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Clinical Trial Results:
A Pivotal Randomized, Single-Blind, Dose-Finding Study to Evaluate Immunogenicity, Safety and Tolerability of Different Formulations of an Adjuvanted and Non-Adjuvanted Egg-Derived, Inactivated Novel Swine Origin A/H1N1 Monovalent Subunit Influenza Virus Vaccine in Healthy Pediatric Subjects 3 to < 9 Years of Age

Summary
EudraCT number	2014-005106-38
Trial protocol	Outside EU/EEA
Global end of trial date	03 Nov 2010

Results information
Results version number	v2(current)
This version publication date	28 Jul 2016
First version publication date	09 May 2015
Other versions	v1 (removed from public view)
Version creation reason	Correction of full data set Required for the re-QC because of EudraCT system glitch as possible updates to results are required. Moreover, the study is now transferred to another primary user.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

V112_02

ISRCTN number

US NCT number

NCT00972816

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Vaccines and Diagnostics

Sponsor organisation address

350 Massachusetts Ave, Cambridge, MA, United States, 02139

Public contact

Posting Director, Novartis Vaccines and Diagnostics, RegistryContactVaccinesUS@novartis.com

Scientific contact

Posting Director, Novartis Vaccines and Diagnostics, RegistryContactVaccinesUS@novartis.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

31 Mar 2011

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Nov 2010

Was the trial ended prematurely?

Main objective of the trial

To see if one or more A/H1N1 S-OIV vaccine groups meet CBER criteria for immunogenicity in a population of children aged 3 to < 9 yrs (CBER 2007)

Protection of trial subjects

This trial was performed with the ethical principles that have their origin in the Declaration of Helsinki, that are consistent with Good Clinical Practice (GCP) according to International Conference on Harmonisation (ICH) guidelines, the applicable regulatory requirements(s) for the country in which the study is conducted, and applicable standard operating procedures (SOPs).

Background therapy

Evidence for comparator

Actual start date of recruitment

12 Sep 2009

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Regulatory reason

Long term follow-up duration

13 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 1357

Worldwide total number of subjects

1357

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

1357

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

36 centers in the United States, of which 34 centers enrolled subjects

Screening details

All enrolled subjects were included in the trial

Period 1 title

Enrolled (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Are arms mutually exclusive

Yes

Group A

Arm description

3.75_(50) MF59-[3.75 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Arm type

Experimental

Investigational medicinal product name

Monovalent H1N1 influenza virus vaccine with MF59 adjuvant

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

0.25mL dose/IM

Group B

Arm description

7.5_(0) MF59-[7.5 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Arm type

Experimental

Investigational medicinal product name

Monovalent H1N1 influenza virus vaccine without MF59 adjuvant

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

0.50 mL dose/IM

Group C

Arm description

7.5_(50) MF59-[7.5 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Arm type

Experimental

Investigational medicinal product name

Monovalent H1N1 influenza virus vaccine with MF59 adjuvant

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

0.50 mL dose/IM

Group D

Arm description

7.5_(100) MF59-[7.5 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22]

Arm type

Experimental

Investigational medicinal product name

Monovalent H1N1 influenza virus vaccine with MF59 adjuvant

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

0.50 mL dose/IM

Group E

Arm description

15_(0) MF59-[15 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Arm type

Experimental

Investigational medicinal product name

Monovalent H1N1 influenza virus vaccine without MF59 adjuvant

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

0.50 mL dose/IM

Group F

Arm description

15_(50) MF59-[15 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Arm type

Experimental

Investigational medicinal product name

Monovalent H1N1 influenza virus vaccine with MF59 adjuvant

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

0.50 mL dose/IM

Group G

Arm description

15_(100) MF59-[15 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22]

Arm type

Experimental

Investigational medicinal product name

Monovalent H1N1 influenza virus vaccine with MF59 adjuvant

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

0.50 mL dose/IM

Group H

Arm description

30_(0) MF59-[30 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Arm type

Experimental

Investigational medicinal product name

Monovalent H1N1 influenza virus vaccine without MF59 adjuvant

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

0.50 mL dose/IM

Number of subjects in period 1	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Started	173	169	169	169	169	169	169	170
Completed	156	158	160	161	157	158	159	161
Not completed	17	11	9	8	12	11	10	9
Consent withdrawn by subject	4	2	1	3	-	1	1	2
Adverse event, non-fatal	-	-	1	-	-	-	-	-
Unable to classify	2	-	-	-	1	-	-	-
Inappropriate enrolment	-	-	-	-	-	-	2	-
Lost to follow-up	11	9	7	5	11	10	7	7

Baseline characteristics

Top of page

Reporting group title

Group A

Reporting group description

3.75_(50) MF59-[3.75 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group B

Reporting group description

7.5_(0) MF59-[7.5 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group C

Reporting group description

7.5_(50) MF59-[7.5 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group D

Reporting group description

7.5_(100) MF59-[7.5 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group E

Reporting group description

15_(0) MF59-[15 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group F

Reporting group description

15_(50) MF59-[15 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group G

Reporting group description

15_(100) MF59-[15 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group H

Reporting group description

30_(0) MF59-[30 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Reporting group values	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H	Total
Number of subjects	173	169	169	169	169	169	169	170	1357
Age categorical
Units: Subjects
In utero									0
Preterm newborn infants (gestational age < 37 wks)									0
Newborns (0-27 days)									0
Infants and toddlers (28 days-23 months)									0
Children (2-11 years)									0
Adolescents (12-17 years)									0
Adults (18-64 years)									0
From 65-84 years									0
85 years and over									0
Age continuous
Units: years
arithmetic mean (standard deviation)	5.6 ( 1.7 )	5.2 ( 1.7 )	5.5 ( 1.8 )	5.9 ( 1.7 )	5.6 ( 1.7 )	5.5 ( 1.7 )	5.5 ( 1.7 )	5.5 ( 1.7 )	-
Gender categorical
Units: Subjects
Female	81	88	83	83	79	80	75	83	652
Male	92	81	86	86	90	89	94	87	705

End points

Top of page

Reporting group title

Group A

Reporting group description

3.75_(50) MF59-[3.75 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group B

Reporting group description

7.5_(0) MF59-[7.5 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group C

Reporting group description

7.5_(50) MF59-[7.5 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group D

Reporting group description

7.5_(100) MF59-[7.5 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group E

Reporting group description

15_(0) MF59-[15 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group F

Reporting group description

15_(50) MF59-[15 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group G

Reporting group description

15_(100) MF59-[15 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group H

Reporting group description

30_(0) MF59-[30 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Primary: 1. Antibody Responses After the First and Second Vaccinations

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End point title

1. Antibody Responses After the First and Second Vaccinations ^[1]

End point description

CBER guidance (<65 years of age): The lower bound of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody should be ≥ 40% and the lower bound of the two-sided 95% CI for the percentages of subjects achieving an HI antibody titer ≥ 1:40 should be ≥ 70%. PPS Day 1–29 analysis set. N= 143, 149, 149, 146, 147, 147, 144, and 144 for Groups A, B, C, D, E, F, G,and H, respectively. PPS Day 1–202 analysis set. N= 82, 85, 84, 84, 86, 87, 82, and 79 for Groups A, B, C, D, E, F, G, and H,respectively. PPS Day 1–387 analysis set. N= 55, 63, 61, 58, 61, 65, 59, and 63 for Groups A, B, C, D, E, F, G, and H,respectively.

End point type

Primary

End point timeframe

Day 22, Day 29, Day 43, Day 202 and Day 387

Notes
[1] - 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: No statistical analyses for this end point.

End point values	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Number of subjects analysed	152	156	156	156	155	157	156	153
Units: Percentages of Subjects
number (confidence interval 95%)
HI titer ≥1:40 (Baseline)	11 (6 to 17)	9 (5 to 15)	13 (8 to 19)	11 (6 to 170)	15 (10 to 22)	9 (5 to 15)	8 (4 to 13)	12 (8 to 19)
HI titer ≥1:40 (Day 22)	84 (77 to 89)	48 (40 to 56)	81 (74 to 87)	91 (85 to 95)	61 (52 to 68)	82 (75 to 88)	94 (89 to 97)	65 (57 to 73)
Seroconversion (Day 22)	82 (74 to 87)	46 (38 to 54)	78 (70 to 84)	88 (82 to 93)	58 (50 to 66)	82 (75 to 87)	92 (86 to 95)	60 (52 to 68)
HI titer ≥1:40 (Day 29)	99 (96 to 100)	79 (71 to 85)	100 (98 to 100)	99 (95 to 100)	88 (82 to 93)	100 (98 to 100)	100 (97 to 100)	97 (92 to 99)
Seroconversion (Day 29)	99 (95 to 100)	78 (70 to 84)	99 (95 to 100)	99 (95 to 100)	87 (81 to 92)	100 (98 to 100)	100 (97 to 100)	94 (88 to 97)
HI titer ≥1:40 (Day 43)	99 (96 to 100)	79 (72 to 85)	100 (98 to 100)	99 (95 to 100)	87 (81 to 92)	99 (97 to 100)	100 (98 to 100)	92 (86 to 95)
Seroconversion (Day 43)	98 (94 to 100)	78 (70 to 84)	97 (93 to 99)	97 (94 to 99)	85 (78 to 90)	99 (95 to 100)	99 (96 to 100)	88 (82 to 93)
HI titer ≥1:40 (Day 202)	95 (88 to 99)	65 (54 to 75)	93 (85 to 97)	95 (88 to 99)	74 (64 to 83)	95 (89 to 99)	95 (88 to 99)	81 (71 to 89)
Seroconversion (Day 202)	83 (73 to 90)	55 (44 to 66)	83 (74 to 91)	83 (74 to 91)	63 (52 to 73)	90 (81 to 95)	90 (82 to 96)	66 (54 to 76)
HI titer ≥1:40 (Day 387)	80 (67 to 90)	56 (42 to 68)	75 (63 to 86)	88 (77 to 95)	49 (36 to 62)	78 (67 to 88)	81 (69 to 90)	65 (52 to 77)
Seroconversion (Day 387)	65 (51 to 78)	49 (36 to 62)	69 (56 to 80)	78 (65 to 87)	44 (32 to 58)	75 (63 to 85)	71 (58 to 82)	51 (38 to 64)

