Trial Outcomes & Findings for Evaluation of the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine Influsplit™ Tetra (Fluarix™ Tetra) (GSK2321138A) When Co-administered With Pneumovax™ 23 in Adults 50 Years of Age and Older (NCT NCT02218697)

NCT ID: NCT02218697

Last Updated: 2018-04-03

Results Overview

HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios (Control Group/Co-Ad Group). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), FluA/Texas/50/2012 (H3N2), Flu B/Brisbane/60/2008 (Victoria) and Flu B/Massachusetts/2/2012 (Yamagata).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 357 participants
• Primary outcome timeframe: At Day 28 post Influsplit™ Tetra vaccination
• Results posted on: 2018-04-03

Participant Flow

In the Control Group, 2 subjects withdrew at Day 0. In the Co-Ad Group, 4 subjects withdrew at Day 0, 1 subject withdrew at Day 28 and 1 subject withdrew at Day 56.

Of the 357 subjects enrolled, 1 subject failed to meet the inclusion criteria hence he/she was excluded from study start.

Participant milestones

Measure	Control Group Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Overall Study STARTED	179	177
Overall Study COMPLETED	177	171
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Measure	Control Group Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Overall Study Adverse Event	0	2
Overall Study Unwilling to be vaccinated in left arm	0	1
Overall Study Withdrawal by Subject	2	3

Baseline Characteristics

Evaluation of the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine Influsplit™ Tetra (Fluarix™ Tetra) (GSK2321138A) When Co-administered With Pneumovax™ 23 in Adults 50 Years of Age and Older

Baseline characteristics by cohort

Measure	Control Group n=179 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=177 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.	Total n=356 Participants Total of all reporting groups
Age, Continuous	68.4 Years STANDARD_DEVIATION 9.4 • n=5 Participants	68.1 Years STANDARD_DEVIATION 9.0 • n=7 Participants	68.3 Years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	76 Participants n=7 Participants	153 Participants n=5 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	101 Participants n=7 Participants	203 Participants n=5 Participants
Race/Ethnicity, Customized African Heritage / African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic / North African Heritage	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized White - Caucasian / European Heritage	175 Participants n=5 Participants	172 Participants n=7 Participants	347 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Origin	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Day 28 post Influsplit™ Tetra vaccination

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios (Control Group/Co-Ad Group). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), FluA/Texas/50/2012 (H3N2), Flu B/Brisbane/60/2008 (Victoria) and Flu B/Massachusetts/2/2012 (Yamagata).

Outcome measures

Measure	Control Group n=170 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=163 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies Titers Against the 4 Vaccine Strains. H1N1	253.2 Titers Interval 205.3 to 312.1	235.5 Titers Interval 195.0 to 284.5
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies Titers Against the 4 Vaccine Strains. H3N2	73.6 Titers Interval 62.1 to 87.1	78.6 Titers Interval 65.2 to 94.7
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies Titers Against the 4 Vaccine Strains. Victoria	178.7 Titers Interval 154.9 to 206.2	157.9 Titers Interval 136.4 to 182.9
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies Titers Against the 4 Vaccine Strains. Yamagata	346.5 Titers Interval 302.3 to 397.1	353.8 Titers Interval 310.5 to 403.2

PRIMARY outcome

Timeframe: At 28 days after Pneumovax™ 23 vaccination

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

Anti-pneumococcal antibody concentrations were expressed as adjusted geometric mean concentrations (GMCs) and adjusted GMC ratio (Control Group/Co-Ad Group).

Outcome measures

Measure	Control Group n=169 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=162 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 6 Pneumococcal Serotypes (1, 3, 4, 7F, 14 and 19A). Polysaccharide 01 IgG	5.5 ug per ml Interval 4.3 to 7.0	4.9 ug per ml Interval 3.9 to 6.2
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 6 Pneumococcal Serotypes (1, 3, 4, 7F, 14 and 19A). Polysaccharide 03 IgG	1.7 ug per ml Interval 1.4 to 2.1	1.7 ug per ml Interval 1.4 to 2.0
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 6 Pneumococcal Serotypes (1, 3, 4, 7F, 14 and 19A). Polysaccharide 04 IgG	2.3 ug per ml Interval 1.8 to 2.9	1.7 ug per ml Interval 1.4 to 2.2
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 6 Pneumococcal Serotypes (1, 3, 4, 7F, 14 and 19A). Polysaccharide 7F IgG	9.0 ug per ml Interval 6.9 to 11.8	8.1 ug per ml Interval 6.2 to 10.6
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 6 Pneumococcal Serotypes (1, 3, 4, 7F, 14 and 19A). Polysaccharide 14 IgG	20.2 ug per ml Interval 16.0 to 25.6	14.1 ug per ml Interval 11.3 to 17.6
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 6 Pneumococcal Serotypes (1, 3, 4, 7F, 14 and 19A). Polysaccharide 19A IgG	9.2 ug per ml Interval 7.1 to 11.9	7.7 ug per ml Interval 6.1 to 9.8

SECONDARY outcome

Timeframe: Within 7 days (Days 0 - 6) after each dose and across doses.

Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.

Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain = significant pain at rest and pain that prevented normal everyday activities. Grade 3 redness and swelling = greater than 50 millimeters (mm) i.e. > 100mm.

Outcome measures

Measure	Control Group n=177 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=173 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Redness, Across Doses (Placebo)	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Redness, Across Doses (Pneumovax™ 23)	8 Subjects	8 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Redness, Across Doses (Pneumovax™23)	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Swelling, Across Doses (Influsplit™Tetra)	1 Subjects	3 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Swelling, Across Doses (Influsplit™Tetra)	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Swelling, Across Doses (Placebo)	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Swelling, Across Doses (Placebo)	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Swelling, Across Doses (Pneumovax™23)	5 Subjects	7 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Swelling, Across Doses (Pneumovax™23)	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Pain, Dose 2 (Placebo)	—	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Pain, Dose 2 (Pneumovax™ 23)	63 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Pain, Dose 1 (Influsplit™ Tetra)	28 Subjects	58 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Pain,Dose 1(Influsplit™ Tetra)	0 Subjects	2 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Pain, Dose 1 (Placebo)	10 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Pain, Dose 1 (Placebo)	0 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Pain, Dose 1 (Pneumovax™ 23)	—	76 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Pain, Dose 1 (Pneumovax™ 23)	—	6 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Redness, Dose 1 (Influsplit™ Tetra)	3 Subjects	2 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade3 Redness,Dose 1(Influsplit™ Tetra)	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Redness, Dose 1 (Placebo)	3 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Redness, Dose 1 (Placebo)	0 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Redness, Dose 1 (Pneumovax™ 23)	—	8 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Redness, Dose 1 (Pneumovax™ 23)	—	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Swelling, Dose1 (Influsplit™ Tetra)	1 Subjects	3 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade3 Swelling,Dose1(Influsplit™ Tetra)	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Swelling, Dose 1 (Placebo)	1 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Swelling, Dose 1 (Placebo)	0 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Swelling, Dose 1 (Pneumovax™ 23)	—	7 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Swelling,Dose 1 (Pneumovax™ 23)	—	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Pain, Dose 2 (Placebo)	—	8 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Pain, Dose 2 (Pneumovax™ 23)	8 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Redness, Dose 2 (Placebo)	—	1 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Redness, Dose 2 (Placebo)	—	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Redness, Dose 2 (Pneumovax™ 23)	8 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Redness, Dose 2 (Pneumovax™ 23)	1 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Swelling, Dose 2 (Placebo)	—	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Swelling, Dose 2 (Placebo)	—	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Swelling, Dose 2 (Pneumovax™ 23)	5 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Swelling, Dose 2 (Pneumovax™ 23)	1 Subjects	—
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Pain, Across Doses (Influsplit™ Tetra)	28 Subjects	58 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Pain, Across Doses (Influsplit™Tetra)	0 Subjects	2 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Pain, Across Doses (Placebo)	10 Subjects	8 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Pain, Across Doses (Placebo)	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Pain, Across Doses (Pneumovax™ 23)	63 Subjects	76 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Pain, Across Doses (Pneumovax™ 23)	8 Subjects	6 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Redness, Across Doses (Influsplit™Tetra)	3 Subjects	2 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Grade 3 Redness, Across Doses (Influsplit™ Tetra)	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Local Adverse Events (AEs) Any Redness, Across Doses (Placebo)	3 Subjects	1 Subjects

SECONDARY outcome

Timeframe: Within 7 days (Days 0 - 6) after each dose and across doses.

Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.

Solicited general symptoms assessed were fatigue, gastrointestinal symptoms*, headache, joint pain, muscle aches, shivering, sweating and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 was defined as symptoms that prevented normal everyday activities. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 fever was defined as temperature greater than (>)39.0°C.

