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A Study to Evaluate the Efficacy of GSK Biologicals' Influenza Vaccine in Children

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01218308
Recruitment Status : Completed
First Posted : October 11, 2010
Results First Posted : April 2, 2013
Last Update Posted : August 1, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Influenza
Interventions Biological: FluLaval® Quadrivalent
Biological: Havrix™
Enrollment 5220
Recruitment Details A total of 5168 subjects have been enrolled in this study. Primed subjects had received at least 1 dose of an influenza A (H1N1) 2009 monovalent vaccine and had received 2 doses of seasonal influenza vaccine. Unprimed subjects had not received any influenza A (H1N1) 2009 monovalent vaccine or seasonal influenza vaccine.
Pre-assignment Details The duration of the study was approximately 4-8 weeks to complete enrolment, with at least six months extended safety follow-up (ESFU) after first vaccination, and lasted until the end of the influenza like illness (ILI) surveillance period.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm. Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Period Title: Overall Study
Started 2584 2584
Completed 2481 2464
Not Completed 103 120
Reason Not Completed
Adverse Event             1             2
Protocol Violation             0             2
Withdrawal by Subject             61             64
Lost to Follow-up             27             31
Other             14             21
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group Total
Hide Arm/Group Description Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm. Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm. Total of all reporting groups
Overall Number of Baseline Participants 2584 2584 5168
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2584 participants 2584 participants 5168 participants
5.4  (1.66) 5.4  (1.65) 5.4  (1.65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2584 participants 2584 participants 5168 participants
Female
1251
  48.4%
1245
  48.2%
2496
  48.3%
Male
1333
  51.6%
1339
  51.8%
2672
  51.7%
1.Primary Outcome
Title Number of Subjects Reporting at Least One Confirmed Occurrence of Influenza A or B.
Hide Description To confirm influenza A and/or B disease, a positive reverse transcriptase polymerase chain reaction (RT-PCR) result for influenza A or B virus from a nose and throat swab obtained concurrently with an influenza like illness (ILI) was required. ILI was defined as the presence of an oral or axillary temperature ≥ 37.8 degrees Celsius (°C) in the presence of at least one of the following symptoms on the same day: cough, sore throat, runny nose or nasal congestion.
Time Frame From Day 14 to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the According-To-Protocol cohort for efficacy - Time to event, which included all eligible subjects who met all inclusion criteria and no exclusion criteria, followed their study treatment assignment and were successfully contacted at least once after the first vaccination.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 2379 2398
Measure Type: Number
Unit of Measure: subjects
58 128
2.Secondary Outcome
Title Number of Subjects Reporting at Least One Moderate to Severe Occurrence of Influenza A or B.
Hide Description

To confirm influenza A and/or B disease moderate to severe cases, a positive RT-PCR result for influenza A or B virus from a nose and throat swab obtained concurrently with an ILI was required. Moderate to severe influenza was defined as RT-PCR-confirmed ILI with:

  • Fever >39°C, and/or at least one of the following manifestations,
  • Physician-verified shortness of breath, pulmonary congestion, pneumonia, bronchiolitis, bronchitis, wheezing, croup, or acute otitis media, and/or one of the following,
  • Physician-diagnosed serious extra-pulmonary complication of influenza, including myositis, encephalitis, seizure, or myocarditis
Time Frame From Day 14 to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the According-To-Protocol cohort for efficacy - Time to event, which included all eligible subjects who met all inclusion criteria and no exclusion criteria, followed their study treatment assignment and were successfully contacted at least once after the first vaccination.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 2379 2398
Measure Type: Number
Unit of Measure: subjects
14 52
3.Secondary Outcome
Title Number of Subjects Reporting at Least One Culture Confirmed Occurrence of Influenza A or B Due to Antigenically Matched Strain.
Hide Description To confirm influenza A and/or B disease due to antigenically matched strain, a positive reverse transcriptase polymerase chain reaction (RT-PCR) result for influenza A or B virus from a nose and throat swab obtained concurrently with an influenza like illness (ILI) was required. ILI was defined as the presence of an oral or axillary temperature ≥ 37.8 degrees Celsius (°C) in the presence of at least one of the following symptoms on the same day: cough, sore throat, runny nose or nasal congestion.
