Safety and Immunogenicity of RSVpreF Coadministered With SIIV in Adults ≥65 Years of Age

Geometric mean titer (GMT) of RSV A and RSV B neutralizing titers for the Coadministration Group and Sequential-Administration Group were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CI were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the lower limit of quantification (LLOQ) were set to 0.5\*LLOQ. Geometric mean ratio (GMR) was reported in the statistical analysis section and was calculated as ratio of GMTs in the Coadministration Group to the Sequential-Administration Group.

Time frame: 1 month after Vaccination 1 for Coadministration Group and 1 month after Vaccination 2 for Sequential-Administration Group

Population: Evaluable RSV immunogenicity population: eligible par who received study interventions (RSVpreF, placebo, or SIIV) as randomized at both Visit (V) 1 \& V 2; had 1-month RSVpreF postvaccination (PV) blood collection 25-49 days after RSVpreF Vax; no major protocol violation from randomization through 1-month RSVpreF PV blood draw; had at least 1 valid \& determinate assay result 1 month after RSVpreF Vax. N= par evaluable for this OM \& 'Number Analyzed'(n) = par evaluable for specified rows.

GMTs of strain-specific HAI titers for the Coadministration Group and Sequential-Administration Group were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. GMR was reported in the statistical analysis section and was calculated as ratio of GMT in the Coadministration Group to the Sequential-Administration Group.

Time frame: 1 month after Vaccination 1

Population: Evaluable SIIV immunogenicity population: eligible participants who received study interventions (RSVpreF, placebo, or SIIV) as randomized with SIIV at Visit 1; had 1-month postvaccination blood collection 25-49 days after SIIV vaccination; no major protocol violation from randomization through 1-month postvaccination blood draw; had at least 1 valid and determinate assay result 1 month after SIIV vaccination. N= participants evaluable for this OM \& n= participants evaluable for specified rows.

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs within 1 month after Vaccination 1 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: Within 1 month after Vaccination 1

Population: Safety population = all enrolled participants who received study intervention (RSVpreF, placebo). N = participants evaluable for this outcome measure. 1 participant randomized in SAG incorrectly received RSVpreF + SIIV at Vax 1; hence, participant was included in (RSVpreF + SIIV)/Placebo. 1 participant randomized in SAG incorrectly received placebo at Vax 2; hence, participant was included in vaccine group administered at Vax 1 and excluded from safety analysis at Vax 2.

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs within 1 month after Vaccination 2 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: Within 1 month after Vaccination 2

Population: Safety population = all enrolled participants who received study intervention (RSVpreF, placebo). N = participants evaluable for this outcome measure. 1 participant randomized in SAG incorrectly received RSVpreF + SIIV at Vax 1; hence, participant was included in (RSVpreF + SIIV)/Placebo. 1 participant randomized in SAG incorrectly received placebo at Vax 2; hence, participant was included in vaccine group administered at Vax 1 and excluded from safety analysis at Vax 2.

Local reactions were collected at the RSVpreF or placebo injection site after Vaccination 1 and Vaccination 2 and were recorded by participants using electronic diary (e-diary). Local reactions included redness, swelling and pain at injection site. Redness and swelling were measured and recorded in measuring device units where, 1 measuring device unit =0.5 centimeter (cm) and were graded as mild (greater than \[\>\] 2.0 to 5.0 cm), moderate (\>5.0 to 10.0 cm), and severe (\>10.0 cm). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity). Percentage of participants reporting local reactions at injection site in Coadministration Group, and Sequential-Administration Group and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented in this outcome measure (OM). Safety population=all enrolled participants who received study intervention (RSVpreF, placebo).

Time frame: Within 7 days after Vaccination 1 or Vaccination 2

Population: Safety population was analyzed. 'Overall Number of Participants (Par) Analyzed' (N)= par with at least 1 e-diary (within 7 days through Vaccination \[vax\]) transmitted. 1 par randomized in Sequential-Administration Group (SAG) incorrectly received RSVpreF + SIIV at Vax 1; hence, par was included in (RSVpreF + SIIV)/Placebo. 1 par randomized in SAG incorrectly received placebo at Vax 2; hence, par was included in vaccine group administered at Vax 1 and excluded from safety analysis at Vax 2.

An SAE was defined as an AE that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or nonpathogenic or that was considered to be an important medical event. Percentage of participants with SAEs and the associated 2-sided 95% CI based on the Clopper and Pearson method was presented. Percentage of participants reporting SAEs within 1 month after Vaccination 1 were reported in this outcome measure.

Time frame: Within 1 month after Vaccination 1

Population: Safety population = all enrolled participants who received study intervention (RSVpreF, placebo). N = participants evaluable for this outcome measure. 1 participant randomized in SAG incorrectly received RSVpreF + SIIV at Vax 1; hence, participant was included in (RSVpreF + SIIV)/Placebo. 1 participant randomized in SAG incorrectly received placebo at Vax 2; hence, participant was included in vaccine group administered at Vax 1 and excluded from safety analysis at Vax 2.

An SAE was defined as an AE that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or nonpathogenic or that was considered to be an important medical event. Percentage of participants with SAEs and the associated 2-sided 95% CI based on the Clopper and Pearson method was presented. Percentage of participants reporting SAEs within 1 month after Vaccination 2 were reported in this outcome measure.