*Gastrointestinal (GI) symptoms included nausea, vomiting, diarrhoea and/or abdominal pain

Outcome measures

Measure	Control Group n=178 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=175 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Fatigue, Dose 1	30 Subjects	39 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Fatigue, Dose 1	1 Subjects	2 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Fatigue, Dose 1	23 Subjects	33 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any GI symptoms, Dose 1	16 Subjects	12 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 GI symptoms, Dose 1	1 Subjects	1 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related GI symptoms, Dose 1	9 Subjects	5 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Headache, Dose 1	21 Subjects	20 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Headache, Dose 1	0 Subjects	2 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Headache, Dose 1	13 Subjects	17 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Joint pain, Dose 1	11 Subjects	16 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Joint pain, Dose 1	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Joint pain, Dose 1	6 Subjects	14 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Muscle aches, Dose 1	15 Subjects	20 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Muscle aches, Dose 1	0 Subjects	1 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Muscle aches, Dose 1	12 Subjects	19 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Shivering, Dose 1	6 Subjects	10 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Shivering, Dose 1	0 Subjects	1 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Shivering, Dose 1	5 Subjects	8 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Sweating, Dose 1	11 Subjects	16 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Sweating, Dose 1	0 Subjects	1 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Sweating, Dose 1	9 Subjects	10 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Fever, Dose 1	0 Subjects	2 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Fever, Dose 1	0 Subjects	1 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Fever, Dose 1	0 Subjects	2 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Fatigue, Dose 2	25 Subjects	12 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Fatigue, Dose 2	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Fatigue, Dose 2	22 Subjects	6 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any GI symptoms, Dose 2	11 Subjects	7 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 GI symptoms, Dose 2	0 Subjects	1 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related GI symptoms, Dose 2	9 Subjects	2 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Headache, Dose 2	18 Subjects	10 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Headache, Dose 2	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Headache, Dose 2	14 Subjects	3 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Joint pain, Dose 2	17 Subjects	11 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Joint pain, Dose 2	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Joint pain, Dose 2	12 Subjects	7 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Muscle aches, Dose 2	21 Subjects	12 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Muscle aches, Dose 2	4 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Muscle aches, Dose 2	19 Subjects	6 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Shivering, Dose 2	8 Subjects	5 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Shivering, Dose 2	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Shivering, Dose 2	5 Subjects	3 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Sweating, Dose 2	10 Subjects	8 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Sweating, Across Doses	16 Subjects	19 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Sweating, Dose 2	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Sweating, Dose 2	5 Subjects	5 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Fever, Dose 2	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Fever, Dose 2	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Fever, Dose 2	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Fatigue, Across Doses	43 Subjects	43 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Fatigue, Across Doses	2 Subjects	2 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Fatigue, Across Doses	34 Subjects	37 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any GI symptoms, Across Doses	23 Subjects	17 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 GI symptoms, Across Doses	1 Subjects	2 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related GI symptoms, Across Doses	15 Subjects	7 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Headache, Across Doses	30 Subjects	27 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Headache, Across Doses	1 Subjects	2 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Headache, Across Doses	22 Subjects	20 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Joint pain, Across Doses	25 Subjects	23 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Shivering, Across Doses	13 Subjects	14 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Joint pain, Across Doses	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Joint pain, Across Doses	16 Subjects	20 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Shivering, Across Doses	1 Subjects	1 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Muscle aches, Across Doses	32 Subjects	28 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Muscle aches, Across Doses	4 Subjects	1 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Muscle aches, Across Doses	28 Subjects	24 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Shivering, Across Doses	9 Subjects	10 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Sweating, Across Doses	1 Subjects	1 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Sweating, Across Doses	11 Subjects	14 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Any Fever, Across Doses	1 Subjects	2 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Grade 3 Fever, Across Doses	0 Subjects	1 Subjects
Number of Subjects Reporting Solicited General Adverse Events (AEs) Related Fever, Across Doses	1 Subjects	2 Subjects

SECONDARY outcome

Timeframe: During the 7-day (Days 0-6) post-vaccination period

Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.

Duration was defined as number of days with any grade of local symptoms.

Outcome measures

Measure	Control Group n=63 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=90 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Duration of Local Adverse Events Pain, Dose 1	2.0 Days Interval 1.0 to 3.0	2.0 Days Interval 1.0 to 3.0
Duration of Local Adverse Events Pain, Dose 2	2.0 Days Interval 1.0 to 3.0	2.0 Days Interval 1.0 to 3.0
Duration of Local Adverse Events Redness, Dose 1	4.0 Days Interval 3.0 to 4.0	2.0 Days Interval 2.0 to 3.0
Duration of Local Adverse Events Redness, Dose 2	2.0 Days Interval 1.0 to 2.5	1.0 Days Interval 1.0 to 1.0
Duration of Local Adverse Events Swelling, Dose 1	4.5 Days Interval 4.0 to 5.0	2.0 Days Interval 2.0 to 4.0
Duration of Local Adverse Events Swelling, Dose 2	3.0 Days Interval 1.0 to 5.0	—

SECONDARY outcome

Timeframe: During the 7-day (Days 0-6) post-vaccination period

Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.

Duration was defined as number of days with any grade of general symptoms.

