Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 When Administered Concomitantly With Influenza Vaccine in Healthy Adults 50 Years of Age or Older (V114-021/PNEU-FLU) (NCT NCT03615482)

Last Updated: 2024-05-22

Results Overview

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Solicited injection-site AEs included injection-site erythema /redness, pain /tenderness, swelling.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1200 participants

Primary outcome timeframe

Up to Day 5 after vaccination

Results posted on

2024-05-22

Participant Flow

Participant milestones

Participant milestones
Measure	Concomitant Group Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of quadrivalent influenza vaccine (QIV) on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Overall Study STARTED	600	600
Overall Study Vaccinated	599	598
Overall Study COMPLETED	583	583
Overall Study NOT COMPLETED	17	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Concomitant Group Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of quadrivalent influenza vaccine (QIV) on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Overall Study Death	1	0
Overall Study Lost to Follow-up	7	7
Overall Study Physician Decision	2	3
Overall Study Withdrawal by Subject	7	7

Baseline Characteristics

A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 When Administered Concomitantly With Influenza Vaccine in Healthy Adults 50 Years of Age or Older (V114-021/PNEU-FLU)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.	Total n=1197 Participants Total of all reporting groups
Age, Continuous	64.2 years STANDARD_DEVIATION 8.3 • n=5 Participants	64.2 years STANDARD_DEVIATION 8.1 • n=7 Participants	64.2 years STANDARD_DEVIATION 8.2 • n=5 Participants
Sex: Female, Male Female	330 Participants n=5 Participants	342 Participants n=7 Participants	672 Participants n=5 Participants
Sex: Female, Male Male	269 Participants n=5 Participants	256 Participants n=7 Participants	525 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	120 Participants n=5 Participants	119 Participants n=7 Participants	239 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	471 Participants n=5 Participants	472 Participants n=7 Participants	943 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	25 Participants n=5 Participants	30 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	73 Participants n=5 Participants	63 Participants n=7 Participants	136 Participants n=5 Participants
Race (NIH/OMB) White	493 Participants n=5 Participants	495 Participants n=7 Participants	988 Participants n=5 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 5 after vaccination

Population: All randomized participants who received at least 1 dose of study vaccination were included. Of the 598 randomized to non-concomitant group, 1 received vaccination with concomitant group and was included (concomitant=600); 1 received 2 doses and was excluded (non-concomitant=596).

Outcome measures

Outcome measures
Measure	Concomitant Group n=600 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=596 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Percentage of Participants With a Solicited Injection-site Adverse Event Injection-Site Erythema /Redness	10.7 Percentage of Participants	11.6 Percentage of Participants
Percentage of Participants With a Solicited Injection-site Adverse Event Injection-Site Pain /Tenderness	68.5 Percentage of Participants	71.1 Percentage of Participants
Percentage of Participants With a Solicited Injection-site Adverse Event Injection-Site Swelling	14.2 Percentage of Participants	16.3 Percentage of Participants

PRIMARY outcome

Timeframe: Up to Day 14 after any vaccination

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Solicited systemic AEs included myalgia/muscle pain, arthralgia/joint pain, headache, and fatigue/tiredness.

Outcome measures

Outcome measures
Measure	Concomitant Group n=600 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=596 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Percentage of Participants With a Solicited Systemic Adverse Event Joint Pain /Arthralgia	9.3 Percentage of Participants	11.6 Percentage of Participants
Percentage of Participants With a Solicited Systemic Adverse Event Tiredness/Fatigue	27.2 Percentage of Participants	30.0 Percentage of Participants
Percentage of Participants With a Solicited Systemic Adverse Event Headache	21.5 Percentage of Participants	23.7 Percentage of Participants
Percentage of Participants With a Solicited Systemic Adverse Event Muscle Pain /Myalgia	23.7 Percentage of Participants	21.3 Percentage of Participants

PRIMARY outcome

Timeframe: Up to 7 months

A serious adverse event (SAE) is an AE that results in death, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. Relatedness of an SAE to the study vaccine was determined by the investigator.

