Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Influenza Vaccine When Administered in Children Who Previously Participated in Study 115345

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01702454
• Collaborator: (none)
• Enrollment: 470
• Locations: 33
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 14.2
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and immunogenicity of GSK Biologicals' investigational vaccine GSK2321138A in children who previously participated in study 115345 (FLU D-QIV-004 PRI) (NCT01439360).

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: Fluarix Quadrivalent	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 470 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity, Safety and Reactogenicity Study of GSK Biologicals' Quadrivalent Seasonal Influenza Candidate Vaccine GSK2321138A, Administered to Children Who Previously Participated in Study 115345
• Study Start Date: Oct 6, 2012
• Actual Primary Completion Date: May 6, 2013
• Actual Study Completion Date: Jun 5, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluarix Quadrivalent Primed Group Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Biological: Fluarix Quadrivalent; 1 or 2 doses administered intramuscularly (IM) in deltoid region depending on the priming status
Experimental: Fluarix Quadrivalent Unprimed Group Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Biological: Fluarix Quadrivalent; 1 or 2 doses administered intramuscularly (IM) in deltoid region depending on the priming status

Outcome Measures

Primary Outcome Measures

1. Serum Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine [At Day 0 and Day 7]

   Antibody titers were expressed as Geometric Mean Titers (GMTs). The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

2. Number of Seropositive Subjects Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine [At Day 0 and Day 7]

   Seropositivity was defined as number of subjects with antibody titers greater than or equal to (≥) 1:10. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

3. Number of Subjects Seroconverted for HI Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 7 post dose 1]

   A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 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 included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

4. Mean Geometric Increase (MGI) for HI Antibody Titer Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 7 post dose 1]

   MGI was defined as the fold increase in serum HI GMT post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

5. Number of Subjects Seroprotected for Anti-HA Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 0 and Day 7]

   Seroprotection rate (SPR) was defined as the number of vaccinees with serum haemagglutination inhibition (HI) titer ≥ 1:40 that usually is accepted as indicating protection in adults. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

6. Serum Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 0 and Day 7]

   Antibody titers were expressed as Geometric Mean Titers (GMTs). The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

7. Number of Subjects Seropositive for HI Antibody Titers Against Each of the Four Vaccine Strains After Dose 1 of Fluarix Quadrivalent Vaccine [At Day 0 and Day 7]

   Seropositivity was defined as number of subjects with antibody titers greater than or equal to (≥) 1:10. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

8. Number of Subjects Seroconverted for HI Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 7 post dose 1]

   A seroconverted subject was defined as a subject who had either a pre-vaccination titer <1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a four-fold increase in post-vaccination titer. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria)and B/Hubei-Wujiagang/158/2009 (Yamagata )antigens.

9. Mean Geometric Increase (MGI) for HI Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 7 post dose 1]

   Mean geometric increase was defined as the geometric mean of the within subject ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011(H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

10. Number of Subjects Seroprotected for HI Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 0 and Day 7]

    Seroprotection rate was defined as the number of vaccinees with a serum HI titer greater than or equal to(≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011(H3N2), B/Brisbane/60/2008 (Victoria)and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

Secondary Outcome Measures

1. Number of Subjects With HI Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 0 and Day 7]

   The cut-off values assessed were less than (<) 1:10, 1:10 to < 1:40 and ≥ 1:40. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

2. Serum Neutralising Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine [At Day 0 and Day 7]

   Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

3. Serum Anti-neuraminidase Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine [At Day 0 and Day 7]

   Antibody titers were expressed as GMTs. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

4. Vaccine Response Rate (VRR) for Neutralising Antibody Titers Against Each of the Four Vaccine Strains. [At Day 7 post dose 1]

   VRR was defined as the number of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

5. MGI for Neutralising Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 7 post dose 1]

   MGI was defined as the fold increase in serum HI GMT post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

6. Vaccine Response Rate(VRR) for Anti-neuraminidase Antibody Titers Against Each of the Four Vaccine Strains. [At Day 7 post dose 1]

   VRR was defined as the number of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

7. MGI for Anti-neuraminidase Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 7 post dose 1]

   MGI was defined as the fold increase in serum HI GMT post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

8. Number of Subjects With HI Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 0 and Day 7]

   The cut-off values assessed were less than (<) 1:10, 1:10 to < 1:40,≥ 1:40, ≥1:60 and ≥1:80 . The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

9. Serum Micro Neutralizing(MN) Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 0 and Day 7]

   MN antibody titers were expressed as geometric mean titers(GMTs). The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

10. Serum Anti-neuraminidase Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine [At Day 0 and Day 7]

    NI (Neuraminidase inhibitor) antibody titers were expressed as geometric mean titers(GMTs).The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

11. Vaccine Response Rate(VRR) for Serum Neutralising Antibody Titers Against Each of the Four Vaccine Strains [At Day 7 post dose 1]

    VRR was defined as the number of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

12. MGI for Neutralising Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [At Day 7 post dose 1]

    MGI was defined as the fold increase in GMTs post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

13. Vaccine Response Rate(VRR) for Anti-neuraminidase Antibodies Against Each of the Four Vaccine Strains. [At Day 7 post dose 1]

    VRR was defined as the percentage of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

14. MGI for Anti-neuraminidase Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine [At Day 7 post dose 1]

    MGI was defined as the fold increase in GMTs post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

15. Serum Neutralising Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata. [At Day 0 and Day 7]

    Antibody titers were expressed as geometric mean titers. The vaccine strains included A/Christchurch/16/2010 (H1N1),A/Victoria/361/2011 (H3N2), A/Victoria/361/2011 and B/Hubei-Wujiagang/158/2009)(Yamagata) antigens. The humoral response in terms of neutralising antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.

16. Serum Anti-neuraminidase Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata [At Day 0 and Day 7]

    Antibody titers were expressed as geometric mean titers. The vaccine strains included A/Christchurch/16/2010(H1N1), A/Victoria/361/2011(H3N2),B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009(Yamagata) antigens. The humoral response in terms of anti-neuraminidase antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.

