Clinical Trial Results:
A phase III, open-label, multicentre study to evaluate the immunogenicity, safety and reactogenicity of a re-vaccination dose of the GlaxoSmithKline Biologicals' quadrivalent seasonal influenza candidate vaccine GSK2321138A, administered to children who previously participated in study 115345 (FLU D-QIV-004 PRI).
Summary
|
|
EudraCT number |
2012-001230-34 |
Trial protocol |
ES CZ GB PL |
Global end of trial date |
05 Jun 2013
|
Results information
|
|
Results version number |
v4(current) |
This version publication date |
16 Sep 2018
|
First version publication date |
02 May 2015
|
Other versions |
v1 (removed from public view) , v2 , v3 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
116023
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01702454 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
GlaxoSmithKline Biologicals
|
||
Sponsor organisation address |
Rue de l'Institut 89, Rixensart, Belgium,
|
||
Public contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
|
||
Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-000817-PIP02-11 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
11 Dec 2013
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
05 Jun 2013
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
05 Jun 2013
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To assess the immune response in terms of Haemagglutination Inhibition (HI) antibody titre at Day 7 after one dose of FLU D-QIV vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all strains included in the vaccine.
|
||
Protection of trial subjects |
All subjects were supervised closely for at least 30 minutes following vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines/products were administered only to eligible subjects that had no contraindications to any components of the vaccines. Subjects were followed-up from the time the subject consents to participate in the study until she/he is discharged.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Oct 2012
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Poland: 103
|
||
Country: Number of subjects enrolled |
Spain: 149
|
||
Country: Number of subjects enrolled |
United Kingdom: 83
|
||
Country: Number of subjects enrolled |
Czech Republic: 135
|
||
Worldwide total number of subjects |
470
|
||
EEA total number of subjects |
470
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
470
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||
Recruitment details |
An additional pre-specified immunogenicity analysis was conducted on According-to-Protocol cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 and was dependent on the unblinding of the parent study, 115345. Micro-neutralising/Anti-neuraminidase analysis was done by age strata too. | |||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||
Screening details |
During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms. | |||||||||||||||||||||
Period 1
|
||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
|||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||
Arms
|
||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||
Arm title
|
Fluarix Quadrivalent Primed Group | |||||||||||||||||||||
Arm 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. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Fluarix Quadrivalent
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
|||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||
Dosage and administration details |
Vaccine-primed subjects received a single 0.5 mL dose administered intramuscularly at Visit 1 (Day 0). Vaccines were administered in the deltoid region.
|
|||||||||||||||||||||
Arm title
|
Fluarix Quadrivalent Unprimed Group | |||||||||||||||||||||
Arm description |
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. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Fluarix Quadrivalent
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
|||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||
Dosage and administration details |
Vaccine-unprimed subjects received one 0.5 mL dose administered intramuscularly at Visit 1 (Day 0) and one 0.5 mL dose administered intramuscularly at Visit 3 (Day 28). Vaccines were administered in the deltoid region.
|
|||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fluarix Quadrivalent Primed Group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fluarix Quadrivalent Unprimed Group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Fluarix Quadrivalent Primed Group
|
||
Reporting 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. | ||
Reporting group title |
Fluarix Quadrivalent Unprimed Group
|
||
Reporting group description |
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. |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Serum Hemagglutination Inhibition (HI) antibody titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine | ||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted GMT ratio for A/Christchurch antibodies | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
433
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [1] | ||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||
Parameter type |
Adjusted GMT Ratio | ||||||||||||||||||||||||||||||||||||
Point estimate |
8.97
|
||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||
lower limit |
6.21 | ||||||||||||||||||||||||||||||||||||
upper limit |
12.96 | ||||||||||||||||||||||||||||||||||||
Notes [1] - Criterion: The lower limit (LL) of the two-sided 95% Confidence Interval (CI) for the GMT ratio is above 1. 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 title |
Adjusted GMT ratio for A/Victoria antibodies | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
433
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [2] | ||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||
Parameter type |
Adjusted GMT Ratio | ||||||||||||||||||||||||||||||||||||
Point estimate |
2.7
|
||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||
lower limit |
1.81 | ||||||||||||||||||||||||||||||||||||
upper limit |
4.02 | ||||||||||||||||||||||||||||||||||||
Notes [2] - Criterion: The lower limit (LL) of the two-sided 95% Confidence Interval (CI) for the GMT ratio is above 1. 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 title |
Adjusted GMT ratio for B/Brisbane antibodies | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
433
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [3] | ||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||
Parameter type |
Adjusted GMT Ratio | ||||||||||||||||||||||||||||||||||||
Point estimate |
3.94
|
||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||
lower limit |
2.89 | ||||||||||||||||||||||||||||||||||||
upper limit |
5.37 | ||||||||||||||||||||||||||||||||||||
Notes [3] - Criterion: The lower limit (LL) of the two-sided 95% Confidence Interval (CI) for the GMT ratio is above 1. 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 title |
Adjusted GMT ratio for B/Hub-Wuj antibodies | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
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.
