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    Clinical Trial Results:
    Safety and immunogenicity of an intramuscular, inactivated, split-virion, pandemic influenza A/H5N1 vaccine in adults and the elderly

    Summary
    EudraCT number
    2006-000477-29
    Trial protocol
    BE   GB  
    Global end of trial date
    23 Dec 2008

    Results information
    Results version number
    v1(current)
    This version publication date
    05 Feb 2016
    First version publication date
    03 Dec 2014
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GPA02
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00415129
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Sanofi Pasteur SA
    Sponsor organisation address
    1541, Avenue Marcel Mérieux, Marcy L’Etoile, France, 69280
    Public contact
    Director, Clinical Development, Sanofi Pasteur SA, 1 57 09 57 61 25, sanjay.gurunathan@sanofipasteur.com
    Scientific contact
    Director, Clinical Development, Sanofi Pasteur SA, 1 57 09 57 61 25, sanjay.gurunathan@sanofipasteur.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Sep 2009
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Dec 2008
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • To describe the injection site reactions and systemic safety profile during the 21 days after each of two primary series and one booster (as applicable) intramuscular (IM) injections in two age groups: subjects aged 18 to 60 years (adults) or >60 years (elderly). • To describe the immune response 21 days after each of two primary series IM injections in two age groups: subjects aged 18 to 60 years and >60 years. • To describe the antibody persistence at month 6 (all subjects) and months 15 and 22 (subsets of subjects) after the first vaccination in two age groups: subjects aged 18 to 60 years or >60 years. • To describe the immune response 21 days after a booster vaccination administered at either 6 months (A/Vietnam booster) or 7 and 21 days after a booster vaccination administered at 22 months (A/Indonesia booster) after the first vaccination in two age groups: subjects aged 18 to 60 years or >60 years. • To describe any serious adverse event during the trial.
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment were also available on site in case of any immediate allergic reactions.
    Background therapy
    Not applicable
    Evidence for comparator
    -
    Actual start date of recruitment
    16 May 2006
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 150
    Country: Number of subjects enrolled
    Belgium: 450
    Worldwide total number of subjects
    600
    EEA total number of subjects
    600
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    390
    From 65 to 84 years
    210
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Study subjects were enrolled from 16 May 2006 to 12 June 2006 in 3 clinical centers in Belgium and 1 in the United Kingdom.

    Pre-assignment
    Screening details
    A total of 600 subjects who met all inclusion criteria and none of the exclusion criteria were enrolled and vaccinated.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded
    Blinding implementation details
    Not applicable

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    18-60 years 30μg+Adjuvant
    Arm description
    Subjects aged 18-60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 30μg anti-hemagglutination [HA]) with aluminum hydroxide adjuvant 21 days apart as primary series and a booster vaccination at either 6 months (A/Vietnam 7.5μg HA) or 22 months (A/Indonesia 30μg HA plus adjuvant) after the first vaccination or no booster vaccination.
    Arm type
    Experimental

    Investigational medicinal product name
    A/H5N1 inactivated, adjuvanted, split virion influenza vaccine made in embryonated eggs
    Investigational medicinal product code
    402
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, two doses 21 days apart as primary series and booster at either 6 or 22 months after first vaccination or no booster vaccination.

    Arm title
    18-60 years 7.5μg
    Arm description
    Subjects aged 18-60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 7.5μg anti-hemagglutination [HA] ) without adjuvant 21 days apart as primary series and a booster vaccination at 6 months (A/Vietnam 7.5μg HA) after the first vaccination or no booster at 22 months.
    Arm type
    Experimental

    Investigational medicinal product name
    A/H5N1 inactivated, adjuvanted, split virion influenza vaccine made in embryonated eggs
    Investigational medicinal product code
    402
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, two doses 21 days apart as primary series and booster at either 6 or 22 months after first vaccination or no booster vaccination.

    Arm title
    >60 years 30μg+Adjuvant
    Arm description
    Subjects aged >60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 30μg anti-hemagglutination [HA]) with aluminum hydroxide adjuvant 21 days apart as primary series and a booster vaccination at either 6 months (A/Vietnam 7.5μg HA) or 22 months (A/Indonesia 30μg HA plus adjuvant) after the first vaccination or no booster vaccination.
    Arm type
    Experimental

    Investigational medicinal product name
    A/H5N1 inactivated, adjuvanted, split virion influenza vaccine made in embryonated eggs
    Investigational medicinal product code
    402
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, two doses 21 days apart as primary series and booster at either 6 or 22 months after first vaccination or no booster vaccination.

    Arm title
    >60 years 7.5μg
    Arm description
    Subjects aged >60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 7.5μg anti-hemagglutination [HA]) without adjuvant 21 days apart as primary series and a booster vaccination at 6 months (A/Vietnam 7.5μg HA) after the first vaccination or no booster at 22 months.
    Arm type
    Experimental

    Investigational medicinal product name
    A/H5N1 inactivated, adjuvanted, split virion influenza vaccine made in embryonated eggs
    Investigational medicinal product code
    402
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, two doses 21 days apart as primary series and booster at either 6 or 22 months after first vaccination or no booster vaccination.

