Trial Outcomes & Findings for Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of an MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared to Non-influenza Vaccine Comparator in Adults ≥ 65 Years of Age (NCT NCT02587221)

Last Updated: 2020-06-17

Results Overview

The primary efficacy endpoint was the time of first-occurrence of RT-PCR-confirmed influenza due to any strain of influenza regardless of antigenic match to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the primary endpoint.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

6790 participants

Primary outcome timeframe

Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

Results posted on

2020-06-17

Participant Flow

The study enrolled male and female adults ≥ 65 years old who were healthy or had co-morbidities.

Screening criteria applied.

Participant milestones

Participant milestones
Measure	aQIV A single dose of approximately 0.5 mL of aQIV was administered on Day 1.	Non-influenza Comparator Vaccine A single dose of approximately 0.5 mL dose of Boostrix was administered on Day 1. (Boostrix = Non-influenza comparator vaccine)
Overall Study STARTED	3394	3396
Overall Study Treated	3379	3382
Overall Study COMPLETED	3263	3273
Overall Study NOT COMPLETED	131	123

Reasons for withdrawal

Reasons for withdrawal
Measure	aQIV A single dose of approximately 0.5 mL of aQIV was administered on Day 1.	Non-influenza Comparator Vaccine A single dose of approximately 0.5 mL dose of Boostrix was administered on Day 1. (Boostrix = Non-influenza comparator vaccine)
Overall Study Adverse Event	3	3
Overall Study Death	33	34
Overall Study Withdrawal by Subject	66	61
Overall Study Lost to Follow-up	21	19
Overall Study Protocol Violation	6	5
Overall Study Other Reason or Unspecified	2	1

Baseline Characteristics

According to data availability.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	aQIV n=3394 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3396 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)	Total n=6790 Participants Total of all reporting groups
Age, Continuous	71.9 years STANDARD_DEVIATION 5.53 • n=3394 Participants	71.8 years STANDARD_DEVIATION 5.36 • n=3396 Participants	71.9 years STANDARD_DEVIATION 5.44 • n=6790 Participants
Age, Customized 65 to 74 years	2416 Participants n=3394 Participants	2406 Participants n=3396 Participants	4822 Participants n=6790 Participants
Age, Customized 75 to 84 years	893 Participants n=3394 Participants	928 Participants n=3396 Participants	1821 Participants n=6790 Participants
Age, Customized . 85 years	85 Participants n=3394 Participants	62 Participants n=3396 Participants	147 Participants n=6790 Participants
Sex: Female, Male Female	2105 Participants n=3394 Participants	2089 Participants n=3396 Participants	4194 Participants n=6790 Participants
Sex: Female, Male Male	1289 Participants n=3394 Participants	1307 Participants n=3396 Participants	2596 Participants n=6790 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	615 Participants n=3394 Participants	607 Participants n=3396 Participants	1222 Participants n=6790 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2773 Participants n=3394 Participants	2779 Participants n=3396 Participants	5552 Participants n=6790 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=3394 Participants	10 Participants n=3396 Participants	16 Participants n=6790 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	62 participants n=3394 Participants	59 participants n=3396 Participants	121 participants n=6790 Participants
Race/Ethnicity, Customized Asian	1139 participants n=3394 Participants	1159 participants n=3396 Participants	2298 participants n=6790 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=3394 Participants	0 participants n=3396 Participants	1 participants n=6790 Participants
Race/Ethnicity, Customized White	1642 participants n=3394 Participants	1629 participants n=3396 Participants	3271 participants n=6790 Participants
Race/Ethnicity, Customized Other	550 participants n=3394 Participants	549 participants n=3396 Participants	1099 participants n=6790 Participants
Region of Enrollment Bulgaria	183 participants n=3394 Participants	183 participants n=3396 Participants	366 participants n=6790 Participants
Region of Enrollment Colombia	613 participants n=3394 Participants	611 participants n=3396 Participants	1224 participants n=6790 Participants
Region of Enrollment Czechia	182 participants n=3394 Participants	184 participants n=3396 Participants	366 participants n=6790 Participants
Region of Enrollment Estonia	324 participants n=3394 Participants	317 participants n=3396 Participants	641 participants n=6790 Participants
Region of Enrollment Latvia	142 participants n=3394 Participants	140 participants n=3396 Participants	282 participants n=6790 Participants
Region of Enrollment Lithuania	223 participants n=3394 Participants	224 participants n=3396 Participants	447 participants n=6790 Participants
Region of Enrollment Malaysia	446 participants n=3394 Participants	453 participants n=3396 Participants	899 participants n=6790 Participants
Region of Enrollment Philippines	453 participants n=3394 Participants	457 participants n=3396 Participants	910 participants n=6790 Participants
Region of Enrollment Poland	361 participants n=3394 Participants	358 participants n=3396 Participants	719 participants n=6790 Participants
Region of Enrollment Romania	180 participants n=3394 Participants	176 participants n=3396 Participants	356 participants n=6790 Participants
Region of Enrollment Thailand	242 participants n=3394 Participants	248 participants n=3396 Participants	490 participants n=6790 Participants
Region of Enrollment Turkey	45 participants n=3394 Participants	45 participants n=3396 Participants	90 participants n=6790 Participants
Body Mass Index	27.05 kg/m^2 STANDARD_DEVIATION 4.989 • n=3391 Participants • According to data availability.	26.96 kg/m^2 STANDARD_DEVIATION 4.995 • n=3393 Participants • According to data availability.	27.00 kg/m^2 STANDARD_DEVIATION 4.992 • n=6784 Participants • According to data availability.
Previous Seasonal Influenza Vaccine in the Past 5 Years Yes	991 Participants n=3394 Participants	1021 Participants n=3396 Participants	2012 Participants n=6790 Participants
Previous Seasonal Influenza Vaccine in the Past 5 Years No	2403 Participants n=3394 Participants	2375 Participants n=3396 Participants	4778 Participants n=6790 Participants
Comorbidity Score < 50	2472 Participants n=3394 Participants	2474 Participants n=3396 Participants	4946 Participants n=6790 Participants
Comorbidity Score ≥ 50	922 Participants n=3394 Participants	922 Participants n=3396 Participants	1844 Participants n=6790 Participants
Smoking Status Smoking	325 Participants n=3394 Participants	335 Participants n=3396 Participants	660 Participants n=6790 Participants
Smoking Status Not smoking	3069 Participants n=3394 Participants	3061 Participants n=3396 Participants	6130 Participants n=6790 Participants

