Trial Outcomes & Findings for Study to Evaluate the Consistency of Three Consecutive Production Lots of Influenza Vaccine in Healthy Subjects 18 to 49 Years Old (NCT NCT00617851)

Last Updated: 2012-05-08

Results Overview

The immunologic equivalence of three consecutive production lots of the influenza virus vaccine was measured in terms of GMTs for all vaccine influenza strains.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1507 participants

Primary outcome timeframe

21 days after vaccination

Results posted on

2012-05-08

Participant Flow

Participants were recruited at 1 Center along with a satellite center in the Dominican Republic.

Participant milestones

Participant milestones
Measure	Influenza Virus Vaccine (Lot A) One injection of lot A of the investigational influeza virus vaccine	Influenza Virus Vaccine (Lot B) One injection of lot B of the investigational influeza virus vaccine	Influenza Virus Vaccine (Lot C) One injection of lot C of the investigational influeza virus vaccine	Comparator Influenza Vaccine One injection of the comparator influeza virus vaccine
Overall Study STARTED	430	431	429	217
Overall Study COMPLETED	383	391	384	192
Overall Study NOT COMPLETED	47	40	45	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Influenza Virus Vaccine (Lot A) One injection of lot A of the investigational influeza virus vaccine	Influenza Virus Vaccine (Lot B) One injection of lot B of the investigational influeza virus vaccine	Influenza Virus Vaccine (Lot C) One injection of lot C of the investigational influeza virus vaccine	Comparator Influenza Vaccine One injection of the comparator influeza virus vaccine
Overall Study Death	0	0	0	1
Overall Study Withdrawal by Subject	14	7	12	4
Overall Study Lost to Follow-up	27	29	31	19
Overall Study Inappropriate Enrollment	5	4	1	1
Overall Study Unable to classify	1	0	1	0

Baseline Characteristics

Study to Evaluate the Consistency of Three Consecutive Production Lots of Influenza Vaccine in Healthy Subjects 18 to 49 Years Old

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Influenza Virus Vaccine (Lot A) n=430 Participants One injection of lot A of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot B) n=431 Participants One injection of lot B of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot C) n=429 Participants One injection of lot C of the investigational influenza virus vaccine	Comparator Influenza Vaccine n=217 Participants One injection of the comparator influenza virus vaccine	Total n=1507 Participants Total of all reporting groups
Age Continuous	31.1 years STANDARD_DEVIATION 8.8 • n=5 Participants	31.2 years STANDARD_DEVIATION 8.6 • n=7 Participants	31.3 years STANDARD_DEVIATION 8.9 • n=5 Participants	31.3 years STANDARD_DEVIATION 8.7 • n=4 Participants	31.2 years STANDARD_DEVIATION 8.7 • n=21 Participants
Sex: Female, Male Female	309 Participants n=5 Participants	306 Participants n=7 Participants	291 Participants n=5 Participants	154 Participants n=4 Participants	1060 Participants n=21 Participants
Sex: Female, Male Male	121 Participants n=5 Participants	125 Participants n=7 Participants	138 Participants n=5 Participants	63 Participants n=4 Participants	447 Participants n=21 Participants
Race/Ethnicity, Customized Arabic	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Black	7 participants n=5 Participants	11 participants n=7 Participants	9 participants n=5 Participants	3 participants n=4 Participants	30 participants n=21 Participants
Race/Ethnicity, Customized Caucasian	1 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	4 participants n=21 Participants
Race/Ethnicity, Customized Hispanic	421 participants n=5 Participants	418 participants n=7 Participants	418 participants n=5 Participants	214 participants n=4 Participants	1471 participants n=21 Participants
Race/Ethnicity, Customized Native Amer/Alaskan	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants

PRIMARY outcome

Timeframe: 21 days after vaccination

Population: The analysis was performed on the per-protocol population, defined as all subjects enrolled who: * received all the relevant doses of vaccine correctly, and * provided evaluable serum samples at the relevant time points, and * had no major protocol deviation

The immunologic equivalence of three consecutive production lots of the influenza virus vaccine was measured in terms of GMTs for all vaccine influenza strains.