    Number of subjects in period 1
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Started
    151
    149
    150
    150
    Completed
    148
    148
    150
    149
    Not completed
    3
    1
    0
    1
         Protocol deviation
             1
             1
             -
             1
         Adverse event, serious fatal
             1
             -
             -
             -
         Adverse event, non-fatal
             1
             -
             -
             -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    18-60 years 30μg+Adjuvant
    Reporting group description
    Subjects aged 18-60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 30μg anti-hemagglutination [HA]) with aluminum hydroxide adjuvant 21 days apart as primary series and a booster vaccination at either 6 months (A/Vietnam 7.5μg HA) or 22 months (A/Indonesia 30μg HA plus adjuvant) after the first vaccination or no booster vaccination.

    Reporting group title
    18-60 years 7.5μg
    Reporting group description
    Subjects aged 18-60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 7.5μg anti-hemagglutination [HA] ) without adjuvant 21 days apart as primary series and a booster vaccination at 6 months (A/Vietnam 7.5μg HA) after the first vaccination or no booster at 22 months.

    Reporting group title
    >60 years 30μg+Adjuvant
    Reporting group description
    Subjects aged >60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 30μg anti-hemagglutination [HA]) with aluminum hydroxide adjuvant 21 days apart as primary series and a booster vaccination at either 6 months (A/Vietnam 7.5μg HA) or 22 months (A/Indonesia 30μg HA plus adjuvant) after the first vaccination or no booster vaccination.

    Reporting group title
    >60 years 7.5μg
    Reporting group description
    Subjects aged >60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 7.5μg anti-hemagglutination [HA]) without adjuvant 21 days apart as primary series and a booster vaccination at 6 months (A/Vietnam 7.5μg HA) after the first vaccination or no booster at 22 months.

    Reporting group values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg Total
    Number of subjects
    151 149 150 150 600
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0
        Children (2-11 years)
    0 0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0 0
        Adults (18-64 years)
    151 149 44 46 390
        From 65-84 years
    0 0 106 104 210
        85 years and over
    0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    37.3 ± 13.7 37.6 ± 13.7 68.3 ± 5.1 68.3 ± 5.3 -
    Gender categorical
    Units: Subjects
        Female
    82 95 71 75 323
        Male
    69 54 79 75 277

    End points

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    End points reporting groups
    Reporting group title
    18-60 years 30μg+Adjuvant
    Reporting group description
    Subjects aged 18-60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 30μg anti-hemagglutination [HA]) with aluminum hydroxide adjuvant 21 days apart as primary series and a booster vaccination at either 6 months (A/Vietnam 7.5μg HA) or 22 months (A/Indonesia 30μg HA plus adjuvant) after the first vaccination or no booster vaccination.

    Reporting group title
    18-60 years 7.5μg
    Reporting group description
    Subjects aged 18-60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 7.5μg anti-hemagglutination [HA] ) without adjuvant 21 days apart as primary series and a booster vaccination at 6 months (A/Vietnam 7.5μg HA) after the first vaccination or no booster at 22 months.

    Reporting group title
    >60 years 30μg+Adjuvant
    Reporting group description
    Subjects aged >60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 30μg anti-hemagglutination [HA]) with aluminum hydroxide adjuvant 21 days apart as primary series and a booster vaccination at either 6 months (A/Vietnam 7.5μg HA) or 22 months (A/Indonesia 30μg HA plus adjuvant) after the first vaccination or no booster vaccination.

    Reporting group title
    >60 years 7.5μg
    Reporting group description
    Subjects aged >60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 7.5μg anti-hemagglutination [HA]) without adjuvant 21 days apart as primary series and a booster vaccination at 6 months (A/Vietnam 7.5μg HA) after the first vaccination or no booster at 22 months.

    Primary: Summary of Geometric Mean Titers (GMTs) of Antibody Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Summary of Geometric Mean Titers (GMTs) of Antibody Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [1]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using horse erythrocytes method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    146
    149
    Units: Titers
    geometric mean (confidence interval 95%)
        Day 0
    4.14 (3.98 to 4.31)
    4.15 (3.97 to 4.34)
    5.51 (4.84 to 6.29)
    6.17 (5.2 to 7.32)
        Day 21
    8.61 (6.92 to 10.72)
    8.76 (7 to 10.97)
    18.7 (14 to 25)
    16.6 (12.6 to 21.7)
        Day 42
    19.4 (15.1 to 24.9)
    13 (10.3 to 16.4)
    28.9 (22.1 to 37.9)
    21.4 (16.5 to 27.8)
    No statistical analyses for this end point

