Study to Evaluate the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine (GSK2282512A) Compared to Fluzone® Quadrivalent in Children 6 to 35 Months of Age

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02242643
• Collaborator: (none)
• Enrollment: 2,432
• Locations: 66
• Arms: 2
• Duration (Months): 8.7
• Patients Per Site: 36.8
• Patients Per Site Per Month: 4.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the immunogenicity and safety of GSK Biologicals' quadrivalent influenza vaccine (GSK2282512A) compared to Sanofi Pasteur's Fluzone® Quadrivalent in children 6 to 35 months of age.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: FluLaval™ Quadrivalent; Biological: Fluzone® Quadrivalent	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2432 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety Study of GSK Biologicals' Quadrivalent Influenza Vaccine (GSK2282512A) Compared to Fluzone® Quadrivalent in Children 6 to 35 Months of Age
• Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Mar 16, 2015
• Actual Study Completion Date: Jun 23, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FluLaval™ Quadrivalent Group Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Biological: FluLaval™ Quadrivalent; 1 or 2 doses administered intramusculary (IM) in deltoid region of non-dominant arm (for subjects ≥12 months of age) or anterolateral region of left thigh (for subjects <12 months of age) on Day 0 (primed subjects) and on Day 0 and Day 28 (unprimed subjects), respectively; Other Names: FLU Q-QIV (GSK2282512A)
Active Comparator: Fluzone® Quadrivalent Group Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Biological: Fluzone® Quadrivalent; 1 or 2 doses administered IM in deltoid region of non-dominant arm (for subjects ≥12 months of age) or anterolateral region of left thigh (for subjects <12 months of age) on Day 0 (primed subjects) and on Day 0 and Day 28 (unprimed subjects), respectively; Other Names: F-QIV

Outcome Measures

Primary Outcome Measures

1. Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 4 Vaccine Influenza Strains [28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)]

   Antibody titers were expressed as Seroconversion rate (SCR) and SCR difference. SCR was defined as the proportion of vaccinees who had either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), B/Massachusetts/2/2012 (Yamagata) and B/Brisbane/60/2008 (Victoria).

2. Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Vaccine Strains. [At 28 days after the last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)]

   HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios. The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria).

Secondary Outcome Measures

1. Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) [At Day 0 and 28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)]

   Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), B/Massachusetts/2/2012 (Yamagata) and B/Brisbane/60/2008 (Victoria).

2. Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) [At Day 0 and 28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)]

   A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40. The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria).

3. Number of Seroconverted Subjects for Anti-HA Antibodies Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) [28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)]

   A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria).

4. Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) [28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)]

   MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria).

5. Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) [During a 7-day (Day 0 - Day 6) follow-up period after each vaccination]

   Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity and all subjects reporting 'Yes' for solicited symptom occurred but with missing values for at least one day during the solicited period. Grade 3 pain = Cried when limb is moved/spontaneously painful. Grade 3 redness and swelling was greater than 100 millimeters (mm) i.e. >100mm.

6. Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) [During the 7-day (Days 0-6) follow-up period after each vaccination]

   Solicited general symptoms assessed were drowsiness, irritability/fussiness, loss of appetite and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 irritability/fussiness was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Grade 3 drowsiness was defined as drowsiness that prevented normal activity. Any fever was defined as subjects with a documented temperature of greater than or equal to (≥) 38°C/100.4°F by any route and all subjects reporting temperature less than (< )38°C but with missing values for at least one day during the solicited period. Grade 3 fever was defined as temperature greater than (>) 39.0°C.

7. Duration of Solicited Local and General AEs, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) [During the 7-day (Days 0-6) follow-up period after each vaccination.]

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

8. Number of Subjects Reporting Any Fever Following Each Dose and Across Doses. [During a 2-day (Days 0-1) follow-up period after each vaccination]

   Any Fever = all subjects with a documented temperature of ≥38.0°C /100.4°F by axillary route and all subjects reporting temperature < 38.0°C but with missing values for at least one day during the solicited period. Grade 3 fever was defined as temperature greater than (>) 39.0°C.

9. Number of Subjects Reporting the Occurrence of All Medically Attended Events (MAEs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed). [During the entire study period (Days 0 -180)]

   MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s).

10. Number of Subjects Reporting the Occurrence of Any and Related Potential Immune-Mediated Disease (pIMDs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) [During the entire study period (Days 0 -180)]

    pIMDs are a subset of adverse events (AEs) that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Related = symptom assed by the investigator as causally related to the study vaccination.

11. Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) [During a 28-day (Days 0-27 for primed and unprimed subjects and Days 28-56 for unprimed subjects) post-vaccination period]

    An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 unsolicited AE was defined as an event that prevented normal activity. Related unsolicited AE was defined as an event assessed by the investigator to be causally related to the study vaccination.

12. Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed) [During the entire study period (Days 0 -180)]

    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. Related = symptom assessed by the investigator as causally related to the study vaccination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 35 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply with the requirements of the protocol.

• A male or female between, and including, 6 and 35 months of age at the time of the first vaccination.

• Written informed consent obtained from the parent(s)/LAR(s) of the subject.

• Subjects in stable health as determined by investigator's clinical examination and assessment of subject's medical history.

• Subjects are eligible regardless of history of administration of influenza vaccine in a previous season.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. Routine registered childhood vaccinations are permitted.

• Child in care.

• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will mean a dose equivalent to either > 2 mg/kg/day of body weight, or to ≥ 20 mg/day of prednisone for persons who weigh ≥ 10 kg, when administered for more than 2 weeks. Inhaled and topical steroids are allowed.

• Prior receipt of any seasonal or pandemic influenza vaccine (registered or investigational) within six months preceding the first dose of study vaccine, or planned use during the study period.

• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

• History of Guillain-Barré syndrome within six weeks of receipt of prior influenza vaccine.

• Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.

• Acute disease and/or fever at the time of enrolment.

• Fever is defined as temperature ≥ 38.0°C/100.4°F by any route.

• Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.

• Any significant disorder of coagulation or treatment with warfarin derivatives or heparin.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

• Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35235
2	GSK Investigational Site	Dothan	Alabama	United States	36305
3	GSK Investigational Site	Tucson	Arizona	United States	85741
4	GSK Investigational Site	Jonesboro	Arkansas	United States	72401
5	GSK Investigational Site	Anaheim	California	United States	92804
6	GSK Investigational Site	Chino	California	United States	91710
7	GSK Investigational Site	Daly City	California	United States	94015
8	GSK Investigational Site	Fresno	California	United States	93726
9	GSK Investigational Site	Hayward	California	United States	94545
10	GSK Investigational Site	Oakland	California	United States	94611
11	GSK Investigational Site	Paramount	California	United States	90723
12	GSK Investigational Site	Pleasanton	California	United States	94588
13	GSK Investigational Site	Sacramento	California	United States	95815
14	GSK Investigational Site	Sacramento	California	United States	95822
15	GSK Investigational Site	Sacramento	California	United States	95823
16	GSK Investigational Site	Santa Clara	California	United States	95051
17	GSK Investigational Site	Walnut Creek	California	United States	94596
18	GSK Investigational Site	West Covina	California	United States	91790
19	GSK Investigational Site	Colorado Springs	Colorado	United States	80920
20	GSK Investigational Site	Colorado Springs	Colorado	United States	80922
21	GSK Investigational Site	Lake Mary	Florida	United States	32736
22	GSK Investigational Site	Miami Lakes	Florida	United States	33014
23	GSK Investigational Site	Nampa	Idaho	United States	83686
24	GSK Investigational Site	Augusta	Kansas	United States	67010
25	GSK Investigational Site	Newton	Kansas	United States	67114
26	GSK Investigational Site	Topeka	Kansas	United States	66604
27	GSK Investigational Site	Wichita	Kansas	United States	67207
28	GSK Investigational Site	Louisville	Kentucky	United States	40291
29	GSK Investigational Site	Bossier City	Louisiana	United States	71111
30	GSK Investigational Site	Metairie	Louisiana	United States	70006
31	GSK Investigational Site	Columbia	Maryland	United States	21045
32	GSK Investigational Site	Woburn	Massachusetts	United States	01801
33	GSK Investigational Site	Saint Louis	Missouri	United States	63141
34	GSK Investigational Site	Lincoln	Nebraska	United States	68504
35	GSK Investigational Site	Lincoln	Nebraska	United States	68505
36	GSK Investigational Site	Lincoln	Nebraska	United States	68516
37	GSK Investigational Site	Las Vegas	Nevada	United States	89104
38	GSK Investigational Site	Binghamton	New York	United States	13901
39	GSK Investigational Site	Syracuse	New York	United States	13210
40	GSK Investigational Site	Raleigh	North Carolina	United States	27609
41	GSK Investigational Site	Beavercreek	Ohio	United States	45431
42	GSK Investigational Site	Cleveland	Ohio	United States	44121
43	GSK Investigational Site	Dayton	Ohio	United States	45406
44	GSK Investigational Site	Erie	Pennsylvania	United States	16505
45	GSK Investigational Site	Hermitage	Pennsylvania	United States	16148
46	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19107
47	GSK Investigational Site	Sellersville	Pennsylvania	United States	18960
48	GSK Investigational Site	Charleston	South Carolina	United States	29406
49	GSK Investigational Site	Cheraw	South Carolina	United States	29520
50	GSK Investigational Site	Kingsport	Tennessee	United States	37660
51	GSK Investigational Site	Austin	Texas	United States	78705
52	GSK Investigational Site	Fort Worth	Texas	United States	76135
53	GSK Investigational Site	Galveston	Texas	United States	77555-1119
54	GSK Investigational Site	Tomball	Texas	United States	77375
55	GSK Investigational Site	Layton	Utah	United States	84041
56	GSK Investigational Site	Orem	Utah	United States	84057
57	GSK Investigational Site	Payson	Utah	United States	84651
58	GSK Investigational Site	Provo	Utah	United States	84604
59	GSK Investigational Site	Roy	Utah	United States	84067
60	GSK Investigational Site	Salt Lake City	Utah	United States	84124
61	GSK Investigational Site	South Jordan	Utah	United States	84095
62	GSK Investigational Site	Charlottesville	Virginia	United States	22902
63	GSK Investigational Site	Ellensburg	Washington	United States	98926
64	GSK Investigational Site	Marshfield	Wisconsin	United States	54449
65	GSK Investigational Site	San Nicolas de los Garza	Nuevo León	Mexico	66480
66	GSK Investigational Site	Mexico city		Mexico	04530

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02242643
• Other Study ID Numbers: 201234
• First Posted: Sep 17, 2014
• Last Update Posted: Sep 7, 2018
• Last Verified: Oct 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Fluzone Quadrivalent; Comparator; Children; Seasonal influenza; Safety; Immunogenicity
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	Primed subjects:Received atleast 2 doses of seasonal influenza vaccine since 1 July 2010 or atleast 1 dose of the 2013-2014 seasonal influenza vaccine. Unprimed subjects:Did not receive any seasonal influenza vaccine or received only 1 dose of seasonal influenza vaccine since 1 July 2010, but did not receive any 2013-2014 seasonal influenza vaccine
Pre-assignment Detail	Data has been analyzed in sub-groups by age: 6-17 months and 18-35 months and by priming status. 6 subjects were allocated subject numbers but did not receive the study vaccine dose and for 2 subjects the blood samples were withdrawn but they did not participate in the study due to screening failure.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Period Title: Overall Study
STARTED	1207	1217
COMPLETED	1132	1139
NOT COMPLETED	75	78

Baseline Characteristics

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group	Total
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Total of all reporting groups
Overall Participants	1207	1217	2424
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	19.4 (8.7)	19.5 (8.9)	19.45 (8.80)
Sex: Female, Male (Count of Participants)
Female	547 45.3%	582 47.8%	1129 46.6%
Male	660 54.7%	635 52.2%	1295 53.4%

Outcome Measures

1. Primary Outcome

Title	Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 4 Vaccine Influenza Strains
Description	Antibody titers were expressed as Seroconversion rate (SCR) and SCR difference. SCR was defined as the proportion of vaccinees who had either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), B/Massachusetts/2/2012 (Yamagata) and B/Brisbane/60/2008 (Victoria).
Time Frame	28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	974	980
H1N1 [N=972,980]	716	660
H3N2 [N=972,980]	740	680
Victoria [N=973,980]	631	475
Yamagata [N=974,980]	833	723

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FluLaval™ Quadrivalent Group, Fluzone® Quadrivalent Group
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority criterion: The upper limit of the two-sided 95% CI for the difference in SCR (Fluzone® Quadrivalent Group minus FluLaval™ Quadrivalent Group) did not exceed 10% for each of the four strains.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Seroconversion rate (SCR) Difference (%)
	Estimated Value	-6.32
	Confidence Interval	(2-Sided) 95%; -10.34 to -2.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	For A/California/7/2009 (H1N1) vaccine strain.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FluLaval™ Quadrivalent Group, Fluzone® Quadrivalent Group
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority criterion: The upper limit of the two-sided 95% CI for the difference in SCR (Fluzone® Quadrivalent Group minus FluLaval™ Quadrivalent Group) did not exceed 10% for each of the four strains.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	SCR Difference (%)
	Estimated Value	-6.74
	Confidence Interval	(2-Sided) 95%; -10.68 to -2.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	For A/Texas/50/2012 (H3N2) vaccine strain

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	FluLaval™ Quadrivalent Group, Fluzone® Quadrivalent Group
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority criterion: The upper limit of the two-sided 95% CI for the difference in SCR (Fluzone® Quadrivalent Group minus FluLaval™ Quadrivalent Group) did not exceed 10% for each of the four strains.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	SCR Difference (%)
	Estimated Value	-16.38
	Confidence Interval	(2-Sided) 95%; -20.68 to -12.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	For B/Massachusetts/2/2012 (Yamagata) vaccine strain

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FluLaval™ Quadrivalent Group, Fluzone® Quadrivalent Group
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority criterion: The upper limit of the two-sided 95% CI for the difference in SCR (Fluzone® Quadrivalent Group minus FluLaval™ Quadrivalent Group) did not exceed 10% for each of the four strains.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	SCR Difference (%)
	Estimated Value	-11.75
	Confidence Interval	(2-Sided) 95%; -15.28 to -8.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	For B/Brisbane/60/2008 (Victoria) vaccine strain.

2. Primary Outcome

Title	Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Vaccine Strains.
Description	HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios. The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria).
Time Frame	At 28 days after the last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	1013	1028
H1N1	98.8	84.4
H3N2	97.7	84.3
Yamagata	257.5	164.2
Victoria	55.1	33.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FluLaval™ Quadrivalent Group, Fluzone® Quadrivalent Group
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority criterion: The upper limit of the two-sided 95% confidence interval (CI) for the GMT ratio (Fluzone® Quadrivalent Group/FluLaval™ Quadrivalent Group) did not exceed 1.5 for each of the four strains.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted GMT ratio
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.77 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	The GMTs were used to calculate the Adjusted GMTs, which in turn were used to calculate the Adjusted GMT ratio with 95% confidence interval (Ancova model: adjustment for baseline titer - pooled variance).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FluLaval™ Quadrivalent Group, Fluzone® Quadrivalent Group
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority criterion: The upper limit of the two-sided 95% confidence interval (CI) for the GMT ratio (Fluzone® Quadrivalent Group/FluLaval™ Quadrivalent Group) did not exceed 1.5 for each of the four strains.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted GMT Ratio
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.77 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	The GMTs were used to calculate the Adjusted GMTs, which in turn were used to calculate the Adjusted GMT ratio with 95% confidence interval (Ancova model: adjustment for baseline titer - pooled variance).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	FluLaval™ Quadrivalent Group, Fluzone® Quadrivalent Group
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority criterion: The upper limit of the two-sided 95% confidence interval (CI) for the GMT ratio (Fluzone® Quadrivalent Group/FluLaval™ Quadrivalent Group) did not exceed 1.5 for each of the four strains.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted GMT Ratio
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.59 to 0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	The GMTs were used to calculate the Adjusted GMTs, which in turn were used to calculate the Adjusted GMT ratio with 95% confidence interval (Ancova model: adjustment for baseline titer - pooled variance).