Outcome measures

Outcome measures
Measure	Influenza Virus Vaccine (Lot A) n=393 Participants One injection of lot A of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot B) n=396 Participants One injection of lot B of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot C) n=393 Participants One injection of lot C of the investigational influenza virus vaccine	Comparator Influenza Vaccine (Strain A/H1N1) One injection of the comparator influenza virus vaccine-Strain A/H1N1	Comparator Influenza Vaccine (Strain A/H3N2) One injection of the comparator influenza virus vaccine-Strain A/H3N2	Comparator Influenza Vaccine (Strain B) One injection of the comparator influenza virus vaccine-Strain B
Geometric Mean Titers (GMTs), by Vaccine Lots Strain A/H1N1	566 Titers Interval 503.0 to 637.0	518 Titers Interval 461.0 to 582.0	513 Titers Interval 454.0 to 581.0	—	—	—
Geometric Mean Titers (GMTs), by Vaccine Lots Strain A/H3N2	352 Titers Interval 318.0 to 390.0	313 Titers Interval 282.0 to 348.0	359 Titers Interval 326.0 to 396.0	—	—	—
Geometric Mean Titers (GMTs), by Vaccine Lots Strain B	99 Titers Interval 89.0 to 110.0	93 Titers Interval 84.0 to 104.0	86 Titers Interval 77.0 to 96.0	—	—	—

SECONDARY outcome

Timeframe: 21 days after vaccination

The GMTs and 95% CIs were calculated for each of the vaccine group (three consecutive production lots pooled for the investigational influenza virus vaccine and comparator) and for each strain.

Outcome measures

Outcome measures
Measure	Influenza Virus Vaccine (Lot A) n=1182 Participants One injection of lot A of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot B) n=1182 Participants One injection of lot B of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot C) n=1182 Participants One injection of lot C of the investigational influenza virus vaccine	Comparator Influenza Vaccine (Strain A/H1N1) n=194 Participants One injection of the comparator influenza virus vaccine-Strain A/H1N1	Comparator Influenza Vaccine (Strain A/H3N2) n=194 Participants One injection of the comparator influenza virus vaccine-Strain A/H3N2	Comparator Influenza Vaccine (Strain B) n=194 Participants One injection of the comparator influenza virus vaccine-Strain B
Geometric Mean Titers (GMTs), by Vaccine Group and Strain	532 titers Interval 497.0 to 570.0	341 titers Interval 321.0 to 361.0	93 titers Interval 87.0 to 98.0	799 titers Interval 666.0 to 957.0	683 titers Interval 590.0 to 790.0	99 titers Interval 85.0 to 115.0

SECONDARY outcome

Timeframe: 7 days after vaccination

Population: The analysis was performed on the safety population, defined as all subjects who provided post-baseline safety data.

Solicited local and systemic reactions were assessed after vaccination for the two vaccines (three consecutive production lots pooled for the investigational influenza virus vaccine and comparator) and for each of the three consecutive production lots of the investigational influenza virus vaccine.

Outcome measures

Outcome measures
Measure	Influenza Virus Vaccine (Lot A) n=403 Participants One injection of lot A of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot B) n=404 Participants One injection of lot B of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot C) n=402 Participants One injection of lot C of the investigational influenza virus vaccine	Comparator Influenza Vaccine (Strain A/H1N1) n=1209 Participants One injection of the comparator influenza virus vaccine-Strain A/H1N1	Comparator Influenza Vaccine (Strain A/H3N2) n=202 Participants One injection of the comparator influenza virus vaccine-Strain A/H3N2	Comparator Influenza Vaccine (Strain B) One injection of the comparator influenza virus vaccine-Strain B
Number of Subjects Reporting Solicited Local and Systemic Symptoms Any Local Reaction	114 Participants	96 Participants	100 Participants	310 Participants	54 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Erythema (mm)	15 Participants	12 Participants	17 Participants	44 Participants	9 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Induration (mm)	19 Participants	19 Participants	24 Participants	62 Participants	12 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Swelling (mm)	15 Participants	24 Participants	14 Participants	53 Participants	14 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Ecchymosis (mm)	14 Participants	13 Participants	14 Participants	41 Participants	9 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Pain	96 Participants	87 Participants	85 Participants	268 Participants	44 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Any Systemic Reaction	148 Participants	148 Participants	147 Participants	443 Participants	76 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Chills	30 Participants	28 Participants	29 Participants	87 Participants	17 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Malaise	45 Participants	52 Participants	47 Participants	144 Participants	25 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Myalgia	73 Participants	75 Participants	65 Participants	213 Participants	40 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Arthralgia	19 Participants	25 Participants	25 Participants	69 Participants	14 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Headache	100 Participants	94 Participants	98 Participants	292 Participants	48 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Sweating	14 Participants	14 Participants	20 Participants	48 Participants	9 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Fatigue	29 Participants	41 Participants	41 Participants	111 Participants	16 Participants	—
Number of Subjects Reporting Solicited Local and Systemic Symptoms Fever (≥38C)	17 Participants	24 Participants	13 Participants	54 Participants	7 Participants	—

SECONDARY outcome

Timeframe: 3 weeks after vaccination

Population: The analysis was performed on the safety population, defined as all subjects who provided post-baseline safety data.

