (ED60)] at 1 Month After the RSVPreF3 OA Vaccination
Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. The ED60 was defined as the dose that produced an effect in 60% of the population.
Time frame: At Day 31 for Co-administration Group and at Day 61 for Control Group
Population: Per protocol set for RSVPreF3 OA included all eligible participants in the exposed set who: received the RSVPreF3 OA vaccine, had immunogenicity results for RSV neutralizing titers, complied with the blood draw interval, without intercurrent medical conditions and without prohibited concomitant medication/vaccination and who did not met any of the criteria for elimination up to blood sample collection.Participants with data available at the time of analysis were reported in this outcome measure
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-administration Group | Adjusted Geometric Mean Titers (GMT) of Respiratory Syncytial Virus-A (RSV-A) Neutralizing Titers [Estimated Dilution 60 (ED60)] at 1 Month After the RSVPreF3 OA Vaccination | 8426.8 Titers |
| Control Group | Adjusted Geometric Mean Titers (GMT) of Respiratory Syncytial Virus-A (RSV-A) Neutralizing Titers [Estimated Dilution 60 (ED60)] at 1 Month After the RSVPreF3 OA Vaccination | 9628.7 Titers |
Comparison: To demonstrate the non-inferiority of RSVPreF3 OA investigational vaccine when co-administered with the first dose of HZ/su vaccine, compared to RSVPreF3 OA investigational vaccine administered alone.95% CI: [0.97, 1.35]
Primary
Adjusted GMTs of RSV-B Neutralizing Titers (ED60) at 1 Month After the RSVPreF3 OA Vaccination
Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. The ED60 was defined as the dose that produced an effect in 60% of the population.
Time frame: At Day 31 for Co-administration Group and at Day 61 for Control Group
Population: Per protocol set for RSVPreF3 OA. Participants with data available at the time of analysis were reported in this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-administration Group | Adjusted GMTs of RSV-B Neutralizing Titers (ED60) at 1 Month After the RSVPreF3 OA Vaccination | 10354.2 Titers |
| Control Group | Adjusted GMTs of RSV-B Neutralizing Titers (ED60) at 1 Month After the RSVPreF3 OA Vaccination | 10143.4 Titers |
Comparison: To demonstrate the non-inferiority of RSVPreF3 OA investigational vaccine when co-administered with the first dose of HZ/su vaccine, compared to RSVPreF3 OA investigational vaccine administered alone.95% CI: [0.84, 1.15]
Secondary
GMC of Anti-glycoprotein Antibodies at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination
Anti-gE antibodies were measured with ELISA and the results were expressed as GMC.
Time frame: Pre-vaccination (Day 1) and 1 month post-second dose of HZ/su vaccination (Day 91)
Population: Per protocol set for HZ/su. Only those participants with available data at specified timepoints were included in this analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-administration Group | GMC of Anti-glycoprotein Antibodies at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | Pre-vaccination (Day 1) | 1739.4 mIU/mL |
| Co-administration Group | GMC of Anti-glycoprotein Antibodies at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | 1 month post-second dose of HZ/su vaccination (Day 91) | 50235.2 mIU/mL |
| Control Group | GMC of Anti-glycoprotein Antibodies at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | Pre-vaccination (Day 1) | 1492.2 mIU/mL |
| Control Group | GMC of Anti-glycoprotein Antibodies at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | 1 month post-second dose of HZ/su vaccination (Day 91) | 61204.7 mIU/mL |
Secondary
GMT of RSV-A Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination
Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. The ED60 was defined as the dose that produced an effect in 60% of the population.
Time frame: At pre-vaccination (Day 1) and Day 31 for Co-administration Group and at pre-vaccination (Day 1) and Day 61 for Control Group
Population: Per protocol set for RSVPreF3 OA. Only those participants with available data at specified timepoints were included in this analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-administration Group | GMT of RSV-A Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination | Pre-vaccination (Day 1) | 1005.4 Titers |
| Co-administration Group | GMT of RSV-A Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination | Day 31 | 8553.3 Titers |
| Control Group | GMT of RSV-A Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination | Pre-vaccination (Day 1) | 961.2 Titers |
| Control Group | GMT of RSV-A Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination | Day 61 | 9689.4 Titers |
Secondary
GMT of RSV-B Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination
Neutralizing titers were measured with neutralization assay and the results were expressed as GMT. The ED60 was defined as the dose that produced an effect in 60% of the population.
Time frame: At pre-vaccination (Day 1) and Day 31 for Co-administration Group and at pre-vaccination (Day 1) and Day 61 for Control Group
Population: Per protocol set for RSVPreF3 OA. Only those participants with available data at specified timepoints were included in this analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Co-administration Group | GMT of RSV-B Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination | Pre-vaccination (Day 1) | 1148.8 Titers |
| Co-administration Group | GMT of RSV-B Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination | Day 31 | 10521.3 Titers |
| Control Group | GMT of RSV-B Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination | Pre-vaccination (Day 1) | 1167.9 Titers |
| Control Group | GMT of RSV-B Neutralizing Titers (ED60) at Pre-vaccination and 1 Month After the RSVPreF3 OA Vaccination | Day 61 | 10352.2 Titers |
Secondary
Mean Geometric Increase (MGI) of Anti-glycoprotein Antibodies at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination
The MGI was defined as the geometric mean of the within participant ratios of the post-vaccination titer over the pre-vaccination titer. Anti-gE antibodies were measured with ELISA.