    Primary: Summary of Geometric Mean Titers Ratios (GMTR) Antibody Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Summary of Geometric Mean Titers Ratios (GMTR) Antibody Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [2]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using horse erythrocytes method. Geometric mean titer ratio is the geometric mean of the individual post-vaccination/pre-vaccination titer of antibodies to the influenza virus antigens.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    146
    149
    Units: Titer ratios
    geometric mean (confidence interval 95%)
        Day 21/Day 0
    2.08 (1.69 to 2.56)
    2.11 (1.7 to 2.62)
    3.36 (2.64 to 4.29)
    2.71 (2.2 to 3.35)
        Day 42/Day 21
    2.26 (1.86 to 2.75)
    1.48 (1.29 to 1.69)
    1.54 (1.32 to 1.79)
    1.33 (1.18 to 1.48)
        Day 42/Day 0
    4.68 (3.66 to 5.97)
    3.13 (2.49 to 3.93)
    5.21 (4.12 to 6.59)
    3.6 (2.91 to 4.46)
    No statistical analyses for this end point

    Primary: Percentage of Subjects with Antibody Titers <8 (1/dil) Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects with Antibody Titers <8 (1/dil) Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [3]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using horse erythrocytes method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    146
    149
    Units: Percentage of subjects
    number (not applicable)
        Day 0
    98
    98
    84.7
    83.9
        Day 21
    72.2
    72.5
    50.7
    50
        Day 42
    43.2
    54.1
    34
    38.9
    No statistical analyses for this end point

    Primary: Percentage of Subjects Achieving Seroconversion or Significant Increase in Antibody Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects Achieving Seroconversion or Significant Increase in Antibody Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [4]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using horse erythrocytes method. Seroconversion (for subjects with a titer <10 [turkey] or <8 [horse] [1/dil] on Day 0: post-injection titer ≥40 [turkey] or ≥32 [horse] [1/dil]), or significant increase (for subjects with a titer ≥10 [turkey] or ≥8 [horse] [1/dil]: ≥four-fold increase of the titer) at Day 21 and Day 42.
    End point type
    Primary
    End point timeframe
    Day 21 and Day 42 post-vaccination
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    146
    149
    Units: Percentage of subjects
    number (not applicable)
        Day 21
    20.5
    21.5
    34.9
    26.2
        Day 42
    45.9
    33.1
    51.7
    36.5
    No statistical analyses for this end point

    Primary: Summary of Geometric Mean Titers (GMTs) of Antibody Assayed by HI Turkey Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Summary of Geometric Mean Titers (GMTs) of Antibody Assayed by HI Turkey Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [5]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using turkey erythrocytes method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    43
    42
    38
    36
    Units: Titers
    geometric mean (confidence interval 95%)
        Day 0
    5.04 (4.96 to 5.12)
    5 (5 to 5)
    6.41 (5.02 to 8.18)
    8.94 (5.87 to 13.61)
        Day 21
    6.48 (4.88 to 8.61)
    8.11 (5.84 to 11.28)
    11.72 (7.33 to 18.76)
    12.94 (7.88 to 21.23)
        Day 42
    9.37 (6.73 to 13.05)
    9.82 (7.09 to 13.62)
    13.79 (8.55 to 22.25)
    12.15 (7.45 to 19.83)
    No statistical analyses for this end point

    Primary: Summary of Geometric Mean Titers Ratios (GMTR) Antibody Assayed by HI Turkey Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

    Close Top of page
    End point title
    Summary of Geometric Mean Titers Ratios (GMTR) Antibody Assayed by HI Turkey Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [6]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using turkey erythrocytes method. Geometric mean titer ratio is the geometric mean of the individual post-vaccination/pre-vaccination titer of antibodies to the influenza virus antigens.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    43
    42
    38
    36
    Units: Titer ratios
    geometric mean (confidence interval 95%)
        Day 21/Day 0
    1.286 (0.981 to 1.684)
    1.62 (1.17 to 2.26)
    1.83 (1.29 to 2.6)
    1.45 (1.14 to 1.84)
        Day 42/Day 21
    1.44 (1.15 to 1.79)
    1.211 (0.987 to 1.486)
    1.177 (0.981 to 1.411)
    1.05 (0.938 to 1.175)
        Day 42/Day 0
    1.86 (1.35 to 2.56)
    1.96 (1.42 to 2.72)
    2.15 (1.53 to 3.02)
    1.49 (1.1 to 2.03)
    No statistical analyses for this end point

    Primary: Percentage of Subjects with Antibody titers <10 (1/dil) Assayed by HI Turkey Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects with Antibody titers <10 (1/dil) Assayed by HI Turkey Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [7]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using turkey erythrocytes method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    43
    42
    38
    36
    Units: Percentage of subjects
    number (not applicable)
        Day 0
    100
    100
    84.2
    77.8
        Day 21
    88.4
    81
    68.4
    61.1
        Day 42
    61.9
    66.7
    55.3
    62.9
    No statistical analyses for this end point

    Primary: Percentage of Subjects Achieving Seroconversion or Significant Increase in Antibody Assayed by HI Turkey Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

