Trial Outcomes & Findings for 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 (NCT NCT05071313)

Last Updated: 2025-05-25

Results Overview

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 \[B/Washington and B/Phuket\]).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

777 participants

Primary outcome timeframe

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

Results posted on

2025-05-25

Participant Flow

Participant milestones

Participant milestones
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).
Overall Study STARTED	389	388
Overall Study Received Ad26/Protein preF RSV Vaccine With Fluzone in CoAd Group at Day 1	385	0
Overall Study Received Placebo With Fluzone in Control Group at Day 1	0	386
Overall Study Received Placebo in CoAd Group at Day 29	357	0
Overall Study Received Ad26/Protein preF RSV Vaccine in Control Group at Day 29	0	363
Overall Study COMPLETED	355	355
Overall Study NOT COMPLETED	34	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).
Overall Study Lost to Follow-up	17	10
Overall Study Physician Decision	1	6
Overall Study Death	1	0
Overall Study Withdrawal by Subject	10	15
Overall Study Other	1	0
Overall Study Randomized but not vaccinated	4	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=385 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=386 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Total n=771 Participants Total of all reporting groups
Age, Continuous	70.4 years STANDARD_DEVIATION 4.94 • n=5 Participants	70.7 years STANDARD_DEVIATION 4.72 • n=7 Participants	70.5 years STANDARD_DEVIATION 4.83 • n=5 Participants
Sex: Female, Male Female	223 Participants n=5 Participants	208 Participants n=7 Participants	431 Participants n=5 Participants
Sex: Female, Male Male	162 Participants n=5 Participants	178 Participants n=7 Participants	340 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	39 Participants n=5 Participants	33 Participants n=7 Participants	72 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	339 Participants n=5 Participants	344 Participants n=7 Participants	683 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	38 Participants n=5 Participants	39 Participants n=7 Participants	77 Participants n=5 Participants
Race (NIH/OMB) White	336 Participants n=5 Participants	333 Participants n=7 Participants	669 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment UNITED STATES	385 Participants n=5 Participants	386 Participants n=7 Participants	771 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=338 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=338 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibodies Against Each of the Four Influenza Vaccine Strains as Measured by HI Assay A/Victoria	178 Titers Interval 145.0 to 217.0	179 Titers Interval 146.0 to 219.0	—	—
Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibodies Against Each of the Four Influenza Vaccine Strains as Measured by HI Assay A/Tasmania	111 Titers Interval 89.0 to 139.0	123 Titers Interval 98.0 to 155.0	—	—
Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibodies Against Each of the Four Influenza Vaccine Strains as Measured by HI Assay B/Washington	93 Titers Interval 74.0 to 117.0	84 Titers Interval 67.0 to 106.0	—	—
Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibodies Against Each of the Four Influenza Vaccine Strains as Measured by HI Assay B/Phuket	38 Titers Interval 31.0 to 47.0	37 Titers Interval 30.0 to 46.0	—	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=338 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
GMTs of Prefusion F-protein (preF) Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) on Day 29	2665 ELISA units per liter (EU/L) Interval 2209.0 to 3216.0	—	—	—

PRIMARY outcome

Timeframe: 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 57 were reported. This outcome measure was planned to be analyzed for specified arm only.

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=318 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
GMTs of PreF Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) on Day 57	3206 EU/L Interval 2648.0 to 3881.0	—	—	—

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=371 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=371 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) n=373 Participants Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) n=373 Participants Participants received placebo as an IM injection on Day 1 on left arm.
Number of Participants With Solicited Local Adverse Events (AEs) After Study Vaccination 1	237 Participants	263 Participants	219 Participants	98 Participants

SECONDARY outcome

Timeframe: 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 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).

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=341 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=343 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Participants With Solicited Local AEs After Study Vaccination 2	53 Participants	241 Participants	—	—

SECONDARY outcome

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

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).

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=371 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=373 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Participants With Solicited Systemic AEs After Study Vaccination 1	285 Participants	181 Participants	—	—

SECONDARY outcome

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

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).

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=341 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=343 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Participants With Solicited Systemic AEs After Study Vaccination 2	80 Participants	218 Participants	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=385 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=386 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Participants With Unsolicited AEs After Study Vaccination 1	57 Participants	61 Participants	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=357 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=363 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Participants With Unsolicited AEs After Study Vaccination 2	34 Participants	35 Participants	—	—

SECONDARY outcome

Timeframe: From Day 1 up to Day 29

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.

