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    Clinical Trial Results:
    Immunogenicity and safety of Sanofi Pasteur’s DTaP-IPV combined vaccine (TETRAXIM™) given as a three-dose primary vaccination in South Korean healthy infants, as compared to commercially available DTaP and IPV monovalent vaccines

    Summary
    EudraCT number
    2015-005348-33
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    23 Jun 2007

    Results information
    Results version number
    v1(current)
    This version publication date
    09 Jun 2016
    First version publication date
    09 Jun 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    E2I28
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00319852
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Sanofi Pasteur Ltd
    Sponsor organisation address
    8th floor, Handok Building, 735, Yoksam 1-dong, Kangnam-ku, Seoul, Korea, Republic of,
    Public contact
    Medical Director, Sanofi Pasteur Ltd, 33 4 37 65 67 99, Emmanuel.vidor@sanofipasteur.com
    Scientific contact
    Medical Director, Sanofi Pasteur Ltd, 33 4 37 65 67 99, Emmanuel.vidor@sanofipasteur.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 May 2008
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Jun 2007
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the non-inferiority in terms of seroprotection rates (Diphtheria, Tetanus, Polio types 1, 2 and 3) and seroconversion/vaccine response rates to Pertussis antigens (PT, FHA) of Sanofi Pasteur’s DTaP-IPV combined vaccine versus commercially available Biken’s DTaP (CJ purified PDT vaccine ™) and Aventis Pasteur’s IPV (IMOVAX POLIO™) monovalent vaccines, one month after the three-dose primary vaccination.
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.
    Background therapy
    Not applicable
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    18 Apr 2006
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Korea, Republic of: 442
    Worldwide total number of subjects
    442
    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)
    442
    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
    Study subjects were enrolled from 18 April 2006 to 23 January 2007 at 9 clinic sites in South Korea.

    Pre-assignment
    Screening details
    A total of 442 infants who met all inclusion and none of the exclusion criteria were randomized and vaccinated in this study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    DTaP-IPV combined vaccine
    Arm description
    Healthy infants received Sanofi Pasteur's DTaP-IPV combined vaccine (TETRAXIM™) at 2, 4, and 6 months of age.
    Arm type
    Experimental

    Investigational medicinal product name
    DTaP-IPV combined vaccine (TETRAXIM™)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular injection into the right anterolateral thigh, 1 injection each at 2, 4, and 6 months of age

    Arm title
    DTaP and IPV monovalent vaccines
    Arm description
    Healthy infants received Biken's DTaP (Cheil Jedang [CJ] purified PDT vaccine™) and Sanofi Pasteur's IPV (IMOVAX POLIO™) monovalent vaccines at separate injection sites at 2, 4, and 6 months of age.
    Arm type
    Active comparator

    Investigational medicinal product name
    DTaP vaccine (CJ purified PDT vaccine™)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular injection into the right anterolateral thigh, 1 injection each at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Inactivated polio virus (IPV) vaccine (IMOVAX POLIO™)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular injection into the left anterolateral thigh, 1 injection each at 2, 4, and 6 months of age.

    Number of subjects in period 1
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines
    Started
    219
    223
    Completed
    216
    218
    Not completed
    3
    5
         Protocol deviation
             -
             1
         Consent withdrawn by subject
             3
             4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    DTaP-IPV combined vaccine
    Reporting group description
    Healthy infants received Sanofi Pasteur's DTaP-IPV combined vaccine (TETRAXIM™) at 2, 4, and 6 months of age.

    Reporting group title
    DTaP and IPV monovalent vaccines
    Reporting group description
    Healthy infants received Biken's DTaP (Cheil Jedang [CJ] purified PDT vaccine™) and Sanofi Pasteur's IPV (IMOVAX POLIO™) monovalent vaccines at separate injection sites at 2, 4, and 6 months of age.

    Reporting group values
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines Total
    Number of subjects
    219 223 442
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    219 223 442
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    0 0 0
        From 65-84 years
    0 0 0
        85 years and over
    0 0 0
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    2 ± 0.1 2 ± 0.1 -
    Gender categorical
    Units: Subjects
        Female
    103 102 205
        Male
    116 121 237

    End points

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    End points reporting groups
    Reporting group title
    DTaP-IPV combined vaccine
    Reporting group description
    Healthy infants received Sanofi Pasteur's DTaP-IPV combined vaccine (TETRAXIM™) at 2, 4, and 6 months of age.

    Reporting group title
    DTaP and IPV monovalent vaccines
    Reporting group description
    Healthy infants received Biken's DTaP (Cheil Jedang [CJ] purified PDT vaccine™) and Sanofi Pasteur's IPV (IMOVAX POLIO™) monovalent vaccines at separate injection sites at 2, 4, and 6 months of age.