    Close Top of page
    End point title
    Percentage of Subjects Achieving Seroconversion or Significant Increase in Antibody Assayed by HI Turkey Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [8]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using turkey erythrocytes method. Seroconversion (for subjects with a titer <10 [turkey] or <8 [horse] [1/dil] on Day 0: post-injection titer ≥40 [turkey] or ≥32 [horse] [1/dil]), or significant increase (for subjects with a titer ≥10 [turkey] or ≥8 [horse] [1/dil]: ≥four-fold increase of the titer) at Day 21 and Day 42.
    End point type
    Primary
    End point timeframe
    Day 21 and Day 42 post-vaccination
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    43
    42
    38
    36
    Units: Percentage of subjects
    number (not applicable)
        Day 21
    4.7
    14.3
    15.8
    11.1
        Day 42
    7.1
    19
    15.8
    11.4
    No statistical analyses for this end point

    Primary: Summary of Geometric Mean Titers (GMTs) of Antibody Assayed Seroneutralization Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Summary of Geometric Mean Titers (GMTs) of Antibody Assayed Seroneutralization Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [9]
    End point description
    Influenza vaccine antibodies were assessed using the seroneutralization method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    150
    150
    Units: Titers
    geometric mean (confidence interval 95%)
        Day 0
    10.09 (9.99 to 10.2)
    10.22 (9.89 to 10.55)
    10.9 (10.3 to 11.6)
    11.8 (10.8 to 13)
        Day 21
    12.8 (11.5 to 14.2)
    12.5 (11.3 to 13.9)
    20 (16.7 to 24)
    16.6 (14.2 to 19.5)
        Day 42
    20.7 (17.9 to 23.9)
    15.6 (13.8 to 17.7)
    23.4 (19.6 to 27.8)
    17.6 (15 to 20.6)
    No statistical analyses for this end point

    Primary: Summary of Geometric Mean Titers Ratios (GMTR) Antibody Assayed by Seroneutralization Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Summary of Geometric Mean Titers Ratios (GMTR) Antibody Assayed by Seroneutralization Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [10]
    End point description
    Influenza vaccine antibodies were assessed using the seroneutralization method. Geometric mean titer ratio is the geometric mean of the individual post-vaccination/pre-vaccination titer of antibodies to the influenza virus antigens.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    150
    150
    Units: Titer ratios
    geometric mean (confidence interval 95%)
        Day 21/Day 0
    1.27 (1.14 to 1.4)
    1.23 (1.11 to 1.35)
    1.83 (1.54 to 2.17)
    1.41 (1.24 to 1.59)
        Day 42/Day 21
    1.61 (1.42 to 1.83)
    1.25 (1.15 to 1.35)
    1.17 (1.08 to 1.27)
    1.08 (1.03 to 1.13)
        Day 42/Day 0
    2.05 (1.78 to 2.37)
    1.53 (1.35 to 1.73)
    2.13 (1.81 to 2.52)
    1.51 (1.33 to 1.72)
    No statistical analyses for this end point

    Primary: Percentage of Subjects with Antibody titers <20 (1/dil) Assayed by Seroneutralization Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects with Antibody titers <20 (1/dil) Assayed by Seroneutralization Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [11]
    End point description
    Influenza vaccine antibodies were assessed using the seroneutralization method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    150
    150
    Units: Percentage of subjects
    number (not applicable)
        Day 0
    100
    98.7
    96.7
    92.7
        Day 21
    86.8
    89.9
    69.3
    78.7
        Day 42
    61.2
    77
    57.3
    73.8
    No statistical analyses for this end point

    Primary: Percentage of Subjects with 2- and 4-fold Increase in Antibody titers Assayed by Seroneutralization Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects with 2- and 4-fold Increase in Antibody titers Assayed by Seroneutralization Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [12]
    End point description
    Influenza vaccine antibodies were assessed using the seroneutralization method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    150
    150
    Units: Percentage of subjects
    number (not applicable)
        2-fold increase from Day 0 (Day 21/Day 0)
    13.2
    9.4
    28.7
    15.3
        2-fold increase from Day 0 (Day 42/Day 0)
    38.8
    22.3
    40
    20.8
        4-fold increase from Day 0 (Day 21/Day 0)
    8.6
    5.4
    19.3
    10
        4-fold increase from Day 0 (Day 42/Day 0)
    27.2
    14.2
    21.3
    11.4
    No statistical analyses for this end point

    Primary: Summary of Geometric Mean Titers of Antibody (Ab) Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain In Subjects with Undetectable Ab After Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Summary of Geometric Mean Titers of Antibody (Ab) Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain In Subjects with Undetectable Ab After Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [13]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using horse erythrocytes method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    148
    146
    123
    125
    Units: Titers
    geometric mean (confidence interval 95%)
        Day 0
    4 (4 to 4)
    4 (4 to 4)
    4.03 (4 to 4.07)
    4 (4 to 4)
        Day 21
    8.06 (6.54 to 9.92)
    8.27 (6.64 to 10.3)
    12.14 (9.27 to 15.89)
    10.64 (8.37 to 13.53)
        Day 42
    18.3 (14.3 to 23.5)
    12.48 (9.9 to 15.73)
    20 (15.4 to 26)
    14.7 (11.6 to 18.7)
    No statistical analyses for this end point