No statistical analyses for this end point

Secondary: 2. Geometric Mean Titer After Each Vaccination by Vaccine Group

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End point title

2. Geometric Mean Titer After Each Vaccination by Vaccine Group

End point description

Immunogenicity was measured in terms of GMTs After Each Vaccination by Vaccine Group. PPS Day1–29 analysis set. N=143, 149, 149, 146, 147, 147, 144, and 144 for Groups A, B, C, D, E, F, G, and H, respectively. PPS Day 1–202 analysis set. N= 82, 85, 84, 84, 86, 87, 82, and 79 for Groups A, B, C, D, E, F, G, and H, respectively. PPS Day 1–387 analysis set. N= 55, 63, 61, 58, 61, 65, 59, and 63 for Groups A, B, C, D, E, F, G, and H, respectively.

End point type

Secondary

End point timeframe

Day 22, Day 29, Day 43, Day 202 and Day 387

End point values	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Number of subjects analysed	152	156	156	156	155	157	156	153
Units: Titers
geometric mean (confidence interval 95%)
GMT Baseline	8.5 (7 to 10)	7.3 (6 to 8.8)	8.7 (7.2 to 11)	8.1 (6.7 to 9.9)	9.1 (7.5 to 11)	7.5 (6.2 to 9.1)	7 (5.8 to 8.4)	9.1 (7.5 to 11)
GMT Day 22	107 (78 to 148)	27 (20 to 37)	88 (64 to 121)	163 (118 to 223)	49 (36 to 68)	106 (77 to 145)	160 (116 to 220)	62 (45 to 85)
GMT Day 29	747 (588 to 950)	138 (109 to 174)	685 (542 to 866)	984 (775 to 1249)	214 (169 to 271)	761 (600 to 966)	1070 (841 to 1360)	297 (235 to 377)
GMT Day 43	560 (450 to 699)	113 (91 to 140)	480 (386 to 597)	637 (511 to 793)	174 (140 to 217)	524 (420 to 652)	778 (625 to 969)	223 (179 to 278)
GMT Day 202	117 (88 to 157)	45 (34 to 59)	107 (80 to 144)	132 (99 to 177)	55 (41 to 74)	134 (100 to 179)	131 (97 to 176)	81 (60 to 109)
GMT Day 387	54 (37 to 78)	28 (20 to 40)	57 (40 to 82)	70 (49 to 102)	30 (21 to 42)	59 (41 to 83)	63 (44 to 90)	45 (31 to 64)

1. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Day 22-For pairwise vaccine group compared, least squares GMT and associated 2-sided 95% CI, median, minimum, and maximum HI titer values were determined. The two-sided 95% CIs was calculated and assessed against a non-inferiority margin of 0.5. Subsequently the same non-inferiority hypothesis was tested using a non-inferiority margin of 0.67

Comparison groups

Group A v Group B

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

3.998

Confidence interval

level

95%

sides

2-sided

lower limit

2.659

upper limit

6.009

Notes
[2] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

2. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group C

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

1.222

Confidence interval

level

95%

sides

2-sided

lower limit

0.813

upper limit

1.838

Notes
[3] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

3. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group D

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.661

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

0.994

Notes
[4] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

4. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group E

Number of subjects included in analysis

307

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

2.178

Confidence interval

level

95%

sides

2-sided

lower limit

1.449

upper limit

3.276

Notes
[5] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

5.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group F

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

1.017

Confidence interval

level

95%

sides

2-sided

lower limit

0.676

upper limit

1.528

Notes
[6] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

6.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group G

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.673

Confidence interval

level

95%

sides

2-sided

lower limit

0.448

upper limit

1.012

Notes
[7] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

7.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group H

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

1.742

Confidence interval

level

95%

sides

2-sided

lower limit

1.156

upper limit

2.626

Notes
[8] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

8.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group C

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.306

Confidence interval

level

95%

sides

2-sided

lower limit

0.204

upper limit

0.458

Notes
[9] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

9.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group D

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.165

Confidence interval

level

95%

sides

2-sided

lower limit

0.11

upper limit

0.248

Notes
[10] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

10.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group B

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.545

Confidence interval

level

95%

sides

2-sided

lower limit

0.363

upper limit

0.818

Notes
[11] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

11.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.254

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

0.381

Notes
[12] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

12.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.168

Confidence interval

level

95%

sides

2-sided

lower limit

0.112

upper limit

0.252

Notes
[13] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

13.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

Method

ANOVA

Parameter type

Geometric.Mean Ratio at day 22

Point estimate

0.436

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

0.655

Notes
[14] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

14.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group C

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.541

Confidence interval

level

95%

sides

2-sided

lower limit

0.361

upper limit

0.811

Notes
[15] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

15.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

1.783

Confidence interval

level

95%

sides

2-sided

lower limit

1.188

upper limit

2.676

Notes
[16] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

16.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.832

Confidence interval

level

95%

sides

2-sided

lower limit

0.555

upper limit

1.246

Notes
[17] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

17.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.551

Confidence interval

level

95%

sides

2-sided

lower limit

0.367

upper limit

0.826

Notes
[18] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

18.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

1.426

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

2.14

Notes
[19] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

19.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

3.295

Confidence interval

level

95%

sides

2-sided

lower limit

2.196

upper limit

4.944

Notes
[20] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

20. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

1.538

Confidence interval

level

95%

sides

2-sided

lower limit

1.026

upper limit

2.303

Notes
[21] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

21. GMT After Each Vaccination by Vaccination

Statistical analysis description

Comparison groups

Group D v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

1.018

Confidence interval

level

95%

sides

2-sided

lower limit

0.679

upper limit

1.526

Notes
[22] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

22. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

2.635

Confidence interval

level

95%

sides

2-sided

lower limit

1.754

upper limit

3.959

Notes
[23] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

23. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group F v Group E

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.467

Confidence interval

level

95%

sides

2-sided

lower limit

0.311

upper limit

0.7

Notes
[24] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

24. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group G

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.309

Confidence interval

level

95%

sides

2-sided

lower limit

0.206

upper limit

0.463

Notes
[25] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

26. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group F v Group G

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.662

Confidence interval

level

95%

sides

2-sided

lower limit

0.442

upper limit

0.992

Notes
[26] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

27. GMT After Each Vaccination by Vaccination

Statistical analysis description

Comparison groups

Group H v Group F

Number of subjects included in analysis

310

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[27]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

1.714

Confidence interval

level

95%

sides

2-sided

lower limit

1.142

upper limit

2.572

Notes
[27] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

28. GMT After Each Vaccination by Vaccination

Statistical analysis description

Comparison groups

Group H v Group G

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[28]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

2.589

Confidence interval

level

95%

sides

2-sided

lower limit

1.723

upper limit

3.889

Notes
[28] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

29. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Day 29-For pairwise vaccine group compared, least squares GMT and associated 2-sided 95% CI, median, minimum, and maximum HI titer values were determined. The two-sided 95% CIs was calculated and assessed against a non-inferiority margin of 0.5. Subsequently the same non-inferiority hypothesis was tested using a non-inferiority margin of 0.67

Comparison groups

Group A v Group B

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

5.428

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

7.365

Notes
[29] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

30. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group C

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

1.091

Confidence interval

level

95%

sides

2-sided

lower limit

0.804

upper limit

1.481

Notes
[30] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

31.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group D

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[31]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.759

Confidence interval

level

95%

sides

2-sided

lower limit

0.559

upper limit

1.031

Notes
[31] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

32.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group E

Number of subjects included in analysis

307

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[32]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