Outcome measures

Outcome measures
Measure	Concomitant Group n=600 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=596 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Percentage of Participants With a Vaccine-Related Serious Adverse Event	0 Percentage of Participants	0 Percentage of Participants

PRIMARY outcome

Timeframe: 30 days after V114 vaccination (Day 30 for concomitant vaccination group and Day 60 for non-concomitant vaccination group)

Population: The analysis population consisted of all randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity analyses and had data available for this endpoint.

Serotype-specific OPA GMTs (estimated) and GMT ratios with 95% confidence intervals (CIs) and 1-sided p-values were calculated using a constrained longitudinal data analysis (cLDA) method utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMT ratios); within-group CIs were not calculated.

Outcome measures

Outcome measures
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 1	140.1 Titers	211.5 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 3	137.9 Titers	147.4 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 4	901.3 Titers	1078.5 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 5	396.1 Titers	500.6 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 6A	5564.2 Titers	6615.9 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 6B	3904.0 Titers	4436.5 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 7F	3563.2 Titers	4119.5 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 9V	2859.6 Titers	2874.1 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 14	2024.8 Titers	2228.6 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 18C	3022.8 Titers	3802.7 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 19A	3208.4 Titers	3849.0 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 19F	2523.2 Titers	2473.9 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 22F	2243.4 Titers	2932.5 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 23F	2206.2 Titers	2592.2 Titers
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Serotype 33F	8142.9 Titers	9807.4 Titers

PRIMARY outcome

Timeframe: Day 30

Activity for the 4 strains contained in QIV vaccine was determined using an hemagglutination inhibition (HAI) assay. Serotype-specific HAI GMTs (estimated) and GMT ratios with 95% confidence intervals (CIs) and 1-sided p-values were calculated using a constrained longitudinal data analysis (cLDA) method utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMT ratios); within-group CIs were not calculated.

Outcome measures

Outcome measures
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
GMT of Influenza Strain-Specific Hemagglutination Inhibition H1N1	124.82 Titers	115.00 Titers
GMT of Influenza Strain-Specific Hemagglutination Inhibition H3N2	87.85 Titers	85.62 Titers
GMT of Influenza Strain-Specific Hemagglutination Inhibition B-Victoria	35.53 Titers	36.88 Titers
GMT of Influenza Strain-Specific Hemagglutination Inhibition B-Yamagata	33.47 Titers	33.13 Titers

SECONDARY outcome

Timeframe: 30 days after V114 vaccination (Day 30 for concomitant vaccination group and Day 60 for non-concomitant vaccination group)

Serotype-specific IgG GMC ratios (estimated) and GMC ratios with 95% confidence intervals (CIs) were calculated using a constrained longitudinal data analysis (cLDA) method utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMC ratios); within-group CIs were not calculated.

Outcome measures

Outcome measures
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 1	4.19 µg/mL	5.41 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 3	0.75 µg/mL	0.86 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 4	1.47 µg/mL	1.86 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 5	4.65 µg/mL	5.23 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 6A	6.07 µg/mL	8.29 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 6B	7.11 µg/mL	9.26 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 7F	4.68 µg/mL	5.33 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 9V	3.84 µg/mL	4.26 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 14	8.30 µg/mL	9.80 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 18C	9.99 µg/mL	12.75 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 19A	13.43 µg/mL	15.09 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 19F	8.68 µg/mL	9.75 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 22F	3.29 µg/mL	4.33 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 23F	5.68 µg/mL	6.82 µg/mL
Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Serotype 33F	9.19 µg/mL	10.69 µg/mL

SECONDARY outcome

Timeframe: Baseline and 30 days after V114 vaccination (Day 1 and Day 30 for concomitant vaccination group, and Day 30 and Day 60 for non-concomitant vaccination group, respectively)

Activity for the 15 serotypes contained in V114 vaccine will be determined using a Multiplex Opsonophagocytic Assay. GMFR is the geometric mean of fold rise from baseline to postvaccination.

