Trial Outcomes & Findings for Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Children (NCT NCT01776554)

NCT ID: NCT01776554

Last Updated: 2019-01-16

Results Overview

The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 6 to \<36 months, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years). CBER criterion is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 662 participants
• Primary outcome timeframe: Three weeks after 2nd vaccination (day 43)
• Results posted on: 2019-01-16

Participant Flow

Subjects were enrolled at 10 centers in United States and 2 centers in Thailand.

All enrolled subjects were included in the trial.

Participant milestones

Measure	High Dose Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Study STARTED	332	330
Overall Study COMPLETED	315	307
Overall Study NOT COMPLETED	17	23

Reasons for withdrawal

Measure	High Dose Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	3	8
Overall Study Lost to Follow-up	6	9
Overall Study Administrative Reason	2	5
Overall Study Protocol Violation	1	0
Overall Study Unclassified	4	1

Baseline Characteristics

Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Children

Baseline characteristics by cohort

Measure	High Dose n=332 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=330 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Total n=662 Participants Total of all reporting groups
Age, Continuous	78.7 Months STANDARD_DEVIATION 55.9 • n=5 Participants	78.1 Months STANDARD_DEVIATION 55.6 • n=7 Participants	78.4 Months STANDARD_DEVIATION 55.7 • n=5 Participants
Sex: Female, Male FEMALE	152 Participants n=5 Participants	164 Participants n=7 Participants	316 Participants n=5 Participants
Sex: Female, Male MALE	180 Participants n=5 Participants	166 Participants n=7 Participants	346 Participants n=5 Participants

PRIMARY outcome

Timeframe: Three weeks after 2nd vaccination (day 43)

Population: Analysis was done on the Full Analysis Set (FAS) i.e., the subjects who actually received at least one dose of study vaccination and provided at least one evaluable serum sample both before (baseline) and after vaccination.

The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 6 to <36 months, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion.

As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years).

CBER criterion is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.

Outcome measures

Measure	High Dose n=93 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=90 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain Day 1	1 Percentages of subjects Interval 0.027 to 6.0	0 Percentages of subjects Interval 0.0 to 4.0
The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain Day 43 (N=91,85)	98 Percentages of subjects Interval 92.0 to 100.0	94 Percentages of subjects Interval 87.0 to 98.0

PRIMARY outcome

Timeframe: Three weeks after 2nd vaccination (day 43)

Population: Analysis was done on FAS.

The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 3 to <9 years, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the CBER criterion.

As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years).

CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.

Outcome measures

Measure	High Dose n=98 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=101 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain Day 1	0 Percentages of subjects Interval 0.0 to 4.0	0 Percentages of subjects Interval 0.0 to 4.0
The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain Day 43 (N=94,98)	98 Percentages of subjects Interval 93.0 to 100.0	86 Percentages of subjects Interval 77.0 to 92.0

PRIMARY outcome

Timeframe: Three weeks after 2nd vaccination (day 43)

Population: Analysis was done on FAS.

The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 9 to <18 years, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the CBER criterion.

As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years).

CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.

Outcome measures

Measure	High Dose n=103 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=109 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
The Percentages Of Subjects Aged 9 to <18 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain Day 1	2 Percentages of subjects Interval 0.0 to 7.0	1 Percentages of subjects Interval 0.023 to 5.0
The Percentages Of Subjects Aged 9 to <18 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain Day 43 (N=102,105)	92 Percentages of subjects Interval 85.0 to 97.0	79 Percentages of subjects Interval 70.0 to 86.0

PRIMARY outcome

Timeframe: Three weeks after 2nd vaccination (day 43)

Population: Analysis was done was FAS.

Immunogenicity was measured in terms of the percentages of subjects aged 6 to <36 months, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria.

Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer.

CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.

Outcome measures

Measure	High Dose n=84 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=85 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain	99 Percentages of subjects Interval 94.0 to 100.0	94 Percentages of subjects Interval 87.0 to 98.0

PRIMARY outcome

Timeframe: Three weeks after 2nd vaccination (day 43)

Population: Analysis was done on FAS.