Number of subjects reporting at least one unsolicited adverse event, regardless of the assessement of relatedness to the study vaccines (each of the three consecutive production lots of the investigational influenza virus vaccine, the pooled influenza virus vaccine, and the comparator influenza vaccine).

Outcome measures

Outcome measures
Measure	Influenza Virus Vaccine (Lot A) n=1209 Participants One injection of lot A of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot B) n=202 Participants One injection of lot B of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot C) n=403 Participants One injection of lot C of the investigational influenza virus vaccine	Comparator Influenza Vaccine (Strain A/H1N1) n=404 Participants One injection of the comparator influenza virus vaccine-Strain A/H1N1	Comparator Influenza Vaccine (Strain A/H3N2) n=402 Participants One injection of the comparator influenza virus vaccine-Strain A/H3N2	Comparator Influenza Vaccine (Strain B) One injection of the comparator influenza virus vaccine-Strain B
Number of Subjects With at Least One Unsolicited Adverse Event	189 participants	33 participants	56 participants	68 participants	65 participants	—

SECONDARY outcome

Timeframe: 21 days after vaccination

The percentage of subjects who were seroprotected and seroconverted were considered statistically compliant with the stated CBER guidance criteria if: * the lower bound of the two-sided 95% CI for the percentage of seroprotected subjects (HI antibody titer ≥1:40) met or exceeded 70%. * the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion rate (prevaccination HI\<10/ postvaccination HI ≥40 or at least a fourfold increase in titer from non-negative prevaccination serum \[HI≥10\]), for HI antibody met or exceeded 40%.

Outcome measures

Outcome measures
Measure	Influenza Virus Vaccine (Lot A) n=393 Participants One injection of lot A of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot B) n=396 Participants One injection of lot B of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot C) n=393 Participants One injection of lot C of the investigational influenza virus vaccine	Comparator Influenza Vaccine (Strain A/H1N1) n=1182 Participants One injection of the comparator influenza virus vaccine-Strain A/H1N1	Comparator Influenza Vaccine (Strain A/H3N2) n=194 Participants One injection of the comparator influenza virus vaccine-Strain A/H3N2	Comparator Influenza Vaccine (Strain B) One injection of the comparator influenza virus vaccine-Strain B
Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) Seroprotection (HI titer => 40)	98 percentages of participants Interval 96.0 to 99.0	99 percentages of participants Interval 97.0 to 100.0	98 percentages of participants Interval 96.0 to 99.0	98 percentages of participants Interval 97.0 to 99.0	98 percentages of participants Interval 95.0 to 99.0	—
Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) Seroconversion	95 percentages of participants Interval 92.0 to 97.0	94 percentages of participants Interval 92.0 to 96.0	93 percentages of participants Interval 90.0 to 95.0	94 percentages of participants Interval 93.0 to 95.0	96 percentages of participants Interval 92.0 to 98.0	—

SECONDARY outcome

Timeframe: 21 days after vaccination

Outcome measures

Outcome measures
Measure	Influenza Virus Vaccine (Lot A) n=393 Participants One injection of lot A of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot B) n=396 Participants One injection of lot B of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot C) n=393 Participants One injection of lot C of the investigational influenza virus vaccine	Comparator Influenza Vaccine (Strain A/H1N1) n=1182 Participants One injection of the comparator influenza virus vaccine-Strain A/H1N1	Comparator Influenza Vaccine (Strain A/H3N2) n=194 Participants One injection of the comparator influenza virus vaccine-Strain A/H3N2	Comparator Influenza Vaccine (Strain B) One injection of the comparator influenza virus vaccine-Strain B
Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) Seroprotection (HI titer ≥40)	99 percentages of participants Interval 98.0 to 100.0	98 percentages of participants Interval 97.0 to 99.0	99 percentages of participants Interval 98.0 to 100.0	99 percentages of participants Interval 98.0 to 100.0	99 percentages of participants Interval 97.0 to 100.0	—
Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) Seroconversion	70 percentages of participants Interval 65.0 to 74.0	64 percentages of participants Interval 59.0 to 69.0	68 percentages of participants Interval 63.0 to 72.0	67 percentages of participants Interval 65.0 to 70.0	84 percentages of participants Interval 78.0 to 88.0	—