17. Vaccine Response Rate(VRR) for Serum Neutralising Antibody Titers Against Each of the Four Vaccine Strains by Age Strata [At Day 7 post dose 1]

    VRR was defined as the percentage of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011(H3N2), B/Brisbane/60/2008(Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens. The humoral response in terms of neutralising antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.

18. MGI for Neutralising Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata [At Day 7 post dose 1]

    MGI was defined as the fold increase in GMTs post-vaccination compared to Day 0.The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.The humoral response in terms of neutralising antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.

19. Vaccine Response Rate(VRR) for Anti-neuraminidase Antibody Titers Against Each of the Four Vaccine Strains by Age Strata. [At Day 7 post dose 1]

    VRR was defined as the percentage of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria /361/2011(H3N2), B/Brisbane /60/2008(Victoria ) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens. The humoral response in terms of anti-neuraminidase antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.

20. MGI for Anti-neuraminidase Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata. [At Day 7 post dose 1]

    MGI was defined as the fold increase in GMTs post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens. The humoral response in terms of anti-neuraminidase antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.

21. Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) [During a 7-day (Day 0 to 6) follow-up period after first vaccination]

    Solicited local AEs assessed were pain, redness and swelling. Any = any solicited local AE reported irrespective of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).

22. Duration of Solicted Symptoms [During the 7-day (Days 0-6) post-vaccination Dose 1 period]

    Duration was defined as number of days with any grade of solicted local and/or general symptoms

23. Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. [During the 7 days (Days 0 - 6) post dose 1 vaccination]

    Solicited general symptoms assessed were drowsiness, Irritability/Fussiness, loss of appetite and Temperature. Any Temperature = axillary temperature ≥37.5 degrees Celsius (°C). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 Irritability/Fussiness = Crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = did not eat at all. Grade 3 temperature = axillary temperature > 39.0°C.

24. Number of Subjects Reporting AEs With Medically Attended Visits (MAV) [During the entire study period (Day 0 - Day 179)]

    MAVs were defined as an AEs with a medically-attended visits i.e. prompting emergency room (ER) visits, hospitalizations or physician visits and that were not routine visits for physical examination or vaccination. Any MAV was defined as at least one MAV experienced. Grade 3 was a MAV that prevented normal activities and related was defined as a MAV assessed by the investigator to be causally related to the study vaccination.

25. Number of Subjects Reporting Potential Immune-Mediated Diseases (pIMDs) [During the entire study period (Days 0 - 179)]

    pIMDs were defined as a subset of AEs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune aetiology. Any pIMDs= Any AEs that occured regardless of the relation with vaccination. Related pIMDs= Any pIMD assessed by the investigator as casually related to the study vaccination.

26. Number of Subjects Reporting Any, Grade 3 and Related Unsolicited AEs. [Within 28 days (Days 0-27) after first vaccination]

    Unsolicited AE covers any AE 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 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination.

27. Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) [During the entire study period (Day 0 - Day 179)]

    A serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Months to 48 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects who the investigator believes that parent(s)/LAR(s) can and will comply with the requirements of the protocol.

• Children, male or female who received a 2-dose vaccination in the study 115345 (NCT01439360).

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

• Subjects in stable health as determined by medical history and clinical examination before entering into the study.

Exclusion Criteria:

• Child in care.

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

• Since the start of study 115345 (NCT01439360), receipt of any seasonal influenza vaccine other than the study vaccines of study 115345 or planned administration of any influenza vaccine other than the study vaccine during the study.

• Administration of any vaccine not foreseen by the study protocol within 4 weeks preceding the first dose of study vaccine or planned use until Visit 2.

• Laboratory confirmed influenza infection outside of the 115345 (NCT01439360) study.

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

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to enrolment in the study or planned administration during the study period. Inhaled and topical steroids are allowed.

• Administration of immunoglobulins and/ or any blood products within 3 months preceding the first dose of study vaccine or planned administration during the study period.

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.

• Any contraindication to intramuscular injection.

• Acute disease and/or fever at the time of enrollment:

• Fever is defined as temperature ≥ 37.5°C 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 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	Decin		Czechia	405 01
2	GSK Investigational Site	Jindrichuv Hradec		Czechia	37701
3	GSK Investigational Site	Lipnik nad Becvou		Czechia	75131
4	GSK Investigational Site	Nachod		Czechia	547 01
5	GSK Investigational Site	Odolena voda		Czechia	25070
6	GSK Investigational Site	Ostrava - Poruba		Czechia	70800
7	GSK Investigational Site	Pardubice		Czechia	532 03
8	GSK Investigational Site	Praha 6		Czechia	1600
9	GSK Investigational Site	Tabor		Czechia	390 02
10	GSK Investigational Site	Debica		Poland	39-200
11	GSK Investigational Site	Katowice		Poland	40-018
12	GSK Investigational Site	Siemianowice Slaskie		Poland	41-103
13	GSK Investigational Site	Antequera/Málaga		Spain	29200
14	GSK Investigational Site	Blanes (Girona)		Spain	17300
15	GSK Investigational Site	Castellón		Spain	12004
16	GSK Investigational Site	Castellón		Spain	12530
17	GSK Investigational Site	Centelles (Barcelona)		Spain	08540
18	GSK Investigational Site	Madrid		Spain	28046
19	GSK Investigational Site	Paiporta, Valencia		Spain	46200
20	GSK Investigational Site	Quart De Poblet, Valencia		Spain	46930
21	GSK Investigational Site	Santiago de Compostela		Spain	15706
22	GSK Investigational Site	Sevilla		Spain	41014
23	GSK Investigational Site	Valencia		Spain	46011
24	GSK Investigational Site	Valencia		Spain	46024
25	GSK Investigational Site	St Austell	Cornwall	United Kingdom	PL26 7RL
26	GSK Investigational Site	Coventry	Warwickshire	United Kingdom	CV6 4DD
27	GSK Investigational Site	Belfast		United Kingdom	BT7 2EB
28	GSK Investigational Site	Bristol		United Kingdom	BS2 8AE
29	GSK Investigational Site	Exeter		United Kingdom	EX2 5DW
30	GSK Investigational Site	Gloucester		United Kingdom	GL1 3NN
31	GSK Investigational Site	London		United Kingdom	SW17 0QT
32	GSK Investigational Site	Oxford		United Kingdom	OX3 7LJ
33	GSK Investigational Site	Southampton		United Kingdom	SO16 6YD