3.499

Confidence interval

level

95%

sides

2-sided

lower limit

2.577

upper limit

4.751

Notes
[32] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

33.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group F

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[33]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.982

Confidence interval

level

95%

sides

2-sided

lower limit

0.722

upper limit

1.334

Notes
[33] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

34.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group G

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[34]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.699

Confidence interval

level

95%

sides

2-sided

lower limit

0.513

upper limit

0.95

Notes
[34] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

35.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group H

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[35]

Method

ANOVA

Parameter type

GMR at day 29

Point estimate

2.513

Confidence interval

level

95%

sides

2-sided

lower limit

1.846

upper limit

3.421

Notes
[35] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

36.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group C

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[36]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.201

Confidence interval

level

95%

sides

2-sided

lower limit

0.149

upper limit

0.272

Notes
[36] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

37.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group D

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[37]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.103

upper limit

0.189

Notes
[37] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

38.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[38]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.645

Confidence interval

level

95%

sides

2-sided

lower limit

0.476

upper limit

0.873

Notes
[38] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

39.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[39]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.181

Confidence interval

level

95%

sides

2-sided

lower limit

0.134

upper limit

0.245

Notes
[39] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

40.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[40]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.129

Confidence interval

level

95%

sides

2-sided

lower limit

0.095

upper limit

0.174

Notes
[40] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

41.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[41]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.463

Confidence interval

level

95%

sides

2-sided

lower limit

0.341

upper limit

0.628

Notes
[41] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

42.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group D

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[42]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.696

Confidence interval

level

95%

sides

2-sided

lower limit

0.514

upper limit

0.943

Notes
[42] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

43.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group C

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

3.207

Confidence interval

level

95%

sides

2-sided

lower limit

2.368

upper limit

4.343

Notes
[43] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

44.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[44]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.665

upper limit

1.218

Notes
[44] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

45.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[45]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.472

upper limit

0.868

Notes
[45] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

46.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[46]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

2.303

Confidence interval

level

95%

sides

2-sided

lower limit

1.7

upper limit

3.121

Notes
[46] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

47.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[47]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

4.608

Confidence interval

level

95%

sides

2-sided

lower limit

3.398

upper limit

6.249

Notes
[47] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

48.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

1.293

Confidence interval

level

95%

sides

2-sided

lower limit

0.954

upper limit

1.753

Notes
[48] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

49.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[49]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.677

upper limit

1.249

Notes
[49] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

50.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group H v Group D

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[50]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

3.31

Confidence interval

level

95%

sides

2-sided

lower limit

2.436

upper limit

4.496

Notes
[50] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

51.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group F

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[51]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.281

Confidence interval

level

95%

sides

2-sided

lower limit

0.207

upper limit

0.38

Notes
[51] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

52.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group G

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[52]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.147

upper limit

0.271

Notes
[52] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

53.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group H v Group E

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[53]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.718

Confidence interval

level

95%

sides

2-sided

lower limit

0.529

upper limit

0.975

Notes
[53] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

54.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group F v Group G

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[54]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

0.712

Confidence interval

level

95%

sides

2-sided

lower limit

0.524

upper limit

0.966

Notes
[54] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

55.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group H v Group F

Number of subjects included in analysis

310

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[55]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

2.56

Confidence interval

level

95%

sides

2-sided

lower limit

1.886

upper limit

3.474

Notes
[55] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

56.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group H v Group G

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[56]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 29

Point estimate

3.597

Confidence interval

level

95%

sides

2-sided

lower limit

2.646

upper limit

4.89

Notes
[56] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

57.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Day 43-For pairwise vaccine group compared, least squares GMT and associated 2-sided 95% CI, median, minimum, and maximum HI titer values were determined. The two-sided 95% CIs was calculated and assessed against a non-inferiority margin of 0.5. Subsequently the same non-inferiority hypothesis was tested using a non-inferiority margin of 0.67

Comparison groups

Group B v Group A

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[57]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

4.975

Confidence interval

level

95%

sides

2-sided

lower limit

3.757

upper limit

6.589

Notes
[57] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

58.GMT After Each Vaccination by Vaccination

Statistical analysis description

Comparison groups

Group A v Group C

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[58]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

1.168

Confidence interval

level

95%

sides

2-sided

lower limit

0.881

upper limit

1.547

Notes
[58] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

59.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group D

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[59]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.665

upper limit

1.166

Notes
[59] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

60.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group E

Number of subjects included in analysis

307

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[60]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

3.219

Confidence interval

level

95%

sides

2-sided

lower limit

2.43

upper limit

4.264

Notes
[60] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

61.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group F

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[61]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.808

upper limit

1.417

Notes
[61] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

62.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group G

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[62]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.544

upper limit

0.954

Notes
[62] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

63.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group H

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[63]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

2.509

Confidence interval

level

95%

sides

2-sided

lower limit

1.891

upper limit

3.33

Notes
[63] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

64.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group B

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[64]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.235

Confidence interval

level

95%

sides

2-sided

lower limit

0.178

upper limit

0.31

Notes
[64] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

65. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group D

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[65]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.177

Confidence interval

level

95%

sides

2-sided

lower limit

0.134

upper limit

0.234

Notes
[65] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

66.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[66]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.647

Confidence interval

level

95%

sides

2-sided

lower limit

0.489

upper limit

0.856

Notes
[66] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

67. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[67]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.215

Confidence interval

level

95%

sides

2-sided

lower limit

0.163

upper limit

0.284

Notes
[67] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

68.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[68]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.145

Confidence interval

level

95%

sides

2-sided

lower limit

0.109

upper limit

0.191

Notes
[68] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

69.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[69]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.504

Confidence interval

level

95%

sides

2-sided

lower limit

0.381

upper limit

0.668

Notes
[69] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

70.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group D

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[70]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.754

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

0.997

Notes
[70] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

71.GMTAfter Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[71]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

2.756

Confidence interval

level

95%

sides

2-sided

lower limit

2.083

upper limit

3.647

Notes
[71] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

72. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[72]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.916

Confidence interval

level

95%

sides

2-sided

lower limit

0.694

upper limit

1.211

Notes
[72] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

73.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[73]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.616

Confidence interval

level

95%

sides

2-sided

lower limit

0.466

upper limit

0.815

Notes
[73] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

74.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[74]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

2.149

Confidence interval

level

95%

sides

2-sided

lower limit

1.624

upper limit

2.843

Notes
[74] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

75.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[75]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

3.656

Confidence interval

level

95%

sides

2-sided

lower limit

2.764

upper limit

4.836

Notes
[75] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

76.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[76]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

1.216

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.606

Notes
[76] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

77.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[77]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.818

Confidence interval

level

95%

sides

2-sided

lower limit

0.619

upper limit

1.081

Notes
[77] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

78.GMTAfter Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[78]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

2.85

Confidence interval

level

95%

sides

2-sided

lower limit

2.152

upper limit

3.773

Notes
[78] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

79.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group F

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[79]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.332

Confidence interval

level

95%

sides

2-sided

lower limit

0.251

upper limit

0.44

Notes
[79] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

80.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group G

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[80]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.224

Confidence interval

level

95%

sides

2-sided

lower limit

0.169

upper limit

0.296

Notes
[80] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

81.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group H

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[81]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.588

upper limit

1.033

Notes
[81] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

82.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group F v Group G

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[82]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

0.673

Confidence interval

level

95%

sides

2-sided

lower limit

0.509

upper limit

0.889

Notes
[82] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

83.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group F v Group H

Number of subjects included in analysis

310

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[83]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

2.345

Confidence interval

level

95%

sides

2-sided

lower limit

1.772

upper limit

3.102

Notes
[83] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

84.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group G v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[84]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 43

Point estimate

3.485

Confidence interval

level

95%

sides

2-sided

lower limit

2.633

upper limit

4.614

Notes
[84] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

85.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Day 202-For pairwise vaccine group compared, least squares GMT and associated 2-sided 95% CI, median, minimum, and maximum HI titer values were determined. The two-sided 95% CIs was calculated and assessed against a non-inferiority margin of 0.5. Subsequently the same non-inferiority hypothesis was tested using a non-inferiority margin of 0.67

Comparison groups

Group A v Group B

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[85]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

2.624

Confidence interval

level

95%

sides

2-sided

lower limit

1.817

upper limit

3.789

Notes
[85] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

86.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group C

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[86]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

1.096

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.58

Notes
[86] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

87.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group D

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[87]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.888

Confidence interval

level

95%

sides

2-sided

lower limit

0.615

upper limit

1.282

Notes
[87] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

88.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group E

Number of subjects included in analysis

307

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[88]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

2.12

Confidence interval

level

95%

sides

2-sided

lower limit

1.473

upper limit

3.052

Notes
[88] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

89.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group F

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[89]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.876

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.26

Notes
[89] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

90.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group G

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[90]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.898

Confidence interval

level

95%

sides

2-sided

lower limit

0.622

upper limit

1.298

Notes
[90] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

91.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group H

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[91]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