Time Frame From Day 14 to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the According-To-Protocol cohort for efficacy - Time to event, which included all eligible subjects who met all inclusion criteria and no exclusion criteria, followed their study treatment assignment and were successfully contacted at least once after the first vaccination.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 2379 2398
Measure Type: Number
Unit of Measure: subjects
31 56
4.Secondary Outcome
Title Number of Subjects Reporting at Least One Culture Confirmed Occurrence of Influenza A or B Due to Any Strain.
Hide Description To confirm influenza A and/or B disease due to any strain, a positive reverse transcriptase polymerase chain reaction (RT-PCR) result for influenza A or B virus from a nose and throat swab obtained concurrently with an influenza like illness (ILI) was required. ILI was defined as the presence of an oral or axillary temperature ≥ 37.8 degrees Celsius (°C) in the presence of at least one of the following symptoms on the same day: cough, sore throat, runny nose or nasal congestion.
Time Frame From Day 14 to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the According-To-Protocol cohort for efficacy - Time to event, which included all eligible subjects who met all inclusion criteria and no exclusion criteria, followed their study treatment assignment and were successfully contacted at least once after the first vaccination.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 2379 2398
Measure Type: Number
Unit of Measure: subjects
50 112
5.Secondary Outcome
Title Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease.
Hide Description Titers are presented as geometric mean titers (GMTs). The reference cut-off value was the seropositivity cut-off of 1:10. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).
Time Frame At Day 0 [PRE] and 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST]
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects (those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome measure were available.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 457 122
Geometric Mean (95% Confidence Interval)
Unit of Measure: titers
H1N1, PRE [N=457;117]
15.3
(13.6 to 17.3)
16.1
(12.6 to 20.5)
H1N1, POST [N=457;121]
318.8
(291.0 to 349.2)
16.1
(12.8 to 20.2)
H3N2, PRE [N=457;117]
24.3
(21.9 to 27.0)
28.6
(23.5 to 34.8)
H3N2, POST [N=457;122]
264.7
(244.3 to 286.8)
30.3
(24.8 to 36.9)
Victoria, PRE [N=457;117]
13.7
(12.2 to 15.4)
15.6
(12.2 to 20.1)
Victoria, POST [N=457;120]
239.9
(214.6 to 268.2)
17.8
(13.7 to 23.1)
Yamagata, PRE [N=457;117]
16.2
(14.3 to 18.4)
18.8
(14.4 to 24.5)
Yamagata, POST [N=457;117]
361.5
(330.7 to 395.3)
19.2
(14.9 to 24.7)
6.Secondary Outcome
Title Number of Seroconverted Subjects Against 4 Strains of Influenza Disease.
Hide Description A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).
Time Frame At 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST]
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects (those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome measure were available.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 457 117
Measure Type: Number
Unit of Measure: subjects
H1N1, POST 438 1
H3N2, POST 385 2
Victoria, POST 425 3
Yamagata, POST 435 1
7.Secondary Outcome
Title Number of Seroprotected Subjects Against 4 Strains of Influenza Disease.
Hide Description A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).
Time Frame At Day 0 [PRE] and 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST]
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects (those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome measure were available.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 457 122
Measure Type: Number
Unit of Measure: subjects
H1N1, PRE [N=457;117] 151 37
H1N1, POST [N=457;121] 451 39
H3N2, PRE [N=457;117] 205 63
H3N2, POST [N=457;122] 445 63
Victoria, PRE [N=457;117] 127 35
Victoria, POST [N=457;120] 443 38
Yamagata, PRE [N=457;117] 159 45
Yamagata, POST [N=457;117] 452 45
8.Secondary Outcome
Title Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease.
Hide Description The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).
