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    Clinical Trial Results:
    Immunogenicity and Safety of DTaP-IPV-HB-PRP~T Combined Vaccine Given at 3, 5, and 12 Months of Age Concomitantly or Sequentially with 4CMenB Vaccine in Italian and Finnish Infants

    Summary
    EudraCT number
    		 2019-002585-12
    Trial protocol
    		 IT   FI  
    Global end of trial date
    13 Dec 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 May 2025
    First version publication date
    01 May 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    A3L00057
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 U1111-1239-0365
    Sponsors
    Sponsor organisation name
    Sanofi Winthrop Industrie
    Sponsor organisation address
    82 Avenue Raspail, Gentilly, France, 94250
    Public contact
    Trial Transparency team, Sanofi Winthrop Industrie, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency team, Sanofi Winthrop Industrie, Contact-US@sanofi.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
    04 Oct 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Dec 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the non-inferiority of the co-administration of diphtheria (D), tetanus (T), pertussis (acellular, component), hepatitis B (recombinant deoxyribonucleic acid [rDNA]), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed) (DTaP-IPV-HB-PRP~T combined vaccine) with 4-component meningococcal B (4CMenB) vaccine in terms of seroprotection rates for anti-hepatitis B surface antigen (HBsAg) and anti-haemophilus influenzae type b polyribosyl ribitol phosphate (Hib PRP) antibodies (Ab) compared to the sequential administration of the same vaccines.
    Protection of trial subjects
    Vaccinations were performed by qualified and trained study personnel. Participants with allergy to any of the vaccine components were not vaccinated. After vaccination, participants were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment were also available on site in case of any immediate allergic reactions.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Jan 2021
    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: 98
    Country: Number of subjects enrolled
    Italy: 299
    Worldwide total number of subjects
    397
    EEA total number of subjects
    397
    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)
    397
    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
    		 The study was conducted at 11 sites in Italy and Finland.

    Pre-assignment
    Screening details
    		 A total of 397 participants were randomized in this study.

    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
    		 Group 1: Co-administration
    Arm description
    		 Participants received 0.5 milliliter (mL) intramuscular (IM) injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection each of pneumococcal polysaccharide conjugate (13-valent, adsorbed) (PCV13) vaccine and 4CMenB vaccine at 3, 5, and 12 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    DTaP-IPV-HB-PRP~T combined vaccine
    Investigational medicinal product code
    Other name
    Hexyon®, Hexaxim®, Hexacima®
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine at 3, 5 and 12 months of age.

    Investigational medicinal product name
    4CMenB vaccine
    Investigational medicinal product code
    Other name
    Bexsero®
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received 0.5 mL IM injection of 4CMenB vaccine at 3, 5, and 12 months of age.

    Investigational medicinal product name
    PCV13 vaccine
    Investigational medicinal product code
    Other name
    Prevenar® 13
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age.

    Arm title
    		 Group 2: Sequential administration
    Arm description
    		 Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age and a sequential administration of 0.5 mL IM injection of 4CMenB vaccine at 4, 6, and 13 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    DTaP-IPV-HB-PRP~T combined vaccine
    Investigational medicinal product code
    Other name
    Hexyon®, Hexaxim®, Hexacima®
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine at 3, 5 and 12 months of age.

    Investigational medicinal product name
    4CMenB vaccine
    Investigational medicinal product code
    Other name
    Bexsero®
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received 0.5 mL IM injection of 4CMenB vaccine at 4, 6 and 13 months of age.

    Investigational medicinal product name
    PCV13 vaccine
    Investigational medicinal product code
    Other name
    Prevenar® 13
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age.

    Number of subjects in period 1
    		Group 1: Co-administration Group 2: Sequential administration
    Started
    201
    196
    Completed
    186
    175
    Not completed
    15
    21
         Adverse event, non-fatal
    1
    -
         Protocol deviation
    3
    5
         Unspecified
    1
    -
         Lost to follow-up
    2
    4
         Withdrawal by parent/guardian
    8
    12

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group 1: Co-administration
    Reporting group description
    		 Participants received 0.5 milliliter (mL) intramuscular (IM) injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection each of pneumococcal polysaccharide conjugate (13-valent, adsorbed) (PCV13) vaccine and 4CMenB vaccine at 3, 5, and 12 months of age.

    Reporting group title
    Group 2: Sequential administration
    Reporting group description
    		 Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age and a sequential administration of 0.5 mL IM injection of 4CMenB vaccine at 4, 6, and 13 months of age.

    Reporting group values
    		 Group 1: Co-administration Group 2: Sequential administration Total
    Number of subjects
    		 201 196 397
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: weeks
        arithmetic mean (standard deviation)
    		 12.9 ( 1.40 ) 12.8 ( 1.33 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 94 91 185
        Male
    		 107 105 212

    End points

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    End points reporting groups
    Reporting group title
    Group 1: Co-administration
    Reporting group description
    		 Participants received 0.5 milliliter (mL) intramuscular (IM) injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection each of pneumococcal polysaccharide conjugate (13-valent, adsorbed) (PCV13) vaccine and 4CMenB vaccine at 3, 5, and 12 months of age.