Immunogenicity was measured in terms of the percentages of subjects aged 3 to <9 years, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria.

Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer.

CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.

Outcome measures

Measure	High Dose n=93 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=98 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain	98 Percentages of subjects Interval 92.0 to 100.0	86 Percentages of subjects Interval 77.0 to 92.0

PRIMARY outcome

Timeframe: Three weeks after 2nd vaccination (day 43)

Population: This analysis was done on the FAS.

Immunogenicity was measured in terms of the percentages of subjects aged 9 to <18 years, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria.

Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer.

CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.

Outcome measures

Measure	High Dose n=102 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=105 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain	92 Percentages of subjects Interval 85.0 to 97.0	79 Percentages of subjects Interval 70.0 to 86.0

PRIMARY outcome

Timeframe: From day 1 through day 7 after each vaccination.

Population: Analysis was done on the safety dataset, i.e. the subjects in the exposed population who provided postvaccination safety data.

Safety was assessed using the number of subjects who reported solicited local and systemic adverse events following vaccination with either low or high dose of aH5N1c vaccine.

Outcome measures

Measure	High Dose n=166 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=164 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Any Local	89 Number of subjects	92 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Injection site erythema (N=159,162)	4 Number of subjects	2 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Injection site induration (N=159,162)	2 Number of subjects	2 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Injection site ecchymosis (N=159,162)	0 Number of subjects	1 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Injection site tenderness (N=159,162)	89 Number of subjects	91 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Any Systemic	68 Number of subjects	65 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Change in eating habits (N=159,162)	29 Number of subjects	20 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Irritability (N=159,162)	47 Number of subjects	45 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Sleepiness (N=159,162)	40 Number of subjects	40 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Fever (≥38°C; N=160,162)	25 Number of subjects	13 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Prevention of pain and/or fever (N=160,161)	18 Number of subjects	25 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Treatment of pain and/or fever (N=160,161)	37 Number of subjects	26 Number of subjects
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Fever (≥40°C; N=160,162)	1 Number of subjects	0 Number of subjects

PRIMARY outcome

Timeframe: From day 1 through day 7 after any vaccination.

Population: Analysis was done on the safety dataset.

Safety was assessed using the number of subjects who reported solicited local and systemic adverse events following vaccination with either low or high dose of aH5N1c vaccine.

Outcome measures

Measure	High Dose n=163 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=165 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Any Local	111 Number of subjects	115 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Injection site erythema (N=163,161)	2 Number of subjects	0 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Injection site induration (N=163,160)	4 Number of subjects	2 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Injection site ecchymosis (N=163,160)	0 Number of subjects	0 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Injection site pain (N=163,160)	111 Number of subjects	115 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Any Systemic	79 Number of subjects	82 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Myalgia (N=162,160)	49 Number of subjects	44 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Arthralgia (N=162,160)	21 Number of subjects	19 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Headache (N=162,160)	36 Number of subjects	47 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Fatigue (N=162,160)	43 Number of subjects	48 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Loss of Appetite (N=162,160)	22 Number of subjects	18 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Malaise (N=162,160)	40 Number of subjects	38 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Fever (≥38°C; N=163,161)	7 Number of subjects	5 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Prevention of pain and/or fever (N=163,161)	14 Number of subjects	10 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Treatment of pain and/or fever (N=163,161)	24 Number of subjects	23 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Fever (≥40°C; N=163,161)	0 Number of subjects	0 Number of subjects
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination Nausea (N=162,160)	21 Number of subjects	26 Number of subjects

PRIMARY outcome

Timeframe: Any unsolicited AEs - day 1 through day 22 after any vaccination; SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387

Population: Analysis was done on the safety dataset.

Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine.