Time Frame At 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST]
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects (those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome measure were available.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 457 117
Mean (95% Confidence Interval)
Unit of Measure: fold increase
H1N1, POST
20.8
(19.0 to 22.8)
1.0
(0.9 to 1.1)
H3N2, POST
10.9
(9.8 to 12.1)
1.0
(0.9 to 1.2)
Victoria, POST
17.5
(16.0 to 19.1)
1.1
(1.0 to 1.3)
Yamagata, POST
22.3
(20.1 to 24.8)
1.0
(1.0 to 1.1)
9.Secondary Outcome
Title Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 4 Vaccine Strains
Hide Description HI antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/California/7/2009 (H1N1), Flu A/Victoria/210/09 (H3N2), Flu B/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).
Time Frame On Day 0 and at least 6 months after first vaccination (Month 6)
Hide Outcome Measure Data
Hide Analysis Population Description
The ATP Cohort for persistence included, in terms of antibody response measured by the HI assay, all evaluable subjects for whom data concerning immunogenicity outcome measure were available and for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 444 112
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titer
H1N1, PRE [N=444;112]
15.5
(13.8 to 17.6)
16.5
(12.9 to 21.2)
H1N1, POST [N=444;112]
138.6
(122.6 to 156.6)
23.2
(17.9 to 30.1)
H3N2, PRE [N=444;112]
24.6
(22.1 to 27.4)
29.1
(23.8 to 35.5)
H3N2, POST [N=443;112]
136.5
(124.3 to 149.9)
43.6
(34.9 to 54.5)
Victoria, PRE [N=444;112]
13.7
(12.2 to 15.4)
15.1
(11.8 to 19.5)
Victoria, POST [N=443;112]
110.2
(97.1 to 125.0)
19.7
(15.0 to 25.8)
Yamagata, PRE [N=444;112]
16.1
(14.2 to 18.4)
18.7
(14.3 to 24.6)
Yamagata, POST [N=444;112]
157.0
(143.1 to 172.3)
21.8
(16.5 to 28.9)
10.Secondary Outcome
Title Number of Seroconverted Subjects for HI Antibody Titers Against Each of the 4 Vaccine Influenza Strains.
Hide Description A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).
Time Frame At least 6 months after first vaccination (Month 6)
Hide Outcome Measure Data
Hide Analysis Population Description
The ATP Cohort for persistence included, in terms of antibody response measured by the HI assay, all evaluable subjects for whom data concerning immunogenicity outcome measure were available and for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 444 112
Measure Type: Number
Unit of Measure: Subjects
H1N1, POST [N=444;112] 349 9
H3N2, POST [N=443;112] 290 10
Victoria, POST [N=443;112] 323 12
Yamagata, POST [N=444;112] 354 8
11.Secondary Outcome
Title Number of Seroprotected Subjects for HI Antibody Titers Against Each of the 4 Vaccine Influenza Strains.
Hide Description A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).
Time Frame At Day 0 and at least 6 months after first vaccination (Month 6)
Hide Outcome Measure Data
Hide Analysis Population Description
The ATP Cohort for persistence included, in terms of antibody response measured by the HI assay, all evaluable subjects for whom data concerning immunogenicity outcome measure were available and for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 444 112
Measure Type: Number
Unit of Measure: Subjects
H1N1, PRE [N=444;112] 148 36
H1N1, POST [N=444;112] 383 49
H3N2, PRE [N=444;112] 204 60
H3N2, POST [N=443;112] 412 71
Victoria, PRE [N=444;112] 123 32
Victoria, POST [N=443;112] 374 39
Yamagata, PRE [N=444;112] 153 43
Yamagata, POST [N=444;112] 427 49
12.Secondary Outcome
Title Seroconversion Factors for HI Antibodies Against 4 Strains of Influenza Disease.
Hide Description Seroconversion factors were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).
