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Clinical Trial Results:
A Phase 2/3, randomized, controlled, observer-blind, multi-center trial to evaluate the safety and immunogenicity of a two-dose primary vaccination series of monovalent A/Indonesia/5/2005 (H5N1) vaccine antigen adjuvanted with AS03 in children aged 6 months to < 18 years of age.

Summary
EudraCT number	2012-001683-29
Trial protocol	Outside EU/EEA
Global end of trial date	26 Jan 2014

Results information
Results version number	v2(current)
This version publication date	30 Jul 2022
First version publication date	01 Aug 2015
Other versions	v1
Version creation reason	Correction of full data set Correction of full data set and alignment between registries.

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

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Trial information

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Sponsor protocol code

114464

ISRCTN number

US NCT number

NCT01310413

WHO universal trial number (UTN)

Other trial identifiers

HHS O100200700029C: HHS/BARDA Contract Number

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l’Institut 89, Rixensart, Belgium, B-1330

Public contact

Clinical Trails Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trails Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.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

29 Apr 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

21 Jul 2011

Global end of trial reached?

Yes

Global end of trial date

26 Jan 2014

Was the trial ended prematurely?

Main objective of the trial

To assess whether two doses of H5N1 antigen in association with AS03 adjuvant elicits an immune response, measured by postimmunization vaccine-homologous virus hemagglutination inhibition (HI) titers, that meets or exceeds Center for Biologics Evaluation and Research (CBER)/ Committee for Medicinal Products for Human Use (CHMP) young adult targets for proportion of subjects attaining postimmunization reciprocal HI titres ≥ 40 against A/Indonesia/5/2005 virus (abbreviated seroprotection rate [SPR].

Protection of trial subjects

All subjects were supervised closely for at least 30 minutes following vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines. Subjects were followed-up from the time the subject consents to participate in the study until she/he is discharged.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Mar 2011

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

2 Years

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 453

Country: Number of subjects enrolled

Thailand: 292

Country: Number of subjects enrolled

Canada: 97

Worldwide total number of subjects

842

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)

274

Children (2-11 years)

568

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study included a first 385-days Blinded Phase (all subjects), followed by a 385-days Unblinded Phase. In this phase, subjects who received the placebo in the Blinded Phase were offered, after completing the Blinded Phase, 2 doses of Influenza A (H5N1) Virus monovalent vaccine administered for Dose 1 within a short delay of Day 385 (Day U0).

Screening details

A total of 842 subjects were enrolled in the study in its Blinded Phase part. This number was later amended down to 838, following corrections for wrong subject number allocation and randomization errors.

Period 1 title

Day 0 to Day 385

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Are arms mutually exclusive

Yes

Influenza A (H5N1) adjuvanted 6-<36M Group

Arm description

Subjects aged at enrolment between 3 and 36 months, 36 months excluded, received 2 doses of Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A vaccine or GSK Biologicals’ monovalent A/Indonesia/5/2005 (H5N1) vaccine adjuvanted) at Days 0 and 21. Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly. For children aged up to 12 months, 12 months excluded (< 12 months), Dose 1 was administered in the left anterolateral thigh and Dose 2 in the right anterolateral thigh. For children older than (>=) 12 months, Dose 1 was administered in the deltoid region of the non–dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).

Arm type

Experimental

Investigational medicinal product name

Influenza A (H5N1) Virus monovalent vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Emulsion for injection

Routes of administration

Intramuscular use

Dosage and administration details

All subjects will receive 2 doses administered as an intramuscular (IM) injection.

Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group

Arm description

Subjects aged at enrolment between 3 and 9 years, 9 years excluded, received 2 doses of Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A vaccine or GSK Biologicals’ monovalent A/Indonesia/5/2005 (H5N1) vaccine adjuvanted) at Days 0 and 21. Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly, Dose 1 in the deltoid region of the non–dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).

Arm type

Experimental

Investigational medicinal product name

Influenza A (H5N1) Virus monovalent vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Emulsion for injection

Routes of administration

Intramuscular use

Dosage and administration details

All subjects will receive 2 doses administered as an intramuscular (IM) injection.

Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group

Arm description

Subjects aged at enrolment between 9 and 18 years, 18 years excluded, received 2 doses of Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A vaccine or GSK Biologicals’ monovalent A/Indonesia/5/2005 (H5N1) vaccine adjuvanted) at Days 0 and 21. Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly, Dose 1 in the deltoid region of the non–dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).

Arm type

Experimental

Investigational medicinal product name

Influenza A (H5N1) Virus monovalent vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Emulsion for injection

Routes of administration

Intramuscular use

Dosage and administration details

All subjects will receive 2 doses administered as an intramuscular (IM) injection.

Placebo 6-<36M Group

Arm description

Subjects aged at enrolment between 3 and 36 months, 36 months excluded, received 2 doses of saline placebo at Days 0 and 21. The saline placebo was administered intramuscularly. For children aged up to 12 months, 12 months excluded (< 12 months), Dose 1 was administered in the left anterolateral thigh and Dose 2 in the right anterolateral thigh. For children older than (>=) 12 months, Dose 1 was administered in the deltoid region of the non–dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).

Arm type

Active comparator

Investigational medicinal product name

Saline placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

All subjects will receive 2 doses administered as an intramuscular (IM) injection.

Placebo 3-<9Y Group

Arm description

Subjects aged at enrolment between 3 and 9 years, 9 years excluded, received 2 doses of saline placebo at Days 0 and 21. The saline placebo was administered intramuscularly, Dose 1 in the deltoid region of the non–dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).

Arm type

Active comparator

Investigational medicinal product name

Saline placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

All subjects will receive 2 doses administered as an intramuscular (IM) injection.

Placebo 9-<18Y Group

Arm description

Subjects aged at enrolment between 9 and 18 years, 18 years excluded, received 2 doses of saline placebo at Days 0 and 21. The saline placebo was administered intramuscularly, Dose 1 in the deltoid region of the non–dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).

Arm type

Active comparator

Investigational medicinal product name

Saline placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

All subjects will receive 2 doses administered as an intramuscular (IM) injection.

Number of subjects in period 1 ^[1]	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Started	199	198	210	75	76	80
Completed	172	190	203	67	73	77
Not completed	27	8	7	8	3	3
Consent withdrawn by subject	5	2	-	2	1	1
Migrated/moved from study are	3	3	1	1	1	-
Unspecified	1	-	3	-	-	-
Lost to follow-up	18	3	3	5	1	2

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: A total of 842 subjects were enrolled in the study in its Blinded Phase part. This number was later amended down to 838, following corrections for wrong subject number allocation and randomization errors.

Period 2 title

Day Uo to Day U385

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Placebo/Influenza A (H5N1) Adjuvanted Group

Arm description

Subjects in this group were those who were administered the saline placebo solution in the Blinded Phase of the study (either in the Placebo 6-<36M, Placebo 3-<9Y or Placebo 9-<18Y Group). These were subjects aged at enrolment between 6 months and 18 years, 18 years excluded, who had received 2 doses of saline placebo at Days 0 and 21 in the Blinded Phase of the study, as per described in the descriptions of the Placebo 6-<36M, Placebo 3-<9Y and Placebo 9-<18Y groups. After consenting to participating to the Unblinded Phase of the study, these subjects received in addition 2 doses of Influenza A (H5N1) Virus monovalent vaccine at Days 385 (Day U0) and Day 385 + 21 days (Day U21). Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly. Dose 1 was administered in the deltoid region of the non–dominant arm and Dose 2 in the deltoid region of the dominant arm.

Arm type

Experimental

Investigational medicinal product name

Influenza A (H5N1) Virus monovalent vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Emulsion for injection

Routes of administration

Intramuscular use

Dosage and administration details

All subjects will receive 2 doses administered as an intramuscular (IM) injection at Days U0 and U21.

Number of subjects in period 2 ^[2]	Placebo/Influenza A (H5N1) Adjuvanted Group
Started	155
Completed	152
Not completed	3
Consent withdrawn by subject	1
Lost to follow-up	2

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Out of the 782 subjects aged 6 months to <18 years that completed the Blinded phase of the study (Day 0 to Day 385), only 155 subjects consented to participate in the Unblinded phase of the study (Day U0 to Day U385). Thus, the number of subjects starting the period is not consistent with the number completing the preceding period.