Outcome measures

Measure	High Dose n=329 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=329 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination Any AEs	149 Number of subjects	156 Number of subjects
Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination At least possibly related AEs (N=326,324)	15 Number of subjects	12 Number of subjects
Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination Any SAEs (N=326,324)	8 Number of subjects	11 Number of subjects
Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination Deaths (N=326,324)	0 Number of subjects	0 Number of subjects
Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination Medically attended AEs (N=326,324)	110 Number of subjects	113 Number of subjects
Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination AEs resulting in premature withdrawal (N=326,324)	1 Number of subjects	0 Number of subjects
Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination AEs of Special Interest (N=326,324)	0 Number of subjects	0 Number of subjects
Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination New Onset of Chronic Disease(N=326,324)	0 Number of subjects	3 Number of subjects

SECONDARY outcome

Timeframe: Day 1, day 22, day 43 and day 387

Population: Analysis was done on the FAS.

Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 6 to <36 months is reported.

The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5.

As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied.

Outcome measures

Measure	High Dose n=84 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=86 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. A/H5N1 (Day22/Day1)	12 Ratio Interval 7.28 to 19.0	4.56 Ratio Interval 2.78 to 7.47
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. A/H5N1 (Day43/Day1; N=84,85)	302 Ratio Interval 192.0 to 476.0	116 Ratio Interval 74.0 to 181.0
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. A/H5N1 (Day387/Day1; N=78,77)	52 Ratio Interval 25.0 to 106.0	19 Ratio Interval 9.3 to 37.0

SECONDARY outcome

Timeframe: Day 1, day 22, day 43 and day 387

Population: Analysis was done on the FAS.

Immunogenicity was measured as geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 3 to <9 years is reported.

As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied.

The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5.

Outcome measures

Measure	High Dose n=95 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=98 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. A/H5N1 (Day22/Day1)	9.81 Ratio Interval 5.96 to 16.0	8.22 Ratio Interval 4.84 to 14.0
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. A/H5N1 (Day43/Day1; N=93,98)	249 Ratio Interval 153.0 to 404.0	73 Ratio Interval 44.0 to 121.0
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. A/H5N1 (Day387/Day1; N=89,94)	11 Ratio Interval 7.32 to 18.0	4.62 Ratio Interval 2.92 to 7.31

SECONDARY outcome

Timeframe: Day 1, day 22, day 43 and day 387

Population: Analysis was done on the FAS.

Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 9 to <18 years is reported.

As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied.

The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5.

Outcome measures

Measure	High Dose n=102 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=105 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. A/H5N1 (Day22/Day1; N=102,103)	15 Ratio Interval 8.78 to 27.0	6.74 Ratio Interval 3.93 to 12.0
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. A/H5N1 (Day43/Day1)	186 Ratio Interval 105.0 to 328.0	58 Ratio Interval 34.0 to 101.0
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. A/H5N1 (Day387/Day1; N=97,100)	4.05 Ratio Interval 2.76 to 5.94	2.64 Ratio Interval 1.83 to 3.81

SECONDARY outcome

Timeframe: Day 1, day 22, day 43 and day 387.

Population: Analysis was done on the FAS.

Immunogenicity was assessed in terms of percentage of subjects aged 6 to <36 months, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion.

European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.

Outcome measures

Measure	High Dose n=93 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=90 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain Day 1	1 Percentages of subjects Interval 0.027 to 6.0	0 Percentages of subjects Interval 0.0 to 4.0
Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain Day 22 (N=85,86)	58 Percentages of subjects Interval 46.0 to 68.0	36 Percentages of subjects Interval 26.0 to 47.0
Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain Day 43 (N=91,85)	98 Percentages of subjects Interval 92.0 to 100.0	94 Percentages of subjects Interval 87.0 to 98.0
Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain Day 387 (N=84,77)	71 Percentages of subjects Interval 61.0 to 81.0	61 Percentages of subjects Interval 49.0 to 72.0

SECONDARY outcome

Timeframe: Day 1, day 22, day 43 and day 387.