Time Frame At least 6 months after first vaccination (Month 6)
Hide Outcome Measure Data
Hide Analysis Population Description
The ATP Cohort for persistence included, in terms of antibody response measured by the HI assay, all evaluable subjects for whom data concerning immunogenicity outcome measure were available and for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 444 112
Geometric Mean (95% Confidence Interval)
Unit of Measure: Fold increase
H1N1, POST [N=444;112]
8.9
(8.1 to 9.8)
1.4
(1.2 to 1.6)
H3N2, POST [N=443;112]
5.5
(5.0 to 6.1)
1.5
(1.2 to 1.8)
Victoria, POST [N=443;112
8.0
(7.3 to 8.9)
1.3
(1.1 to 1.6)
Yamagata, POST [N=444;112]
9.7
(8.7 to 10.8)
1.2
(1.0 to 1.4)
13.Secondary Outcome
Title Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms.
Hide Description Assessed solicited local symptoms were pain, redness and swelling at the injection site. Any = Incidence of a particular symptom regardless of intensity grade. Grade 3 pain = Cried when limb was moved/spontaneously painful for subjects < 5 years of age or significant pain at rest that prevented normal, everyday activities for subjects ≥ 5 years of age. Grade 3 redness/swelling = Redness/swelling above 100 millimeters (mm) of the injection site. All solicited local symptoms were considered related to vaccination.
Time Frame During the 7-day (Days 0-6) follow-up period after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented and with the symptom sheet completed.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
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Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 2546 2551
Measure Type: Number
Unit of Measure: subjects
Any Pain 1215 888
Grade 3 Pain 36 20
Any Redness 17 5
Grade 3 Redness 0 0
Any Swelling 46 10
Grade 3 Swelling 0 0
14.Secondary Outcome
Title Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Subjects Below 5 Years of Age.
Hide Description Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature. Any = Occurrence of any solicited general symptom regardless of intensity grade and relation to vaccination. Any temperature = Axillary temperature ≥ 38.0 °C. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = not eating at all. Related = General symptom assessed by the investigator as causally related to the study vaccination. Grade 3 temperature = Axillary temperature ≥ 39.0°C.
Time Frame During the 7-day (Days 0-6) follow-up period after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented and with the symptom sheet completed.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 899 896
Measure Type: Number
Unit of Measure: subjects
Any Drowsiness 100 93
Grade 3 Drowsiness 5 4
Related Drowsiness 57 61
Any Irritability 102 91
Grade 3 Irritability 5 4
Related Irritability 60 59
Any Loss of appetite 119 120
Grade 3 Loss of appetite 6 7
Related Loss of appetite 55 61
Any Temperature 74 74
Grade 3 Temperature 21 18
Related Temperature 35 35
15.Secondary Outcome
Title Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Subjects of 5 Years of Age and Above.
Hide Description Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (Gastro.), headache, joint pain at other location (Joint pain), muscle aches, shivering and temperature. Any = Occurrence of any solicited general symptom regardless of intensity grade or relation to vaccination. Any temperature = Axillary temperature ≥ 38.0 °C. Grade 3 symptom = Symptom that prevented normal activity. Related = Symptom assessed by the investigator as causally related to the vaccination. Grade 3 temperature = Axillary temperature ≥ 39.0°C.
Time Frame During the 7-day (Days 0-6) follow-up period after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented and with the symptom sheet completed.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 1648 1654
Measure Type: Number
Unit of Measure: subjects
Any Fatigue 188 145
Grade 3 Fatigue 1 6
Related Fatigue 101 78
Any Gastro. 133 146
Grade 3 Gastro. 9 9
Related Gastro. 68 54
Any Headache 243 217
Grade 3 Headache 9 14
Related Headache 154 125
Any Joint pain 143 93
Grade 3 Joint pain 3 2
Related Joint pain 98 54
Any Muscle aches 257 194
Grade 3 Muscle aches 3 5
Related Muscle aches 162 109
Any Shivering 63 59
Grade 3 Shivering 2 2
Related Shivering 32 26
Any Temperature 72 82
Grade 3 Temperature 21 17
Related Temperature 46 37
16.Secondary Outcome
Title Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
Hide 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 = Any unsolicited AE regardless of intensity or relationship to vaccination. Grade 3 = Unsolicited AE that prevented normal activity. Related = Unsolicited AE assessed by the investigator as causally related to the vaccination.