1.451

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

2.105

Notes
[91] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

92.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group C

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[92]

Method

ANOVA

Parameter type

Geometric.Mean Ratio at day 202

Point estimate

0.418

Confidence interval

level

95%

sides

2-sided

lower limit

0.289

upper limit

0.603

Notes
[92] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

93.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group D

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[93]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.338

Confidence interval

level

95%

sides

2-sided

lower limit

0.235

upper limit

0.487

Notes
[93] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

94.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[94]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.808

Confidence interval

level

95%

sides

2-sided

lower limit

0.561

upper limit

1.165

Notes
[94] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

95.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[95]

Method

ANOVA

Parameter type

Geometric.Mean Ratio at day 202

Point estimate

0.334

Confidence interval

level

95%

sides

2-sided

lower limit

0.233

upper limit

0.479

Notes
[95] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

96.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[96]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.342

Confidence interval

level

95%

sides

2-sided

lower limit

0.237

upper limit

0.494

Notes
[96] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

97.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[97]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.553

Confidence interval

level

95%

sides

2-sided

lower limit

0.382

upper limit

0.801

Notes
[97] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

98.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group D

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[98]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.811

Confidence interval

level

95%

sides

2-sided

lower limit

0.562

upper limit

1.169

Notes
[98] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

99.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[99]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

1.935

Confidence interval

level

95%

sides

2-sided

lower limit

1.347

upper limit

2.78

Notes
[99] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

100.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[100]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.558

upper limit

1.147

Notes
[100] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

101.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[101]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.568

upper limit

1.184

Notes
[101] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

102.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[102]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

1.324

Confidence interval

level

95%

sides

2-sided

lower limit

0.915

upper limit

1.917

Notes
[102] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

103.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[103]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

2.388

Confidence interval

level

95%

sides

2-sided

lower limit

1.658

upper limit

3.438

Notes
[103] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

104.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[104]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.987

Confidence interval

level

95%

sides

2-sided

lower limit

0.688

upper limit

1.416

Notes
[104] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

105.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[105]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

1.012

Confidence interval

level

95%

sides

2-sided

lower limit

0.701

upper limit

1.46

Notes
[105] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

106.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group H v Group D

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[106]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

1.634

Confidence interval

level

95%

sides

2-sided

lower limit

1.128

upper limit

2.366

Notes
[106] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

107.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group F

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[107]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.413

Confidence interval

level

95%

sides

2-sided

lower limit

0.288

upper limit

0.592

Notes
[107] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

108. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group G

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[108]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.424

Confidence interval

level

95%

sides

2-sided

lower limit

0.294

upper limit

0.61

Notes
[108] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

109.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group H

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[109]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

0.684

Confidence interval

level

95%

sides

2-sided

lower limit

0.473

upper limit

0.99

Notes
[109] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

110.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group F v Group G

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[110]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

1.025

Confidence interval

level

95%

sides

2-sided

lower limit

0.714

upper limit

1.473

Notes
[110] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

111.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group F v Group H

Number of subjects included in analysis

310

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[111]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

1.656

Confidence interval

level

95%

sides

2-sided

lower limit

1.15

upper limit

2.385

Notes
[111] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

112.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group G v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[112]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 202

Point estimate

1.615

Confidence interval

level

95%

sides

2-sided

lower limit

1.115

upper limit

2.339

Notes
[112] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

113.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Day 387-For pairwise vaccine group compared, least squares GMT and associated 2-sided 95% CI, median, minimum, and maximum HI titer values were determined. The two-sided 95% CIs was calculated and assessed against a non-inferiority margin of 0.5. Subsequently the same non-inferiority hypothesis was tested using a non-inferiority margin of 0.67

Comparison groups

Group A v Group B

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[113]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

1.906

Confidence interval

level

95%

sides

2-sided

lower limit

1.177

upper limit

3.087

Notes
[113] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

114.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group C

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[114]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.945

Confidence interval

level

95%

sides

2-sided

lower limit

0.583

upper limit

1.533

Notes
[114] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

115. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group D

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[115]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.763

Confidence interval

level

95%

sides

2-sided

lower limit

0.468

upper limit

1.245

Notes
[115] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

116. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group E

Number of subjects included in analysis

307

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[116]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

1.818

Confidence interval

level

95%

sides

2-sided

lower limit

1.119

upper limit

2.956

Notes
[116] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

117.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group F

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[117]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.917

Confidence interval

level

95%

sides

2-sided

lower limit

0.568

upper limit

1.481

Notes
[117] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

118. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group G

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[118]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.855

Confidence interval

level

95%

sides

2-sided

lower limit

0.524

upper limit

1.396

Notes
[118] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

119. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group A v Group H

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[119]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

1.203

Confidence interval

level

95%

sides

2-sided

lower limit

0.745

upper limit

1.943

Notes
[119] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

120. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group C

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[120]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.496

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

0.794

Notes
[120] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

121.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group D

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[121]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.25

upper limit

0.641

Notes
[121] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

122.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[122]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.954

Confidence interval

level

95%

sides

2-sided

lower limit

0.596

upper limit

1.528

Notes
[122] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

123.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[123]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.481

Confidence interval

level

95%

sides

2-sided

lower limit

0.306

upper limit

0.758

Notes
[123] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

124.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group G v Group B

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[124]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.449

Confidence interval

level

95%

sides

2-sided

lower limit

0.279

upper limit

0.722

Notes
[124] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

125.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group B v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[125]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.631

Confidence interval

level

95%

sides

2-sided

lower limit

0.398

upper limit

1.002

Notes
[125] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

126.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group D

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[126]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.807

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.304

Notes
[126] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

127.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[127]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

1.924

Confidence interval

level

95%

sides

2-sided

lower limit

1.193

upper limit

3.102

Notes
[127] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

128.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[128]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.611

upper limit

1.541

Notes
[128] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

129.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[129]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.905

Confidence interval

level

95%

sides

2-sided

lower limit

0.561

upper limit

1.46

Notes
[129] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

130.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group C v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[130]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

1.273

Confidence interval

level

95%

sides

2-sided

lower limit

0.798

upper limit

2.03

Notes
[130] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

131.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group E

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[131]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

2.383

Confidence interval

level

95%

sides

2-sided

lower limit

1.474

upper limit

3.851

Notes
[131] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

132. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group F

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[132]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

1.202

Confidence interval

level

95%

sides

2-sided

lower limit

0.754

upper limit

1.915

Notes
[132] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

133.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group G

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[133]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.689

upper limit

1.821

Notes
[133] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

134.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group D v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[134]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

1.576

Confidence interval

level

95%

sides

2-sided

lower limit

0.987

upper limit

2.516

Notes
[134] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

135.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group F

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[135]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.504

Confidence interval

level

95%

sides

2-sided

lower limit

0.316

upper limit

0.805

Notes
[135] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

136.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group G

Number of subjects included in analysis

311

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[136]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.47

Confidence interval

level

95%

sides

2-sided

lower limit

0.293

upper limit

0.754

Notes
[136] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

137.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group H

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[137]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.662

Confidence interval

level

95%

sides

2-sided

lower limit

0.414

upper limit

1.056

Notes
[137] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

138.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group F v Group G

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[138]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

0.932

Confidence interval

level

95%

sides

2-sided

lower limit

0.583

upper limit

1.492

Notes
[138] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

139.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group F v Group H

Number of subjects included in analysis

310

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[139]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

1.312

Confidence interval

level

95%

sides

2-sided

lower limit

0.831

upper limit

2.071

Notes
[139] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

140. GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group G v Group H

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[140]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 387

Point estimate

1.407

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

2.249

Notes
[140] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center

25.GMT After Each Vaccination by Vaccine Group

Statistical analysis description

Comparison groups

Group E v Group H

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[141]

Method

ANOVA

Parameter type

Geometric Mean Ratio at day 22

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.532

upper limit

1.203

Notes
[141] - Log10-transformed HI antibody responses were modelled using analysis of variance (ANOVA) including factors for vaccine group and center.

Secondary: 3. Antibody Responses With and Without Seasonal Influenza Vaccination for Year 2009 to 2010

Top of page

End point title

3. Antibody Responses With and Without Seasonal Influenza Vaccination for Year 2009 to 2010

End point description

Subgroup analysis based on receipt of recent seasonal vaccination. Comparison between subjects previously vaccinated versus not vaccinated with seasonal influenza vaccines Subgroups without recent seasonal flu vaccine: PPS Day 1, Day 1–22 and Day 1–43 analysis set. N= 141, 147, 150, 148, 146, 146, 150, and 146 for Groups A, B, C, D, E, F, G, and H, respectively. PPS Day 1–29 analysis set. N= 132, 140, 143, 139, 138, 136, 139, and 138 for Groups A, B, C, D, E, F, G, and H, respectively. Subgroups with recent seasonal flu vaccine: PPS Day 1–22 and Day 1-43 analysis set. N= 11, 9, 6, 8, 9, 11, 6, and 7 for Groups A, B, C, D, E, F, G, and H, respectively PPS Day 1–29 analysis set. N= 11, 9, 6, 7, 9, 11, 5, and 6 for Groups A, B, C, D, E, F, G, and H, respectively.