SECONDARY outcome

Timeframe: 21 days after vaccination

Outcome measures

Outcome measures
Measure	Influenza Virus Vaccine (Lot A) n=393 Participants One injection of lot A of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot B) n=396 Participants One injection of lot B of the investigational influenza virus vaccine	Influenza Virus Vaccine (Lot C) n=393 Participants One injection of lot C of the investigational influenza virus vaccine	Comparator Influenza Vaccine (Strain A/H1N1) n=1182 Participants One injection of the comparator influenza virus vaccine-Strain A/H1N1	Comparator Influenza Vaccine (Strain A/H3N2) n=194 Participants One injection of the comparator influenza virus vaccine-Strain A/H3N2	Comparator Influenza Vaccine (Strain B) One injection of the comparator influenza virus vaccine-Strain B
Percentage of Subjects With Seroprotection and Seroconversion (Strain B) Seroprotection (HI titer ≥40)	88 percentages of participants Interval 85.0 to 91.0	88 percentages of participants Interval 85.0 to 91.0	84 percentages of participants Interval 80.0 to 87.0	87 percentages of participants Interval 85.0 to 89.0	90 percentages of participants Interval 85.0 to 94.0	—
Percentage of Subjects With Seroprotection and Seroconversion (Strain B) Seroconversion	85 percentages of participants Interval 81.0 to 88.0	86 percentages of participants Interval 82.0 to 89.0	81 percentages of participants Interval 76.0 to 84.0	84 percentages of participants Interval 82.0 to 86.0	86 percentages of participants Interval 80.0 to 90.0	—

Adverse Events

Influenza Virus Vaccine (Pooled)

Serious events: 11 serious events

Other events: 0 other events

Deaths: 0 deaths

Comparator Influenza Vaccine

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Influenza Virus Vaccine (Pooled) n=1209 participants at risk One injection of the investigational influenza virus vaccine (all lots pooled)	Comparator Influenza Vaccine n=202 participants at risk One injection of the comparator influenza virus vaccine
Surgical and medical procedures Abortion Induced	0.17% 2/1209 • Number of events 2 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.00% 0/202 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Pregnancy, puerperium and perinatal conditions Abortion Spontaneous	0.25% 3/1209 • Number of events 3 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.50% 1/202 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Infections and infestations Abscess Limb	0.00% 0/1209 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.50% 1/202 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/1209 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.50% 1/202 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Hepatobiliary disorders Cholecystitis	0.00% 0/1209 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.50% 1/202 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Hepatobiliary disorders Cholelithiasis	0.08% 1/1209 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.00% 0/202 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroadenoma of Breast	0.00% 0/1209 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.50% 1/202 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Injury, poisoning and procedural complications Fractured Coccyx	0.08% 1/1209 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.00% 0/202 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Infections and infestations Gas Gangrene	0.00% 0/1209 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.50% 1/202 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Endocrine disorders Goitre	0.08% 1/1209 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.00% 0/202 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Nervous system disorders Headache	0.08% 1/1209 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.00% 0/202 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Surgical and medical procedures Hysterectomy	0.08% 1/1209 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.00% 0/202 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Nervous system disorders Intracranial Aneurysm	0.08% 1/1209 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.00% 0/202 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
General disorders Multi-Organ Failure	0.00% 0/1209 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.50% 1/202 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
General disorders Pyrexia	0.08% 1/1209 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.00% 0/202 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Injury, poisoning and procedural complications Road Traffic Accident	0.17% 2/1209 • Number of events 2 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.00% 0/202 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Infections and infestations Sepsis	0.00% 0/1209 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.50% 1/202 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	0.08% 1/1209 • Number of events 1 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.	0.00% 0/202 • Serious adverse events were collected for 6 months after vaccination. All adverse events were collected for 21 days after vaccination. Of the 1507 subjects enrolled and randomized in this study, 96 were not included in the safety analysis (82 in the pooled influenza virus vaccine group and 14 in the comparator influenza vaccine group) as they had no safety data. These subjects have been excluded from the safety analysis to avoid underestimating the incidence rates of reactions.