Time Frame During the 28-day (Days 0-27) follow-up period after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 2584 2584
Measure Type: Number
Unit of Measure: subjects
Any unsolicited AE(s) 843 855
Grade 3 unsolicited AE(s) 25 20
Related unsolicited AE(s) 30 37
17.Secondary Outcome
Title Number of Subjects With Any and Related Medically Attended Adverse Events (MAEs).
Hide Description MAEs were defined as AEs that resulted in medical attention (defined as hospitalization, an emergency room visit or a visit to or from medical personnel for any reason). Any = Any MAE regardless of intensity or relationship to vaccination. Related = MAE assessed by the investigator as causally related to the vaccination.
Time Frame During the entire study period (Day 0 - Day 180)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 2584 2584
Measure Type: Number
Unit of Measure: subjects
Any MAE(s) 792 749
Related MAE(s) 6 13
18.Secondary Outcome
Title Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs).
Hide Description pIMDs were defined as a subset of AEs that included both clearly autoimmune diseases (AID) and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Any = Any pIMD(s) regardless of intensity or relationship to vaccination. Related = pIMDs assessed by the investigator as causally related to the vaccination.
Time Frame During the entire study period (Day 0 - Day 180)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 2584 2584
Measure Type: Number
Unit of Measure: subjects
Any pIMD(s) 0 1
Related pIMD(s) 0 0
19.Secondary Outcome
Title Number of Subjects With Any and Related Serious Adverse Events (SAEs).
Hide Description Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Any = Any SAE(s) regardless of intensity or relationship to vaccination. Related = SAEs assessed by the investigator as causally related to the vaccination.
Time Frame During the entire study period (Day 0 - Day 180)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description:
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Overall Number of Participants Analyzed 2584 2584
Measure Type: Number
Unit of Measure: subjects
Any SAE(s) 36 24
Related SAE(s) 1 0
Time Frame SAEs: during the entire study period (Day 0-Day 180); Unsolicited AEs: during the 28-day (Day 0-Day 27) follow-up period after vaccination; Solicited local/general symptoms: during the 7-day (Day 0-Day 6) follow-up period after any vaccination.
Adverse Event Reporting Description For the systematically assessed other non-serious AEs, the number of participants at risk included those from Total Vaccinated cohort whose symptom sheet had been completed.
 
Arm/Group Title FluLaval® Quadrivalent Group Havrix Group
Hide Arm/Group Description Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm. Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
All-Cause Mortality
FluLaval® Quadrivalent Group Havrix Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
FluLaval® Quadrivalent Group Havrix Group
Affected / at Risk (%) Affected / at Risk (%)
Total   36/2584 (1.39%)   24/2584 (0.93%) 
Gastrointestinal disorders     
Gastritis *  1/2584 (0.04%)  0/2584 (0.00%) 
General disorders     
Drowning *  1/2584 (0.04%)  1/2584 (0.04%) 
Influenza like illness *  1/2584 (0.04%)  1/2584 (0.04%) 
Pyrexia *  0/2584 (0.00%)  1/2584 (0.04%) 
Infections and infestations     
Gastroenteritis *  6/2584 (0.23%)  3/2584 (0.12%) 