    Reporting group title
    Group 2: Sequential administration
    Reporting group description
    		 Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age and a sequential administration of 0.5 mL IM injection of 4CMenB vaccine at 4, 6, and 13 months of age.

    Primary: Percentage of Participants who Achieved Anti-Hepatitis B Surface Antigen (HBsAg) Antibodies Concentration Above Predefined Threshold

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    End point title
    		 Percentage of Participants who Achieved Anti-Hepatitis B Surface Antigen (HBsAg) Antibodies Concentration Above Predefined Threshold
    End point description
    Anti-HBsAg Ab were measured by the commercially available VITROS ECi/ECiQ immunodiagnostic system using chemiluminescence detection technology. The percentage of participants with an anti-HBsAg Ab concentration >=10 milli international units per mL (mIU/mL) was assessed. Percentages are rounded off to the tenth decimal place. Analysis was performed on per protocol analysis set (PPAS) which was a subset of the full analysis set (FAS: a subset of randomized participants who received at least 1 dose of the study vaccine) that included participants who did not present with any of the protocol deviations.
    End point type
    Primary
    End point timeframe
    Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    149
    97
    Units: percentage of participants
        number (confidence interval 95%)
    98.0 (94.2 to 99.6)
    95.9 (89.8 to 98.9)
    Statistical analysis title
    		 Difference in percentage of participants
    Comparison groups
    Group 1: Co-administration v Group 2: Sequential administration
    Number of subjects included in analysis
    246
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Difference in percentage of participants
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 8.3
    Notes
    [1] - Non-inferiority concluded if the lower limit of 2-sided 95% confidence interval (CI) of difference between groups was greater than -10%

    Primary: Percentage of Participants who Achieved Anti-polyribosyl Ribitol Phosphate (PRP) Antibodies Concentration Above Predefined Threshold

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    End point title
    		 Percentage of Participants who Achieved Anti-polyribosyl Ribitol Phosphate (PRP) Antibodies Concentration Above Predefined Threshold
    End point description
    Anti-PRP Ab were measured using a Farr-type radioimmunoassay (RIA). The percentage of participants with an anti-PRP Ab concentration >=1.0 microgram [mcg]/mL was assessed. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations.
    End point type
    Primary
    End point timeframe
    Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    149
    97
    Units: percentage of participants
        number (confidence interval 95%)
    86.6 (80.0 to 91.6)
    94.8 (88.4 to 98.3)
    Statistical analysis title
    		 Difference in percentage of participants
    Comparison groups
    Group 1: Co-administration v Group 2: Sequential administration
    Number of subjects included in analysis
    246
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Difference in percentage of participants
    Point estimate
    -8.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.3
         upper limit
    		 -0.4
    Notes
    [2] - Non-inferiority concluded if the lower limit of 2-sided 95% CI of difference between groups was greater than -10%

    Secondary: Percentage of Participants who Achieved Antibodies Against all Antigens of DTaP-IPV-HB-PRP~T Combined Vaccine Above Predefined Thresholds