Population: Analysis was done on the FAS.

Immunogenicity was assessed in terms of percentage of subjects aged 3 to <9 years, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion.

European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.

Outcome measures

Measure	High Dose n=98 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=101 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain Day 1	0 Percentages of subjects Interval 0.0 to 4.0	0 Percentages of subjects Interval 0.0 to 4.0
Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain Day 22 (N=96,98)	43 Percentages of subjects Interval 33.0 to 53.0	41 Percentages of subjects Interval 31.0 to 51.0
Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain Day 43 (N=94,98)	98 Percentages of subjects Interval 93.0 to 100.0	86 Percentages of subjects Interval 77.0 to 92.0
Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain Day 387 (90,94)	44 Percentages of subjects Interval 34.0 to 55.0	22 Percentages of subjects Interval 14.0 to 32.0

SECONDARY outcome

Timeframe: Day 1, day 22, day 43 and day 387.

Population: Analysis was done on the FAS.

Immunogenicity was assessed in terms of percentage of subjects aged 9 to <18 years, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion.

European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.

Outcome measures

Measure	High Dose n=103 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=109 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain Day 1	2 Percentages of subjects Interval 0.0 to 7.0	1 Percentages of subjects Interval 0.023 to 5.0
Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain Day 22 (N=102,103)	54 Percentages of subjects Interval 44.0 to 64.0	37 Percentages of subjects Interval 28.0 to 47.0
Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain Day 43 (N=102,105)	92 Percentages of subjects Interval 85.0 to 97.0	79 Percentages of subjects Interval 70.0 to 86.0
Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain Day 387 (N=97,100)	29 Percentages of subjects Interval 20.0 to 39.0	17 Percentages of subjects Interval 10.0 to 26.0

SECONDARY outcome

Timeframe: Day 22, day 43 and day 387

Population: Analysis was done on the FAS.

Immunogenicity was assessed in terms of percentages of subjects aged 6 to <36 months achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion.

Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer.

The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%.

Outcome measures

Measure	High Dose n=84 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=86 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain Day 22	58 Percentages of subjects Interval 47.0 to 69.0	36 Percentages of subjects Interval 26.0 to 47.0
The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain Day 43 (N=84,85)	99 Percentages of subjects Interval 94.0 to 100.0	94 Percentages of subjects Interval 87.0 to 98.0
The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain Day 387 (N=78,77)	73 Percentages of subjects Interval 62.0 to 82.0	61 Percentages of subjects Interval 49.0 to 72.0

SECONDARY outcome

Timeframe: Day 22, day 43 and day 387

Population: Analysis was done on FAS.

Immunogenicity was assessed in terms of percentages of subjects aged 3 to <9 years achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion.

Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer.

The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%.

Outcome measures

Measure	High Dose n=95 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=98 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain Day 22	43 Percentages of subjects Interval 33.0 to 54.0	41 Percentages of subjects Interval 31.0 to 51.0
The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain Day 43 (N=93,98)	98 Percentages of subjects Interval 92.0 to 100.0	86 Percentages of subjects Interval 77.0 to 92.0
The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain Day 387 (N=89,94)	45 Percentages of subjects Interval 34.0 to 56.0	22 Percentages of subjects Interval 14.0 to 32.0

SECONDARY outcome

Timeframe: Day 22, day 43 and day 387

Population: Analysis was done the FAS.

Immunogenicity was assessed in terms of percentages of subjects aged 9 to <18 years achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion.

Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer.

The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%.