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: NCT01702454
• Other Study ID Numbers: 116023; 2012-001230-34
• First Posted: Oct 8, 2012
• Last Update Posted: Sep 7, 2018
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: GSK Biologicals quadrivalent influenza vaccine; Influenza; Children; Safety; Immunogenicity
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Period Title: Overall Study
STARTED	241	229
COMPLETED	238	221
NOT COMPLETED	3	8

Baseline Characteristics

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group	Total
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Total of all reporting groups
Overall Participants	241	229	470
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	33.2 (7.54)	32.5 (7.39)	32.8 (7.47)
Sex: Female, Male (Count of Participants)
Female	114 47.3%	96 41.9%	210 44.7%
Male	127 52.7%	133 58.1%	260 55.3%

Outcome Measures

1. Primary Outcome

Title	Serum Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine
Description	Antibody titers were expressed as Geometric Mean Titers (GMTs). The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	224	209
H1N1, Day 0 [N=221,202]	43.1	14.5
H1N1, Day 7 [N=224,209]	445.6	45.8
H3N2, Day 0 [N=221,202]	12.3	16.4
H3N2, Day 7 [N=224,209]	135.3	47.5
Victoria, Day 0 [N=221,202]	28.5	10.0
Victoria, Day 7 [N=224,209]	193.9	47.1
Yamagata, Day 0 [N=221,202]	11.9	6.5
Yamagata, Day 7 [N=224,209]	182.6	26.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	The adjusted GMT of HI antibodies for A/Christchurch strain at post-vaccination dose 1, the GMT ratio of Fluarix Quadrivalent Primed Group/Fluarix Quadrivalent Unprimed Group and the 2-sided 95% CI on each GMT ratio were computed after fitting an ANCOVA model on the logarithm10 transformation of the titers, including the vaccine group as fixed effect and the pre-vaccination log-10 titer and age as regressors.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Criterion: The lower limit (LL) of the two-sided 95% Confidence Interval (CI) for the GMT ratio is above 1
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted GMT ratio
	Estimated Value	8.97
	Confidence Interval	(2-Sided) 95%; 6.21 to 12.96
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	The adjusted GMT of HI antibodies for A/Victoria strain at post-vaccination dose 1, the GMT ratio of Fluarix Quadrivalent Primed Group/Fluarix Quadrivalent Unprimed Group and the 2-sided 95% CI on each GMT ratio were computed after fitting an ANCOVA model on the logarithm10 transformation of the titers, including the vaccine group as fixed effect and the pre-vaccination log-10 titer and age as regressors.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Criterion: The lower limit (LL) of the two-sided 95% Confidence Interval (CI) for the GMT ratio is above 1
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted GMT ratio
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 95%; 1.81 to 4.02
	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

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	The adjusted GMT of HI antibodies for B/Brisbane strain at post-vaccination dose 1, the GMT ratio of Fluarix Quadrivalent Primed Group/Fluarix Quadrivalent Unprimed Group and the 2-sided 95% CI on each GMT ratio were computed after fitting an ANCOVA model on the logarithm10 transformation of the titers, including the vaccine group as fixed effect and the pre-vaccination log-10 titer and age as regressors.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Criterion: The lower limit (LL) of the two-sided 95% Confidence Interval (CI) for the GMT ratio is above 1
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted GMT ratio
	Estimated Value	3.94
	Confidence Interval	(2-Sided) 95%; 2.89 to 5.37
	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	The adjusted GMT of HI antibodies for B/Hub-Wuj strain at post-vaccination dose 1, the GMT ratio of Fluarix Quadrivalent Primed Group/Fluarix Quadrivalent Unprimed Group and the 2-sided 95% CI on each GMT ratio were computed after fitting an ANCOVA model on the logarithm10 transformation of the titers, including the vaccine group as fixed effect and the pre-vaccination log-10 titer and age as regressors.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Criterion: The lower limit (LL) of the two-sided 95% Confidence Interval (CI) for the GMT ratio is above 1
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted GMT ratio
	Estimated Value	6.71
	Confidence Interval	(2-Sided) 95%; 5.21 to 8.63
	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.

2. Primary Outcome

Title	Number of Seropositive Subjects Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine
Description	Seropositivity was defined as number of subjects with antibody titers greater than or equal to (≥) 1:10. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	224	209
H1N1, Day 0 [N=221,202]	189	64
H1N1, Day 7 [N=224,209]	220	137
H3N2, Day 0 [N=221,202]	131	79
H3N2, Day 7 [N=224,209]	218	99
Victoria, Day 0 [N=221,202]	187	58
Victoria, Day 7 [N=224,209]	224	174
Yamagata, Day 0 [N=221,202]	134	36
Yamagata, Day 7 [N=224,209]	222	144

3. Primary Outcome

Title	Number of Subjects Seroconverted for HI Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 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 included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	221	202
H1N1	170	65
H3N2	180	73
Victoria	169	78
Yamagata	208	77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	To assess the immune response in terms of SCR difference at Day 7 after one dose of Fluarix Quadrivalent vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all the strains.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	SCR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	44.74
	Confidence Interval	(2-Sided) 95%; 35.87 to 52.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	To assess the immune response in terms of SCR difference at Day 7 after one dose of Fluarix Quadrivalent vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all the strains.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	SCR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	45.31
	Confidence Interval	(2-Sided) 95%; 36.58 to 53.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	To assess the immune response in terms of SCR difference at Day 7 after one dose of Fluarix Quadrivalent vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all the strains.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	SCR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	37.86
	Confidence Interval	() 95%; 28.83 to 46.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	To assess the immune response in terms of SCR difference at Day 7 after one dose of Fluarix Quadrivalent vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all the strains. B/Hu-Wuj = B/Hubei-Wujiagang/158/2009 (Yamagata)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	SCR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	56
	Confidence Interval	() 95%; 48.32 to 63.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Mean Geometric Increase (MGI) for HI Antibody Titer Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	MGI was defined as the fold increase in serum HI GMT post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	221	202
H1N1	10.3	3.2
H3N2	10.9	2.9
Victoria	6.7	4.6
Yamagata	15.2	4.0