End point type

Secondary

End point timeframe

Day 22, Day 29, Day 43

End point values	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Number of subjects analysed	152	156	156	156	155	157	156	153
Units: Percentages of Subjects
number (confidence interval 95%)
Seroconversion (Day 22/Day 1)with seasonal flu vac	73 (39 to 94)	22 (3 to 60)	83 (36 to 100)	100 (63 to 100)	44 (14 to 79)	73 (39 to 94)	100 (54 to 100)	71 (29 to 96)
Seroconversion (Day 29/Day 1)with seasonal flu vac	100 (72 to 100)	67 (30 to 93)	83 (36 to 100)	100 (59 to 100)	67 (30 to 93)	100 (72 to 100)	100 (48 to 100)	83 (36 to 100)
Seroconversion (Day 43/Day 1)with seasonal flu vac	91 (59 to 100)	78 (40 to 97)	67 (22 to 96)	88 (47 to 100)	78 (40 to 97)	100 (72 to 100)	100 (54 to 100)	86 (42 to 100)
HI titer ≥1:40 (Day 1)_ with seasonal flu vac	18 (2 to 52)	22 (3 to 60)	50 (12 to 88)	38 (9 to 76)	0 (0 to 34)	9 (0 to 41)	17 (0 to 64)	0 (0 to 41)
HI titer ≥1:40 (Day 22)_ with seasonal flu vac	73 (39 to 94)	33 (7 to 70)	100 (54 to 100)	100 (63 to 100)	44 (14 to 79)	73 (39 to 94)	100 (54 to 100)	71 (29 to 96)
HI titer ≥1:40 (Day 29)_ with seasonal flu vac	100 (72 to 100)	67 (30 to 93)	100 (54 to 100)	100 (59 to 100)	67 (30 to 93)	100 (72 to 100)	100 (48 to 100)	100 (54 to 100)
HI titer ≥1:40 (Day 43)_ with seasonal flu vac	100 (72 to 100)	78 (40 to 97)	100 (54 to 100)	100 (63 to 100)	78 (40 to 97)	100 (72 to 100)	100 (54 to 100)	86 (42 to 100)
Seroconversion (Day 22/Day 1)without flu vac	82 (75 to 88)	47 (39 to 55)	77 (70 to 84)	88 (81 to 93)	59 (50 to 67)	82 (75 to 88)	91 (86 to 95)	60 (51 to 68)
Seroconversion (Day 29/Day 1)without flu vac	98 (95 to 100)	79 (71 to 85)	99 (96 to 100)	99 (95 to 100)	88 (82 to 93)	100 (97 to 100)	100 (97 to 100)	94 (89 to 97)
Seroconversion (Day 43/Day 1)without flu vac	99 (95 to 100)	78 (70 to 84)	98 (94 to 100)	98 (94 to 100)	85 (78 to 90)	99 (95 to 100)	99 (96 to 100)	88 (82 to 93)
HI titer ≥1:40 (Day 1) without flu vac	10 (6 to 16)	8 (4 to 14)	11 (7 to 18)	9 (5 to 15)	16 (11 to 23)	9 (5 to 15)	7 (4 to 13)	13 (8 to 20)
HI titer ≥1:40 (Day 22)without flu vac	84 (77 to 90)	49 (41 to 57)	80 (73 to 86)	91 (85 to 95)	62 (53 to 70)	83 (76 to 89)	93 (88 to 97)	65 (57 to 73)
HI titer ≥1:40 (Day 29) without flu vac	99 (96 to 100)	79 (72 to 86)	100 (97 to 100)	99 (95 to 100)	90 (84 to 94)	100 (97 to 100)	100 (97 to 100)	96 (92 to 99)
HI titer ≥1:40 (Day 43) without flu vac	99 (96 to 100)	79 (71 to 85)	100 (98 to 100)	99 (95 to 100)	88 (81 to 93)	99 (96 to 100)	100 (98 to 100)	92 (86 to 96)

No statistical analyses for this end point

Secondary: 4. Geometric Mean Titers (GMTs) With and Without Seasonal Influenza Vaccination for Year 2009 to 2010

Top of page

End point title

4. Geometric Mean Titers (GMTs) With and Without Seasonal Influenza Vaccination for Year 2009 to 2010

End point description

End point type

Secondary

End point timeframe

Day 1, Day 22, Day 29, Day 43

End point values	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Number of subjects analysed	152	156	156	156	155	157	156	153
Units: Titer
geometric mean (confidence interval 95%)
Day 1_with seasonal flu vaccination	6.22 (2.16 to 18)	12 (3.63 to 42)	22 (5.54 to 90)	15 (4.5 to 47)	5.42 (1.75 to 17)	5.99 (2.16 to 17)	15 (3.94 to 565)	9.36 (2.69 to 33)
Day 22_ with seasonal flu vaccination	36 (9.11 to 146)	44 (8.93 to 217)	196 (32 to 1213)	209 (45 to 976)	48 (11 to 210)	44 (11 to 166)	345 (61 to 1961)	111 (22 to 567)
Day 29_ with seasonal flu vaccination	278 (90 to 856)	171 (47 to 625)	785 (178 to 3450)	1186 (317 to 4440)	137 (41 to 457)	670 (226 to 1988)	771 (164 to 3628)	184 (43 to 791)
Day 43_ with seasonal flu vaccination	260 (102 to 665)	182 (62 to 537)	503 (146 to 1729)	594 (209 to 1687)	81 (30 to 221)	663 (268 to 1639)	1035 (319 to 3363)	228 (75 to 689)
Day 1_without seasonal flu vaccination	8.54 (7.03 to 10)	7.08 (5.84 to 8.59)	8.3 (6.86 to 10)	7.76 (6.41 to 9.41)	9.35 (7.71 to 11)	7.47 (6.15 to 9.08)	6.8 (5.61 to 8.24)	9.1 (7.51 to 11)
Day 22_ without seasonal flu vaccination	115 (83 to 161)	28 (20 to 38)	85 (61 to 117)	159 (115 to 220)	52 (38 to 72)	109 (79 to 152)	158 (114 to 218)	62 (45 to 85)
Day 29_ without seasonal flu vaccination	810 (633 to 1037)	144 (113 to 183)	669 (527 to 849)	968 (760 to 1232)	228 (179 to 291)	756 (591 to 966)	1080 (847 to 1377)	297 (233 to 377)
Day 43_ without seasonal flu vaccination	600 (477 to 753)	115 (92 to 144)	477 (381 to 596)	643 (514 to 805)	182 (145 to 228)	520 (414 to 653)	770 (615 to 963)	224 (179 to 281)

No statistical analyses for this end point

Secondary: 5. Antibody Response Based on Baseline Seropositivity

Top of page

End point title

5. Antibody Response Based on Baseline Seropositivity

End point description

Subgroup analysis based on Subjects with a pre-vaccination HI antibody titer < 1:10 and pre-vaccination HI antibody titer ≥ 1:10 Subgroups with baseline HI titer < 1:10: PPS Day 1–29 analysis set. N= 104, 116, 111, 107, 109, 113, 120, and 103 for Groups A, B, C, D, E, F, G, and H, respectively. Subgroups with baseline HI titer ≥ 1:10: PPS Day 1–29 analysis set. N= 39, 33, 38, 39, 38, 34, 24, and 41 for Groups A, B, C, D, E, F, G, and H, respectively