PRIMARY outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

Population: The Full Analysis Set (FAS) Efficacy, consisting of all randomized subjects who received a study treatment, were under observation for at least 21 days post-vaccination and provided efficacy data, was used for analysis

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on RT-PCR-confirmed Influenza Due to Any Strain Using Protocol Defined ILI Definition.	122 Number of cases	151 Number of cases

PRIMARY outcome

Timeframe: Day 1 through Day 7

Population: SOLICITED SAFETY SET = randomly selected subset of all treated subjects, with solicited safety assessments beyond 30 minutes

Safety of vaccination was assessed in terms of percentage of subjects reporting solicited local and systemic AEs up to 7 days after vaccination.

Outcome measures

Outcome measures
Measure	aQIV n=665 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=667 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Safety Endpoint: The Percentage of Subjects in the Solicited Safety Subset With Solicited Local and Systemic Adverse Events (AE) Any solicited AE	34.3 Percentage of subjects	32.2 Percentage of subjects
Safety Endpoint: The Percentage of Subjects in the Solicited Safety Subset With Solicited Local and Systemic Adverse Events (AE) Any local solicited AE	24.4 Percentage of subjects	19.6 Percentage of subjects
Safety Endpoint: The Percentage of Subjects in the Solicited Safety Subset With Solicited Local and Systemic Adverse Events (AE) Any systemic solicited AE	19.2 Percentage of subjects	16.3 Percentage of subjects
Safety Endpoint: The Percentage of Subjects in the Solicited Safety Subset With Solicited Local and Systemic Adverse Events (AE) Other	6.2 Percentage of subjects	3.9 Percentage of subjects

PRIMARY outcome

Timeframe: Within 30 days after of first occurrence RT-PCR confirmed Influenza

Population: UNSOLICITED SAFETY SET - consisting of treated subjects with unsolicited AE data was used for analysis.

Safety of vaccination was assessed in terms of percentage of subjects reporting medically attended AEs within 30 days after of first occurrence RT-PCR confirmed influenza.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Safety Endpoint: Percentage of Subjects With Medically-attended Adverse Events (MAAEs)	0.7 Percentage of subjects	0.4 Percentage of subjects

PRIMARY outcome

Timeframe: Day 1 through Day 366

Population: UNSOLICITED SAFETY SET - treated subjects with unsolicited AE data was used for analysis.

Safety of vaccination was assessed in terms of percentage of subjects reporting unsolicited AEs up to 21 days after vaccination.