Baseline characteristics

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Reporting group title

Influenza A (H5N1) adjuvanted 6-<36M Group

Reporting group description

Reporting group title

Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group

Reporting group description

Reporting group title

Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group

Reporting group description

Reporting group title

Placebo 6-<36M Group

Reporting group description

Reporting group title

Placebo 3-<9Y Group

Reporting group description

Reporting group title

Placebo 9-<18Y Group

Reporting group description

Reporting group values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group	Total
Number of subjects	199	198	210	75	76	80	838
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: months
arithmetic mean (standard deviation)	21.7 ( 8.17 )	70.5 ( 21.71 )	160.8 ( 28.21 )	22.6 ( 8.17 )	65.2 ( 20.2 )	156 ( 31.29 )	-
Gender categorical
Units: Subjects
Female	92	90	103	39	35	42	401
Male	107	108	107	36	41	38	437

End points

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Reporting group title

Influenza A (H5N1) adjuvanted 6-<36M Group

Reporting group description

Reporting group title

Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group

Reporting group description

Reporting group title

Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group

Reporting group description

Reporting group title

Placebo 6-<36M Group

Reporting group description

Reporting group title

Placebo 3-<9Y Group

Reporting group description

Reporting group title

Placebo 9-<18Y Group

Reporting group description

Reporting group title

Placebo/Influenza A (H5N1) Adjuvanted Group

Reporting group description

Subject analysis set title

Influenza A (H5N1) adjuvanted Group

Subject analysis set type

Sub-group analysis

Subject analysis set description

This group results from the pooling of the Influenza A (H5N1) adjuvanted 6-<36M, Influenza A (H5N1) adjuvanted 3-<9Y and Influenza A (H5N1) adjuvanted months and 18 years, 18 years excluded, who received 2 doses of Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A or GSK Biologicals’ monovalent A/Indonesia/5/2005 (H5N1) vaccine adjuvanted) at Days 0 and 21. Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly. For children aged up to 12 months, 12 months excluded (< 12 months), Dose 1 was administered in the left anterolateral thigh and Dose 2 in the right anterolateral thigh. For children older than (>=) 12 months, Dose 1 was administered in the deltoid region of the non–dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).

Subject analysis set title

Placebo Group

Subject analysis set type

Sub-group analysis

Subject analysis set description

This group results from the pooling of the Placebo 6-<36M, Placebo 3-<9Y and Placebo 9-<18Y groups and includes subjects aged at enrolment between 6 months and 18 years, 18 years excluded, who received 2 doses of 2 doses of saline placebo at Days 0 and 21. The saline placebo was administered intramuscularly. For children aged up to 12 months, 12 months excluded (< 12 months), Dose 1 was administered in the left anterolateral thigh and Dose 2 in the right anterolateral thigh. For children older than (>=) 12 months, Dose 1 was administered in the deltoid region of the non–dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).

Primary: Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

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End point title

Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain. ^[1]

End point description

End point type

Primary

End point timeframe

At Day 42.

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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	175	185	203	64	71	76
Units: Subjects
A/INDO, Day 42	175	184	201	0	0	1

No statistical analyses for this end point

Primary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain

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End point title

Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain ^[2]

End point description

End point type

Primary

End point timeframe

At Day 42.

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	175	185	203	64	71	76
Units: Titer
geometric mean (confidence interval 95%)
A/INDO, Day 42	777.1 (705.6 to 855.9)	543.8 (484.9 to 609.8)	416.2 (371.5 to 466.2)	5.1 (4.9 to 5.3)	5.4 (5 to 5.7)	5.8 (5.3 to 6.3)

No statistical analyses for this end point

Secondary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

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End point title

Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

End point description

End point type

Secondary

End point timeframe

At Days 0 and 21

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	182	184	204	67	71	76
Units: Titer
geometric mean (confidence interval 95%)
A/INDO, Day 0 [N=182;184;204;67;71;76]	5.3 (5.1 to 5.5)	5.6 (5.3 to 5.9)	5.7 (5.4 to 6.1)	5.3 (5 to 5.7)	5.6 (5.1 to 6)	5.4 (5.1 to 5.8)
A/INDO, Day 21 [N=179;184;204;67;70;76]	38.7 (33.9 to 44.2)	44.6 (39.2 to 50.9)	35.3 (31.7 to 39.5)	5.2 (5 to 5.4)	5.4 (5 to 5.7)	5.4 (5.1 to 5.7)

No statistical analyses for this end point

Secondary: Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

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End point title

Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

End point description

End point type

Secondary

End point timeframe

At Days 0 and 21

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	182	184	204	67	71	76
Units: Subjects
A/INDO, Day 0 [N=182;184;204;67;71;76]	1	2	1	0	0	0
A/INDO, Day 21 [N=179;184;204;67;70;76]	105	110	108	0	1	0

No statistical analyses for this end point

Secondary: Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

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End point title

Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

End point description

GMI also known as the seroconversion factor (SCF) or geometric mean fold rise (GMFR) was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titre to the pre-vaccination reciprocal HI titre for the vaccine virus.

End point type

Secondary

End point timeframe

At Days 21 and 42

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	179	185	204	67	71	76
Units: Ratio
geometric mean (confidence interval 95%)
A/INDO, Day 21 [N=179;184;204;67;70;76]	7.3 (6.4 to 8.4)	8 (7 to 9.1)	6.2 (5.5 to 6.9)	1 (0.9 to 1)	1 (0.9 to 1)	1 (0.9 to 1.1)
A/INDO, Day 42 [N=175;185;203;64;71;76]	148.5 (134.5 to 164.1)	96.9 (85.3 to 110.1)	72.4 (63.9 to 82)	1 (0.9 to 1)	1 (0.9 to 1)	1.1 (1 to 1.2)

No statistical analyses for this end point

Secondary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

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End point title

Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

End point description

HI antibody titers against the H5N1 A/Indonesia virus strain (A/INDO) were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of higher than or equal to (>=) 1:10. Adapted ATP cohort for immunogenicity included all evaluable subjects for which Day 21 and Day 42 data were obtained from the ATP cohort for immunogenicity at Day 42; Day 182 data were obtained from the ATP cohort for immunogenicity at Day 182, and Day 385 data were obtained from the ATP cohort for immunogenicity at Day 385.

End point type

Secondary

End point timeframe

At Day 0 and Day 182.

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	107	101	100	36	37	35
Units: Titre
geometric mean (confidence interval 95%)
A/INDO, Day 0 [N=107;101;100;36;37;35]	5.1 (5 to 5.2)	5.2 (5 to 5.4)	5.6 (5.2 to 6)	5.3 (4.9 to 5.7)	5.2 (4.8 to 5.8)	5.4 (4.8 to 6)
A/INDO, Day 182 [N=84;89;87;29;34;31]	90.6 (78.1 to 105)	57.4 (50.8 to 64.9)	50.2 (43.3 to 58.2)	5 (5 to 5)	5.4 (4.9 to 6)	5.4 (4.9 to 5.9)

No statistical analyses for this end point

Secondary: Number of subjects seroprotected as regards haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

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End point title

Number of subjects seroprotected as regards haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

End point description

A seroprotected subject against the a/Indonesia/5/2005 (A/INDO) virus strain was defined as a subject with H5N1 reciprocal haemagglutination inhibition (HI) antibody titers greater than or equal to (>=) the seroprotection cut-off of 1:40. As the analyses were performed and disclosed stepwise - i.e. as soon as a study phase was completed - several releases of the CTRS (result summaries) were published. To generate an integrated Clinical Study Report, one set of domain datasets covering all analyses was used and the Adapted ATP cohort for immunogenicity has been defined. As a consequence, some of the data previously disclosed and based on ATP cohort for immunogenicity at Day 42, Day 182 and Day 385 have been replaced in this summary with data generated with the Adapted ATP cohort for immunogenicity.

End point type

Secondary

End point timeframe

At Day 0 and Day 182

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	182	184	204	67	71	76
Units: Subjects
A/INDO, Day 0 [N=182,184,204,67,71,76]	1	2	1	0	0	0
A/INDO, Day 182 [N=84;89;87;29;34;31]	80	75	63	0	0	0

No statistical analyses for this end point

Secondary: Number of seroconverted subjects for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Top of page

End point title

Number of seroconverted subjects for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

End point description

End point type

Secondary

End point timeframe

At Day 182

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	84	89	87	29	34	31
Units: Subjects
A/INDO	80	75	61	0	0	0

No statistical analyses for this end point

Secondary: Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Top of page

End point title

Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

End point description

End point type

Secondary

End point timeframe

At Day 182

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	84	89	87	29	34	31
Units: Ratio
geometric mean (confidence interval 95%)
A/INDO	17.8 (15.3 to 20.8)	11 (9.7 to 12.4)	8.8 (7.5 to 10.4)	1 (0.9 to 1)	1.1 (1 to 1.2)	1 (0.9 to 1.2)

No statistical analyses for this end point

Secondary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

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End point title

Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

End point description

HI antibody titers against the H5N1 A/Indonesia virus strain (A/INDO) were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of higher than or equal to (>=) 1:10. As the analyses were performed and disclosed stepwise - i.e. as soon as a study phase was completed - several releases of the CTRS (result summaries) were published. To generate an integrated Clinical Study Report, one set of domain datasets covering all analyses was used and the Adapted ATP cohort for immunogenicity has been defined. As a consequence, some of the data previously disclosed and based on ATP cohort for immunogenicity at Day 42, Day 182 and Day 385 have been replaced in this summary with data generated with the Adapted ATP cohort for immunogenicity.