End point type

Secondary

End point timeframe

Day 22, Day 29, Day 43

End point values	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Number of subjects analysed	152	156	156	156	155	157	156	153
Units: Percentages of subjects
number (confidence interval 95%)
Seroconversion (Day 22/Day 1)_ baseline HI < 1:10	81 (72 to 88)	39 (30 to 48)	79 (71 to 86)	90 (84 to 95)	54 (44 to 63)	78 (69 to 85)	92 (86 to 96)	61 (52 to 70)
Seroconversion (Day 29/Day 1)_ baseline HI < 1:10	99 (95 to 100)	75 (66 to 83)	100 (97 to 100)	98 (93 to 100)	85 (77 to 91)	100 (97 to 100)	100 (97 to 100)	97 (92 to 99)
Seroconversion (Day 43/Day 1)_ baseline HI < 1:10	99 (95 to 100)	75 (67 to 83)	100 (97 to 100)	98 (94 to 100)	83 (75 to 90)	99 (95 to 100)	100 (97 to 100)	91 (84 to 96)
HI titer ≥1:40 (Day 1)_ baseline HI < 1:10	0 (0 to 3)	0 (0 to 3)	0 (0 to 3)	0 (0 to 3)	0 (0 to 3)	0 (0 to 3)	0 (0 to 3)	0 (0 to 3)
HI titer ≥1:40 (Day 22)_ baseline HI < 1:10	81 (72 to 88)	39 (30 to 48)	79 (71 to 86)	90 (84 to 95)	54 (44 to 63)	78 (69 to 85)	92 (86 to 96)	61 (52 to 70)
HI titer ≥1:40 (Day 29)_ baseline HI < 1:10	99 (95 to 100)	75 (66 to 83)	100 (97 to 100)	98 (93 to 100)	85 (77 to 91)	100 (97 to 100)	100 (97 to 100)	97 (92 to 99)
HI titer ≥1:40 (Day 43)_ baseline HI < 1:10	99 (95 to 100)	75 (67 to 83)	100 (97 to 100)	98 (94 to 100)	83 (75 to 90)	99 (95 to 100)	100 (97 to 100)	91 (84 to 96)
Seroconversion (Day 22/Day 1)_ baseline HI ≥ 1:10	83 (69 to 93)	69 (51 to 83)	73 (57 to 86)	83 (68 to 93)	71 (54 to 84)	95 (82 to 99)	89 (72 to 98)	57 (41 to 72)
Seroconversion (Day 29/Day 1)_ baseline HI ≥ 1:10	97 (87 to 100)	88 (72 to 97)	95 (82 to 99)	100 (91 to 100)	92 (79 to 98)	100 (90 to 100)	100 (86 to 100)	85 (71 to 94)
Seroconversion (Day 43/Day 1)_ baseline HI ≥ 1:10	95 (84 to 99)	86 (70 to 95)	88 (74 to 96)	95 (83 to 99)	88 (74 to 96)	97 (86 to 100)	96 (82 to 100)	81 (66 to 91)
HI titer ≥1:40 (Day 1)_ baseline HI ≥ 1:10	38 (24 to 54)	40 (24 to 58)	49 (33 to 65)	41 (26 to 58)	59 (42 to 74)	38 (22 to 55)	43 (24 to 63)	45 (30 to 61)
HI titer ≥1:40 (Day 22)_ baseline HI ≥ 1:10	90 (77 to 97)	80 (63 to 92)	85 (71 to 94)	93 (80 to 98)	80 (65 to 91)	97 (86 to 100)	100 (88 to 100)	76 (61 to 88)
HI titer ≥1:40 (Day 29)_ baseline HI ≥ 1:10	100 (91 to 100)	91 (76 to 98)	100 (91 to 100)	100 (91 to 100)	97 (86 to 100)	100 (90 to 100)	100 (86 to 100)	95 (83 to 99)
HI titer ≥1:40 (Day 43)_ baseline HI ≥ 1:10	100 (92 to 100)	91 (77 to 98)	100 (91 to 100)	100 (91 to 100)	98 (87 to 100)	100 (91 to 100)	100 (88 to 100)	93 (81 to 99)

No statistical analyses for this end point

Secondary: 6. Geometric Mean Titers (GMTs) Based on Baseline Seropositivity

Top of page

End point title

6. Geometric Mean Titers (GMTs) Based on Baseline Seropositivity

End point description

Subgroup analysis based on Subjects with a pre-vaccination HI antibody titer < 1:10 and pre-vaccination HI antibody titer ≥ 1:10 Immunogenicity responses in subjects who are seropositive (A/H1N1 2009 HI titer ≥ 1:10) at Baseline (Day 1 (pre-vaccination)) as compared to those who are seronegative (HI titer < 1:10)

End point type

Secondary

End point timeframe

Day 1, Day 22, Day 29, Day 43.

End point values	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Number of subjects analysed	152	156	156	156	155	157	156	153
Units: Titer
geometric mean (confidence interval 95%)
GMTDay 1 HI < 1:10(110,121,115,115,114,120,128,111	5 (5 to 5.1)	5 (5 to 5.1)	5.1 (5 to 5.1)	5.1 (5 to 5.1)	5 (5 to 5.1)	5 (5 to 5.07)	5.1 (5 to 5.2)	5.1 (5 to 5.2)
GMTDay 22 HI< 1:10(110,121,115,115,114,120,128,111	80 (57 to 111)	18 (13 to 25)	62 (45 to 85)	130 (94 to 180)	26 (19 to 36)	72 (52 to 98)	130 (96 to 177)	39 (28 to 54)
GMTDay 29HI < 1:10(110,121,115,115,114,120,128,111	664 (505 to 872)	100 (78 to 130)	638 (490 to 830)	885 (676 to 1157)	149 (114 to 194)	685 (527 to 890)	950 (736 to 1227)	234 (179 to 307)
GMTDay 43HI < 1:10(110,121,115,115,114,120,128,111	490 (381 to 630)	85 (67 to 108)	437 (342 to 559)	568 (444 to 727)	121 (95 to 155)	463 (363 to 590)	717 (566 to 908)	177 (138 to 227)
GMT Day 1 HI ≥ 1:10 (42,35,41,41,41,37,28,42)	40 (28 to 57)	32 (21 to 47)	47 (32 to 68)	32 (22 to 46)	52 (36 to 75)	35 (24 to 52)	40 (26 to 63)	48 (33 to 69)
GMT Day 22_HI ≥ 1:10(42,35,41,41,41,37,28,42)	343 (187 to 628)	132 (68 to 258)	311 (164 to 590)	320 (171 to 599)	284 (151 to 532)	417 (217 to 802)	460 (219 to 965)	252 (134 to 475)
GMT Day 29_HI ≥ 1:10(42,35,41,41,41,37,28,42)	1178 (782 to 1776)	460 (294 to 721)	1063 (689 to 1640)	1281 (843 to 1948)	543 (356 to 830)	1197 (771 to 1857)	2088 (1240 to 3516)	641 (422 to 973)
GMT Day 43_HI ≥ 1:10(42,35,41,41,41,37,28,42)	876 (604 to 1271)	320 (212 to 482)	657 (443 to 974)	881 (599 to 1295)	464 (316 to 684)	838 (561 to 1253)	1184 (751 to 1867)	428 (290 to 631)

No statistical analyses for this end point

Secondary: 7. Number of Participants Reporting Solicited Local and Systemic Reactions After First Vaccination

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End point title

7. Number of Participants Reporting Solicited Local and Systemic Reactions After First Vaccination

End point description

Safety was measured in terms of the Number of Participants Reporting Solicited Local and Systemic Reactions After First Vaccination

End point type

Secondary

End point timeframe

Days 1 to 7

End point values	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Number of subjects analysed	171	167	167	168	167	168	166	165
Units: Number of subjects
Pain	62	43	52	86	47	65	72	51
Erythema	3	2	4	3	1	1	6	5
Swelling	8	5	5	7	11	11	10	6
Induration	14	5	10	12	10	11	15	12
Tenderness	72	49	59	96	50	78	69	60
Chills	8	3	9	11	5	8	8	8
Myalgia	16	8	13	27	8	15	17	12
Arthralgia	7	3	9	7	3	8	7	3
Headache	24	15	30	37	16	25	27	17
Nausea	10	14	13	14	7	11	12	9
Vomiting	4	5	10	4	5	8	5	5
Diarrhea	12	7	6	2	10	3	4	6
Fatigue	27	17	23	29	17	23	29	16
Fever	9	10	13	14	9	17	16	7
Stayed home	1	0	0	0	0	1	1	0
Analg./antip.used	1	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: 8. Number of Participants Reporting Solicited Local and Systemic Reactions After Second Vaccination

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End point title

8. Number of Participants Reporting Solicited Local and Systemic Reactions After Second Vaccination

End point description

Safety was measured in terms of the Number of Participants Reporting Solicited Local and Systemic Reactions After Second Vaccination

End point type

Secondary

End point timeframe

Day 22 to 28

End point values	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Number of subjects analysed	165	163	164	163	162	167	162	164
Units: Number of subjects
Pain	53	35	46	59	42	57	48	50
Erythema	3	1	4	4	5	4	5	5
Swelling	8	5	10	9	11	10	12	10
Induration	10	2	9	6	9	15	13	10
Tenderness	55	42	50	65	38	67	57	54
Chills	7	5	5	4	7	4	3	3
Myalgia	12	4	9	16	6	8	9	15
Arthralgia	2	0	1	4	2	2	0	2
Headache	12	12	12	19	14	11	13	9
Nausea	11	7	5	6	8	16	4	5
Vomiting	6	3	4	7	3	3	3	3
Diarrhea	6	6	5	5	7	7	2	4
Fatigue	16	11	15	14	17	10	13	6
Fever	10	6	5	5	10	8	7	4
Stayed home	1	0	0	0	1	0	0	0
Analg./antip.used	0	0	0	0	0	0	0	1

No statistical analyses for this end point

Secondary: 9. Number of Participants Reporting Unsolicited Adverse Events(AEs)

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End point title

9. Number of Participants Reporting Unsolicited Adverse Events(AEs)

End point description

Safety was measured in terms of the Number of Participants Reporting Unsolicited AEs

