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    Clinical Trial Results:
    A phase I/II, double-blind, randomized, multicentre study to evaluate the safety and immunogenicity of new formulations of GlaxoSmithKline Biologicals’ DTPa-HBV-IPV/Hib vaccine when administered to healthy infants as a primary vaccination course at 2, 3 and 4 months of age.

    Summary
    EudraCT number
    		 2010-021569-58
    Trial protocol
    		 FI  
    Global end of trial date
    05 Jan 2012

    Results information
    Results version number
    		 v2(current)
    This version publication date
    16 Sep 2018
    First version publication date
    02 Jul 2015
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Minor corrections of the full study results.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    113948
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01248884
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Mar 2012
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Jan 2012
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Jan 2012
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that the immunogenicity of at least one DTPa-HBVIPV/Hib formulation is non-inferior to the licensed formulation in terms of seroprotection rates to diphtheria, tetanus, hepatitis B and PRP antigens and in terms of antibody geometric mean concentrations (GMCs) for pertussis antigens one month after the third dose of the primary vaccination.
    Protection of trial subjects
    As with all injectable vaccines, appropriate medical treatment was readily available in case of anaphylactic reactions following the administration of the vaccine. For this reason, the vaccine remained under medical supervision for 30 minutes after vaccination.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Dec 2010
    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
    Finland: 456
    Country: Number of subjects enrolled
    Dominican Republic: 265
    Worldwide total number of subjects
    721
    EEA total number of subjects
    456
    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)
    721
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 721 subjects were enrolled in the study.

    Pre-assignment
    Screening details
    		 During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    This study is a double-blind study in which the parent(s)/LAR(s) and investigators were unaware of the treatment administered. The laboratory in charge of the laboratory testing was blinded to the treatment, and codes were used to link the subject and study (without any link to the treatment attributed to the subject) to each sample.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK217744 Group 1
    Arm description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation A vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Prevenar 13
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 co-administered doses, intramuscular into right thigh

    Investigational medicinal product name
    GSK217744
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses, intramuscular into left thigh

    Arm title
    		 GSK217744 Group 2
    Arm description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation B vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Prevenar 13
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 co-administered doses, intramuscular into right thigh

    Investigational medicinal product name
    GSK217744
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses, intramuscular into left thigh

    Arm title
    		 Infanrix hexa Group
    Arm description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of Infanrix hexa vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The Infanrix hexa and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Infanrix hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses, intramuscular into left thigh

    Investigational medicinal product name
    Prevenar 13
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 co-administered doses, intramuscular into right thigh

    Number of subjects in period 1
    		GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Started
    240
    242
    239
    Completed
    238
    239
    238
    Not completed
    2
    3
    1
         Consent withdrawn by subject
    1
    3
    1
         Adverse event, non-fatal
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GSK217744 Group 1
    Reporting group description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation A vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.

    Reporting group title
    GSK217744 Group 2
    Reporting group description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation B vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.

    Reporting group title
    Infanrix hexa Group
    Reporting group description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of Infanrix hexa vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The Infanrix hexa and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.

    Reporting group values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group Total
    Number of subjects
    		 240 242 239 721
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: weeks
        arithmetic mean (standard deviation)
    		 9.7 ( 1.36 ) 9.8 ( 1.29 ) 9.7 ( 1.21 ) -
    Gender categorical
    Units: Subjects
        Female
    		 119 138 99 356
        Male
    		 121 104 140 365
    Race/Ethnicity
    Units: Subjects
        African heritage/African American
    		 1 0 1 2
        White-Arabic/north African heritage
    		 3 1 6 10
        White-Caucasian/European heritage
    		 144 148 140 432
        Unspecified
    		 92 93 92 277

    End points

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    End points reporting groups
    Reporting group title
    GSK217744 Group 1
    Reporting group description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation A vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.

    Reporting group title
    GSK217744 Group 2
    Reporting group description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation B vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.