End point type

Secondary

End point timeframe

At Day 0 and Day 385

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	182	184	204	67	71	76
Units: Titer
geometric mean (confidence interval 95%)
A/INDO, Day 0 [N=182,184,204,67,71,76]	5.3 (5.1 to 5.5)	5.6 (5.3 to 5.9)	5.7 (5.4 to 6.1)	5.3 (5 to 5.7)	5.6 (5.1 to 6)	5.4 (5.1 to 5.8)
A/INDO, Day 385 [N=63;85;95;26;34;36]	65.6 (55.9 to 76.9)	32.8 (28.1 to 38.4)	21.6 (18.6 to 25.1)	5.1 (4.9 to 5.4)	5.4 (4.9 to 5.8)	5.3 (4.8 to 5.9)

No statistical analyses for this end point

Secondary: Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

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End point title

Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

End point description

End point type

Secondary

End point timeframe

At Day 0 and Day 385

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	182	184	204	67	71	76
Units: Subjects
A/INDO, Day 0 [N=182, 184,204,67,71,76]	1	2	1	0	0	0
A/INDO, Day 385 [N=63;85;95;26;34;36]	54	47	27	0	0	0

No statistical analyses for this end point

Secondary: Number of seroconverted subjects for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

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End point title

Number of seroconverted subjects for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

End point description

End point type

Secondary

End point timeframe

At Day 385

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	63	84	95	26	34	36
Units: Subjects
A/INDO	53	45	23	0	0	0

No statistical analyses for this end point

Secondary: Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

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End point title

Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

End point description

GMI also known as the seroconversion factor (SCF) or geometric mean fold rise (GMFR) was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus.

End point type

Secondary

End point timeframe

At Day 385.

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	63	85	95	26	34	36
Units: Fold increase
geometric mean (confidence interval 95%)
Fold increase	12.1 (10.3 to 14.2)	5.5 (4.7 to 6.6)	3.6 (3.1 to 4.3)	1 (0.9 to 1.1)	0.9 (0.8 to 1)	1 (0.8 to 1.1)

No statistical analyses for this end point

Secondary: Microneutralization (MN) antibody titers against the H5N1 A/Indonesia and H5N1 A/Vietnam virus strains.

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End point title

Microneutralization (MN) antibody titers against the H5N1 A/Indonesia and H5N1 A/Vietnam virus strains.

End point description

MN HI antibody titers against the H5N1 A/Indonesia (A/INDO) and H5N1 A/Vietnam (A/VIET) virus strains were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of higher than or equal to (>=) 1:28.

End point type

Secondary

End point timeframe

At Days 0, 42, 182 and 385

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	36	39	40	10	11	11
Units: Titer
geometric mean (confidence interval 95%)
A/INDO, Day 0 [N=36;37;40;7;10;11]	14 (14 to 14)	15.67 (14.37 to 17.08)	15.54 (14.13 to 17.09)	15.46 (12.13 to 19.7)	14 (14 to 14)	14.91 (12.96 to 17.16)
A/INDO, Day 42 [N=34;37;40;6;10;11]	855.62 (597.88 to 1224.47)	657.6 (453.13 to 954.33)	380.62 (277.43 to 522.2)	14 (14 to 14)	14 (14 to 14)	14.91 (12.96 to 17.16)
A/INDO, Day 182 [N=33;39;33;10;10;9]	216.82 (162.03 to 290.14)	130.32 (107.3 to 158.26)	104.18 (86.95 to 124.82)	16.11 (11.73 to 22.13)	14 (14 to 14)	17.67 (12.08 to 25.86)
A/INDO, Day 385 [N=25;33;37;8;11;9]	166.64 (135.9 to 204.32)	108.59 (87.88 to 134.19)	82.26 (67.27 to 100.59)	15.27 (12.44 to 18.74)	14.91 (12.96 to 17.16)	16.33 (12.91 to 20.66)
A/VIET, Day 0 [N=36;36;40;7;10;11]	14.83 (13.89 to 15.84)	19.84 (16.82 to 23.4)	24.88 (20.75 to 29.85)	17.11 (10.47 to 27.95)	16.08 (13.05 to 19.82)	20.47 (14.82 to 28.26)
A/VIET, Day 42 [N=34;37;40;6;10;11]	68.18 (58.05 to 80.07)	71.15 (61.62 to 82.15)	65.25 (57.03 to 74.64)	17.69 (9.69 to 32.28)	19.87 (12.97 to 30.43)	28.14 (19.53 to 40.54)
A/VIET, Day 182 [N=33;39;33;10;10;9]	48.77 (36.56 to 65.06)	44.11 (36.19 to 53.77)	61.67 (51.38 to 74.01)	19.82 (12.22 to 32.14)	17.24 (13.56 to 21.9)	24.14 (14.29 to 40.78)
A/VIET, Day 385 [N=25;33;37;8;11;9]	59.83 (48.09 to 74.43)	38.62 (30.6 to 48.73)	47.73 (38.76 to 58.79)	14 (14 to 14)	18.07 (12.34 to 26.47)	35.42 (19.45 to 64.49)

No statistical analyses for this end point

Secondary: Vaccine response rate (VRR) for microneutralization (MN) antibodies against the H5N1 A/Indonesia and H5N1 A/Vietnam virus strains.

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End point title

Vaccine response rate (VRR) for microneutralization (MN) antibodies against the H5N1 A/Indonesia and H5N1 A/Vietnam virus strains.

End point description

A subject with a vaccine response was defined either as a seronegative subject with an antibody titre < 1:28 for H5N1 Flu A/Indonesia MN and H5N1 A/Vietnam or as a seropositive subject with an antibody titre ≥ 1:28 for H5N1 Flu A/Indonesia MN and H5N1 A/Vietnam. VRR for MN was defined as the incidence rate of vaccinees with a 4-fold increase in post vaccination reciprocal titer relative to Day 0.

End point type

Secondary

End point timeframe

At Day 42

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	34	37	40	6	11	11
Units: Subjects
A/INDO [N=34;37;40;6;10;11]	34	37	39	0	0	0
A/VIET [N=34;36;40;6;10;11]	30	26	16	0	1	0

No statistical analyses for this end point

Secondary: Number of subjects reporting solicited local symptoms.

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End point title

Number of subjects reporting solicited local symptoms.

End point description

Solicited local symptoms assessed were pain, redness and swelling. “Any” was defined as any occurrence of the specified solicited local symptom reported, regardless of intensity. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness and swelling were defined as redness/swelling above 100 millimeter (mm).

End point type

Secondary

End point timeframe

During the 7-day (Days 0-6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 1)

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	603	229
Units: Subjects
Any pain	405	69
Grade 3 pain	25	4
Any redness	29	0
Grade 3 redness	1	0
Any swelling	41	1
Grade 3 swelling	1	0

No statistical analyses for this end point

Secondary: Number of subjects reporting solicited local symptoms.

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End point title

Number of subjects reporting solicited local symptoms.

End point description

Solicited local symptoms assessed were pain and swelling. “Any” was defined as any occurrence of the specified solicited local symptom reported, regardless of intensity. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness and swelling were defined as redness/swelling above 100 millimeter (mm).

End point type

Secondary

End point timeframe

During the 7-day (Days U0-U6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 2)

End point values	Placebo/Influenza A (H5N1) Adjuvanted Group
Number of subjects analysed	154
Units: Subjects
Any Pain	111
Grade 3 Pain	8
Any Redness	6
Grade 3 Redness	0
Any Swelling	5
Grade 3 Swelling	0

No statistical analyses for this end point

Secondary: Number of subjects of less than 6 years of age reporting solicited general symptoms

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End point title

Number of subjects of less than 6 years of age reporting solicited general symptoms

End point description

Solicited general symptoms assessed in subjects of less than 6 years of age were drowsiness, irritability/fussiness, loss of appetite and fever [axillary temperature (T) higher than or equal to (>=) 38.0 degrees Celsius (°C)]. “Any” was defined as any occurrence of the specified solicited general symptom reported, regardless of intensity or relationship to vaccination. Grade 3 was defined as a general symptom that prevented normal activity. Related was defined as a general symptom assessed by the investigator as causally related to the study vaccination. Any fever was defined as axillary temperature above 38.0 degrees Celsius (°C). Grade 3 fever was axillary temperature above 39.0°C.

