A Study of an Ad26.RSV.preF-based Vaccine and High-dose Seasonal Influenza Vaccine, With and Without Coadministration, in Adults Aged 65 Years and Older

Hemagglutination is a phenomenon by which the hemagglutinin protein of influenza viruses can bind to sialic acid receptors on the red blood cell membrane, thereby forming clumps and is the basis for the HI assay. GMTs of HI antibodies against each of the four influenza vaccine strains as measured by HI assay at 28 days after the administration of a quadrivalent high-dose seasonal influenza vaccine (fluzone) were reported. The analysis was performed on 2 influenza A strains \[A/Victoria and A/Tasmania\] and 2 influenza B strains \[B/Washington and B/Phuket\]).

Time frame: 28 days after vaccination with Fluzone on Day 1 (Day 29)

Population: Per-protocol influenza immunogenicity (PPII) set included all randomized participants who received the first study vaccination, and for whom immunogenicity data are available for at least one of the influenza strains in the vaccine. Samples taken after participant experienced major protocol deviation expected to impact the immunogenicity outcomes were excluded from this analysis, including those who were collected out of window.

GMTs of preF antibodies at 28 days after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA on Day 57 were reported. This outcome measure was planned to be analyzed for specified arm only.

Time frame: 28 days after vaccination with Ad26.RSV.preF-based vaccine on Day 29 (Day 57)

Population: The PPRI set included all randomized participants who received Ad26/protein preF RSV vaccine in combination with seasonal influenza vaccine for the CoAd group and Ad26/protein preF RSV vaccine alone for the control group and for whom RSV immunogenicity data were available. Samples taken after participant experienced major protocol deviation expected to impact the immunogenicity outcomes were excluded from this analysis, including those who were collected out of window.

GMTs of preF antibodies at 28 days after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA on Day 29 were reported. This outcome measure was planned to be analyzed for specified arm only.

Time frame: 28 days after vaccination with Ad26.RSV.preF-based vaccine on Day 1 (Day 29)

Population: Per-protocol RSV immunogenicity (PPRI) set included all randomized participants who received Ad26/protein preF RSV vaccine in combination with seasonal influenza vaccine in the CoAd group and Ad26/protein preF RSV vaccine alone in the control group and for which RSV immunogenicity data were available. Samples taken after participant experienced major protocol deviation expected to impact immunogenicity outcomes were excluded from this analysis, including those who were collected out of window.

Number of participants with AESI up to study vaccination 1 were reported. Thrombosis with thrombocytopenia syndrome (TTS) was considered to be an AESI.

Time frame: From Day 1 up to Day 29

Population: The FAS included all participants who received at least 1 study vaccination, regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, Ad26/protein preF RSV vaccine, or placebo).

Number of participants with AESI up to study vaccination 2 were reported. Thrombosis with thrombocytopenia syndrome (TTS) was considered to be an AESI.

Time frame: From Day 29 up to 6 months after study vaccination 2 (up to 7 months)

Population: The FAS included all participants who received at least 1 study vaccination, regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, Ad26/protein preF RSV vaccine, or placebo).

Number of participants with SAEs up to study vaccination 1 were reported. SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

Time frame: From Day 1 up to Day 29

Population: The FAS included all participants who received at least 1 study vaccination, regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, Ad26/protein preF RSV vaccine, or placebo).

Number of participants with SAEs up to study vaccination 2 were reported. SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

Time frame: From Day 29 up to 6 months after study vaccination 2 (up to 7 months)

Population: The FAS included all participants who received at least 1 study vaccination, regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, Ad26/protein preF RSV vaccine, or placebo).

Number of participants with solicited local AEs after study vaccination 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, were used to assess the reactogenicity of the study vaccine and were pre-defined local (injection site). Solicited local AEs were reported separately for all vaccines because fluzone and RSV vaccine mixture (containing both Ad26. RSV. preF 1\*10\^11 vp and RSV preF protein 150 mcg) in group 1 were administered in opposite arms on Day 1. Similarly, fluzone and placebo in group 2 were administered in opposite arms on Day 1. Hence, the data for this outcome measure was analyzed separately for each vaccine.

Time frame: Up to 7 days after study vaccination 1 on Day 1 (Day 8)

Population: The full analysis set (FAS) included all participants who received at least 1 study vaccination, regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, Ad26/protein preF RSV vaccine, or placebo). Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure.

Number of participants with solicited local AEs after study vaccination 2 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, were used to assess the reactogenicity of the study vaccine and were pre-defined local (injection site).

Time frame: Up to 7 days after study vaccination 2 on Day 29 (Day 36)

Population: The FAS included all participants who received at least 1 study vaccination, regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, Ad26/protein preF RSV vaccine, or placebo). Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure.

Number of participants with solicited systemic AEs after study vaccination 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which were noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).

Time frame: Up to 7 days after study vaccination 1 on Day 1 (Day 8)

Population: The FAS included all participants who received at least 1 study vaccination, regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, Ad26/protein preF RSV vaccine, or placebo). Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure.

Number of participants with solicited systemic AEs after study vaccination 2 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants will be specifically questioned and which will be noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).

Time frame: Up to 7 days after study vaccination 2 on Day 29 (Day 36)

Population: The FAS included all participants who received at least 1 study vaccination, regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, Ad26/protein preF RSV vaccine, or placebo). Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure.

Number of participants with unsolicited AEs after study vaccination 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary.

Time frame: Up to 28 days after study vaccination 1 on Day 1 (Day 29)

Population: The FAS included all participants who received at least 1 study vaccination, regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, Ad26/protein preF RSV vaccine, or placebo).

Number of participants with unsolicited AEs after study vaccination 2 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary.

Time frame: Up to 28 days after study vaccination 2 on Day 29 (Day 57)

Population: The FAS included all participants who received at least 1 study vaccination, regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, Ad26/protein preF RSV vaccine, or placebo).

Number of seroconverted participants after 28 days of administration of influenza vaccine (fluzone) were reported. Seroconversion is defined for each of the 4 influenza vaccine strains at 28 days after the administration of a quadrivalent high-dose seasonal influenza vaccine: HI titer greater than or equal to (\>=) 1:40 in participants with a pre-vaccination HI titer of less than (\<) 1:10, or a \>=4-fold HI titer increase in participants with a pre-vaccination HI titer of \>=1:10.

Time frame: 28 days after vaccination with fluzone on Day 1 (up to Day 29)

Population: PPII set included all randomized participants who received the first study vaccination, and for whom immunogenicity data were available for at least one of the influenza strains in the vaccine. Samples taken after participant experienced major protocol deviation expected to impact the immunogenicity outcomes were excluded from this analysis, including those who were collected out of window.

Number of seroprotected participants after 28 days of administration of influenza vaccine (fluzone) were reported. Seroprotection is defined for each of the 4 influenza vaccine strains as HI titer \>=1:40 at 28 days after the administration of a quadrivalent high-dose seasonal influenza vaccine.

Time frame: 28 days after vaccination with fluzone on Day 1 (up to Day 29)

Population: PPII set included all randomized participants who received the first study vaccination, and for whom immunogenicity data were available for at least one of the influenza strains in the vaccine. Samples taken after participant experienced major protocol deviation expected to impact the immunogenicity outcomes were excluded from this analysis, including those who were collected out of window.