Outcome measures

Outcome measures
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 1	8.0 Ratio Interval 6.8 to 9.3	11.8 Ratio Interval 10.1 to 13.9
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 3	4.7 Ratio Interval 4.3 to 5.3	4.8 Ratio Interval 4.3 to 5.4
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 4	9.4 Ratio Interval 8.0 to 11.0	11.5 Ratio Interval 9.7 to 13.6
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 5	8.1 Ratio Interval 7.0 to 9.4	10.2 Ratio Interval 8.7 to 12.0
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 6A	10.5 Ratio Interval 9.1 to 12.1	12.1 Ratio Interval 10.5 to 14.0
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 6B	17.6 Ratio Interval 14.8 to 20.9	20.5 Ratio Interval 17.3 to 24.4
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 7F	9.2 Ratio Interval 7.9 to 10.8	8.0 Ratio Interval 6.9 to 9.4
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 9V	5.8 Ratio Interval 5.1 to 6.6	5.3 Ratio Interval 4.6 to 6.1
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 14	3.9 Ratio Interval 3.3 to 4.4	4.1 Ratio Interval 3.5 to 4.7
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 18C	9.8 Ratio Interval 8.6 to 11.2	11.6 Ratio Interval 10.0 to 13.4
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 19A	6.2 Ratio Interval 5.4 to 7.2	6.6 Ratio Interval 5.7 to 7.6
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 19F	5.2 Ratio Interval 4.6 to 5.9	4.7 Ratio Interval 4.2 to 5.4
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 22F	15.9 Ratio Interval 12.8 to 19.8	20.6 Ratio Interval 16.4 to 25.9
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 23F	13.9 Ratio Interval 11.7 to 16.6	11.9 Ratio Interval 9.9 to 14.3
Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA Serotype 33F	4.3 Ratio Interval 3.8 to 4.9	4.6 Ratio Interval 4.0 to 5.3

SECONDARY outcome

Timeframe: Baseline and 30 days after V114 vaccination (Day 1 and Day 30 for concomitant vaccination group, and Day 30 and Day 60 for non-concomitant vaccination group, respectively)

Immunoglobulin G for the 15 serotypes contained in V114 vaccine will be determined using an electrochemiluminescence assay. GMFR is the geometric mean of fold rise from baseline to postvaccination.

Outcome measures

Outcome measures
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
GMFR in Pneumococcal Serotype-Specific IgG Serotype 23F	10.7 Ratio Interval 9.4 to 12.2	11.9 Ratio Interval 10.3 to 13.7
GMFR in Pneumococcal Serotype-Specific IgG Serotype 1	6.1 Ratio Interval 5.5 to 6.9	7.5 Ratio Interval 6.6 to 8.5
GMFR in Pneumococcal Serotype-Specific IgG Serotype 3	4.4 Ratio Interval 4.0 to 4.8	5.1 Ratio Interval 4.6 to 5.7
GMFR in Pneumococcal Serotype-Specific IgG Serotype 4	5.3 Ratio Interval 4.8 to 5.9	6.5 Ratio Interval 5.8 to 7.4
GMFR in Pneumococcal Serotype-Specific IgG Serotype 5	3.5 Ratio Interval 3.2 to 3.9	4.0 Ratio Interval 3.5 to 4.5
GMFR in Pneumococcal Serotype-Specific IgG Serotype 6A	15.6 Ratio Interval 13.7 to 17.8	19.9 Ratio Interval 17.3 to 22.9
GMFR in Pneumococcal Serotype-Specific IgG Serotype 6B	14.0 Ratio Interval 12.2 to 15.9	17.8 Ratio Interval 15.5 to 20.5
GMFR in Pneumococcal Serotype-Specific IgG Serotype 7F	6.7 Ratio Interval 6.0 to 7.5	7.2 Ratio Interval 6.4 to 8.2
GMFR in Pneumococcal Serotype-Specific IgG Serotype 9V	5.9 Ratio Interval 5.3 to 6.6	6.6 Ratio Interval 5.8 to 7.4
GMFR in Pneumococcal Serotype-Specific IgG Serotype 14	3.8 Ratio Interval 3.4 to 4.3	4.4 Ratio Interval 3.9 to 5.0
GMFR in Pneumococcal Serotype-Specific IgG Serotype 18C	11.2 Ratio Interval 9.8 to 12.8	12.9 Ratio Interval 11.2 to 14.9
GMFR in Pneumococcal Serotype-Specific IgG Serotype 19A	6.4 Ratio Interval 5.7 to 7.1	6.8 Ratio Interval 6.1 to 7.7
GMFR in Pneumococcal Serotype-Specific IgG Serotype 19F	8.1 Ratio Interval 7.2 to 9.2	8.9 Ratio Interval 7.9 to 10.1
GMFR in Pneumococcal Serotype-Specific IgG Serotype 22F	7.6 Ratio Interval 6.6 to 8.6	10.1 Ratio Interval 8.8 to 11.6
GMFR in Pneumococcal Serotype-Specific IgG Serotype 33F	5.5 Ratio Interval 4.8 to 6.1	6.0 Ratio Interval 5.3 to 6.8