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    End point title
    		 Percentage of Participants who Achieved Antibodies Against all Antigens of DTaP-IPV-HB-PRP~T Combined Vaccine Above Predefined Thresholds
    End point description
    The following cut-off values were considered: • >=0.01 IU/mL, >=0.1 IU/mL, and >=1.0 IU/mL for anti-D and anti-T Ab concentrations • >=8 (1/dilution) for anti-poliovirus 1, 2, and 3 Ab titers • >=lower limit of quantification (LLOQ) and >=4 times (*) LLOQ for anti-pertussis (PT) and anti-filamentous hemagglutinin (FHA) Ab concentrations • >=0.15 mcg/mL and >=1.0 mcg/mL for anti-PRP Ab concentrations • >=10 mIU/mL and >=100 mIU/mL for anti-HBsAg Ab concentrations. The Ab concentrations against diphtheria, pertussis, tetanus antigens were assayed using electrochemiluminescence (ECL) immunoassay method. Anti-poliovirus types 1, 2, and 3 was measured by a neutralization assay. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Here ’n’= number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    Pre-dose 1 (Month 3) and Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    149
    97
    Units: percentage of participants
    number (confidence interval 95%)
        Anti-D, >=0.01 IU/mL, Month 3 (n=149,97)
    93.3 (88.0 to 96.7)
    92.8 (85.7 to 97.0)
        Anti-D, >=0.1 IU/mL, Month 3 (n=149,97)
    55.7 (47.3 to 63.8)
    48.5 (38.2 to 58.8)
        Anti-D, >=1.0 IU/mL, Month 3 (n=149,97)
    4.0 (1.5 to 8.6)
    5.2 (1.7 to 11.6)
        Anti-D, >=0.01 IU/mL, Month 13 (n=149,97)
    100 (97.6 to 100)
    100 (96.3 to 100)
        Anti-D, >=0.1 IU/mL, Month 13 (n=149,97)
    100 (97.6 to 100)
    100 (96.3 to 100)
        Anti-D, >=1.0 IU/mL, Month 13 (n=149,97)
    92.6 (87.2 to 96.3)
    96.9 (91.2 to 99.4)
        Anti-T, >=0.01 IU/mL, Month 3 (n=149,96)
    99.3 (96.3 to 100)
    100 (96.2 to 100)
        Anti-T, >=0.1 IU/mL, Month 3 (n=149,96)
    95.3 (90.6 to 98.1)
    92.7 (85.6 to 97.0)
        Anti-T, >=1.0 IU/mL, Month 3 (n=149,96)
    55.7 (47.3 to 63.8)
    46.9 (36.6 to 57.3)
        Anti-T, >= 0.01 IU/mL, Month 13 (n=149,97)
    100 (97.6 to 100)
    100 (96.3 to 100)
        Anti-T, >=0.1 IU/mL, Month 13 (n=149,97)
    100 (97.6 to 100)
    100 (96.3 to 100)
        Anti-T, >=1.0 IU/mL, Month 13 (n=149,97)
    90.6 (84.7 to 94.8)
    95.9 (89.8 to 98.9)
        Anti-Polio 1, Month 3 (n=91,60)
    36.3 (26.4 to 47.0)
    41.7 (29.1 to 55.1)
        Anti-Polio 1, Month 13 (n=128,95)
    100 (97.2 to 100)
    100 (96.2 to 100)
        Anti-Polio 2, Month 3 (n=107,64)
    64.5 (54.6 to 73.5)
    79.7 (67.8 to 88.7)
        Anti-Polio 2, Month 13 (n=129,96)
    100 (97.2 to 100)
    100 (96.2 to 100)
        Anti-Polio 3, Month 3 (n=113,70)
    46.0 (36.6 to 55.6)
    44.3 (32.4 to 56.7)
        Anti-Polio 3, Month 13 (n=131,96)
    100 (97.2 to 100)
    100 (96.2 to 100)
        Anti-PT, >=LLOQ, Month 3 (n=149,96)
    100 (97.6 to 100)
    100 (96.2 to 100)
        Anti-PT, >=4*LLOQ, Month 3 (n=149,96)
    100 (97.6 to 100)
    100 (96.2 to 100)
        Anti-PT, >=LLOQ, Month 13 (n=149,97)
    100 (97.6 to 100)
    100 (96.3 to 100)
        Anti-PT, >=4*LLOQ, Month 13 (n=149,97)
    100 (97.6 to 100)
    100 (96.3 to 100)
        Anti-FHA, >=LLOQ, Month 3 (n=148,94)
    100 (97.5 to 100)
    100 (96.2 to 100)
        Anti-FHA, >=4*LLOQ, Month 3 (n=148,94)
    100 (97.5 to 100)
    100 (96.2 to 100)
        Anti-FHA, >=LLOQ, Month 13 (n=149,97)
    100 (97.6 to 100)
    100 (96.3 to 100)
        Anti-FHA, >=4*LLOQ, Month 13 (n=149,97)
    100 (97.6 to 100)
    100 (96.3 to 100)
        Anti-PRP, >=0.15 mcg/mL, Month 3 (n=149,97)
    26.8 (19.9 to 34.7)
    26.8 (18.3 to 36.8)
        Anti-PRP, >=1 mcg/mL, Month 3 (n=149,97)
    2.7 (0.7 to 6.7)
    2.1 (0.3 to 7.3)
        Anti-PRP, >=0.15 mcg/mL, Month 13 (n=149,97)
    98.0 (94.2 to 99.6)
    99.0 (94.4 to 100)
        Anti-HBsAg, >=10 mIU/mL, Month 3 (n=146,95)
    41.1 (33.0 to 49.5)
    31.6 (22.4 to 41.9)
        Anti-HBsAg, >=100 mIU/mL, Month 3 (n=146,95)
    16.4 (10.8 to 23.5)
    11.6 (5.9 to 19.8)
        Anti-HBsAg, >=100 mIU/mL, Month 13 (n=149,97)
    90.6 (84.7 to 94.8)
    82.5 (73.4 to 89.4)
    No statistical analyses for this end point

    Secondary: Geometric Mean Concentrations (GMCs) of Antibodies Against all Antigens of the DTaP-IPV-HB-PRP~T Combined Vaccine Except Polio 1, 2 and 3