    Primary: Summary of Geometric Mean Titers Ratios Antibody (Ab) Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain In Subjects with Undetectable Ab After Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Summary of Geometric Mean Titers Ratios Antibody (Ab) Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain In Subjects with Undetectable Ab After Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [14]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using horse erythrocytes method. Geometric mean titer ratio is the geometric mean of the individual post-vaccination/pre-vaccination titer of antibodies to the influenza virus antigens.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    148
    146
    123
    125
    Units: Titer ratios
    geometric mean (confidence interval 95%)
        Day 21/Day 0
    2.01 (1.64 to 2.48)
    2.07 (1.66 to 2.57)
    3.01 (2.3 to 3.93)
    2.66 (2.09 to 3.38)
        Day 42/Day 21
    2.29 (1.88 to 2.79)
    1.5 (1.31 to 1.72)
    1.64 (1.37 to 1.95)
    1.38 (1.21 to 1.58)
        Day 42/Day 0
    4.58 (3.58 to 5.87)
    3.12 (2.47 to 3.93)
    4.96 (3.82 to 6.45)
    3.68 (2.89 to 4.68)
    No statistical analyses for this end point

    Primary: Percentage of Subjects with Undetectable Antibody Achieving Antibody titers <8 (1/dil) Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain After Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects with Undetectable Antibody Achieving Antibody titers <8 (1/dil) Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain After Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [15]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using horse erythrocytes method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    148
    146
    123
    125
    Units: Percentage of subjects
    number (not applicable)
        Day 0
    100
    100
    100
    100
        Day 21
    73.6
    74
    60.2
    59.2
        Day 42
    44.1
    55.2
    40.3
    45.6
    No statistical analyses for this end point

    Primary: Percentage of Subjects with Undetectable Antibody (Ab) Achieving Seroconversion/Significant Increase in Ab Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain After Inactivated Split-Virion, Influenza Vaccine

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    End point title
    Percentage of Subjects with Undetectable Antibody (Ab) Achieving Seroconversion/Significant Increase in Ab Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain After Inactivated Split-Virion, Influenza Vaccine [16]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using horse erythrocytes method. Seroconversion (for subjects with a titer <10 [turkey] or <8 [horse] [1/dil] on Day 0: post-injection titer ≥40 [turkey] or ≥32 [horse] [1/dil]), or significant increase (for subjects with a titer ≥10 [turkey] or ≥8 [horse] [1/dil]: ≥four-fold increase of the titer) at Day 21 and Day 42.
    End point type
    Primary
    End point timeframe
    Day 21 and Day 42 post-vaccination
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    148
    146
    123
    125
    Units: Percentage of subjects
    number (not applicable)
        Day 21
    18.9
    20.5
    31.7
    24.8
        Day 42
    44.8
    32.4
    49.2
    36
    No statistical analyses for this end point

    Primary: Summary of Geometric Mean Titers (GMTs) of Neuraminidase Assay - Anti-neuraminidase Antibody Against A/Vietnam/1194/2004 (H5N1)_RG14 Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Summary of Geometric Mean Titers (GMTs) of Neuraminidase Assay - Anti-neuraminidase Antibody Against A/Vietnam/1194/2004 (H5N1)_RG14 Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [17]
    End point description
    Influenza vaccine antibodies were assessed using the neuraminidase assay.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 42 post-vaccination
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    21
    21
    16
    15
    Units: Titers
    geometric mean (confidence interval 95%)
        Day 0
    6.51 (4.45 to 9.52)
    6.3 (4.64 to 8.54)
    7.97 (5.15 to 12.33)
    11.05 (5.49 to 22.26)
        Day 42
    7.33 (4.58 to 11.73)
    7.66 (5.24 to 11.19)
    11.77 (6.49 to 21.32)
    13.77 (6.3 to 30.12)
    No statistical analyses for this end point

    Primary: Summary of Geometric Mean Titers Assayed by HI Horse Erythrocyte Method of Neuraminidase Assay - Anti-neuraminidase Antibody Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain After Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Summary of Geometric Mean Titers Assayed by HI Horse Erythrocyte Method of Neuraminidase Assay - Anti-neuraminidase Antibody Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain After Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [18]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using horse erythrocytes method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21, Day 42, and Day 180 post-vaccination
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    150
    149
    Units: Titers
    geometric mean (confidence interval 95%)
        Day 0
    4.14 (3.98 to 4.31)
    4.15 (3.97 to 4.34)
    5.51 (4.84 to 6.29)
    6.17 (5.2 to 7.32)
        Day 21
    8.61 (6.92 to 10.72)
    8.76 (7 to 10.97)
    18.7 (14 to 25)
    16.6 (12.6 to 21.7)
        Day 42
    19.4 (15.1 to 24.9)
    13 (10.3 to 16.4)
    28.9 (22.1 to 37.9)
    21.4 (16.5 to 27.8)
        Day 180
    5.99 (5.33 to 6.73)
    5.43 (4.85 to 6.08)
    9.42 (7.78 to 11.42)
    7.63 (6.41 to 9.08)
    No statistical analyses for this end point

