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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01776554
Recruitment Status : Completed
First Posted : January 28, 2013
Results First Posted : April 20, 2015
Last Update Posted : January 16, 2019
Sponsor:
Collaborator:
Department of Health and Human Services
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Prevention
Condition Pandemic H5N1 Influenza
Intervention Biological: Adjuvanted H5N1 pandemic influenza vaccine
Enrollment 662
Recruitment Details Subjects were enrolled at 10 centers in United States and 2 centers in Thailand.
Pre-assignment Details All enrolled subjects were included in the trial.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Period Title: Overall Study
Started 332 330
Completed 315 307
Not Completed 17 23
Reason Not Completed
Adverse Event             1             0
Withdrawal by Subject             3             8
Lost to Follow-up             6             9
Administrative Reason             2             5
Protocol Violation             1             0
Unclassified             4             1
Arm/Group Title High Dose Low Dose Total
Hide Arm/Group Description Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. Total of all reporting groups
Overall Number of Baseline Participants 332 330 662
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 332 participants 330 participants 662 participants
78.7  (55.9) 78.1  (55.6) 78.4  (55.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 332 participants 330 participants 662 participants
FEMALE
152
  45.8%
164
  49.7%
316
  47.7%
MALE
180
  54.2%
166
  50.3%
346
  52.3%
1.Primary Outcome
Title The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain
Hide Description

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%.

Time Frame Three weeks after 2nd vaccination (day 43)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 93 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1
1
(0.027 to 6)
0
(0 to 4)
Day 43 (N=91,85)
98
(92 to 100)
94
(87 to 98)
2.Primary Outcome
Title The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain
Hide Description

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%.

Time Frame Three weeks after 2nd vaccination (day 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 98 101
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1
0
(0 to 4)
0
(0 to 4)
Day 43 (N=94,98)
98
(93 to 100)
86
(77 to 92)
3.Primary Outcome
Title The Percentages Of Subjects Aged 9 to <18 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain
Hide Description

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%.

Time Frame Three weeks after 2nd vaccination (day 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 103 109
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1
2
(0 to 7)
1
(0.023 to 5)
Day 43 (N=102,105)
92
(85 to 97)
79
(70 to 86)
4.Primary Outcome
Title The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain
Hide Description

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%.

Time Frame Three weeks after 2nd vaccination (day 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done was FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 84 85
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
99
(94 to 100)
94
(87 to 98)
5.Primary Outcome
Title The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain
Hide Description

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%.

Time Frame Three weeks after 2nd vaccination (day 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 93 98
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
98
(92 to 100)
86
(77 to 92)
6.Primary Outcome
Title The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain
Hide Description

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%.

Time Frame Three weeks after 2nd vaccination (day 43)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was done on the FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 102 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
92
(85 to 97)
79
(70 to 86)
7.Primary Outcome
Title Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination
Hide Description 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.
Time Frame From day 1 through day 7 after each vaccination.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the safety dataset, i.e. the subjects in the exposed population who provided postvaccination safety data.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 166 164
Measure Type: Number
Unit of Measure: Number of subjects
Any Local 89 92
Injection site erythema (N=159,162) 4 2
Injection site induration (N=159,162) 2 2
Injection site ecchymosis (N=159,162) 0 1
Injection site tenderness (N=159,162) 89 91
Any Systemic 68 65
Change in eating habits (N=159,162) 29 20
Irritability (N=159,162) 47 45
Sleepiness (N=159,162) 40 40
Fever (≥38°C; N=160,162) 25 13
Prevention of pain and/or fever (N=160,161) 18 25
Treatment of pain and/or fever (N=160,161) 37 26
Fever (≥40°C; N=160,162) 1 0
8.Primary Outcome
Title Number of Subjects (≥6 Years – 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination
Hide Description 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.
Time Frame From day 1 through day 7 after any vaccination.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the safety dataset.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 163 165
Measure Type: Number
Unit of Measure: Number of subjects
Any Local 111 115
Injection site erythema (N=163,161) 2 0
Injection site induration (N=163,160) 4 2
Injection site ecchymosis (N=163,160) 0 0
Injection site pain (N=163,160) 111 115
Any Systemic 79 82
Myalgia (N=162,160) 49 44
Arthralgia (N=162,160) 21 19
Headache (N=162,160) 36 47
Fatigue (N=162,160) 43 48
Loss of Appetite (N=162,160) 22 18
Malaise (N=162,160) 40 38
Fever (≥38°C; N=163,161) 7 5
Prevention of pain and/or fever (N=163,161) 14 10
Treatment of pain and/or fever (N=163,161) 24 23
Fever (≥40°C; N=163,161) 0 0
Nausea (N=162,160) 21 26
9.Primary Outcome
Title Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the safety dataset.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 329 329
Measure Type: Number
Unit of Measure: Number of subjects
Any AEs 149 156
At least possibly related AEs (N=326,324) 15 12
Any SAEs (N=326,324) 8 11
Deaths (N=326,324) 0 0
Medically attended AEs (N=326,324) 110 113
AEs resulting in premature withdrawal (N=326,324) 1 0
AEs of Special Interest (N=326,324) 0 0
New Onset of Chronic Disease(N=326,324) 0 3
10.Secondary Outcome
Title 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.
Hide Description

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.