Outcome measures

Outcome measures
Measure	aQIV n=3380 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3377 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Safety Endpoint: Percentages of Subjects With Any Unsolicited AE	21.5 Percentage of subjects	21.2 Percentage of subjects

PRIMARY outcome

Timeframe: Day 1 to Day 366

Population: UNSOLICITED SAFETY SET - treated subjects with unsolicited AE data was used for analysis.

Safety of vaccination was assessed in terms of percentage of subjects reporting SAEs, AEs leading to withdrawal, NOCDs, and AESIs up to 366 days after vaccination.

Outcome measures

Outcome measures
Measure	aQIV n=3380 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3377 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Safety Endpoint: Percentages of Subjects With Serious Adverse Events (SAE), AEs Leading to Withdrawal, New Onset of Chronic Disease (NOCD), and Adverse Events of Special Interest (AESI) Any AESI	0.1 Percentage of subjects	0.2 Percentage of subjects
Safety Endpoint: Percentages of Subjects With Serious Adverse Events (SAE), AEs Leading to Withdrawal, New Onset of Chronic Disease (NOCD), and Adverse Events of Special Interest (AESI) Any unsolicited SAE	7.0 Percentage of subjects	6.9 Percentage of subjects
Safety Endpoint: Percentages of Subjects With Serious Adverse Events (SAE), AEs Leading to Withdrawal, New Onset of Chronic Disease (NOCD), and Adverse Events of Special Interest (AESI) Any related SAE	0.0 Percentage of subjects	0.0 Percentage of subjects
Safety Endpoint: Percentages of Subjects With Serious Adverse Events (SAE), AEs Leading to Withdrawal, New Onset of Chronic Disease (NOCD), and Adverse Events of Special Interest (AESI) Any unsolicited AEs leading to withdrawal	1.1 Percentage of subjects	1.1 Percentage of subjects
Safety Endpoint: Percentages of Subjects With Serious Adverse Events (SAE), AEs Leading to Withdrawal, New Onset of Chronic Disease (NOCD), and Adverse Events of Special Interest (AESI) Any NOCD	9.5 Percentage of subjects	9.0 Percentage of subjects

SECONDARY outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

The secondary efficacy endpoint was the time of first-occurrence of RT-PCR-confirmed influenza due to any strain of influenza regardless of antigenic match to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary efficacy endpoint.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on RT-PCR-confirmed Influenza Due to Any Strain Using Modified CDC ILI Definition.	83 Number of cases	121 Number of cases

SECONDARY outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically matched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Antigenically Matched to the Strains Selected for the Seasonal Vaccine Using Protocol Defined ILI Definition.	7 Number of cases	14 Number of cases

SECONDARY outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically matched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Antigenically Matched to the Strains Selected for the Seasonal Vaccine Using Modified CDC ILI Definition.	5 Number of cases	13 Number of cases

SECONDARY outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza regardless of antigenic match from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Regardless of Antigenic Match Using Protocol Defined ILI Definition.	58 Number of cases	81 Number of cases

SECONDARY outcome

Timeframe: Day 7 to Day 180 after vaccination or end of influenza season, whichever is longer

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza regardless of antigenic match from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Regardless of Antigenic Match Using Modified CDC ILI Definition.	44 Number of cases	66 Number of cases

SECONDARY outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically unmatched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Antigenically Unmatched to the Strains Selected for the Seasonal Vaccine Using Protocol Defined ILI Definition.	51 Number of cases	67 Number of cases

SECONDARY outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically unmatched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Antigenically Unmatched to the Strains Selected for the Seasonal Vaccine Using Modified CDC ILI Definition.	39 Number of cases	53 Number of cases

SECONDARY outcome

Timeframe: Days 1 and 22

Population: The FAS Immunogenicity, consisting of all randomized subjects who received a study treatment, and provided immunogenicity data at Days 1 and 22, was used for analysis

The log-transformed antibody titers (GMT) at Day 1 and Day 22 were evaluated using an analysis of covariance (ANCOVA) model including factors for site/country, pre-vaccination titer, age, and comorbidity.