5. Primary Outcome

Title	Number of Subjects Seroprotected for Anti-HA Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	Seroprotection rate (SPR) was defined as the number of vaccinees with serum haemagglutination inhibition (HI) titer ≥ 1:40 that usually is accepted as indicating protection in adults. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	224	209
H1N1, Day 0 [N=221,202]	89	61
H1N1, Day 7 [N=224,209]	217	72
H3N2, Day 0 [N=221,202]	37	74
H3N2, Day 7 [N=224,209]	193	81
Victoria, Day 0 [N=221,202]	72	39
Victoria, Day 7 [N=224,209]	217	84
Yamagata, Day 0 [N=221,202]	27	12
Yamagata, Day 7 [N=224,209]	216	83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	To assess the immune response in terms of SPR difference at Day 7 after one dose of Fluarix Quadrivalent vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all the strains
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	SPR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in SPR
	Estimated Value	62.43
	Confidence Interval	(2-Sided) 95%; 55.27 to 68.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	To assess the immune response in terms of SPR difference at Day 7 after one dose of Fluarix Quadrivalent vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all the strains.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	SPR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in SPR
	Estimated Value	47.4
	Confidence Interval	(2-Sided) 95%; 39.08 to 55.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	To assess the immune response in terms of SPR difference at Day 7 after one dose of Fluarix Quadrivalent vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all the strains.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	SPR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in SPR
	Estimated Value	56.68
	Confidence Interval	(2-Sided) 95%; 49.44 to 63.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Fluarix Quadrivalent Primed Group, Fluarix Quadrivalent Unprimed Group
	Comments	To assess the immune response in terms of SPR difference at Day 7 after one dose of Fluarix Quadrivalent vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all the strains. B/Hu-Wuj = B/Hubei-Wujiagang/158/2009 (Yamagata)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	SPR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in SPR
	Estimated Value	56.72
	Confidence Interval	(2-Sided) 95%; 49.41 to 63.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Serum Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	Antibody titers were expressed as Geometric Mean Titers (GMTs). The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NC T01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	213	179
H1N1, Day 0 [N=210,173]	44.0	14.3
H1N1, Day 7 [N=213,179]	442.3	42.7
H3N2, Day 0 [N=210,173]	11.0	11.9
H3N2, Day 7 [N=213,179]	125.9	28.7
Victoria, Day 0 [N=210,173]	27.8	10.3
Victoria, Day 7 [N=213,179]	193.3	46.1
Yamagata, Day 0 [N=210,173]	11.9	6.5
Yamagata, Day 7 [N=213,179]	184.1	25.2

7. Primary Outcome

Title	Number of Subjects Seropositive for HI Antibody Titers Against Each of the Four Vaccine Strains After Dose 1 of Fluarix Quadrivalent Vaccine
Description	Seropositivity was defined as number of subjects with antibody titers greater than or equal to (≥) 1:10. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	213	179
H1N1, Day 0 [N=210,173]	178	54
H1N1, Day 7 [N=213,179]	209	113
H3N2, Day 0 [N=210,173]	120	52
H3N2, Day 7 [N=213,179]	207	72
Victoria, Day 0[ N=210,173]	177	50
Victoria, Day 7[ N=213,179]	213	145
Yamagata, Day 0[ N=210,173]	127	31
Yamagata, Day 7 [N=213,179]	211	120

8. Primary Outcome

Title	Number of Subjects Seroconverted for HI Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	A seroconverted subject was defined as a subject who had either a pre-vaccination titer <1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a four-fold increase in post-vaccination titer. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria)and B/Hubei-Wujiagang/158/2009 (Yamagata )antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	210	173
H1N1, Day 7 [N=210,173]	160	54
H3N2, Day 7 [N=210,173]	173	49
Victoria, Day 7 [N=210,173]	162	66
Yamagata, Day 7 [N=210,173]	197	65

9. Primary Outcome

Title	Mean Geometric Increase (MGI) for HI Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	Mean geometric increase was defined as the geometric mean of the within subject ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011(H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	210	173
H1N1, Day 7 [N=210,173]	10.0	3.1
H3N2, Day 7 [N=210,173]	11.2	2.4
Victoria, Day 7 [N=210,173]	6.9	4.5
Yamagata, Day 7 [N=210,173]	15.2	4.0

10. Primary Outcome

Title	Number of Subjects Seroprotected for HI Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	Seroprotection rate was defined as the number of vaccinees with a serum HI titer greater than or equal to(≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011(H3N2), B/Brisbane/60/2008 (Victoria)and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	213	179
H1N1,Day 0 [N=210,173]	87	51
H1N1, Day 7 [N=213,179]	206	59
H3N2, Day 0 [N=210,173]	29	48
H3N2, Day 7 [N=213,179]	182	54
Victoria, Day 0 [N=210,173]	68	35
Victoria, Day 7 [N=213,179]	206	70
Yamagata, Day 0 [N=210,173]	27	10
Yamagata, Day 7 [N=213,179]	205	70

11. Secondary Outcome

Title	Number of Subjects With HI Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	The cut-off values assessed were less than (<) 1:10, 1:10 to < 1:40 and ≥ 1:40. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	224	209
H1N1 (<1:10), Day 0 [N=221,202]	32	138
H1N1 (<1:10), Day 7 [N=224,209]	4	72
H3N2 (<1:10), Day 0 [N=221,202]	90	123
H3N2 (<1:10), Day 7 [N=224,209]	6	110
Victoria (<1:10), Day 0 [N=221,202]	34	144
Victoria (<1:10), Day 7 [N=224,209]	0	35
Yamagata (<1:10), Day 0 [N=221,202]	87	166
Yamagata (<1:10), Day 7 [N=224,209]	2	65
H1N1 (1:10 to <1:40), Day 0 [N=221,202]	100	3
H1N1 (1:10 to <1:40), Day 7 [N=224,209]	3	65
H3N2 (1:10 to <1:40), Day 0 [N=221,202]	94	5
H3N2 (1:10 to <1:40), Day 7 [N=224,209]	25	18
Victoria (1:10 to <1:40), Day 0 [N=221,202]	115	19
Victoria (1:10 to <1:40), Day 7 [N=224,209]	7	90
Yamagata (1:10 to <1:40), Day 0 [N=221,202]	107	24
Yamagata (1:10 to <1:40), Day 7 [N=224,209]	6	61
H1N1 (≥1: 40), Day 0 [N=221,202]	89	61
H1N1 (≥1: 40), Day 7 [N=224,209]	217	72
H3N2 (≥1: 40), Day 0 [N=221,202]	37	74
H3N2 (≥1: 40), Day 7 [N=224,209]	193	81
Victoria (≥1: 40), Day 0 [N=221,202]	72	39
Victoria (≥1: 40), Day 7 [N=224,209]	217	84
Yamagata (≥1: 40), Day 0 [N=221,202]	27	12
Yamagata (≥1: 40), Day 7 [N=224,209]	216	83