Time Frame Day 1, day 22, day 43 and day 387
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 84 86
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
A/H5N1 (Day22/Day1)
12
(7.28 to 19)
4.56
(2.78 to 7.47)
A/H5N1 (Day43/Day1; N=84,85)
302
(192 to 476)
116
(74 to 181)
A/H5N1 (Day387/Day1; N=78,77)
52
(25 to 106)
19
(9.3 to 37)
11.Secondary Outcome
Title 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.
Hide Description

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.

Time Frame Day 1, day 22, day 43 and day 387
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 95 98
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
A/H5N1 (Day22/Day1)
9.81
(5.96 to 16)
8.22
(4.84 to 14)
A/H5N1 (Day43/Day1; N=93,98)
249
(153 to 404)
73
(44 to 121)
A/H5N1 (Day387/Day1; N=89,94)
11
(7.32 to 18)
4.62
(2.92 to 7.31)
12.Secondary Outcome
Title 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.
Hide Description

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.

Time Frame Day 1, day 22, day 43 and day 387
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 102 105
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
A/H5N1 (Day22/Day1; N=102,103)
15
(8.78 to 27)
6.74
(3.93 to 12)
A/H5N1 (Day43/Day1)
186
(105 to 328)
58
(34 to 101)
A/H5N1 (Day387/Day1; N=97,100)
4.05
(2.76 to 5.94)
2.64
(1.83 to 3.81)
13.Secondary Outcome
Title Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain
Hide Description

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%.

Time Frame Day 1, day 22, day 43 and day 387.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 93 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1
1
(0.027 to 6)
0
(0 to 4)
Day 22 (N=85,86)
58
(46 to 68)
36
(26 to 47)
Day 43 (N=91,85)
98
(92 to 100)
94
(87 to 98)
Day 387 (N=84,77)
71
(61 to 81)
61
(49 to 72)
14.Secondary Outcome
Title Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain
Hide Description

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%.

Time Frame Day 1, day 22, day 43 and day 387.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 98 101
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1
0
(0 to 4)
0
(0 to 4)
Day 22 (N=96,98)
43
(33 to 53)
41
(31 to 51)
Day 43 (N=94,98)
98
(93 to 100)
86
(77 to 92)
Day 387 (90,94)
44
(34 to 55)
22
(14 to 32)
15.Secondary Outcome
Title Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain
Hide Description

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%.

Time Frame Day 1, day 22, day 43 and day 387.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 103 109
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1
2
(0 to 7)
1
(0.023 to 5)
Day 22 (N=102,103)
54
(44 to 64)
37
(28 to 47)
Day 43 (N=102,105)
92
(85 to 97)
79
(70 to 86)
Day 387 (N=97,100)
29
(20 to 39)
17
(10 to 26)
16.Secondary Outcome
Title The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain
Hide Description

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%.

Time Frame Day 22, day 43 and day 387
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 84 86
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 22
58
(47 to 69)
36
(26 to 47)
Day 43 (N=84,85)
99
(94 to 100)
94
(87 to 98)
Day 387 (N=78,77)
73
(62 to 82)
61
(49 to 72)
17.Secondary Outcome
Title The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain
Hide Description

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%.

Time Frame Day 22, day 43 and day 387
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 95 98
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 22
43
(33 to 54)
41
(31 to 51)
Day 43 (N=93,98)
98
(92 to 100)
86
(77 to 92)
Day 387 (N=89,94)
45
(34 to 56)
22
(14 to 32)
18.Secondary Outcome
Title The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain
Hide Description

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%.