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
433
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [4] | ||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||
Parameter type |
Adjusted GMT Ratio | ||||||||||||||||||||||||||||||||||||
Point estimate |
6.71
|
||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||
lower limit |
5.21 | ||||||||||||||||||||||||||||||||||||
upper limit |
8.63 | ||||||||||||||||||||||||||||||||||||
Notes [4] - Criterion: The lower limit (LL) of the two-sided 95% Confidence Interval (CI) for the GMT ratio is above 1. The GMTs were used to calculate the Adjusted GMTs, which in turn were used to calculate the Adjusted GMT ratio with 95% confidence interval. |
|
||||||||||||||||||||||||||||||||||
End point title |
Number of seropositive subjects against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine [5] | |||||||||||||||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
|||||||||||||||||||||||||||||||||
Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Number of subjects seroconverted for HI antibodies against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. | |||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Statistical analysis title |
Difference in SCR for A/Christchurch antibodies | |||||||||||||||||||||
Statistical analysis description |
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.
|
|||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
|||||||||||||||||||||
Number of subjects included in analysis |
423
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
non-inferiority [6] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Difference in percentages | |||||||||||||||||||||
Point estimate |
44.74
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
35.87 | |||||||||||||||||||||
upper limit |
52.84 | |||||||||||||||||||||
Notes [6] - SCR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion. |
||||||||||||||||||||||
Statistical analysis title |
Difference in SCR for A/Victoria antibodies | |||||||||||||||||||||
Statistical analysis description |
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.
|
|||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
|||||||||||||||||||||
Number of subjects included in analysis |
423
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
non-inferiority [7] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Difference in percentages | |||||||||||||||||||||
Point estimate |
45.31
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
36.58 | |||||||||||||||||||||
upper limit |
53.3 | |||||||||||||||||||||
Notes [7] - SCR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion. |
||||||||||||||||||||||
Statistical analysis title |
Difference in SCR for B/Brisbane antibodies | |||||||||||||||||||||
Statistical analysis description |
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.
|
|||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
|||||||||||||||||||||
Number of subjects included in analysis |
423
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
non-inferiority [8] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Difference in percentages | |||||||||||||||||||||
Point estimate |
37.86
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
28.83 | |||||||||||||||||||||
upper limit |
46.26 | |||||||||||||||||||||
Notes [8] - SCR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion. |
||||||||||||||||||||||
Statistical analysis title |
Difference in SCR for B/Hu-Wuj antibodies | |||||||||||||||||||||
Statistical analysis description |
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)
|
|||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
|||||||||||||||||||||
Number of subjects included in analysis |
423
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
non-inferiority [9] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Difference in percentages | |||||||||||||||||||||
Point estimate |
56
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
48.32 | |||||||||||||||||||||
upper limit |
63.04 | |||||||||||||||||||||
Notes [9] - SCR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion. |
|
|||||||||||||||||||||||||
End point title |
Mean geometric increase (MGI) for HI antibody titer against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. [10] | ||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
||||||||||||||||||||||||
Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Number of subjects seroprotected for anti-HA antibodies against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. | |||||||||||||||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Difference in SPR for A/Christ antibodies | |||||||||||||||||||||||||||||||||
Statistical analysis description |
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.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
433
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [11] | |||||||||||||||||||||||||||||||||
Method |
||||||||||||||||||||||||||||||||||
Parameter type |
Difference in SPR | |||||||||||||||||||||||||||||||||
Point estimate |
62.43
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
55.27 | |||||||||||||||||||||||||||||||||
upper limit |
68.89 | |||||||||||||||||||||||||||||||||
Notes [11] - SPR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion. |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Difference in SPR for A/Victoria antibodies | |||||||||||||||||||||||||||||||||
Statistical analysis description |
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.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
433
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [12] | |||||||||||||||||||||||||||||||||
Method |
||||||||||||||||||||||||||||||||||
Parameter type |
Difference in SPR | |||||||||||||||||||||||||||||||||
Point estimate |
47.4
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
39.08 | |||||||||||||||||||||||||||||||||
upper limit |
55.06 | |||||||||||||||||||||||||||||||||
Notes [12] - SPR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion. |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Difference in SPR for B/Brisbane antibodies | |||||||||||||||||||||||||||||||||
Statistical analysis description |
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.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
433
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [13] | |||||||||||||||||||||||||||||||||
Method |
||||||||||||||||||||||||||||||||||
Parameter type |
Difference in SPR | |||||||||||||||||||||||||||||||||
Point estimate |
56.68
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
49.44 | |||||||||||||||||||||||||||||||||
upper limit |
63.43 | |||||||||||||||||||||||||||||||||
Notes [13] - SPR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion. |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Difference in SPR for B/Hub-Wuj antibodies | |||||||||||||||||||||||||||||||||
Statistical analysis description |
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.