    Reporting group title
    Infanrix hexa Group
    Reporting group description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of Infanrix hexa vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The Infanrix hexa and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.

    Primary: Number of seroprotected subjects for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibodies.

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    End point title
    		 Number of seroprotected subjects for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibodies.
    End point description
    A seroprotected subject was defined as a vaccinated subject who had anti-D and anti-T antibody concentrations ≥ 0.1 international units per milliliter (IU/mL).
    End point type
    Primary
    End point timeframe
    At Months 0 and 3
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    214
    217
    219
    Units: Subjects
        Anti-D at Month 0 [N=200;210;211]
    154
    165
    160
        Anti-D at Month 3 [N=214;217;219]
    214
    217
    219
        Anti-T at Month 0 [N=200;210;211]
    197
    206
    209
        Anti-T at Month 3 [N=214;217;219]
    214
    217
    219
    Statistical analysis title
    		 Immune response non-inferiority - anti-D (ELISA)
    Comparison groups
    Infanrix hexa Group v GSK217744 Group 1
    Number of subjects included in analysis
    433
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -2.25
         upper limit
    		 2.3
    Statistical analysis title
    		 Immune response non-inferiority - anti-T
    Comparison groups
    GSK217744 Group 1 v Infanrix hexa Group
    Number of subjects included in analysis
    433
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -2.25
         upper limit
    		 2.3
    Statistical analysis title
    		 Immune response non-inferiority - anti-D (ELISA)
    Comparison groups
    GSK217744 Group 2 v Infanrix hexa Group
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -2.25
         upper limit
    		 2.27
    Statistical analysis title
    		 Immune response non-inferiority - anti-T
    Comparison groups
    GSK217744 Group 2 v Infanrix hexa Group
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -2.25
         upper limit
    		 2.27

    Primary: Concentrations for anti-pertussis toxoid (anti-PT) and anti-pertactin (anti-PRN) antibodies.

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    End point title
    		 Concentrations for anti-pertussis toxoid (anti-PT) and anti-pertactin (anti-PRN) antibodies.
    End point description
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliters (EL.U/mL).
    End point type
    Primary
    End point timeframe
    At Months 0 and 3.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    215
    217
    219
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-PT at Month 0 [N=199;210;210]
    3.3 (3 to 3.6)
    3.4 (3.1 to 3.7)
    3.1 (2.9 to 3.4)
        Anti-PT at Month 3 [N=215;217;218]
    57.7 (52.9 to 62.9)
    57.5 (53.1 to 62.4)
    73.2 (67.7 to 79.2)
        Anti-PRN at Month 0 [N=200;210;210]
    5.1 (4.5 to 5.9)
    4.9 (4.3 to 5.5)
    4.9 (4.3 to 5.7)
        Anti-PRN at Month 3 [N=214;215;219]
    76.6 (68.1 to 86.3)
    65.7 (58.9 to 73.3)
    106.6 (96.6 to 117.8)
    Statistical analysis title
    		 Immune response non-inferiority - anti-PT
    Comparison groups
    GSK217744 Group 1 v Infanrix hexa Group
    Number of subjects included in analysis
    434
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    1.26
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 1.11
         upper limit
    		 1.44
    Statistical analysis title
    		 Immune response non-inferiority - anti-PRN
    Comparison groups
    GSK217744 Group 1 v Infanrix hexa Group
    Number of subjects included in analysis
    434
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    1.33
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 1.14
         upper limit
    		 1.54
    Statistical analysis title
    		 Immune response non-inferiority - anti-PT
    Comparison groups
    Infanrix hexa Group v GSK217744 Group 2
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    1.25
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 1.1
         upper limit
    		 1.43
    Statistical analysis title
    		 Immune response non-inferiority - anti-PRN
    Comparison groups
    GSK217744 Group 2 v Infanrix hexa Group
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    1.58
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 1.37
         upper limit
    		 1.84

    Primary: Number of seroprotected subjects for anti-polyribosyl-ribitol-phosphate (anti-PRP) antibodies.