    Primary: Percentage of Subjects with Antibody titers <32 (1/dil) Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects with Antibody titers <32 (1/dil) Assayed by HI Horse Erythrocytes Method Against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [19]
    End point description
    Influenza vaccine antibodies were assessed using the hemagglutination inhibition using horse erythrocytes method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21, Day 42, and Day 180 post-vaccination
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    150
    149
    Units: Percentage of subjects
    number (not applicable)
        Day 0
    1.3
    1.3
    6
    12.8
        Day 21
    20.5
    22.1
    42.5
    36.7
        Day 42
    45.9
    33.8
    57.1
    45.6
        Day 180
    6.2
    6.2
    18.9
    14.4
    No statistical analyses for this end point

    Primary: Summary of Geometric Mean Titers (GMTs) Assayed by Seroneutralization Method – Neutralizing Antibody Against A/Vietnam (H5N1) Strains Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Summary of Geometric Mean Titers (GMTs) Assayed by Seroneutralization Method – Neutralizing Antibody Against A/Vietnam (H5N1) Strains Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [20]
    End point description
    Influenza vaccine antibodies were assessed using the seroneutralization method. [Day 0 to Day 42]: Neutralizing Antibody (1/dil) against A/Vietnam/1194/2004/NIBRG-14 (H5N1) Strain and [Day 180 to Day 201]: Neutralizing Antibody (1/dil) against rg A/Vietnam/1203/2004 (H5N1) Strain.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21, Day 42, and Day 180 post-vaccination
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    150
    150
    Units: Titers
    geometric mean (confidence interval 95%)
        Day 0
    10.09 (9.99 to 10.2)
    10.22 (9.89 to 10.55)
    10.9 (10.3 to 11.6)
    11.8 (10.8 to 13)
        Day 21
    12.8 (11.5 to 14.2)
    12.5 (11.3 to 13.9)
    20 (16.7 to 24)
    16.6 (14.2 to 19.5)
        Day 42
    20.7 (17.9 to 23.9)
    15.6 (13.8 to 17.7)
    23.4 (19.6 to 27.8)
    17.6 (15 to 20.6)
        Day 180
    12.4 (11.3 to 13.5)
    12.2 (11 to 13.5)
    17.9 (15 to 21.4)
    14.7 (12.5 to 17.3)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Solicited Injection-site or Systemic Reactions within 7 Days After Each Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects Reporting Solicited Injection-site or Systemic Reactions within 7 Days After Each Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [21]
    End point description
    Solicited injection site: Pain, Erythema, Swelling, Induration and Ecchymosis. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering.
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 7 post- each vaccination
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    150
    150
    Units: Percentage of subjects
    number (not applicable)
        Injection site Pain (Post-injection 1)
    49
    26.8
    17.3
    4.7
        Injection site Erythema (Post-injection 1)
    13.9
    10.7
    4.7
    5.3
        Injection site Swelling (Post-injection 1)
    11.3
    4
    0.7
    1.3
        Injection site Induration (Post-injection 1)
    14.6
    8.1
    3.3
    4.7
        Injection site Ecchymosis (Post-injection 1)
    4.6
    6.7
    1.3
    4.7
        Fever (Post-injection 1)
    2
    0.7
    1.3
    2
        Headache (Post-injection 1)
    29.1
    29.5
    12.7
    15.3
        Malaise (Post-injection 1)
    11.9
    16.1
    8.7
    10.7
        Myalgia (Post-injection 1)
    17.2
    16.1
    10
    11.3
        Shivering (Post-injection 1)
    7.3
    6
    4.7
    4
        Injection site Pain (Post-injection 2)
    31.1
    18.8
    19.3
    9.4
        Injection site Erythema (Post-injection 2)
    12.8
    10.1
    4
    4.7
        Injection site Swelling (Post-injection 2)
    8.8
    1.3
    1.3
    1.3
        Injection site Induration (Post-injection 2)
    5.4
    7.4
    2
    1.3
        Injection site Ecchymosis (Post-injection 2)
    6.1
    2
    3.3
    1.3
        Fever (Post-injection 2)
    2
    1.3
    5.3
    2.7
        Headache (Post-injection 2)
    18.9
    22.1
    11.3
    12.8
        Malaise (Post-injection 2)
    10.8
    6.7
    6.7
    8.1
        Myalgia (Post-injection 2)
    12.2
    9.4
    9.3
    10.1
        Shivering (Post-injection 2)
    0.7
    2.7
    2.7
    2.7
    No statistical analyses for this end point