12. Secondary Outcome

Title	Serum Neutralising Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine
Description	Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	107	109
H1N1, Day 0 [N=97,90]	138.2	48.3
H1N1, Day 7 [N=107, 96]	1500.9	139.4
H3N2, Day 0 [N=99,96]	66.5	82.8
H3N2, Day 7 [N=104,100]	422.9	325.1
Victoria, Day 0 [N=107,109]	38.6	22.2
Victoria, Day 7 [N=107, 108]	193.7	47.0
Yamagata, Day 0 [N=107,107]	36.9	30.8
Yamagata, Day 7 [N=107,107]	182.7	51.7

13. Secondary Outcome

Title	Serum Anti-neuraminidase Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine
Description	Antibody titers were expressed as GMTs. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	107	109
H1N1, Day 0 [N=106,106]	34.6	24.1
H1N1, Day 7 [N=106, 109]	293.9	41.3
H3N2, Day 0 [N=107,106]	38.4	58.8
H3N2, Day 7 [N=107, 109]	189.4	114.2
Victoria, Day 0 [N=106,106]	17.4	14.3
Victoria, Day 7 [N=106,109]	90.6	27.6
Yamagata, Day 0 [N=106, 106]	25.3	15.4
Yamagata, Day 7 [N=106,109]	222.0	40.6

14. Secondary Outcome

Title	Vaccine Response Rate (VRR) for Neutralising Antibody Titers Against Each of the Four Vaccine Strains.
Description	VRR was defined as the number of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	107	108
H1N1 [N=97,89]	74	36
H3N2 [N=97,94]	72	48
Victoria [N=107,108]	78	24
Yamagata [N=107,105]	45	15

15. Secondary Outcome

Title	MGI for Neutralising Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	MGI was defined as the fold increase in serum HI GMT post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	107	108
H1N1 [N=97, 89]	10.6	3.1
H3N2 [N=97, 94]	6.4	4.5
Victoria [N=107,108]	5.0	2.1
Yamagata [N=107,105]	5.0	1.7

16. Secondary Outcome

Title	Vaccine Response Rate(VRR) for Anti-neuraminidase Antibody Titers Against Each of the Four Vaccine Strains.
Description	VRR was defined as the number of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	107	106
H1N1 [N=105,106]	75	31
H3N2 [N=107,106]	75	31
Victoria [N=105,106]	79	24
Yamagata [N=105,106]	90	29

17. Secondary Outcome

Title	MGI for Anti-neuraminidase Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	MGI was defined as the fold increase in serum HI GMT post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	107	106
H1N1 [N=105,106]	8.3	1.8
H3N2 [N=105,106]	5.2	1.9
Victoria [N=105,106]	8.8	2.7
Yamagata [N=107,106]	4.9	2.0

18. Secondary Outcome

Title	Number of Subjects With HI Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	The cut-off values assessed were less than (<) 1:10, 1:10 to < 1:40,≥ 1:40, ≥1:60 and ≥1:80 . The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	213	179
H1N1, Day 0, <1:10 [N=210,173]	32	119
H1N1, Day 7, <1:10 [N=213,179]	4	66
H1N1, Day 0, 1:10 to <1:40 [N=210,173]	178	54
H1N1, Day 7, 1:10 to <1:40 [N=213,179]	209	113
H1N1, Day 0, ≥1:40 [N=210,173]	87	51
H1N1, Day 7, ≥1:40 [N=213,179]	206	59
H1N1, Day 0, ≥1:60 [N=210,173]	73	47
H1N1, Day 7, ≥1:60 [N=213,179]	204	57
H1N1, Day 0, ≥1:80 [N=210,173]	73	47
H1N1, Day 7, ≥1:80 [N=213,179]	204	57
H3N2, Day 0, <1:10 [N=210,173]	90	121
H3N2, Day 7, <1:10 [N=213,179]	6	107
H3N2, Day 0,1:10 to 1:40 [N=210,173]	120	52
H3N2, Day 7,1:10 to 1:40 [N=213,179]	207	72
H3N2, Day 0, ≥1:40 [N=210,173]	29	48
H3N2, Day 7, ≥1:40 [N=213,179]	182	54
H3N2, Day 0, ≥1:60 [N=210,173]	12	36
H3N2, Day 7, ≥1:60 [N=213,179]	147	52
H3N2, Day 0, ≥1:80 [N=210,173]	12	36
H3N2, Day 7, ≥1:80 [N=213,179]	147	52
Victoria, Day 0, <1:10 [N=210,173]	33	123
Victoria, Day 7, <1:10 [N=213,179]	0	34
Victoria, Day 0,1:10 to 1:40 [N=210,173]	177	50
Victoria, Day 7,1:10 to 1:40 [N=213,179]	213	145
Victoria, Day 0, ≥1:40 [N=210,173]	68	35
Victoria, Day 7, ≥1:40 [N=213,179]	206	70
Victoria, Day 0, ≥1:60 [N=210,173]	40	27
Victoria, Day 7, ≥1:60 [N=213,179]	182	51
Victoria, Day 0, ≥1:80 [N=210,173]	40	27
Victoria, Day 7, ≥1:80 [N=213,179]	182	51
Yamagata, Day 0, <1:10 [N=210,173]	83	142
Yamagata, Day 7, <1:10 [N=213,179]	2	59
Yamagata, Day 0,1:10 to 1:40 [N=210,173]	127	31
Yamagata, Day 7,1:10 to 1:40 [N=213,179]	211	120
Yamagata, Day 0, ≥1:40 [N=210,173]	27	10
Yamagata, Day 7, ≥1:40 [N=213,179]	205	70
Yamagata, Day 0, ≥1:60 [N=210,173]	7	4
Yamagata, Day 7, ≥1:60 [N=213,179]	177	44
Yamagata, Day 0, ≥1:80 [N=210,173]	7	4
Yamagata, Day 7, ≥1:80 [N=213,179]	177	44