SECONDARY outcome

Timeframe: Baseline and 30 days after V114 vaccination (Day 1 and Day 30 for concomitant vaccination group, and Day 30 and Day 60 for non-concomitant vaccination group, respectively)

Activity for the 15 serotypes contained in V114 vaccine will be determined using a Multiplex Opsonophagocytic Assay. GMFR is the geometric mean of fold rise from baseline to postvaccination. The percentage of participants who had ≥ 4-fold rise in GMFR were calculated from baseline to postvaccination.

Outcome measures

Outcome measures
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 1	57.8 Percentage of Participants Interval 53.4 to 62.1	66.3 Percentage of Participants Interval 62.0 to 70.5
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 3	54.7 Percentage of Participants Interval 50.2 to 59.2	54.8 Percentage of Participants Interval 50.3 to 59.2
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 4	63.1 Percentage of Participants Interval 58.5 to 67.4	66.4 Percentage of Participants Interval 61.9 to 70.6
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 5	60.5 Percentage of Participants Interval 56.1 to 64.7	63.4 Percentage of Participants Interval 59.0 to 67.6
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 6A	71.1 Percentage of Participants Interval 66.6 to 75.3	75.6 Percentage of Participants Interval 71.4 to 79.5
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 6B	72.5 Percentage of Participants Interval 68.2 to 76.5	76.1 Percentage of Participants Interval 72.0 to 79.8
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 7F	63.0 Percentage of Participants Interval 58.6 to 67.3	59.7 Percentage of Participants Interval 55.2 to 64.1
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 9V	54.9 Percentage of Participants Interval 50.3 to 59.4	53.4 Percentage of Participants Interval 48.9 to 57.9
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 14	38.6 Percentage of Participants Interval 34.3 to 43.0	40.9 Percentage of Participants Interval 36.6 to 45.4
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 18C	67.4 Percentage of Participants Interval 63.1 to 71.5	70.3 Percentage of Participants Interval 66.0 to 74.3
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 19A	53.7 Percentage of Participants Interval 49.2 to 58.3	57.1 Percentage of Participants Interval 52.6 to 61.6
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 19F	53.7 Percentage of Participants Interval 49.1 to 58.2	48.8 Percentage of Participants Interval 44.3 to 53.3
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 22F	64.2 Percentage of Participants Interval 59.5 to 68.7	67.5 Percentage of Participants Interval 62.9 to 71.8
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 23F	73.1 Percentage of Participants Interval 68.6 to 77.2	67.2 Percentage of Participants Interval 62.6 to 71.6
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA Serotype 33F	44.1 Percentage of Participants Interval 39.8 to 48.5	44.9 Percentage of Participants Interval 40.4 to 49.4

SECONDARY outcome

Timeframe: Baseline and 30 days after V114 vaccination (Day 1 and Day 30 for concomitant vaccination group, and Day 30 and Day 60 for non-concomitant vaccination group, respectively)

Immunoglobulin G for the 15 serotypes contained in V114 vaccine will be determined using an electrochemiluminescence assay. GMFR is the geometric mean of fold rise from baseline to postvaccination. The percentage of participants who had ≥ 4-fold rise in GMFR are calculated from baseline to postvaccination.