Outcome measures

Outcome measures
Measure	aQIV n=1324 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=332 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Immunogenicity Endpoint: Geometric Mean Hemagglutination Inhibition (HI) Titers (GMT) A/H1N1 Day 1	31.86 titer Interval 28.49 to 35.63	36.19 titer Interval 30.05 to 43.57
Immunogenicity Endpoint: Geometric Mean Hemagglutination Inhibition (HI) Titers (GMT) A/H1N1 Day 22	438.79 titer Interval 403.82 to 476.79	29.43 titer Interval 25.63 to 33.79
Immunogenicity Endpoint: Geometric Mean Hemagglutination Inhibition (HI) Titers (GMT) A/H3N2 Day 1	28.31 titer Interval 25.43 to 31.52	27.56 titer Interval 23.05 to 32.95
Immunogenicity Endpoint: Geometric Mean Hemagglutination Inhibition (HI) Titers (GMT) A/H3N2 Day 22	572.80 titer Interval 525.08 to 624.86	27.06 titer Interval 23.42 to 31.25
Immunogenicity Endpoint: Geometric Mean Hemagglutination Inhibition (HI) Titers (GMT) B/Yamagata Day 1	13.83 titer Interval 12.81 to 14.92	13.13 titer Interval 11.57 to 14.91
Immunogenicity Endpoint: Geometric Mean Hemagglutination Inhibition (HI) Titers (GMT) B/Yamagata Day 22	86.77 titer Interval 79.94 to 94.19	12.49 titer Interval 10.9 to 14.3
Immunogenicity Endpoint: Geometric Mean Hemagglutination Inhibition (HI) Titers (GMT) B/Victoria Day 1	12.77 titer Interval 11.81 to 13.81	12.26 titer Interval 10.77 to 13.96
Immunogenicity Endpoint: Geometric Mean Hemagglutination Inhibition (HI) Titers (GMT) B/Victoria Day 22	104.26 titer Interval 95.77 to 113.5	11.25 titer Interval 9.77 to 12.94

SECONDARY outcome

Timeframe: Day 22/Day 1

Population: The FAS Immunogenicity, consisting of all randomized subjects who received a study treatment, and provided immunogenicity data at Days 1 and 22, was used for analysis GMR B/Vic: 0.94 to )

The GMR was assessed as the postvaccination HI titer divided by the prevaccination HI titer (Day 22/Day 1).

Outcome measures

Outcome measures
Measure	aQIV n=1324 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=332 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) of Post-vaccination HI Titer Over the Pre-vaccination HI Titer A/H1N1	14.17 ratio Interval 12.84 to 15.64	0.89 ratio Interval 0.76 to 1.05
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) of Post-vaccination HI Titer Over the Pre-vaccination HI Titer A/H3N2	22.65 ratio Interval 20.48 to 25.06	1.08 ratio Interval 0.92 to 1.28
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) of Post-vaccination HI Titer Over the Pre-vaccination HI Titer B/Yamagata	6.58 ratio Interval 6.02 to 7.2	0.97 ratio Interval 0.84 to 1.13
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) of Post-vaccination HI Titer Over the Pre-vaccination HI Titer B/Victoria	8.59 ratio Interval 7.83 to 9.42	0.94 ratio Interval 0.81 to 1.1

SECONDARY outcome

Timeframe: Day 22

Population: The FAS Immunogenicity, consisting of all randomized subjects who received a study treatment, and provided immunogenicity data at Days 1 and 22, was used for analysis

The percentage of subjects vaccinated with aQIV with a HI antibody titers ≥1:40 was assessed for each of the 4 strains Assessment criteria was considered fulfilled if the lower bound of the two-sided 95% CI for percent of subjects with HI antibody titer ≥1:40 met or exceeded 60% at Day 22.

Outcome measures

Outcome measures
Measure	aQIV n=1324 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=332 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Immunogenicity Endpoint: Percentages of Subjects With an HI Titer ≥1:40 A/H1N1	96.2 Percentage of subjects Interval 95.05 to 97.18	46.7 Percentage of subjects Interval 41.18 to 52.21
Immunogenicity Endpoint: Percentages of Subjects With an HI Titer ≥1:40 A/H3N2	95.6 Percentage of subjects Interval 94.37 to 96.66	41.7 Percentage of subjects Interval 36.32 to 47.21
Immunogenicity Endpoint: Percentages of Subjects With an HI Titer ≥1:40 B/Yamagata	79.2 Percentage of subjects Interval 76.95 to 81.4	21.5 Percentage of subjects Interval 17.2 to 26.35
Immunogenicity Endpoint: Percentages of Subjects With an HI Titer ≥1:40 B/Victoria	81.6 Percentage of subjects Interval 79.39 to 83.65	18.4 Percentage of subjects Interval 14.4 to 23.03

SECONDARY outcome

Timeframe: Day 22

Population: analysis.