Time frame: At 1 month post-second dose of HZ/su vaccination (Day 91) compared to Pre-vaccination (Day 1)
Population: Per protocol set for HZ/su. Only those participants with available data at specified timepoints were included in this analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-administration Group | Mean Geometric Increase (MGI) of Anti-glycoprotein Antibodies at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | 28.24 Ratio |
| Control Group | Mean Geometric Increase (MGI) of Anti-glycoprotein Antibodies at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | 43.24 Ratio |
Secondary
MGI of Respiratory Syncytial Virus-A Neutralizing Titers at 1 Month After the 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. Neutralizing titers were measured with neutralization assay.
Time frame: At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for Co-administration Group and Day 61 for Control Group) compared to Pre-vaccination (Day 1 for Co-administration Group and Control Group)
Population: Per protocol set for RSVPreF3 OA. Only those participants with available data at specified timepoints were included in this analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-administration Group | MGI of Respiratory Syncytial Virus-A Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | 8.55 Ratio |
| Control Group | MGI of Respiratory Syncytial Virus-A Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | 9.91 Ratio |
Secondary
MGI of RSV-B Neutralizing Titers at 1 Month After the 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. Neutralizing titers were measured with neutralization assay.
Time frame: At 1 month after the RSVPreF3 OA vaccine dose (Day 31 for Co-administration Group and Day 61 for Control Group) compared to Pre-vaccination (Day 1 for Co-administration Group and Control Group)
Population: Per protocol set for RSVPreF3 OA. Only those participants with available data at specified timepoints were included in this analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Co-administration Group | MGI of RSV-B Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | 9.01 Ratio |
| Control Group | MGI of RSV-B Neutralizing Titers at 1 Month After the RSVPreF3 OA Vaccination | 8.69 Ratio |
Secondary
Percentage of Participants With Potential Immune-mediated Diseases (pIMDs)
The pIMD was 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.
Time frame: From first dose of study vaccine administration (Day 1) up to 6 months after last dose of study vaccine administration, approximately 241 days
Population: Exposed set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-administration Group | Percentage of Participants With Potential Immune-mediated Diseases (pIMDs) | 0.4 Percentage of participants |
| Control Group | Percentage of Participants With Potential Immune-mediated Diseases (pIMDs) | 0.8 Percentage of participants |
Secondary
Percentage of Participants With 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.
Time frame: From first dose of study vaccine administration (Day 1) up to 6 months after last dose of study vaccine administration, approximately 241 days
Population: Exposed set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-administration Group | Percentage of Participants With Serious Adverse Events (SAEs) | 4.9 Percentage of participants |
| Control Group | Percentage of Participants With Serious Adverse Events (SAEs) | 2.3 Percentage of participants |
Secondary
Percentage of Participants With Seropositivity at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination
Seropositivity was defined as the percentage of participants whose antibody concentration was greater than or equal to the assay cut-off value (97 mIU/mL).
Time frame: Pre-vaccination (Day 1) and 1 month post-second dose of HZ/su vaccination (Day 91)
Population: Per protocol set for HZ/su. Only those participants with available data at specified timepoints were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-administration Group | Percentage of Participants With Seropositivity at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | Pre-vaccination (Day 1) | 98.5 Percentage of participants |
| Co-administration Group | Percentage of Participants With Seropositivity at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | 1 month post-second dose of HZ/su vaccination (Day 91) | 100.0 Percentage of participants |
| Control Group | Percentage of Participants With Seropositivity at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | Pre-vaccination (Day 1) | 97.3 Percentage of participants |
| Control Group | Percentage of Participants With Seropositivity at Pre-vaccination and 1 Month Post-second Dose of HZ/su Vaccination | 1 month post-second dose of HZ/su vaccination (Day 91) | 100.0 Percentage of participants |
Secondary
Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration
The solicited administration site events after vaccination included pain, erythema/redness, and swelling.