    Primary: Percentage of Subjects with at Least One Reaction Within 3 Days after Any Vaccine Injection Listed in the EMEA Note for Guidance Strains Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects with at Least One Reaction Within 3 Days after Any Vaccine Injection Listed in the EMEA Note for Guidance Strains Following Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [22]
    End point description
    Solicited injection site: Induration and Ecchymosis. Solicited systemic reactions: Fever, Malaise, and Shivering.
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 3 post-each vaccination
    Notes
    [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    151
    149
    150
    150
    Units: Percentage of subjects
    number (not applicable)
        Inj. site Induration >5cm for >3 days
    0
    0
    0
    0
        Inj. site Induration >5cm for >3 days; Post-inj. 1
    0
    0
    0
    0
        Inj. site Induration >5cm for >3 days; Post-inj. 2
    0
    0
    0
    0
        Inj. site Ecchymosis (Hemorrhage)
    9.9
    8.1
    4.7
    5.3
        Inj. site Ecchymosis (Hemorrhage); Post-inj. 1
    4.6
    6.7
    1.3
    4
        Inj. site Ecchymosis (Hemorrhage); Post-inj. 2
    6
    1.3
    3.3
    1.3
        Fever (rectal temp. >38°C) for ≥24 hr
    2.6
    0.7
    3.3
    0.7
        Fever (rectal temp. >38°C) for ≥24 hr; Post-inj. 1
    2
    0.7
    1.3
    0.7
        Fever (rectal temp. >38°C) for ≥24 hr; Post-inj. 2
    1.3
    0
    2.7
    0
        Malaise
    13.2
    16.1
    10
    14.7
        Malaise; Post-inj. 1
    8.6
    13.4
    6.7
    9.3
        Malaise; Post-inj. 2
    5.3
    4
    4.7
    6.7
        Shivering
    5.3
    7.4
    5.3
    4
        Shivering; Post-inj. 1
    5.3
    6
    4
    2.7
        Shivering; Post-inj. 2
    0.7
    2
    2
    2
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Solicited Injection-site or Systemic Reactions Within 7 Days after Clade 1 A/Vietnam Booster Vaccine Injection Following Primary Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects Reporting Solicited Injection-site or Systemic Reactions Within 7 Days after Clade 1 A/Vietnam Booster Vaccine Injection Following Primary Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [23]
    End point description
    Solicited injection site: Pain, Erythema, Swelling, Induration and Ecchymosis. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering.
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 7 post-vaccination
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    38
    39
    41
    36
    Units: Percentage of subjects
    number (not applicable)
        Injection site Pain
    28.9
    20.5
    7.3
    8.3
        Injection site Erythema
    13.2
    12.8
    0
    2.8
        Injection site Swelling
    2.6
    0
    0
    5.6
        Injection site Induration
    2.6
    7.7
    0
    0
        Injection site Ecchymosis
    0
    0
    2.4
    0
        Fever
    2.6
    0
    2.4
    2.8
        Headache
    18.4
    17.9
    9.8
    13.9
        Malaise
    7.9
    5.1
    2.4
    2.8
        Myalgia
    7.9
    5.1
    4.9
    5.6
        Shivering
    5.3
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects with at least one Reaction within 3 Days after the Clade 1 A/Vietnam Booster Vaccine Injection Listed in the EMEA Note for Guidance Following Primary Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine

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    End point title
    Percentage of Subjects with at least one Reaction within 3 Days after the Clade 1 A/Vietnam Booster Vaccine Injection Listed in the EMEA Note for Guidance Following Primary Vaccination with Inactivated Split-Virion, Pandemic Influenza Vaccine [24]
    End point description
    Solicited injection site: Induration and Ecchymosis. Solicited systemic reactions: Fever, Malaise, and Shivering.
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 3 post-vaccination
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    18-60 years 30μg+Adjuvant 18-60 years 7.5μg >60 years 30μg+Adjuvant >60 years 7.5μg
    Number of subjects analysed
    38
    39
    41
    36
    Units: Percentage of subjects
    number (not applicable)
        Injection site Induration >5cm for >3 days
    0
    0
    0
    0
        Injection site Ecchymosis (Hemorrhage)
    0
    0
    2.4
    0
        Fever (rectal temperature >38°C) ≥24 hr
    2.6
    0
    2.4
    2.8
        Malaise
    5.3
    2.6
    2.4
    2.8
        Shivering (Chills)
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse event data were collected from Day 0 (post vaccination) up to Day 7 post vaccination.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    7.1
    Reporting groups
    Reporting group title
    18-60 years 30μg+Ad
    Reporting group description
    Subjects aged 18-60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 30μg anti-hemagglutination [HA]) with aluminum hydroxide adjuvant 21 days apart as primary series and a booster vaccination at either 6 months (A/Vietnam 7.5μg HA) or 22 months (A/Indonesia 30μg HA plus adjuvant) after the first vaccination or no booster vaccination.

    Reporting group title
    18-60 years 7.5μg
    Reporting group description
    Subjects aged 18-60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 7.5μg anti-hemagglutination [HA] ) without adjuvant 21 days apart as primary series and a booster vaccination at 6 months (A/Vietnam 7.5μg HA) after the first vaccination or no booster at 22 months.

    Reporting group title
    >60 years 30μg+Ad
    Reporting group description
    Subjects aged >60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 30μg anti-hemagglutination [HA]) with aluminum hydroxide adjuvant 21 days apart as primary series and a booster vaccination at either 6 months (A/Vietnam 7.5μg HA) or 22 months (A/Indonesia 30μg HA plus adjuvant) after the first vaccination or no booster vaccination.