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    End point title
    		 Number of seroprotected subjects for anti-polyribosyl-ribitol-phosphate (anti-PRP) antibodies.
    End point description
    A seroprotected subject was defined as a vaccinated subject who had anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL).
    End point type
    Primary
    End point timeframe
    At Month 3.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    214
    216
    218
    Units: Subjects
        Anti-PRP
    197
    190
    193
    Statistical analysis title
    		 Immune response non-inferiority - anti-PRP
    Comparison groups
    GSK217744 Group 1 v Infanrix hexa Group
    Number of subjects included in analysis
    432
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -3.52
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -10.19
         upper limit
    		 3
    Statistical analysis title
    		 Immune response non-inferiority - anti-PRP
    Comparison groups
    GSK217744 Group 2 v Infanrix hexa Group
    Number of subjects included in analysis
    434
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0.57
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -6.53
         upper limit
    		 7.7

    Primary: Number of subjects with anti-hepatitis B (anti-HBs) antibody concentration equal to or above (≥) 10 and 100 milli-International units per milliliter (mIU/mL).

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    End point title
    		 Number of subjects with anti-hepatitis B (anti-HBs) antibody concentration equal to or above (≥) 10 and 100 milli-International units per milliliter (mIU/mL).
    End point description
    A seroprotected subject was defined as a vaccinated subject who had anti-HBs antibody concentrations ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.
    End point type
    Primary
    End point timeframe
    At Month 3.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    202
    205
    209
    Units: Subjects
        Anti-HBs ≥ 10 mIU/mL (ELISA)
    197
    203
    205
        Anti-HBs ≥ 100 mIU/mL (ELISA)
    184
    183
    196
        Anti-HBs ≥ 10 mIU/mL (CLIA)
    197
    201
    203
    Statistical analysis title
    		 Immune response non-inferiority - anti-HBs(ELISA)
    Comparison groups
    GSK217744 Group 1 v Infanrix hexa Group
    Number of subjects included in analysis
    411
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0.56
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -3.27
         upper limit
    		 4.63
    Statistical analysis title
    		 Immune response non-inferiority - anti-HBs(ELISA)
    Comparison groups
    GSK217744 Group 2 v Infanrix hexa Group
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.94
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -4.57
         upper limit
    		 2.36
    Statistical analysis title
    		 Immune response non-inferiority - anti-HBs (CLIA)
    Comparison groups
    GSK217744 Group 1 v Infanrix hexa Group
    Number of subjects included in analysis
    411
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.4
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -4.62
         upper limit
    		 3.8
    Statistical analysis title
    		 Immune response non-inferiority - anti-HBs (CLIA)
    Comparison groups
    GSK217744 Group 2 v Infanrix hexa Group
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.92
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -5.07
         upper limit
    		 3.02

    Primary: Concentrations for anti-HBs antibodies ≥ 10 and 100 mIU/mL.

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    End point title
    		 Concentrations for anti-HBs antibodies ≥ 10 and 100 mIU/mL. [1]
    End point description
    A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. Concentrations were expressed as geometric mean concentrations (GMCs) in milli-International units per milliliter (mIU/mL).
    End point type
    Primary
    End point timeframe
    At Month 3.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    202
    205
    209
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        Anti-HBs
    639.5 (523.6 to 781.2)
    602.6 (492.1 to 737.9)
    799 (662.2 to 964)
    No statistical analyses for this end point

    Secondary: Concentrations for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibodies.