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FluLaval™ Quadrivalent Group, Fluzone® Quadrivalent Group
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority criterion: The upper limit of the two-sided 95% confidence interval (CI) for the GMT ratio (Fluzone® Quadrivalent Group/FluLaval™ Quadrivalent Group) did not exceed 1.5 for each of the four strains.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted GMT Ratio
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.56 to 0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	The GMTs were used to calculate the Adjusted GMTs, which in turn were used to calculate the Adjusted GMT ratio with 95% confidence interval (Ancova model: adjustment for baseline titer - pooled variance).

3. Secondary Outcome

Title	Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed)
Description	Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), B/Massachusetts/2/2012 (Yamagata) and B/Brisbane/60/2008 (Victoria).
Time Frame	At Day 0 and 28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	1013	1028
H1N1, Day 0	11.0	11.1
H1N1, Day 28/Day 56	98.8	84.4
H3N2, Day 0	9.2	9.6
H3N2, Day 28/Day 56	97.7	84.3
Yamagata, Day 0	20.3	20.6
Yamagata, Day 28/Day 56	257.5	164.2
Victoria, Day 0	6.2	6.3
Victoria, Day 28/Day 56	55.1	33.4
H1N1, 6-17M, Day 0	7.2	7.1
H1N1, 6-17M, Day 28/Day 56	42.7	43.2
H1N1, 18-35M, Day 0	14.5	14.6
H1N1, 18-35M, Day 28/Day 56	170.9	129.6
H3N2, 6-17M, Day 0	5.8	6.2
H3N2, 6-17M, Day 28/Day 56	58.9	54.8
H3N2, 18-35M, Day 0	12.3	12.5
H3N2, 18-35M, Day 28/Day 56	136.0	111.1
Yamagata, 6-17M, Day 0	12.2	13.0
Yamagata, 6-17M, Day 28/Day 56	151.0	79.1
Yamagata, 18-35M, Day 0	28.0	27.4
Yamagata, 18-35M, Day 28/Day 56	364.8	262.1
Victoria, 6-17M, Day 0	5.5	5.6
Victoria, 6-17M, Day 28/Day 56	68.7	31.9
Victoria, 18-35M, Day 0	6.8	6.8
Victoria, 18-35M, Day 28/Day 56	47.8	34.4
H1N1, Unprimed, Day 0	7.5	8.2
H1N1, Unprimed, Day 56	51.4	56.0
H1N1, Primed, Day 0	14.4	13.8
H1N1, Primed, Day 28	158.8	115.0
H3N2, Unprimed, Day 0	6.4	6.9
H3N2, Unprimed, Day 56	75.0	76.8
H3N2, Primed, Day 0	11.8	12.2
H3N2, Primed, Day 28	118.4	90.4
Yamagata, Unprimed, Day 0	11.4	12.4
Yamagata, Unprimed, Day 56	179.8	98.1
Yamagata, Primed, Day 0	30.5	30.1
Yamagata, Primed, Day 28	334.3	242.2
Victoria, Unprimed, Day 0	5.6	5.6
Victoria, Unprimed, Day 56	91.7	44.8
Victoria, Primed, Day 0	6.7	6.8
Victoria, Primed, Day 28	38.1	26.7

4. Secondary Outcome

Title	Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed)
Description	A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40. The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria).
Time Frame	At Day 0 and 28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)

Outcome Measure Data

Analysis Population Description

The ATP cohort for immunogenicity included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	1013	1028
H1N1, Day 0	191	190
H1N1, Day 28/56	814	775
H3N2, Day 0	135	140
H3N2, Day 28/56	833	800
Yamagata, Day 0	324	336
Yamagata, Day 28/56	983	911
Victoria, Day 0	40	46
Victoria, Day 28/56	669	512
H1N1, 6-17M, Day 0	32	25
H1N1, 6-17M, Day 28/Day 56	245	240
H1N1, 18-35M, Day 0	159	165
H1N1, 18-35M, Day 28/Day 56	569	535
H3N2, 6-17M, Day 0	12	15
H3N2, 6-17M, Day 28/Day 56	281	272
H3N2, 18-35M, Day 0	123	125
H3N2, 18-35M, Day 28/Day 56	552	528
Yamagata, 6-17M, Day 0	64	70
Yamagata, 6-17M, Day 28/Day 56	377	311
Yamagata, 18-35M, Day 0	260	266
Yamagata, 18-35M, Day 28/Day 56	606	600
Victoria, 6-17M, Day 0	2	7
Victoria, 6-17M, Day 28/Day 56	313	206
Victoria, 18-35M, Day 0	38	39
Victoria, 18-35M, Day 28/Day 56	356	306
H1N1, Unprimed, Day 0	42	46
H1N1, Unprimed, Day 56	282	294
H1N1, Primed, Day 0	149	144
H1N1, Primed, Day 28	532	481
H3N2, Unprimed, Day 0	27	31
H3N2, Unprimed, Day 56	321	330
H3N2, Primed, Day 0	108	109
H3N2, Primed, Day 28	512	470
Yamagata, Unprimed, Day 0	65	80
Yamagata, Unprimed, Day 56	407	362
Yamagata, Primed, Day 0	259	256
Yamagata, Primed, Day 28	576	549
Victoria, Unprimed, Day 0	9	11
Victoria, Unprimed, Day 56	379	277
Victoria, Primed, Day 0	31	35
Victoria, Primed, Day 28	290	235

5. Secondary Outcome

Title	Number of Seroconverted Subjects for Anti-HA Antibodies Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed)
Description	A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria).
Time Frame	28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	974	980
H1N1 [N=972,980]	716	660
H3N2 [N=972,980]	740	680
Yamagata [N=974,980]	833	723
Victoria [N=973,980]	631	475
H1N1, 6-17M [N=376,375]	220	216
H1N1, 18-35M [N=596,605]	496	444
H3N2, 6-17M [N=376,375]	260	250
H3N2, 18-35M [N=596,605]	480	430
Yamagata, 6-17M [N=376,375]	299	232
Yamagata, 18-35M [N=598,605]	534	491
Victoria, 6-17M [N=376,375]	291	189
Victoria, 18-35M [N=597,605]	340	286

6. Secondary Outcome

Title	Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the 4 Vaccine Influenza Strains, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed)
Description	MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/California/7/2009 (H1N1) HI, A/Texas/50/2012 (H3N2) HI, B/Massachusetts/2/2012 (Yamagata) HI and B/Brisbane/60/2008 (Victoria).
Time Frame	28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects)