End point type

Secondary

End point timeframe

During the 7-day (Days 0-6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 1)

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	294	122
Units: Subjects
Any Drowsiness	101	29
Grade 3 Drowsiness	9	2
Related Drowsiness	81	21
Any Irritability/fussiness	128	40
Grade 3 Irritability/fussiness	10	2
Related Irritability/fussiness	111	33
Any Loss of appetite	79	29
Grade 3 Loss of appetite	8	4
Related Loss of appetite	63	20
Any Fever (Axillary T >= 38.0°C)	59	21
Grade 3 Fever	14	5
Related Fever	41	14

No statistical analyses for this end point

Secondary: Number of subjects of less than 6 years of age reporting solicited general symptoms

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End point title

Number of subjects of less than 6 years of age reporting solicited general symptoms

End point description

End point type

Secondary

End point timeframe

During the 7-day (Days U0-U6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, for each dose (Year 2)

End point values	Placebo/Influenza A (H5N1) Adjuvanted Group
Number of subjects analysed	79
Units: Subjects
Any Drowsiness	23
Grade 3 Drowsiness	1
Related Drowsiness	17
Any Irritability/Fussiness	28
Grade 3 Irritability/Fussiness	1
Related Irritability/Fussiness	23
Any Loss of appetite	18
Grade 3 Loss of appetite	0
Related Loss of appetite	13
Any Fever	4
Grade 3 Fever	2
Related Fever	3

No statistical analyses for this end point

Secondary: Number of subjects at least 6 years of age reporting solicited general symptoms

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End point title

Number of subjects at least 6 years of age reporting solicited general symptoms

End point description

Solicited general symptoms assessed in subjects of at least 6 years of age were fatigue, gastrointestinal symptoms, headache, joint pain at other location, muscle aches, shivering, sweating and fever [axillary temperature (T) >= 38.0 degrees Celsius (°C)]. Gastrointestinal symptoms included nausea, vomiting, diarrhea and/or abdominal pain. “Any” was defined as any occurrence of the specified solicited general symptom reported, regardless of intensity or relationship to vaccination. Grade 3 was defined as a general symptom that prevented normal activity. Related was defined as a general symptom assessed by the investigator as causally related to the study vaccination.

End point type

Secondary

End point timeframe

During the 7-day (Days 0-6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 1)

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	309	107
Units: Subjects
Any fatigue	89	19
Grade 3 fatigue	4	2
Related fatigue	77	16
Any gastrointestinal symptoms	43	18
Grade 3 gastrointestinal symptoms	4	2
Related gastrointestinal symptoms	27	11
Any headache	100	18
Grade 3 headache	8	3
Related headache	87	15
Any joint pain	50	9
Grade 3 joint pain	2	0
Related joint pain	43	8
Any muscle aches	123	17
Grade 3 muscle aches	7	1
Related muscle aches	114	14
Any shivering	25	7
Grade 3 shivering	2	1
Related shivering	19	5
Any sweating	25	4
Grade 3 sweating	2	0
Related sweating	22	1
Any fever [axillary temperature >= 38.0 °C]	19	3
Grade 3 fever	5	1
Related fever	13	2

No statistical analyses for this end point

Secondary: Number of subjects at least 6 years of age reporting solicited general symptoms

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End point title

Number of subjects at least 6 years of age reporting solicited general symptoms

End point description

End point type

Secondary

End point timeframe

During the 7-day (Days U0-U6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, for each dose (Year 2)

End point values	Placebo/Influenza A (H5N1) Adjuvanted Group
Number of subjects analysed	75
Units: Subjects
Any Fatigue	18
Grade 3 Fatigue	1
Related Fatigue	13
Any Gastrointestinal	7
Grade 3 Gastrointestinal	0
Related Gastrointestinal	5
Any Headache	24
Grade 3 Headache	1
Related Headache	20
Any Increased Sweating	5
Grade 3 Increased Sweating	0
Related Increased Sweating	3
Any Joint Pain	14
Grade 3 Joint Pain	0
Related Joint Pain	12
Any Muscle Aches	34
Grade 3 Muscle Aches	0
Related Muscle Aches	28
Any Shivering (Chills)	7
Grade 3 Shivering (Chills)	2
Related Shivering (Chills)	4
Any Fever	1
Grade 3 Fever	0
Related Fever	0

No statistical analyses for this end point

Secondary: Number of subjects with medically-attended adverse events (MAEs)

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End point title

Number of subjects with medically-attended adverse events (MAEs)

End point description

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination. Any MAE was defined as at least 1 MAE experienced.

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
Subject(s) with any MAE(s)	189	77

No statistical analyses for this end point

Secondary: Number of subjects with medically-attended adverse events (MAEs)

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End point title

Number of subjects with medically-attended adverse events (MAEs)

End point description

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination. Any MAE was defined as at least 1 MAE experienced.

End point type

Secondary

End point timeframe

From Day U0 up to Day U385

End point values	Placebo/Influenza A (H5N1) Adjuvanted Group
Number of subjects analysed	155
Units: Subjects
Any MAEs	36

No statistical analyses for this end point

Secondary: Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

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End point title

Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

End point description

Potential immune-mediated diseases (pIMDs) were defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune aetiology. “Any pIMD” was defined as at least one pIMD experienced by the study subject.

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
Subject(s) with any pIMD(s)	1	1

No statistical analyses for this end point

Secondary: Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

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End point title

Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

End point description

End point type

Secondary

End point timeframe

From Day U0 to Day U385

End point values	Placebo/Influenza A (H5N1) Adjuvanted Group
Number of subjects analysed	155
Units: Subjects
Subjects with any pIMD(s)	0

No statistical analyses for this end point

Secondary: Number of subjects reporting pregnancies, and outcomes of these reported pregnancies

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End point title

Number of subjects reporting pregnancies, and outcomes of these reported pregnancies

End point description

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
Subject(s) with any pregnancy	2	0
Subject(s) with related pregnancy	0	0
Spontaneous abortion	1	0
Healthy live birth	1	0

No statistical analyses for this end point

Secondary: Number of subjects reporting pregnancies, and outcomes of these reported pregnancies

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End point title

Number of subjects reporting pregnancies, and outcomes of these reported pregnancies

End point description

End point type

Secondary

End point timeframe

From Day U0 up to Day U385

End point values	Placebo/Influenza A (H5N1) Adjuvanted Group
Number of subjects analysed	155
Units: Subjects
Subject(s) with any pregnancy	0

No statistical analyses for this end point

Secondary: Number of subjects with normal and abnormal biochemical parameters assessed with respect to alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT)

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End point title

Number of subjects with normal and abnormal biochemical parameters assessed with respect to alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT)

End point description

Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	606	231
Units: Subjects
ALAT, PRE Unknown [N=606,231]	15	4
ALAT, PRE Below [N=606,231]	0	0
ALAT, PRE Normal [N=606,231]	586	221
ALAT, PRE Above [N=606,231]	5	6
ALAT, Day 42 Unknown [N=583,220]	17	4
ALAT, Day 42 Below [N=583,220]	0	0
ALAT, Day 42 Normal [N=583,220]	562	212
ALAT, Day 42 Above [N=583,220]	4	4
ALAT, Day 182 Unknown [N=304,110]	6	0
ALAT, Day 182 Below [N=304,110]	0	0
ALAT, Day 182 Normal [N=304,110]	289	110
ALAT, Day 182 Above [N=304,110]	9	0
ALAT, Day 385 Unknown [N=251,104]	5	0
ALAT, Day 385 Below [N=251,104]	0	0
ALAT, Day 385 Normal [N=251,104]	245	100
ALAT, Day 385 Above [N=251,104]	1	4
ASAT, PRE Unknown [N=606,231]	15	4
ASAT, PRE Below [N=606,231]	0	0
ASAT, PRE Normal [N=606,231]	577	219
ASAT, PRE Above [N=606,231]	14	8
ASAT, Day 42 Unknown [N=583,220]	19	4
ASAT, Day 42 Below [N=583,220]	0	0
ASAT, Day 42 Normal [N=583,220]	552	208
ASAT, Day 42 Above [N=583,220]	12	8
ASAT, Day 182 Unknown [N=304,110]	8	0
ASAT, Day 182 Below [N=304,110]	0	0
ASAT, Day 182 Normal [N=304,110]	284	108
ASAT, Day 182 Above [N=304,110]	12	2
ASAT, Day 385 Unknown [N=251,104]	7	0
ASAT, Day 385 Below [N=251,104]	0	0
ASAT, Day 385 Normal [N=251,104]	240	100
ASAT, Day 385 Above [N=251,104]	4	4

No statistical analyses for this end point

Secondary: Number of subjects with normal and abnormal biochemical parameters assessed with respect to total bilirubin (T-BIL) and bilirubin conjugated/direct (BIL-C/D)

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End point title

Number of subjects with normal and abnormal biochemical parameters assessed with respect to total bilirubin (T-BIL) and bilirubin conjugated/direct (BIL-C/D)