Time frame: Within 7 days (the day of vaccination and 6 subsequent days) after each vaccine administration (vaccines administered at Days 1 and 61 for Co-Administration Group and at Days 1, 31 and 61 for Control group)
Population: Exposed set included all participants in the enrolled set who received at least 1 study intervention. Only those participants with solicited AEs were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-administration Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Pain at injection site, RSV dose, given at Day 1 | 63.1 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Erythema at injection site, HZ/su dose 2, given at Day 61 | 16.0 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Erythema at injection site, HZ/su dose 1, given at Day 1 | 14.6 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Swelling at injection site, HZ/su dose 1, given at Day 1 | 8.7 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Pain at injection site, HZ/su dose 2, given at Day 61 | 57.3 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Swelling at injection site, RSV dose, given at Day 1 | 6.0 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Erythema at injection site, RSV dose, given at Day 1 | 7.9 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Swelling at injection site, HZ/su dose 2, given at Day 61 | 8.9 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Pain at injection site, HZ/su dose 1, given at Day 1 | 67.6 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Swelling at injection site, HZ/su dose 2, given at Day 61 | 8.5 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Pain at injection site, HZ/su dose 1, given at Day 1 | 59.8 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Pain at injection site, RSV dose, given at Day 31 | 49.6 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Pain at injection site, HZ/su dose 2, given at Day 61 | 63.4 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Erythema at injection site, HZ/su dose 1, given at Day 1 | 13.1 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Erythema at injection site, RSV dose, given at Day 31 | 7.6 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Erythema at injection site, HZ/su dose 2, given at Day 61 | 11.9 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Swelling at injection site, HZ/su dose 1, given at Day 1 | 8.8 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Administration Site Adverse Events (AEs) After Each Vaccine Dose Administration | Swelling at injection site, RSV dose, given at Day 31 | 5.5 Percentage of participants |
Secondary
Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration
The solicited systemic events after vaccination included arthralgia, fatigue, fever (pyrexia), headache, myalgia, shivering/chills, and gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain).
Time frame: Within 7 days (the day of vaccination and 6 subsequent days) after each vaccine administration (vaccines administered at Days 1 and 61 for Co-Administration Group and at Days 1, 31 and 61 for Control group)
Population: Exposed set. Only those participants with solicited AEs were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Fatigue, Dosing at Day 61 | 39.6 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Fever, Dosing at Day 61 | 3.0 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Arthralgia, Dosing at Day 61 | 20.9 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Myalgia, Dosing at Day 1 | 51.9 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Chills, Dosing at Day 1 | 22.9 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Fatigue, Dosing at Day 1 | 48.8 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Headache, Dosing at Day 1 | 37.2 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Chills, Dosing at Day 61 | 23.0 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Myalgia, Dosing at Day 61 | 37.0 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Gastrointestinal Symptoms, Dosing at Day 1 | 15.9 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Headache, Dosing at Day 61 | 30.9 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Arthralgia, Dosing at Day 1 | 24.0 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Gastrointestinal Symptoms, Dosing at Day 61 | 9.1 Percentage of participants |
| Co-administration Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Fever, Dosing at Day 1 | 8.9 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Arthralgia, Dosing at Day 31 | 12.7 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Arthralgia, Dosing at Day 61 | 21.0 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Chills, Dosing at Day 1 | 12.7 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Chills, Dosing at Day 31 | 13.1 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Chills, Dosing at Day 61 | 25.9 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Gastrointestinal Symptoms, Dosing at Day 1 | 15.0 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Gastrointestinal Symptoms, Dosing at Day 31 | 11.4 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Gastrointestinal Symptoms, Dosing at Day 61 | 12.3 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Fever, Dosing at Day 1 | 6.2 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Fever, Dosing at Day 31 | 3.3 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Fever, Dosing at Day 61 | 7.4 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Headache, Dosing at Day 1 | 30.0 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Headache, Dosing at Day 31 | 22.9 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Headache, Dosing at Day 61 | 33.3 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Fatigue, Dosing at Day 1 | 36.2 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Fatigue, Dosing at Day 31 | 31.8 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Fatigue, Dosing at Day 61 | 46.5 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Myalgia, Dosing at Day 1 | 40.4 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Myalgia, Dosing at Day 31 | 26.9 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Myalgia, Dosing at Day 61 | 41.6 Percentage of participants |
| Control Group | Percentage of Participants With Solicited Systemic AEs After Each Vaccine Dose Administration | Arthralgia, Dosing at Day 1 | 16.2 Percentage of participants |
Secondary
Percentage of Participants With Unsolicited Adverse Events
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.
Time frame: Within 30 days (the day of vaccination and 29 subsequent days) after vaccine administration
Population: Exposed set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-administration Group | Percentage of Participants With Unsolicited Adverse Events | 23.4 Percentage of participants |
| Control Group | Percentage of Participants With Unsolicited Adverse Events | 30.2 Percentage of participants |
Secondary
Vaccine Response Rate (VRR) at 1 Month Post-second Dose of HZ/su Vaccination
The VRR was defined as the percentage of participants who had at least: a 4-fold increase post-vaccination anti-gE antibody concentration as compared to (over) the pre-vaccination anti-gE antibody concentration (for participants who were seropositive at pre-vaccination); or, a 4-fold increase post-vaccination anti-gE antibody concentration as compared to (over) the anti-gE antibody cut-off value for seropositivity (97 mIU/mL) (for participants who were seronegative at pre-vaccination).
Time frame: At 1 month post-second dose of HZ/su vaccination (Day 91)
Population: Per protocol set for HZ/su. Only those participants with available data at specified timepoint were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Co-administration Group | Vaccine Response Rate (VRR) at 1 Month Post-second Dose of HZ/su Vaccination | 92.9 Percentage of participants |
| Control Group | Vaccine Response Rate (VRR) at 1 Month Post-second Dose of HZ/su Vaccination | 96.5 Percentage of participants |