Outcome measures

Outcome measures
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 1	54.8 Percentage of Participants Interval 50.6 to 58.9	60.8 Percentage of Participants Interval 56.6 to 64.9
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 3	46.8 Percentage of Participants Interval 42.7 to 51.0	50.6 Percentage of Participants Interval 46.4 to 54.9
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 4	53.7 Percentage of Participants Interval 49.5 to 57.9	57.2 Percentage of Participants Interval 52.9 to 61.4
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 5	38.0 Percentage of Participants Interval 34.0 to 42.2	40.4 Percentage of Participants Interval 36.2 to 44.6
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 6A	77.3 Percentage of Participants Interval 73.6 to 80.7	79.2 Percentage of Participants Interval 75.6 to 82.6
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 6B	74.9 Percentage of Participants Interval 71.1 to 78.4	79.1 Percentage of Participants Interval 75.4 to 82.4
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 7F	60.2 Percentage of Participants Interval 56.1 to 64.3	59.6 Percentage of Participants Interval 55.4 to 63.8
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 9V	54.4 Percentage of Participants Interval 50.2 to 58.6	55.4 Percentage of Participants Interval 51.1 to 59.6
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 14	39.8 Percentage of Participants Interval 35.7 to 43.9	43.0 Percentage of Participants Interval 38.8 to 47.2
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 18C	67.5 Percentage of Participants Interval 63.5 to 71.4	68.9 Percentage of Participants Interval 64.8 to 72.7
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 19A	59.3 Percentage of Participants Interval 55.1 to 63.3	60.1 Percentage of Participants Interval 55.9 to 64.2
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 19F	63.7 Percentage of Participants Interval 59.6 to 67.6	66.7 Percentage of Participants Interval 62.6 to 70.6
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 22F	56.5 Percentage of Participants Interval 52.3 to 60.6	64.9 Percentage of Participants Interval 60.8 to 68.9
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 23F	67.4 Percentage of Participants Interval 63.4 to 71.3	69.7 Percentage of Participants Interval 65.7 to 73.5
Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG Serotype 33F	50.4 Percentage of Participants Interval 46.2 to 54.5	53.9 Percentage of Participants Interval 49.6 to 58.1

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 30

Activity for the 4 strains contained in QIV vaccine will be determined using an HAI assay. GMFR is the geometric mean of fold rise from baseline to postvaccination.

Outcome measures

Outcome measures
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
GMFR of Influenza Strain-Specific HAI H3N2	2.2 Ratio Interval 2.0 to 2.4	2.2 Ratio Interval 2.0 to 2.4
GMFR of Influenza Strain-Specific HAI H1N1	4.2 Ratio Interval 3.8 to 4.7	4.2 Ratio Interval 3.8 to 4.8
GMFR of Influenza Strain-Specific HAI B-Victoria	2.1 Ratio Interval 2.0 to 2.3	2.2 Ratio Interval 2.0 to 2.4
GMFR of Influenza Strain-Specific HAI B-Yamagata	2.3 Ratio Interval 2.1 to 2.5	2.3 Ratio Interval 2.1 to 2.4

SECONDARY outcome

Timeframe: Day 30

Activity for the 4 strains contained in QIV vaccine will be determined using an HAI assay. Seroconversion is defined as achieving a 4-fold rise from baseline to postvaccination among participants who are seropositive at baseline (HAI titer ≥ 1:10) or a titer of ≥ 1:40 at postvaccination among participants who are seronegative at baseline (HAI titer \< 1:10).