End point description

Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	606	231
Units: Subjects
T-BIL, PRE Unknown [N=606,231]	15	4
T-BIL, PRE Below [N=606,231]	0	0
T-BIL, PRE Normal [N=606,231]	587	224
T-BIL, PRE Above [N=606,231]	4	3
T-BIL, Day 42 Unknown [N=583,220]	16	4
T-BIL, Day 42 Below [N=583,220]	0	0
T-BIL, Day 42 Normal [N=583,220]	558	214
T-BIL, Day 42 Above [N=583,220]	9	2
T-BIL, Day 182 Unknown [N=304,110]	6	0
T-BIL, Day 182 Below [N=304,110]	0	0
T-BIL, Day 182 Normal [N=304,110]	296	110
T-BIL, Day 182 Above [N=304,110]	2	0
T-BIL, Day 385 Unknown [N=251,104]	7	1
T-BIL, Day 385 Below [N=251,104]	0	0
T-BIL, Day 385 Normal [N=251,104]	240	102
T-BIL, Day 385 Above [N=251,104]	4	1
BIL-C/D, PRE Unknown [N=606,231]	15	4
BIL-C/D, PRE Below [N=606,231]	0	0
BIL-C/D, PRE Normal [N=606,231]	591	226
BIL-C/D, PRE Above [N=606,231]	0	1
BIL-C/D, Day 42 Unknown [N=583,220]	16	4
BIL-C/D, Day 42 Below [N=583,220]	0	0
BIL-C/D, Day 42 Normal [N=583,220]	558	214
BIL-C/D, Day 42 Above [N=583,220]	9	2
BIL-C/D, Day 182 Unknown [N=304,110]	7	0
BIL-C/D, Day 182 Below [N=304,110]	0	0
BIL-C/D, Day 182 Normal [N=304,110]	297	110
BIL-C/D, Day 182 Above [N=304,110]	0	0
BIL-C/D, Day 385 Unknown [N=251,104]	8	1
BIL-C/D, Day 385 Below [N=251,104]	0	0
BIL-C/D, Day 385 Normal [N=251,104]	240	103
BIL-C/D, Day 385 Above [N=251,104]	3	0

No statistical analyses for this end point

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

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End point title

Number of subjects reporting any unsolicited adverse events (AEs).

End point description

An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. “Any” was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.

End point type

Secondary

End point timeframe

During the 21-day (Days 0-20) post-vaccination period following Dose 1 of vaccine/placebo

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
Subject(s) with any unsolicited AEs	153	63

No statistical analyses for this end point

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

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End point title

Number of subjects reporting any unsolicited adverse events (AEs).

End point description

End point type

Secondary

End point timeframe

During the 21-day (Days 21-41) post-vaccination period following Dose 2 of vaccine/placebo

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	593	224
Units: Subjects
Subject(s) with any unsolicited AEs	135	54

No statistical analyses for this end point

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

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End point title

Number of subjects reporting any unsolicited adverse events (AEs).

End point description

End point type

Secondary

End point timeframe

During the 42-day (Days 0-41) post-vaccination period following Dose 1 of vaccine/placebo

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
Subject(s) with any unsolicited AEs	243	97

No statistical analyses for this end point

Secondary: Number of subjects reporting serious adverse events (SAEs)

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End point title

Number of subjects reporting serious adverse events (SAEs)

End point description

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

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
Subject(s) with any SAE(s)	8	4

No statistical analyses for this end point

Secondary: Number of subjects reporting serious adverse events (SAEs)

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End point title

Number of subjects reporting serious adverse events (SAEs)

End point description

End point type

Secondary

End point timeframe

From Day U0 up to Day U385

End point values	Placebo/Influenza A (H5N1) Adjuvanted Group
Number of subjects analysed	155
Units: Subjects
Subject(s) with any SAE(s)	2

No statistical analyses for this end point

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

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End point title

Number of subjects reporting any unsolicited adverse events (AEs).

End point description

End point type

Secondary

End point timeframe

During the 21-day (Days U0-U20) post-vaccination period following Dose 1 of Influenza A (H5N1) Virus monovalent vaccine

End point values	Placebo/Influenza A (H5N1) Adjuvanted Group
Number of subjects analysed	155
Units: Subjects
Subject(s) with any unsolicited AEs	21

No statistical analyses for this end point

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

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End point title

Number of subjects reporting any unsolicited adverse events (AEs).

End point description

End point type

Secondary

End point timeframe

During the 21-day (Days U21-U41) post-vaccination period following Dose 2 of Influenza A (H5N1) Virus monovalent vaccine

End point values	Placebo/Influenza A (H5N1) Adjuvanted Group
Number of subjects analysed	155
Units: Subjects
Subject(s) with any unsolicited AEs	27

No statistical analyses for this end point

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

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End point title

Number of subjects reporting any unsolicited adverse events (AEs).

End point description

End point type

Secondary

End point timeframe

During the 42-day (Days U0-U41) post-vaccination period following Dose 1 of Influenza A (H5N1) Virus monovalent vaccine

End point values	Placebo/Influenza A (H5N1) Adjuvanted Group
Number of subjects analysed	155
Units: Subjects
Subject(s) with any unsolicited AEs	41

No statistical analyses for this end point

Secondary: Number of subjects with normal and abnormal biochemical parameters assessed with respect to creatinine (CREA) and blood urea nitrogen (BUN)

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End point title

Number of subjects with normal and abnormal biochemical parameters assessed with respect to creatinine (CREA) and blood urea nitrogen (BUN)

End point description

Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
CREA, PRE Unknown [N=606,231]	15	4
CREA, PRE Below [N=606, 231]	142	61
CREA, PRE Within [N=606, 231]	447	165
CREA, PRE Above [N=606, 231]	2	1
CREA, Day 42 Unknown [N=583,220]	17	4
CREA, Day 42 Below [N=583,220]	130	48
CREA, Day 42 Within [N=583,220]	432	166
CREA, Day 42 Above [N=583,220]	4	2
CREA, Day 182 Unknown [N=304,110]	6	1
CREA, Day 182 Below [N=304,110]	66	26
CREA, Day 182 Within [N=304,110]	231	83
CREA, Day 182 Above [N=304,110]	1	0
CREA, Day 385 Unknown [N=251,104]	6	0
CREA, Day 385 Below [N=251,104]	51	24
CREA, Day 385 Within [N=251,104]	191	80
CREA, Day 385 Above [N=251,104]	3	0
BUN, PRE Unknown [N=606,231]	15	4
BUN, PRE Below [N=606,231]	13	4
BUN, PRE Within [N=606,231]	553	218
BUN, PRE Above [N=606,231]	25	5
BUN, Day 42 Unknown [N=583,220]	17	4
BUN, Day 42 Below [N=583,220]	11	3
BUN, Day 42 Within [N=583,220]	531	209
BUN, Day 42 Above [N=583,220]	24	4
BUN, Day 182 Unknown [N=304,110]	6	0
BUN, Day 182 Below [N=304,110]	8	2
BUN, Day 182 Within [N=304,110]	281	105
BUN, Day 182 Above [N=304,110]	9	3
BUN, Day 385 Unknown [N=251,104]	7	0
BUN, Day 385 Below [N=251,104]	3	2
BUN, Day 385 Within [N=251,104]	237	100
BUN, Day 385 Above [N=251,104]	4	2

No statistical analyses for this end point

Secondary: Number of subjects with normal and abnormal haematological parameters assessed with respect to basophils (BAS) and eosinophils (EOS)

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End point title

Number of subjects with normal and abnormal haematological parameters assessed with respect to basophils (BAS) and eosinophils (EOS)

End point description

Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
BAS, PRE Unknown [N=606,231]	29	12
BAS, PRE Below [N=606,231]	0	0
BAS, PRE Within [N=606,231]	576	219
BAS, PRE Above [N=606,231]	1	0
BAS, Day 42 Unknown [N=583,220]	34	13
BAS, Day 42 Below [N=583,220]	0	0
BAS, Day 42 Within [N=583,220]	549	207
BAS, Day 42 Above [N=583,220]	0	0
BAS, Day 182 Unknown [N=304,110]	17	2
BAS, Day 182 Below [N=304,110]	0	0
BAS, Day 182 Within [N=304,110]	287	108
BAS, Day 182 Above [N=304,110]	0	0
BAS, Day 385 Unknown [N=251,104]	6	3
BAS, Day 385 Below [N=251,104]	0	0
BAS, Day 385 Within [N=251,104]	245	101
BAS, Day 385 Above [N=251,104]	0	0
EOS, PRE Unknown [N=606,231]	29	12
EOS, PRE Below [N=606,231]	68	19
EOS, PRE Within [N=606,231]	473	187
EOS, PRE Above [N=606,231]	36	13
EOS, Day 42 Unknown [N=583,220]	34	13
EOS, Day 42 Below [N=583,220]	49	15
EOS, Day 42 Within [N=583,220]	452	175
EOS, Day 42 Above [N=583,220]	48	17
EOS, Day 182 Unknown [N=304,110]	17	2
EOS, Day 182 Below [N=304,110]	33	11
EOS, Day 182 Within [N=304,110]	237	85
EOS, Day 182 Above [N=304,110]	17	12
EOS, Day 385 Unknown [N=251,104]	6	3
EOS, Day 385 Below [N=251,104]	32	17
EOS, Day 385 Within [N=251,104]	198	77
EOS, Day 385 Above [N=251,104]	15	7