    Primary: Percentage of Subjects with Seroprotection Against Vaccine Antigens Following A Three-Dose Primary Series Vaccination with Either DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercially Available DTaP and IPV Monovalent Vaccines

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    End point title
    Percentage of Subjects with Seroprotection Against Vaccine Antigens Following A Three-Dose Primary Series Vaccination with Either DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercially Available DTaP and IPV Monovalent Vaccines
    End point description
    Anti-Tetanus, Anti-Pertussis toxoid (PT), and Anti-Filamentous hemagglutinin (FHA) antibody titers were measured using an enzyme-linked immunosorbent assay (ELISA), Anti-Diphtheria and Anti-Poliovirus types 1, 2, 3 antibody titers were measured using seroneutralization. Seroprotection for Anti-Tetanus and Anti-Diptheria was defined as antibody titers ≥ 0.1 IU/mL and for Anti-Poliovirus types 1, 2, and 3 antibody titers ≥ 8 (1/dil). Seroconversion or vaccine response for Anti-PT and Anti-FHA was defined as ≥ 4-fold increase.
    End point type
    Primary
    End point timeframe
    1 month post-dose 3 of primary vaccination
    End point values
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines
    Number of subjects analysed
    198
    205
    Units: Percentage of subjects
    number (not applicable)
        Anti-Tetanus
    99
    99
        Anti-Diphtheria
    100
    100
        Anti-Polio 1
    100
    99.5
        Anti-Polio 2
    100
    99
        Anti-Polio 3
    100
    99
        Anti-PT
    97
    94.6
        Anti-FHA
    92.4
    78.4
    Statistical analysis title
    Non-inferiority; Anti-Tetanus
    Statistical analysis description
    Non-inferiority analysis of Anti-Tetanus in DTaP-IPV vaccine (TETRAXIM™) minus DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines group.
    Comparison groups
    DTaP-IPV combined vaccine v DTaP and IPV monovalent vaccines
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [1]
    Method
    Parameter type
    Percentage observed (TETRAXIM-Control)
    Point estimate
    -0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.75
         upper limit
    2.61
    Notes
    [1] - The 95% CI was calculated based on the Wilson score method without continuity correction as described by Newcombe R.G. If the lower bound of the 95% CI was greater than -10% than the null hypothesis H0 was rejected and it could be concluded for the non-inferiority of valence i. DTaP-IPV vaccine (TETRAXIM™) was non-inferior to DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines.
    Statistical analysis title
    Non-inferiority; Anti-Diphtheria
    Statistical analysis description
    Non-inferiority analysis of Anti-Diphtheria in DTaP-IPV vaccine (TETRAXIM™) minus DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines group.
    Comparison groups
    DTaP-IPV combined vaccine v DTaP and IPV monovalent vaccines
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [2]
    Method
    Parameter type
    Percentage observed (TETRAXIM-Control)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.94
         upper limit
    1.88
    Notes
    [2] - The 95% CI was calculated based on the Wilson score method without continuity correction as described by Newcombe R.G. If the lower bound of the 95% CI was greater than -10% than the null hypothesis H0 was rejected and it could be concluded for the non-inferiority of valence i. DTaP-IPV vaccine (TETRAXIM™) was non-inferior to DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines.
    Statistical analysis title
    Non-inferiority; Anti-Polio 1
    Statistical analysis description
    Non-inferiority analysis of Anti-Polio 1 in DTaP-IPV vaccine (TETRAXIM™) minus DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines group.
    Comparison groups
    DTaP-IPV combined vaccine v DTaP and IPV monovalent vaccines
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [3]
    Method
    Parameter type
    Percentage observed (TETRAXIM-Control)
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.48
         upper limit
    2.75
    Notes
    [3] - The 95% CI was calculated based on the Wilson score method without continuity correction as described by Newcombe R.G. If the lower bound of the 95% CI was greater than -10% than the null hypothesis H0 was rejected and it could be concluded for the non-inferiority of valence i. DTaP-IPV vaccine (TETRAXIM™) was non-inferior to DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines.
    Statistical analysis title
    Non-inferiority; Anti-Polio 2
    Statistical analysis description
    Non-inferiority analysis of Anti-Polio 2 in DTaP-IPV vaccine (TETRAXIM™) minus DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines group.
    Comparison groups
    DTaP-IPV combined vaccine v DTaP and IPV monovalent vaccines
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [4]
    Method
    Parameter type
    Percentage observed (TETRAXIM-Control)
    Point estimate
    0.99
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.06
         upper limit
    3.52
    Notes
    [4] - The 95% CI was calculated based on the Wilson score method without continuity correction as described by Newcombe R.G. If the lower bound of the 95% CI was greater than -10% than the null hypothesis H0 was rejected and it could be concluded for the non-inferiority of valence i. DTaP-IPV vaccine (TETRAXIM™) was non-inferior to DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines.
    Statistical analysis title
    Non-inferiority; Anti-Polio 3
    Statistical analysis description
    Non-inferiority analysis of Anti-Polio 3 in DTaP-IPV vaccine (TETRAXIM™) minus DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines group.
    Comparison groups
    DTaP-IPV combined vaccine v DTaP and IPV monovalent vaccines
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [5]
    Method
    Parameter type
    Percentage observed (TETRAXIM-Control)
    Point estimate
    0.99
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.06
         upper limit
    3.52
    Notes
    [5] - The 95% CI was calculated based on the Wilson score method without continuity correction as described by Newcombe R.G. If the lower bound of the 95% CI was greater than -10% than the null hypothesis H0 was rejected and it could be concluded for the non-inferiority of valence i. DTaP-IPV vaccine (TETRAXIM™) was non-inferior to DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines.
    Statistical analysis title
    Non-inferiority; Anti-PT
    Statistical analysis description
    Non-inferiority analysis of Anti-PT in DTaP-IPV vaccine (TETRAXIM™) minus DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines group.
    Comparison groups
    DTaP-IPV combined vaccine v DTaP and IPV monovalent vaccines
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [6]
    Method
    Parameter type
    Percentage observed (TETRAXIM-Control)
    Point estimate
    2.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.82
         upper limit
    6.67
    Notes
    [6] - The 95% CI was calculated based on the Wilson score method without continuity correction as described by Newcombe R.G. If the lower bound of the 95% CI was greater than -10% than the null hypothesis H0 was rejected and it could be concluded for the non-inferiority of valence i. DTaP-IPV vaccine (TETRAXIM™) was non-inferior to DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines.
    Statistical analysis title
    Non-inferiority; Anti-FHA
    Statistical analysis description
    Non-inferiority analysis of Anti-FHA in DTaP-IPV vaccine (TETRAXIM™) minus DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines group.
    Comparison groups
    DTaP-IPV combined vaccine v DTaP and IPV monovalent vaccines
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [7]
    Method
    Parameter type
    Percentage observed (TETRAXIM-Control)
    Point estimate
    13.95
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7.12
         upper limit
    20.77
    Notes
    [7] - The 95% CI was calculated based on the Wilson score method without continuity correction as described by Newcombe R.G. If the lower bound of the 95% CI was greater than -10% than the null hypothesis H0 was rejected and it could be concluded for the non-inferiority of valence i. DTaP-IPV vaccine (TETRAXIM™) was non-inferior to DTaP (CJ purified PDT vaccine) and IPV (IMOVAX POLIO™) monovalent vaccines.