Outcome measures

Outcome measures
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Percentage of Participants With Influenza Strain-specific HAI Titer ≥1:40 H1N1	85.9 Percentage of Participants Interval 82.8 to 88.7	84.7 Percentage of Participants Interval 81.4 to 87.5
Percentage of Participants With Influenza Strain-specific HAI Titer ≥1:40 H3N2	77.4 Percentage of Participants Interval 73.8 to 80.8	79.2 Percentage of Participants Interval 75.6 to 82.5
Percentage of Participants With Influenza Strain-specific HAI Titer ≥1:40 B-Victoria	55.0 Percentage of Participants Interval 50.9 to 59.1	54.9 Percentage of Participants Interval 50.6 to 59.0
Percentage of Participants With Influenza Strain-specific HAI Titer ≥1:40 B-Yamagata	52.4 Percentage of Participants Interval 48.3 to 56.6	50.8 Percentage of Participants Interval 46.6 to 55.0

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 30

Activity for the 4 strains contained in QIV vaccine will be determined using an HAI assay. Seroconversion for HAI responses is defined as achieving either 1) a 4-fold rise in influenza strain-specific HAI titer from Baseline to Day 30 among participants who are seropositive at Baseline (HAI titer ≥1:10) or 2) a influenza strain-specific HAI titer of ≥1:40 at Day 30 among participants who are seronegative at Baseline (HAI titer \<1:10).

Outcome measures

Outcome measures
Measure	Concomitant Group n=599 Participants Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Non-Concomitant Group n=598 Participants Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
Percentage of Participants Who Seroconvert for Influenza Strain-specific HAI H1N1	48.5 Percentage of Participants Interval 44.3 to 52.7	48.3 Percentage of Participants Interval 44.1 to 52.5
Percentage of Participants Who Seroconvert for Influenza Strain-specific HAI H3N2	27.8 Percentage of Participants Interval 24.1 to 31.6	25.3 Percentage of Participants Interval 21.8 to 29.1
Percentage of Participants Who Seroconvert for Influenza Strain-specific HAI B-Victoria	29.2 Percentage of Participants Interval 25.5 to 33.1	28.7 Percentage of Participants Interval 25.0 to 32.6
Percentage of Participants Who Seroconvert for Influenza Strain-specific HAI B-Yamagata	31.1 Percentage of Participants Interval 27.3 to 35.1	30.5 Percentage of Participants Interval 26.7 to 34.5

Adverse Events

Concomitant Group (V114, QIV, Placebo)

Serious events: 22 serious events

Other events: 458 other events

Deaths: 1 deaths

Noncomitant Group (Placebo, QIV, V114)

Serious events: 14 serious events

Other events: 473 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Concomitant Group (V114, QIV, Placebo) n=600 participants at risk Participants received a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30.	Noncomitant Group (Placebo, QIV, V114) n=596 participants at risk Participants received a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30.
General disorders Fatigue	27.2% 163/600 • Number of events 242 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.	30.0% 179/596 • Number of events 274 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.
General disorders Injection site erythema	10.8% 65/600 • Number of events 94 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.	11.7% 70/596 • Number of events 87 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.
General disorders Injection site pain	68.8% 413/600 • Number of events 684 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.	71.1% 424/596 • Number of events 710 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.
General disorders Injection site swelling	14.3% 86/600 • Number of events 124 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.	16.6% 99/596 • Number of events 128 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Arthralgia	9.3% 56/600 • Number of events 69 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.	11.6% 69/596 • Number of events 88 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.
Musculoskeletal and connective tissue disorders Myalgia	23.7% 142/600 • Number of events 180 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.	21.3% 127/596 • Number of events 154 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.
Nervous system disorders Headache	21.5% 129/600 • Number of events 183 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.	24.0% 143/596 • Number of events 215 • Non-serious adverse events were collected up to 14 days following each vaccination. Serious adverse events and all-cause mortality were reported throughout the duration of the study, up to 7 months. The analysis population consisted of all randomized participants who received at least 1 dose of study vaccination. Of 598 participants randomized to non-concomitant group, 1 participant received vaccination with concomitant group and was included for safety analyses (concomitant=600); 1 participant received V114 at both vaccination visits and was excluded from the safety analyses (non-concomitant=596). The all-cause mortality was assessed in all randomized participants.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments. Authorship will be determined by mutual agreement and in line with International Committee of Medical Journal Editors authorship requirements.
Publication restrictions are in place

Restriction type: OTHER