End point type

Secondary

End point timeframe

Safety monitoring periods were the Primary Period: Day 1 (1st vaccination) through ≤21 days post second vaccination, and the Follow-up Period: >21 Days post second vaccination to 12 months after second vaccination

End point values	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Number of subjects analysed	171	168	169	168	168	168	167	169
Units: Number of Subjects
AEs: all (Days 1–43)	98	80	80	85	86	93	79	79
SAEs: all (Days 1–43)	0	0	1	0	0	0	0	0
AEs leading to premature withdrawal (Days 1–43)	0	0	1	0	0	0	0	0
AEs leading to new onset of chronic disorder	0	0	0	0	0	1	0	0
AE leading to medically attended visits(Days 1–43)	31	34	25	40	34	35	28	24
AEs: all (Days 44–387)	95	98	102	93	90	101	90	95
SAEs: all (Days 44–387)	0	5	6	4	3	4	1	0
AEs leading to premature withdrawal (Days 44–387)	0	0	1	0	0	0	0	0
AEs leading to new onset of chronic dis.	2	7	4	3	4	3	6	3
AE leading to medically attended visit(Days44–387)	95	97	102	93	90	100	89	95

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Day 1 through Day 387

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

Group A

Reporting group description

3.75_(50) MF59-[3.75 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group B

Reporting group description

7.5_(0) MF59-[7.5 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group C

Reporting group description

7.5_(50) MF59-[7.5 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group D

Reporting group description

7.5_(100) MF59-[7.5 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group E

Reporting group description

15_(0) MF59-[15 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group F

Reporting group description

15_(50) MF59-[15 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group G

Reporting group description

15_(100) MF59-[15 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22]

Reporting group title

Group H

Reporting group description

30_(0) MF59-[30 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22]

Serious adverse events	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 171 (0.00%)	5 / 168 (2.98%)	7 / 169 (4.14%)	4 / 168 (2.38%)	3 / 168 (1.79%)	4 / 168 (2.38%)	1 / 167 (0.60%)	0 / 169 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foreign Body
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ulna Fracture
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Hydrocele
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	1 / 169 (0.59%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Altered state of consciousness
subjects affected / exposed	0 / 171 (0.00%)	1 / 168 (0.60%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile convulsion
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	1 / 169 (0.59%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Cerumen Impaction
subjects affected / exposed	0 / 171 (0.00%)	1 / 168 (0.60%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian Mass
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngeal stenosis
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumomediastinum
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wheezing
subjects affected / exposed	0 / 171 (0.00%)	1 / 168 (0.60%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Swelling Face
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Aggression
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bipolar Disorder
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 167 (0.60%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intermittent explosive disorder
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 167 (0.60%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oppositional defiant disorder
subjects affected / exposed	0 / 171 (0.00%)	1 / 168 (0.60%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post-traumtic Stress Disorder
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	1 / 169 (0.59%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis perforated
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	1 / 169 (0.59%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic Tonsillitis
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media chronic
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonsillar abscess
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	1 / 169 (0.59%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharngitis Streptococcal
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pharngotonsillitis
subjects affected / exposed	0 / 171 (0.00%)	1 / 168 (0.60%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	1 / 169 (0.59%)	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal scalded skin syndrome
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral Infection
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	0 / 169 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 171 (0.00%)	0 / 168 (0.00%)	1 / 169 (0.59%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 167 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Group A	Group B	Group C	Group D	Group E	Group F	Group G	Group H
Total subjects affected by non serious adverse events
subjects affected / exposed	148 / 171 (86.55%)	125 / 168 (74.40%)	141 / 169 (83.43%)	152 / 168 (90.48%)	139 / 168 (82.74%)	146 / 168 (86.90%)	140 / 167 (83.83%)	138 / 169 (81.66%)
Nervous system disorders
Headache
subjects affected / exposed	37 / 171 (21.64%)	31 / 168 (18.45%)	41 / 169 (24.26%)	46 / 168 (27.38%)	29 / 168 (17.26%)	38 / 168 (22.62%)	38 / 167 (22.75%)	29 / 169 (17.16%)
occurrences all number	51	44	49	72	38	52	54	41
General disorders and administration site conditions
Chills
subjects affected / exposed	17 / 171 (9.94%)	8 / 168 (4.76%)	14 / 169 (8.28%)	14 / 168 (8.33%)	12 / 168 (7.14%)	12 / 168 (7.14%)	11 / 167 (6.59%)	11 / 169 (6.51%)
occurrences all number	17	8	16	15	12	12	13	11
Fatigue
subjects affected / exposed	35 / 171 (20.47%)	24 / 168 (14.29%)	31 / 169 (18.34%)	34 / 168 (20.24%)	30 / 168 (17.86%)	31 / 168 (18.45%)	36 / 167 (21.56%)	20 / 169 (11.83%)
occurrences all number	48	32	43	47	36	41	46	27
Injection site erythema
subjects affected / exposed	7 / 171 (4.09%)	3 / 168 (1.79%)	7 / 169 (4.14%)	8 / 168 (4.76%)	8 / 168 (4.76%)	7 / 168 (4.17%)	15 / 167 (8.98%)	12 / 169 (7.10%)
occurrences all number	7	3	8	8	9	8	19	13
Injection site induration
subjects affected / exposed	6 / 171 (3.51%)	0 / 168 (0.00%)	4 / 169 (2.37%)	5 / 168 (2.98%)	4 / 168 (2.38%)	5 / 168 (2.98%)	9 / 167 (5.39%)	6 / 169 (3.55%)
occurrences all number	6	0	5	6	4	5	11	8
Injection site Pain
subjects affected / exposed	102 / 171 (59.65%)	73 / 168 (43.45%)	86 / 169 (50.89%)	119 / 168 (70.83%)	86 / 168 (51.19%)	100 / 168 (59.52%)	103 / 167 (61.68%)	93 / 169 (55.03%)
occurrences all number	251	178	212	316	185	271	248	220
Injection site swelling
subjects affected / exposed	7 / 171 (4.09%)	4 / 168 (2.38%)	8 / 169 (4.73%)	8 / 168 (4.76%)	10 / 168 (5.95%)	9 / 168 (5.36%)	9 / 167 (5.39%)	8 / 169 (4.73%)
occurrences all number	8	4	10	9	11	12	12	8
Pyrexia
subjects affected / exposed	41 / 171 (23.98%)	34 / 168 (20.24%)	38 / 169 (22.49%)	34 / 168 (20.24%)	44 / 168 (26.19%)	34 / 168 (20.24%)	34 / 167 (20.36%)	26 / 169 (15.38%)
occurrences all number	49	42	47	38	51	39	41	36
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	22 / 171 (12.87%)	16 / 168 (9.52%)	17 / 169 (10.06%)	10 / 168 (5.95%)	22 / 168 (13.10%)	13 / 168 (7.74%)	12 / 167 (7.19%)	16 / 169 (9.47%)
occurrences all number	28	19	21	14	29	19	13	19
Nausea
subjects affected / exposed	21 / 171 (12.28%)	22 / 168 (13.10%)	14 / 169 (8.28%)	22 / 168 (13.10%)	16 / 168 (9.52%)	23 / 168 (13.69%)	16 / 167 (9.58%)	15 / 169 (8.88%)
occurrences all number	30	26	20	24	19	31	18	17
Vomiting
subjects affected / exposed	22 / 171 (12.87%)	14 / 168 (8.33%)	27 / 169 (15.98%)	20 / 168 (11.90%)	19 / 168 (11.31%)	18 / 168 (10.71%)	20 / 167 (11.98%)	21 / 169 (12.43%)
occurrences all number	23	19	32	23	24	20	27	24
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	14 / 171 (8.19%)	8 / 168 (4.76%)	10 / 169 (5.92%)	10 / 168 (5.95%)	6 / 168 (3.57%)	7 / 168 (4.17%)	11 / 167 (6.59%)	6 / 169 (3.55%)
occurrences all number	21	13	13	14	8	8	18	8
Cough
subjects affected / exposed	34 / 171 (19.88%)	35 / 168 (20.83%)	30 / 169 (17.75%)	27 / 168 (16.07%)	34 / 168 (20.24%)	35 / 168 (20.83%)	40 / 167 (23.95%)	38 / 169 (22.49%)
occurrences all number	50	43	34	37	40	40	47	48
Nasal Congestion
subjects affected / exposed	12 / 171 (7.02%)	7 / 168 (4.17%)	6 / 169 (3.55%)	4 / 168 (2.38%)	11 / 168 (6.55%)	6 / 168 (3.57%)	8 / 167 (4.79%)	8 / 169 (4.73%)
occurrences all number	12	8	6	4	14	7	8	9
Oropharyngeal Pain
subjects affected / exposed	13 / 171 (7.60%)	9 / 168 (5.36%)	5 / 169 (2.96%)	11 / 168 (6.55%)	12 / 168 (7.14%)	12 / 168 (7.14%)	14 / 167 (8.38%)	5 / 169 (2.96%)
occurrences all number	14	10	5	15	14	13	14	5
Rhinitis allergic
subjects affected / exposed	8 / 171 (4.68%)	11 / 168 (6.55%)	6 / 169 (3.55%)	6 / 168 (3.57%)	9 / 168 (5.36%)	9 / 168 (5.36%)	15 / 167 (8.98%)	8 / 169 (4.73%)
occurrences all number	8	11	6	7	13	9	16	9
Rhinorrhoea
subjects affected / exposed	10 / 171 (5.85%)	9 / 168 (5.36%)	7 / 169 (4.14%)	9 / 168 (5.36%)	11 / 168 (6.55%)	17 / 168 (10.12%)	15 / 167 (8.98%)	11 / 169 (6.51%)
occurrences all number	15	11	7	10	12	23	17	12
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	9 / 171 (5.26%)	3 / 168 (1.79%)	13 / 169 (7.69%)	9 / 168 (5.36%)	6 / 168 (3.57%)	9 / 168 (5.36%)	8 / 167 (4.79%)	4 / 169 (2.37%)
occurrences all number	10	3	14	11	6	12	8	5
Myalgia
subjects affected / exposed	24 / 171 (14.04%)	11 / 168 (6.55%)	18 / 169 (10.65%)	37 / 168 (22.02%)	13 / 168 (7.74%)	20 / 168 (11.90%)	23 / 167 (13.77%)	22 / 169 (13.02%)
occurrences all number	30	12	25	47	14	24	27	30
Infections and infestations
Bronchitis
subjects affected / exposed	13 / 171 (7.60%)	8 / 168 (4.76%)	5 / 169 (2.96%)	10 / 168 (5.95%)	7 / 168 (4.17%)	4 / 168 (2.38%)	6 / 167 (3.59%)	3 / 169 (1.78%)
occurrences all number	14	8	5	11	7	5	7	3
Conjunctivitis
subjects affected / exposed	3 / 171 (1.75%)	8 / 168 (4.76%)	6 / 169 (3.55%)	17 / 168 (10.12%)	8 / 168 (4.76%)	7 / 168 (4.17%)	7 / 167 (4.19%)	6 / 169 (3.55%)
occurrences all number	3	8	6	18	8	9	7	6
Nasopharyngitis
subjects affected / exposed	14 / 171 (8.19%)	4 / 168 (2.38%)	10 / 169 (5.92%)	10 / 168 (5.95%)	7 / 168 (4.17%)	10 / 168 (5.95%)	9 / 167 (5.39%)	7 / 169 (4.14%)
occurrences all number	14	5	10	11	8	10	9	7
Otitis Media
subjects affected / exposed	17 / 171 (9.94%)	14 / 168 (8.33%)	28 / 169 (16.57%)	18 / 168 (10.71%)	21 / 168 (12.50%)	18 / 168 (10.71%)	23 / 167 (13.77%)	23 / 169 (13.61%)
occurrences all number	21	16	37	25	28	23	30	35
Otitis Media acute
subjects affected / exposed	9 / 171 (5.26%)	3 / 168 (1.79%)	4 / 169 (2.37%)	4 / 168 (2.38%)	7 / 168 (4.17%)	3 / 168 (1.79%)	5 / 167 (2.99%)	9 / 169 (5.33%)
occurrences all number	10	3	4	4	10	3	10	9
Pharyngitis
subjects affected / exposed	13 / 171 (7.60%)	9 / 168 (5.36%)	14 / 169 (8.28%)	15 / 168 (8.93%)	12 / 168 (7.14%)	10 / 168 (5.95%)	6 / 167 (3.59%)	6 / 169 (3.55%)
occurrences all number	16	11	20	18	15	11	6	6
Pharyngitis streptococcal
subjects affected / exposed	17 / 171 (9.94%)	19 / 168 (11.31%)	18 / 169 (10.65%)	20 / 168 (11.90%)	15 / 168 (8.93%)	20 / 168 (11.90%)	13 / 167 (7.78%)	17 / 169 (10.06%)
occurrences all number	28	24	23	27	19	22	15	19
Upper respiratory tract infection
subjects affected / exposed	29 / 171 (16.96%)	36 / 168 (21.43%)	23 / 169 (13.61%)	26 / 168 (15.48%)	25 / 168 (14.88%)	21 / 168 (12.50%)	21 / 167 (12.57%)	22 / 169 (13.02%)
occurrences all number	40	46	28	38	29	23	29	26
Viral Infection
subjects affected / exposed	13 / 171 (7.60%)	5 / 168 (2.98%)	11 / 169 (6.51%)	13 / 168 (7.74%)	10 / 168 (5.95%)	17 / 168 (10.12%)	13 / 167 (7.78%)	12 / 169 (7.10%)
occurrences all number	13	5	12	13	11	18	16	15
Sinusitis
subjects affected / exposed	9 / 171 (5.26%)	7 / 168 (4.17%)	7 / 169 (4.14%)	11 / 168 (6.55%)	9 / 168 (5.36%)	13 / 168 (7.74%)	3 / 167 (1.80%)	9 / 169 (5.33%)
occurrences all number	11	8	8	12	10	14	3	9