    Secondary: Geometric Mean Titers of Antibodies Against Vaccine Antigens Before and Following A Three-Dose Primary Series Vaccination with Either DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercially Available DTaP and IPV Monovalent Vaccines

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    End point title
    Geometric Mean Titers of Antibodies Against Vaccine Antigens Before and Following A Three-Dose Primary Series Vaccination with Either DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercially Available DTaP and IPV Monovalent Vaccines
    End point description
    Anti-Tetanus, Anti-Pertussis toxoid (PT), and Anti-Filamentous hemagglutinin (FHA) antibody titers were measured using an enzyme-linked immunosorbent assay (ELISA), Anti-Diphtheria and Anti-Poliovirus types 1, 2, 3 antibody titers were measured using seroneutralization.
    End point type
    Secondary
    End point timeframe
    Day 0 (pre-primary vaccination) and Day 30 post-dose 3 primary vaccination
    End point values
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines
    Number of subjects analysed
    197
    205
    Units: Titers (1/dil)
    geometric mean (confidence interval 95%)
        Anti-Diphtheria; Pre-vaccination
    0.005 (0.004 to 0.006)
    0.004 (0.004 to 0.005)
        Anti-Diphtheria; Post-vaccination
    0.718 (0.623 to 0.826)
    0.705 (0.616 to 0.807)
        Anti-Tetanus; Pre-vaccination
    0.022 (0.018 to 0.026)
    0.019 (0.016 to 0.023)
        Anti-Tetanus; Post-vaccination
    3.98 (3.53 to 4.5)
    3.68 (3.28 to 4.13)
        Anti-Polio 1; Pre-vaccination
    4.18 (3.59 to 4.85)
    4.65 (3.99 to 5.43)
        Anti-Polio 1; Post-vaccination
    1385 (1158 to 1657)
    497 (425 to 581)
        Anti-Polio 2; Pre-vaccination
    6.69 (5.74 to 7.8)
    9.52 (8 to 11.3)
        Anti-Polio 2; Post-vaccination
    1554 (1284 to 1880)
    605 (518 to 708)
        Anti-Polio 3; Pre-vaccination
    3.93 (3.43 to 4.5)
    4.35 (3.82 to 4.95)
        Anti-Polio 3; Post-vaccination
    1718 (1410 to 2093)
    632 (531 to 752)
        Anti-PT; Pre-vaccination
    2.24 (1.96 to 2.57)
    2.78 (2.38 to 3.24)
        Anti-PT; Post-vaccination
    206 (180 to 236)
    199 (172 to 230)
        Anti-FHA; Pre-vaccination
    4.09 (3.6 to 4.65)
    4.15 (3.61 to 4.78)
        Anti-FHA; Post-vaccination
    134 (121 to 148)
    44.5 (40.7 to 48.6)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titer Ratios of Antibodies Against Vaccine Antigens Following A Three-Dose Primary Series Vaccination with Either DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercially Available DTaP and IPV Monovalent Vaccines

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    End point title
    Geometric Mean Titer Ratios of Antibodies Against Vaccine Antigens Following A Three-Dose Primary Series Vaccination with Either DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercially Available DTaP and IPV Monovalent Vaccines
    End point description
    Anti-Tetanus, Anti-Pertussis toxoid (PT), and Anti-Filamentous hemagglutinin (FHA) antibody titers were measured using an enzyme-linked immunosorbent assay (ELISA), Anti-Diphtheria and Anti-Poliovirus types 1, 2, 3 antibody titers were measured using seroneutralization. The post-primary/pre-primary vaccination geometric mean ratio is reported.
    End point type
    Secondary
    End point timeframe
    Day 0 (pre-vaccination) and Day 30 post-primary vaccination
    End point values
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines
    Number of subjects analysed
    196
    204
    Units: Titer ratios (1/dil)
    geometric mean (confidence interval 95%)
        Anti-Diphtheria
    141 (110 to 180)
    175 (145 to 212)
        Anti-Tetanus
    186 (145 to 239)
    199 (159 to 250)
        Anti-Polio 1
    341 (270 to 430)
    108 (85.2 to 138)
        Anti-Polio 2
    234 (179 to 307)
    65.3 (49.8 to 85.7)
        Anti-Polio 3
    439 (347 to 554)
    148 (120 to 182)
        Anti-PT
    91.3 (74.5 to 112)
    71.3 (56.8 to 89.5)
        Anti-FHA
    32.5 (27.3 to 38.7)
    10.9 (9.11 to 13.1)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Seroprotection Against Diphtheria, Tetanus, and Polio Types 1, 2 and 3 Antigens Before and After A Three-Dose Primary Series Vaccination with DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercial DTaP and IPV Monovalent Vaccines

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    End point title
    Percentage of Subjects with Seroprotection Against Diphtheria, Tetanus, and Polio Types 1, 2 and 3 Antigens Before and After A Three-Dose Primary Series Vaccination with DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercial DTaP and IPV Monovalent Vaccines
    End point description
    Anti-Tetanus antibody titers were measured using an enzyme-linked immunosorbent assay (ELISA) and Anti-Diphtheria and Anti-Poliovirus types 1, 2, 3 antibody titers were measured using seroneutralization. Seroprotection for Anti-Tetanus and Anti-Diptheria was defined as antibody titers ≥ 0.01 IU/mL and ≥ 0.1 IU/mL and for Anti-Poliovirus types 1, 2, and 3 antibody titers ≥ 8 (1/dil).
    End point type
    Secondary
    End point timeframe
    Day 0 (pre-primary vaccination) and Day 30 post-primary vaccination
    End point values
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines
    Number of subjects analysed
    197
    205
    Units: Percentage of subjects
    number (not applicable)
        Anti-Diphtheria; ≥ 0.01 IU/mL; Pre-vaccination
    27.4
    21
        Anti-Diphtheria; ≥ 0.01 IU/mL; Post-vaccination
    100
    100
        Anti-Diphtheria; ≥ 0.1 IU/mL; Pre-vaccination
    3
    0
        Anti-Diphtheria; ≥ 0.1 IU/mL; Post-vaccination
    93.8
    95.5
        Anti-Tetanus; ≥ 0.01 IU/mL; Pre-vaccination
    65.3
    65
        Anti-Tetanus; ≥ 0.01 IU/mL; Post-vaccination
    100
    100
        Anti-Tetanus; ≥ 0.1 IU/mL; Pre-vaccination
    15.8
    13.3
        Anti-Tetanus; ≥ 0.1 IU/mL; Post-vaccination
    99
    99
        Anti-Polio 1; Pre-vaccination
    24.5
    30.2
        Anti-Polio 1; Post-vaccination
    100
    99.5
        Anti-Polio 2; Pre-vaccination
    45.2
    56.9
        Anti-Polio 2; Post-vaccination
    100
    99
        Anti-Polio 3; Pre-vaccination
    20.8
    27.3
        Anti-Polio 3; Post-vaccination
    100
    99
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with ≥ 2-Fold and ≥ 4-Fold Increases Against Anti-Pertussis Toxoid and Anti-Filamentous Haemagglutinin Antigens After A Three-Dose Primary Series with DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercial DTaP and IPV Vaccines

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    End point title
    Percentage of Subjects with ≥ 2-Fold and ≥ 4-Fold Increases Against Anti-Pertussis Toxoid and Anti-Filamentous Haemagglutinin Antigens After A Three-Dose Primary Series with DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercial DTaP and IPV Vaccines
    End point description
    Anti-Pertussis toxoid (PT) and Anti-Filamentous hemagglutinin (FHA) antibody titers were measured using an enzyme-linked immunosorbent assay (ELISA). The percentage of subjects with ≥ 2-fold and ≥ 4-fold increases (post-primary/pre-primary vaccination) against Anti-PT and Anti-FHA antigens is reported.
    End point type
    Secondary
    End point timeframe
    Day 0 (pre-vaccination) and Day 30 post-primary vaccination
    End point values
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines
    Number of subjects analysed
    196
    204
    Units: Percentage of subjects
    number (not applicable)
        Anti-PT; ≥ 2-fold increase
    97.5
    95.1
        Anti-PT; ≥ 4-fold increase
    97
    94.6
        Anti-FHA; ≥ 2-fold increase
    97
    89.7
        Anti-FHA; ≥ 4-fold increase
    92.4
    78.4
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Solicited Injection-site and Systemic Reactions Following Any of Three-Dose Primary Series Vaccination with Either DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercially Available DTaP and IPV Monovalent Vaccines

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    End point title
    Percentage of Subjects with Solicited Injection-site and Systemic Reactions Following Any of Three-Dose Primary Series Vaccination with Either DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercially Available DTaP and IPV Monovalent Vaccines
    End point description
    Solicited injection site reactions: Tenderness, Erythema, Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3 Solicited injection site reactions: Tenderness, Cries when injected limb is moved or the movement of the injected limb is reduced; Erythema and Swelling, ≥ 5 cm. Grade 3 Solicited systemic reactions: Fever, ≥ 39°C, Vomiting, ≥ 6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, > 3 hours; Drowsiness, Sleeping most of the time or difficulty to wake up; Appetite lost, Refuses ≥ 3 feeds/meals or refuses most meals; Irritability, Inconsolable. The DTaP-IPV (TETRAXIM™) group reported solicited injection site and systemic reactions following vaccination with DTaP-IPV combined vaccine whereas solicited injection site reactions in the DTaP and IPV monovalent vaccine group are reported by vaccine (DTaP and IPV).
    End point type
    Secondary
    End point timeframe
    Day 0 up to Day 7 post-any vaccination
    End point values
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines
    Number of subjects analysed
    217
    222
    Units: Percentage of subjects
    number (not applicable)
        Any Injection site Tenderness; Post-Any injection
    50.2
    40.5
        Grade 3 Injection site Tenderness; Post-Any inj.
    0.9
    1.4
        Any Inj. site Tenderness; Post-Any inj. (DTaP)
    0
    38.7
        Grade 3 Inj. site Tenderness; Post-Any inj. (DTaP)
    0
    0.9
        Any Inj. site Tenderness; Post-Any inj. (IPV)
    0
    34.7
        Grade 3 Inj. site Tenderness; Post-Any inj. (IPV)
    0
    0.9
        Any Inj. site Erythema; Post-Any injection
    60.4
    42.3
        Grade 3 Inj. site Erythema; Post-Any injection
    0.5
    1.4
        Any Inj. site Erythema; Post-Any inj. (DTaP)
    0
    41
        Grade 3 Inj. site Erythema; Post-Any inj. (DTaP)
    0
    1.4
        Any Inj. site Erythema; Post-Any inj. (IPV)
    0
    17.1
        Grade 3 Inj. site Erythema; Post-Any inj. (IPV)
    0
    0.5
        Any Injection site Swelling; Post-Any injection
    45.6
    29.3
        Grade 3 Injection site Swelling; Post-Any inj.
    0.5
    0.5
        Any Injection site Swelling; Post-Any inj. (DTaP)
    0
    26.6
        Grade 3 Inj. site Swelling; Post-Any inj. (DTaP)
    0
    0.5
        Any Injection site Swelling; Post-Any inj. (IPV)
    0
    11.7
        Grade 3 Inj. site Swelling; Post-Any inj. (IPV)
    0
    0.5
        Any Fever; Post-Any injection
    23.5
    17.1
        Grade 3 Fever; Post-Any injection
    0.9
    0.5
        Any Vomiting; Post-Any injection
    41
    39.6
        Grade 3 Vomiting; Post-Any injection
    0.5
    0
        Any Crying abnormal; Post-Any injection
    46.1
    41.4
        Grade 3 Crying abnormal; Post-Any injection
    0.9
    0.5
        Any Drowsiness; Post-Any injection
    42.9
    38.7
        Grade 3 Drowsiness; Post-Any injection
    0.5
    0
        Any Appetite lost; Post-Any injection
    51.2
    47.7
        Grade 3 Appetite lost; Post-Any injection
    1.4
    0.5
        Any Irritability; Post-Any injection
    45.6
    46.4
        Grade 3 Irritability; Post-Any injection
    1.8
    0.5
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Solicited Injection-site and Systemic Reactions Following Each of Three-Dose Primary Series Vaccination with Either DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercially Available DTaP and IPV Monovalent Vaccines

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    End point title
    Percentage of Subjects with Solicited Injection-site and Systemic Reactions Following Each of Three-Dose Primary Series Vaccination with Either DTaP-IPV Combined Vaccine (TETRAXIM™) or Commercially Available DTaP and IPV Monovalent Vaccines
    End point description
    Solicited injection site reactions: Tenderness, Erythema, Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3 Solicited injection site reactions: Tenderness, Cries when injected limb is moved or the movement of the injected limb is reduced; Erythema and Swelling, ≥ 5 cm. Grade 3 Solicited systemic reactions: Fever, ≥ 39°C, Vomiting, ≥ 6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, > 3 hours; Drowsiness, Sleeping most of the time or difficulty to wake up; Appetite lost, Refuses ≥ 3 feeds/meals or refuses most meals; Irritability, Inconsolable. The DTaP-IPV (TETRAXIM™) group reported solicited injection site and systemic reactions following vaccination with DTaP-IPV combined vaccine whereas solicited injection site reactions in the DTaP and IPV monovalent vaccine group are reported by vaccine (DTaP and IPV).
    End point type
    Secondary
    End point timeframe
    Day 0 up to Day 7 post-each vaccination
    End point values
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines
    Number of subjects analysed
    217
    222
    Units: Percentage of subjects
    number (not applicable)
        Any Injection site Tenderness; Post-injection 1
    37.8
    28.8
        Grade 3 Injection site Tenderness; Post-inj. 1
    0
    0.5
        Any Injection site Tenderness; Post-inj. 1 (DTaP)
    0
    26.1
        Grade 3 Inj. site Tenderness; Post-inj. 1 (DTaP)
    0
    0.5
        Any Injection site Tenderness; Post-inj. 1 (IPV)
    0
    26.6
        Grade 3 Inj. site Tenderness; Post-inj. 1 (IPV)
    0
    0.5
        Any Injection site Tenderness; Post-injection 2
    31.3
    26.1
        Grade 3 Injection site Tenderness; Post-inj. 2
    0.9
    0
        Any Injection site Tenderness; Post-inj. 2 (DTaP)
    0
    23.4
        Grade 3 Inj. site Tenderness; Post-inj. 2 (DTaP)
    0
    0
        Any Injection site Tenderness; Post-inj. 2 (IPV)
    0
    17.1
        Grade 3 Inj. site Tenderness; Post-inj. 2 (IPV)
    0
    0
        Any Injection site Tenderness; Post-injection 3
    30
    24.5
        Grade 3 Injection site Tenderness; Post-inj. 3
    0
    0.9
        Any Injection site Tenderness; Post-inj. 3 (DTaP)
    0
    22.3
        Grade 3 Inj. site Tenderness; Post-inj. 3 (DTaP)
    0
    0.5
        Any Injection site Tenderness; Post-inj. 3 (IPV)
    0
    16.8
        Grade 3 Inj. site Tenderness; Post-inj. 3 (IPV)
    0
    0.5
        Any Injection site Erythema; Post-injection 1
    0
    23.9
        Grade 3 Injection site Erythema; Post-injection 1
    0
    0.3
        Any Injection site Erythema; Post-inj. 1 (DTaP)
    0
    20.2
        Grade 3 Inj. site Erythema; Post-inj. 1 (DTaP)
    0
    0.3
        Any Injection site Erythema; Post-inj. 1 (IPV)
    31.3
    10.4
        Grade 3 Injection site Erythema; Post-inj. 1 (IPV)
    0.5
    0
        Any Injection site Erythema; Post-injection 2
    0
    7.2
        Grade 3 Injection site Erythema; Post-injection 2
    0
    0
        Any Injection site Erythema; Post-inj. 2 (DTaP)
    0
    9.5
        Grade 3 Inj. site Erythema; Post-inj. 2 (DTaP)
    0
    0
        Any Injection site Erythema; Post-inj. 2 (IPV)
    41.9
    33.8
        Grade 3 Injection site Erythema; Post-inj. 2 (IPV)
    0
    1.4
        Any Injection site Erythema; Post-injection 3
    0
    32.9
        Grade 3 Injection site Erythema; Post-injection 3
    0
    1.4
        Any Injection site Erythema; Post-inj. 3 (DTaP)
    0
    9.9
        Grade 3 Inj. site Erythema; Post-inj. 3 (DTaP)
    0
    0.5
        Any Injection site Erythema; Post-inj. 3 (IPV)
    37.3
    23.2
        Grade 3 Injection site Erythema; Post-inj. 3 (IPV)
    0
    0.5
        Any Injection site Swelling; Post-injection 1
    0
    20.8
        Grade 3 Injection site Swelling; Post-injection 1
    0
    0.6
        Any Injection site Swelling; Post-inj. 1 (DTaP)
    0
    10.4
        Grade 3 Inj. site Swelling; Post-inj. 1 (DTaP)
    0
    0.2
        Any Injection site Swelling; Post-inj. 1 (IPV)
    22.1
    5.9
        Grade 3 Injection site Swelling; Post-inj. 1 (IPV)
    0.5
    0
        Any Injection site Swelling; Post-injection 2
    0
    4.1
        Grade 3 Injection site Swelling; Post-injection 2
    0
    0
        Any Injection site Swelling; Post-inj. 2 (DTaP)
    0
    5.4
        Grade 3 Inj. site Swelling; Post-inj. 2 (DTaP)
    0
    0
        Any Injection site Swelling; Post-inj. 2 (IPV)
    30
    19.4
        Grade 3 Injection site Swelling; Post-inj. 2 (IPV)
    0
    0.5
        Any Injection site Swelling; Post-injection 3
    0
    18.5
        Grade 3 Injection site Swelling; Post-injection 3
    0
    0.5
        Any Injection site Swelling; Post-inj. 3 (DTaP)
    0
    5.9
        Grade 3 Inj. site Swelling; Post-inj. 3 (DTaP)
    0
    0.5
        Any Injection site Swelling; Post-inj. 3 (IPV)
    29
    14.5
        Grade 3 Injection site Swelling; Post-inj. 3 (IPV)
    0
    0
        Any Fever; Post-injection 1
    0
    11.6
        Grade 3 Fever; Post-injection 1
    0
    0.2
        Any Fever; Post-injection 2
    0
    6
        Grade 3 Fever; Post-injection 2
    0
    0.2
        Any Fever; Post-injection 3
    9.7
    6.3
        Grade 3 Fever; Post-injection 3
    0
    0
        Any Vomiting; Post-injection 1
    9.7
    8.6
        Grade 3 Vomiting; Post-injection 1
    0.5
    0.5
        Any Vomiting; Post-injection 2
    9.5
    7.1
        Grade 3 Vomiting; Post-injection 2
    0.3
    0.2
        Any Vomiting; Post-injection 3
    30.9
    27.5
        Grade 3 Vomiting; Post-injection 3
    0.5
    0
        Any Crying abnormal; Post-injection 1
    13.4
    12.7
        Grade 3 Crying abnormal; Post-injection 1
    0
    0
        Any Crying abnormal; Post-injection 2
    20.6
    19.1
        Grade 3 Crying abnormal; Post-injection 2
    0.2
    0
        Any Crying abnormal; Post-injection 3
    33.6
    28.4
        Grade 3 Crying abnormal; Post-injection 3
    0.9
    0.5
        Any Drowsiness; Post-injection 1
    18.9
    18.6
        Grade 3 Drowsiness; Post-injection 1
    0
    0
        Any Drowsiness; Post-injection 2
    25.7
    23.6
        Grade 3 Drowsiness; Post-injection 2
    0.3
    0.2
        Any Drowsiness; Post-injection 3
    32.7
    29.3
        Grade 3 Drowsiness; Post-injection 3
    0.5
    0
        Any Appetite lost; Post-injection 1
    15.2
    15.5
        Grade 3 Appetite lost; Post-injection 1
    0
    0
        Any Appetite lost; Post-injection 2
    22.4
    21.1
        Grade 3 Appetite lost; Post-injection 2
    0.2
    0
        Any Appetite lost; Post-injection 3
    32.7
    32.4
        Grade 3 Appetite lost; Post-injection 3
    0.9
    0
        Any Irritability; Post-injection 1
    22.6
    18.6
        Grade 3 Irritability; Post-injection 1
    0
    0
        Any Irritability; Post-injection 2
    27
    24.5
        Grade 3 Irritability; Post-injection 2
    0.5
    0.2
        Any Irritability; Post-injection 3
    34.1
    32.4
        Grade 3 Irritability; Post-injection 3
    0.5
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse event data were collected from Day 0 up to Day 30 post-dose 3 of the primary vaccination series.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    9.0
    Reporting groups
    Reporting group title
    DTaP-IPV combined vaccine
    Reporting group description
    Healthy infants received Sanofi Pasteur's DTaP-IPV combined vaccine (TETRAXIM™) at 2, 4, and 6 months of age.

    Reporting group title
    DTaP and IPV monovalent vaccines
    Reporting group description
    Healthy infants received Biken's DTaP (Cheil Jedang [CJ] purified PDT vaccine™) and Sanofi Pasteur's IPV (IMOVAX POLIO™) monovalent vaccines at separate injection sites at 2, 4, and 6 months of age.

    Serious adverse events
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 217 (6.45%)
    12 / 222 (5.41%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Infections and infestations
    Bronchiolitis
         subjects affected / exposed
    6 / 217 (2.76%)
    4 / 222 (1.80%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiopneumonia
         subjects affected / exposed
    1 / 217 (0.46%)
    0 / 222 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute pyelonephritis
         subjects affected / exposed
    1 / 217 (0.46%)
    0 / 222 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abcess axilla left after BCG vaccination
         subjects affected / exposed
    1 / 217 (0.46%)
    0 / 222 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 217 (0.92%)
    2 / 222 (0.90%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suspected gastroenteritis
         subjects affected / exposed
    1 / 217 (0.46%)
    0 / 222 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suspected sepsis
         subjects affected / exposed
    1 / 217 (0.46%)
    2 / 222 (0.90%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute bronchiolitis
         subjects affected / exposed
    1 / 217 (0.46%)
    2 / 222 (0.90%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    1 / 217 (0.46%)
    0 / 222 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 217 (0.46%)
    0 / 222 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 217 (0.00%)
    2 / 222 (0.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    DTaP-IPV combined vaccine DTaP and IPV monovalent vaccines
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    131 / 217 (60.37%)
    106 / 222 (47.75%)
    Nervous system disorders
    Drowsiness
    alternative assessment type: Systematic
         subjects affected / exposed
    93 / 217 (42.86%)
    86 / 222 (38.74%)
         occurrences all number
    93
    86
    General disorders and administration site conditions
    Injection site Tenderness
    alternative assessment type: Systematic
         subjects affected / exposed
    109 / 217 (50.23%)
    86 / 222 (38.74%)
         occurrences all number
    109
    86
    Injection site Erythema
    alternative assessment type: Systematic
         subjects affected / exposed
    131 / 217 (60.37%)
    91 / 222 (40.99%)
         occurrences all number
    131
    91
    Injection site Swelling
    alternative assessment type: Systematic
         subjects affected / exposed
    99 / 217 (45.62%)
    59 / 222 (26.58%)
         occurrences all number
    99
    59
    Fever
    alternative assessment type: Systematic
         subjects affected / exposed
    51 / 217 (23.50%)
    38 / 222 (17.12%)
         occurrences all number
    51
    38
    Psychiatric disorders
    Crying abnormal
    alternative assessment type: Systematic
         subjects affected / exposed
    100 / 217 (46.08%)
    92 / 222 (41.44%)
         occurrences all number
    100
    92
    Irritability
    alternative assessment type: Systematic
         subjects affected / exposed
    99 / 217 (45.62%)
    103 / 222 (46.40%)
         occurrences all number
    99
    103
    Gastrointestinal disorders
    Vomiting
    alternative assessment type: Systematic
         subjects affected / exposed
    89 / 217 (41.01%)
    88 / 222 (39.64%)
         occurrences all number
    89
    88
    Metabolism and nutrition disorders
    Appetite lost
    alternative assessment type: Systematic
         subjects affected / exposed
    111 / 217 (51.15%)
    106 / 222 (47.75%)
         occurrences all number
    111
    106

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Sep 2006
    Added clarification of the stipends for participation, the approval of the administration of other vaccines during the trial period, and clarified that only the Hib vaccine would be free of charge to subjects.

    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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