Outcome measures

Measure	High Dose n=102 Participants Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=105 Participants Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain Day 22 (N=102,103)	54 Percentages of subjects Interval 44.0 to 64.0	36 Percentages of subjects Interval 27.0 to 46.0
The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain Day 43	92 Percentages of subjects Interval 85.0 to 97.0	79 Percentages of subjects Interval 70.0 to 86.0
The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain Day 387 (N=97,100)	29 Percentages of subjects Interval 20.0 to 39.0	16 Percentages of subjects Interval 9.0 to 25.0

Adverse Events

High Dose

Serious events: 8 serious events

Other events: 263 other events

Deaths: 0 deaths

Low Dose

Serious events: 11 serious events

Other events: 257 other events

Deaths: 0 deaths

Total

Serious events: 19 serious events

Other events: 520 other events

Deaths: 0 deaths

Serious adverse events

Measure	High Dose n=329 participants at risk Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=329 participants at risk Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Total n=658 participants at risk Total of subjects in both high dose and low dose groups.
Gastrointestinal disorders FOOD POISONING	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 2/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations BRONCHOPNEUMONIA	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations CELLULITIS ORBITAL	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations DENGUE FEVER	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 2/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations GASTROENTERITIS	0.61% 2/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.46% 3/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations INFLUENZA	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations PNEUMONIA	0.61% 2/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 2/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations PNEUMONIA INFLUENZAL	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations STREPTOCOCCAL SEPSIS	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Injury, poisoning and procedural complications CLAVICLE FRACTURE	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Injury, poisoning and procedural complications FEMUR FRACTURE	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Injury, poisoning and procedural complications LACERATION	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Injury, poisoning and procedural complications TIBIA FRACTURE	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Injury, poisoning and procedural complications UPPER LIMB FRACTURE	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Musculoskeletal and connective tissue disorders MYALGIA	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Nervous system disorders CONVULSION	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Nervous system disorders FEBRILE CONVULSION	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Respiratory, thoracic and mediastinal disorders APNOEIC ATTACK	0.00% 0/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.30% 1/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	0.15% 1/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set

Other adverse events

Measure	High Dose n=329 participants at risk Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Low Dose n=329 participants at risk Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.	Total n=658 participants at risk Total of subjects in both high dose and low dose groups.
Gastrointestinal disorders NAUSEA	7.6% 25/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	8.8% 29/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	8.2% 54/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
General disorders FATIGUE	13.4% 44/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	15.2% 50/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	14.3% 94/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
General disorders INJECTION SITE ERYTHEMA	18.2% 60/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	16.4% 54/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	17.3% 114/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
General disorders INJECTION SITE HAEMORRHAGE	7.0% 23/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	5.8% 19/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	6.4% 42/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
General disorders INJECTION SITE INDURATION	13.7% 45/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	11.9% 39/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	12.8% 84/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
General disorders INJECTION SITE PAIN	63.5% 209/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	64.7% 213/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	64.1% 422/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
General disorders MALAISE	12.2% 40/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	11.6% 38/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	11.9% 78/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
General disorders PYREXIA	14.6% 48/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	9.7% 32/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	12.2% 80/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations NASOPHARYNGITIS	5.5% 18/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	4.9% 16/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	5.2% 34/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	16.7% 55/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	17.6% 58/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	17.2% 113/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Metabolism and nutrition disorders DECREASED APPETITE	6.7% 22/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	6.4% 21/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	6.5% 43/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Musculoskeletal and connective tissue disorders ARTHRALGIA	7.0% 23/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	6.1% 20/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	6.5% 43/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Musculoskeletal and connective tissue disorders MYALGIA	15.2% 50/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	13.7% 45/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	14.4% 95/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Nervous system disorders HEADACHE	12.2% 40/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	14.6% 48/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	13.4% 88/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Nervous system disorders SOMNOLENCE	12.8% 42/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	12.5% 41/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	12.6% 83/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Psychiatric disorders EATING DISORDER	8.8% 29/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	6.1% 20/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	7.4% 49/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set
Psychiatric disorders IRRITABILITY	14.9% 49/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	14.3% 47/329 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set	14.6% 96/658 • Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387. All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment. In total 658 subjects, who were exposed to at least one study vaccination were considered for the safety evaluation and included in overall safety set

Additional Information

Posting Director

Novartis Vaccines

Email: RegistryContactVaccinesUS@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place