Outcome measures

Measure	Control Group n=30 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=39 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Duration of Solicited General AEs. Fatigue, Dose 1	2.0 Days Interval 1.0 to 3.0	2.0 Days Interval 1.0 to 3.0
Duration of Solicited General AEs. Fatigue, Dose 2	3.0 Days Interval 2.0 to 4.0	3.5 Days Interval 1.5 to 6.5
Duration of Solicited General AEs. Gastrointestinal symptoms, Dose 1	2.0 Days Interval 1.0 to 4.0	2.0 Days Interval 1.0 to 2.0
Duration of Solicited General AEs. Gastrointestinal symptoms, Dose 2	3.0 Days Interval 2.0 to 3.0	3.0 Days Interval 2.0 to 6.0
Duration of Solicited General AEs. Headache, Dose 1	1.0 Days Interval 1.0 to 2.0	1.5 Days Interval 1.0 to 2.5
Duration of Solicited General AEs. Headache, Dose 2	2.0 Days Interval 1.0 to 3.0	2.0 Days Interval 1.0 to 3.0
Duration of Solicited General AEs. Joint pain, Dose 1	2.0 Days Interval 1.0 to 3.0	2.0 Days Interval 1.0 to 4.0
Duration of Solicited General AEs. Joint pain, Dose 2	2.0 Days Interval 2.0 to 3.0	2.0 Days Interval 1.0 to 7.0
Duration of Solicited General AEs. Muscle aches, Dose 1	2.0 Days Interval 1.0 to 3.0	3.0 Days Interval 1.5 to 4.5
Duration of Solicited General AEs. Muscle aches, Dose 2	2.0 Days Interval 1.0 to 3.0	2.0 Days Interval 1.0 to 4.0
Duration of Solicited General AEs. Sweating, Dose 1	2.0 Days Interval 1.0 to 6.0	2.0 Days Interval 1.0 to 3.5
Duration of Solicited General AEs. Sweating, Dose 2	2.0 Days Interval 1.0 to 5.0	2.0 Days Interval 1.5 to 2.0
Duration of Solicited General AEs. Shivering, Dose 1	2.0 Days Interval 1.0 to 2.0	1.0 Days Interval 1.0 to 2.0
Duration of Solicited General AEs. Shivering, Dose 2	1.0 Days Interval 1.0 to 2.0	3.0 Days Interval 1.0 to 3.0
Duration of Solicited General AEs. Fever, Dose 1	—	1.0 Days Interval 1.0 to 1.0
Duration of Solicited General AEs. Fever, Dose 2	1.0 Days Interval 1.0 to 1.0	—

SECONDARY outcome

Timeframe: Throughout the study period (Days 0-180)

Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s) regardless of intensity grade or relationship to vaccination. Related was defined as MAE assessed by the investigator to be causally related to the study vaccination.

Outcome measures

Measure	Control Group n=179 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=177 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Number of Subjects Reporting the Occurrence of Medically Attended Adverse Events (MAEs) Any MAE(s)	37 Subjects	43 Subjects
Number of Subjects Reporting the Occurrence of Medically Attended Adverse Events (MAEs) Related MAE(s)	2 Subjects	2 Subjects

SECONDARY outcome

Timeframe: During the entire study period (Days 0-180)

Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.

Potential immune-mediated diseases (pIMDs) were defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

Any was defined as any occurrence of pIMD(s) regardless of intensity grade or relationship to vaccination. Related was defined as pIMD assessed by the investigator to be causally related to the study vaccination.

Outcome measures

Measure	Control Group n=179 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=177 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Number of Subjects Reporting the Occurrence of Potential Immune Mediated Diseases (pIMDs) Any pIMD(s)	0 Subjects	1 Subjects
Number of Subjects Reporting the Occurrence of Potential Immune Mediated Diseases (pIMDs) Related pIMD(s)	0 Subjects	0 Subjects

SECONDARY outcome

Timeframe: Within the 28-day (Days 0-27) post-vaccination period

Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.

An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.

Outcome measures

Measure	Control Group n=179 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=177 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). Any Unsolicited AEs	35 Subjects	42 Subjects
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). Grade 3 Unsolicited AEs	5 Subjects	8 Subjects
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). Related Unsolicited AEs	5 Subjects	5 Subjects

SECONDARY outcome

Timeframe: Throughout the study period (Days 0-180)

Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

Outcome measures

Measure	Control Group n=179 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=177 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Number of Subjects Reporting Serious Adverse Events (SAEs) Any SAE(s)	11 Subjects	7 Subjects
Number of Subjects Reporting Serious Adverse Events (SAEs) Related SAE(s)	0 Subjects	0 Subjects
Number of Subjects Reporting Serious Adverse Events (SAEs) Fatal SAE(s)	0 Subjects	1 Subjects
Number of Subjects Reporting Serious Adverse Events (SAEs) Related Fatal SAE(s)	0 Subjects	0 Subjects

SECONDARY outcome

Timeframe: At Day 0 and Day 28

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

HI antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Brisbane/60/2008 (Victoria) and Flu B/Massachusetts/02/2012 (Yamagata).