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    End point title
    		 Concentrations for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antibodies.
    End point description
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was 0.1 IU/mL.
    End point type
    Secondary
    End point timeframe
    At Months 0 and 3.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    214
    217
    219
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Anti-D at Month 0 [N=200;210;211]
    0.292 (0.247 to 0.347)
    0.281 (0.238 to 0.332)
    0.29 (0.245 to 0.343)
        Anti-D at Month 3 [N=214;217;219]
    1.499 (1.367 to 1.644)
    1.704 (1.564 to 1.856)
    1.839 (1.686 to 2.005)
        Anti-T at Month 0 [N=200;210;211]
    0.936 (0.832 to 1.053)
    0.92 (0.822 to 1.029)
    0.907 (0.812 to 1.013)
        Anti-T at Month 3 [N=214;217;219]
    1.761 (1.624 to 1.91)
    1.726 (1.597 to 1.865)
    1.947 (1.818 to 2.085)
    No statistical analyses for this end point

    Secondary: Number of seropositive subjects for anti-pertussis toxoid (anti-PT) and anti-pertactin (anti-PRN) antibodies.

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    End point title
    		 Number of seropositive subjects for anti-pertussis toxoid (anti-PT) and anti-pertactin (anti-PRN) antibodies.
    End point description
    A seropositive subject was defined as a vaccinated subject who had anti-PT and anti-PRN antibody concentrations ≥ 5 EL.U/mL.
    End point type
    Secondary
    End point timeframe
    At Months 0 and 3.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    215
    217
    219
    Units: Subjects
        Anti-PT at Month 0 [N=199;210;210]
    33
    38
    31
        Anti-PT at Month 3 [N=215;217;218]
    215
    217
    218
        Anti-PRN at Month 0 [N=200;210;210]
    84
    89
    76
        Anti-PRN at Month 3 [N=214;215;219]
    214
    215
    219
    No statistical analyses for this end point

    Secondary: Concentrations for anti-polyribosyl-ribitol-phosphate (anti-PRP) antibodies.

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    End point title
    		 Concentrations for anti-polyribosyl-ribitol-phosphate (anti-PRP) antibodies.
    End point description
    Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was ≥ 0.15 µg/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    214
    216
    218
    Units: µg/mL
    geometric mean (confidence interval 95%)
        Anti-PRP
    0.951 (0.793 to 1.142)
    0.73 (0.606 to 0.88)
    1.082 (0.884 to 1.324)
    No statistical analyses for this end point

    Secondary: Number of seropositive subjects for anti-pneumococcal (anti-PNE) serotypes.

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    End point title
    		 Number of seropositive subjects for anti-pneumococcal (anti-PNE) serotypes.
    End point description
    A seropositive subject was defined as a vaccinated subject who had anti- pneumococcal antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL). The anti-PNE serotypes assessed were 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.
    End point type
    Secondary
    End point timeframe
    At Month 3.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    108
    112
    114
    Units: Subjects
        Anti- PNE 1 [N=107;112;112]
    107
    112
    111
        Anti- PNE 3 [N=106;105;107]
    106
    105
    107
        Anti- PNE 4 [N=108;112;114]
    108
    112
    114
        Anti- PNE 5 [N=108;111;112]
    107
    109
    109
        Anti- PNE 6A [N=108;112;114]
    108
    111
    112
        Anti- PNE 6B [N=107;112;113]
    97
    104
    102
        Anti- PNE 7F [N=108;112;114]
    107
    111
    114
        Anti- PNE 9V [N=108;112;114]
    107
    112
    113
        Anti- PNE 14 [N=108;112;114]
    108
    112
    114
        Anti- PNE 18C [N=108;112;113]
    106
    112
    109
        Anti- PNE 19A [N=106;112;114]
    106
    112
    114
        Anti- PNE 19F [N=108;112;114]
    107
    111
    114
        Anti- PNE 23F [N=108;112;114]
    103
    104
    108
    No statistical analyses for this end point

    Secondary: Concentrations for anti-PNE antibodies.