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    End point title
    		 Geometric Mean Concentrations (GMCs) of Antibodies Against all Antigens of the DTaP-IPV-HB-PRP~T Combined Vaccine Except Polio 1, 2 and 3
    End point description
    GMCs of Abs against diphtheria, pertussis, tetanus antigens were assayed using ECL immunoassay method. GMCs of Abs against PRP were measured using a Farr-type RIA. Anti-HBsAg Ab were measured by the commercially available VITROSECi/ECiQ immunodiagnostic system using chemiluminescence detection technology. Individual Ab concentrations for D, T, PT, FHA, PRP, and HBsAg are presented. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Here ’n’= number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    Pre-dose 1 (Month 3) and Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    149
    97
    Units: units/mL
    geometric mean (confidence interval 95%)
        Anti-D, Month 3 (n=149,97)
    0.107 (0.083 to 0.137)
    0.102 (0.075 to 0.139)
        Anti-D, Month 13 (n=149,97)
    2.45 (2.22 to 2.70)
    2.73 (2.39 to 3.11)
        Anti-T, Month 3 (n=149,96)
    0.968 (0.773 to 1.21)
    0.841 (0.613 to 1.16)
        Anti-T, Month 13 (n=149,97)
    3.59 (3.11 to 4.14)
    4.62 (3.84 to 5.56)
        Anti-PT, Month 3 (n=149,96)
    6.55 (5.20 to 8.26)
    5.04 (3.78 to 6.71)
        Anti-PT, Month 13 (n=149,97)
    101 (91.0 to 112)
    98.3 (84.5 to 114)
        Anti-FHA, Month 3 (n=148,94)
    34.6 (27.6 to 43.3)
    23.2 (16.0 to 33.7)
        Anti-FHA, Month 13 (n=149,97)
    149 (132 to 167)
    152 (133 to 173)
        Anti-PRP, Month 3 (n=149,97)
    0.073 (0.060 to 0.090)
    0.068 (0.055 to 0.086)
        Anti-PRP, Month 13 (n=149,97)
    6.41 (4.89 to 8.40)
    10.0 (7.55 to 13.3)
        Anti-HBsAg, Month 3 (n=146,95)
    10.9 (8.08 to 14.6)
    7.87 (5.52 to 11.2)
        Anti-HBsAg, Month 13 (n=149,97)
    1296 (957 to 1754)
    1037 (657 to 1638)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers (GMTs) of Antibodies Against Polio 1, 2 and 3

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    End point title
    		 Geometric Mean Titers (GMTs) of Antibodies Against Polio 1, 2 and 3
    End point description
    Anti-poliovirus types 1, 2, and 3 were measured by a neutralization assay. Individual Ab titers for poliovirus types 1, 2, and 3 are presented. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoint are reported. Here ’n’= number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    Pre-dose 1 (Month 3) and Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    131
    96
    Units: 1/dilution
    geometric mean (confidence interval 95%)
        Anti-polio 1, Month 3 (n=91,60)
    5.68 (4.41 to 7.32)
    5.93 (4.49 to 7.82)
        Anti-polio 1, Month 13 (n=128,95)
    875 (730 to 1049)
    1738 (1377 to 2193)
        Anti-polio 2, Month 3 (n=107,64)
    11.7 (9.21 to 14.8)
    14.9 (11.4 to 19.6)
        Anti-polio 2, Month 13 (n=129,96)
    2299 (1877 to 2816)
    3263 (2695 to 3950)
        Anti-polio 3, Month 3 (n=113,70)
    7.15 (5.74 to 8.90)
    6.50 (5.06 to 8.36)
        Anti-polio 3, Month 13 (n=131,96)
    1511 (1213 to 1881)
    1933 (1460 to 2560)
    No statistical analyses for this end point

    Secondary: Geometric Mean Ratio (GMRs) of Antibodies Against all Antigens of the DTaP-IPV-HB-PRP~T Combined Vaccine

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    End point title
    		 Geometric Mean Ratio (GMRs) of Antibodies Against all Antigens of the DTaP-IPV-HB-PRP~T Combined Vaccine
    End point description
    GMR was the ratio of the individual titers post vaccination over pre-vaccination (30 days post-dose 3 over pre-dose 1). GMRs for D, T, poliovirus types 1, 2, and 3, PT, FHA, PRP, and HBsAg are presented. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Here ’n’= number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    Pre-dose 1 (Month 3) and Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    149
    97
    Units: ratio
    geometric mean (confidence interval 95%)
        Anti-D (n=149,97)
    22.9 (17.1 to 30.8)
    26.8 (18.5 to 38.9)
        Anti-T (n=149,96)
    3.71 (2.83 to 4.87)
    5.62 (3.90 to 8.09)
        Anti-Polio 1 (n=83,60)
    163 (110 to 242)
    289 (183 to 456)
        Anti-Polio 2 (n=98,64)
    212 (146 to 308)
    204 (139 to 300)
        Anti-Polio 3 (n=104,70)
    219 (155 to 308)
    298 (196 to 455)
        Anti-PT (n=149,96)
    15.4 (11.5 to 20.6)
    19.6 (13.6 to 28.4)
        Anti-FHA (n=148,94)
    4.32 (3.28 to 5.70)
    6.61 (4.20 to 10.4)
        Anti-PRP (n=149,97)
    87.4 (61.5 to 124)
    146 (104 to 206)
        Anti-HBsAg (n=146,95)
    125 (79.6 to 195)
    133 (74.1 to 238)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Seroconversion for Anti-pertussis Toxoid and Anti-filamentous Hemagglutinin Adhesion

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    End point title
    		 Percentage of Participants With Seroconversion for Anti-pertussis Toxoid and Anti-filamentous Hemagglutinin Adhesion
    End point description
    The Ab concentrations against pertussis antigens were assayed using ECL immunoassay method. Seroconversion was defined as >=4-fold increase from pre-dose 1 to post-dose 3 Ab concentrations. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoints are reported. Here ’n’= number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    From pre-dose 1 (Month 3) up to Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    149
    96
    Units: percentage of participants
    number (confidence interval 95%)
        Anti-PT (n=149,96)
    71.8 (63.9 to 78.9)
    78.1 (68.5 to 85.9)
        Anti-FHA (n=148,94)
    48.0 (39.7 to 56.3)
    54.3 (43.7 to 64.6)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Antibodies Against 4-component Meningococcal B Vaccine Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Above Predefined Threshold

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    End point title
    		 Percentage of Participants With Antibodies Against 4-component Meningococcal B Vaccine Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Above Predefined Threshold
    End point description
    Functional Ab activity against a panel of different nesseiria meningitidis antigens (neisseria adhesin A [NadA], factor H binding protein [fHbp] and outer membrane vesicles containing outer membrane protein [PorA P1.4]) were measured using an hSBA assay. Cut-off value was >=5 (1/dilution) Ab titers. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoints are reported. Here ’n’= number of participants with data collected for each specified category. 99999=no participants experiencing the endpoint.
    End point type
    Secondary
    End point timeframe
    Pre-dose 1 (Month 3) and Day 30 post-dose 3 of 4CMenB vaccine (Month 13 for Group 1; Month 14 for Group 2)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    127
    94
    Units: percentage of participants
    number (confidence interval 95%)
        Anti-NadA, Month 3 (n=123,83)
    0.8 (0 to 4.4)
    99999 (99999 to 99999)
        Anti-NadA, Month 13 or 14 (n=127,93)
    100 (97.1 to 100)
    100 (96.1 to 100)
        Anti-fHbp, Month 3 (n=123,83)
    4.1 (1.3 to 9.2)
    2.4 (0.3 to 8.4)
        Anti-fHbp, Month 13 or 14 (n=127,94)
    98.4 (94.4 to 99.8)
    100 (96.2 to 100)
        Anti-PorA P1.4, Month 3 (n=123,83)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Anti-PorA P1.4, Month 13 or 14 (n=127,94)
    97.6 (93.3 to 99.5)
    98.9 (94.2 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a Vaccine Response to Pertussis Toxoid and Filamentous Hemagglutinin Adhesion

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    End point title
    		 Percentage of Participants With a Vaccine Response to Pertussis Toxoid and Filamentous Hemagglutinin Adhesion
    End point description
    The Ab concentrations against pertussis antigens were assayed using ECL immunoassay method. Vaccine response was defined as post-dose 3 Ab concentrations >=4 * LLOQ, if pre-dose 1 Ab concentrations <4 * LLOQ or post-dose 3 Ab concentration >=pre-dose 1 Ab concentration, if pre-dose 1 Ab concentrations >=4 * LLOQ. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoints are reported. Here ’n’= number of participants with data collected for a particular category.
    End point type
    Secondary
    End point timeframe
    Pre-dose 1 (Month 3) and Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    149
    96
    Units: percentage of participants
    number (confidence interval 95%)
        Anti-PT (n=149,96)
    97.3 (93.3 to 99.3)
    95.8 (89.7 to 98.9)
        Anti-FHA (n=148,94)
    81.1 (73.8 to 87.0)
    76.6 (66.7 to 84.7)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers of Antibodies Against Antigens of the 4-component Meningococcal B Vaccine

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    End point title
    		 Geometric Mean Titers of Antibodies Against Antigens of the 4-component Meningococcal B Vaccine
    End point description
    Functional Ab activity against a panel of different N. meningitidis antigens (NadA, fHbp and PorA P1.4) were measured using an hSBA assay. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoints are reported. Here ’n’= number of participants with data collected for each specified category. -99999 and 99999=not calculated.
    End point type
    Secondary
    End point timeframe
    Pre-dose 1 (Month 3) and Day 30 post-dose 3 of 4CMenB vaccine (Month 13 for Group 1; Month 14 for Group 2)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    127
    94
    Units: 1/dilution
    geometric mean (confidence interval 95%)
        Anti-NadA, Month 3 (n=123,83)
    2.06 (1.96 to 2.15)
    2.00 (-99999 to 99999)
        Anti-NadA, Month 13 or 14 (n=127,93)
    2412 (2029 to 2868)
    3040 (2411 to 3834)
        Anti-fHbp, Month 3 (n=123,83)
    2.33 (2.16 to 2.51)
    2.17 (2.03 to 2.33)
        Anti-fHbp, Month 13 or 14 (n=127,94)
    68.0 (57.8 to 79.9)
    111 (91.8 to 135)
        Anti-PorA P1.4, Month 3 (n=123,83)
    2.00 (-99999 to 99999)
    2.00 (-99999 to 99999)
        Anti-PorA P1.4, Month 13 or 14 (n=127,94)
    50.9 (41.3 to 62.7)
    102 (79.9 to 130)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titer Ratio (GMTRs) of Antibodies Against Antigens of the 4-component Meningococcal B Vaccine (4CMenB)

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    End point title
    		 Geometric Mean Titer Ratio (GMTRs) of Antibodies Against Antigens of the 4-component Meningococcal B Vaccine (4CMenB)
    End point description
    GMTR was the ratio of the individual titers post-vaccination over pre-vaccination (Day 30 post-dose 3 over pre-dose 1). Functional Ab activity against a panel of different N. meningitidis strains (NadA, fHbp and PorA P1.4) were measured using an hSBA assay. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoints are reported. Here ’n’= number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    Pre-dose 1 (Month 3) and Day 30 post-dose 3 of 4CMenB vaccine (Month 13 for Group 1; Month 14 for Group 2)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    111
    82
    Units: ratio
    geometric mean (confidence interval 95%)
        Anti-NadA (n=111,81)
    1212 (1008 to 1458)
    1518 (1188 to 1939)
        Anti-fHbp (n=111,82)
    29.9 (24.7 to 36.1)
    50.5 (40.5 to 63.0)
        Anti-PorA P1.4 (n=111,82)
    26.7 (21.3 to 33.5)
    52.2 (40.3 to 67.7)
    No statistical analyses for this end point

    Secondary: Geometric Mean Concentrations of Antibodies Against Pneumococcal Capsular Polysaccharide (PnPS) Antigens of the Pneumococcal Polysaccharide Conjugate Vaccine (13-valent, Adsorbed) Vaccine

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    End point title
    		 Geometric Mean Concentrations of Antibodies Against Pneumococcal Capsular Polysaccharide (PnPS) Antigens of the Pneumococcal Polysaccharide Conjugate Vaccine (13-valent, Adsorbed) Vaccine
    End point description
    Anti-pneumococcal Ab was assessed by pneumococcal capsular polysaccharide (PnPS) immunoglobulin G (IgG) ECL assay which is used to quantitate the amount of anti-streptococcus pneumoniae PS (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Ab in human serum. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. GMC for the study population was calculated. Only those participants with data collected at specified timepoint are reported. Here ’n’= number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    Day 30 post-dose 3 of PCV13 vaccine (Month 13)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    119
    94
    Units: mcg/mL
    geometric mean (confidence interval 95%)
        Serotype 1 (n=116,94)
    5.44 (4.64 to 6.38)
    3.72 (3.15 to 4.39)
        Serotype 3 (n=117,94)
    1.10 (0.962 to 1.25)
    0.929 (0.810 to 1.07)
        Serotype 4 (n=116,94)
    3.23 (2.82 to 3.69)
    2.65 (2.25 to 3.12)
        Serotype 5 (n=116,94)
    3.59 (3.13 to 4.13)
    2.83 (2.43 to 3.31)
        Serotype 6A (n=117,94)
    11.0 (9.76 to 12.4)
    8.12 (6.97 to 9.47)
        Serotype 6B (n=119,94)
    6.49 (5.55 to 7.59)
    5.38 (4.46 to 6.49)
        Serotype 7F (n=119,94)
    5.48 (4.93 to 6.08)
    4.52 (3.98 to 5.13)
        Serotype 9V (n=117,94)
    5.28 (4.61 to 6.05)
    4.07 (3.44 to 4.81)
        Serotype 14 (n=119,94)
    10.9 (9.11 to 13.1)
    10.1 (8.58 to 11.9)
        Serotype 18C (n=115,94)
    3.38 (2.98 to 3.84)
    2.82 (2.43 to 3.28)
        Serotype 19A (n=116,94)
    8.12 (6.92 to 9.53)
    5.73 (4.77 to 6.89)
        Serotype 19F (n=117,94)
    10.5 (9.06 to 12.1)
    7.29 (6.24 to 8.52)
        Serotype 23F (n=118,94)
    3.23 (2.78 to 3.75)
    2.75 (2.25 to 3.37)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a Vaccine Response to Pneumococcal Capsular Polysaccharide Antigens