Outcome measures

Measure	Control Group n=171 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=163 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Influenza Vaccine Strains H1N1, Day 0	32.4 Titers Interval 26.3 to 39.9	253.2 Titers Interval 205.3 to 312.1
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Influenza Vaccine Strains H1N1, Day 28	34.0 Titers Interval 27.8 to 41.7	235.5 Titers Interval 195.0 to 284.5
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Influenza Vaccine Strains H3N2, Day 0	20.8 Titers Interval 17.5 to 24.9	21.8 Titers Interval 18.2 to 26.2
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Influenza Vaccine Strains H3N2, Day 28	73.6 Titers Interval 62.1 to 87.1	78.6 Titers Interval 65.2 to 94.7
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Influenza Vaccine Strains Victoria, Day 0	48.7 Titers Interval 41.6 to 57.1	51.5 Titers Interval 43.9 to 60.3
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Influenza Vaccine Strains Victoria, Day 28	178.7 Titers Interval 154.9 to 206.2	157.9 Titers Interval 136.4 to 182.9
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Influenza Vaccine Strains Yamagata, Day 0	120.7 Titers Interval 104.3 to 139.8	119.9 Titers Interval 103.0 to 139.5
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Influenza Vaccine Strains Yamagata, Day 28	346.5 Titers Interval 302.3 to 397.1	353.8 Titers Interval 310.5 to 403.2

SECONDARY outcome

Timeframe: At Day 0 and Day 28

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Brisbane/60/2008 (Victoria) and Flu B/Massachusetts/2/2012 (Yamagata).

Outcome measures

Measure	Control Group n=171 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=163 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. H1N1, Day 0	83 Subjects	77 Subjects
Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. H1N1, Day 28	160 Subjects	157 Subjects
Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. H3N2, Day 0	57 Subjects	50 Subjects
Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. H3N2, Day 28	131 Subjects	128 Subjects
Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. Victoria, Day 0	106 Subjects	113 Subjects
Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. Victoria, Day 28	167 Subjects	154 Subjects
Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. Yamagata, Day 0	159 Subjects	146 Subjects
Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. Yamagata, Day 28	169 Subjects	162 Subjects

SECONDARY outcome

Timeframe: At Day 28

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Brisbane/60/2008 (Victoria) and Flu B/Massachusetts/02/2012 (Yamagata).

Outcome measures

Measure	Control Group n=170 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=162 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Number of Seroconverted Subjects for Anti-Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. H1N1	110 Subjects	101 Subjects
Number of Seroconverted Subjects for Anti-Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. H3N2	62 Subjects	61 Subjects
Number of Seroconverted Subjects for Anti-Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. Victoria	73 Subjects	55 Subjects
Number of Seroconverted Subjects for Anti-Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. Yamagata	60 Subjects	54 Subjects

SECONDARY outcome

Timeframe: At Day 28

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

MGI was defined as the fold increase in serum haemagglutination inhibition (HI) GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Brisbane/60/2008 (Victoria) and Flu B/Massachusetts/02/2012 (Yamagata).

Outcome measures

Measure	Control Group n=170 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=162 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. H1N1	7.7 Fold increase Interval 6.1 to 9.7	6.9 Fold increase Interval 5.5 to 8.6
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. H3N2	3.5 Fold increase Interval 3.0 to 4.2	3.6 Fold increase Interval 3.0 to 4.4
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. Victoria	3.6 Fold increase Interval 3.1 to 4.3	3.1 Fold increase Interval 2.6 to 3.6
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. Yamagata	2.8 Fold increase Interval 2.5 to 3.3	3.0 Fold increase Interval 2.5 to 3.4

SECONDARY outcome

Timeframe: At Days 0 (Co-Ad group only), 28 (both groups), and 56 (Control group only)

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

The pneumococcal antigen testing was performed, as determined by ELISA cut-offs of ≥0.05 µg/mL and a seroprotection cut-off of ≥ 0.2 µg/ml.

PRE = Pre-vaccination i.e. at Day 0 for Co-Ad Group and at Day 28 for Control Group.

POST = Post-vaccination i.e. at Day 28 for Co-Ad Group and at Day 56 for Control Group.