No statistical analyses for this end point

Secondary: Number of subjects with normal and abnormal haematological parameters assessed with respect to haematocrit (Hcr) and haemoglobin (Hgb)

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End point title

Number of subjects with normal and abnormal haematological parameters assessed with respect to haematocrit (Hcr) and haemoglobin (Hgb)

End point description

Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
Hcr, PRE Unknown [N=606,231]	26	10
Hcr, PRE Below [N=606,231]	53	21
Hcr, PRE Within [N=606,231]	480	181
Hcr, PRE Above [N=606,231]	47	19
Hcr, Day 42 Unknown [N=583,220]	19	7
Hcr, Day 42 Below [N=583,220]	45	13
Hcr, Day 42 Within [N=583,220]	477	178
Hcr, Day 42 Above [N=583,220]	42	22
Hcr, Day 182 Unknown [N=304,110]	12	2
Hcr, Day 182 Below [N=304,110]	38	7
Hcr, Day 182 Within [N=304,110]	238	91
Hcr, Day 182 Above [N=304,110]	16	10
Hcr, Day 385 Unknown [N=251,104]	5	3
Hcr, Day 385 Below [N=251,104]	18	12
Hcr, Day 385 Within [N=251,104]	215	85
Hcr, Day 385 Above [N=251,104]	13	4
Hgb, PRE Unknown [N=606,231]	26	10
Hgb, PRE Below [N=606,231]	61	26
Hgb, PRE Within [N=606,231]	497	182
Hgb, PRE Above [N=606,231]	22	13
Hgb, Day 42 Unknown [N=583,220]	19	8
Hgb, Day 42 Below [N=583,220]	69	19
Hgb, Day 42 Within [N=583,220]	476	185
Hgb, Day 42 Above [N=583,220]	19	8
Hgb, Day 182 Unknown [N=304,110]	11	2
Hgb, Day 182 Below [N=304,110]	42	16
Hgb, Day 182 Within [N=304,110]	241	89
Hgb, Day 182 Above [N=304,110]	10	3
Hgb, Day 385 Unknown [N=251,104]	5	3
Hbg, Day 385 Below [N=251,104]	27	15
Hbg, Day 385 Within [N=251,104]	210	84
Hbg, Day 385 Above [N=251,104]	9	2

No statistical analyses for this end point

Secondary: Number of subjects with normal and abnormal haematological parameters assessed with respect to neutrophils (NEU) and platelets (PLA)

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End point title

Number of subjects with normal and abnormal haematological parameters assessed with respect to neutrophils (NEU) and platelets (PLA)

End point description

Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
NEU, PRE Unknown [N=606,231]	29	12
NEU, PRE Below [N=606,231]	26	10
NEU, PRE Within [N=606,231]	534	202
NEU, PRE Above [N=606,231]	17	7
NEU, Day 42 Unknown [N=583,220]	34	13
NEU, Day 42 Below [N=583,220]	29	8
NEU, Day 42 Within [N=583,220]	505	189
NEU, Day 42 Above [N=583,220]	15	10
NEU, Day 182 Unknown [N=304,110]	17	2
NEU, Day 182 Below [N=304,110]	14	3
NEU, Day 182 Within [N=304,110]	266	105
NEU, Day 182 Above [N=304,110]	7	0
NEU, Day 385 Unknown [N=251,104]	6	3
NEU, Day 385 Below [N=251,104]	12	3
NEU, Day 385 Within [N=251,104]	227	96
NEU, Day 385 Above [N=251,104]	6	2
PLA, PRE Unknown [N=606,231]	35	17
PLA, PRE Below [N=606,231]	3	0
PLA, PRE Within [N=606,231]	518	187
PLA, PRE Above [N=606,231]	50	27
PLA, Day 42 Unknown [N=583,220]	32	12
PLA, Day 42 Below [N=583,220]	1	0
PLA, Day 42 Within [N=583,220]	500	184
PLA, Day 42 Above [N=583,220]	50	24
PLA, Day 182 Unknown [N=304,110]	20	5
PLA, Day 182 Below [N=304,110]	0	0
PLA, Day 182 Within [N=304,110]	260	96
PLA, Day 182 Above [N=304,110]	24	9
PLA, Day 385 Unknown [N=251,104]	8	8
PLA, Day 385 Below [N=251,104]	1	0
PLA, Day 385 Within [N=251,104]	234	94
PLA, Day 385 Above [N=251,104]	8	2

No statistical analyses for this end point

Secondary: Number of subjects with normal and abnormal haematological parameters assessed with respect to lymphocytes (LYM) and monocytes (MON)

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End point title

Number of subjects with normal and abnormal haematological parameters assessed with respect to lymphocytes (LYM) and monocytes (MON)

End point description

Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
LYM, PRE Unknown [N=606,231]	29	12
LYM, PRE Below [N=606,231]	7	1
LYM, PRE Within [N=606,231]	441	161
LYM, PRE Above [N=606,231]	129	57
LYM, Day 42 Unknown [N=583,220]	34	13
LYM, Day 42 Below [N=583,220]	6	2
LYM, Day 42 Within [N=583,220]	446	162
LYM, Day 42 Above [N=583,220]	97	43
LYM, Day 182 Unknown [N=304,110]	17	2
LYM, Day 182 Below [N=304,110]	0	1
LYM, Day 182 Within [N=304,110]	235	93
LYM, Day 182 Above [N=304,110]	52	14
LYM, Day 385 Unknown [N=251,104]	6	3
LYM, Day 385 Below [N=251,104]	0	0
LYM, Day 385 Within [N=251,104]	223	86
LYM, Day 385 Above [N=251,104]	22	15
MON, PRE Unknown [N=606,231]	29	12
MON, PRE Below [N=606,231]	94	46
MON, PRE Within [N=606,231]	480	170
MON, PRE Above [N=606,231]	3	3
MON, Day 42 Unknown [N=583,220]	34	13
MON, Day 42 Below [N=583,220]	110	37
MON, Day 42 Within [N=583,220]	434	167
MON, Day 42 Above [N=583,220]	5	3
MON, Day 182 Unknown [N=304,110]	17	2
MON, Day 182 Below [N=304,110]	61	20
MON, Day 182 Within [N=304,110]	221	88
MON, Day 182 Above [N=304,110]	5	0
MON, Day 385 Unknown [N=251,104]	6	3
MON, Day 385 Below [N=251,104]	31	18
MON, Day 385 Within [N=251,104]	211	83
MON, Day 385 Above [N=251,104]	3	0

No statistical analyses for this end point

Secondary: Number of subjects with normal and abnormal haematological parameters assessed with respect to red and white blood cells (RBC and WBC)

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End point title

Number of subjects with normal and abnormal haematological parameters assessed with respect to red and white blood cells (RBC and WBC)

End point description

Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.

End point type

Secondary

End point timeframe

From Day 0 up to Day 385

End point values	Influenza A (H5N1) adjuvanted Group	Placebo Group
Number of subjects analysed	607	231
Units: Subjects
RBC, PRE Unknown [N=606,231]	26	10
RBC, PRE Below [N=606,231]	25	4
RBC, PRE Within [N=606,231]	504	198
RBC, PRE Above [N=606,231]	51	19
RBC, Day 42 Unknown [N=583,220]	19	8
RBC, Day 42 Below [N=583,220]	21	6
RBC, Day 42 Within [N=583,220]	496	189
RBC, Day 42 Above [N=583,220]	47	17
RBC, Day 182 Unknown [N=304,110]	11	2
RBC, Day 182 Below [N=304,110]	13	5
RBC, Day 182 Within [N=304,110]	266	93
RBC, Day 182 Above [N=304,110]	14	10
RBC, Day 385 Unknown [N=251,104]	5	3
RBC, Day 385 Below [N=251,104]	8	2
RBC, Day 385 Within [N=251,104]	214	90
RBC, Day 385 Above [N=251,104]	24	9
WBC, PRE Unknown [N=606,231]	29	12
WBC, PRE Below [N=606,231]	27	9
WBC, PRE Within [N=606,231]	543	207
WBC, PRE Above [N=606,231]	7	3
WBC, Day 42 Unknown [N=583,220]	34	13
WBC, Day 42 Below [N=583,220]	38	8
WBC, Day 42 Within [N=583,220]	508	198
WBC, Day 42 Above [N=583,220]	3	1
WBC, Day 182 Unknown [N=304,110]	17	2
WBC, Day 182 Below [N=304,110]	21	7
WBC, Day 182 Within [N=304,110]	264	101
WBC, Day 182 Above [N=304,110]	2	0
WBC, Day 385 Unknown [N=251,104]	6	3
WBC, Day 385 Below [N=251,104]	15	6
WBC, Day 385 Within [N=251,104]	230	94
WBC, Day 385 Above [N=251,104]	0	1

No statistical analyses for this end point

Secondary: Number of subjects seropositive for microneutralization (MN) antibodies against the H5N1 A/Indonesia virus strain.

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End point title

Number of subjects seropositive for microneutralization (MN) antibodies against the H5N1 A/Indonesia virus strain.

End point description

End point type

Secondary

End point timeframe

At Days 0 and 42

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	36	37	40	7	10	11
Units: Subjects
At Day 0	0	6	5	1	0	1
At Day 42	34	37	40	0	0	1

No statistical analyses for this end point

Secondary: Number of seroconverted subjects for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain

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End point title

Number of seroconverted subjects for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain

End point description

A subject seroconverted for HI antibodies against the H5N1 A/Indonesia virus strain (A/INDO) was defined as a vaccinee with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer higher than or equal to (>=) 1:40, or with a pre-vaccination titer >= 1:10 and at least a 4-fold increase in post-vaccination titer. As the analyses were performed and disclosed stepwise - i.e. as soon as a study phase was completed - several releases of the CTRS (result summaries) were published. To generate an integrated Clinical Study Report, one set of domain datasets covering all analyses was used and the Adapted ATP cohort for immunogenicity has been defined. As a consequence, some of the data previously disclosed and based on ATP cohort for immunogenicity at Day 42, Day 182 and Day 385 have been replaced in this summary with data generated with the Adapted ATP cohort for immunogenicity.

End point type

Secondary

End point timeframe

At Days 21 and 42

End point values	Influenza A (H5N1) adjuvanted 6-<36M Group	Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group	Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group	Placebo 6-<36M Group	Placebo 3-<9Y Group	Placebo 9-<18Y Group
Number of subjects analysed	179	185	204	67	71	76
Units: Subjects
A/INDO, Day 21 [N=179;183;204;67;70;76]	103	107	105	0	0	0
A/INDO, Day 42 [N=175;184;203;64;71;76]	175	183	201	0	0	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Serious Adverse events (SAE) = Day 0 to Day 385 and Day U0 to U385. Solicited local and general symptoms = During the 7-day period post vaccine/placebo administration. Unsolicited AEs = During the 42-day post vaccine/placebo administration.

Adverse event reporting additional description

For the systematically assessed other (non-serious) adverse events, number of participants at risk included those from Total Vaccinated cohort who had the symptom sheet completed. The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

15.1

Reporting group title

Influenza A (H5N1) adjuvanted Group

Reporting group description

This group results from the pooling of the Influenza A (H5N1) adjuvanted 6-<36M, Influenza A (H5N1) adjuvanted 3-<9Y and Influenza A (H5N1) adjuvanted 9-<18Y groups and includes subjects aged at enrolment between 6 months and 18 years, 18 years excluded, who received 2 doses of Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A vaccine or GSK Biologicals’ monovalent A/Indonesia/5/2005 (H5N1) vaccine adjuvanted) at Days 0 and 21. Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly. For children aged up to 12 months, 12 months excluded (< 12 months), Dose 1 was administered in the left anterolateral thigh and Dose 2 in the right anterolateral thigh. For children older than (>=) 12 months, Dose 1 was administered in the deltoid region of the non–dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).

Reporting group title

Placebo/Influenza A (H5N1) adjuvanted Group

Reporting group description

Subjects in this group were those who were administered the saline placebo solution in the Blinded Phase of the study (either in the Placebo 6-<36M, Placebo 3-<9Y or Placebo 9-<18Y Group). These were subjects aged at enrolment between 6 months and 18 years, 18 years excluded, who had received 2 doses of saline placebo at Days 0 and 21 in the Blinded Phase of the study, as per described in the descriptions of the Placebo 6-<36M, Placebo 3-<9Y and Placebo 9-<18Y groups. After consenting to participating to the Unblinded Phase of the study, these subjects received in addition 2 doses of Influenza A (H5N1) Virus monovalent vaccine at Days 385 (Day U0) and Day 385 + 21 days (Day U21). Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly. Dose 1 of was administered in the deltoid region of the non–dominant arm and Dose 2 in the deltoid region of the dominant arm.

Reporting group title

Placebo Group

Reporting group description

Serious adverse events	Influenza A (H5N1) adjuvanted Group	Placebo/Influenza A (H5N1) adjuvanted Group	Placebo Group
Total subjects affected by serious adverse events
subjects affected / exposed	8 / 607 (1.32%)	2 / 155 (1.29%)	4 / 231 (1.73%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Injury, poisoning and procedural complications
Skeletal injury
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	1 / 607 (0.16%)	0 / 155 (0.00%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	0 / 607 (0.00%)	1 / 155 (0.65%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Febrile convulsion
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	1 / 607 (0.16%)	0 / 155 (0.00%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	1 / 607 (0.16%)	0 / 155 (0.00%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	0 / 607 (0.00%)	0 / 155 (0.00%)	1 / 231 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	1 / 607 (0.16%)	0 / 155 (0.00%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	0 / 607 (0.00%)	0 / 155 (0.00%)	1 / 231 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchial hyperreactivity
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	1 / 607 (0.16%)	0 / 155 (0.00%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	0 / 607 (0.00%)	0 / 155 (0.00%)	1 / 231 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Infectious mononucleosis
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	2 / 607 (0.33%)	0 / 155 (0.00%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	1 / 607 (0.16%)	0 / 155 (0.00%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	1 / 607 (0.16%)	0 / 155 (0.00%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	1 / 607 (0.16%)	0 / 155 (0.00%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Scarlet fever
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	0 / 607 (0.00%)	1 / 155 (0.65%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	1 / 607 (0.16%)	0 / 155 (0.00%)	0 / 231 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Type 1 diabetes mellitus
Additional description: SAE assessed during Day 0 to Day 385 for Influenza A (H5N1) adjuvanted and Placebo Groups and from Day U0 to U385 for the Placebo/Influenza A (H5N1) adjuvanted Group.
subjects affected / exposed	0 / 607 (0.00%)	0 / 155 (0.00%)	1 / 231 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Influenza A (H5N1) adjuvanted Group	Placebo/Influenza A (H5N1) adjuvanted Group	Placebo Group
Total subjects affected by non serious adverse events
subjects affected / exposed	502 / 607 (82.70%)	124 / 155 (80.00%)	189 / 231 (81.82%)
General disorders and administration site conditions
Pain
alternative assessment type: Systematic
subjects affected / exposed ^[1]	405 / 603 (67.16%)	111 / 154 (72.08%)	69 / 229 (30.13%)
occurrences all number	405	111	69
Swelling
alternative assessment type: Systematic
subjects affected / exposed ^[2]	41 / 603 (6.80%)	5 / 154 (3.25%)	1 / 229 (0.44%)
occurrences all number	41	5	1
Drowsiness
alternative assessment type: Systematic
subjects affected / exposed ^[3]	101 / 294 (34.35%)	23 / 79 (29.11%)	29 / 122 (23.77%)
occurrences all number	101	23	29
Irritability/fussiness
alternative assessment type: Systematic
subjects affected / exposed ^[4]	128 / 294 (43.54%)	28 / 79 (35.44%)	40 / 122 (32.79%)
occurrences all number	128	28	40
Loss of appetite
alternative assessment type: Systematic
subjects affected / exposed ^[5]	79 / 294 (26.87%)	18 / 79 (22.78%)	29 / 122 (23.77%)
occurrences all number	79	18	29
Fever (axillary temperature >= 38.0°C) (children less than 6 years of age)
alternative assessment type: Systematic
subjects affected / exposed ^[6]	59 / 294 (20.07%)	4 / 79 (5.06%)	21 / 122 (17.21%)
occurrences all number	59	4	21
Fatigue
alternative assessment type: Systematic
subjects affected / exposed ^[7]	89 / 309 (28.80%)	18 / 75 (24.00%)	19 / 107 (17.76%)
occurrences all number	89	18	19
Gastrointestinal disorders
alternative assessment type: Systematic
subjects affected / exposed ^[8]	43 / 309 (13.92%)	7 / 75 (9.33%)	18 / 107 (16.82%)
occurrences all number	42	7	17
Headache
alternative assessment type: Systematic
subjects affected / exposed ^[9]	100 / 309 (32.36%)	24 / 75 (32.00%)	18 / 107 (16.82%)
occurrences all number	100	24	18
Joint pain at other location
alternative assessment type: Systematic
subjects affected / exposed ^[10]	50 / 309 (16.18%)	14 / 75 (18.67%)	9 / 107 (8.41%)
occurrences all number	50	14	9
Muscle aches
alternative assessment type: Systematic
subjects affected / exposed ^[11]	123 / 309 (39.81%)	34 / 75 (45.33%)	17 / 107 (15.89%)
occurrences all number	123	34	17
Shivering
alternative assessment type: Systematic
subjects affected / exposed ^[12]	25 / 309 (8.09%)	7 / 75 (9.33%)	7 / 107 (6.54%)
occurrences all number	25	7	7
Sweating
alternative assessment type: Systematic
subjects affected / exposed ^[13]	25 / 309 (8.09%)	5 / 75 (6.67%)	4 / 107 (3.74%)
occurrences all number	25	5	4
Fever (axillary temperature >= 38.0°C) (children with at least 6 years of age)
alternative assessment type: Systematic
subjects affected / exposed ^[14]	19 / 309 (6.15%)	1 / 75 (1.33%)	3 / 107 (2.80%)
occurrences all number	19	1	3
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	13 / 607 (2.14%)	3 / 155 (1.94%)	12 / 231 (5.19%)
occurrences all number	15	3	14
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	36 / 607 (5.93%)	9 / 155 (5.81%)	17 / 231 (7.36%)
occurrences all number	36	9	17
Rhinorrhoea
subjects affected / exposed	27 / 607 (4.45%)	3 / 155 (1.94%)	13 / 231 (5.63%)
occurrences all number	27	3	13
Infections and infestations
Nasopharyngitis
subjects affected / exposed	29 / 607 (4.78%)	10 / 155 (6.45%)	18 / 231 (7.79%)
occurrences all number	29	10	18

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented and symptom sheet completed only on subjects that reported the specific symptom. Subjects who missed reporting symptoms (solicited/unsolicited or concomitant medications) were treated as subjects without symptoms (solicited/unsolicited or concomitant medications, respectively).

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Were there any global substantial amendments to the protocol? Yes

15 Sep 2010

At the request of the U.S. Center for Biologics Research (CBER): (1) an independent data monitoring committee (IDMC) replaces the internal Safety Review Committee (iSRC) described in the previous version of the protocol, and (2) a blood sample for immunogenicity assessment has been added at the Day 21 visit. To facilitate receipt of immune-response information by participating study sites before epochs 4 and 5 begin, unblinding will occur after completion of the Day 182 visit. The language describing randomization of supplies has been modified to clarify that the vaccine will be presented in multi-dose vials that will be used as monodose vials in this study. Finally, several minor editorial errors have been corrected.

08 Dec 2010

The total volume of blood collected on Days 0, 42, and 182 or 385 has been decreased from 8.5 mL to 7 mL. The total volume of blood collected on Day 21 has been increased from 3.5 mL to 5 mL. These changes reflect a decrease in blood volume for safety laboratory assessments from 5 mL to 2 mL, as only a 2 mL sample is required by the central laboratory performing the tests. The total volume of blood collected for immune response assessments has been increased to 5 mL rather than 3.5 mL to allow for expanded testing for cross-reactive antibodies. Unblinding at the subject level will take place following the Day 385 analysis, as earlier unblinding potentially compromises assessment of adverse events during the interval between Days 183 and 385. A limit has been placed on the amount of time that may elapse following Day 385 during which placebo subjects may receive open-label, AS03-adjuvanted Q-PAN H5N1 vaccine. A table replaces the list of potential immune mediated diseases in Section 8.3.2.5. Minor editorial changes have also been made.

11 Apr 2011

Subject (family) unblinding will occur for each subject after completion of RDE, following the Day 385 contact, so the investigator can communicate treatment assignments to facilitate start of the unblinded portion of study (2nd year) for subjects who received placebo. Day U0 no longer can start on the same day as Day 385 due to the process by which unblinding at the subject level occurs. The process for allocation of subjects to a time point for the fourth blood sampling has been clarified. Assignment to a visit (and fourth blood sampling) at Day 182 and a phone call at Day 385 or the opposite will occur through an algorithm outside the randomization system and will be relayed to the investigator through the RDE system. The requirement for assessment of blood pressure during the Day 0/Screening visit physical exam has been removed, to align with clinical practice. In study procedure (Table 2), the activity “Randomization” had been inadvertently omitted and now has been added. In study procedure (Table 2), footnote # 10 was added to note that families with more than one child in the study may choose to have the follow-up phone contact for one child by interview at the time of the sibling’s follow-up clinic visit (provided timings are within specified windows). To align study procedures (Table 3) with Section 5.7.3, the activity “Physical Exam” has been removed and the activity “Targeted physical exam, prn” has been added to Visit U1 (Day U0). In study procedures (Table 3), the activity “Targeted physical exam, prn” has been removed from Day U7 and Day U28 because these are telephone contacts.In Section 9.5 (Screen and baseline failures), “Influenza disease severity risk data” was removed as such data is not entered into the eCRF for this study. Edits have been made to the footnotes of study procedure (Table 2 and Table 3) for clarification purposes.The GSK Asset Number for the monovalent H5N1 vaccine was corrected. Minor editorial changes have also been made.

19 Jun 2012

At the European Medicines Agency’s (EMA) request, GSK Biologicals has updated its procedure for emergency unblinding during the conduct of a clinical study. According to the revised procedure, the responsibility and the decision to break the treatment code in emergency situations resides solely with the investigator and consequently, the investigator will have full authority to break the treatment code. Clarification that unblinding at the subject level for site personnel, families, and monitors will occur after completion of RDE for all subjects, following their Day 385 contacts, rather than a batch of subjects at a time. In addition, a minor editorial error has been corrected.

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

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Clinical trials

Trial information

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Subject disposition

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Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Primary: Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Primary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain

Primary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain

Secondary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Secondary: Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Secondary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Number of subjects seroprotected as regards haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Number of subjects seroprotected as regards haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Number of seroconverted subjects for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Secondary: Number of seroconverted subjects for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Secondary: Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Secondary: Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Secondary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Number of subjects seroprotected for haemagglutination inhibition (HI) antibody titers against the H5N1 A/Indonesia virus strain.

Secondary: Number of seroconverted subjects for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Secondary: Number of seroconverted subjects for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Secondary: Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Secondary: Geometric Mean Increase (GMI) for haemagglutination inhibition (HI) antibodies against the H5N1 A/Indonesia virus strain.

Secondary: Microneutralization (MN) antibody titers against the H5N1 A/Indonesia and H5N1 A/Vietnam virus strains.

Secondary: Microneutralization (MN) antibody titers against the H5N1 A/Indonesia and H5N1 A/Vietnam virus strains.

Secondary: Vaccine response rate (VRR) for microneutralization (MN) antibodies against the H5N1 A/Indonesia and H5N1 A/Vietnam virus strains.

Secondary: Vaccine response rate (VRR) for microneutralization (MN) antibodies against the H5N1 A/Indonesia and H5N1 A/Vietnam virus strains.

Secondary: Number of subjects reporting solicited local symptoms.

Secondary: Number of subjects reporting solicited local symptoms.

Secondary: Number of subjects reporting solicited local symptoms.

Secondary: Number of subjects reporting solicited local symptoms.

Secondary: Number of subjects of less than 6 years of age reporting solicited general symptoms

Secondary: Number of subjects of less than 6 years of age reporting solicited general symptoms

Secondary: Number of subjects of less than 6 years of age reporting solicited general symptoms

Secondary: Number of subjects of less than 6 years of age reporting solicited general symptoms

Secondary: Number of subjects at least 6 years of age reporting solicited general symptoms

Secondary: Number of subjects at least 6 years of age reporting solicited general symptoms

Secondary: Number of subjects at least 6 years of age reporting solicited general symptoms

Secondary: Number of subjects at least 6 years of age reporting solicited general symptoms

Secondary: Number of subjects with medically-attended adverse events (MAEs)

Secondary: Number of subjects with medically-attended adverse events (MAEs)

Secondary: Number of subjects with medically-attended adverse events (MAEs)

Secondary: Number of subjects with medically-attended adverse events (MAEs)

Secondary: Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

Secondary: Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

Secondary: Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

Secondary: Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

Secondary: Number of subjects reporting pregnancies, and outcomes of these reported pregnancies

Secondary: Number of subjects reporting pregnancies, and outcomes of these reported pregnancies

Secondary: Number of subjects reporting pregnancies, and outcomes of these reported pregnancies

Secondary: Number of subjects reporting pregnancies, and outcomes of these reported pregnancies

Secondary: Number of subjects with normal and abnormal biochemical parameters assessed with respect to alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT)

Secondary: Number of subjects with normal and abnormal biochemical parameters assessed with respect to alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT)

Secondary: Number of subjects with normal and abnormal biochemical parameters assessed with respect to total bilirubin (T-BIL) and bilirubin conjugated/direct (BIL-C/D)

Secondary: Number of subjects with normal and abnormal biochemical parameters assessed with respect to total bilirubin (T-BIL) and bilirubin conjugated/direct (BIL-C/D)

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

Secondary: Number of subjects reporting serious adverse events (SAEs)

Secondary: Number of subjects reporting serious adverse events (SAEs)

Secondary: Number of subjects reporting serious adverse events (SAEs)

Secondary: Number of subjects reporting serious adverse events (SAEs)

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).

Secondary: Number of subjects reporting any unsolicited adverse events (AEs).