Time frame: Within 1 month after Vaccination 2

Population: Safety population = all enrolled participants who received study intervention (RSVpreF, placebo). N = participants evaluable for this outcome measure. 1 participant randomized in SAG incorrectly received RSVpreF + SIIV at Vax 1; hence, participant was included in (RSVpreF + SIIV)/Placebo. 1 participant randomized in SAG incorrectly received placebo at Vax 2; hence, participant was included in vaccine group administered at Vax 1 and excluded from safety analysis at Vax 2.

Systemic events included fever, fatigue, headache, nausea, vomiting, diarrhea, muscle pain and joint pain and were recorded by participants using an e-diary. Fever was defined as an oral temperature \>=38.0 degree Celsius (deg C) and categorized as \>=38.0 to 38.4 deg C (mild), \>38.4 to 38.9 deg C (moderate), \>38.9 to 40.0 deg C (severe) and \>40.0 deg C (grade 4). Fatigue, headache, nausea, muscle pain and joint pain were graded as mild (did not interfere with activity), moderate (some interference with activity) and severe (prevented daily routine activity). Vomiting was graded mild: 1 to 2 times in 24 hours (h), moderate: \>2 times in 24h, and severe: required intravenous hydration. Diarrhea was graded mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. Percentage of participants with systemic events within 7 days after each vaccination and the associated 2-sided 95% CI based on the Clopper and Pearson method was presented.

Time frame: Within 7 days after Vaccination 1 or Vaccination 2

Population: Safety population= all enrolled participants who received study intervention (RSVpreF, placebo). N= participant with at least 1 e-diary (within 7 days through vax) transmitted. 1 participant randomized in SAG incorrectly received RSVpreF + SIIV at Vax 1; hence, participant was included in (RSVpreF + SIIV)/Placebo. 1 participant randomized in SAG incorrectly received placebo at Vax 2; hence,participant was included in vaccine group administered at Vax 1 and excluded from safety analysis at Vax 2.

GMFR of neutralizing titers of RSV A and RSV B before vaccination and at 1 month and 2 months after vaccination was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the Student's t distribution).

Time frame: Coadministration Group: before RSVpreF vaccination, and 1 and 2 months after vaccination; Sequential-Administration Group: before RSVpreF vaccination (most recent serology results before RSVpreF) and 1 month after vaccination

Population: Evaluable RSV immunogenicity population: eligible participants who received study interventions (RSVpreF, placebo, or SIIV) as randomized at both V 1 \& V 2; had 1-month RSVpreF PV blood collection 25-49 days after RSVpreF Vax; no major protocol violation from randomization through 1-month RSVpreF PV blood draw; had at least 1 valid and determinate assay result 1 month after RSVpreF Vax. 'N' = participants evaluable for this outcome measure and 'n' = participants evaluable for specified rows.

GMT of neutralizing titers of RSV A and RSV B before vaccination, at 1 month and 2 months after vaccination was reported in this outcome measure. Assay results below the LLOQ were set to 0.5\*LLOQ. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). For Sequential-Administration Group, the time point for 2 months after vaccination was not reported since the participants received RSVpreF at Vaccination 2 and were followed up for 1 month after Vaccination 2.

Time frame: Coadministration Group: before RSVpreF vaccination, and 1 and 2 months after RSVpreF vaccination; Sequential-Administration Group: before RSVpreF vaccination (most recent serology results before RSVpreF) and 1 month after RSVpreF vaccination

Population: Evaluable RSV immunogenicity population: eligible participants who received study interventions (RSVpreF, placebo, or SIIV) as randomized at both V 1 \& V 2; had 1-month RSVpreF PV blood collection 25-49 days after RSVpreF Vax; no major protocol violation from randomization through 1-month RSVpreF PV blood draw; had at least 1 valid and determinate assay result 1 month after RSVpreF Vax. 'N' = participants evaluable for this outcome measure and 'n' = participants evaluable for specified rows.

GMFR of strain-specific HAI titers before vaccination and 1 month after vaccination with SIIV was reported in this outcome measure. GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of fold rises (later time point over earlier time point) and the corresponding CIs (based on Student's t distribution).

Time frame: Before SIIV vaccination, and 1 month after vaccination

Population: Evaluable SIIV immunogenicity population: eligible participants who received study interventions (RSVpreF, placebo, or SIIV) as randomized with SIIV at Visit 1; had 1-month PV blood collection 25-49 days after SIIV vaccination; no major protocol violation from randomization through 1-month PV blood draw; had at least 1 valid and determinate assay result 1 month after SIIV vaccination. 'N' = participants evaluable for this outcome measure and 'n' = participants evaluable for specified rows.

HAI GMT before vaccination and 1 month after vaccination with SIIV was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).

Time frame: Before SIIV vaccination, and 1 month after vaccination

Population: Evaluable SIIV immunogenicity population: eligible participants who received study interventions (RSVpreF, placebo, or SIIV) as randomized with SIIV at Visit 1; had 1-month PV blood collection 25-49 days after SIIV vaccination; no major protocol violation from randomization through 1-month PV blood draw; had at least 1 valid and determinate assay result 1 month after SIIV vaccination. 'N' = participants evaluable for this outcome measure and 'n' = participants evaluable for specified rows.