Outcome measures

Measure	Control Group n=170 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=163 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 01 Ab.IgG (≥ 0.05 µg/ml) (PRE)	162 Subjects	152 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 01 Ab.IgG (≥ 0.05 µg/ml) (POST)	169 Subjects	162 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 01 Ab.IgG (≥ 0.2 µg/ml) (PRE)	112 Subjects	118 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 01 Ab.IgG (≥ 0.2 µg/ml) (POST)	167 Subjects	159 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 03 Ab.IgG (≥ 0.05 µg/ml) (PRE)	158 Subjects	149 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 03 Ab.IgG (≥ 0.05 µg/ml) (POST)	167 Subjects	161 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 6B Ab.IgG (≥ 0.05 µg/ml) (PRE)	158 Subjects	149 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 6B Ab.IgG (≥ 0.2 µg/ml) (PRE)	106 Subjects	110 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 6B Ab.IgG (≥ 0.2 µg/ml) (POST)	157 Subjects	147 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 9V Ab.IgG (≥ 0.05 µg/ml) (POST)	168 Subjects	160 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 9V Ab.IgG (≥ 0.2 µg/ml) (PRE)	123 Subjects	117 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 9V Ab.IgG (≥ 0.2 µg/ml) (POST)	166 Subjects	157 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 14 Ab.IgG (≥ 0.05 µg/ml) (PRE)	170 Subjects	163 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 19F Ab.IgG (≥ 0.05 µg/ml) (PRE)	169 Subjects	160 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 03 Ab.IgG (≥ 0.2 µg/ml) (PRE)	114 Subjects	121 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 03 Ab.IgG (≥ 0.2 µg/ml) (POST)	158 Subjects	153 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 04 Ab.IgG (≥ 0.05 µg/ml) (PRE)	138 Subjects	129 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 04 Ab.IgG (≥ 0.05 µg/ml) (POST)	167 Subjects	158 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 04 Ab.IgG (≥ 0.2 µg/ml) (PRE)	77 Subjects	82 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 04 Ab.IgG (≥ 0.2 µg/ml) (POST)	158 Subjects	149 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 05 Ab.IgG5 (≥ 0.05 µg/ml) (PRE)	165 Subjects	159 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 05 Ab.IgG5 (≥ 0.05 µg/ml) (POST)	169 Subjects	162 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 05 Ab.IgG5 (≥ 0.2 µg/ml) (PRE)	130 Subjects	115 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 05 Ab.IgG5 (≥ 0.2 µg/ml) (POST)	163 Subjects	155 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 6B Ab.IgG (≥ 0.05 µg/ml) (POST)	164 Subjects	160 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 7F Ab.IgG (≥ 0.05 µg/ml) (PRE)	159 Subjects	154 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 7F Ab.IgG (≥ 0.05 µg/ml) (POST)	169 Subjects	162 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 7F Ab.IgG (≥ 0.2 µg/ml) (PRE)	127 Subjects	130 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 7F Ab.IgG (≥ 0.2 µg/ml) (POST)	165 Subjects	161 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 9V Ab.IgG (≥ 0.05 µg/ml) (PRE)	165 Subjects	150 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 14 Ab.IgG (≥ 0.05 µg/ml) (POST)	169 Subjects	162 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 14 Ab.IgG (≥ 0.2 µg/ml) (PRE)	168 Subjects	160 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 14 Ab.IgG (≥ 0.2 µg/ml) (POST)	168 Subjects	162 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 18C Ab.IgG (≥ 0.05 µg/ml) (PRE)	166 Subjects	161 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 18C Ab.IgG (≥ 0.05 µg/ml) (POST)	169 Subjects	162 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 18C Ab.IgG (≥ 0.2 µg/ml) (PRE)	154 Subjects	148 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 18C Ab.IgG (≥ 0.2 µg/ml) (POST)	168 Subjects	159 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 19A Ab.IgG (≥ 0.05 µg/ml) (PRE)	168 Subjects	160 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 19A Ab.IgG (≥ 0.05 µg/ml) (POST)	169 Subjects	161 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 19A Ab.IgG (≥ 0.2 µg/ml) (PRE)	146 Subjects	148 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 19A Ab.IgG (≥ 0.2 µg/ml) (POST)	165 Subjects	158 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 19F Ab.IgG (≥ 0.05 µg/ml) (POST)	169 Subjects	162 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 19F Ab.IgG (≥ 0.2 µg/ml) (PRE)	151 Subjects	152 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 19F Ab.IgG (≥ 0.2 µg/ml) (POST)	169 Subjects	161 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 23F Ab.IgG (≥ 0.05 µg/ml) (PRE)	151 Subjects	151 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 23F Ab.IgG (≥ 0.05 µg/ml) (POST)	165 Subjects	159 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 23F Ab.IgG (≥ 0.2 µg/ml) (PRE)	112 Subjects	125 Subjects
Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F Polysaccharide 23F Ab.IgG (≥ 0.2 µg/ml) (POST)	155 Subjects	147 Subjects

SECONDARY outcome

Timeframe: At Days 0 (Co-Ad group only), 28 (both groups), and 56 (Control group only)

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

Anti-pneumococcal antibody concentrations were expressed as adjusted geometric mean concentrations (GMCs) PRE = Pre -vaccination i.e. at Day 0 for Co-Ad Group and at Day 28 for Control Group.