    Reporting group title
    >60 years 7.5μg
    Reporting group description
    Subjects aged >60 years of age who received two doses of A/H5N1 inactivated, split-virion influenza virus (A/Vietnam 7.5μg anti-hemagglutination [HA] ) without adjuvant 21 days apart as primary series and a booster vaccination at 6 months (A/Vietnam 7.5μg HA) after the first vaccination or no booster at 22 months.

    Serious adverse events
    18-60 years 30μg+Ad 18-60 years 7.5μg >60 years 30μg+Ad >60 years 7.5μg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 151 (0.00%)
    0 / 149 (0.00%)
    0 / 150 (0.00%)
    0 / 150 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    18-60 years 30μg+Ad 18-60 years 7.5μg >60 years 30μg+Ad >60 years 7.5μg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    74 / 151 (49.01%)
    44 / 149 (29.53%)
    29 / 150 (19.33%)
    23 / 150 (15.33%)
    Nervous system disorders
    Headache
    alternative assessment type: Systematic
         subjects affected / exposed
    44 / 151 (29.14%)
    44 / 149 (29.53%)
    19 / 150 (12.67%)
    23 / 150 (15.33%)
         occurrences all number
    44
    44
    19
    23
    General disorders and administration site conditions
    Injection site pain
    alternative assessment type: Systematic
         subjects affected / exposed [1]
    74 / 151 (49.01%)
    40 / 149 (26.85%)
    29 / 150 (19.33%)
    14 / 149 (9.40%)
         occurrences all number
    74
    40
    29
    14
    Injection site erythema
    alternative assessment type: Systematic
         subjects affected / exposed
    21 / 151 (13.91%)
    16 / 149 (10.74%)
    7 / 150 (4.67%)
    8 / 150 (5.33%)
         occurrences all number
    21
    16
    7
    8
    Injection site swelling
    alternative assessment type: Systematic
         subjects affected / exposed
    17 / 151 (11.26%)
    6 / 149 (4.03%)
    2 / 150 (1.33%)
    2 / 150 (1.33%)
         occurrences all number
    17
    6
    2
    2
    Injection site induration
    alternative assessment type: Systematic
         subjects affected / exposed
    22 / 151 (14.57%)
    12 / 149 (8.05%)
    5 / 150 (3.33%)
    7 / 150 (4.67%)
         occurrences all number
    22
    12
    5
    7
    Injection site ecchymosis
    alternative assessment type: Systematic
         subjects affected / exposed
    15 / 151 (9.93%)
    12 / 149 (8.05%)
    7 / 150 (4.67%)
    8 / 150 (5.33%)
         occurrences all number
    15
    12
    7
    8
    Fever
    alternative assessment type: Systematic
         subjects affected / exposed [2]
    3 / 148 (2.03%)
    2 / 149 (1.34%)
    8 / 150 (5.33%)
    4 / 149 (2.68%)
         occurrences all number
    3
    2
    8
    4
    Malaise
    alternative assessment type: Systematic
         subjects affected / exposed
    20 / 151 (13.25%)
    24 / 149 (16.11%)
    15 / 150 (10.00%)
    22 / 150 (14.67%)
         occurrences all number
    20
    24
    15
    22
    Shivering
    alternative assessment type: Systematic
         subjects affected / exposed
    11 / 151 (7.28%)
    11 / 149 (7.38%)
    8 / 150 (5.33%)
    6 / 150 (4.00%)
         occurrences all number
    11
    11
    8
    6
    Musculoskeletal and connective tissue disorders
    Myalgia
    alternative assessment type: Systematic
         subjects affected / exposed
    26 / 151 (17.22%)
    24 / 149 (16.11%)
    15 / 150 (10.00%)
    17 / 150 (11.33%)
         occurrences all number
    26
    24
    15
    17
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Feb 2006
    Clarification of the timing and type of booster; inclusion of additional subjects aged 18 to 60 years to receive two administrations of the new vaccine strain (Clade 2 A/Indonesia) in order to assess the priming immunogenicity response to this strain and the concomitant production other randomization lists for the Clade 2 A/Indonesia vaccinations and an increase of planned sample size for the analysis; Ethnicity and seasonal influenza vaccination history added to the CRF; Deletion of the Single Radial Hemolysis (SRH) analysis method.
    06 Sep 2006
    Modification of the timing of the 12-month (Clade 2 A/Indonesia) booster vaccination and the timing of the assessment for 12-month Antibody persistence.
    20 Apr 2007
    Determination of the timing of the Clade 2 A/Indonesia booster in a subset of subjects primed with the 30µgHA+aluminum hydroxide vaccine; Modification of the design of the study regarding the administration of the booster, and the additional subjects included at the time of the Clade 2 A/Indonesia booster; addition of an additional visit 7 days after the Clade 2 A/Indonesia booster for immunogenicity assessment and elimination of the CMI evaluation after booster with the A/Indonesia strain.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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