19. Secondary Outcome

Title	Serum Micro Neutralizing(MN) Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	MN antibody titers were expressed as geometric mean titers(GMTs). The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	100	89
H1N1,Day 0[N=90,72]	141.4	47.3
H1N1,Day 7[N=100,76]	1461.3	138.4
H3N2,Day 0[N=92,76]	60.0	59.6
H3N2,Day 7[N=97,80]	374.6	177.7
Victoria,Day 0[N=100,89]	37.1	23.5
Victoria,Day 7[N=100,88]	189.9	52.0
Yamagata,day 0[N=100,87]	37.1	30.9
Yamagata, Day 7[N=100,88]	177.5	49.8

20. Secondary Outcome

Title	Serum Anti-neuraminidase Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine
Description	NI (Neuraminidase inhibitor) antibody titers were expressed as geometric mean titers(GMTs).The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	100	89
H1N1, Day 0[N=99,86]	34.8	23.5
H1N1, Day 7[N=99,89]	287.1	38.3
H3N2, Day 0[N=100,86]	35.0	45.9
H3N2, Day 7[N=100,89]	175.8	84.5
Victoria, Day 0[N=99,86]	16.8	15.0
Victoria, Day 7[N=99,89]	89.2	29.1
Yamagata, Day 0[N=99,86]	25.1	15.4
Yamagata, Day 7[N=100,89]	216.5	39.7

21. Secondary Outcome

Title	Vaccine Response Rate(VRR) for Serum Neutralising Antibody Titers Against Each of the Four Vaccine Strains
Description	VRR was defined as the number of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	100	88
H1N1, Day 7[N=90,71]	67	28
H3N2, Day 7[N=90,74]	66	31
Victoria, Day 7[N=100,88]	74	21
Yamagata, Day 7[N=100,86]	42	11

22. Secondary Outcome

Title	MGI for Neutralising Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.
Description	MGI was defined as the fold increase in GMTs post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	100	88
H1N1, Day 7[N=90,71]	10.0	3.1
H3N2, Day 7[N=90,74]	6.2	3.4
Victoria, Day 7[N=100,88]	5.1	2.2
Yamagata, Day 7[N=100,86]	4.8	1.6

23. Secondary Outcome

Title	Vaccine Response Rate(VRR) for Anti-neuraminidase Antibodies Against Each of the Four Vaccine Strains.
Description	VRR was defined as the percentage of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	100	86
H1N1, Day 7[N=98,86]	70	23
H3N2, Day 7[N=100,86]	70	22
Victoria, Day 7[N=98,86]	74	20
Yamagata, Day 7[N=99,86]	85	23

24. Secondary Outcome

Title	MGI for Anti-neuraminidase Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine
Description	MGI was defined as the fold increase in GMTs post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analyses was performed on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	100	86
H1N1, Day 7[N=98,86]	8.1	1.7
H3N2, Day 7[N=100,86]	5.0	1.8
Victoria, Day 7[N=98,86]	5.2	1.9
Yamagata, Day 7[N=99,86]	8.7	2.6

25. Secondary Outcome

Title	Serum Neutralising Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata.
Description	Antibody titers were expressed as geometric mean titers. The vaccine strains included A/Christchurch/16/2010 (H1N1),A/Victoria/361/2011 (H3N2), A/Victoria/361/2011 and B/Hubei-Wujiagang/158/2009)(Yamagata) antigens. The humoral response in terms of neutralising antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects who received study vaccine according to their treatment assignment, for whom assay results for antibodies against at least 1 study vaccine strain after vaccination and data concerning immunogenicity outcome measures were available

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	54	55
H1N1, Day 0,17-29M[N=47,44]	76.8	29.0
H1N1, Day 7,17-29M [N=53,48]	1112.0	53.0
H1N1, Day 0,30-48M[N=50,46]	240.0	78.8
H1N1, Day 7,30-48M[N=54,48]	2014.5	366.9
H3N2,Day 0,17-29M[N=49,47]	58.1	74.5
H3N2,Day 7,17-29M[N=51,50]	370.5	217.5
H3N2,Day 0,30-48M[N=50,49]	76.0	91.5
H3N2,Day 7,30-48M[N=53,50]	480.3	485.8
Victoria,Day 0,17-29M[N=53,54]	29.2	19.8
Victoria,Day 7,17-29M[N=53,53]	156.3	35.5
Victoria,Day 0,30-48M[N=54,55]	50.9	24.7
Victoria,Day 7,30-48M[N=54,55]	239.1	61.8
Yamagata, Day 0,17-29M[N=53,53]	35.6	29.6
Yamagata, Day 7,17-29M[N=53,52]	156.9	45.6
Yamagata, Day 0,30-48M[N=54,54]	38.3	32.0
Yamagata, Day 7,30-48M[N=54,55]	212.2	58.3

26. Secondary Outcome

Title	Serum Anti-neuraminidase Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata
Description	Antibody titers were expressed as geometric mean titers. The vaccine strains included A/Christchurch/16/2010(H1N1), A/Victoria/361/2011(H3N2),B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009(Yamagata) antigens. The humoral response in terms of anti-neuraminidase antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.
Time Frame	At Day 0 and Day 7