POST = Post-vaccination i.e. at Day 28 for Co-Ad Group and at Day 56 for Control Group.

Outcome measures

Measure	Control Group n=170 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=163 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 04 Ab.IgG (POST)	2.3 Titers Interval 1.8 to 2.9	1.7 Titers Interval 1.4 to 2.2
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 7F Ab.IgG (POST)	9.0 Titers Interval 6.9 to 11.8	8.1 Titers Interval 6.2 to 10.6
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 9V Ab.IgG (PRE)	0.5 Titers Interval 0.4 to 0.7	0.5 Titers Interval 0.4 to 0.6
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 19A Ab.IgG (PRE)	1.3 Titers Interval 1.0 to 1.6	1.5 Titers Interval 1.2 to 1.9
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 19A Ab.IgG (POST)	9.2 Titers Interval 7.1 to 11.9	7.7 Titers Interval 6.1 to 9.8
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 19F Ab.IgG (PRE)	1.3 Titers Interval 1.1 to 1.7	1.4 Titers Interval 1.2 to 1.8
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 01 Ab.IgG (PRE)	0.4 Titers Interval 0.3 to 0.5	0.4 Titers Interval 0.3 to 0.5
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 01 Ab.IgG (POST)	5.5 Titers Interval 4.3 to 7.0	4.9 Titers Interval 3.9 to 6.2
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 03 Ab.IgG (PRE)	0.4 Titers Interval 0.3 to 0.5	0.5 Titers Interval 0.4 to 0.6
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 03 Ab.IgG (POST)	1.7 Titers Interval 1.4 to 2.1	1.7 Titers Interval 1.4 to 2.0
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 04 Ab.IgG (PRE)	0.2 Titers Interval 0.2 to 0.3	0.2 Titers Interval 0.2 to 0.2
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 05 Ab.IgG5 (PRE)	0.6 Titers Interval 0.5 to 0.7	0.5 Titers Interval 0.4 to 0.6
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 05 Ab.IgG5 (POST)	7.8 Titers Interval 5.9 to 10.4	5.7 Titers Interval 4.3 to 7.5
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 6B Ab.IgG (PRE)	0.4 Titers Interval 0.3 to 0.6	0.4 Titers Interval 0.3 to 0.5
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 6B Ab.IgG (POST)	3.9 Titers Interval 2.9 to 5.1	3.1 Titers Interval 2.3 to 4.1
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 7F Ab.IgG (PRE)	0.6 Titers Interval 0.5 to 0.8	0.7 Titers Interval 0.6 to 0.9
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 9V Ab.IgG (POST)	5.9 Titers Interval 4.8 to 7.4	4.4 Titers Interval 3.6 to 5.5
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 14 Ab.IgG (PRE)	3.7 Titers Interval 3.1 to 4.6	2.9 Titers Interval 2.4 to 3.5
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 14 Ab.IgG (POST)	20.2 Titers Interval 16.0 to 25.6	14.1 Titers Interval 11.3 to 17.6
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 18C Ab.IgG (PRE)	1.4 Titers Interval 1.1 to 1.7	1.2 Titers Interval 1.0 to 1.5
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 18C Ab.IgG (POST)	13.5 Titers Interval 10.7 to 16.8	11.1 Titers Interval 9.0 to 13.6
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 19F Ab.IgG (POST)	11.9 Titers Interval 9.3 to 15.2	10.6 Titers Interval 8.4 to 13.6
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 23F Ab.IgG (PRE)	0.4 Titers Interval 0.3 to 0.6	0.5 Titers Interval 0.4 to 0.7
Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Polysaccharide 23F Ab.IgG (POST)	3.1 Titers Interval 2.3 to 4.1	2.9 Titers Interval 2.2 to 3.8

SECONDARY outcome

Timeframe: At 28 days post-vaccination with Pneumovax™ 23

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

Fold antibody concentration increases post-vaccination/pre-vaccination ≥ 2 and ≥ 4.