Time Frame Day 22, day 43 and day 387
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done the FAS.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 102 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 22 (N=102,103)
54
(44 to 64)
36
(27 to 46)
Day 43
92
(85 to 97)
79
(70 to 86)
Day 387 (N=97,100)
29
(20 to 39)
16
(9 to 25)
Time Frame Solicited local and systemic adverse events from day 1 to 7. Unsolicited AEs (other than SAEs) from day 1 to 387.
Adverse Event Reporting Description

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

 
Arm/Group Title High Dose Low Dose Total
Hide Arm/Group Description Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. Total of subjects in both high dose and low dose groups.
All-Cause Mortality
High Dose Low Dose Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
High Dose Low Dose Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/329 (2.43%)   11/329 (3.34%)   19/658 (2.89%) 
Gastrointestinal disorders       
FOOD POISONING * 1  1/329 (0.30%)  1/329 (0.30%)  2/658 (0.30%) 
Infections and infestations       
BRONCHOPNEUMONIA * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
CELLULITIS ORBITAL * 1  1/329 (0.30%)  0/329 (0.00%)  1/658 (0.15%) 
DENGUE FEVER * 1  1/329 (0.30%)  1/329 (0.30%)  2/658 (0.30%) 
GASTROENTERITIS * 1  2/329 (0.61%)  1/329 (0.30%)  3/658 (0.46%) 
INFLUENZA * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
PNEUMONIA * 1  2/329 (0.61%)  0/329 (0.00%)  2/658 (0.30%) 
PNEUMONIA INFLUENZAL * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
STREPTOCOCCAL SEPSIS * 1  1/329 (0.30%)  0/329 (0.00%)  1/658 (0.15%) 
UPPER RESPIRATORY TRACT INFECTION * 1  1/329 (0.30%)  0/329 (0.00%)  1/658 (0.15%) 
Injury, poisoning and procedural complications       
CLAVICLE FRACTURE * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
FEMUR FRACTURE * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
LACERATION * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
TIBIA FRACTURE * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
UPPER LIMB FRACTURE * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
Musculoskeletal and connective tissue disorders       
MYALGIA * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
Nervous system disorders       
CONVULSION * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
FEBRILE CONVULSION * 1  1/329 (0.30%)  0/329 (0.00%)  1/658 (0.15%) 
Respiratory, thoracic and mediastinal disorders       
APNOEIC ATTACK * 1  0/329 (0.00%)  1/329 (0.30%)  1/658 (0.15%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
High Dose Low Dose Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   263/329 (79.94%)   257/329 (78.12%)   520/658 (79.03%) 
Gastrointestinal disorders       
NAUSEA  1  25/329 (7.60%)  29/329 (8.81%)  54/658 (8.21%) 
General disorders       
FATIGUE  1  44/329 (13.37%)  50/329 (15.20%)  94/658 (14.29%) 
INJECTION SITE ERYTHEMA  1  60/329 (18.24%)  54/329 (16.41%)  114/658 (17.33%) 
INJECTION SITE HAEMORRHAGE  1  23/329 (6.99%)  19/329 (5.78%)  42/658 (6.38%) 
INJECTION SITE INDURATION  1  45/329 (13.68%)  39/329 (11.85%)  84/658 (12.77%) 
INJECTION SITE PAIN  1  209/329 (63.53%)  213/329 (64.74%)  422/658 (64.13%) 
MALAISE  1  40/329 (12.16%)  38/329 (11.55%)  78/658 (11.85%) 
PYREXIA  1  48/329 (14.59%)  32/329 (9.73%)  80/658 (12.16%) 
Infections and infestations       
NASOPHARYNGITIS  1  18/329 (5.47%)  16/329 (4.86%)  34/658 (5.17%) 
UPPER RESPIRATORY TRACT INFECTION  1  55/329 (16.72%)  58/329 (17.63%)  113/658 (17.17%) 
Metabolism and nutrition disorders       
DECREASED APPETITE  1  22/329 (6.69%)  21/329 (6.38%)  43/658 (6.53%) 
Musculoskeletal and connective tissue disorders       
ARTHRALGIA  1  23/329 (6.99%)  20/329 (6.08%)  43/658 (6.53%) 
MYALGIA  1  50/329 (15.20%)  45/329 (13.68%)  95/658 (14.44%) 
Nervous system disorders       
HEADACHE  1  40/329 (12.16%)  48/329 (14.59%)  88/658 (13.37%) 
SOMNOLENCE  1  42/329 (12.77%)  41/329 (12.46%)  83/658 (12.61%) 
Psychiatric disorders       
EATING DISORDER  1  29/329 (8.81%)  20/329 (6.08%)  49/658 (7.45%) 
IRRITABILITY  1  49/329 (14.89%)  47/329 (14.29%)  96/658 (14.59%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Posting Director
Organization: Novartis Vaccines
Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT01776554     History of Changes
Other Study ID Numbers: V89_11
First Submitted: January 20, 2013
First Posted: January 28, 2013
Results First Submitted: April 2, 2015
Results First Posted: April 20, 2015
Last Update Posted: January 16, 2019