Outcome Measure Data

Analysis Population Description

Analyses were performed on the ATP cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment, for whom the assay results for antibodies against at least one study vaccine strain after vaccination and for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	54	55
H1N1, Day 0,17-29M[N=53,52]	21.6	15.8
H1N1, Day 7,17-29M[N=53,54]	246.3	22.9
H1N1, Day 0,30-48M[N=53,54]	55.5	36.1
H1N1, Day 7,30-48M[N=53,55]	350.7	73.7
H3N2, Day 0,17-29M[N=53,52]	34.7	49.8
H3N2, Day 7,17-29M[N=53,54]	158.0	85.3
H3N2, Day 0,30-48M[N=54,54]	42.4	69.0
H3N2, Day 7,30-48M[N=54,55]	226.4	152.2
Victoria, Day 0,17-29M[N=53,52]	13.2	13.1
Victoria, Day 7,17-29M[N=53,54]	68.8	21.1
Victoria, Day 0,30-48M[N=53,54]	22.8	15.7
Victoria, Day 7,30-48M[N=53,55]	119.2	35.9
Yamagata, Day 0,17-29M[N=53,52]	20.5	13.2
Yamagata, Day 7,17-29M[N=53,54]	181.4	29.3
Yamagata, Day 0,30-48M[N=53,54]	31.1	17.9
Yamagata, Day 7,30-48M[N=53,55]	271.8	55.8

27. Secondary Outcome

Title	Vaccine Response Rate(VRR) for Serum Neutralising Antibody Titers Against Each of the Four Vaccine Strains by Age Strata
Description	VRR was defined as the percentage of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011(H3N2), B/Brisbane/60/2008(Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens. The humoral response in terms of neutralising antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analyses were perfomed on the ATP cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment, for whom the assay results for antibodies against at least one study vaccine strain after vaccination and for whom data concerning immunogenicity outcome measures were available

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	54	55
H1N1, Day 7, 17-29M[47,44]	39	12
H1N1, Day 7, 30-48M[50,45]	35	24
H3N2, Day 7,17-29M[N=48,46]	36	19
H3N2, Day 7,30-48M[N=49,48]	36	29
Victoria, Day 7,17-29M[N=53,53]	41	9
Victoria, Day 7,30-48M[N=54,55]	37	15
Yamagata, Day 7,17-29M[N=53,51]	17	6
Yamagata, Day 7,30-48M[N=54,54]	28	9

28. Secondary Outcome

Title	MGI for Neutralising Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata
Description	MGI was defined as the fold increase in GMTs post-vaccination compared to Day 0.The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.The humoral response in terms of neutralising antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analyses were performed on the ATP cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment, for whom the assay results for antibodies against at least one study vaccine strain after vaccination and for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	54	55
H1N1, Day 7, 17-29M[N=47,44]	13.1	2.0
H1N1, Day 7, 30-48M[N=50,45]	8.7	4.7
H3N2, Day 7,17-29M[N=48,46]	6.1	3.4
H3N2, Day 7,30-48M[N=49,48]	6.7	5.9
Victoria, Day 7,17-29M[N=53,53]	5.4	1.8
Victoria, Day 7,30-48M[N=54,55]	4.7	2.5
Yamagata, Day 7,17-29M[N=53,51]	4.4	1.5
Yamagata, Day 7,30-48M[N=54,54]	5.5	1.8

29. Secondary Outcome

Title	Vaccine Response Rate(VRR) for Anti-neuraminidase Antibody Titers Against Each of the Four Vaccine Strains by Age Strata.
Description	VRR was defined as the percentage of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria /361/2011(H3N2), B/Brisbane /60/2008(Victoria ) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens. The humoral response in terms of anti-neuraminidase antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analyses were performed on the ATP cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment, for whom the assay results for antibodies against at least one study vaccine strain after vaccination and for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	54	54
H1N1, Day 7,17-29M[N=53,52]	43	11
H1N1, Day 7,30-48M[N=52,54]	32	20
H3N2, Day 7,17-29M[N=53,52]	36	8
H3N2, Day 7,30-48M[N=54,54]	39	23
Victoria, Day 7,17-29M[N=53,52]	40	8
Victoria, Day 7,30-48M[N=52,54]	39	16
Yamagata, Day 7, 17-29M[N=53,52]	46	10
Yamagata, Day 7, 30-48M[N=52,54]	44	19

30. Secondary Outcome

Title	MGI for Anti-neuraminidase Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata.
Description	MGI was defined as the fold increase in GMTs post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens. The humoral response in terms of anti-neuraminidase antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.
Time Frame	At Day 7 post dose 1

Outcome Measure Data

Analysis Population Description

Analyses were performed on the ATP cohort for immunogenicity which included all evaluable subjects who received the study vaccine according to their treatment assignment, for whom the assay results for antibodies against at least one study vaccine strain after vaccination and for whom data concerning immunogenicity outcome measures were available

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	54	54
H1N1, Day 7,17-29M[53,52]	11.4	1.5
H1N1, Day 7,30-48M[N=52,54]	6.0	2.1
H3N2, Day 7,17-29M[N=53,52]	4.6	1.7
H3N2, Day 7,30-48M[N=54,54]	5.3	2.3
Victoria, Day 7,17-29M[N=53,52]	5.2	1.5
Victoria, Day 7,30-48M[N=52,54]	5.1	2.3
Yamagata, Day 7, 17-29M[N=53,52]	8.8	2.2
Yamagata, Day 7, 30-48M[N=52,54]	8.7	3.2

31. Secondary Outcome

Title	Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs)
Description	Solicited local AEs assessed were pain, redness and swelling. Any = any solicited local AE reported irrespective of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).
Time Frame	During a 7-day (Day 0 to 6) follow-up period after first vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated cohort included all subjects with at least one vaccine administration documented and symptom sheet completed.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	239	228
Any Pain	96	61
Grade 3 Pain	2	1
Any Redness	82	48
Grade 3 Redness	2	0
Any Swelling	49	25
Grade 3 Swelling	2	0

32. Secondary Outcome

Title	Duration of Solicted Symptoms
Description	Duration was defined as number of days with any grade of solicted local and/or general symptoms
Time Frame	During the 7-day (Days 0-6) post-vaccination Dose 1 period