Outcome Measure Data

Analysis Population Description

The ATP cohort for immunogenicity included all evaluable subjects who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	974	980
H1N1 [N=972,980]	9.0	7.7
H3N2 [N=972,980]	10.7	8.9
Yamagata [N=974,980]	12.7	8.1
Victoria [N=973,980]	8.7	5.4
H1N1, 6-17M [N=376,375]	6.0	6.1
H1N1, 18-35M [N=596,605]	11.7	8.9
H3N2, 6-17M [N=376,375]	10.2	8.8
H3N2, 18-35M [N=596,605]	11.1	9.0
Yamagata, 6-17M [N=376,375]	12.3	6.1
Yamagata, 18-35M [N=598,605]	12.9	9.7
Victoria, 6-17M [N=376,375]	12.3	5.7
Victoria, 18-35M [N=597,605]	7.0	5.2
H1N1, Unprimed [N=402,417]	6.9	6.8
H1N1, Primed [N=570, 563]	10.9	8.5
H3N2, Unprimed [N=402,417]	11.8	11.2
H3N2, Primed [N=570, 563]	10.0	7.6
Yamagata, Unprimed [N=402,417]	16.0	8.0
Yamagata, Primed [N=572, 563]	10.7	8.2
Victoria, Unprimed [N=402,417]	16.2	8.0
Victoria, Primed [N=571, 563]	5.6	4.0

7. Secondary Outcome

Title	Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed)
Description	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity and all subjects reporting 'Yes' for solicited symptom occurred but with missing values for at least one day during the solicited period. Grade 3 pain = Cried when limb is moved/spontaneously painful. Grade 3 redness and swelling was greater than 100 millimeters (mm) i.e. >100mm.
Time Frame	During a 7-day (Day 0 - Day 6) follow-up period after each vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented and for whom data were available.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	1156	1151
Any Pain, Dose 1 [N=1151,1146]	464	429
Grade 3 Pain, Dose 1 [N=1151,1146]	28	16
Any Redness, Dose 1 [N=1151,1146]	15	15
Grade 3 Redness, Dose 1 [N=1151,1146]	0	0
Any Swelling, Dose 1 [N=1151,1146]	11	5
Grade 3 Swelling, Dose 1 [N=1151,1146]	0	0
Any Pain, Dose 2 [N=490,493]	138	147
Grade 3 Pain, Dose 2 [N=490,493]	9	3
Any Redness, Dose 2 [N=490,493]	1	2
Grade 3 Redness, Dose 2 [N=490,493]	0	0
Any Swelling, Dose 2 [N=490,493]	0	0
Grade 3 Swelling, Dose 2 [N=490,493]	0	0
Any Pain, Across doses [N=1156,1151]	509	462
Grade 3 Pain, Across doses [N=1156,1151]	34	19
Any Redness, Across doses [N=1156,1151]	16	16
Grade 3 Redness, Across doses [N=1156,1151]	0	0
Any Swelling, Across doses [N=1156,1151]	11	5
Grade 3 Swelling, Across doses [N=1156,1151]	0	0
Any Pain, 6-17M, Dose 1 [N=478,465]	175	173
Grade 3 Pain, 6-17M, Dose 1 [N=478,465]	11	12
Any Redness, 6-17M, Dose 1 [N=478,465]	2	2
Grade 3 Redness, 6-17M, Dose 1 [N=478,465]	0	0
Any Swelling, 6-17M, Dose 1 [N=478,465]	4	0
Grade 3 Swelling, 6-17M, Dose 1 [N=478,465]	0	0
Any Pain, 18-35M, Dose 1 [N=673,681]	289	256
Grade 3 Pain, 18-35M, Dose 1 [N=673,681]	17	4
Any Redness, 18-35M, Dose 1 [N=673,681]	13	13
Grade 3 Redness, 18-35M, Dose 1 [N=673,681]	0	0
Any Swelling, 18-35M, Dose 1 [N=673,681]	7	5
Grade 3 Swelling, 18-35M, Dose 1 [N=673,681]	0	0
Any Pain, 6-17M, Dose 2 [N=373,372]	103	108
Grade 3 Pain, 6-17M, Dose 2 [N=373,372]	6	1
Any Redness, 6-17M, Dose 2 [N=373,372]	1	0
Grade 3 Redness, 6-17M, Dose 2 [N=373,372]	0	0
Any Swelling, 6-17M, Dose 2 [N=373,372]	0	0
Grade 3 Swelling, 6-17M, Dose 2 [N=373,372]	0	0
Any Pain, 18-35M, Dose 2 [N=117,121]	35	39
Grade 3 Pain, 18-35M, Dose 2 [N=117,121]	3	2
Any Redness, 18-35M, Dose 2 [N=117,121]	0	2
Grade 3 Redness, 18-35M, Dose 2 [N=117,121]	0	0
Any Swelling, 18-35M, Dose 2 [N=117,121]	0	0
Grade 3 Swelling, 18-35M, Dose 2 [N=117,121]	0	0
Any Pain, 6-17M, Across Doses [N=481,469]	211	196
Grade 3 Pain, 6-17M, Across Doses [N=481,469]	15	13
Any Redness, 6-17M, Across Doses [N=481,469]	3	2
Grade 3 Redness, 6-17M, Across Doses [N=481,469]	0	0
Any Swelling, 6-17M, Across Doses [N=481,469]	4	0
Grade 3 Swelling, 6-17M, Across Doses [N=481,469]	0	0
Any Pain, 18-35M, Across Doses [N=675,682]	298	266
Grade 3 Pain, 18-35M, Across Doses [N=675,682]	19	6
Any Redness, 18-35M, Across Doses [N=675,682]	13	14
Grade 3 Redness, 18-35M, Across Doses [N=675,682]	0	0
Any Swelling, 18-35M, Across Doses [N=675,682]	7	5
Grade 3 Swelling, 18-35M, Across Doses [N=675,682]	0	0
Any Pain, Unprimed, Dose 1 [N=518,516]	187	190
Grade 3 Pain, Unprimed, Dose 1 [N=518,516]	12	11
Any Redness, Unprimed, Dose 1 [N=518,516]	2	2
Grade 3 Redness, Unprimed, Dose 1 [N=518,516]	0	0
Any Swelling, Unprimed, Dose 1 [N=518,516	4	0
Grade 3 Swelling, Unprimed, Dose 1 [N=518,516]	0	0
Any Pain, Primed, Dose 1 [N=633,630]	277	239
Grade 3 Pain, Primed, Dose 1 [N=633,630]	16	5
Any Redness, Primed, Dose 1 [N=633,630]	13	13
Grade 3 Redness, Primed, Dose 1 [N=633,630]	0	0
Any Swelling, Primed, Dose 1 [N=633,630]	7	5
Grade 3 Swelling, Primed, Dose 1 [N=633,630]	0	0
Any Pain, Unprimed, Dose 2 [N=490,493]	138	147
Grade 3 Pain, Unprimed, Dose 2 [N=490,493]	9	3
Any Redness, Unprimed, Dose 2 [N=490,493]	1	2
Grade 3 Redness, Unprimed, Dose 2 [N=490,493]	0	0
Any Swelling, Unprimed, Dose 2 [N=490,493]	0	0
Grade 3 Swelling, Unprimed, Dose 2 [N=490,493]	0	0
Any Pain, Unprimed, Across Doses [N=523,521]	232	223
Grade 3 Pain, Unprimed, Across Doses [N=523,521]	18	14
Any Redness, Unprimed, Across Doses [N=523,521]	3	3
Grade 3 Redness, Unprimed, Across Doses[N=523,521]	0	0
Any Swelling, Unprimed, Across Doses [N=523,521]	4	0
Grade 3 Swelling,Unprimed, Across Doses[N=523,521]	0	0
Any Pain, Primed, Across Doses [N=633,630]	277	239
Grade 3 Pain, Primed, Across Doses [N=633,630]	16	5
Any Redness, Primed, Across Doses [N=633,630]	13	13
Grade 3 Redness, Primed, Across Doses [N=633,630]	0	0
Any Sweling, Primed, Across Doses [N=633,630]	7	5
Grade 3 Swelling, Primed, Across Doses [N=633,630]	0	0