The B/Hub-Wuj = B/Hubei-Wujiagang/158/2009 (Yamagata)
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Fluarix Quadrivalent Primed Group v Fluarix Quadrivalent Unprimed Group
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
433
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [14] | |||||||||||||||||||||||||||||||||
Method |
||||||||||||||||||||||||||||||||||
Parameter type |
Difference in SPR | |||||||||||||||||||||||||||||||||
Point estimate |
56.72
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
49.41 | |||||||||||||||||||||||||||||||||
upper limit |
63.49 | |||||||||||||||||||||||||||||||||
Notes [14] - SPR difference was calculated using standardized asymptotic 95% CI for the group difference in proportion. |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Serum Hemagglutination Inhibition (HI) antibody titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. [15] | ||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
||||||||||||||||||||||||||||||||||||
Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Number of subjects seropositive for HI antibody titers against each of the four vaccine strains after dose 1 of Fluarix Quadrivalent vaccine [16] | |||||||||||||||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
|||||||||||||||||||||||||||||||||
Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Number of subjects seroconverted for HI antibodies against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. [17] | |||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
|||||||||||||||||||||
Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
||||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean geometric increase (MGI) for HI antibody titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. [18] | ||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
||||||||||||||||||||||||
Notes [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Number of subjects seroprotected for HI antibodies against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. [19] | |||||||||||||||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
|||||||||||||||||||||||||||||||||
Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects with HI antibody titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Serum neutralising antibody titers against each of the vaccine strains after 1 dose of Fluarix Quadrivalent vaccine | ||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Serum anti-neuraminidase antibody titers against each of the vaccine strains after 1 dose of Fluarix Quadrivalent vaccine | ||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Vaccine response rate (VRR) for neutralising antibody titers against each of the four vaccine strains. | |||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
MGI for neutralising antibodies titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. | ||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Vaccine response rate(VRR) for anti-neuraminidase antibody titers against each of the four vaccine strains. | |||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
MGI for anti-neuraminidase antibodies titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. | ||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects with HI antibody titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent Vaccine. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Serum micro neutralizing(MN) antibody titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. | ||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Serum anti-neuraminidase antibody titers against each of the vaccine strains after 1 dose of Fluarix Quadrivalent vaccine | ||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Vaccine response rate(VRR) for serum neutralising antibody titers against each of the four vaccine strains | |||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
MGI for neutralising antibodies titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine. | ||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Vaccine response rate(VRR) for anti-neuraminidase antibodies against each of the four vaccine strains. | |||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
MGI for anti-neuraminidase antibodies titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine | ||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Serum neutralising antibody titers against each of the vaccine strains after 1 dose of Fluarix Quadrivalent vaccine by age strata. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Serum anti-neuraminidase antibody titers against each of the vaccine strains after 1 dose of Fluarix Quadrivalent vaccine by age strata | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 0 and Day 7
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Vaccine response rate(VRR) for serum neutralising antibody titers against each of the four vaccine strains by age strata | |||||||||||||||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
MGI for neutralising antibodies titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine by age strata | ||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Vaccine response rate(VRR) for anti-neuraminidase antibody titers against each of the four vaccine strains by age strata. | |||||||||||||||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
MGI for anti-neuraminidase antibodies titers against each of the four vaccine strains after 1 dose of Fluarix Quadrivalent vaccine by age strata. | ||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 7 post dose 1
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Number of subjects reporting any and grade 3 solicited local adverse events (AEs) | |||||||||||||||||||||||||||
End point 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).
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
During a 7-day (Day 0 to 6) follow-up period after first vaccination
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Duration of solicted symptoms | |||||||||||||||||||||||||||||||||
End point description |
Duration was defined as number of days with any grade of solicted local and/or general symptoms
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
During the 7-day (Days 0-6) post-vaccination Dose 1 period
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting any, grade 3 and related solicited general symptoms. | |||||||||||||||||||||||||||||||||||||||||||||
End point 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.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During the 7 days (Days 0 – 6) post dose 1 vaccination
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of subjects reporting AEs with Medically Attended Visits (MAV) | ||||||||||||||||||
End point 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.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
During the entire study period (Day 0 – Day 179)
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of subjects reporting Potential Immune-Mediated Diseases (pIMDs) | |||||||||||||||
End point 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.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
During the entire study period (Days 0 - 179)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of subjects reporting any, grade 3 and related unsolicited AEs. | ||||||||||||||||||
End point 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.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Within 28 days (Days 0-27) after first vaccination
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of subjects reporting any and related serious adverse events (SAEs) | |||||||||||||||
End point 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.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
During the entire study period (Day 0 – Day 179)
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
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 additional description |
For the frequent adverse events, the number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fluarix Quadrivalent Unprimed Group
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fluarix Quadrivalent Primed Group
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed. [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed. [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed. [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed. [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed. [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed. [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed. |
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |