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Clinical Trial Results:
A phase II observer-blind, multicentre, dose-ranging study of children 6 to less than 36 months of age who are to be primed with a 2-dose series of GSK Biologicals’ AS03 adjuvanted A/Indonesia/05/2005 (H5N1) vaccine.

Summary
EudraCT number	2015-003458-42
Trial protocol	PL Outside EU/EEA
Global end of trial date	13 Feb 2018

Results information
Results version number	v1(current)
This version publication date	08 Sep 2018
First version publication date	08 Sep 2018
Other versions

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

116938

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

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

Public contact

Clinical Disclosure Advisor, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Disclosure Advisor, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000160-PIP01-07

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

15 Jun 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

13 Feb 2018

Global end of trial reached?

Yes

Global end of trial date

13 Feb 2018

Was the trial ended prematurely?

Main objective of the trial

Primary Doses • To assess the performance of alternative dosing regimens for primary immunization with Q-Pan H5N1 vaccine using an immunogenicity-fever index that considers: - immunogenicity by Hemagglutination Inhibition (HI) assay 21 days after the second priming dose. - fever scores after the first and second priming doses. - immunogenicity by Microneutralization (MN) assay 21 days after the second priming dose. - fever scores after the first and second priming doses. Booster Dose • To assess the performance of dosing regimens for booster immunization with Q-Pan H5N1 vaccine considering: - immune response (IR) by HI assay 7 days after a 12-month booster dose of Hemagglutinin (HA) Q-Pan H5N1 plain antigen. - immune response by MN assay 7 days after a 12-month booster dose of HA Q-Pan H5N1 plain antigen.

Protection of trial subjects

All subjects were supervised/observed for 30 minutes after vaccination/product administration with appropriate medical treatment readily available. Vaccines/products were administered by qualified and trained personnel. Vaccines/products were administered only to eligible subjects that had no contraindications to any components of the vaccines/products. Subjects were fol-lowed-up for 30 days after the last vaccination/product administration.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Jul 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Taiwan: 105

Country: Number of subjects enrolled

Thailand: 80

Worldwide total number of subjects

185

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)

110

Children (2-11 years)

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

Screening details

Number of subjects started

185

Number of subjects completed

185

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind ^[1]

Roles blinded

Subject, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

Observer-blind study

Are arms mutually exclusive

Yes

H5N1 Formulation 1 Group

Arm description

Subjects received 2 primary doses (adjuvanted) at Days 0 and 21 of H5N1 vaccine Formulation 1 and a booster dose (unadjuvanted) at Day 385 of H5N1 vaccine (GSK1557484A). All doses were administered intramuscularly (IM) in anterolateral thigh.

Arm type

Experimental

Investigational medicinal product name

Influenza A (H5N1) Virus Monovalent Vaccine 1.9 mcg, Adjuvanted with AS03B

Investigational medicinal product code

Other name

Split-virion Monovalent, A/Indonesia/5/2005 (H5N1)

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 primary doses and 1 booster dose (unadjuvanted) were administered IM in anterolateral thigh.

H5N1 Formulation 2 Group

Arm description

Subjects received 2 primary doses (adjuvanted) at Days 0 and 21 of H5N1 vaccine Formulation 2 and a booster dose (unadjuvanted) at Day 385 of H5N1 vaccine (GSK1557484A). All doses were administered IM in anterolateral thigh.

Arm type

Experimental

Investigational medicinal product name

Influenza A (H5N1) Virus Monovalent Vaccine 0.9 mcg, Adjuvanted with AS03C

Investigational medicinal product code

Other name

Split-virion Monovalent, A/Indonesia/5/2005 (H5N1)

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 primary doses and 1 booster dose (unadjuvanted) were administered IM in anterolateral thigh.

H5N1 Formulation 3 Group

Arm description

Subjects received 2 primary doses (adjuvanted) at Days 0 and 21 of H5N1 vaccine Formulation 3 and a booster dose (unadjuvanted) at Day 385 of H5N1 vaccine (GSK1557484A). All doses were administered IM in anterolateral thigh.

Arm type

Experimental

Investigational medicinal product name

Influenza A (H5N1) Virus Monovalent Vaccine 1.9 mcg, Adjuvanted with AS03C

Investigational medicinal product code

Other name

Split-virion Monovalent, A/Indonesia/5/2005 (H5N1)

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 primary doses and 1 booster dose (unadjuvanted) were administered IM in anterolateral thigh.

H5N1 Formulation 4 Group

Arm description

Subjects received 2 primary doses (adjuvanted) at Days 0 and 21 of H5N1 vaccine Formulation 4 and a booster dose (unadjuvanted) at Day 385 of H5N1 vaccine (GSK1557484A). All doses were administered IM in anterolateral thigh.

Arm type

Experimental

Investigational medicinal product name

Influenza A (H5N1) Virus Monovalent Vaccine 3.75 mcg, Adjuvanted with AS03C

Investigational medicinal product code

Other name

Split-virion Monovalent, A/Indonesia/5/2005 (H5N1)

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 primary doses and 1 booster dose (unadjuvanted) were administered IM in anterolateral thigh.

H5N1 Formulation 5 Group

Arm description

Subjects received 2 primary doses (adjuvanted) at Days 0 and 21 of H5N1 vaccine Formulation 5 and a booster dose (unadjuvanted) at Day 385 of H5N1 vaccine (GSK1557484A). All doses were administered IM in anterolateral thigh.

Arm type

Experimental

Investigational medicinal product name

Influenza A (H5N1) Virus Monovalent Vaccine 3.75 mcg, Adjuvanted with AS03D

Investigational medicinal product code

Other name

Split-virion Monovalent, A/Indonesia/5/2005 (H5N1)

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 primary doses and 1 booster dose (unadjuvanted) were administered IM in anterolateral thigh.

Notes
[1] - The roles blinded appear to be inconsistent with a double blind trial.
Justification: During the course of the study, the vaccine recipient, the subject’s parent(s)/LAR(s) and the site and sponsor personnel involved in the clinical evaluation of the subjects are blinded while other study personnel may be aware of the treatment assignment. The laboratory in charge of the laboratory testing will be blinded to the treatment, and codes will be used to link the subject and study (without any link to the treatment attributed to the subject) to each sample.

Number of subjects in period 1	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Started	38	37	38	37	35
Completed	37	34	38	36	33
Not completed	1	3	0	1	2
Consent withdrawal	-	2	-	1	-
Migrated/moved from study area	-	-	-	-	2
Lost to follow-up	1	1	-	-	-

Baseline characteristics

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Reporting group title

H5N1 Formulation 1 Group

Reporting group description

Reporting group title

H5N1 Formulation 2 Group

Reporting group description

Reporting group title

H5N1 Formulation 3 Group

Reporting group description

Reporting group title

H5N1 Formulation 4 Group

Reporting group description

Reporting group title

H5N1 Formulation 5 Group

Reporting group description

Reporting group values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group	Total
Number of subjects	38	37	38	37	35	185
Age categorical
Units: Subjects
Infants and toddlers	22	18	22	23	25	110
Children	16	19	16	14	10	75
Age continuous
Units: months
arithmetic mean (standard deviation)	21.9 ( 8.0 )	22.6 ( 8.1 )	21.6 ( 9.2 )	20.8 ( 8.3 )	20.3 ( 7.8 )	-
Gender categorical
Units: Subjects
Female	17	14	16	23	18	88
Male	21	23	22	14	17	97
Race/Ethnicity, Customized
Units: Subjects
Asian - East Asian Heritage	21	21	22	21	19	104
Asian - South East Asian Heritage	16	16	16	16	16	80
Unspecified	1	0	0	0	0	1

End points

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Reporting group title

H5N1 Formulation 1 Group

Reporting group description

Reporting group title

H5N1 Formulation 2 Group

Reporting group description

Reporting group title

H5N1 Formulation 3 Group

Reporting group description

Reporting group title

H5N1 Formulation 4 Group

Reporting group description

Reporting group title

H5N1 Formulation 5 Group

Reporting group description

Primary: Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Haemagglutination Inhibition (HI) antibody titers following primary vaccination

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End point title

Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Haemagglutination Inhibition (HI) antibody titers following primary vaccination ^[1]

End point description

The HI antibody titres were expressed in terms of immunogenicity indices for each group. Immunogenicity index (DGMT) = If the LL of the 95% CI for GMT group ratio is less than 0.25 then DGMT =0. If the LL of the 95% CI for GMT group ratio is greater than 1 then DGMT =1.

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	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	33	37	31	35
Units: Immunogenicity Index
arithmetic mean (full range (min-max))
Immunogenicity Index	1 (0 to 1)	0.54 (0 to 1)	0.57 (0 to 1)	0.40 (0 to 1)	0.34 (0 to 1)

No statistical analyses for this end point

Primary: Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Microneutralization (MN) antibody titers following primary vaccination

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End point title

Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Microneutralization (MN) antibody titers following primary vaccination ^[2]

End point description

The MN antibody titres were expressed in terms of immunogenicity indices for each group. Immunogenicity index (DGMT) = If the LL of the 95% CI for GMT group ratio is less than 0.25 then DGMT =0. If the LL of the 95% CI for GMT group ratio is greater than 1 then DGMT =1.

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	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	31	37	29	35
Units: Immunogenicity Index
arithmetic mean (full range (min-max))
Immunogenicity Index	1 (0 to 1)	0.56 (0 to 1)	0.57 (0 to 1)	0.32 (0 to 1)	0.33 (0 to 1)

No statistical analyses for this end point

Primary: Evaluation of Fever index for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Haemagglutination Inhibition (HI) antibody titers following primary vaccination.

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End point title

Evaluation of Fever index for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Haemagglutination Inhibition (HI) antibody titers following primary vaccination. ^[3]

End point description

Fever index was defined as the average temperature for each vaccine group. Fever index (DR) = The average temperature measurement for each vaccine group. Fever index from Days 0-2 after each dose Any temperature < 38°C (100.4 F) was assigned a value of 0. Any temperature > 40.5°C was assigned a value of 40.5. DR correspond to 243 minus the sum of recorded temperature values for 3 days after (dose 1 and dose 2)/243.

End point type

Primary

End point timeframe

During the 3-day follow-up period (i.e. on the day of vaccination and 2 subsequent days) after Dose 1 and Dose 2.

Notes
[3] - 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	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	33	37	31	35
Units: Degrees Celsius
arithmetic mean (full range (min-max))
Degrees Celsius	0.84 (0 to 1)	0.91 (0 to 1)	0.95 (0 to 1)	0.93 (0 to 1)	0.94 (0 to 1)

No statistical analyses for this end point

Primary: Evaluation of Fever index for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Microneutralization (MN) antibody titers following primary vaccination.

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End point title

Evaluation of Fever index for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Microneutralization (MN) antibody titers following primary vaccination. ^[4]

End point description

Fever index was defined as the average temperature for each vaccine group. Fever index (DR)= The average temperature measurement for each vaccine group. Fever index from Days 0-2 after each dose Any temperature < 38°C (100.4 F) was assigned a value of 0. Any temperature > 40.5°C was assigned a value of 40.5. DR correspond to 243 minus the sum of recorded temperature values for 3 days after (dose 1 and dose 2)/243.

End point type

Primary

End point timeframe

During the 3-day follow-up period (i.e. on the day of vaccination and 2 subsequent days) after Dose 1 and Dose 2.

Notes
[4] - 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	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	31	37	29	35
Units: Degrees Celsius
arithmetic mean (full range (min-max))
Degrees Celsius	0.84 (0 to 1)	0.91 (0 to 1)	0.95 (0 to 1)	0.93 (0 to 1)	0.94 (0 to 1)

No statistical analyses for this end point

Primary: Mean Geometric Increase (MGI) for vaccine homologous and heterologous HI antibody titers against each of the four vaccine influenza strains.

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End point title

Mean Geometric Increase (MGI) for vaccine homologous and heterologous HI antibody titers against each of the four vaccine influenza strains. ^[5]

End point description

MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer (Day 392) to the pre-vaccination (Day 385) reciprocal HI titer for the vaccine virus. The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam/1194/2004 H5N1 (heterologous), Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous) and Flu A/gyrfalcon/Washington/41088-6/2014 H5N8 (heterologous).

End point type

Primary

End point timeframe

At Day 392 (relative to Day 385) post booster vaccination

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

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	34	33	37	31	32
Units: Fold change
geometric mean (confidence interval 95%)
Flu A/Indonesia/5/2005 H5N1 HI	4.9 (3.8 to 6.3)	6.6 (4.9 to 9.0)	4.2 (3.4 to 5.3)	3.6 (2.9 to 4.5)	3.4 (2.8 to 4.1)
Flu A/duck/Bangladesh/19097/2013 H5N1 HI	5.2 (3.9 to 7.0)	6.0 (4.2 to 8.5)	4.0 (3.0 to 5.2)	3.4 (2.7 to 4.2)	2.7 (2.3 to 3.3)
Flu A/Vietnam/1194/2004 H5N1 HI	5.0 (3.7 to 6.8)	6.3 (4.5 to 8.7)	3.8 (3.0 to 4.8)	3.6 (2.9 to 4.5)	2.8 (2.2 to 3.4)
Flu A/gyrfalcon/Washington/41088-6/2014 H5N8 HI	4.5 (3.2 to 6.5)	4.9 (3.5 to 6.9)	3.1 (2.3 to 4.2)	2.9 (2.2 to 3.8)	2.4 (2.0 to 3.0)

No statistical analyses for this end point

Primary: Mean Geometric Increase (MGI) for vaccine homologous and heterologous MN antibody titers against each of the 3 vaccine influenza strains.

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End point title

Mean Geometric Increase (MGI) for vaccine homologous and heterologous MN antibody titers against each of the 3 vaccine influenza strains. ^[6]

End point description

MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination (Day 392) reciprocal MN titer to the pre-vaccination (Day 385) reciprocal MN titer for the vaccine virus. The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam /1194/2004 H5N (heterologous) and Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous).

End point type

Primary

End point timeframe

At Day 392 (relative to Day 385) post booster vaccination

Notes
[6] - 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	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	34	33	37	31	32
Units: Fold change
geometric mean (confidence interval 95%)
Flu A/Indonesia/5/2005 H5N1 MN	4.3 (3.3 to 5.7)	4.8 (3.4 to 6.6)	3.2 (2.3 to 4.3)	2.8 (2.0 to 3.8)	2.5 (2.0 to 3.0)
Flu A/Vietnam/1194/2004 H5N1 MN	2.9 (2.2 to 3.8)	2.9 (2.1 to 4.1)	2.9 (2.2 to 3.8)	2.6 (2.1 to 3.3)	2.4 (1.9 to 3.1)
Flu A/duck/Bangladesh/19097/2013 H5N1 MN	2.6 (1.9 to 3.5)	3.0 (2.3 to 4.1)	2.6 (2.0 to 3.2)	2.1 (1.6 to 2.8)	2.8 (2.2 to 3.5)

No statistical analyses for this end point

Secondary: Number of seroconverted subjects for HI antibodies against each of the 4 vaccine influenza strains.

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End point title

Number of seroconverted subjects for HI antibodies against each of the 4 vaccine influenza strains.

End point description

Seroconversion rate (SCR) was defined as the proportion of subjects who have either a pre-vaccination reciprocal HI titer less than (<) 10 and a post-vaccination reciprocal titer greater than or equal to (≥) 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus. The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam/1194/2004 H5N1 (heterologous), Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous) and Flu A/gyrfalcon/Washington/41088-6/2014 H5N8 (heterologous).

End point type

Secondary

End point timeframe

At Days 42, 385 and 392

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	33	37	31	35
Units: Participants
Flu A/Indonesia/5/2005 H5N1 HI, Day 42	36	33	37	31	35
Flu A/Indonesia/5/2005 H5N1 HI, Day 385	33	26	28	28	21
Flu A/Indonesia/5/2005 H5N1 HI, Day 392	34	33	37	31	32
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 42	30	22	33	23	25
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 385	7	6	7	5	6
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 392	27	29	26	21	18
Flu A/Vietnam/1194/2004 H5N1 HI, Day 42	30	22	29	21	24
Flu A/Vietnam/1194/2004 H5N1 HI, Day 385	12	8	9	5	6
Flu A/Vietnam/1194/2004 H5N1 HI, Day 392	29	29	28	22	20
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 42	17	9	10	5	8
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 385	1	0	1	0	0
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 392	18	15	16	9	6

No statistical analyses for this end point

Secondary: Number of subjects who were seroprotected for HI antibodies against each of the 4 vaccine influenza strains.

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End point title

Number of subjects who were seroprotected for HI antibodies against each of the 4 vaccine influenza strains.

End point description

Seroprotection rate (SPR) was defined as the proportion of subjects with H5N1 reciprocal HI titers ≥ 40 against the tested vaccine virus The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam/1194/2004 H5N1 (heterologous), Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous) and Flu A/gyrfalcon/Washington/41088-6/2014 H5N8 (heterologous).

End point type

Secondary

End point timeframe

At Days 0, 42, 385, 392

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	33	37	31	35
Units: Participants
Flu A/Indonesia/5/2005 H5N1 HI, Day 0	0	0	0	0	0
Flu A/Indonesia/5/2005 H5N1 HI, Day 42	36	33	37	31	35
Flu A/Indonesia/5/2005 H5N1 HI, Day 385	33	26	28	28	23
Flu A/Indonesia/5/2005 H5N1 HI, Day 392	34	33	37	31	32
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 0	0	0	0	0	2
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 42	32	25	35	28	31
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 385	9	8	8	7	6
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 392	30	32	27	27	22
Flu A/Vietnam/1194/2004 H5N1 HI, Day 0	0	0	0	0	2
Flu A/Vietnam/1194/2004 H5N1 HI, Day 42	32	25	31	26	29
Flu A/Vietnam/1194/2004 H5N1 HI, Day 385	15	10	10	7	8
Flu A/Vietnam/1194/2004 H5N1 HI, Day 392	32	32	29	28	24
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 0	0	0	0	0	0
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 42	19	10	11	7	9
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 385	1	1	1	0	1
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 392	20	18	16	10	8

No statistical analyses for this end point

Secondary: Geometric mean titers (GMTs) for humoral immune response in terms of HI antibodies against vaccine-homologous/heterologous antigens

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End point title

Geometric mean titers (GMTs) for humoral immune response in terms of HI antibodies against vaccine-homologous/heterologous antigens

End point description

GMTs were defined as the geometric mean antibody titres calculated on all subjects post the primary immunization (at Day 0, 42, 385) and 7 days post booster dose (at Day 392). The aggregate variables were calculated for each group. The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam/1194/2004 H5N1 (heterologous), Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous) and Flu A/gyrfalcon/Washington/41088-6/2014 H5N8 (heterologous).

End point type

Secondary

End point timeframe

At Days 0, 42 and 385 (post the primary immunization), at Day 392 (7 days post booster dose)

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	33	37	31	35
Units: Titers
geometric mean (confidence interval 95%)
Flu A/Indonesia/5/2005 H5N1 HI, Day 0	5.1 (4.9 to 5.3)	5.1 (4.9 to 5.3)	5.1 (4.9 to 5.4)	5.0 (5.0 to 5.0)	5.6 (4.9 to 6.5)
Flu A/Indonesia/5/2005 H5N1 HI, Day 42	1118.6 (884.4 to 1414.9)	858.8 (659.2 to 1118.8)	913.6 (672.6 to 1241.1)	640.0 (488.3 to 839.0)	568.4 (442.7 to 729.8)
Flu A/Indonesia/5/2005 H5N1 HI, Day 385	98.1 (76.7 to 125.4)	61.5 (47.1 to 80.3)	72.1 (51.6 to 100.7)	79.1 (59.2 to 105.6)	59.6 (45.0 to 79.0)
Flu A/Indonesia/5/2005 H5N1 HI, Day 392	476.2 (348.4 to 650.9)	407.6 (315.0 to 527.4)	305.4 (227.1 to 410.6)	286.2 (216.0 to 379.1)	201.0 (156.1 to 258.7)
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 0	5.3 (5.0 to 5.7)	5.4 (4.8 to 5.9)	5.3 (5.0 to 5.7)	5.0 (5.0 to 5.0)	6.1 (4.9 to 7.6)
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 42	167.1 (128.4 to 217.3)	135.3 (97.6 to 187.5)	109.9 (81.2 to 148.7)	91.5 (70.2 to 119.1)	78.5 (58.5 to 105.3)
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 385	23.4 (18.8 to 29.2)	20.8 (16.3 to 26.6)	17.8 (13.2 to 24.1)	20.9 (16.1 to 26.9)	19.5 (14.2 to 26.8)
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 392	125.6 (89.4 to 176.5)	126.1 (95.2 to 167.0)	77.6 (54.5 to 110.4)	70.7 (52.7 to 95.0)	53.5 (38.6 to 74.2)
Flu A/Vietnam/1194/2004 H5N1 HI, Day 0	5.3 (5.0 to 5.7)	5.0 (5.0 to 5.0)	5.1 (4.9 to 5.5)	5.1 (4.9 to 5.4)	5.8 (4.7 to 7.2)
Flu A/Vietnam/1194/2004 H5N1 HI, Day 42	128.9 (103.1 to 161.2)	104.7 (79.0 to 138.6)	88.9 (63.2 to 125.0)	77.2 (59.7 to 99.9)	69.0 (51.7 to 92.0)
Flu A/Vietnam/1194/2004 H5N1 HI, Day 385	26.0 (20.0 to 33.8)	21.5 (16.8 to 27.5)	18.4 (13.2 to 25.7)	21.3 (16.3 to 27.9)	20.6 (14.8 to 28.7)
Flu A/Vietnam/1194/2004 H5N1 HI, Day 392	133.9 (95.5 to 187.7)	137.5 (107.3 to 176.1)	76.2 (53.9 to 107.7)	76.5 (56.8 to 103.1)	57.8 (41.5 to 80.4)
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 0	5.3 (4.9 to 5.7)	5.0 (5.0 to 5.0)	5.1 (4.9 to 5.3)	5.2 (4.8 to 5.7)	5.3 (4.9 to 5.8)
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 42	35.8 (27.9 to 46.0)	27.8 (21.1 to 36.7)	22.8 (17.2 to 30.3)	21.6 (16.7 to 27.8)	19.9 (15.4 to 25.8)
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 385	9.2 (7.6 to 11.2)	8.0 (6.4 to 9.9)	7.4 (6.0 to 9.0)	7.7 (6.6 to 9.1)	7.2 (5.8 to 8.8)
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 392	42.6 (29.8 to 60.8)	37.0 (27.1 to 50.6)	24.0 (17.1 to 33.6)	22.6 (16.7 to 30.5)	17.9 (13.4 to 23.9)

No statistical analyses for this end point

Secondary: Mean geometric increase (MGI) for haemagglutination inhibition (HI) antibody titer against each of the 4 vaccine influenza strains

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End point title

Mean geometric increase (MGI) for haemagglutination inhibition (HI) antibody titer against each of the 4 vaccine influenza strains

End point description

MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination (Day 42) reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer for the vaccine virus. The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam/1194/2004 H5N1 (heterologous), Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous) and Flu A/gyrfalcon/Washington/41088-6/2014 H5N8 (heterologous).

End point type

Secondary

End point timeframe

At Day 42 (relative to Day 0), at Day 385 (relative to Day 0) and at Day 392 (relative to Day 0)

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	33	37	31	35
Units: Fold change
geometric mean (confidence interval 95%)
Flu A/Indonesia/5/2005 H5N1 HI, Day 42	219.5 (172.6 to 279.0)	168.2 (127.4 to 222.0)	177.7 (131.5 to 240.1)	128.0 (97.7 to 167.8)	101.0 (74.8 to 136.4)
Flu A/Indonesia/5/2005 H5N1 HI, Day 385	19.2 (14.8 to 24.9)	12.0 (9.2 to 15.8)	14.0 (10.0 to 19.7)	15.8 (11.8 to 21.1)	10.5 (7.6 to 14.5)
Flu A/Indonesia/5/2005 H5N1 HI, Day 392	93.3 (67.9 to 128.3)	79.8 (61.5 to 103.5)	59.4 (44.5 to 79.4)	57.2 (43.2 to 75.8)	35.3 (25.9 to 48.1)
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 42	31.3 (23.5 to 41.6)	22.9 (17.2 to 30.6)	20.4 (14.9 to 28.1)	18.9 (14.0 to 25.5)	12.6 (9.0 to 17.6)
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 385	4.2 (3.3 to 5.3)	3.6 (2.9 to 4.6)	3.3 (2.4 to 4.5)	3.9 (2.9 to 5.3)	3.3 (2.3 to 4.7)
Flu A/duck/Bangladesh/19097/2013 H5N1 HI, Day 392	23.4 (16.2 to 33.9)	22.9 (17.1 to 30.7)	14.5 (10.1 to 20.7)	13.9 (9.8 to 19.8)	9.1 (6.0 to 13.7)
Flu A/Vietnam/1194/2004 H5N1 HI, Day 42	24.3 (19.0 to 31.0)	20.1 (15.2 to 26.7)	16.7 (11.7 to 23.8)	15.1 (11.1 to 20.6)	11.4 (8.4 to 15.6)
Flu A/Vietnam/1194/2004 H5N1 HI, Day 385	4.7 (3.5 to 6.2)	4.1 (3.1 to 5.3)	3.5 (2.5 to 5.0)	3.9 (2.8 to 5.4)	3.6 (2.6 to 5.2)
Flu A/Vietnam/1194/2004 H5N1 HI, Day 392	25.1 (17.3 to 36.4)	27.1 (20.9 to 35.0)	14.5 (10.2 to 20.5)	14.5 (10.0 to 21.1)	10.1 (6.7 to 15.2)
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 42	6.7 (5.0 to 9.0)	5.5 (4.0 to 7.4)	4.3 (3.2 to 5.8)	4.1 (3.0 to 5.6)	3.5 (2.7 to 4.6)
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 385	1.7 (1.4 to 2.1)	1.5 (1.2 to 1.8)	1.4 (1.2 to 1.8)	1.5 (1.2 to 1.8)	1.3 (1.1 to 1.6)
Flu A/gyrfalcon/WA/41088-6/2014 H5N8 HI, Day 392	8.1 (5.5 to 12.0)	7.1 (5.1 to 9.9)	4.7 (3.3 to 6.7)	4.2 (3.0 to 6.0)	3.2 (2.3 to 4.3)

No statistical analyses for this end point

Secondary: Mean geometric increase (MGI) for MN antibodies against the 3 vaccine influenza strains.

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End point title

Mean geometric increase (MGI) for MN antibodies against the 3 vaccine influenza strains.

End point description

MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination (Day 385) reciprocal MN titer to the pre-vaccination (Day 0) reciprocal MN titer for the vaccine virus. The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam /1194/2004 H5N (heterologous) and Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous).

End point type

Secondary

End point timeframe

At Day 385 (relative to Day 0)

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	34	32	37	30	32
Units: Fold change
geometric mean (confidence interval 95%)
Flu A/Indonesia/5/2005 H5N1 MN	17.5 (13.7 to 22.4)	14.8 (12.6 to 17.5)	15.3 (12.5 to 18.6)	17.8 (14.3 to 22.1)	14.2 (11.8 to 17.1)
Flu A/Vietnam/1194/2004 H5N1 MN	7.6 (5.5 to 10.3)	5.8 (4.2 to 8.1)	5.4 (4.0 to 7.4)	7.5 (5.8 to 9.8)	6.1 (4.5 to 8.3)
Flu A/duck/Bangladesh/19097/2013 H5N1 MN	7.0 (5.2 to 9.4)	5.5 (4.1 to 7.3)	5.3 (3.8 to 7.3)	6.9 (5.0 to 9.4)	4.2 (3.1 to 5.8)

No statistical analyses for this end point

Secondary: Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of MN antibodies against vaccine-homologous/heterologous antigens

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End point title

Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of MN antibodies against vaccine-homologous/heterologous antigens

End point description

MN antibody titers were expressed as Geometric Mean Titers (GMTs). The cut-off of the assay was the seropositivity cut-off of ≥ 1:28. The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam /1194/2004 H5N (heterologous) and Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous).

End point type

Secondary

End point timeframe

At Days 0, 42, 385 and Day 392

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	33	37	31	35
Units: Titers
geometric mean (confidence interval 95%)
Flu A/Indonesia/5/2005 H5N1 MN, Day 0	14.3 (13.7 to 14.8)	14.0 (14.0 to 14.0)	14.0 (14.0 to 14.0)	14.0 (14.0 to 14.0)	14.0 (14.0 to 14.0)
Flu A/Indonesia/5/2005 H5N1 MN, Day 42	1498.5 (1181.7 to 1900.1)	1214.3 (921.3 to 1600.6)	1211.6 (881.3 to 1665.9)	707.1 (533.1 to 937.9)	727.4 (545.9 to 969.2)
Flu A/Indonesia/5/2005 H5N1 MN, Day 385	250.3 (197.1 to 318.0)	203.6 (172.8 to 239.8)	213.8 (175.2 to 260.9)	247.2 (201.4 to 303.5)	198.5 (165.1 to 238.7)
Flu A/Indonesia/5/2005 H5N1 MN, Day 392	1085.0 (767.5 to 1533.9)	969.1 (710.1 to 1322.6)	674.2 (492.3 to 923.3)	681.0 (496.3 to 934.4)	489.6 (381.7 to 628.0)
Flu A/Vietnam/1194/2004 H5N1 MN, Day 0	14.6 (13.8 to 15.4)	14.6 (13.7 to 15.5)	14.8 (13.6 to 16.1)	14.0 (14.0 to 14.0)	15.2 (13.5 to 17.0)
Flu A/Vietnam/1194/2004 H5N1 MN, Day 42	217.6 (187.7 to 252.2)	195.2 (156.7 to 243.1)	177.3 (147.8 to 212.7)	176.9 (139.0 to 225.2)	149.3 (117.6 to 189.6)
Flu A/Vietnam/1194/2004 H5N1 MN, Day 385	113.0 (85.3 to 149.9)	88.0 (64.0 to 121.0)	80.7 (58.7 to 111.1)	103.6 (80.5 to 133.2)	89.0 (67.2 to 118.0)
Flu A/Vietnam/1194/2004 H5N1 MN, Day 392	320.0 (259.8 to 394.1)	256.6 (212.5 to 309.9)	239.2 (202.5 to 282.7)	270.4 (237.2 to 308.3)	216.5 (179.0 to 261.8)
Flu A/duck/Bangladesh/19097/2013 H5N1 MN, Day 0	14.6 (13.8 to 15.4)	14.3 (13.7 to 15.0)	14.5 (13.5 to 15.7)	14.6 (13.7 to 15.6)	15.2 (13.8 to 16.7)
Flu A/duck/Bangladesh/19097/2013 H5N1 MN, Day 42	179.4 (146.5 to 219.7)	161.6 (129.4 to 201.9)	147.1 (116.6 to 185.7)	161.8 (129.1 to 202.8)	140.6 (111.8 to 176.8)
Flu A/duck/Bangladesh/19097/2013 H5N1 MN, Day 385	102.0 (76.6 to 135.9)	79.2 (59.3 to 105.8)	76.3 (55.7 to 104.7)	100.7 (74.2 to 136.6)	63.0 (47.0 to 84.4)
Flu A/duck/Bangladesh/19097/2013 H5N1 MN, Day 392	262.5 (212.2 to 324.7)	240.9 (197.7 to 293.6)	194.8 (157.7 to 240.7)	202.2 (167.8 to 243.7)	174.5 (140.5 to 216.8)

No statistical analyses for this end point

Secondary: Vaccine response rate (VRR) for homologous and heterologous MN antibodies against each of the 3 vaccine influenza strains.

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End point title

Vaccine response rate (VRR) for homologous and heterologous MN antibodies against each of the 3 vaccine influenza strains.

End point description

VRR for MN was defined as the incidence rate of subjects with at least a 4-fold increase in post vaccination reciprocal titer relative to pre vaccination titers. The vaccine strains assessed were Flu A/Indonesia/5/2005 H5N1 (homologous), Flu A/Vietnam /1194/2004 H5N (heterologous) and Flu A/duck/Bangladesh/19097/2013 H5N1 (heterologous).

End point type

Secondary

End point timeframe

At Day 42, Day 385 (relative to Day 0), Day 392 (relative to Day 0) and D 392 (relative to Day 385)

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	33	37	31	35
Units: Participants
Flu A/Indonesia/5/2005 H5N1 MN, Day 42	36	31	37	29	35
Flu A/Indonesia/5/2005 H5N1 MN, Day 385	34	32	37	29	32
Flu A/Indonesia/5/2005 H5N1 MN, Day 392	34	32	37	29	32
Flu A/Indonesia/5/2005 H5N1 MN, D 392	21	24	14	15	13
Flu A/Vietnam/1194/2004 H5N1 MN, Day 42	34	31	36	29	32
Flu A/Vietnam/1194/2004 H5N1 MN, Day 385	27	27	27	28	25
Flu A/Vietnam/1194/2004 H5N1 MN, Day 392	31	31	37	30	30
Flu A/Vietnam/1194/2004 H5N1 MN, D 392	10	10	10	7	6
Flu A/duck/Bangladesh/19097/2013 H5N1 MN, Day 42	34	31	35	31	32
Flu A/duck/Bangladesh/19097/2013 H5N1 MN, Day 385	28	27	29	25	23
Flu A/duck/Bangladesh/19097/2013 H5N1 MN, Day 392	33	32	36	31	30
Flu A/duck/Bangladesh/19097/2013 H5N1 MN, D 392	9	10	8	6	9

No statistical analyses for this end point

Secondary: Cell mediated Immunity (CMI) in terms of T-cell markers related to Flu A/Indonesia/05/2005 antigen.

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End point title

Cell mediated Immunity (CMI) in terms of T-cell markers related to Flu A/Indonesia/05/2005 antigen.

End point description

Antigen-specific CD4+/CD8+ T Cells identified as CD4/CD8+ were analysed for T cells expressing two or more of the following immune markers: CD40 Ligand, Interleukin (IL)-2, Tumor Necrosis Factor alpha (TNF-a), Interferon-gamma (IFN-g). The frequency was presented as number of cytokine-producing CD4+/CD8+ cells per million CD4+/CD8+ cells repsectively. All doubles = T cell expressing at least 2 cytokines.

End point type

Secondary

End point timeframe

At Days 0, 42, 385 and 392

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	20	19	19	18	19
Units: cells/million T cells
median (inter-quartile range (Q1-Q3))
CD4 dble_All (Polypositives), Day 0	55.5 (1.0 to 227.0)	42.0 (3.0 to 185.0)	43.0 (1.0 to 90.0)	89.5 (26.0 to 217.0)	74.0 (1.0 to 277.0)
CD4 dble_All (Polypositives), Day 42	2711.0 (1669.0 to 5165.0)	1629.0 (707.0 to 4301.0)	960.0 (432.0 to 1379.0)	1337.5 (748.0 to 2793.0)	1372.5 (426.5 to 2911.5)
CD4 dble_All (Polypositives), Day 385	1530.0 (632.5 to 2293.5)	1255.0 (560.0 to 2096.0)	1413.0 (469.0 to 1834.0)	954.0 (495.0 to 1199.0)	596.0 (373.0 to 1167.0)
CD4 dble_All (Polypositives), Day 392	1417.0 (759.5 to 3955.5)	1129.0 (582.0 to 3221.0)	731.0 (448.0 to 1461.0)	722.5 (260.0 to 907.0)	832.0 (345.0 to 1497.0)
CD4 dble_CD40L, Day 0	23.0 (1.0 to 56.0)	19.0 (1.0 to 52.0)	5.0 (1.0 to 60.0)	36.0 (1.0 to 85.0)	26.0 (1.0 to 133.0)
CD4 dble_CD40L, Day 42	1671.0 (635.0 to 3256.0)	1341.0 (378.0 to 2696.0)	514.0 (229.0 to 1200.0)	516.0 (307.5 to 2031.0)	717.0 (295.5 to 1604.5)
CD4 dble_CD40L, Day 385	1074.0 (562.5 to 2637.0)	844.0 (425.0 to 1660.0)	722.0 (323.0 to 1524.0)	315.0 (148.0 to 511.0)	588.0 (154.0 to 902.0)
CD4 dble_CD40L, Day 392	1130.5 (801.0 to 3108.5)	986.0 (340.0 to 1802.0)	660.0 (213.0 to 1706.0)	424.0 (239.0 to 645.0)	325.0 (110.0 to 939.0)
CD4 dble_IFNγ, Day 0	47.0 (4.0 to 391.0)	49.0 (1.0 to 352.0)	24.0 (1.0 to 118.0)	40.5 (1.0 to 681.0)	12.0 (1.0 to 259.0)
CD4 dble_IFNγ, Day 42	803.0 (260.0 to 1627.0)	406.0 (304.0 to 1481.0)	266.0 (206.0 to 394.0)	863.5 (352.5 to 1229.5)	437.5 (158.5 to 1027.0)
CD4 dble_IFNγ, Day 385	200.0 (80.0 to 510.0)	316.5 (70.0 to 569.0)	248.5 (56.0 to 557.0)	589.5 (216.0 to 830.0)	163.0 (62.0 to 355.0)
CD4 dble_IFNγ, Day 392	459.5 (127.0 to 941.5)	329.0 (109.0 to 784.0)	123.0 (74.0 to 465.0)	423.5 (147.0 to 919.0)	253.0 (112.0 to 608.0)
CD4 dble_IL2, Day 0	89.5 (1.0 to 136.5)	72.0 (27.0 to 183.0)	50.0 (1.0 to 76.0)	47.0 (3.0 to 133.0)	75.0 (1.0 to 223.0)
CD4 dble_IL2, Day 42	3399.5 (1593.0 to 5907.0)	2438.0 (759.0 to 6212.0)	1344.0 (508.0 to 1859.0)	1448.0 (1012.5 to 2993.5)	1761.5 (577.5 to 3085.5)
CD4 dble_IL2, Day 385	1676.5 (779.5 to 2551.5)	1394.0 (531.0 to 2151.0)	1366.5 (460.0 to 1938.0)	870.5 (458.0 to 1223.0)	621.0 (410.0 to 1556.0)
CD4 dble_IL2, Day 392	1502.5 (864.5 to 3500.0)	1455.0 (672.0 to 3065.0)	893.0 (627.0 to 1494.0)	840.0 (192.0 to 1067.0)	882.0 (338.0 to 1181.0)
CD4 dble_TNFα, Day 0	49.5 (1.0 to 322.0)	98.0 (1.0 to 249.0)	62.0 (1.0 to 192.0)	52.0 (23.0 to 249.0)	71.0 (29.0 to 296.0)
CD4 dble_TNFα, Day 42	3023.0 (917.0 to 4946.0)	1970.0 (569.0 to 4382.0)	840.0 (705.0 to 1446.0)	1353.0 (723.0 to 2501.0)	1204.5 (582.5 to 2853.0)
CD4 dble_TNFα, Day 385	1339.0 (765.0 to 2419.5)	1233.0 (696.0 to 2030.0)	1277.5 (419.0 to 1921.0)	1097.5 (547.0 to 1517.0)	678.0 (463.0 to 1251.0)
CD4 dble_TNFα, Day 392	1743.5 (741.5 to 3863.0)	1257.0 (504.0 to 2468.0)	740.0 (394.0 to 1266.0)	726.5 (433.0 to 1315.0)	908.0 (620.0 to 1579.0)
CD8 dble_All (Polypositives), Day 0	3.5 (1.0 to 68.5)	5.0 (1.0 to 45.0)	30.0 (1.0 to 40.0)	47.0 (1.0 to 121.0)	1.0 (1.0 to 58.0)
CD8 dble_All (Polypositives), Day 42	48.0 (2.0 to 186.0)	63.0 (42.0 to 238.0)	45.0 (1.0 to 83.0)	125.0 (54.5 to 220.5)	128.0 (10.0 to 323.0)
CD8 dble_All (Polypositives), Day 385	33.5 (1.0 to 108.5)	62.5 (1.0 to 147.0)	1.0 (1.0 to 107.0)	56.0 (1.0 to 194.0)	1.0 (1.0 to 79.0)
CD8 dble_All (Polypositives), Day 392	63.0 (1.0 to 200.0)	33.0 (1.0 to 88.0)	25.0 (1.0 to 70.0)	60.5 (1.0 to 126.0)	26.0 (1.0 to 99.0)
CD8 dble_CD40L, Day 0	1.0 (1.0 to 72.5)	1.0 (1.0 to 21.0)	1.0 (1.0 to 37.0)	46.0 (1.0 to 75.0)	1.0 (1.0 to 57.0)
CD8 dble_CD40L, Day 42	108.0 (7.0 to 147.0)	25.0 (1.0 to 100.0)	1.0 (1.0 to 68.0)	7.5 (1.0 to 60.0)	83.0 (1.0 to 186.0)
CD8 dble_CD40L, Day 385	88.0 (1.0 to 197.5)	70.5 (11.0 to 132.0)	53.0 (1.0 to 93.0)	4.0 (1.0 to 116.0)	1.0 (1.0 to 31.0)
CD8 dble_CD40L, Day 392	40.0 (1.0 to 244.0)	18.0 (1.0 to 95.0)	14.0 (1.0 to 140.0)	80.0 (1.0 to 135.0)	10.0 (1.0 to 55.0)
CD8 dble_IFNγ, Day 0	41.5 (1.0 to 148.0)	33.0 (1.0 to 64.0)	22.0 (1.0 to 53.0)	78.0 (28.0 to 166.0)	1.0 (1.0 to 138.0)
CD8 dble_IFNγ, Day 42	32.0 (1.0 to 129.0)	77.0 (1.0 to 321.0)	67.0 (1.0 to 116.0)	191.5 (60.5 to 329.0)	131.0 (1.0 to 243.0)
CD8 dble_IFNγ, Day 385	99.5 (2.5 to 348.0)	103.0 (1.0 to 322.0)	31.0 (1.0 to 170.0)	165.5 (64.0 to 445.0)	1.0 (1.0 to 251.0)
CD8 dble_IFNγ, Day 392	52.0 (2.0 to 364.0)	174.0 (56.0 to 484.0)	31.0 (1.0 to 206.0)	119.0 (16.0 to 431.0)	28.0 (1.0 to 366.0)
CD8 dble_IL2, Day 0	1.0 (1.0 to 66.0)	22.0 (1.0 to 104.0)	1.0 (1.0 to 49.0)	1.0 (1.0 to 90.0)	1.0 (1.0 to 94.0)
CD8 dble_IL2, Day 42	1.0 (1.0 to 168.0)	48.0 (1.0 to 197.0)	53.0 (1.0 to 166.0)	65.5 (1.0 to 263.0)	1.0 (1.0 to 186.0)
CD8 dble_IL2, Day 385	1.0 (1.0 to 125.0)	32.5 (1.0 to 218.0)	16.0 (1.0 to 111.0)	14.0 (1.0 to 117.0)	1.0 (1.0 to 94.0)
CD8 dble_IL2, Day 392	63.0 (1.0 to 451.0)	99.0 (22.0 to 292.0)	1.0 (1.0 to 70.0)	64.0 (1.0 to 156.0)	45.0 (1.0 to 77.0)
CD8 dble_TNFα, Day 0	120.5 (1.0 to 553.0)	103.0 (1.0 to 516.0)	34.0 (1.0 to 324.0)	163.5 (48.0 to 614.0)	116.0 (1.0 to 521.0)
CD8 dble_TNFα, Day 42	192.0 (52.0 to 485.0)	396.0 (77.0 to 709.0)	125.0 (24.0 to 294.0)	351.5 (153.5 to 970.5)	756.0 (65.0 to 1557.0)
CD8 dble_TNFα, Day 385	77.5 (15.0 to 477.5)	366.5 (1.0 to 559.0)	81.0 (1.0 to 204.0)	301.5 (29.0 to 641.0)	212.0 (85.0 to 411.0)
CD8 dble_TNFα, Day 392	217.0 (36.0 to 699.0)	130.0 (1.0 to 708.0)	121.0 (26.0 to 238.0)	310.0 (68.0 to 953.0)	207.0 (47.0 to 369.0)

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 AEs assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb is moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

End point type

Secondary

End point timeframe

During the 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after any vaccine dose

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	38	37	38	37	35
Units: Participants
Pain, Any	20	15	16	20	17
Pain, Grade 3	2	1	1	1	2
Redness (mm), Any	0	0	0	0	0
Redness (mm), Grade 3	0	0	0	0	0
Swelling (mm), Any	0	0	0	1	0
Swelling (mm), Grade 3	0	0	0	0	0

No statistical analyses for this end point

Secondary: Duration of solicited local symptoms

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End point title

Duration of solicited local symptoms

End point description

Duration was defined as number of days with any grade of local symptoms.

End point type

Secondary

End point timeframe

During the 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after any vaccine dose

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	38	37	38	37	35
Units: Days
median (inter-quartile range (Q1-Q3))
Pain, Dose 1	3.0 (1.0 to 4.0)	2.0 (1.0 to 3.0)	1.0 (1.0 to 2.0)	1.0 (1.0 to 2.0)	1.0 (1.0 to 2.0)
Pain, Dose 2	2.0 (1.0 to 3.0)	2.0 (1.0 to 2.0)	1.5 (1.0 to 2.0)	1.5 (1.0 to 2.0)	1.0 (1.0 to 2.5)
Pain, Dose 3	1.0 (1.0 to 2.0)	1.0 (1.0 to 2.0)	2.0 (1.0 to 2.0)	2.0 (1.0 to 3.0)	1.5 (1.0 to 2.0)
Swelling, Dose 1	0.0 (0 to 0)	0.0 (0 to 0)	0.0 (0 to 0)	3.0 (3.0 to 3.0)	0.0 (0 to 0)

No statistical analyses for this end point

Secondary: Number of subjects reporting solicited general symptoms.

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End point title

Number of subjects reporting solicited general symptoms.

End point description

Assessed solicited general symptoms were fever (defined as temperature ≥ 38.0 degrees Celsius (°C) assessed by any route (oral, axillary, rectal)], irritability/fussiness, drowsiness and. loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 irritability/Fussiness and Drowsiness = Prevented normal activity, Grade3 Loss of appetite = Did not eat at all. Grade 3 fever = fever > 40.0 °C. Related = symptom assessed by the investigator as related to the vaccination

End point type

Secondary

End point timeframe

During the 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after any vaccine dose

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	38	37	38	37	35
Units: Participants
Drowsiness, Any	25	18	13	17	16
Drowsiness, Grade 3	2	3	1	1	0
Drowsiness, Related	22	14	12	13	14
Irritability / Fussiness, Any	24	17	19	22	21
Irritability / Fussiness, Grade 3	3	2	3	2	0
Irritability / Fussiness, Related	22	14	17	16	19
Loss Of Appetite, Any	24	13	14	20	13
Loss Of Appetite, Grade 3	0	1	2	2	0
Loss Of Appetite, Related	21	7	11	15	10
Temperature/(Axillary) (°C), Any	24	17	14	14	10
Temperature/(Axillary) (°C), Grade 3	0	0	1	0	0
Temperature/(Axillary) (°C), Related	22	12	12	14	10

No statistical analyses for this end point

Secondary: Duration of solicited general symptoms.

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End point title

Duration of solicited general symptoms.

End point description

Duration was defined as number of days with any grade of general symptoms.

End point type

Secondary

End point timeframe

During the 7-day follow-up period (i.e. on the day of vaccination and 6 subsequent days) after any vaccine dose

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	38	37	38	37	35
Units: Days
median (inter-quartile range (Q1-Q3))
Drowsiness, Dose 1	2.0 (1.0 to 3.0)	1.5 (1.0 to 3.0)	2.0 (1.0 to 2.0)	2.0 (1.0 to 3.0)	1.0 (1.0 to 2.0)
Drowsiness, Dose 2	1.0 (1.0 to 2.0)	2.0 (1.0 to 2.5)	2.0 (2.0 to 3.5)	2.0 (1.0 to 2.0)	1.5 (1.0 to 2.0)
Drowsiness, Dose 3	2.0 (1.0 to 2.0)	2.0 (2.0 to 2.0)	2.0 (2.0 to 2.0)	2.5 (1.0 to 4.0)	1.0 (1.0 to 3.0)
Irritability / fussiness, Dose 1	2.0 (1.0 to 3.0)	2.0 (1.0 to 2.0)	1.0 (1.0 to 2.0)	2.0 (1.0 to 4.0)	2.0 (1.0 to 2.0)
Irritability / fussiness, Dose 2	2.0 (1.0 to 3.0)	2.0 (1.0 to 3.0)	2.0 (1.0 to 4.0)	2.0 (1.0 to 4.0)	2.0 (1.0 to 3.0)
Irritability / fussiness, Dose 3	2.0 (2.0 to 3.0)	3.0 (2.0 to 3.0)	1.0 (1.0 to 2.0)	4.0 (3.0 to 5.0)	1.5 (1.0 to 3.0)
Loss of appetite, Dose 1	2.0 (1.0 to 2.5)	3.0 (3.0 to 3.0)	2.0 (1.0 to 3.0)	2.5 (2.0 to 5.0)	1.5 (1.0 to 2.5)
Loss of appetite, Dose 2	2.0 (1.0 to 6.0)	2.0 (1.0 to 2.0)	3.0 (2.0 to 4.0)	2.0 (1.0 to 3.0)	2.0 (1.0 to 3.0)
Loss of appetite, Dose 3	2.0 (1.0 to 3.5)	2.5 (1.5 to 4.5)	2.0 (1.5 to 3.0)	3.0 (2.0 to 4.0)	2.0 (1.0 to 3.0)
Temperature, Dose 1	1.0 (1.0 to 1.0)	2.0 (1.0 to 2.0)	1.0 (1.0 to 2.0)	2.0 (1.0 to 4.0)	1.0 (1.0 to 1.0)
Temperature, Dose 2	1.0 (1.0 to 3.0)	1.0 (1.0 to 1.5)	1.0 (1.0 to 1.0)	1.0 (1.0 to 1.5)	1.0 (1.0 to 1.0)
Temperature, Dose 3	1.0 (1.0 to 1.5)	2.0 (1.0 to 3.0)	1.0 (1.0 to 1.0)	3.0 (2.0 to 4.0)	0.0 (0.0 to 0.0)

No statistical analyses for this end point

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

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End point title

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

End point description

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevents normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

End point type

Secondary

End point timeframe

During the 21-day follow-up period (Day 0-Day 20) after each vaccine dose

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	38	37	38	37	35
Units: Participants
Any	21	20	23	20	21
Grade 3	3	1	1	3	5
Related	2	0	1	1	3

No statistical analyses for this end point

Secondary: Number of subjects reporting any unsolicited adverse events (AEs) post booster vaccination

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End point title

Number of subjects reporting any unsolicited adverse events (AEs) post booster vaccination

End point description

End point type

Secondary

End point timeframe

During the 30-day (Day 385-Day 415) follow-up period after vaccination

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	36	34	38	35	33
Units: Participants
Any	16	8	16	19	14
Grade 3	1	0	0	1	0
Related	1	0	1	0	0

No statistical analyses for this end point

Secondary: Number of subjects reporting Medically attended events (MAEs)

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End point title

Number of subjects reporting Medically attended events (MAEs)

End point description

MAEs are 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

During the entire study period (Day 0 to Day 415 approximately)

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	38	37	38	37	35
Units: Participants
Any	29	28	33	27	26
Related	1	0	0	1	0

No statistical analyses for this end point

Secondary: Number of subjects reporting Potential immune mediated diseases (pIMDs)

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End point title

Number of subjects reporting Potential immune mediated diseases (pIMDs)

End point description

Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. “Any pIMD” = at least one pIMD experienced by the study subject. Related = pIMD assessed by the investigator to be causally related to the study vaccination.

End point type

Secondary

End point timeframe

During the entire study period (Day 0 to Day 415 approximately)

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	38	37	38	37	35
Units: Participants
Any	0	0	1	0	0
Related	0	0	0	0	0

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 serious adverse event 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

During the entire study period (Day 0 to Day 415 approximately)

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	38	37	38	37	35
Units: Participants
Any	5	6	10	4	4
Related	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects reporting Adverse events of special interest (AESI)

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End point title

Number of subjects reporting Adverse events of special interest (AESI)

End point description

AESI are a subset of adverse events defined in the Committee for Medicinal Products for Human Use (CHMP) Risk Management Plan for Pandemic Vaccines for safety monitoring.

End point type

Secondary

End point timeframe

During the entire study period (Day 0 to Day 415 approximately)

End point values	H5N1 Formulation 1 Group	H5N1 Formulation 2 Group	H5N1 Formulation 3 Group	H5N1 Formulation 4 Group	H5N1 Formulation 5 Group
Number of subjects analysed	38	37	38	37	35
Units: Participants
Any	4	3	3	2	2
Related	1	0	1	1	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited local and general AEs:during 7-day follow-up period after any vaccine dose. Unsolicited AEs:Days 0-20 after each primary dose and Days 385-415 post booster dose. MAEs, pIMDs, SAEs, AESI:during the entire study period (Days 0-415 approximately).

Adverse event reporting additional description

The analysis was performed solely on vaccinated subjects with symptom sheet completed for the reported specific symptom.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

H5N1 Formulation 2 Group

Reporting group description

Reporting group title

H5N1 Formulation 1 Group

Reporting group description

Reporting group title

H5N1 Formulation 4 Group

Reporting group description

Reporting group title

H5N1 Formulation 3 Group

Reporting group description

Reporting group title

H5N1 Formulation 5 Group

Reporting group description

Serious adverse events	H5N1 Formulation 2 Group	H5N1 Formulation 1 Group	H5N1 Formulation 4 Group	H5N1 Formulation 3 Group	H5N1 Formulation 5 Group
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 37 (16.22%)	5 / 38 (13.16%)	4 / 37 (10.81%)	10 / 38 (26.32%)	4 / 35 (11.43%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Lower limb fracture
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Kawasaki’s disease
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Febrile convulsion
subjects affected / exposed	1 / 37 (2.70%)	1 / 38 (2.63%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal hernia
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Balanoposthitis
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bacteraemia
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	1 / 37 (2.70%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	1 / 37 (2.70%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 37 (2.70%)	1 / 38 (2.63%)	0 / 37 (0.00%)	1 / 38 (2.63%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Conjunctivitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Croup infectious
subjects affected / exposed	1 / 37 (2.70%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea infectious
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	3 / 38 (7.89%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpangina
subjects affected / exposed	1 / 37 (2.70%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 37 (2.70%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nasopharyngitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral herpes
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	2 / 37 (5.41%)	0 / 38 (0.00%)	1 / 37 (2.70%)	3 / 38 (7.89%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia respiratory syncytial viral
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchitis
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	2 / 38 (5.26%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Scarlet fever
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	2 / 38 (5.26%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varicella
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral rash
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	H5N1 Formulation 2 Group	H5N1 Formulation 1 Group	H5N1 Formulation 4 Group	H5N1 Formulation 3 Group	H5N1 Formulation 5 Group
Total subjects affected by non serious adverse events
subjects affected / exposed	31 / 37 (83.78%)	36 / 38 (94.74%)	35 / 37 (94.59%)	35 / 38 (92.11%)	32 / 35 (91.43%)
General disorders and administration site conditions
Feeling hot
subjects affected / exposed	0 / 37 (0.00%)	2 / 38 (5.26%)	1 / 37 (2.70%)	3 / 38 (7.89%)	0 / 35 (0.00%)
occurrences all number	0	4	1	3	0
Influenza like illness
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Injection site erythema
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Injection site urticaria
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Pain
subjects affected / exposed	15 / 37 (40.54%)	20 / 38 (52.63%)	20 / 37 (54.05%)	16 / 38 (42.11%)	17 / 35 (48.57%)
occurrences all number	32	39	31	31	36
Pyrexia
subjects affected / exposed	17 / 37 (45.95%)	24 / 38 (63.16%)	16 / 37 (43.24%)	15 / 38 (39.47%)	12 / 35 (34.29%)
occurrences all number	21	36	20	16	15
Swelling
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Bronchial hyperreactivity
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Cough
subjects affected / exposed	2 / 37 (5.41%)	0 / 38 (0.00%)	3 / 37 (8.11%)	2 / 38 (5.26%)	1 / 35 (2.86%)
occurrences all number	2	0	3	2	2
Increased upper airway secretion
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Productive cough
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Respiration abnormal
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	1	0	0	0	0
Rhinitis allergic
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	1 / 35 (2.86%)
occurrences all number	0	0	0	1	1
Rhinorrhoea
subjects affected / exposed	2 / 37 (5.41%)	1 / 38 (2.63%)	1 / 37 (2.70%)	5 / 38 (13.16%)	2 / 35 (5.71%)
occurrences all number	3	1	3	7	2
Psychiatric disorders
Irritability
subjects affected / exposed	17 / 37 (45.95%)	24 / 38 (63.16%)	22 / 37 (59.46%)	19 / 38 (50.00%)	21 / 35 (60.00%)
occurrences all number	26	39	35	31	38
Product issues
Device breakage
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Investigations
Body height below normal
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Body temperature increased
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	1 / 37 (2.70%)	2 / 38 (5.26%)	1 / 35 (2.86%)
occurrences all number	0	1	1	2	1
Cardiac murmur
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	1	0	0	1
Contusion
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	1	0	0	0	0
Forearm fracture
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Foreign body in eye
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Head injury
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Limb injury
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Skin abrasion
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	1	0	0	0	0
Nervous system disorders
Febrile convulsion
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Headache
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Somnolence
subjects affected / exposed	18 / 37 (48.65%)	25 / 38 (65.79%)	17 / 37 (45.95%)	13 / 38 (34.21%)	16 / 35 (45.71%)
occurrences all number	29	42	29	20	24
Speech disorder developmental
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Iron deficiency anaemia
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Eye disorders
Erythema of eyelid
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Eyelid oedema
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Periorbital oedema
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	1	0	0	0	0
Abdominal pain
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Constipation
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	2 / 35 (5.71%)
occurrences all number	0	0	0	0	2
Diarrhoea
subjects affected / exposed	2 / 37 (5.41%)	2 / 38 (5.26%)	2 / 37 (5.41%)	1 / 38 (2.63%)	3 / 35 (8.57%)
occurrences all number	2	2	2	1	3
Flatulence
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Food poisoning
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Gastritis
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Gastrointestinal inflammation
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Mouth ulceration
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	1 / 38 (2.63%)	1 / 35 (2.86%)
occurrences all number	0	1	0	1	1
Vomiting
subjects affected / exposed	0 / 37 (0.00%)	3 / 38 (7.89%)	2 / 37 (5.41%)	1 / 38 (2.63%)	3 / 35 (8.57%)
occurrences all number	0	3	2	1	3
Skin and subcutaneous tissue disorders
Blister
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Dermatitis allergic
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Dermatitis atopic
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Dermatitis diaper
subjects affected / exposed	1 / 37 (2.70%)	2 / 38 (5.26%)	0 / 37 (0.00%)	1 / 38 (2.63%)	1 / 35 (2.86%)
occurrences all number	1	2	0	1	1
Eczema
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Erythema
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Rash
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	1	0	1
Rash generalised
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	1	0	1
Rash papular
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Urticaria
subjects affected / exposed	1 / 37 (2.70%)	1 / 38 (2.63%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	1	1	1	0	0
Infections and infestations
Acute sinusitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	2 / 38 (5.26%)	0 / 35 (0.00%)
occurrences all number	0	0	0	2	0
Bronchiolitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	2 / 37 (5.41%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	1	0	2	1	0
Bronchitis
subjects affected / exposed	2 / 37 (5.41%)	2 / 38 (5.26%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	2	2	0	0	1
Bronchitis viral
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Candida infection
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Cellulitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Conjunctivitis
subjects affected / exposed	2 / 37 (5.41%)	0 / 38 (0.00%)	0 / 37 (0.00%)	2 / 38 (5.26%)	0 / 35 (0.00%)
occurrences all number	3	0	0	2	0
Enterovirus infection
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Gastroenteritis
subjects affected / exposed	2 / 37 (5.41%)	1 / 38 (2.63%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	3	1	0	1	0
Gastroenteritis viral
subjects affected / exposed	0 / 37 (0.00%)	2 / 38 (5.26%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	2	0	0	0
Hand-foot-and-mouth disease
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Hordeolum
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Impetigo
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Influenza
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Nasopharyngitis
subjects affected / exposed	8 / 37 (21.62%)	10 / 38 (26.32%)	5 / 37 (13.51%)	10 / 38 (26.32%)	9 / 35 (25.71%)
occurrences all number	10	13	6	15	10
Oral herpes
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	1	0	0	0	0
Otitis media
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	1	0	0	0
Otitis media acute
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Paronychia
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1
Pharyngitis
subjects affected / exposed	1 / 37 (2.70%)	3 / 38 (7.89%)	1 / 37 (2.70%)	5 / 38 (13.16%)	3 / 35 (8.57%)
occurrences all number	1	6	1	5	3
Pharyngotonsillitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	1	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Respiratory syncytial virus bronchitis
subjects affected / exposed	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	1	0	1	0
Roseola
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Sinusitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	2	0
Tonsillitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	1 / 38 (2.63%)	0 / 35 (0.00%)
occurrences all number	0	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	8 / 37 (21.62%)	7 / 38 (18.42%)	13 / 37 (35.14%)	6 / 38 (15.79%)	8 / 35 (22.86%)
occurrences all number	10	7	16	6	9
Viral diarrhoea
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Viral infection
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	1	0	1
Viral rash
subjects affected / exposed	0 / 37 (0.00%)	3 / 38 (7.89%)	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	3	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 37 (2.70%)	0 / 38 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	0	1	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	13 / 37 (35.14%)	25 / 38 (65.79%)	20 / 37 (54.05%)	14 / 38 (36.84%)	13 / 35 (37.14%)
occurrences all number	16	39	30	20	19
Failure to thrive
subjects affected / exposed	0 / 37 (0.00%)	0 / 38 (0.00%)	0 / 37 (0.00%)	0 / 38 (0.00%)	1 / 35 (2.86%)
occurrences all number	0	0	0	0	1

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Were there any global substantial amendments to the protocol? No

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 Trial Results: A phase II observer-blind, multicentre, dose-ranging study of children 6 to less than 36 months of age who are to be primed with a 2-dose series of GSK Biologicals’ AS03 adjuvanted A/Indonesia/05/2005 (H5N1) vaccine.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Haemagglutination Inhibition (HI) antibody titers following primary vaccination

Primary: Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Haemagglutination Inhibition (HI) antibody titers following primary vaccination

Primary: Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Microneutralization (MN) antibody titers following primary vaccination

Primary: Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Microneutralization (MN) antibody titers following primary vaccination

Primary: Evaluation of Fever index for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Haemagglutination Inhibition (HI) antibody titers following primary vaccination.

Primary: Evaluation of Fever index for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Haemagglutination Inhibition (HI) antibody titers following primary vaccination.

Primary: Evaluation of Fever index for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Microneutralization (MN) antibody titers following primary vaccination.

Primary: Evaluation of Fever index for A/Indonesia/05/2005 (H5N1) strain in terms of vaccine-homologous Microneutralization (MN) antibody titers following primary vaccination.

Primary: Mean Geometric Increase (MGI) for vaccine homologous and heterologous HI antibody titers against each of the four vaccine influenza strains.

Primary: Mean Geometric Increase (MGI) for vaccine homologous and heterologous HI antibody titers against each of the four vaccine influenza strains.

Primary: Mean Geometric Increase (MGI) for vaccine homologous and heterologous MN antibody titers against each of the 3 vaccine influenza strains.

Primary: Mean Geometric Increase (MGI) for vaccine homologous and heterologous MN antibody titers against each of the 3 vaccine influenza strains.

Secondary: Number of seroconverted subjects for HI antibodies against each of the 4 vaccine influenza strains.

Secondary: Number of seroconverted subjects for HI antibodies against each of the 4 vaccine influenza strains.

Secondary: Number of subjects who were seroprotected for HI antibodies against each of the 4 vaccine influenza strains.

Secondary: Number of subjects who were seroprotected for HI antibodies against each of the 4 vaccine influenza strains.

Secondary: Geometric mean titers (GMTs) for humoral immune response in terms of HI antibodies against vaccine-homologous/heterologous antigens

Secondary: Geometric mean titers (GMTs) for humoral immune response in terms of HI antibodies against vaccine-homologous/heterologous antigens

Secondary: Mean geometric increase (MGI) for haemagglutination inhibition (HI) antibody titer against each of the 4 vaccine influenza strains

Secondary: Mean geometric increase (MGI) for haemagglutination inhibition (HI) antibody titer against each of the 4 vaccine influenza strains

Secondary: Mean geometric increase (MGI) for MN antibodies against the 3 vaccine influenza strains.

Secondary: Mean geometric increase (MGI) for MN antibodies against the 3 vaccine influenza strains.

Secondary: Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of MN antibodies against vaccine-homologous/heterologous antigens

Secondary: Humoral immune response for A/Indonesia/05/2005 (H5N1) strain in terms of MN antibodies against vaccine-homologous/heterologous antigens

Secondary: Vaccine response rate (VRR) for homologous and heterologous MN antibodies against each of the 3 vaccine influenza strains.

Secondary: Vaccine response rate (VRR) for homologous and heterologous MN antibodies against each of the 3 vaccine influenza strains.

Secondary: Cell mediated Immunity (CMI) in terms of T-cell markers related to Flu A/Indonesia/05/2005 antigen.

Secondary: Cell mediated Immunity (CMI) in terms of T-cell markers related to Flu A/Indonesia/05/2005 antigen.

Secondary: Number of subjects reporting solicited local symptoms

Secondary: Number of subjects reporting solicited local symptoms

Secondary: Duration of solicited local symptoms

Secondary: Duration of solicited local symptoms

Secondary: Number of subjects reporting solicited general symptoms.

Secondary: Number of subjects reporting solicited general symptoms.

Secondary: Duration of solicited general symptoms.

Secondary: Duration of solicited general symptoms.

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

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

Secondary: Number of subjects reporting any unsolicited adverse events (AEs) post booster vaccination

Secondary: Number of subjects reporting any unsolicited adverse events (AEs) post booster vaccination

Secondary: Number of subjects reporting Medically attended events (MAEs)

Secondary: Number of subjects reporting Medically attended events (MAEs)

Secondary: Number of subjects reporting Potential immune mediated diseases (pIMDs)

Secondary: Number of subjects reporting Potential immune mediated diseases (pIMDs)

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

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

Secondary: Number of subjects reporting Adverse events of special interest (AESI)

Secondary: Number of subjects reporting Adverse events of special interest (AESI)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A phase II observer-blind, multicentre, dose-ranging study of children 6 to less than 36 months of age who are to be primed with a 2-dose series of GSK Biologicals’ AS03 adjuvanted A/Indonesia/05/2005 (H5N1) vaccine.