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    End point title
    		 Concentrations for anti-PNE antibodies.
    End point description
    Concentrations were expressed as geometric mean concentrations (GMCs). The seropositivity cut-off of the assay was 0.15 µg /mL. The anti-PNE serotypes assessed were 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.
    End point type
    Secondary
    End point timeframe
    At Month 3.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    108
    112
    114
    Units: µg/mL
    geometric mean (confidence interval 95%)
        Anti- PNE 1 [N=107;112;112]
    1.61 (1.42 to 1.83)
    1.48 (1.32 to 1.67)
    1.58 (1.38 to 1.81)
        Anti- PNE 3 [N=106;105;107]
    0.91 (0.8 to 1.03)
    0.91 (0.82 to 1.01)
    0.94 (0.84 to 1.05)
        Anti- PNE 4 [N=108;112;114]
    1.8 (1.61 to 2.03)
    1.62 (1.47 to 1.8)
    1.69 (1.5 to 1.9)
        Anti- PNE 5 [N=108;111;112]
    0.79 (0.69 to 0.89)
    0.77 (0.69 to 0.87)
    0.82 (0.72 to 0.93)
        Anti- PNE 6A [N=108;112;114]
    1.63 (1.39 to 1.91)
    1.43 (1.23 to 1.66)
    1.52 (1.3 to 1.79)
        Anti- PNE 6B [N=107;112;113]
    0.66 (0.53 to 0.82)
    0.64 (0.52 to 0.78)
    0.69 (0.56 to 0.85)
        Anti- PNE 7F [N=108;112;114]
    2.18 (1.91 to 2.49)
    2.3 (2.05 to 2.59)
    2.48 (2.2 to 2.79)
        Anti- PNE 9V [N=108;112;114]
    1.12 (0.97 to 1.28)
    1.11 (0.99 to 1.25)
    1.16 (1.02 to 1.32)
        Anti- PNE 14 [N=108;112;114]
    7.47 (6.33 to 8.81)
    7.8 (6.79 to 8.96)
    8.03 (6.81 to 9.48)
        Anti- PNE 18C [N=108;112;113]
    1.56 (1.33 to 1.84)
    1.55 (1.39 to 1.74)
    1.56 (1.33 to 1.82)
        Anti- PNE 19A [N=106;112;114]
    2.7 (2.35 to 3.09)
    2.75 (2.4 to 3.15)
    2.68 (2.38 to 3.03)
        Anti- PNE 19F [N=108;112;114]
    2.55 (2.16 to 3)
    2.53 (2.19 to 2.92)
    2.79 (2.44 to 3.18)
        Anti- PNE 23F [N=108;112;114]
    0.89 (0.73 to 1.09)
    0.83 (0.69 to 1.01)
    0.91 (0.75 to 1.1)
    No statistical analyses for this end point

    Secondary: Number of subjects with a vaccine response to PT and PRN.

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    End point title
    		 Number of subjects with a vaccine response to PT and PRN.
    End point description
    Vaccine response defined as: for initially seronegative subjects, antibody concentration ≥ 5 EL.U/mL at 1 month post primary vaccination (Month 3); for initially seropositive subjects, antibody concentration at 1 month post primary vaccination (Month 3) ≥ 1 fold the pre-vaccination antibody concentration.
    End point type
    Secondary
    End point timeframe
    At Month 3.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    199
    210
    210
    Units: Subjects
        Anti- PT [N=199;210;209]
    195
    204
    207
        Anti- PRN 3 [N=199;208;210]
    181
    194
    198
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any solicited local symptoms.

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    End point title
    		 Number of subjects reporting any solicited local symptoms.
    End point description
    Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade.
    End point type
    Secondary
    End point timeframe
    During the 8-day (Days 0-7).
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    240
    240
    238
    Units: Subjects
        Any pain
    190
    183
    155
        Any redness
    151
    140
    128
        Any swelling
    124
    122
    115
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any solicited general symptoms.

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    End point title
    		 Number of subjects reporting any solicited general symptoms.
    End point description
    Solicited local symptoms assessed were drowsiness, irritability, loss of appetite and fever [axillary temperature above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of any local symptom regardless of intensity grade.
    End point type
    Secondary
    End point timeframe
    During the 8-day (Days 0-7).
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    240
    240
    238
    Units: Subjects
        Any drowsiness
    188
    185
    171
        Any irritability
    197
    205
    191
        Any loss of appetite
    135
    127
    112
        Any fever
    180
    173
    140
    No statistical analyses for this end point

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

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    End point title
    		 Number of subjects reporting any unsolicited adverse events (AEs).
    End point description
    An unsolicited AE is any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = occurrence of an AE regardless of intensity grade or relationship to study vaccination.
    End point type
    Secondary
    End point timeframe
    Within the 31-day (Days 0-30) follow up period after vaccination.
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    240
    242
    239
    Units: Subjects
        Any AEs
    153
    165
    159
    No statistical analyses for this end point

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

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    End point title
    		 Number of subjects reporting any serious adverse events (SAEs).
    End point description
    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. Any SAE = any SAE regardless of assessment of relationship to study vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (Month 0 to Month 3).
    End point values
    		 GSK217744 Group 1 GSK217744 Group 2 Infanrix hexa Group
    Number of subjects analysed
    240
    242
    239
    Units: Subjects
        Any SAEs
    9
    5
    4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited symptoms: 8-day follow-up period after vaccination; unsolicited AEs: 31-day follow-up period after vaccination; SAEs: during the entire study period (Months 0-3).
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14.1
    Reporting groups
    Reporting group title
    GSK217744 Group 1
    Reporting group description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation A vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.

    Reporting group title
    Infanrix hexa Group
    Reporting group description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of Infanrix hexa vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The Infanrix hexa and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.

    Reporting group title
    GSK217744 Group 2
    Reporting group description
    		 Subjects aged between and including 60 and 90 days of age at the time of first vaccination received 3 doses of GSK217744 formulation B vaccine, co-administered with Prevenar 13 at 2, 3 and 4 months of age. The GSK217744 and Prevenar 13 vaccines were administered intramuscularly into the left and right sides of the thigh, respectively.