The anti-pneumococcal serotypes assessed were 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

Outcome measures

Measure	Control Group n=169 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=163 Participants Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 23F Ab.IgG (≥ 2)	133 Subjects	122 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 6B Ab.IgG (≥ 4)	113 Subjects	109 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 7F Ab.IgG (≥ 2)	155 Subjects	144 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 7F Ab.IgG (≥ 4)	138 Subjects	119 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 01 Ab.IgG (≥ 2)	149 Subjects	144 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 01 Ab.IgG (≥ 4)	134 Subjects	126 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 03 Ab.IgG (≥ 2)	121 Subjects	97 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 03 Ab.IgG (≥ 4)	80 Subjects	65 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 04 Ab.IgG (≥ 2)	149 Subjects	137 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 04 Ab.IgG (≥ 4)	127 Subjects	112 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 05 Ab.IgG5 (≥ 2)	156 Subjects	138 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 05 Ab.IgG5 (≥ 4)	127 Subjects	114 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 14 Ab.IgG (≥ 2)	123 Subjects	102 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 14 Ab.IgG (≥ 4)	90 Subjects	82 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 18C Ab.IgG (≥ 2)	149 Subjects	133 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 18C Ab.IgG (≥ 4)	123 Subjects	116 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 19A Ab.IgG (≥ 2)	133 Subjects	123 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 19A Ab.IgG (≥ 4)	111 Subjects	87 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 19F Ab.IgG (≥ 2)	146 Subjects	141 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 19F Ab.IgG (≥ 4)	111 Subjects	109 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 23F Ab.IgG (≥ 4)	108 Subjects	94 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 6B Ab.IgG (≥ 2)	141 Subjects	127 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 9V Ab.IgG (≥ 2)	146 Subjects	140 Subjects
Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects. Polysaccharide 9V Ab.IgG (≥ 4)	131 Subjects	121 Subjects

Adverse Events

Control Group

Serious events: 11 serious events

Other events: 117 other events

Deaths: 0 deaths

Co-Ad Group

Serious events: 7 serious events

Other events: 127 other events

Deaths: 0 deaths

Serious adverse events

Measure	Control Group n=179 participants at risk Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=177 participants at risk Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Blood and lymphatic system disorders Anaemia	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Cardiac disorders Angina pectoris	0.00% 0/179 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Cardiac disorders Arrhythmia	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Cardiac disorders Cardiac failure	0.00% 0/179 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/179 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Cardiac disorders Coronary artery stenosis	1.1% 2/179 • Number of events 2 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Cardiac disorders Myocardial infarction	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Congenital, familial and genetic disorders Intestinal malrotation	0.00% 0/179 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/179 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
General disorders Calcinosis	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
General disorders Chest pain	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Infections and infestations Erysipelas	0.00% 0/179 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Infections and infestations Lung infection	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/179 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/179 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Metabolism and nutrition disorders Hyperkalaemia	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/179 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer stage ii	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the oral cavity	0.00% 0/179 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Nervous system disorders Carotid artery stenosis	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Nervous system disorders Cerebral thrombosis	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Psychiatric disorders Depression	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Renal and urinary disorders Acute kidney injury	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.56% 1/177 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Vascular disorders Hypertension	0.56% 1/179 • Number of events 1 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	0.00% 0/177 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.

Other adverse events

Measure	Control Group n=179 participants at risk Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of placebo at Day 0 and 1 dose of Pneumovax™ 23 vaccine at Day 28.	Co-Ad Group n=177 participants at risk Subjects received 1 dose of Influsplit™ Tetra vaccine and 1 dose of Pneumovax™ 23 vaccine at Day 0 and 1 dose of placebo at Day 28.
Musculoskeletal and connective tissue disorders Arthralgia	14.0% 25/179 • Number of events 28 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	14.1% 25/177 • Number of events 30 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
General disorders Chills	7.3% 13/179 • Number of events 14 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	7.9% 14/177 • Number of events 15 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Skin and subcutaneous tissue disorders Erythema	7.3% 13/179 • Number of events 14 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	5.6% 10/177 • Number of events 10 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
General disorders Fatigue	24.0% 43/179 • Number of events 55 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	24.3% 43/177 • Number of events 51 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Gastrointestinal disorders Gastrointestinal disorder	12.8% 23/179 • Number of events 27 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	9.6% 17/177 • Number of events 19 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Nervous system disorders Headache	17.3% 31/179 • Number of events 41 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	15.3% 27/177 • Number of events 30 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Skin and subcutaneous tissue disorders Hyperhidrosis	8.9% 16/179 • Number of events 21 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	10.7% 19/177 • Number of events 24 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Musculoskeletal and connective tissue disorders Myalgia	17.9% 32/179 • Number of events 36 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	15.8% 28/177 • Number of events 32 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
General disorders Pain	42.5% 76/179 • Number of events 98 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	52.0% 92/177 • Number of events 98 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
General disorders Swelling	3.4% 6/179 • Number of events 7 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.	5.1% 9/177 • Number of events 9 • Serious Adverse Events: During the entire study period (Day 0 to 180); Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited adverse events: During the 28-day (Days 0-27) post-vaccination period. For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER