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    Clinical Trial Results:
    A randomised, open-label study to assess the immunogenicity and safety of GSK Biologicals’ DTPa-IPV/Hib vaccine administered as a three-dose primary vaccination course at 2-3-4 or 3-4-5 months of age in healthy infants in China.

    Summary
    EudraCT number
    		 2011-005868-25
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    19 Nov 2010

    Results information
    Results version number
    		 v3(current)
    This version publication date
    13 May 2018
    First version publication date
    24 Jun 2015
    Other versions
    		 v1 (removed from public view) , v2
    Version creation reason
    • Correction of full data set
    Minor corrections of the full study results.

    Trial information

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    Trial identification
    Sponsor protocol code
    112584
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01086423
    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, 44 2089904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, 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
    26 Oct 2011
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Nov 2010
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Nov 2010
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that the immunogenicity of DTPa-IPV/Hib vaccine administered at 2, 3 and 4 months of age (DTPa Combo-1 Group) was non-inferior to that of the concomitant administration of DTPa/Hib and IPV vaccines at the same age (Control Group), in terms of immune response to all vaccine antigens, one month after the third vaccine dose.
    Protection of trial subjects
    The vaccines will be observed closely for at least 30 minutes following the administration of vaccines, with appropriate medical treatment readily available in case of a rare anaphylactic reaction.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 Mar 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
    China: 984
    Worldwide total number of subjects
    984
    EEA total number of subjects
    0
    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)
    984
    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
    		 Out of the 985 subjects originally enrolled in the study, 984 subjects were vaccinated with at least one dose of the study vaccine.

    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
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Infanrix-IPV+Hib 1 Group
    Arm description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Infanrix IPV/Hib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 3 doses of Infanrix-IPV+Hib vaccine intramuscularly, in the upper side of the right thigh at 2, 3 and 4 months of age.

    Arm title
    		 Infanrix-IPV+Hib 2 Group
    Arm description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Infanrix IPV/Hib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 3 doses of Infanrix-IPV+Hib vaccine intramuscularly in the upper side of the right thigh at 3, 4 and 5 months of age.

    Arm title
    		 Infanrix-Hib + Poliorix Group
    Arm description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Infanrix-Hib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 3 doses of Infanrix-Hib vaccine intramuscularly in the upper side of the right thigh at 2, 3 and 4 months of age.

    Investigational medicinal product name
    Poliorix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 3 doses of Poliorix vaccine intramuscularly in the upper side of the left thigh at 2, 3 and 4 months of age.

    Number of subjects in period 1
    		Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Started
    330
    324
    330
    Completed
    320
    321
    321
    Not completed
    10
    3
    9
         Adverse event, serious fatal
    1
    1
    -
         Consent withdrawn by subject
    5
    1
    3
         Adverse event, non-fatal
    2
    1
    -
         Protocol violation
    -
    -
    1
         Migrated/moved from study area
    2
    -
    4
         Lost to follow-up
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Infanrix-IPV+Hib 1 Group
    Reporting group description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.

    Reporting group title
    Infanrix-IPV+Hib 2 Group
    Reporting group description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.

    Reporting group title
    Infanrix-Hib + Poliorix Group
    Reporting group description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.

    Reporting group values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group Total
    Number of subjects
    		 330 324 330 984
    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)
    		 9.9 ± 1.12 14.3 ± 1.14 9.9 ± 1.17 -
    Gender categorical
    Units: Subjects
        Female
    		 155 147 141 443
        Male
    		 175 177 189 541
    Race/Ethnicity
    Units: Subjects
        Asian-Chinese heritage
    		 330 324 330 984

    End points

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    End points reporting groups
    Reporting group title
    Infanrix-IPV+Hib 1 Group
    Reporting group description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.

    Reporting group title
    Infanrix-IPV+Hib 2 Group
    Reporting group description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.

    Reporting group title
    Infanrix-Hib + Poliorix Group
    Reporting group description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.

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

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    End point title
    		 Number of seroprotected subjects for anti-diphtheria (anti-D) and anti-tetanus (anti-T) antigens
    End point description
    A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations greater than or equal to (≥) 0.1 international units per milliliter (IU/mL).
    End point type
    Primary
    End point timeframe
    At Month 3 (for Infanrix-IPV+Hib 1 Group and Infanrix-Hib + Poliorix Group) and Month 4 (for Infanrix-IPV+Hib 2 Group)
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    147
    156
    147
    Units: Subjects
        Anti-D
    146
    156
    147
        Anti-T
    147
    156
    147
    Statistical analysis title
    		 Difference in seroprotection rates for anti-D
    Statistical analysis description
    To demonstrate that the immunogenicity of Infanrix™ IPV/Hib vaccine administered at 2, 3 and 4 months of age (Infanrix-IPV+Hib 1 Group) was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age (Infanrix-Hib + Poliorix Group), in terms of immune response to anti-diphteria, one month after the third vaccine dose.
    Comparison groups
    Infanrix-Hib + Poliorix Group v Infanrix-IPV+Hib 1 Group
    Number of subjects included in analysis
    294
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Difference in seroprotection rate
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.88
         upper limit
    		 3.76
    Notes
    [1] - The upper limit of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.
    Statistical analysis title
    		 Difference in seroprotection rates for anti-T
    Statistical analysis description
    To demonstrate that the immunogenicity of Infanrix™ IPV/Hib vaccine administered at 2, 3 and 4 months of age (Infanrix-IPV+Hib 1 Group) was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age (Infanrix-Hib + Poliorix Group), in terms of immune response to anti-tetanus, one month after the third vaccine dose.
    Comparison groups
    Infanrix-Hib + Poliorix Group v Infanrix-IPV+Hib 1 Group
    Number of subjects included in analysis
    294
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Difference in seroprotection rate
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.56
         upper limit
    		 2.56
    Notes
    [2] - The upper limit of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.

    Primary: Number of seroprotected subjects for anti-poly-ribosyl-ribitol phosphate (anti-PRP) antigens

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    End point title
    		 Number of seroprotected subjects for anti-poly-ribosyl-ribitol phosphate (anti-PRP) antigens
    End point description
    A seroprotected subject was defined as a subject with anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (μg/mL)
    End point type
    Primary
    End point timeframe
    At Month 3 (for Infanrix-IPV+Hib 1 Group and Infanrix-Hib + Poliorix Group) and Month 4 (for Infanrix-IPV+Hib 2 Group)
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    147
    157
    150
    Units: Subjects
    142
    155
    133
    Statistical analysis title
    		 Difference in seroprotection rates for anti-PRP
    Statistical analysis description
    To demonstrate that the immunogenicity of Infanrix™ IPV/Hib vaccine administered at 2, 3 and 4 months of age (Infanrix-IPV+Hib 1 Group) was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age (Infanrix-Hib + Poliorix Group), in terms of immune response to anti-PRP antibodies, one month after the third vaccine dose.
    Comparison groups
    Infanrix-IPV+Hib 1 Group v Infanrix-Hib + Poliorix Group
    Number of subjects included in analysis
    297
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 Difference in seroprotection rate
    Point estimate
    -7.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.44
         upper limit
    		 -2.13
    Notes
    [3] - The upper limit of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.

    Primary: Number of seroprotected subjects for anti-poliovirus (anti-polio) types 1, 2 and 3 antigens

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    End point title
    		 Number of seroprotected subjects for anti-poliovirus (anti-polio) types 1, 2 and 3 antigens
    End point description
    A seroprotected subject was defined as a subject with anti-poliovirus (anti-polio) types 1, 2 and 3 antibody titres ≥ the value of 8.
    End point type
    Primary
    End point timeframe
    At Month 3 (for Infanrix-IPV+Hib 1 Group and Infanrix-Hib + Poliorix Group) and Month 4 (for Infanrix-IPV+Hib 2 Group)
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    147
    157
    150
    Units: Subjects
        Anti-polio 1
    147
    157
    150
        Anti-polio 2
    147
    157
    150
        Anti-polio 3
    147
    157
    150
    Statistical analysis title
    		 Seroprotection rates difference for anti-Polio1
    Statistical analysis description
    To demonstrate that the immunogenicity of Infanrix™ IPV/Hib vaccine administered at 2, 3 and 4 months of age (Infanrix-IPV+Hib 1 Group) was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age (Infanrix-Hib + Poliorix Group), in terms of immune response to anti-Polio type 1 antibodies, one month after the third vaccine dose.
    Comparison groups
    Infanrix-IPV+Hib 1 Group v Infanrix-Hib + Poliorix Group
    Number of subjects included in analysis
    297
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    Method
    Parameter type
    		 Difference in seroprotection rate
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.51
         upper limit
    		 2.56
    Notes
    [4] - The upper limit of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.
    Statistical analysis title
    		 Seroprotection rates difference for anti-Polio2
    Statistical analysis description
    To demonstrate that the immunogenicity of Infanrix™ IPV/Hib vaccine administered at 2, 3 and 4 months of age (Infanrix-IPV+Hib 1 Group) was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age (Infanrix-Hib + Poliorix Group), in terms of immune response to anti-Polio type 2 antibodies, one month after the third vaccine dose.
    Comparison groups
    Infanrix-IPV+Hib 1 Group v Infanrix-Hib + Poliorix Group
    Number of subjects included in analysis
    297
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    Parameter type
    		 Difference in seroprotection rate
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.51
         upper limit
    		 2.56
    Notes
    [5] - The upper limit of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.
    Statistical analysis title
    		 Seroprotection rates difference for anti-Polio3
    Statistical analysis description
    To demonstrate that the immunogenicity of Infanrix™ IPV/Hib vaccine administered at 2, 3 and 4 months of age (Infanrix-IPV+Hib 1 Group) was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age (Infanrix-Hib + Poliorix Group), in terms of immune response to anti-Polio type 3 antibodies, one month after the third vaccine dose.
    Comparison groups
    Infanrix-IPV+Hib 1 Group v Infanrix-Hib + Poliorix Group
    Number of subjects included in analysis
    297
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    Parameter type
    		 Difference in seroprotection rate
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.51
         upper limit
    		 2.56
    Notes
    [6] - The upper limit of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.