Pneumonia *  4/2584 (0.15%)  3/2584 (0.12%) 
Dengue fever *  1/2584 (0.04%)  3/2584 (0.12%) 
Bronchopneumonia *  2/2584 (0.08%)  1/2584 (0.04%) 
Upper respiratory tract infection *  1/2584 (0.04%)  2/2584 (0.08%) 
Urinary tract infection *  3/2584 (0.12%)  0/2584 (0.00%) 
Amoebiasis *  1/2584 (0.04%)  1/2584 (0.04%) 
Bronchitis *  2/2584 (0.08%)  0/2584 (0.00%) 
Acute tonsillitis *  0/2584 (0.00%)  1/2584 (0.04%) 
Amoebic dysentery *  0/2584 (0.00%)  1/2584 (0.04%) 
Appendicitis *  1/2584 (0.04%)  0/2584 (0.00%) 
Bronchiolitis *  1/2584 (0.04%)  0/2584 (0.00%) 
Cellulitis *  0/2584 (0.00%)  1/2584 (0.04%) 
Croup infectious *  1/2584 (0.04%)  0/2584 (0.00%) 
Diarrhoea infectious *  1/2584 (0.04%)  0/2584 (0.00%) 
Endocarditis *  0/2584 (0.00%)  1/2584 (0.04%) 
Gastroenteritis viral *  1/2584 (0.04%)  0/2584 (0.00%) 
Herpangina *  0/2584 (0.00%)  1/2584 (0.04%) 
Herpes zoster *  1/2584 (0.04%)  0/2584 (0.00%) 
Nasopharyngitis *  0/2584 (0.00%)  1/2584 (0.04%) 
Respiratory tract infection *  0/2584 (0.00%)  1/2584 (0.04%) 
Tonsillitis *  0/2584 (0.00%)  1/2584 (0.04%) 
Visceral leishmaniasis *  0/2584 (0.00%)  1/2584 (0.04%) 
Injury, poisoning and procedural complications     
Animal bite *  3/2584 (0.12%)  1/2584 (0.04%) 
Animal scratch *  1/2584 (0.04%)  0/2584 (0.00%) 
Head injury *  1/2584 (0.04%)  0/2584 (0.00%) 
Joint injury *  1/2584 (0.04%)  0/2584 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Optic nerve glioma *  0/2584 (0.00%)  1/2584 (0.04%) 
Nervous system disorders     
Convulsion *  1/2584 (0.04%)  1/2584 (0.04%) 
Renal and urinary disorders     
Urinary retention *  1/2584 (0.04%)  0/2584 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma *  1/2584 (0.04%)  0/2584 (0.00%) 
Bronchial hyperreactivity *  0/2584 (0.00%)  1/2584 (0.04%) 
Bronchial obstruction *  1/2584 (0.04%)  0/2584 (0.00%) 
Bronchospasm *  1/2584 (0.04%)  0/2584 (0.00%) 
Pneumonitis *  1/2584 (0.04%)  0/2584 (0.00%) 
Respiratory distress *  1/2584 (0.04%)  0/2584 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
FluLaval® Quadrivalent Group Havrix Group
Affected / at Risk (%) Affected / at Risk (%)
Total   1215/2584 (47.02%)   1297/2584 (50.19%) 
General disorders     
Pain †  1215/2546 (47.72%)  888/2551 (34.81%) 
Drowsiness † [1]  100/899 (11.12%)  93/896 (10.38%) 
Irritability † [1]  102/899 (11.35%)  91/896 (10.16%) 
Loss of appetite † [1]  119/899 (13.24%)  120/896 (13.39%) 
Temperature † [1]  74/899 (8.23%)  74/896 (8.26%) 
Fatigue † [2]  188/1648 (11.41%)  145/1654 (8.77%) 
Gastro. † [2]  133/1648 (8.07%)  146/1654 (8.83%) 
Headache † [2]  243/1648 (14.75%)  217/1654 (13.12%) 
Joint pain † [2]  143/1648 (8.68%)  93/1654 (5.62%) 
Muscle aches † [2]  257/1648 (15.59%)  194/1654 (11.73%) 
Infections and infestations     
Nasopharyngitis *  213/2584 (8.24%)  231/2584 (8.94%) 
Respiratory, thoracic and mediastinal disorders     
Cough *  145/2584 (5.61%)  137/2584 (5.30%) 
†
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
Symptom reported for subjects below 5 years of age.
[2]
Symptom reported for subjects of 5 years of age and above
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01218308    
Other Study ID Numbers: 114541
First Submitted: October 7, 2010
First Posted: October 11, 2010
Results First Submitted: February 21, 2013
Results First Posted: April 2, 2013
Last Update Posted: August 1, 2018