8. Secondary Outcome

Title	Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed)
Description	Solicited general symptoms assessed were drowsiness, irritability/fussiness, loss of appetite and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 irritability/fussiness was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Grade 3 drowsiness was defined as drowsiness that prevented normal activity. Any fever was defined as subjects with a documented temperature of greater than or equal to (≥) 38°C/100.4°F by any route and all subjects reporting temperature less than (< )38°C but with missing values for at least one day during the solicited period. Grade 3 fever was defined as temperature greater than (>) 39.0°C.
Time Frame	During the 7-day (Days 0-6) follow-up period after each vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented and for whom data were available.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	1159	1152
Any Drowsiness, Dose 1 [N=1155,1148]	424	424
Grade 3 Drowsiness, Dose 1 [N=1155,1148]	31	30
Related Drowsiness, Dose 1 [N=1155,1148]	365	381
Any Fever, Dose 1 [N=1155,1148]	146	147
Fever (≥38.0°C), Dose 1 [N=1155,1148]	65	67
Grade 3 Fever, Dose 1 [N=1155,1148]	16	11
Related Fever, Dose 1 [N=1155,1148]	41	50
≥38.0°C Related Fever, Dose 1 [N=1155,1148]	41	50
Any Irritability, Dose 1 [N=1155,1148]	570	527
Grade 3 Irritability, Dose 1 [N=1155,1148]	44	34
Related Irritability, Dose 1 [N=1155,1148]	499	473
Any Loss of Appetite, Dose 1 [N=1155,1148]	334	328
Grade 3 Loss of Appetite, Dose 1 [N=1155,1148]	19	15
Related Loss of Appetite, Dose 1 [N=1155,1148]	280	290
Any Drowsiness, Dose 2 [N=490,495]	157	166
Grade 3 Drowsiness, Dose 2 [N=490,495]	10	6
Related Drowsiness, Dose 2 [N=490,495]	133	136
Any Fever, Dose 2 [N=490,495]	60	48
Fever (≥38.0°C), Dose 2 [N=490,495]	31	22
Grade 3 Fever, Dose 2 [N=490,495]	9	6
Related Fever, Dose 2 [N=490,495]	22	14
≥38.0°C Related Fever, Dose 2 [N=490,495]	20	13
Any Irritability, Dose 2 [N=490,495]	211	214
Grade 3 Irritability, Dose 2 [N=490,495]	21	14
Related Irritability, Dose 2 [N=490,495]	185	175
Any Loss of Appetite, Dose 2 [N=490,495]	110	116
Grade 3 Loss of Appetite, Dose 2 [N=490,495]	8	5
Related Loss of Appetite, Dose 2 [N=490,495]	91	87
Any Drowsiness, Across Doses [N=1159,1152]	471	471
Grade 3 Drowsiness, Across Doses [N=1159,1152]	36	34
Related Drowsiness, Across Doses [N=1159,1152]	411	425
Any Fever, Across Doses [N=1159,1152]	183	178
Fever (≥38.0°C), Across Doses [N=1159,1152	91	86
Grade 3 Fever, Across Doses [N=1159,1152]	25	17
Related Fever, Across Doses [N=1159,1152]	62	63
≥38.0°C Related Fever, Across Doses [N=1159,1152]	60	62
Any Irritability, Across Doses [N=1159,1152]	630	582
Grade 3 Irritability, Across Doses [N=1159,1152]	61	45
Related Irritability, Across Doses [N=1159,1152]	558	525
Any Loss of Appetite, Across Doses [N=1159,1152]	391	385
Grade 3 Loss of Appetite,Across Doses[N=1159,1152	26	19
Related Loss of Appetite,Across Doses[N=1159,1152]	328	337
Any Drowsiness, 6-17M, Dose 1 [N=478,467]	200	210
Grade 3 Drowsiness, 6-17M, Dose 1 [N=478,467]	16	17
Related Drowsiness, 6-17M, Dose 1 [N=478,467]	171	189
Any Fever, 6-17M, Dose 1 [N=478,467]	80	70
Fever (≥38.0°C), 6-17M, Dose 1 [N=478,467]	40	31
Grade 3 Fever, 6-17M, Dose 1 [N=478,467]	12	4
Related Fever, 6-17M, Dose 1 [N=478,467]	25	26
≥38.0°C Related Fever, 6-17M, Dose 1 [N=478,467]	25	26
Any Irritability, 6-17M, Dose 1 [N=478,467]	273	252
Grade 3 Irritability, 6-17M, Dose 1 [N=478,467]	24	15
Related Irritability, 6-17M, Dose 1 [N=478,467]	239	227
Any Loss of Appetite, 6-17M, Dose 1 [N=478,467]	141	131
Grade 3 Loss of Appetite, 6-17M,Dose 1 [N=478,467]	7	4
Related Loss of Appetite, 6-17M, Dose 1[N=478,467]	122	115
Any Drowsiness, 18-35M, Dose 1 [N=677,681]	224	214
Grade 3 Drowsiness, 18-35M, Dose 1 [N=677,681]	15	13
Related Drowsiness, 18-35M, Dose 1 [N=677,681]	194	192
Any Fever, 18-35M, Dose 1 [N=677,681]	66	77
Fever (≥38.0°C), 18-35M, Dose 1 [N=677,681]	25	36
Grade 3 Fever, 18-35M, Dose 1 [N=677,681]	4	7
Related Fever, 18-35M, Dose 1 [N=677,681]	16	24
≥38.0°C Related Fever, 18-35M, Dose 1 [N=677,681]	16	24
Any Irritability, 18-35M, Dose 1 [N=677,681]	297	275
Grade 3 Irritability, 18-35M, Dose 1 [N=677,681]	20	19
Related Irritability, 18-35M, Dose 1 [N=677,681]	260	246
Any Loss of Appetite, 18-35M, Dose 1 [N=677,681]	193	197
Grade 3 Loss of Appetite,18-35M,Dose 1 [N=677,681]	12	11
Related Loss of Appetite,18-35M,Dose 1 [N=677,681]	158	175
Any Drowsiness, 6-17M, Dose 2 [N=373,374]	129	142
Grade 3 Drowsiness, 6-17M, Dose 2 [N=373,374]	10	6
Related Drowsiness, 6-17M, Dose 2 [N=373,374]	111	115
Any Fever, 6-17M, Dose 2 [N=373,374]	47	38
Fever (≥38.0°C), 6-17M, Dose 2 [N=373,374]	23	16
Grade 3 Fever, 6-17M, Dose 2 [N=373,374]	5	3
Related Fever, 6-17M, Dose 2 [N=373,374]	17	11
≥38.0°C Related Fever, 6-17M, Dose 2 [N=373,374]	15	10
Any Irritability, 6-17M, Dose 2 [N=373,374]	168	177
Grade 3 Irritability, 6-17M, Dose 2 [N=373,374]	16	12
Related Irritability, 6-17M, Dose 2 [N=373,374]	150	141
Any Loss of Appetite, 6-17M, Dose 2 [N=373,374]	90	91
Grade 3 Loss of Appetite, 6-17M, Dose 2[N=373,374]	8	3
Related Loss of Appetite, 6-17M Dose 2[N=373,374]	73	66
Any Drowsiness, 18-35M, Dose 2 [N=117,121]	28	24
Grade 3 Drowsiness, 18-35M, Dose 2 [N=117,121]	0	0
Related Drowsiness, 18-35M, Dose 2 [N=117,121]	22	21
Any Fever, 18-35M, Dose 2 [N=117,121]	13	10
Fever (≥38.0°C), 18-35M, Dose 2 [N=117,121]	8	6
Grade 3 Fever, 18-35M, Dose 2 [N=117,121]	4	3
Related Fever, 18-35M, Dose 2 [N=117,121]	5	3
≥38.0°C Related Fever, 18-35M, Dose 2 [N=117,121]	5	3
Any Irritability, 18-35M, Dose 2 [N=117,121]	43	37
Grade 3 Irritability, 18-35M, Dose 2 [N=117,121]	5	2
Related Irritability, 18-35M, Dose 2 [N=117,121]	35	34
Any Loss of Appetite, 18-35M, Dose 2 [N=117,121]	20	25
Grade 3 Loss of Appetite, 18-35M,Dose 2[N=117,121]	0	2