    Serious adverse events
    		 GSK217744 Group 1 Infanrix hexa Group GSK217744 Group 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 240 (3.75%)
    4 / 239 (1.67%)
    5 / 242 (2.07%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Haemangioma of skin
         subjects affected / exposed
    0 / 240 (0.00%)
    0 / 239 (0.00%)
    1 / 242 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Scaphocephaly
         subjects affected / exposed
    1 / 240 (0.42%)
    0 / 239 (0.00%)
    0 / 242 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 240 (0.00%)
    0 / 239 (0.00%)
    1 / 242 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asphyxia
         subjects affected / exposed
    1 / 240 (0.42%)
    0 / 239 (0.00%)
    0 / 242 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 240 (0.42%)
    0 / 239 (0.00%)
    0 / 242 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 240 (0.42%)
    0 / 239 (0.00%)
    0 / 242 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Respiratory tract congestion
         subjects affected / exposed
    1 / 240 (0.42%)
    0 / 239 (0.00%)
    0 / 242 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchiolitis
         subjects affected / exposed
    4 / 240 (1.67%)
    3 / 239 (1.26%)
    0 / 242 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 240 (0.42%)
    1 / 239 (0.42%)
    1 / 242 (0.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Amoebiasis
         subjects affected / exposed
    1 / 240 (0.42%)
    0 / 239 (0.00%)
    0 / 242 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 240 (0.00%)
    0 / 239 (0.00%)
    1 / 242 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 240 (0.42%)
    0 / 239 (0.00%)
    0 / 242 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 240 (0.00%)
    0 / 239 (0.00%)
    1 / 242 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 GSK217744 Group 1 Infanrix hexa Group GSK217744 Group 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    240 / 240 (100.00%)
    235 / 239 (98.33%)
    239 / 242 (98.76%)
    General disorders and administration site conditions
    Injection site induration
         subjects affected / exposed
    22 / 240 (9.17%)
    25 / 239 (10.46%)
    14 / 242 (5.79%)
         occurrences all number
    22
    25
    14
    Pain
    alternative assessment type: Systematic
         subjects affected / exposed
    190 / 240 (79.17%)
    155 / 239 (64.85%)
    183 / 242 (75.62%)
         occurrences all number
    190
    155
    183
    Redness
    alternative assessment type: Systematic
         subjects affected / exposed
    151 / 240 (62.92%)
    128 / 239 (53.56%)
    140 / 242 (57.85%)
         occurrences all number
    151
    128
    140
    Swelling
    alternative assessment type: Systematic
         subjects affected / exposed
    124 / 240 (51.67%)
    115 / 239 (48.12%)
    122 / 242 (50.41%)
         occurrences all number
    124
    115
    122
    Drowsiness
    alternative assessment type: Systematic
         subjects affected / exposed
    188 / 240 (78.33%)
    171 / 239 (71.55%)
    185 / 242 (76.45%)
         occurrences all number
    188
    171
    185
    Irritability
    alternative assessment type: Systematic
         subjects affected / exposed
    197 / 240 (82.08%)
    191 / 239 (79.92%)
    205 / 242 (84.71%)
         occurrences all number
    197
    191
    205
    Loss of appetite
    alternative assessment type: Systematic
         subjects affected / exposed
    135 / 240 (56.25%)
    112 / 239 (46.86%)
    127 / 242 (52.48%)
         occurrences all number
    135
    112
    127
    Fever
    alternative assessment type: Systematic
         subjects affected / exposed
    180 / 240 (75.00%)
    140 / 239 (58.58%)
    173 / 242 (71.49%)
         occurrences all number
    180
    140
    173
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    8 / 240 (3.33%)
    14 / 239 (5.86%)
    7 / 242 (2.89%)
         occurrences all number
    8
    14
    7
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    13 / 240 (5.42%)
    21 / 239 (8.79%)
    13 / 242 (5.37%)
         occurrences all number
    13
    21
    13
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    7 / 240 (2.92%)
    8 / 239 (3.35%)
    14 / 242 (5.79%)
         occurrences all number
    7
    8
    14
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    53 / 240 (22.08%)
    51 / 239 (21.34%)
    64 / 242 (26.45%)
         occurrences all number
    53
    51
    64
    Upper respiratory tract infection
         subjects affected / exposed
    14 / 240 (5.83%)
    15 / 239 (6.28%)
    21 / 242 (8.68%)
         occurrences all number
    14
    15
    21
    Rhinitis
         subjects affected / exposed
    18 / 240 (7.50%)
    8 / 239 (3.35%)
    14 / 242 (5.79%)
         occurrences all number
    18
    8
    14

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Feb 2011
    Due to slow recruitment, the study from now on will also be conducted in countries outside Europe. In order to allow recruitment in other countries, hepatitis b vaccination at birth will now be allowed and preferred route for recording temperature in this study will be axillary or rectal. In countries outside Finland, Prevenar 13 will not be associated with any clinical endpoints. Due to the multi-country approach, one of the statistical methods has been updated.
    19 Sep 2011
    The protocol is being amended to allow a preliminary descriptive analysis of the available immunogenicity data. In order to ensure validity of the study results and integrity of data, the preliminary analysis will be performed by a statistician not otherwise involved with the conduct of the study, and results will be shared only with a restricted group of individuals within GSK Biologicals. The study team and the investigators will remain blinded until the study end. The 95% confidence interval (CI) criteria in the primary objectives have been updated to 97.5% CI to reflect the adjustment for multiplicity planned in the sample size consideration and to align to the wording used in the Booster DTPAHBV-IPV-125 (114843) protocol. A sequential list will be generated to allocate treatment numbers to the Prevenar 13 doses. The same has been reflected in the Randomization of supplies section. At the discretion of GSK Biologicals, pneumococcal testing may be done at a GSK Biologicals laboratory or the World Health Organisation (WHO) reference laboratory. Since the 22F-inhibition ELISA assay used at the WHO reference laboratory has a different assay cut-off, different thresholds are mentioned in the statistical analysis description. The threshold for the 22F-inhibition non-GSK ELISA assay performed at the WHO reference laboratory is 0.35 μg/ml.

    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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