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    End point title
    		 Percentage of Participants With a Vaccine Response to Pneumococcal Capsular Polysaccharide Antigens
    End point description
    The PnPS IgG ECL assay is used to quantitate the amount of anti-Streptococcus pneumoniae PS (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Ab in human serum. Vaccine response was defined as Day 30 post-dose 3 Ab concentration >=0.35 mcg/mL. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoint are reported. Here ’n’= number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    Day 30 post-dose 3 of PCV13 vaccine (Month 13)
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    119
    94
    Units: percentage of participants
    number (confidence interval 95%)
        Serotype 1 (n=116,94)
    100 (96.9 to 100)
    100 (96.2 to 100)
        Serotype 3 (n=117,94)
    92.3 (85.9 to 96.4)
    95.7 (89.5 to 98.8)
        Serotype 4 (n=116,94)
    100 (96.9 to 100)
    100 (96.2 to 100)
        Serotype 5 (n=116,94)
    100 (96.9 to 100)
    98.9 (94.2 to 100)
        Serotype 6A (n=117,94)
    100 (96.9 to 100)
    100 (96.2 to 100)
        Serotype 6B (n=119,94)
    100 (96.9 to 100)
    100 (96.2 to 100)
        Serotype 7F (n=119,94)
    100 (96.9 to 100)
    100 (96.2 to 100)
        Serotype 9V (n=117,94)
    100 (96.9 to 100)
    100 (96.2 to 100)
        Serotype 14 (n=119,94)
    99.2 (95.4 to 100)
    100 (96.2 to 100)
        Serotype 18C (n=115,94)
    100 (96.8 to 100)
    100 (96.2 to 100)
        Serotype 19A (n=116,94)
    100 (96.9 to 100)
    98.9 (94.2 to 100)
        Serotype 19F (n=117,94)
    100 (96.9 to 100)
    100 (96.2 to 100)
        Serotype 23F (n=118,94)
    98.3 (94.0 to 99.8)
    98.9 (94.2 to 100)
    No statistical analyses for this end point

    Secondary: Number of Participants With Immediate Unsolicited Adverse Events

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    End point title
    		 Number of Participants With Immediate Unsolicited Adverse Events
    End point description
    An AE was any untoward medical occurrence in a participant or in a clinical investigation participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Immediate events were recorded to capture medically relevant unsolicited systemic AEs (including those related to the product administered) that occurred within the first 30 minutes after vaccination. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination and included both serious adverse events (SAEs) and non-serious unsolicited AEs. Analysis was performed on the safety analysis set (SafAS) which included those participants who received at least 1 dose of the study vaccine (i.e., 1 dose of the hexavalent vaccine) and had any safety data available.
    End point type
    Secondary
    End point timeframe
    Up to 30 minutes post each vaccination
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    194
    192
    Units: participants
    1
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Solicited Injection Site and Systemic Reactions

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    End point title
    		 Number of Participants With Solicited Injection Site and Systemic Reactions
    End point description
    A solicited reaction was a "pre-listed" adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted in the protocol and CRB and were considered to be related to the product administered. An injection site reaction was an adverse reaction at and around the injection site which were commonly inflammatory reactions. Solicited injection site reactions included tenderness, erythema and swelling around the injection site. Solicited systemic reactions included fever, vomiting, abnormal crying, drowsiness, appetite loss, and irritability. Analysis was performed on SafAS which included those participants who received at least 1 dose of the study vaccine (i.e., 1 dose of the hexavalent vaccine) and had any safety data available. Only those participants with data collected at specified timepoint are reported.
    End point type
    Secondary
    End point timeframe
    Up to 7 days post each vaccination
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    194
    191
    Units: participants
        Solicited injection site reactions
    177
    176
        Solicited systemic reactions
    186
    186
    No statistical analyses for this end point

    Secondary: Number of Participants With Unsolicited Non-serious Adverse Events

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    End point title
    		 Number of Participants With Unsolicited Non-serious Adverse Events
    End point description
    An AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product, and which did not necessarily have a causal relationship with this treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Unsolicited non-serious AEs are reported. Analysis was performed on SafAS which included those participants who received at least 1 dose of the study vaccine (i.e., 1 dose of the hexavalent vaccine) and had any safety data available.
    End point type
    Secondary
    End point timeframe
    Up to 30 days post each vaccination
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    194
    192
    Units: participants
    107
    134
    No statistical analyses for this end point

    Secondary: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

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    End point title
    		 Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
    End point description
    An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. The following AE were captured as AESI throughout the study: extensive limb swelling, hypotonic hyporesponsive episode, convulsions (whether febrile or not), anaphylactic reactions, apnea, and severe neurological conditions. Analysis was performed on SafAS.
    End point type
    Secondary
    End point timeframe
    From Day 0 (Month 3) up to Month 13 for Group 1 and Month 14 for Group 2
    End point values
    		 Group 1: Co-administration Group 2: Sequential administration
    Number of subjects analysed
    194
    192
    Units: participants
        Any SAE
    10
    8
        Any AESI
    0
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Day 0 (Month 3) up to Month 13 for Group 1 and Month 14 for Group 2
    Adverse event reporting additional description
    Analysis was performed on SafAS which included those participants who received at least 1 dose of the study vaccine (i.e., 1 dose of the hexavalent vaccine) and had any safety data available.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Group 2: Sequential administration
    Reporting group description
    		 Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age and a sequential administration of 0.5 mL IM injection of 4CMenB vaccine at 4, 6, and 13 months of age.

    Reporting group title
    Group 1: Co-administration
    Reporting group description
    		 Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection each of PCV13 vaccine and 4CMenB vaccine at 3, 5, and 12 months of age.

    Serious adverse events
    		 Group 2: Sequential administration Group 1: Co-administration
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 192 (4.17%)
    10 / 194 (5.15%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Hand Fracture
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Aortic Valve Stenosis
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic Shock
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 194 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 194 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 192 (1.04%)
    0 / 194 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower Respiratory Tract Infection Viral
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower Respiratory Tract Infection
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Covid-19
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 194 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    3 / 192 (1.56%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 192 (0.00%)
    2 / 194 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinitis
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Syncytial Virus Infection
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 194 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Syncytial Virus Bronchiolitis
         subjects affected / exposed
    1 / 192 (0.52%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Bacterial
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 194 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Group 2: Sequential administration Group 1: Co-administration
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    188 / 192 (97.92%)
    191 / 194 (98.45%)
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    164 / 192 (85.42%)
    164 / 194 (84.54%)
         occurrences all number
    549
    370
    General disorders and administration site conditions
    Injection Site Pain
         subjects affected / exposed
    158 / 192 (82.29%)
    169 / 194 (87.11%)
         occurrences all number
    739
    999
    Injection Site Erythema
         subjects affected / exposed
    141 / 192 (73.44%)
    147 / 194 (75.77%)
         occurrences all number
    534
    695
    Crying
         subjects affected / exposed
    168 / 192 (87.50%)
    171 / 194 (88.14%)
         occurrences all number
    590
    411
    Pyrexia
         subjects affected / exposed
    120 / 192 (62.50%)
    146 / 194 (75.26%)
         occurrences all number
    242
    276
    Injection Site Swelling
         subjects affected / exposed
    117 / 192 (60.94%)
    138 / 194 (71.13%)
         occurrences all number
    398
    545
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    60 / 192 (31.25%)
    49 / 194 (25.26%)
         occurrences all number
    107
    67
    Teething
         subjects affected / exposed
    10 / 192 (5.21%)
    8 / 194 (4.12%)
         occurrences all number
    20
    9
    Diarrhoea
         subjects affected / exposed
    15 / 192 (7.81%)
    11 / 194 (5.67%)
         occurrences all number
    16
    14
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    37 / 192 (19.27%)
    18 / 194 (9.28%)
         occurrences all number
    45
    20
    Rhinorrhoea
         subjects affected / exposed
    11 / 192 (5.73%)
    5 / 194 (2.58%)
         occurrences all number
    12
    5
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    172 / 192 (89.58%)
    177 / 194 (91.24%)
         occurrences all number
    703
    446
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    13 / 192 (6.77%)
    8 / 194 (4.12%)
         occurrences all number
    15
    9
    Ear Infection
         subjects affected / exposed
    10 / 192 (5.21%)
    1 / 194 (0.52%)
         occurrences all number
    11
    1
    Conjunctivitis
         subjects affected / exposed
    12 / 192 (6.25%)
    6 / 194 (3.09%)
         occurrences all number
    13
    6
    Covid-19
         subjects affected / exposed
    16 / 192 (8.33%)
    13 / 194 (6.70%)
         occurrences all number
    16
    13
    Nasopharyngitis
         subjects affected / exposed
    20 / 192 (10.42%)
    14 / 194 (7.22%)
         occurrences all number
    32
    15
    Upper Respiratory Tract Infection
         subjects affected / exposed
    23 / 192 (11.98%)
    11 / 194 (5.67%)
         occurrences all number
    39
    12
    Rhinitis
         subjects affected / exposed
    26 / 192 (13.54%)
    20 / 194 (10.31%)
         occurrences all number
    33
    23
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    134 / 192 (69.79%)
    133 / 194 (68.56%)
         occurrences all number
    316
    254

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Jul 2020
    Updated version following the Italian Medicines Agency (AIFA) feedback.
    29 Jan 2021
    Update of responsible personnel list and study plan.
    21 Jan 2022
    Enrollment of participants in study A3L00057 was slower than anticipated. Therefore, to limit the duration of the study, additional sites in 1 European country where the tested vaccines (Hexyon, Bexsero, Prevenar 13) were licensed (Finland) were added.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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