Related Loss of Appetite, 18-35M,Dose 2[N=117,121]	18	21
Any Drowsiness, 6-17M, Across Doses [N=481,470]	238	248
Grade 3 Drowsiness, 6-17M, Across Doses[N=481,470]	21	21
Related Drowsiness, 6-17M, Across Doses[N=481,470]	209	224
Any Fever, 6-17M, Across Doses [N=481,470]	109	93
Fever (≥38.0°C), 6-17M, Across Doses [N=481,470]	60	45
Grade 3 Fever, 6-17M, Across Doses [N=481,470]	17	7
Related Fever, 6-17M, Across Doses [N=481,470]	41	36
≥38.0°CRelated Fever,6-17M,Across Doses[N=481,470]	39	35
Any Irritability, 6-17M, Across Doses [N=481,470]	315	297
Grade 3 Irritability,6-17M,Across Doses[N=481,470]	36	25
Related Irritability,6-17M,Across Doses[N=481,470]	280	269
Any Loss of Appetite,6-17M,Across Doses[N=481,470]	188	175
Grade3 LossofAppetite,6-17M,AcrossDoses[N=481,470]	14	6
Related LossofAppetite,6-17M,AcrossDoses[N=481,470	159	148
Any Drowsiness, 18-35M, Across Doses [N=678,682]	233	223
Grade 3 Drowsiness,18-35M, Across Doses[N=678,682]	15	13
Related Drowsiness,18-35M,Across Doses [N=678,682]	202	201
Any Fever, 18-35M, Across Doses [N=678,682]	74	85
Fever (≥38.0°C), 18-35M, Across Doses [N=678,682]	31	41
Grade 3 Fever, 18-35M, Across Doses [N=678,682]	8	10
Related Fever, 18-35M, Across Doses [N=678,682]	21	27
≥38.0°CRelated Fever,18-35M,Across Doses[N=678,682	21	27
Any Irritability, 18-35M, Across Doses [N=678,682]	315	285
Grade3 Irritability,18-35M,Across Doses[N=678,682]	25	20
Related Irritability,18-35M,Across Doses[N=678,682	278	256
Any Loss ofAppetite,18-35M,Across Doses[N=678,682]	203	210
Grade3LossofAppetite,18-35M,AcrossDoses[N=678,682]	12	13
RelatedLossofAppetite,18-35M,AcrossDoses[N=678,682	169	189
Any Drowsiness, Unprimed, Dose 1 [N=520,518]	212	211
Grade 3 Drowsiness, Unprimed, Dose 1 [N=520,518]	15	19
Related Drowsiness, Unprimed, Dose 1 [N=520,518]	182	189
Any Fever, Unprimed, Dose 1 [N=520,518]	80	69
Fever (≥38.0°C), Unprimed, Dose 1 [N=520,518]	41	33
Grade 3 Fever, Unprimed, Dose 1 [N=520,518]	12	3
Related Fever, Unprimed, Dose 1 [N=520,518]	24	25
≥38.0°C Related Fever, Unprimed, Dose 1[N=520,518]	24	25
Any Irritability, Unprimed, Dose 1 [N=520,518]	274	256
Grade 3 Irritability, Unprimed, Dose 1 [N=520,518]	21	14
Related Irritability, Unprimed, Dose 1 [N=520,518]	240	227
Any Loss of Appetite, Unprimed, Dose 1 [N=520,518]	154	138
Grade3 Loss of Appetite,Unprimed,Dose 1[N=520,518]	7	6
Related Loss of Appetite,Unprimed,Dose1[N=520,518]	129	119
Any Drowsiness, Primed, Dose 1 [N=635,630]	212	213
Grade 3 Drowsiness, Primed, Dose 1 [N=635,630]	16	11
Related Drowsiness, Primed, Dose 1 [N=635,630]	183	192
Any Fever, Primed, Dose 1 [N=635,630]	66	78
Fever (≥38.0°C) Primed, Dose 1 [N=635,630]	24	34
Grade 3 Fever, Primed, Dose 1 [N=635,630]	4	8
Related Fevers, Primed, Dose 1 [N=635,630]	17	25
≥38.0°C Related Fever, Primed, Dose 1 [N=635,630]	17	25
Any Irritability, Primed, Dose 1 [N=635,630]	296	271
Grade 3 Irritability, Primed, Dose 1 [N=635,630]	23	20
Related Irritability, Primed, Dose 1 [N=635,630]	259	246
Any Loss of Appetite, Primed, Dose 1 [N=635,630]	180	190
Grade 3 Loss of Appetite, Primed,Dose 1[N=635,630]	12	9
Related Loss of Appetite,Primed,Dose 1 [N=635,630]	151	171
Any Drowsiness, Unprimed, Dose 2 [N=490,495]	157	166
Grade 3 Drowsiness, Unprimed, Dose 2 [N=490,495]	10	6
Related Drowsiness, Unprimed, Dose 2 [N=490,495]	133	136
Any Fever, Unprimed, Dose 2 [N=490,495]	60	48
Fever (≥38.0°C), Unprimed, Dose 2 [N=490,495]	31	22
Grade 3 Fever, Unprimed, Dose 2 [N=490,495]	9	6
Related Fever, Unprimed, Dose 2 [N=490,495]	22	14
≥38.0°C Related Fever, Unprimed,Dose 2 [N=490,495]	20	13
Any Irritability, Unprimed, Dose 2 [N=490,495]	211	214
Grade 3 Irritability, Unprimed, Dose 2 [N=490,495]	21	14
Related Irritability, Unprimed,Dose 2 [N=490,495]	185	175
Any Loss of Appetite, Unprimed, Dose 2 [N=490,495]	110	116
Grade3 Loss of Appetite,Unprimed,Dose 2[N=490,495]	8	5
Related Loss of Appetite,Unprimed,Dose 2[N=490,495	91	87
Any Drowsiness, Unprimed, Across Doses [N=524,522]	259	258
Grade3 Drowsiness,Unprimed,Across Doses[N=524,522]	20	23
RelatedDrowsiness,Unprimed,Across Doses[N=524,522]	228	233
Any Fever, Unprimed, Across Doses [N=524,522]	117	100
Fever (≥38.0°C), Unprimed,Across Doses [N=524,522]	67	52
Grade 3 Fever, Unprimed, Across Doses [N=524,522]	21	9
Related Fever, Unprimed, Across Doses [N=524,522]	45	38
≥38.0°CRelatedFever,Unprimed,AcrossDoses[N=524,522	43	37
Any Irritability,Unprimed, Across Doses[N=524,522]	334	311
Grade3Irritability,Unprimed,AcrossDoses[N=524,522]	38	25
RelatedIrritability,Unprimed,AcrossDoses[N=524,522	299	279
AnyLoss ofAppetite,Unprimed,AcrossDoses[N=524,522]	211	195
Grade3LossofAppetite,Unprimed,AcrossDosesN=524,522	14	10
RelatedLossofAppetite,UnprimedAcrossDosesN=524,522	177	166
Any Drowsiness, Primed, Across Doses [N=635,630]	212	213
Grade 3 Drowsiness, Primed,Across Doses[N=635,630]	16	11
Related Drowsiness,Primed,Across Doses[N=635,630]	183	192
Any Fever, Primed, Across Doses [N=635,630]	66	78
Fever (≥38.0°C), Primed, Across Doses [N=635,630]	24	34
Grade 3 Fever, Primed, Across Doses [N=635,630]	4	8
Related Fever, Primed, Across Doses [N=635,630]	17	25
≥38.0°C RelatedFever,Primed,Across Doses[N=635,630	17	25
Any Irritability, Primed, Across Doses [N=635,630]	296	271
Grade3 Irritability,Primed,Across Doses[N=635,630]	23	20
Related Irritability,Primed,AcrossDoses[N=635,630]	259	246
Any Loss of Appetite,Primed,AcrossDoses[N=635,630]	180	190
Grade3 LossofAppetite,Primed,AcrossDoses[N=635,630	12	9
RelatedLossofAppetite,Primed,AcrossDoses[N=635,630	151	171

9. Secondary Outcome

Title	Duration of Solicited Local and General AEs, Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed)
Description	Duration was defined as number of days with any grade of local and general symptoms.
Time Frame	During the 7-day (Days 0-6) follow-up period after each vaccination.

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented and for whom data were available.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	570	527
Drowsiness, Dose 1 [N=424,424]	1.0	1.5
Drowsiness, Dose 2 [N=157,166]	2.0	2.0
Irritability, Dose 1 [N=570, 527]	2.0	2.0
Irritability, Dose 2 [N=211,214]	2.0	2.0
Loss of Appetite, Dose 1 [N=334, 328]	2.0	2.0
Loss of Appetite, Dose 2 [N=110,116]	2.0	2.0
Pain, Dose 1 [N=464,429]	1.0	2.0
Pain, Dose 2 [N=138,147]	1.0	1.0
Redness, Dose 1 [N=15,15]	2.0	1.0
Redness, Dose 2 [N=1,2]	1.0	1.5
Swelling, Dose 1 [N=11,5]	2.0	2.0
Fever, Dose 1 [N=146,147]	1.0	1.0
Fever, Dose 2 [N=60,48]	1.0	2.0
Drowsiness, 6-17M, Dose 1 [N=200,210]	2.0	2.0
Drowsiness, 18-35M, Dose 1 [N=224,214]	1.0	1.0
Drowsiness, 6-17M, Dose 2 [N=129,142]	2.0	2.0
Drowsiness, 18-35M, Dose 2 [N=28,24]	2.0	1.0
Irritability, 6-17M, Dose 1 [N=273,252]	2.0	2.0
Irritability, 18-35M, Dose 1 [N=297,275]	2.0	2.0
Irritability, 6-17M, Dose 2 [N=168,177]	2.0	2.0
Irritability, 18-35M, Dose 2 [N=43,37]	2.0	1.0
Loss of Appetite, 6-17M, Dose 1 [N=141,131]	2.0	2.0
Loss of Appetite, 18-35M, Dose 1 [N=193,197]	2.0	2.0
Loss of Appetite, 6-17M, Dose 2 [N=90,91]	2.0	2.0
Loss of Appetite, 18-35M, Dose 2 [N=20,25]	2.0	2.0
Pain, 6-17M, Dose 1 [N=175,173]	1.0	1.0
Pain, 18-35M, Dose 1 [N=289,256]	2.0	2.0
Pain, 6-17M, Dose 2 [N=103,108]	1.0	2.0
Pain, 18-35M, Dose 2 [N=35,39]	1.0	1.0
Redness, 6-17M, Dose 1 [N=2,2]	1.5	1.0
Redness, 18-35M, Dose 1 [N=13,13]	2.0	1.0
Redness, 6-17M, Dose 2 [N=1,0]	1.0	0.0
Redness, 18-35M, Dose 2 [N=0,2]	0.0	1.5
Swelling, 6-17M, Dose 1 [N=4,0]	1.5	0.0
Swelling, 18-35M, Dose 1 [N=7,5]	2.0	2.0
Fever, 6-17M, Dose 1 [N=80,70]	2.0	1.0
Fever, 18-35M, Dose 1 [N=66,77]	1.0	1.0
Fever, 6-17M, Dose 2 [N=47,38]	1.0	1.5
Fever, 18-35M, Dose 2 [N=13,10]	1.0	2.0
Drowsiness, Unprimed, Dose 1 [N=212,211]	2.0	2.0
Drowsiness, Primed, Dose 1 [N=212,213]	1.0	1.0
Drowsiness, Unprimed, Dose 2 [N=157,166]	2.0	2.0
Irritability, Unprimed, Dose 1 [N=274,256]	2.0	2.0
Irritability, Primed, Dose 1 [N=296,271]	2.0	2.0
Irritability, Unprimed, Dose 2 [N=211,214]	2.0	2.0
Loss of Appetite, Unprimed, Dose 1 [N=154,138]	2.0	2.0
Loss of Appetite, Primed, Dose 1 [N=180,190]	1.0	2.0
Loss of Appetite, Unprimed, Dose 2 [N=110,116]	2.0	2.0
Pain, Unprimed, Dose 1 [N=187,190]	1.0	1.0
Pain, Primed, Dose 1 [N=277,239]	2.0	2.0
Pain, Unprimed, Dose 2 [N=138,147]	1.0	1.0
Redness, Unprimed, Dose 1 [N=2,2]	1.5	2.0
Redness, Primed, Dose 1 [N=13,13]	2.0	1.0
Redness, Unprimed, Dose 2 [N=1,2]	1.0	1.5
Swelling, Unprimed, Dose 1 [N=4,0]	1.5	0.0
Swelling, Primed, Dose 1 [N=7,5]	2.0	2.0
Fever, Unprimed, Dose 1 [N=80,69]	1.0	1.0
Fever, Primed, Dose 1 [N=66,78]	1.0	1.0
Fever, Unprimed, Dose 2 [N=60,48]	1.0	2.0

10. Secondary Outcome

Title	Number of Subjects Reporting Any Fever Following Each Dose and Across Doses.
Description	Any Fever = all subjects with a documented temperature of ≥38.0°C /100.4°F by axillary route and all subjects reporting temperature < 38.0°C but with missing values for at least one day during the solicited period. Grade 3 fever was defined as temperature greater than (>) 39.0°C.
Time Frame	During a 2-day (Days 0-1) follow-up period after each vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented and for whom data were available.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	1159	1152
Any Fever, Dose 1 [N=1155,1148]	63	74
Fever (≥38.0°C), Dose 1 [N=1155,1148]	30	34
Grade 3 Fever (>39.0°C), Dose 1 [N=1155,1148]	6	4
Any Fever, Dose 2 [N=490,495]	21	22
Fever (≥38.0°C), Dose 2 [N=490,495]	12	10
Grade 3 Fever (>39.0°C), Dose 2 [N=490,495]	3	2
Any Fever, Across Doses [N=1159,1152]	82	93
Fever (≥38.0°C), Across Doses [N=1159,1152]	42	43
Grade 3 Fever (>39.0°C), Across Doses[N=1159,1152]	9	6

11. Secondary Outcome

Title	Number of Subjects Reporting the Occurrence of All Medically Attended Events (MAEs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed).
Description	MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s).
Time Frame	During the entire study period (Days 0 -180)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented and for whom data were available.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	1207	1217
Any MAE(s) [N=1207,1217]	727	719
Any MAE(s), 6-17M [N=500,502]	322	323
Any MAE(s), 18-35M [N=707,715]	405	396
Any MAE(s), Unprimed [N=550,560]	344	337
Any MAE(s), Primed [N=657,657]	383	382

12. Secondary Outcome

Title	Number of Subjects Reporting the Occurrence of Any and Related Potential Immune-Mediated Disease (pIMDs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed)
Description	pIMDs are a subset of adverse events (AEs) that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Related = symptom assed by the investigator as causally related to the study vaccination.
Time Frame	During the entire study period (Days 0 -180)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented and for whom data were available.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	1207	1217
Any pIMD(s) [N=1207,1217]	1	1
Related pIMD(s) [N=1207,1217]	0	0
Any pIMD(s), 6-17M [N=500,502]	1	1
Related pIMD(s), 6-17M [N=500,502]	0	0
Any pIMD(s), 18-35M [N=707,715]	0	0
Related pIMD(s), 18-35M [N=707,715]	0	0
Any pIMD(s), Unprimed [N=550,560]	0	0
Related pIMD(s), Unprimed [N=550,560]	0	0
Any pIMD(s), Primed [N=657,657]	1	1
Related pIMD(s), Primed [N=657,657]	0	0