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Were there any global substantial amendments to the protocol? Yes

22 Jul 2009

Arthralgia and chills added to systemic reactions. Added explicit statement about parental/guardian completion of diaries. Clarified blinding procedures.Several clarifications added for consistency with other protocols

24 Jul 2009

Addition of interim analysis at Day 29. Removed red blood cell count from laboratory assessments and clarified white blood cell count.

10 Aug 2009

Local and systemic reactions and applied grading scales adjusted to Center for Biologics Evaluation and Research(CBER) requirements, and language clarified.Safety laboratory assessments list modified to match protocol V112_04 (i.e., analytes to include: hemoglobin, white blood cell count, platelet count, redblood cell count, Alanine Aminotransferase(ALT), Aspartate Aminotransferase(AST), creatinine). Safety laboratory assessments according to standardized toxicity scales, and clarified repeat assessments. Medically attended visits added as a safety endpoint. Definition for new onset of chronic disease added. Clarified populations intended for interim and final immunogenicity analyses. Language clarified to confirm that all concomitant vaccines administered within 21 days of last study vaccination were recorded. Physical assessment procedures at Visit 1 and subsequent visits defined in greater detail. Vital signs and body temperature measurements for each clinic visit added. Several clarifications added. Preferred route of body temperature measurement defined, and conventions for handling measurements obtained via alternate route clarified. Stopping rules added. Minor typographical errors corrected

21 Aug 2009

Changed MF59 adjuvant dose-level in the 75%MF59 vaccine groups to 50%. Added lower dose antigen group, and increased sample size by 170 to 1360 (from 1190). Added height and weight assessments. Clarified timing of informed consent. Instructions for handling subjects with fever within 3 days of planned vaccination, or subjects taking analgesics/antipyretics within 24 hours of planned vaccination. Clarified that child birth with healthy outcome is not a SAE. Added medically attended visits to diary cards. Clarified sample handling for serology (immunogenicity). Clarified exclusion criteria #5 and #7. Clarified volume of administration for all vaccine groups.

08 Feb 2010

Clarified and outlined the procedures related to antibody persistence. Replaced references to 6 and 12 months with references to Day 202 and Day 387, respectively.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/22418661

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Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 1. Antibody Responses After the First and Second Vaccinations

Primary: 1. Antibody Responses After the First and Second Vaccinations

Secondary: 2. Geometric Mean Titer After Each Vaccination by Vaccine Group

Secondary: 2. Geometric Mean Titer After Each Vaccination by Vaccine Group

Secondary: 3. Antibody Responses With and Without Seasonal Influenza Vaccination for Year 2009 to 2010

Secondary: 3. Antibody Responses With and Without Seasonal Influenza Vaccination for Year 2009 to 2010

Secondary: 4. Geometric Mean Titers (GMTs) With and Without Seasonal Influenza Vaccination for Year 2009 to 2010

Secondary: 4. Geometric Mean Titers (GMTs) With and Without Seasonal Influenza Vaccination for Year 2009 to 2010

Secondary: 5. Antibody Response Based on Baseline Seropositivity

Secondary: 5. Antibody Response Based on Baseline Seropositivity

Secondary: 6. Geometric Mean Titers (GMTs) Based on Baseline Seropositivity

Secondary: 6. Geometric Mean Titers (GMTs) Based on Baseline Seropositivity

Secondary: 7. Number of Participants Reporting Solicited Local and Systemic Reactions After First Vaccination

Secondary: 7. Number of Participants Reporting Solicited Local and Systemic Reactions After First Vaccination

Secondary: 8. Number of Participants Reporting Solicited Local and Systemic Reactions After Second Vaccination

Secondary: 8. Number of Participants Reporting Solicited Local and Systemic Reactions After Second Vaccination

Secondary: 9. Number of Participants Reporting Unsolicited Adverse Events(AEs)

Secondary: 9. Number of Participants Reporting Unsolicited Adverse Events(AEs)

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Substantial protocol amendments (globally)

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