    Primary: Number of subjects with a vaccine response to pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) antigens.

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    End point title
    		 Number of subjects with a vaccine response to pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) antigens.
    End point description
    Vaccine response was defined as: For PT and FHA response, antibody concentration ≥ 20 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) at post-vaccination. For PRN response: for initially seronegative subjects [antibody concentration lower than (<) 5 EL.U/mL], post-vaccination antibody concentration ≥ 20 EL.U/mL; for initially seropositive subjects (antibody concentration ≥ 5 EL.U/mL), at least a 4-fold increase in antibody concentration from pre to post-vaccination.
    End point type
    Primary
    End point timeframe
    At Month 3 (for Infanrix-IPV+Hib 1 Group and Infanrix-Hib + Poliorix Group) and Month 4 (for Infanrix-IPV+Hib 2 Group).
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    147
    156
    148
    Units: Subjects
        Anti-PT
    147
    155
    147
        Anti-FHA
    147
    155
    144
        Anti-PRN
    145
    156
    145
    Statistical analysis title
    		 Difference in vaccine response rates for anti-PT
    Statistical analysis description
    To demonstrate that the immunogenicity of Infanrix™ IPV/Hib vaccine administered at 2, 3 and 4 months of age (Infanrix-IPV+Hib 1 Group) was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age (Infanrix-Hib + Poliorix Group), in terms of immune response to anti-PT antigens, one month after the third vaccine dose.
    Comparison groups
    Infanrix-IPV+Hib 1 Group v Infanrix-Hib + Poliorix Group
    Number of subjects included in analysis
    295
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    Parameter type
    		 Difference in seroprotection rate
    Point estimate
    -0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.74
         upper limit
    		 1.89
    Notes
    [7] - The upper limit of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.
    Statistical analysis title
    		 Difference in vaccine response rates for anti-FHA
    Statistical analysis description
    To demonstrate that the immunogenicity of Infanrix™ IPV/Hib vaccine administered at 2, 3 and 4 months of age (Infanrix-IPV+Hib 1 Group) was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age (Infanrix-Hib + Poliorix Group), in terms of immune response to anti-FHA antigens, one month after the third vaccine dose.
    Comparison groups
    Infanrix-IPV+Hib 1 Group v Infanrix-Hib + Poliorix Group
    Number of subjects included in analysis
    295
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    Parameter type
    		 Difference in seroprotection rate
    Point estimate
    -2.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.75
         upper limit
    		 -0.11
    Notes
    [8] - The upper limit of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.
    Statistical analysis title
    		 Difference in vaccine response rates for anti-PRN
    Statistical analysis description
    To demonstrate that the immunogenicity of Infanrix™ IPV/Hib vaccine administered at 2, 3 and 4 months of age (Infanrix-IPV+Hib 1 Group) was non-inferior to that of the concomitant administration of Infanrix™-Hib and Poliorix™ vaccines at the same age (Infanrix-Hib + Poliorix Group), in terms of immune response to anti-PRN antigens, one month after the third vaccine dose.
    Comparison groups
    Infanrix-IPV+Hib 1 Group v Infanrix-Hib + Poliorix Group
    Number of subjects included in analysis
    295
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [9]
    Method
    Parameter type
    		 Difference in seroprotection rate
    Point estimate
    -0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 3.04
    Notes
    [9] - The upper limit of the standardized asymptotic 95% confidence interval (CI) on the group difference [Infanrix-Hib + Poliorix Group minus Infanrix-IPV+Hib 1 Group] in percentage of seroprotected subjects ≤ 10%.

    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
    Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL.
    End point type
    Secondary
    End point timeframe
    At Month 0 [PRE] and Month 3 (for Infanrix-IPV+Hib 1 Group and Infanrix-Hib + Poliorix Group) and Month 4 (for Infanrix-IPV+Hib 2 Group) [POST]
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    147
    157
    151
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Anti-D PRE [N=147;157;151]
    0.052 (0.05 to 0.053)
    0.051 (0.05 to 0.052)
    0.051 (0.049 to 0.052)
        Anti-D POST [N=147;156;147]
    0.719 (0.661 to 0.782)
    0.753 (0.699 to 0.812)
    0.613 (0.565 to 0.666)
        Anti-T PRE [N=147;157;151]
    0.051 (0.05 to 0.052)
    0.052 (0.05 to 0.054)
    0.05 (0.05 to 0.05)
        Anti-T POST [N=147;156;147]
    4.118 (3.779 to 4.488)
    4.124 (3.796 to 4.479)
    3.618 (3.339 to 3.921)
    No statistical analyses for this end point

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

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    End point title
    		 Concentrations for anti-poly-ribosyl-ribitol phosphate (anti-PRP) antibodies.
    End point description
    Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in µg/mL.
    End point type
    Secondary
    End point timeframe
    At Month 0 [PRE] and Month 3 (for Infanrix-IPV+Hib 1 Group and Infanrix-Hib + Poliorix Group) and Month 4 (for Infanrix-IPV+Hib 2 Group) [POST]
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    147
    157
    151
    Units: µg/mL
    geometric mean (confidence interval 95%)
        Anti-PRP PRE [N=146;157;151]
    0.127 (0.104 to 0.154)
    0.135 (0.112 to 0.163)
    0.15 (0.122 to 0.185)
        Anti-PRP POST [N=147;157;150]
    5.601 (4.676 to 6.709)
    9.396 (8.032 to 10.992)
    2.826 (2.235 to 3.572)
    No statistical analyses for this end point

    Secondary: Titers for anti-poliovirus (anti-polio) types 1, 2 and 3 antibodies.

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    End point title
    		 Titers for anti-poliovirus (anti-polio) types 1, 2 and 3 antibodies.
    End point description
    Antibody titers were presented as geometric mean titers (GMTs).
    End point type
    Secondary
    End point timeframe
    At Month 0 [PRE] and Month 3 (for Infanrix-IPV+Hib 1 Group and Infanrix-Hib + Poliorix Group) and Month 4 (for Infanrix-IPV+Hib 2 Group) [POST]
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    147
    157
    151
    Units: titres
    geometric mean (confidence interval 95%)
        Anti-polio 1 PRE [N=146;157;151]
    9.4 (7.7 to 11.5)
    7.1 (6.2 to 8.2)
    9.2 (7.7 to 11)
        Anti-polio 1 POST [N=147;157;150]
    1143.7 (952.7 to 1372.9)
    1328.9 (1137.6 to 1552.4)
    533.6 (469.5 to 606.4)
        Anti-polio 2 PRE [N=146;157;151]
    6.3 (5.5 to 7.2)
    5 (4.6 to 5.5)
    6.9 (6 to 8)
        Anti-polio 2 POST [N=147;157;150]
    416.2 (344.5 to 502.8)
    458.6 (385.6 to 545.5)
    186.4 (160.4 to 216.5)
        Anti-polio 3 PRE [N=146;157;151]
    5.8 (5 to 6.8)
    4.9 (4.3 to 5.6)
    5.7 (5.1 to 6.4)
        Anti-polio 3 POST [N=147;157;150]
    1478.8 (1210.6 to 1806.5)
    1411.6 (1175.3 to 1695.3)
    820.7 (820.7 to 964.4)
    No statistical analyses for this end point

    Secondary: Number of subjects with any solicited local symptoms.

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    End point title
    		 Number of subjects with any solicited local symptoms.
    End point description
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.
    End point type
    Secondary
    End point timeframe
    During the 4-day (Days 0-3) post-vaccination period after each vaccine dose.
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    330
    324
    330
    Units: Subjects
        Any Pain, D1 [N=330;324;330]
    65
    64
    83
        Any Redness, D1 [N=330;324;330]
    16
    19
    15
        Any Swelling, D1 [N=330;324;330]
    8
    9
    9
        Any Pain, D2 [N=321;321;322]
    43
    50
    58
        Any Redness, D2 [N=321;321;322]
    14
    19
    13
        Any Swelling, D2 [N=321;321;322]
    6
    8
    8
        Any Pain, D3 [N=321;321;321]
    39
    41
    39
        Any Redness, D3 [N=321;321;321]
    10
    11
    8
        Any Swelling, D3 [N=321;321;321]
    5
    8
    6
        Any Pain, Across [N=330;324;330]
    90
    91
    102
        Any Redness, Across [N=330;324;330]
    28
    34
    26
        Any Swelling, Across [N=330;324;330]
    14
    17
    19
    No statistical analyses for this end point

    Secondary: Number of subjects with any solicited general symptoms.

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    End point title
    		 Number of subjects with any solicited general symptoms.
    End point description
    Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade or relationship to study vaccination.
    End point type
    Secondary
    End point timeframe
    During the 4-day (Days 0-3) post-vaccination period after each vaccine dose.
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    330
    324
    330
    Units: Subjects
        Any Drowsiness, D1 [N=330;324;330]
    95
    80
    69
        Any Irritability, D1 [N=330;324;330]
    123
    120
    116
        Any Loss of appet., D1 [N=330;324;330]
    77
    86
    76
        Any Fever/Axillary, D1 [N=330;324;330]
    137
    152
    103
        Any Drowsiness, D2 [N=321;321;322]
    53
    47
    53
        Any Irritability, D2 [N=321;321;322]
    96
    100
    103
        Any Loss of appet., D2 [N=321;321;322]
    69
    72
    59
        Any Fever/Axillary, D2 [N=321;321;322]
    131
    144
    102
        Any Drowsiness, D3 [N=321;321;321]
    43
    32
    28
        Any Irritability, D3 [N=321;321;321]
    77
    70
    61
        Any Loss of appet., D3 [N=321;321;321]
    65
    57
    36
        Any Fever/Axillary, D3 [N=321;321;321]
    93
    82
    75
        Any Drowsiness, Across [N=330;324;330]
    124
    102
    99
        Any Irritability, Across [N=330;324;330]
    171
    166
    163
        Any Loss of appet., Across [N=330;324;330]
    131
    136
    114
        Any Fever/Axillary, Across [N=330;324;330]
    217
    217
    183
    No statistical analyses for this end point

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

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    End point title
    		 Number of subjects with unsolicited adverse events (AEs).
    End point description
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
    End point type
    Secondary
    End point timeframe
    During the 31-day (Days 0-30) post-vaccination period after any dose.
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    330
    324
    330
    Units: Subjects
        AEs
    98
    114
    110
    No statistical analyses for this end point

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

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    End point title
    		 Number of subjects with serious adverse events (SAEs).
    End point description
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
    End point type
    Secondary
    End point timeframe
    During the entire study period (from Month 0 to Month 4/5)
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    330
    324
    330
    Units: Subjects
        SAEs
    6
    3
    4
    No statistical analyses for this end point

    Secondary: Concentrations of antibodies against anti-PT, anti-FHA and anti-PRN antigens

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    End point title
    		 Concentrations of antibodies against anti-PT, anti-FHA and anti-PRN antigens
    End point description
    Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in EL.U/mL.
    End point type
    Secondary
    End point timeframe
    At Month 0 [PRE] and Month 3 (for Infanrix-IPV+Hib 1 Group and Infanrix-Hib + Poliorix Group) and Month 4 (for Infanrix-IPV+Hib 2 Group) [POST]
    End point values
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Number of subjects analysed
    147
    157
    151
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-PT, PRE [N=147;157;151]
    2.9 (2.8 to 3.1)
    2.7 (2.6 to 2.8)
    2.8 (2.6 to 2.9)
        Anti-PT, POST [N=147;156;148]
    108.7 (99.2 to 119.1)
    114.7 (105.4 to 124.8)
    97.1 (88.3 to 106.8)
        Anti-FHA, PRE [N=147;157;151]
    2.9 (2.7 to 3.1)
    2.6 (2.5 to 2.7)
    2.9 (2.7 to 3.1)
        Anti-FHA, POST [N=147;156;148]
    87.7 (79.9 to 96.3)
    87.6 (79.6 to 96.4)
    76.3 (68.5 to 85)
        Anti-PRN, PRE [N=147;157;151]
    2.6 (2.5 to 2.7)
    2.6 (2.5 to 2.6)
    2.5 (2.5 to 2.6)
        Anti-PRN, POST [N=147;156;148]
    44.8 (42 to 47.9)
    43.7 (41.3 to 46.3)
    43.2 (39.8 to 47)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited local and general symptoms: during the 4-day (Days 0-3) post-vaccination period. Unsolicited AEs: during the 31-day (Days 0-30) post-vaccination period. SAEs: during the entire study period (from Month 0 up to Month 4/5).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14.0
    Reporting groups
    Reporting group title
    Infanrix-IPV+Hib 1 Group
    Reporting group description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right thigh.

    Reporting group title
    Infanrix-IPV+Hib 2 Group
    Reporting group description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-IPV+Hib vaccine at 3, 4 and 5 months of age, administered intramuscularly in the upper side of the right thigh.

    Reporting group title
    Infanrix-Hib + Poliorix Group
    Reporting group description
    		 Healthy male or female infants, between and including 60 and 90 days of age at the time of the first study visit, received 3 doses of Infanrix-Hib vaccine co-administered with Poliorix vaccine at 2, 3 and 4 months of age, administered intramuscularly in the upper side of the right or left thigh, respectively.

    Serious adverse events
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 330 (1.82%)
    3 / 324 (0.93%)
    4 / 330 (1.21%)
         number of deaths (all causes)
    1
    0
    0
         number of deaths resulting from adverse events
    Gastrointestinal disorders
    Enteritis
         subjects affected / exposed
    1 / 330 (0.30%)
    1 / 324 (0.31%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 330 (0.00%)
    0 / 324 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis neonatal
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 324 (0.31%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchopneumonia
         subjects affected / exposed
    3 / 330 (0.91%)
    2 / 324 (0.62%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    2 / 330 (0.61%)
    0 / 324 (0.00%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 330 (0.00%)
    0 / 324 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 330 (0.00%)
    0 / 324 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 324 (0.00%)
    0 / 330 (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
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 324 (0.00%)
    0 / 330 (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
    Malnutrition
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 324 (0.00%)
    0 / 330 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Infanrix-IPV+Hib 1 Group Infanrix-IPV+Hib 2 Group Infanrix-Hib + Poliorix Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    279 / 330 (84.55%)
    277 / 324 (85.49%)
    272 / 330 (82.42%)
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    19 / 330 (5.76%)
    24 / 324 (7.41%)
    17 / 330 (5.15%)
         occurrences all number
    19
    24
    17
    Nasopharyngitis
         subjects affected / exposed
    42 / 330 (12.73%)
    46 / 324 (14.20%)
    50 / 330 (15.15%)
         occurrences all number
    42
    46
    50
    Pain
         subjects affected / exposed
    90 / 330 (27.27%)
    91 / 324 (28.09%)
    102 / 330 (30.91%)
         occurrences all number
    90
    91
    102
    Redness
         subjects affected / exposed
    28 / 330 (8.48%)
    34 / 324 (10.49%)
    26 / 330 (7.88%)
         occurrences all number
    28
    34
    26
    Swelling
         subjects affected / exposed
    14 / 330 (4.24%)
    17 / 324 (5.25%)
    19 / 330 (5.76%)
         occurrences all number
    14
    17
    19
    Drowsiness
         subjects affected / exposed
    124 / 330 (37.58%)
    102 / 324 (31.48%)
    99 / 330 (30.00%)
         occurrences all number
    124
    102
    99
    Irritability
         subjects affected / exposed
    171 / 330 (51.82%)
    166 / 324 (51.23%)
    163 / 330 (49.39%)
         occurrences all number
    171
    166
    163
    Loss of appetite
         subjects affected / exposed
    131 / 330 (39.70%)
    136 / 324 (41.98%)
    114 / 330 (34.55%)
         occurrences all number
    131
    136
    114
    Fever (Axillary)
         subjects affected / exposed
    217 / 330 (65.76%)
    217 / 324 (66.98%)
    183 / 330 (55.45%)
         occurrences all number
    217
    217
    183
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    23 / 330 (6.97%)
    22 / 324 (6.79%)
    33 / 330 (10.00%)
         occurrences all number
    23
    22
    33

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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