13. Secondary Outcome

Title	Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed)
Description	An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 unsolicited AE was defined as an event that prevented normal activity. Related unsolicited AE was defined as an event assessed by the investigator to be causally related to the study vaccination.
Time Frame	During a 28-day (Days 0-27 for primed and unprimed subjects and Days 28-56 for unprimed subjects) post-vaccination period

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented and for whom data were available.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	1207	1217
Any Unsolicited AEs [N=1207,1217]	549	537
Grade 3 Unsolicited AEs [N=1207,1217]	70	75
Related Unsolicited AEs [N=1207,1217]	71	71
Any Unsolicited AEs, 6-17M [N=500,502]	268	270
Grade 3 Unsolicited AEs, 6-17M [N=500,502]	32	48
Related Unsolicited AEs, 6-17M [N=500,502]	36	33
Any Unsolicited AEs, 18-35M [N=707,715]	281	267
Grade 3 Unsolicited AEs, 18-35M [N=707,715]	38	27
Related Unsolicited AEs, 18-35M [N=707,715]	35	38
Any Unsolicited AEs, Unprimed [N=550,560]	310	302
Grade 3 Unsolicited AEs, Unprimed [N=550,560]	35	48
Related Unsolicited AEs, Unprimed [N=550,560]	40	35
Any Unsolicited AEs, Primed [N=657,657]	239	235
Grade 3 Unsolicited AEs, Primed [N=657,657]	35	27
Related Unsolicited AEs, Primed [N=657,657]	31	36

14. Secondary Outcome

Title	Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs), Overall, by Age Group (6-17 and 18-35 Months of Age) and by Priming Status (Vaccine-primed and Vaccine-unprimed)
Description	SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. Related = symptom assessed by the investigator as causally related to the study vaccination.
Time Frame	During the entire study period (Days 0 -180)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented and for whom data were available.

Arm/Group Title	FluLaval™ Quadrivalent Group	Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
Measure Participants	1207	1217
Any SAE(s) [N=1207,1217]	22	21
Related SAE(s) [N=1207,1217]	0	0
Any SAE(s), 6-17M [N=500,502]	11	11
Related SAE(s), 6-17M [N=500,502]	0	0
Any SAE(s), 18-35M [N=707,715]	11	10
Related SAE(s), 18-35M [N=707,715]	0	0
Any SAE(s), Unprimed [N=550,560]	8	13
Related SAE(s), Unprimed [N=550,560]	0	0
Any SAE(s), Primed [N=657,657]	14	8
Related SAE(s), Primed [N=657,657]	0	0

Adverse Events

Time Frame	Serious Adverse Events: From Day 0 to Day 180; Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period across doses; Unsolicited adverse events: During the 28-day post-vaccination period.
Adverse Event Reporting Description	For the systematically assessed other (non-serious) adverse events, the number of participants at risk included those from Total Vaccinated Cohort who had the symptom sheet completed.
Arm/Group Title	FluLaval™ Quadrivalent Group		Fluzone® Quadrivalent Group
Arm/Group Description	Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of FluLaval™ Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).		Subjects in this group received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluzone® Quadrivalent vaccine. The vaccine was administered intramuscularly into the anterolateral region of the thigh (subjects below 12 months of age) or in the deltoid muscle of the non-dominant arm (subjects ≥12 months of age).
All Cause Mortality
	FluLaval™ Quadrivalent Group		Fluzone® Quadrivalent Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	FluLaval™ Quadrivalent Group		Fluzone® Quadrivalent Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/1207 (0.4%)		4/1217 (0.3%)
Gastrointestinal disorders
Constipation	0/1207 (0%)		1/1217 (0.1%)
Intussusception	0/1207 (0%)		1/1217 (0.1%)
General disorders
Developmental delay	0/1207 (0%)		1/1217 (0.1%)
Infections and infestations
Bronchiolitis	1/1207 (0.1%)		2/1217 (0.2%)
Gastroenteritis	1/1207 (0.1%)		2/1217 (0.2%)
Cellulitis	1/1207 (0.1%)		1/1217 (0.1%)
Respiratory syncytial virus bronchiolitis	2/1207 (0.2%)		0/1217 (0%)
Urinary tract infection	1/1207 (0.1%)		1/1217 (0.1%)
Abscess	0/1207 (0%)		1/1217 (0.1%)
Croup infectious	1/1207 (0.1%)		0/1217 (0%)
Gastroenteritis rotavirus	0/1207 (0%)		1/1217 (0.1%)
Groin abscess	1/1207 (0.1%)		0/1217 (0%)
Lower respiratory tract infection	1/1207 (0.1%)		0/1217 (0%)
Otitis media acute	0/1207 (0%)		1/1217 (0.1%)
Pharyngitis	0/1207 (0%)		1/1217 (0.1%)
Pneumonia	1/1207 (0.1%)		0/1217 (0%)
Respiratory syncytial virus infection	0/1207 (0%)		1/1217 (0.1%)
Staphylococcal abscess	1/1207 (0.1%)		0/1217 (0%)
Injury, poisoning and procedural complications
Accidental exposure to product	1/1207 (0.1%)		0/1217 (0%)
Concussion	1/1207 (0.1%)		0/1217 (0%)
Craniocerebral injury	1/1207 (0.1%)		0/1217 (0%)
Multiple injuries	1/1207 (0.1%)		0/1217 (0%)
Metabolism and nutrition disorders
Dehydration	2/1207 (0.2%)		3/1217 (0.2%)
Failure to thrive	0/1207 (0%)		1/1217 (0.1%)
Hyponatraemia	1/1207 (0.1%)		0/1217 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B precursor type acute leukaemia	0/1207 (0%)		1/1217 (0.1%)
Nervous system disorders
Febrile convulsion	5/1207 (0.4%)		4/1217 (0.3%)
Hemiplegia	0/1207 (0%)		1/1217 (0.1%)
Seizure	0/1207 (0%)		1/1217 (0.1%)
Renal and urinary disorders
Calculus urinary	0/1207 (0%)		1/1217 (0.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/1207 (0.2%)		1/1217 (0.1%)
Hypoxia	1/1207 (0.1%)		0/1217 (0%)
Pneumonitis	1/1207 (0.1%)		0/1217 (0%)
Social circumstances
Sexual abuse	1/1207 (0.1%)		0/1217 (0%)
Vascular disorders
Kawasaki's disease	1/1207 (0.1%)		0/1217 (0%)
Other (Not Including Serious) Adverse Events
	FluLaval™ Quadrivalent Group		Fluzone® Quadrivalent Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	932/1207 (77.2%)		895/1217 (73.5%)
Gastrointestinal disorders
Diarrhoea	66/1207 (5.5%)		53/1217 (4.4%)
General disorders
Drowsiness	471/1159 (40.6%)		471/1152 (40.9%)
Fever	183/1159 (15.8%)		178/1152 (15.5%)
Irritability/Fussiness	630/1159 (54.4%)		582/1152 (50.5%)
Loss of Appetite	391/1159 (33.7%)		385/1152 (33.4%)
Pain	509/1156 (44%)		462/1151 (40.1%)
Fever	82/1159 (7.1%)		93/1152 (8.1%)
Infections and infestations
Upper respiratory tract infection	111/1207 (9.2%)		102/1217 (8.4%)
Nasopharyngitis	66/1207 (5.5%)		54/1217 (4.4%)
Otitis media	61/1207 (5.1%)		49/1217 (4%)
Respiratory, thoracic and mediastinal disorders
Cough	70/1207 (5.8%)		77/1217 (6.3%)
Rhinorrhoea	59/1207 (4.9%)		76/1217 (6.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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