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated cohort included all subjects with at least one vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	96	61
Drowsiness	1.0	1.0
Irritability/fussiness	2.0	2.0
Loss of appetite	2.0	2.0
Pain	1.0	1.0
Redness	2.0	2.0
Swelling	2.0	1.0
Temperature	1.0	2.0

33. Secondary Outcome

Title	Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
Description	Solicited general symptoms assessed were drowsiness, Irritability/Fussiness, loss of appetite and Temperature. Any Temperature = axillary temperature ≥37.5 degrees Celsius (°C). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 Irritability/Fussiness = Crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = did not eat at all. Grade 3 temperature = axillary temperature > 39.0°C.
Time Frame	During the 7 days (Days 0 - 6) post dose 1 vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated cohort included all subjects with at least one vaccine administration documented and symptom sheet completed.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	238	224
Any Drowsiness	54	44
Grade 3 Drowsiness	5	1
Related Drowsiness	36	28
Any Irritability/Fussiness	77	59
Grade 3 Irritability/Fussiness	5	5
Related Irritability/Fussiness	51	43
Any Loss of appetite	51	46
Grade 3 Loss of appetite	8	5
Related Loss of appetite	31	31
Any Temperature	13	26
Grade 3 Temperature	2	1
Related Temperature	6	15

34. Secondary Outcome

Title	Number of Subjects Reporting AEs With Medically Attended Visits (MAV)
Description	MAVs were defined as an AEs with a medically-attended visits i.e. prompting emergency room (ER) visits, hospitalizations or physician visits and that were not routine visits for physical examination or vaccination. Any MAV was defined as at least one MAV experienced. Grade 3 was a MAV that prevented normal activities and related was defined as a MAV assessed by the investigator to be causally related to the study vaccination.
Time Frame	During the entire study period (Day 0 - Day 179)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated cohort included all subjects with at least one vaccine administration documented.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	241	229
Any MAV	149	130
Grade 3 MAV	5	8
Related MAV	0	1

35. Secondary Outcome

Title	Number of Subjects Reporting Potential Immune-Mediated Diseases (pIMDs)
Description	pIMDs were defined as a subset of AEs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune aetiology. Any pIMDs= Any AEs that occured regardless of the relation with vaccination. Related pIMDs= Any pIMD assessed by the investigator as casually related to the study vaccination.
Time Frame	During the entire study period (Days 0 - 179)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated cohort included all subjects with at least one vaccine administration documented.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	241	229
Any pIMD	0	0
Related pIMD	0	0

36. Secondary Outcome

Title	Number of Subjects Reporting Any, Grade 3 and Related Unsolicited AEs.
Description	Unsolicited AE covers any AE 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 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination.
Time Frame	Within 28 days (Days 0-27) after first vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated cohort included all subjects with at least one vaccine administration documented.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	241	229
Any Unsolicted AEs	66	66
Grade 3 Unsolicted AEs	6	7
Related Unsolicted AEs	5	3

37. Secondary Outcome

Title	Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs)
Description	A serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Time Frame	During the entire study period (Day 0 - Day 179)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Total Vaccinated cohort included all subjects with at least one vaccine administration documented.

Arm/Group Title	Fluarix Quadrivalent Primed Group	Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.	SuSubjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Measure Participants	241	229
Any SAE(s)	7	8
Related SAE(s)	0	0

Adverse Events

Time Frame	Serious Adverse Events: From Day 0 to Day 179; Solicited local and general symptoms: During the 7-day (Days 0-6) post-vaccination period; Unsolicited symptoms: During the 28-day (Day 0-27) post-vaccination period.
Adverse Event Reporting Description	For the frequent adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
Arm/Group Title	Fluarix Quadrivalent Primed Group		Fluarix Quadrivalent Unprimed Group
Arm/Group Description	Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.		Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
All Cause Mortality
	Fluarix Quadrivalent Primed Group		Fluarix Quadrivalent Unprimed Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fluarix Quadrivalent Primed Group		Fluarix Quadrivalent Unprimed Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/241 (2.9%)		8/229 (3.5%)
Gastrointestinal disorders
Inguinal hernia	0/241 (0%)		1/229 (0.4%)
Infections and infestations
Gastroenteritis	0/241 (0%)		2/229 (0.9%)
Bronchiolitis	0/241 (0%)		1/229 (0.4%)
Bronchitis	1/241 (0.4%)		0/229 (0%)
Bronchopneumonia	1/241 (0.4%)		0/229 (0%)
Laryngitis	1/241 (0.4%)		0/229 (0%)
Lymphadenitis bacterial	0/241 (0%)		1/229 (0.4%)
Otitis media	1/241 (0.4%)		0/229 (0%)
Otitis media acute	1/241 (0.4%)		0/229 (0%)
Pharyngitis	0/241 (0%)		1/229 (0.4%)
Pneumonia bacterial	0/241 (0%)		1/229 (0.4%)
Rhinitis	1/241 (0.4%)		0/229 (0%)
Sinusitis	1/241 (0.4%)		0/229 (0%)
Injury, poisoning and procedural complications
Thermal burn	1/241 (0.4%)		0/229 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/241 (0.4%)		0/229 (0%)
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy	0/241 (0%)		1/229 (0.4%)
Upper respiratory tract inflammation	1/241 (0.4%)		0/229 (0%)
Skin and subcutaneous tissue disorders
Urticaria	1/241 (0.4%)		0/229 (0%)
Other (Not Including Serious) Adverse Events
	Fluarix Quadrivalent Primed Group		Fluarix Quadrivalent Unprimed Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	145/241 (60.2%)		138/229 (60.3%)
General disorders
Pain	96/239 (40.2%)		61/228 (26.8%)
Redness	82/239 (34.3%)		48/228 (21.1%)
Swelling	49/239 (20.5%)		25/228 (11%)
Drowsiness	54/238 (22.7%)		44/224 (19.6%)
Irritability/Fussiness	77/238 (32.4%)		59/224 (26.3%)
Loss of Appetite	51/238 (21.4%)		46/224 (20.5%)
Temperature	13/238 (5.5%)		26/224 (11.6%)
Respiratory, thoracic and mediastinal disorders
Cough	9/241 (3.7%)		13/229 (5.7%)

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.