The percentage of subjects achieving SCR at Day 22 was assessed for each of the 4 strains. SCR is defined as HI titer ≥1:40 for subjects seronegative at baseline (HI titer \<1:10) or a minimum 4-fold increase in HI titer for subjects seropositive at baseline (HI titer ≥1:10) on Day 22. Assessment criteria was considered fulfilled if the lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody SCR met or exceeded 30% at Day 22.

Outcome measures

Outcome measures
Measure	aQIV n=1324 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=332 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Immunogenicity Endpoint: Percentages of Subjects Who Achieved Seroconversion (SCR) A/H1N1	78.0 Percentage of subjects Interval 75.66 to 80.21	2.1 Percentage of subjects Interval 0.85 to 4.31
Immunogenicity Endpoint: Percentages of Subjects Who Achieved Seroconversion (SCR) A/H3N2	84.6 Percentage of subjects Interval 82.52 to 86.49	3.9 Percentage of subjects Interval 2.11 to 6.62
Immunogenicity Endpoint: Percentages of Subjects Who Achieved Seroconversion (SCR) B/Yamagata	60.8 Percentage of subjects Interval 58.06 to 63.41	3.6 Percentage of subjects Interval 1.89 to 6.27
Immunogenicity Endpoint: Percentages of Subjects Who Achieved Seroconversion (SCR) B/Victoria	65.5 Percentage of subjects Interval 62.88 to 68.1	2.1 Percentage of subjects Interval 0.85 to 4.31

POST_HOC outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

The post-hoc efficacy endpoint was the time of first-occurrence of RT-PCR-confirmed influenza due to any strain of influenza regardless of antigenic match to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using WHO ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the post-hoc efficacy endpoint

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on RT-PCR-confirmed Influenza Due to Any Strain Using WHO ILI Definition.	39 Number of cases	79 Number of cases

POST_HOC outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

The post-hoc efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically matched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using WHO ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the post-hoc endpoint.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Antigenically Matched to the Strains Selected for the Seasonal Vaccine Using WHO ILI Definition.	2 Number of cases	8 Number of cases

POST_HOC outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

The post-hoc efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza regardless of antigenic match from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using WHO ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the post-hoc endpoint.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Regardless of Antigenic Match Using WHO ILI Definition	18 Number of cases	45 Number of cases

POST_HOC outcome

Timeframe: Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

The post-hoc efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically unmatched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using WHO ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the post-hoc endpoint.

Outcome measures

Outcome measures
Measure	aQIV n=3368 Participants Subjects received one dose of aQIV vaccine	Non-influenza Comparator Vaccine n=3372 Participants Subjects received one dose of non-influenza comparator vaccine (Boostrix)
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Antigenically Unmatched to the Strains Selected for the Seasonal Vaccine Using WHO ILI Definition.	16 Number of cases	37 Number of cases

Adverse Events

aQIV

Serious events: 238 serious events

Other events: 227 other events

Deaths: 33 deaths

Non-influenza Comparator Vaccine

Serious events: 234 serious events

Other events: 218 other events

Deaths: 34 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	aQIV n=665 participants at risk；n=3380 participants at risk A single dose of approximately 0.5 mL of aQIV was administered on Day 1 (NH 2016/17, SH 2017).	Non-influenza Comparator Vaccine n=667 participants at risk；n=3377 participants at risk Non-influenza Comparator Vaccine / A single dose of approximately 0.5 mL dose of Boostrix was administered on Day 1 (NH 2016/17, SH 2017). (Boostrix = Non-influenza comparator vaccine)
General disorders Pain	41.9% 106/253 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.	39.9% 77/193 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.
General disorders Erythema	31.7% 69/218 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.	35.8% 69/193 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.
General disorders Fatigue	36.6% 67/183 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.	36.4% 56/154 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.
General disorders Headache	43.5% 70/161 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.	35.3% 53/150 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.
General disorders Induration	32.3% 65/201 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.	26.4% 51/193 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.
General disorders Arthralgia	34.1% 47/138 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.	32.6% 42/129 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.
General disorders Myalgia	36.6% 49/134 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.	35.8% 39/109 • Solicited AEs: Day 1 to Day 7; SAEs: Day 1 to Day 366; and Unsolicited AEs: Day 1 to Day 22.

Additional Information

Seqirus Clinical Trial Disclosure Manager

Seqirus

Phone: 1-855-358-8966

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any formal publication of the study in which contribution of Seqirus personnel exceeded that of conventional monitoring will be considered as a joint publication by the investigator and the appropriate Seqirus personnel. Seqirus must be notified of any intent to publish data collected from the study and prior approval from Seqirus must be obtained prior to submission for publication.
Publication restrictions are in place

Restriction type: OTHER