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=385 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=386 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Participants With Serious Adverse Events (SAEs) Up to Study Vaccination 1	2 Participants	2 Participants	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=357 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=363 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Participants With Serious Adverse Events (SAEs) Up to Study Vaccination 2	11 Participants	11 Participants	—	—

SECONDARY outcome

Timeframe: From Day 1 up to Day 29

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

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=385 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=386 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Participants With Adverse Events of Special Interest (AESI) Up to Study Vaccination 1	0 Participants	0 Participants	—	—

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=357 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=363 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Participants With Adverse Events of Special Interest (AESI) Up to Study Vaccination 2	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=338 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=338 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Seroconverted Participants After 28 Days of Administration of Influenza Vaccine A/Victoria	203 Participants	190 Participants	—	—
Number of Seroconverted Participants After 28 Days of Administration of Influenza Vaccine A/Tasmania	150 Participants	165 Participants	—	—
Number of Seroconverted Participants After 28 Days of Administration of Influenza Vaccine B/Washington	134 Participants	117 Participants	—	—
Number of Seroconverted Participants After 28 Days of Administration of Influenza Vaccine B/Phuket	79 Participants	84 Participants	—	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV + Placebo (CoAd Group) n=338 Participants Participants received intramuscular (IM) injection containing both adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF protein) 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1 (vaccination 1) followed by placebo IM injection on Day 29 (vaccination 2).	Group 2: Placebo With Fluzone HD QIV + Ad26/Protein preF RSV Vaccine (Control Group) n=338 Participants Participants received placebo IM injection coadministered with Fluzone HD QIV 240 mcg IM injection on Day 1 (vaccination 1) followed by an IM injection containing both Ad26.RSV.preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29 (vaccination 2).	Group 2: Fluzone HD QIV (Control Group) Participants received Fluzone HD QIV 240 mcg IM injection on Day 1 on right arm.	Group 2: Placebo (Control Group) Participants received placebo as an IM injection on Day 1 on left arm.
Number of Seroprotected Participants After 28 Days of Administration of Influenza Vaccine A/Victoria	323 Participants	313 Participants	—	—
Number of Seroprotected Participants After 28 Days of Administration of Influenza Vaccine A/Tasmania	282 Participants	285 Participants	—	—
Number of Seroprotected Participants After 28 Days of Administration of Influenza Vaccine B/Washington	247 Participants	245 Participants	—	—
Number of Seroprotected Participants After 28 Days of Administration of Influenza Vaccine B/Phuket	117 Participants	122 Participants	—	—

Adverse Events

Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV (CoAd Group)

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Group 2: Fluzone HD QIV With Placebo (Control Group)

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Group 1: Placebo (CoAd Group)

Serious events: 11 serious events

Other events: 1 other events

Deaths: 1 deaths

Group 2: Ad26/Protein preF RSV Vaccine (Control Group)

Serious events: 11 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Group 1: Ad26/Protein preF RSV Vaccine With Fluzone HD QIV (CoAd Group) n=385 participants at risk Participants received intramuscular (IM) injection containing both Ad26. RSV. preF; 1\*10\^11 viral particles (vp) and RSV preF protein; 150 micrograms (mcg) coadministered with Fluzone high-dose (HD) quadrivalent (QIV) 240 mcg IM injection on Day 1.	Group 2: Fluzone HD QIV With Placebo (Control Group) n=386 participants at risk Participants received Fluzone HD QIV 240 mcg IM injection coadministered with placebo IM injection on Day 1.	Group 1: Placebo (CoAd Group) n=357 participants at risk Participants received placebo IM injection on Day 29.	Group 2: Ad26/Protein preF RSV Vaccine (Control Group) n=363 participants at risk Participants received IM injection containing both Ad26. RSV. preF 1\*10\^11 vp and RSV preF protein 150 mcg on Day 29.
General disorders Chills	2.9% 11/385 • From Day 1 up to 7 months 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).	1.0% 4/386 • From Day 1 up to 7 months 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).	0.28% 1/357 • From Day 1 up to 7 months 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).	2.2% 8/363 • From Day 1 up to 7 months 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).
Vascular disorders Hypertension	1.8% 7/385 • From Day 1 up to 7 months 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).	2.1% 8/386 • From Day 1 up to 7 months 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).	0.00% 0/357 • From Day 1 up to 7 months 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).	0.55% 2/363 • From Day 1 up to 7 months 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).

Additional Information

Director Biomarkers Viral Vaccines

Janssen Vaccines & Prevention B.V.

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER