Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44393   clinical trials with a EudraCT protocol, of which   7405   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Safety and Immunogenicity of GSK Meningococcal Group B Vaccine and 13-valent Pneumococcal Vaccine administered concomitantly with Routine Infant Vaccines to Healthy Infants

    Summary
    EudraCT number
    		 2016-003268-37
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    27 Dec 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Mar 2026
    First version publication date
    13 Mar 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    205239
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03621670
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    79 New Oxford Street, London, WC1A1DG, United Kingdom, TW8 9GS
    Public contact
    GSK Response Center, GlaxoSmithKline, 44 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 44 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Oct 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Dec 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    · To assess the safety and tolerability of rMenB+OMV NZ, PCV13 and other RIV when administered concomitantly to healthy infants at 2, 4, 6 and 12 months of age, throughout the study duration. · To demonstrate the sufficiency of the immune response to rMenB+OMV NZ when administered concomitantly with PCV13 and other RIV to healthy infants at 2, 4 and 6 months of age, at 1 month after the 3rd vaccination. · To demonstrate the sufficiency of the immune response to rMenB+OMV NZ when administered concomitantly with PCV13 and other RIV to healthy infants at 2, 4, 6 and 12 months of age, at 1 month after the 4th vaccination. · To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV to healthy infants 2, 4 and 6 months of age, compared to PCV13 without rMenB+OMV NZ, at 1 month after the 3rd vaccination.
    Protection of trial subjects
    All subjects were observed closely for at least 30 minutes in the clinic after vaccination, with appropriate medical treatment readily available in case of a rare anaphylactic reaction following the administration of vaccines. Study vaccines were administered only by personnel qualified to perform that function according to the routine clinical practice and under applicable local laws and regulations for the specific study site. All subjects were followed up for safety for a period of 6 months to 1 year after the last vaccination.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Jul 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 1196
    Worldwide total number of subjects
    1196
    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)
    1196
    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

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Out of the 1196 participants enrolled, only 1184 participants were included in the Exposed Set and started the study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MenB+PCV Group
    Arm description
    		 Infant participants received rMenB+OMV NZ (Bexsero) along with PCV13 (Prevnar 13), Pediarix, Hiberix and Rotarix on Day 1 and Day 61 followed by rMenB+OMV NZ, PCV13, Pediarix and Hiberix on Day 121 and rMenB+OMV NZ, PCV13/PCV20, M-M-R II and Varivax on Day 301.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bexsero
    Investigational medicinal product code
    Other name
    GSK Biologicals’ Meningococcal group-B vaccine/ rMenB+OMV NZ
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    4 doses per participant

    Investigational medicinal product name
    Prevnar13/20
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    4 doses per participant

    Investigational medicinal product name
    Pediarix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Investigational medicinal product name
    Varivax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 dose per participant

    Investigational medicinal product name
    Rotarix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    2 doses per participant

    Investigational medicinal product name
    M-M-R II
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 dose per participant

    Investigational medicinal product name
    Hiberix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Arm title
    		 Placebo+PCV Group
    Arm description
    		 Infant participants received PCV13 along with placebo, Pediarix, Hiberix and Rotarix on Day 1 and Day 61 followed by PCV13, Placebo, Pediarix and Hiberix on Day 121 and PCV13/PCV20, Placebo M-M-R II and Varivax on Day 301.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    4 doses per participant

    Investigational medicinal product name
    Pediarix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Investigational medicinal product name
    Varivax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 dose per participant

    Investigational medicinal product name
    Rotarix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    2 doses per participant

    Investigational medicinal product name
    M-M-R II
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 dose per participant

    Investigational medicinal product name
    Prevnar13/20
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    4 doses per participant

    Investigational medicinal product name
    Hiberix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Number of subjects in period 1 [1]
    		MenB+PCV Group Placebo+PCV Group
    Started
    781
    403
    Completed
    642
    326
    Not completed
    139
    77
         Adverse event, non-fatal
    3
    1
         Not willing / Not able to be contacted
    9
    13
         Protocol Deviation
    7
    3
         Not specified
    13
    5
         Lost to follow-up
    32
    25
         Consent withdrawal not due to AEs
    54
    18
         Migrated / Moved from the study area
    21
    12
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of the 1196 participants enrolled, only 1184 participants were included in the Exposed Set and started the study.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    MenB+PCV Group
    Reporting group description
    		 Infant participants received rMenB+OMV NZ (Bexsero) along with PCV13 (Prevnar 13), Pediarix, Hiberix and Rotarix on Day 1 and Day 61 followed by rMenB+OMV NZ, PCV13, Pediarix and Hiberix on Day 121 and rMenB+OMV NZ, PCV13/PCV20, M-M-R II and Varivax on Day 301.

    Reporting group title
    Placebo+PCV Group
    Reporting group description
    		 Infant participants received PCV13 along with placebo, Pediarix, Hiberix and Rotarix on Day 1 and Day 61 followed by PCV13, Placebo, Pediarix and Hiberix on Day 121 and PCV13/PCV20, Placebo M-M-R II and Varivax on Day 301.

    Reporting group values
    		 MenB+PCV Group Placebo+PCV Group Total
    Number of subjects
    		 781 403 1184
    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)
    		 781 403 1184
        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
    Sex: Female, Male
    Units: Participants
        Male
    		 401 207 608
        Female
    		 380 196 576
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    		 39 21 60
        Black or African American
    		 84 33 117
        White
    		 531 288 819
        Other (Not specified)
    		 107 56 163
        American Indian or Alaska Native
    		 17 4 21
        Native Hawaiian or Other Pacific Islander
    		 3 1 4

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    MenB+PCV Group
    Reporting group description
    		 Infant participants received rMenB+OMV NZ (Bexsero) along with PCV13 (Prevnar 13), Pediarix, Hiberix and Rotarix on Day 1 and Day 61 followed by rMenB+OMV NZ, PCV13, Pediarix and Hiberix on Day 121 and rMenB+OMV NZ, PCV13/PCV20, M-M-R II and Varivax on Day 301.

    Reporting group title
    Placebo+PCV Group
    Reporting group description
    		 Infant participants received PCV13 along with placebo, Pediarix, Hiberix and Rotarix on Day 1 and Day 61 followed by PCV13, Placebo, Pediarix and Hiberix on Day 121 and PCV13/PCV20, Placebo M-M-R II and Varivax on Day 301.

    Primary: Number of participants reporting any solicited administration site events after the first vaccination administered at Day 1

    		 Close Top of page
    End point title
    		 Number of participants reporting any solicited administration site events after the first vaccination administered at Day 1 [1]
    End point description
    Assessed solicited administration site events include injection site tenderness (administration site pain), erythema (redness), swelling and induration. Any solicited administration site events = occurrence of the event regardless of intensity grade. Data for Rotarix is not presented as it was administered orally. Analysis was performed on the Solicited Safety Set, which included all participants who received a study vaccination and had solicited adverse event data available for the specified duration. Participants in the Placebo+PCV group did not receive Bexsero vaccine, hence they were not analyzed.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 7
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    768
    394
    Units: Participants
        Erythema, Bexsero
    156
    0
        Erythema, Prevnar 13
    100
    39
        Erythema, Placebo
    0
    25
        Erythema, Pediarix
    72
    32
        Erythema, Hiberix
    74
    17
        Induration, Bexsero
    204
    0
        Induration, Prevnar 13
    127
    67
        Induration, Placebo
    0
    22
        Induration, Pediarix
    70
    34
        Induration, Hiberix
    77
    20
        Swelling, Bexsero
    132
    0
        Swelling, Prevnar 13
    77
    34
        Swelling, Placebo
    0
    21
        Swelling, Pediarix
    53
    21
        Swelling, Hiberix
    54
    12
        Tenderness, Bexsero
    352
    0
        Tenderness, Prevnar 13
    310
    107
        Tenderness, Placebo
    0
    81
        Tenderness, Pediarix
    270
    92
        Tenderness, Hiberix
    284
    74
    No statistical analyses for this end point

    Primary: Number of participants reporting any solicited systemic events after the first vaccination administered at Day 1

    		 Close Top of page
    End point title
    		 Number of participants reporting any solicited systemic events after the first vaccination administered at Day 1 [2]
    End point description
    Assessed systemic events include change in eating habits, sleepiness, vomiting, diarrhea, irritability, persistent crying, and fever, defined as body temperature greater than or equal to (≥)38.0°C/100.4°F. Any solicited systemic events = occurrence of the event regardless of intensity grade. Analysis was performed on the Solicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 7
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    768
    394
    Units: Participants
        Change in eating habits
    329
    122
        Diarrhea
    173
    84
        Irritability
    601
    242
        Persistent crying
    248
    89
        Sleepiness
    560
    246
        Vomiting
    176
    79
        Fever
    252
    34
    No statistical analyses for this end point

    Primary: Number of participants reporting any solicited administration site events after the second vaccination administered at Day 61

    		 Close Top of page
    End point title
    		 Number of participants reporting any solicited administration site events after the second vaccination administered at Day 61 [3]
    End point description
    Data for Rotarix is not presented as it was administered orally. Analysis was performed on the Solicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 61 to Day 67
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    699
    364
    Units: Participants
        Erythema, Bexsero
    200
    0
        Erythema, Prevnar 13
    129
    62
        Erythema, Placebo
    0
    44
        Erythema, Pediarix
    99
    54
        Erythema, Hiberix
    86
    41
        Induration, Bexsero
    213
    0
        Induration, Prevnar 13
    142
    63
        Induration, Placebo
    0
    32
        Induration, Pediarix
    109
    55
        Induration, Hiberix
    80
    32
        Swelling, Bexsero
    112
    0
        Swelling, Prevnar 13
    74
    38
        Swelling, Placebo
    0
    19
        Swelling, Pediarix
    52
    33
        Tenderness, Bexsero
    269
    0
        Swelling, Hiberix
    49
    17
        Tenderness, Prevnar 13
    227
    81
        Tenderness, Placebo
    0
    65
        Tenderness, Pediarix
    201
    67
        Tenderness, Hiberix
    207
    52
    No statistical analyses for this end point

    Primary: Number of participants reporting any solicited systemic events after the second vaccination administered at Day 61

    		 Close Top of page
    End point title
    		 Number of participants reporting any solicited systemic events after the second vaccination administered at Day 61 [4]
    End point description
    Analysis was performed on the Solicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 61 to Day 67
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    699
    364
    Units: Participants
        Change in eating habits
    238
    90
        Diarrhea
    119
    66
        Irritability
    514
    215
        Persistent crying
    209
    73
        Sleepiness
    455
    183
        Vomiting
    104
    49
        Fever
    269
    64
    No statistical analyses for this end point

    Primary: Number of participants reporting any solicited administration site events after the third vaccination administered at Day 121

    		 Close Top of page
    End point title
    		 Number of participants reporting any solicited administration site events after the third vaccination administered at Day 121 [5]
    End point description
    Analysis was performed on the Solicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis. Participants in the Placebo+PCV group did not receive Bexsero vaccine, hence they were not analyzed.
    End point type
    Primary
    End point timeframe
    Day 121 to Day 127
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    676
    352
    Units: Participants
        Erythema, Bexsero
    181
    0
        Erythema, Prevnar 13
    127
    71
        Erythema, Placebo
    0
    43
        Erythema, Pediarix
    114
    65
        Erythema, Hiberix
    97
    38
        Induration, Bexsero
    187
    0
        Induration, Prevnar 13
    128
    60
        Induration, Placebo
    0
    26
        Induration, Pediarix
    124
    70
        Induration, Hiberix
    86
    28
        Swelling, Bexsero
    103
    0
        Swelling, Prevnar 13
    67
    39
        Swelling, Placebo
    0
    13
        Swelling, Pediarix
    55
    28
        Swelling, Hiberix
    36
    8
        Tenderness, Bexsero
    244
    0
        Tenderness, Prevnar 13
    210
    66
        Tenderness, Placebo
    0
    52
        Tenderness, Pediarix
    188
    58
        Tenderness, Hiberix
    194
    45
    No statistical analyses for this end point

    Primary: Number of participants reporting any solicited systemic events after the third vaccination administered at Day 121

    		 Close Top of page
    End point title
    		 Number of participants reporting any solicited systemic events after the third vaccination administered at Day 121 [6]
    End point description
    Analysis was performed on the Solicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 121 to Day 127
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    676
    352
    Units: Participants
        Change in eating habits
    205
    94
        Diarrhea
    87
    44
        Irritability
    454
    179
        Persistent crying
    151
    59
        Sleepiness
    326
    142
        Vomiting
    88
    46
        Fever
    216
    55
    No statistical analyses for this end point

    Primary: Number of participants reporting any solicited administration site events after the fourth vaccination administered at Day 301

    		 Close Top of page
    End point title
    		 Number of participants reporting any solicited administration site events after the fourth vaccination administered at Day 301 [7]
    End point description
    Analysis was performed on the Solicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 301 to Day 307
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    579
    299
    Units: Participants
        Erythema, Bexsero
    180
    0
        Erythema, Prevnar 13/20
    119
    37
        Erythema, Placebo
    0
    25
        Erythema, MMR II
    64
    24
        Erythema, Varivax
    62
    20
        Induration, Bexsero
    179
    0
        Induration, Prevnar 13/20
    109
    32
        Induration, Placebo
    0
    24
        Induration, MMR II
    46
    17
        Induration, Varivax
    38
    15
        Swelling, Bexsero
    91
    0
        Swelling, Prevnar 13/20
    52
    18
        Swelling, Placebo
    0
    8
        Swelling, MMR II
    26
    12
        Swelling, Varivax
    23
    9
        Tenderness, Bexsero
    223
    0
        Tenderness, Prevnar 13/20
    181
    35
        Tenderness, Placebo
    0
    31
        Tenderness, MMR II
    130
    28
        Tenderness, Varivax
    119
    27
    No statistical analyses for this end point

    Primary: Number of participants reporting any solicited systemic events after the fourth vaccination administered at Day 301

    		 Close Top of page
    End point title
    		 Number of participants reporting any solicited systemic events after the fourth vaccination administered at Day 301 [8]
    End point description
    Analysis was performed on the Solicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 301 to Day 307
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    614
    314
    Units: Participants
        Change in eating habits
    219
    75
        Diarrhea
    85
    40
        Irritability
    401
    153
        Persistent crying
    115
    29
        Rash
    71
    30
        Sleepiness
    273
    96
        Vomiting
    60
    32
        Fever
    118
    22
    No statistical analyses for this end point

    Primary: Number of participants with any solicited systemic AEs during the 30 days after the fourth vaccination at Day 301

    		 Close Top of page
    End point title
    		 Number of participants with any solicited systemic AEs during the 30 days after the fourth vaccination at Day 301 [9]
    End point description
    Systemic events assessed included rash, parotid/salivary gland swelling, and fever. These systemic adverse events were recorded for 30 days following MMR and VV vaccine administration. Any solicited systemic events = occurrence of the event regardless of intensity grade. Analysis was performed on the Solicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 301 to Day 330
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    627
    321
    Units: Participants
        Parotid/Salivary gland swelling
    20
    17
        Rash
    206
    95
        Fever
    197
    70
    No statistical analyses for this end point

    Primary: Number of participants reporting any unsolicited adverse events (AEs) after the first vaccination administered at Day 1

    		 Close Top of page
    End point title
    		 Number of participants reporting any unsolicited adverse events (AEs) after the first vaccination administered at Day 1 [10]
    End point description
    An unsolicited AEs is an AE that is not solicited using a subject diary and that is spontaneously communicated by the parent(s)/ Legally Authorized Representatives (LARs) who has signed the informed consent or a solicited local or systemic AE that continues beyond the solicited period after vaccination. Any = occurrence of the event regardless of the intensity grade. Analysis was performed on the Unsolicited Safety Set, which included all participants who received a study vaccination and had unsolicited adverse event data available for the specified duration.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 30
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    775
    401
    Units: Participants
    214
    103
    No statistical analyses for this end point

    Primary: Number of participants reporting any SAEs, AEs leading to withdrawal, AESIs and MAAEs

    		 Close Top of page
    End point title
    		 Number of participants reporting any SAEs, AEs leading to withdrawal, AESIs and MAAEs [11]
    End point description
    An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and that results in disability/incapacity. An AE leading to withdrawal includes any AEs/SAEs collected and recorded from the time of the 1st receipt of study vaccines until study end which are identified as reasons for withdrawal of the participant from the study. AESIs are pre-defined (serious or non-serious) AEs of scientific and medical concern specific to the product or program which might warrant further investigation in order to characterize and understand it. MAAEs includes any AEs that required hospitalization, or an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits. Analysis was performed on the Unsolicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 1 up to study end (Day 481 for participants who have not reached 6-month follow-up at the time of Protocol Amendment 7; Day 661 for all others)
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    775
    401
    Units: Participants
        AEs leading to withdrawal
    3
    1
        SAEs
    35
    19
        AESIs
    6
    3
        MAAEs
    375
    177
    No statistical analyses for this end point

    Primary: Number of participants reporting any unsolicited AEs after the fourth vaccination administered at day 301

    		 Close Top of page
    End point title
    		 Number of participants reporting any unsolicited AEs after the fourth vaccination administered at day 301 [12]
    End point description
    Analysis was performed on the Unsolicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 301 to Day 330
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    668
    339
    Units: Participants
    248
    144
    No statistical analyses for this end point

    Primary: Number of participants reporting any unsolicted AEs after the third vaccination administered at Day 121

    		 Close Top of page
    End point title
    		 Number of participants reporting any unsolicted AEs after the third vaccination administered at Day 121 [13]
    End point description
    Analysis was performed on the Unsolicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 121 to Day 150
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    725
    374
    Units: Participants
    230
    120
    No statistical analyses for this end point

    Primary: Number of participants reporting any unsolicited AEs after the second vaccination administered at Day 61

    		 Close Top of page
    End point title
    		 Number of participants reporting any unsolicited AEs after the second vaccination administered at Day 61 [14]
    End point description
    Analysis was performed on the Unsolicited Safety Set. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Day 61 to Day 90
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    745
    388
    Units: Participants
    225
    119
    No statistical analyses for this end point

    Primary: Percentage of participants with human serum bactericidal assay (hSBA) antibody titers >= Lower Limit of Quantitation (LLOQ) for each of the Serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4) and M13520 (NHBA)

    		 Close Top of page
    End point title
    		 Percentage of participants with human serum bactericidal assay (hSBA) antibody titers >= Lower Limit of Quantitation (LLOQ) for each of the Serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4) and M13520 (NHBA) [15] [16]
    End point description
    Serum bactericidal activity is assessed using hSBA against Neisseria meningitidis serogroup B test strains: M14459 (fHbp); 96217 (NadA); NZ98/254 (PorA P1.4); M13520 (NHBA). The sufficiency of the immune response to rMenB+OMV NZ at one month after the third vaccination was to be demonstrated if the lower confidence limit for the percentage of participants achieving hSBA titers ≥ LLOQ is ≥ 60% for each of the M14459, 96217, NZ98/254, M13520 test strain. This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the Per Protocol Set (PPS) for immunogenicity, which included all participants in the Full Analysis Set (FAS) who correctly received the vaccine, with no protocol deviation and are not excluded due to other reasons defined prior to unblinding or analysis. Only participants with data available for the specified analysis at the specified timepoint were included.
    End point type
    Primary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    553
    Units: Percentage of participants
    number (confidence interval 99.2%)
        M14459 (fHbp)
    92.2 (88.6 to 94.9)
        96217 (NadA)
    99.4 (97.9 to 99.9)
        NZ98/254 (PorA)
    73.5 (68.2 to 78.3)
        M13520 (NHBA)
    53.0 (47.3 to 58.6)
    No statistical analyses for this end point

    Primary: Percentage of participants with hSBA titers >= LLOQ against all serogroup B test strains combined (composite response)

    		 Close Top of page
    End point title
    		 Percentage of participants with hSBA titers >= LLOQ against all serogroup B test strains combined (composite response) [17] [18]
    End point description
    The immune response to the rMenB+OMV NZ vaccine is assessed by measuring serum bactericidal activity using hSBA against four Neisseria meningitidis serogroup B test strains: M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA). The composite response is defined as the percentage of participants with hSBA titers ≥ Lower Limit of Quantitation (LLOQ) across all four strains combined. The sufficiency of the immune response to rMenB+OMV NZ at one month after the third vaccination was to be demonstrated if the lower confidence limit for the percentage of participants achieving hSBA titers ≥ LLOQ is ≥ 50% for all strains combined. This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    524
    Units: Percentage of participants
        number (confidence interval 99.2%)
    42.7 (37.0 to 48.6)
    No statistical analyses for this end point

    Primary: Percentage of Participants with hSBA Antibody Titers >= 8 for Strains M14459 (fHbp), NZ98/254 (PorA P1.4), and M13520 (NHBA) and >= 16 for Strain 96217 (NadA) (Composite response across all strains)

    		 Close Top of page
    End point title
    		 Percentage of Participants with hSBA Antibody Titers >= 8 for Strains M14459 (fHbp), NZ98/254 (PorA P1.4), and M13520 (NHBA) and >= 16 for Strain 96217 (NadA) (Composite response across all strains) [19] [20]
    End point description
    The immune response to the rMenB+OMV NZ vaccine is assessed by measuring serum bactericidal activity using hSBA against four Neisseria meningitidis serogroup B test strains: M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA). The composite response is defined as the percentage of participants with hSBA titers ≥ Lower Limit of Quantitation (LLOQ) across all four strains combined. The sufficiency of the immune response to rMenB+OMV NZ at one month after the 4th vaccination was to be demonstrated if the lower confidence limit for the percentage of participants achieving hSBA titers ≥ 8 (for strains M14459, NZ98/254, M13520) and ≥16 (for strain 96217) is ≥65% for all strains combined. This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination)
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    478
    Units: Percentage of participants
        number (confidence interval 95.8%)
    63.2 (58.5 to 67.7)
    No statistical analyses for this end point

    Primary: Percentage of Participants with hSBA Antibody Titers >= 8 for Strains M14459 (fHbp); 96217 (NadA); NZ98/254 (PorA P1.4); M13520 (NHBA) and >= 16 for Strain 96217

    		 Close Top of page
    End point title
    		 Percentage of Participants with hSBA Antibody Titers >= 8 for Strains M14459 (fHbp); 96217 (NadA); NZ98/254 (PorA P1.4); M13520 (NHBA) and >= 16 for Strain 96217 [21] [22]
    End point description
    Serum bactericidal activity is assessed using human complement (hSBA) against Neisseria meningitidis serogroup B test strains: M14459 (fHbp); 96217 (NadA); NZ98/254 (PorA P1.4); M13520 (NHBA). The sufficiency of the immune response to rMenB+OMV NZ at one month after the 4th vaccination was to be demonstrated if the lower confidence limit for the percentage of participants achieving hSBA titers ≥ 8 (for strains M14459, NZ98/254, M13520) and ≥16 (for strain 96217) is ≥75% for each of the M14459, 96217, NZ98/254, M13520 test strains. This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination)
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    505
    Units: Percentage of participants
    number (confidence interval 95.8%)
        M14459 (fHbp)
    89.0 (85.8 to 91.7)
        96217 (NadA)
    99.6 (98.5 to 100)
        NZ98/254 (PorA P1.4)
    83.2 (79.4 to 86.5)
        M13520 (NHBA)
    76.6 (72.5 to 80.4)
    No statistical analyses for this end point

    Primary: Adjusted Geometric Mean Concentrations (GMCs) of Immunoglobubin (IgG) Antibodies Against 13 PCV13 Antigens at 1 Month After Third Vaccination

    		 Close Top of page
    End point title
    		 Adjusted Geometric Mean Concentrations (GMCs) of Immunoglobubin (IgG) Antibodies Against 13 PCV13 Antigens at 1 Month After Third Vaccination
    End point description
    The immune response to PCV13 is evaluated by measuring IgG levels using electrochemiluminescence (ECL) assay. Adjusted GMCs are assessed for each of the 13 PCV13 antigens at 1 month after the third vaccination. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    244
    278
    Units: Microgram per milliliter(µg/mL)
    geometric mean (confidence interval 98.3%)
        Serotype 1
    1.6 (1.4 to 1.9)
    1.5 (1.3 to 1.8)
        Serotype 3
    0.5 (0.4 to 0.6)
    0.5 (0.4 to 0.6)
        Serotype 4
    1.1 (0.9 to 1.3)
    1.1 (1.0 to 1.3)
        Serotype 5
    1.0 (0.8 to 1.2)
    1.0 (0.8 to 1.2)
        Serotype 6
    2.4 (2.0 to 2.8)
    2.5 (2.1 to 2.9)
        Serotype 6B
    1.5 (1.1 to 1.9)
    1.8 (1.4 to 2.3)
        Serotype 7F
    2.8 (2.4 to 3.3)
    2.9 (2.5 to 3.3)
        Serotype 9V
    1.3 (1.1 to 1.6)
    1.4 (1.2 to 1.6)
        Serotype 14
    5.9 (4.7 to 7.4)
    5.8 (4.8 to 7.2)
        Serotype 18C
    1.5 (1.3 to 1.8)
    1.5 (1.3 to 1.8)
        Serotype 19A
    1.7 (1.4 to 2.0)
    1.8 (1.6 to 2.2)
        Serotype 19F
    2.5 (2.1 to 2.9)
    2.5 (2.2 to 2.9)
        Serotype 23F
    0.9 (0.7 to 1.1)
    1.0 (0.8 to 1.2)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [23]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    1.05
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.23
    Notes
    [23] - The non-inferiority (NI) was to be demonstrated if the lower limit of the 2-sided 98.3% confidence interval (CI) of the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 1 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [24]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.9
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.06
    Notes
    [24] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 3 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [25]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.95
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.11
    Notes
    [25] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 6 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [26]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    1.01
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.24
    Notes
    [26] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 14 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [27]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.8
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.02
    Notes
    [27] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 6B antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [28]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.98
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.12
    Notes
    [28] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 7F antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [29]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    1.03
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.22
    Notes
    [29] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 5 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [30]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.98
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.15
    Notes
    [30] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 4 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [31]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.94
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.12
    Notes
    [31] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 9V antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [32]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.91
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.06
    Notes
    [32] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 19A antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [33]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    1
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.18
    Notes
    [33] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 18C antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [34]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.99
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.14
    Notes
    [34] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 19F antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone without rMenB+OMV NZ, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [35]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.87
    Confidence interval
         level
    		 98.3%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.05
    Notes
    [35] - The NI was to be demonstrated if the lower limit of the 2-sided 98.3% CI for the between-group ratio of ECL assay GMC is >0.5 for the PCV13 Serotype 23F antigen.

    Secondary: Adjusted GMCs of IgG Antibodies Against 13 PCV13 Antigens at 1 Month after the fourth vaccination administered at Day 301

    		 Close Top of page
    End point title
    		 Adjusted GMCs of IgG Antibodies Against 13 PCV13 Antigens at 1 Month after the fourth vaccination administered at Day 301
    End point description
    The immune response to PCV13 is evaluated by measuring IgG levels using ECL assay. Adjusted GMCs are assessed for each of the 13 PCV13 antigens at 1 month after the fourth vaccination. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    225
    240
    Units: µg/mL
    geometric mean (confidence interval 95%)
        Serotype 1
    1.8 (1.5 to 2.1)
    1.8 (1.6 to 2.1)
        Serotype 3
    0.5 (0.4 to 0.6)
    0.5 (0.5 to 0.6)
        Serotype 4
    1.5 (1.2 to 1.8)
    1.7 (1.4 to 2.0)
        Serotype 5
    1.8 (1.5 to 2.1)
    1.8 (1.6 to 2.1)
        Serotype 6
    5.2 (4.4 to 6.1)
    6.0 (5.2 to 7.0)
        Serotype 6B
    4.7 (3.9 to 5.6)
    5.4 (4.6 to 6.4)
        Serotype 7F
    3.7 (3.2 to 4.4)
    4.6 (4.0 to 5.3)
        Serotype 9V
    2.3 (2.0 to 2.8)
    2.6 (2.2 to 3.1)
        Serotype 14
    7.0 (5.8 to 8.4)
    7.1 (6.0 to 8.4)
        Serotype 18C
    2.0 (1.7 to 2.4)
    2.2 (1.9 to 2.6)
        Serotype 19A
    4.5 (3.8 to 5.3)
    5.5 (4.7 to 6.4)
        Serotype 19F
    4.8 (4.1 to 5.7)
    5.0 (4.3 to 5.9)
        Serotype 23F
    1.9 (1.5 to 2.3)
    1.9 (1.6 to 2.3)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [36]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.07
    Notes
    [36] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 4 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [37]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.03
    Notes
    [37] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 3 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [38]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.11
    Notes
    [38] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 1 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [39]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.16
    Notes
    [39] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 23F antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [40]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.06
    Notes
    [40] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 9V antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [41]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.17
    Notes
    [41] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 14 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [42]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.04
    Notes
    [42] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 18C antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [43]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 0.95
    Notes
    [43] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 19A antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [44]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.12
    Notes
    [44] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 19F antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [45]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.02
    Notes
    [45] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 6B antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [46]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 0.99
    Notes
    [46] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 6 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [47]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.12
    Notes
    [47] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 5 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    		 [48]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 0.93
    Notes
    [48] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group ratio of ECL assay GMCs is >0.5 for the PCV13 Serotype 7F antigen.

    Secondary: Percentage of participants with serum pneumococcal anti-capsular polysaccharide IgG >= 0.35 μg/mL

    		 Close Top of page
    End point title
    		 Percentage of participants with serum pneumococcal anti-capsular polysaccharide IgG >= 0.35 μg/mL
    End point description
    The immune response to PCV13 is evaluated by measuring the percentage of participants with serum IgG concentrations ≥ 0.35 μg/mL for each of the 13 PCV13 antigens at 1 month after the third and fourth vaccinations. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination) and Day 331 (1 month after the fourth vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    244
    278
    Units: Percentage of participants
    number (confidence interval 95%)
        Serotype 1, At Day 151
    99.2 (97.1 to 99.9)
    97.1 (94.4 to 98.7)
        Serotype 1, At Day 331
    98.7 (96.2 to 99.7)
    97.1 (94.1 to 98.8)
        Serotype 3, At Day 151
    59.8 (53.4 to 66.0)
    61.5 (55.5 to 67.3)
        Serotype 3, At Day 331
    63.6 (56.9 to 69.8)
    69.5 (63.2 to 75.2)
        Serotype 4, At Day 151
    94.3 (90.6 to 96.8)
    96.0 (93.0 to 98.0)
        Serotype 4, At Day 331
    97.8 (94.9 to 99.3)
    96.7 (93.5 to 98.6)
        Serotype 5, At Day 151
    91.0 (86.7 to 94.3)
    87.4 (82.9 to 91.1)
        Serotype 5, At Day 331
    96.0 (92.5 to 98.2)
    98.8 (96.4 to 99.7)
        Serotype 6, At Day 151
    99.2 (97.1 to 99.9)
    99.6 (98.0 to 100)
        Serotype 6, At Day 331
    100 (98.4 to 100)
    99.6 (97.7 to 100)
        Serotype 6B, At Day 151
    89.8 (85.2 to 93.3)
    92.4 (88.7 to 95.3)
        Serotype 6B, At Day 331
    100 (98.4 to 100)
    99.6 (97.7 to 100)
        Serotype 7F, At Day 151
    99.6 (97.7 to 100)
    100 (98.7 to 100)
        Serotype 7F, At Day 331
    99.6 (97.5 to 100)
    100 (98.5 to 100)
        Serotype 9V, At Day 151
    95.1 (91.6 to 97.4)
    93.2 (89.5 to 95.8)
        Serotype 9V, At Day 331
    98.7 (96.1 to 99.7)
    98.8 (96.4 to 99.7)
        Serotype 14, At Day 151
    98.0 (95.3 to 99.3)
    98.6 (96.4 to 99.6)
        Serotype 14, At Day 331
    100 (98.4 to 100)
    100 (98.5 to 100)
        Serotype 18C, At Day 151
    97.5 (94.7 to 99.1)
    96.8 (93.9 to 98.5)
        Serotype 18C, At Day 331
    99.1 (96.8 to 99.9)
    99.2 (97.0 to 99.9)
        Serotype 19A, At Day 151
    96.7 (93.6 to 98.6)
    98.6 (96.4 to 99.6)
        Serotype 19A, At Day 331
    100 (98.4 to 100)
    99.6 (97.7 to 100)
        Serotype 19F, At Day 151
    99.6 (97.7 to 100)
    100 (98.7 to 100)
        Serotype 19F, At Day 331
    100 (98.4 to 100)
    100 (98.5 to 100)
        Serotype 23F, At Day 151
    87.3 (82.5 to 91.2)
    87.0 (82.5 to 90.7)
        Serotype 23F, At Day 331
    97.3 (94.3 to 99.0)
    97.1 (94.1 to 98.8)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [49]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    2.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.38
         upper limit
    		 4.87
    Notes
    [49] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 1 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [50]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    1.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.28
         upper limit
    		 4.74
    Notes
    [50] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 1 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [51]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.29
         upper limit
    		 0.96
    Notes
    [51] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 7F antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [52]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.27
         upper limit
    		 2.33
    Notes
    [52] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 6B antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [53]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -2.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.86
         upper limit
    		 2.21
    Notes
    [53] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 6B antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [54]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.27
         upper limit
    		 2.33
    Notes
    [54] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 6 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [55]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.62
         upper limit
    		 1.27
    Notes
    [55] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 6 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [56]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -2.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.33
         upper limit
    		 0.16
    Notes
    [56] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 5 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [57]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    3.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.86
         upper limit
    		 8.96
    Notes
    [57] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 5 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [58]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.17
         upper limit
    		 4.51
    Notes
    [58] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 4 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [59]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -1.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.87
         upper limit
    		 1.97
    Notes
    [59] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 4 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [60]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -5.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.45
         upper limit
    		 2.69
    Notes
    [60] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 3 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV, compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [61]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -1.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.07
         upper limit
    		 6.7
    Notes
    [61] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 3 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [62]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.48
         upper limit
    		 1.14
    Notes
    [62] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 7F antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [63]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.62
         upper limit
    		 6.07
    Notes
    [63] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 23F antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [64]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.68
         upper limit
    		 1.58
    Notes
    [64] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 19F antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [65]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.29
         upper limit
    		 0.96
    Notes
    [65] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 19F antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [66]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.27
         upper limit
    		 2.33
    Notes
    [66] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 19A antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [67]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -1.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.06
         upper limit
    		 0.83
    Notes
    [67] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 19A antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [68]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.13
         upper limit
    		 3.58
    Notes
    [68] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 23F antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [69]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 3.91
    Notes
    [69] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 18C antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [70]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.68
         upper limit
    		 1.58
    Notes
    [70] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 14 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [71]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.43
         upper limit
    		 1.87
    Notes
    [71] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 14 antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [72]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.76
         upper limit
    		 2.44
    Notes
    [72] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 9V antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [73]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    1.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 6.12
    Notes
    [73] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 9V antigen.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of PCV13 when administered concomitantly with rMenB+OMV NZ and other RIV compared to PCV13 and other RIV alone, at one month after the fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 [74]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.44
         upper limit
    		 2.2
    Notes
    [74] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with IgG ≥ 0.35 µg/mL is >-10% for the PCV13 Serotype 18C antigen.

    Secondary: Adjusted GMCs against 3 pertussis antigens (pertussis toxin [PT], pertactin [PRN], filamentous hemagglutinin [FHA])

    		 Close Top of page
    End point title
    		 Adjusted GMCs against 3 pertussis antigens (pertussis toxin [PT], pertactin [PRN], filamentous hemagglutinin [FHA])
    End point description
    The immune response to DTaP-HBV-IPV (Pediarix) vaccine is evaluated. IgG concentrations for pertussis antigens (PT, FHA, PRN) are measured at 1 month after the third vaccination and are expressed as international units per millilitre (IU/mL). Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    470
    266
    Units: IU/mL
    geometric mean (confidence interval 95%)
        PT
    50.3 (45.1 to 56.0)
    59.6 (53.2 to 66.8)
        FHA
    106.7 (96.4 to 118.0)
    133.1 (119.5 to 148.2)
        Pertactin
    41.7 (36.1 to 48.1)
    65.7 (56.4 to 76.4)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of DTaP-HBV-IPV vaccine when administered concomitantly with rMenB+OMV NZ and PCV13 compared to DTaP-HBV-IPV vaccine concomitantly administered with PCV13 without rMenB+OMV NZ, in terms of PT, FHA and PRN, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    736
    Analysis specification
    Pre-specified
    Analysis type
    		 [75]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 0.94
    Notes
    [75] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group GMC ratio is >0.67 for the antigen PT.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of DTaP-HBV-IPV vaccine when administered concomitantly with rMenB+OMV NZ and PCV13 compared to DTaP-HBV-IPV vaccine concomitantly administered with PCV13 without rMenB+OMV NZ, in terms of PT, FHA and PRN, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    736
    Analysis specification
    Pre-specified
    Analysis type
    		 [76]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 0.73
    Notes
    [76] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group GMC ratio is >0.67 for the antigen PRN.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of DTaP-HBV-IPV vaccine when administered concomitantly with rMenB+OMV NZ and PCV13 compared to DTaP-HBV-IPV vaccine concomitantly administered with PCV13 without rMenB+OMV NZ, in terms of PT, FHA and PRN, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    736
    Analysis specification
    Pre-specified
    Analysis type
    		 [77]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 0.88
    Notes
    [77] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group GMC ratio is >0.67 for the antigen FHA.

    Secondary: Percentage of participants with antibodies concentrations against hepatitis B surface antigen (AntiHBsAg) >= 10 mIU/mL

    		 Close Top of page
    End point title
    		 Percentage of participants with antibodies concentrations against hepatitis B surface antigen (AntiHBsAg) >= 10 mIU/mL
    End point description
    The immune response to DTaP-HBV-IPV vaccine administered with rMenB+OMV NZ and PCV13 is evaluated. IgG concentrations for Hepatitis B (HepB) antigens are measured at 1 month after the third vaccination. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    105
    138
    Units: Percentage of participants
        number (confidence interval 95%)
    100 (96.5 to 100)
    99.3 (96.0 to 100)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of DTaP-HBV-IPV vaccine when administered concomitantly with rMenB+OMV NZ and PCV13 compared to DTaP-HBV-IPV vaccine concomitantly administered with PCV13 without rMenB+OMV NZ, in terms of Hep B, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    243
    Analysis specification
    Pre-specified
    Analysis type
    		 [78]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.83
         upper limit
    		 4
    Notes
    [78] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with anti-HBs >=10 mIU/mL is >-10% for the HBs antigen.

    Secondary: Percentage of participants with anti-diphtheria and anti-tetanus antibody concentrations >= 0.1 IU/mL

    		 Close Top of page
    End point title
    		 Percentage of participants with anti-diphtheria and anti-tetanus antibody concentrations >= 0.1 IU/mL
    End point description
    The immune response to DTaP-HBV-IPV vaccine administered with rMenB+OMV NZ and PCV13 is evaluated. IgG concentrations for diphtheria (D) and tetanus (T) were measured at 1 month after the third vaccination. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    224
    143
    Units: Percentage of participants
    number (confidence interval 95%)
        Tetanus Toxoid
    100 (98.4 to 100)
    100 (97.5 to 100)
        Diphtheria Toxoid
    99.5 (97.5 to 100)
    100 (97.3 to 100)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of DTaP-HBV-IPV vaccine when administered concomitantly with rMenB+OMV NZ and PCV13 compared to DTaP-HBV-IPV vaccine concomitantly administered with PCV13 without rMenB+OMV NZ, in terms of T, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    367
    Analysis specification
    Pre-specified
    Analysis type
    		 [79]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    -0.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.53
         upper limit
    		 2.3
    Notes
    [79] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with anti-tetanus toxoid concentrations >=0.1 IU/mL is >-5%.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of DTaP-HBV-IPV vaccine when administered concomitantly with rMenB+OMV NZ and PCV13 compared to DTaP-HBV-IPV vaccine concomitantly administered with PCV13 without rMenB+OMV NZ, in terms of D, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    367
    Analysis specification
    Pre-specified
    Analysis type
    		 [80]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.69
         upper limit
    		 2.62
    Notes
    [80] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with anti-diphtheria toxoid concentrations >=0.1 IU/mL is >-10%.

    Secondary: Percentage of participants with anti-polyribosyl-ribitol phosphate (PRP) concentration >= 0.15 µg/mL and >= 1 µg/mL

    		 Close Top of page
    End point title
    		 Percentage of participants with anti-polyribosyl-ribitol phosphate (PRP) concentration >= 0.15 µg/mL and >= 1 µg/mL
    End point description
    The immune response to Hib vaccine administered with rMenB+OMV NZ and PCV13 is evaluated. IgG concentrations for Haemophilus influenzae type b (Hib) are measured at 1 month after the third vaccination. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    347
    264
    Units: Percentage of participants
    number (confidence interval 95%)
        >= 0.15 µg/mL
    98.3 (96.3 to 99.4)
    97.7 (95.1 to 99.2)
        >= 1 µg/mL
    87.0 (83.0 to 90.4)
    84.1 (79.1 to 88.3)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of Hib vaccine when administered concomitantly with rMenB+OMV NZ and PCV13 compared to Hib vaccine concomitantly administered with PCV13 without rMenB+OMV NZ, in terms of Hib, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    611
    Analysis specification
    Pre-specified
    Analysis type
    		 [81]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    2.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.63
         upper limit
    		 8.78
    Notes
    [81] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with anti-PRP concentration >=1 µg/mL is >-10%.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of Hib vaccine when administered concomitantly with rMenB+OMV NZ and PCV13 compared to Hib vaccine concomitantly administered with PCV13 without rMenB+OMV NZ, in terms of Hib, at one month after the third vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    611
    Analysis specification
    Pre-specified
    Analysis type
    		 [82]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.79
         upper limit
    		 3.32
    Notes
    [82] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the group differences in percentage of participants with anti-PRP concentration >=0.15 µg/mL is >-5%.

    Secondary: Adjusted GMCs for anti-measles antibodies

    		 Close Top of page
    End point title
    		 Adjusted GMCs for anti-measles antibodies
    End point description
    The immune response to MMR vaccine administered with rMenB+OMV NZ and PCV13 is evaluated. IgG concentrations for measles antigens are measured using adjusted GMCs at 1 month after fourth vaccination and are expressed as milli–International Units per milliliter (mIU/mL). Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    435
    235
    Units: mIU/mL
        geometric mean (confidence interval 95%)
    877.3 (743.7 to 1035.0)
    873.5 (732.2 to 1042.0)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of MMR vaccine when administered concomitantly with rMenB+OMV NZ and PCV13 compared to MMR vaccine concomitantly administered with PCV13, without rMenB+OMV NZ, at one month after fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    670
    Analysis specification
    Pre-specified
    Analysis type
    		 [83]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.17
    Notes
    [83] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group GMC ratio is > 0.67 for the antigen "Measles".

    Secondary: Adjusted GMCs for anti-mumps antibodies

    		 Close Top of page
    End point title
    		 Adjusted GMCs for anti-mumps antibodies
    End point description
    The immune response to MMR vaccine administered with rMenB+OMV NZ and PCV13 is evaluated. IgG concentrations for mumps antigens are measured using adjusted GMCs at 1 month after fourth vaccination. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    435
    235
    Units: Arbitrary Units per milliliter (AU/mL)
        geometric mean (confidence interval 95%)
    744.5 (628.5 to 882.0)
    856.8 (715.0 to 1026.7)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of MMR vaccine when administered concomitantly with rMenB+OMV NZ and PCV13 compared to MMR vaccine concomitantly administered with PCV13, without rMenB+OMV NZ, at one month after fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    670
    Analysis specification
    Pre-specified
    Analysis type
    		 [84]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.02
    Notes
    [84] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group GMC ratio is > 0.67 for the antigen "Mumps".

    Secondary: Adjusted GMCs for anti-rubella antibodies

    		 Close Top of page
    End point title
    		 Adjusted GMCs for anti-rubella antibodies
    End point description
    The immune response to MMR vaccine administered with rMenB+OMV NZ and PCV13 is evaluated. IgG concentrations for rubella antigens are measured using adjusted GMCs at 1 month after fourth vaccination. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    432
    235
    Units: IU/mL
        geometric mean (confidence interval 95%)
    57.7 (50.0 to 66.6)
    54.0 (46.3 to 63.0)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of MMR vaccine when administered concomitantly with rMenB+OMV NZ, VV and PCV13 compared to MMR vaccine concomitantly administered with PCV13, without rMenB+OMV NZ, at one month after fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    667
    Analysis specification
    Pre-specified
    Analysis type
    		 [85]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 1.22
    Notes
    [85] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group GMC ratio is > 0.67 for the antigen "Rubella".

    Secondary: Adjusted GMCs for anti-Varicella (VV) antibodies

    		 Close Top of page
    End point title
    		 Adjusted GMCs for anti-Varicella (VV) antibodies
    End point description
    The immune response to varicella (VV) vaccine administered with rMenB+OMV NZ and PCV13 is evaluated. IgG concentrations for varicella antigens are measured using GMCs at 1 month after fourth vaccination. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    437
    231
    Units: mIU/mL
        geometric mean (confidence interval 95%)
    1283.8 (1137.4 to 1449.2)
    1208.9 (1060.5 to 1378.2)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    To demonstrate the immunological non-inferiority of VV vaccine when administered concomitantly with rMenB+OMV NZ, MMR and PCV13 compared to VV vaccine concomitantly administered with PCV13, without rMenB+OMV NZ, at one month after fourth vaccination.
    Comparison groups
    MenB+PCV Group v Placebo+PCV Group
    Number of subjects included in analysis
    668
    Analysis specification
    Pre-specified
    Analysis type
    		 [86]
    Method
    Parameter type
    		 Group GMC Ratio
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.19
    Notes
    [86] - The NI was to be demonstrated if the lower limit of the 2-sided 95% CI for the between-group GMC ratio is > 0.67 for the antigen "VZV gE".

    Secondary: Percentage of participants with hSBA antibody titers >= 5, >= 8 and >=16 for each of the Serogroup B Test Strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA)

    		 Close Top of page
    End point title
    		 Percentage of participants with hSBA antibody titers >= 5, >= 8 and >=16 for each of the Serogroup B Test Strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA) [87]
    End point description
    This immune response to the rMenB+OMV NZ vaccine only is evaluated, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    Notes
    [87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    553
    Units: Percentage of participants
    number (confidence interval 95%)
        M14459 (fHbp), >= 5
    92.2 (89.6 to 94.3)
        M14459 (fHbp), >= 8
    82.9 (79.4 to 86.0)
        M14459 (fHbp), >= 16
    50.5 (46.2 to 54.8)
        96217 (NadA), >= 5
    99.6 (98.6 to 100)
        96217 (NadA), >= 8
    99.6 (98.6 to 100)
        96217 (NadA), >= 16
    99.4 (98.3 to 99.9)
        NZ98/254 (PorA P1.4), >= 5
    77.7 (74.0 to 81.1)
        NZ98/254 (PorA P1.4), >= 8
    61.8 (57.6 to 65.9)
        NZ98/254 (PorA P1.4), >= 16
    31.1 (27.2 to 35.1)
        M13520 (NHBA), >= 5
    60.4 (56.2 to 64.5)
        M13520 (NHBA), >= 8
    32.4 (28.5 to 36.4)
        M13520 (NHBA), >= 16
    9.4 (7.1 to 12.1)
    No statistical analyses for this end point

    Secondary: Percentage of participants with hSBA antibody titers >= 5 and >= 8 for each of the Serogroup B Test Strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA)

    		 Close Top of page
    End point title
    		 Percentage of participants with hSBA antibody titers >= 5 and >= 8 for each of the Serogroup B Test Strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA) [88]
    End point description
    This immune response to the rMenB+OMV NZ vaccine only is evaluated, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 301 (6 months after third vaccination)
    Notes
    [88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    540
    Units: Percentage of participants
    number (confidence interval 95%)
        M14459 (fHbp), >= 5
    14.5 (11.6 to 17.9)
        M14459 (fHbp), >= 8
    4.8 (3.2 to 7.1)
        96217 (NadA) >= 5
    97.8 (96.1 to 98.9)
        96217 (NadA), >= 8
    96.4 (94.4 to 97.9)
        NZ98/254 (PorA P1.4), >= 5
    20.2 (16.8 to 23.8)
        NZ98/254 (PorA P1.4), >= 8
    12.2 (9.6 to 15.3)
        M13520 (NHBA), >= 5
    10.2 (7.8 to 13.1)
        M13520 (NHBA) >= 8
    5.9 (4.1 to 8.3)
    No statistical analyses for this end point

    Secondary: Percentage of participants with hSBA antibody titers >= 5 for each of the Serogroup B Test Strain M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA)

    		 Close Top of page
    End point title
    		 Percentage of participants with hSBA antibody titers >= 5 for each of the Serogroup B Test Strain M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA) [89]
    End point description
    This immune response to the rMenB+OMV NZ vaccine only is evaluated, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination)
    Notes
    [89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    505
    Units: Percentage of participants
    number (confidence interval 95%)
        M14459 (fHbp), >= 5
    94.5 (92.1 to 96.4)
        96217 (NadA), >= 5
    99.6 (98.5 to 99.9)
        NZ98/254 (PorA P1.4), >= 5
    89.6 (86.6 to 92.1)
        M13520 (NHBA), >= 5
    91.5 (88.7 to 93.8)
    No statistical analyses for this end point

    Secondary: hSBA Geometric Mean Titers (GMTs) against each of the Serogroup B Test Strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA)

    		 Close Top of page
    End point title
    		 hSBA Geometric Mean Titers (GMTs) against each of the Serogroup B Test Strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA) [90]
    End point description
    This immune response to the rMenB+OMV NZ vaccine only is evaluated, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination), Day 301 (6 months after the third vaccination), and Day 331 (1 month after the fourth vaccination)
    Notes
    [90] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    553
    Units: Titer
    geometric mean (confidence interval 95%)
        M14459 (fHbp), Day 151
    15.1 (13.7 to 16.7)
        M14459 (fHbp), Day 301
    3.0 (2.8 to 3.2)
        M14459 (fHbp), Day 331
    24.3 (21.3 to 27.8)
        96217 (NadA), Day 151
    488.2 (437.3 to 545.0)
        96217 (NadA), Day 301
    89.1 (77.3 to 102.7)
        96217 (NadA), Day 331
    1349.0 (1195.3 to 1522.5)
        NZ98/254 (PorA P1.4), Day 151
    10.1 (8.9 to 11.4)
        NZ98/254 (PorA P1.4), Day 301
    3.8 (3.5 to 4.0)
        NZ98/254 (PorA P1.4), Day 331
    20.3 (17.3 to 23.7)
        M13520 (NHBA), Day 151
    5.5 (5.0 to 6.0)
        M13520 (NHBA), Day 301
    3.5 (3.3 to 3.7)
        M13520 (NHBA), Day 331
    12.7 (11.2 to 14.4)
    No statistical analyses for this end point

    Secondary: hSBA Geometric Mean Ratios (GMRs) over pre fourth vaccination against each of the Serogroup B Test Strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA)

    		 Close Top of page
    End point title
    		 hSBA Geometric Mean Ratios (GMRs) over pre fourth vaccination against each of the Serogroup B Test Strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA) [91]
    End point description
    This immune response to the rMenB+OMV NZ vaccine only is evaluated, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination) compared to Day 301 (pre-fourth vaccination)
    Notes
    [91] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    465
    Units: Ratio
    geometric mean (confidence interval 95%)
        M14459 (fHbp)
    8.7 (7.6 to 10.0)
        96217 (NadA)
    17.4 (15.1 to 20.1)
        NZ98/254 (PorA P1.4)
    5.5 (4.7 to 6.5)
        M13520 (NHBA)
    3.9 (3.4 to 4.4)
    No statistical analyses for this end point

    Secondary: Percentage of participants with hSBA antibody titers >= LLOQ for each of the Serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA)

    		 Close Top of page
    End point title
    		 Percentage of participants with hSBA antibody titers >= LLOQ for each of the Serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA) [92]
    End point description
    This immune response to the rMenB+OMV NZ vaccine only is evaluated, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 301 (6 months after the third vaccination) and Day 331 (1 month after the fourth vaccination)
    Notes
    [92] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    540
    Units: Percentage of participants
    number (confidence interval 95%)
        M14459 (fHbp), Day 301
    14.5 (11.6 to 17.9)
        M14459 (fHbp), Day 331
    94.5 (92.1 to 96.4)
        96217 (NadA), Day 301
    94.1 (91.6 to 96.0)
        96217 (NadA), Day 331
    99.6 (98.5 to 99.9)
        M13520 (NHBA), Day 301
    8.5 (6.3 to 11.2)
        M13520 (NHBA), Day 331
    86.1 (82.8 to 89.0)
        NZ98/254 (PorA P1.4), Day 301
    17.5 (14.4 to 21.0)
        NZ98/254 (PorA P1.4), Day 331
    87.6 (84.4 to 90.3)
    No statistical analyses for this end point

    Secondary: Percentage of participants with 4-fold rise in hSBA titers for each of the Serogroup B Test Strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA)

    		 Close Top of page
    End point title
    		 Percentage of participants with 4-fold rise in hSBA titers for each of the Serogroup B Test Strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA P1.4), and M13520 (NHBA) [93]
    End point description
    A 4-fold rise in hSBA titers is defined as - if pre-vaccination titer <Limit of Detection (LOD), then a post-vaccination titer >= 4 times the LOD or >= LLOQ, whichever is greater; - if pre-vaccination titer is >= LOD but <LLOQ, then a post-vaccination titer >= 4 times the LLOQ; - if pre-vaccination titer is >= LLOQ, then a post-vaccination titer >= 4 times the pre-vaccination titer, where pre-vaccination titer=pre-4th dose titers (Day 301). This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination) relative to Day 301 (pre-fourth vaccination)
    Notes
    [93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome measure evaluated immune response to the rMenB+OMV NZ vaccine only, hence it was not applicable to the Placebo+PCV group.
    End point values
    		 MenB+PCV Group
    Number of subjects analysed
    465
    Units: Percentage of participants
    number (confidence interval 95%)
        M14459 (fHbp), Day 331
    72.0 (67.5 to 76.1)
        96217 (NadA), Day 331
    94.8 (92.2 to 96.7)
        M13520 (NHBA), Day 331
    36.1 (31.8 to 40.7)
        NZ98/254 (PorA P1.4), Day 331
    54.2 (49.5 to 58.9)
    No statistical analyses for this end point

    Secondary: Percentage of participants with anti-HBs antibody concentrations >= 100 mIU/mL

    		 Close Top of page
    End point title
    		 Percentage of participants with anti-HBs antibody concentrations >= 100 mIU/mL
    End point description
    Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    105
    138
    Units: Percentage of participants
        number (confidence interval 95%)
    98.1 (93.3 to 99.8)
    96.4 (91.7 to 98.8)
    No statistical analyses for this end point

    Secondary: GMCs for Anti-HBsAg antibodies

    		 Close Top of page
    End point title
    		 GMCs for Anti-HBsAg antibodies
    End point description
    Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    105
    138
    Units: mIU/mL
        geometric mean (confidence interval 95%)
    2201.0 (1554.7 to 3116.0)
    2404.8 (1803.1 to 3207.3)
    No statistical analyses for this end point

    Secondary: Percentage of participants with anti-diphtheria and anti-tetanus antibody concentrations >= 1 IU/mL

    		 Close Top of page
    End point title
    		 Percentage of participants with anti-diphtheria and anti-tetanus antibody concentrations >= 1 IU/mL
    End point description
    Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    224
    143
    Units: Percentage of participants
    number (confidence interval 95%)
        Tetanus Toxoid
    67.0 (60.4 to 73.1)
    69.2 (61.0 to 76.7)
        Diphtheria Toxoid
    40.0 (33.5 to 46.8)
    55.1 (46.4 to 63.7)
    No statistical analyses for this end point

    Secondary: GMCs for anti-diphtheria and anti-tetanus antibodies

    		 Close Top of page
    End point title
    		 GMCs for anti-diphtheria and anti-tetanus antibodies
    End point description
    Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    224
    143
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Tetanus Toxoid
    1.5 (1.3 to 1.8)
    1.6 (1.3 to 1.9)
        Diphtheria Toxoid
    0.9 (0.8 to 1.1)
    1.2 (1.0 to 1.5)
    No statistical analyses for this end point

    Secondary: Percentage of participants with anti-polio type 1, 2 and 3 neutralization antibody titers >= 8

    		 Close Top of page
    End point title
    		 Percentage of participants with anti-polio type 1, 2 and 3 neutralization antibody titers >= 8
    End point description
    Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 151 (1 month after the third vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    106
    120
    Units: Percentage of participants
    number (confidence interval 95%)
        Polio 1
    100 (96.4 to 100)
    100 (97.0 to 100)
        Polio 2
    99.1 (94.9 to 100)
    100 (96.9 to 100)
        Polio 3
    100 (96.3 to 100)
    99.1 (95.1 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of participants with seroresponse for anti-Varicella (VV), anti-measles virus, anti-mumps virus and anti-rubella virus antibodies

    		 Close Top of page
    End point title
    		 Percentage of participants with seroresponse for anti-Varicella (VV), anti-measles virus, anti-mumps virus and anti-rubella virus antibodies
    End point description
    Seroresponse is defined as post-vaccination anti-VZV virus, anti-measles virus, anti-mumps virus and anti-rubella virus antibody concentration >= a protective threshold among participants who were seronegative (antibody concentration < assay cut-off) before vaccination. Analysis was performed on the PPS for immunogenicity. Only participants with data available at the specified timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Day 331 (1 month after the fourth vaccination)
    End point values
    		 MenB+PCV Group Placebo+PCV Group
    Number of subjects analysed
    364
    201
    Units: Percentage of participants
    number (confidence interval 95%)
        Mumps
    81.6 (77.2 to 85.5)
    85.9 (80.2 to 90.4)
        Measles
    94.8 (91.9 to 96.9)
    97.9 (94.7 to 99.4)
        Rubella
    86.4 (82.3 to 89.8)
    83.9 (78.1 to 88.7)
        VZV gE
    97.3 (95.0 to 98.7)
    97.5 (94.3 to 99.2)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Solicited AEs: Day 1 to Day 7 post each vaccination, Solicited systemic AEs of salivary gland swelling, fever and rash: Day 1 to Day 30 post fourth vaccination; Unsolicited AEs: Day 1 to Day 30 post each vaccination.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.1
    Reporting groups
    Reporting group title
    Placebo+PCV Group
    Reporting group description
    		 Infant participants received PCV13 along with placebo, Pediarix, Hiberix and Rotarix on Day 1 and Day 61 followed by PCV13, Placebo, Pediarix and Hiberix on Day 121 and PCV13/PCV20, Placebo M-M-R II and Varivax on Day 301.

    Reporting group title
    MenB+PCV Group
    Reporting group description
    		 Infant participants received rMenB+OMV NZ (Bexsero) along with PCV13 (Prevnar 13), Pediarix, Hiberix and Rotarix on Day 1 and Day 61 followed by rMenB+OMV NZ, PCV13, Pediarix and Hiberix on Day 121 and rMenB+OMV NZ, PCV13/PCV20, M-M-R II and Varivax on Day 301.

    Serious adverse events
    		 Placebo+PCV Group MenB+PCV Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    19 / 403 (4.71%)
    35 / 781 (4.48%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neuroblastoma
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Near drowning
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Bronchogenic cyst
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile convulsion
         subjects affected / exposed
    1 / 403 (0.25%)
    3 / 781 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PFAPA syndrome
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenitis
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Serum sickness
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenoidal hypertrophy
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive sleep apnoea syndrome
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillar hypertrophy
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 403 (0.25%)
    3 / 781 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Picornavirus infection
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coxsackie viral infection
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complicated appendicitis
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         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 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    2 / 403 (0.50%)
    4 / 781 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenovirus infection
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchiolitis
         subjects affected / exposed
    2 / 403 (0.50%)
    3 / 781 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchitis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         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
    2 / 403 (0.50%)
    2 / 781 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         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
    1 / 403 (0.25%)
    0 / 781 (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
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         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: 0%
    Non-serious adverse events
    		 Placebo+PCV Group MenB+PCV Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    389 / 403 (96.53%)
    771 / 781 (98.72%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Haemangioma of skin
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Vascular disorders
    Scalp haematoma
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Cyanosis
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Flushing
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Lymphoedema
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Pallor
         subjects affected / exposed
    1 / 403 (0.25%)
    3 / 781 (0.38%)
         occurrences all number
    1
    3
    General disorders and administration site conditions
    Injection site dryness
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Administration site erythema
         subjects affected / exposed
    170 / 403 (42.18%)
    460 / 781 (58.90%)
         occurrences all number
    170
    460
    Administration site induration
         subjects affected / exposed
    180 / 403 (44.67%)
    480 / 781 (61.46%)
         occurrences all number
    180
    480
    Administration site pain
         subjects affected / exposed
    201 / 403 (49.88%)
    582 / 781 (74.52%)
         occurrences all number
    201
    582
    Administration site swelling
         subjects affected / exposed
    122 / 403 (30.27%)
    322 / 781 (41.23%)
         occurrences all number
    122
    322
    Adverse drug reaction
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Adverse food reaction
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Chills
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Crying
         subjects affected / exposed
    163 / 403 (40.45%)
    432 / 781 (55.31%)
         occurrences all number
    163
    433
    Fatigue
         subjects affected / exposed
    2 / 403 (0.50%)
    2 / 781 (0.26%)
         occurrences all number
    2
    2
    Hypothermia
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Induration
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Inflammation
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Influenza like illness
         subjects affected / exposed
    0 / 403 (0.00%)
    3 / 781 (0.38%)
         occurrences all number
    0
    3
    Injection site bruising
         subjects affected / exposed
    6 / 403 (1.49%)
    6 / 781 (0.77%)
         occurrences all number
    6
    6
    Injection site discolouration
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Injection site erythema
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Injection site laceration
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Injection site nodule
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Injection site rash
         subjects affected / exposed
    2 / 403 (0.50%)
    2 / 781 (0.26%)
         occurrences all number
    6
    2
    Injection site reaction
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    2
    Injection site swelling
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Injection site urticaria
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    2
    Injury associated with device
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Irritability postvaccinal
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Pain
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Peripheral swelling
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    172 / 403 (42.68%)
    521 / 781 (66.71%)
         occurrences all number
    184
    543
    Swelling
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Swelling face
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Tenderness
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Vaccination site bruising
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Vaccination site irritation
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Injection site induration
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Food allergy
         subjects affected / exposed
    2 / 403 (0.50%)
    5 / 781 (0.64%)
         occurrences all number
    2
    5
    Seasonal allergy
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Social circumstances
    Child abuse
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Epididymal cyst
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Genital labial adhesions
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Genital rash
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Penile adhesion
         subjects affected / exposed
    0 / 403 (0.00%)
    3 / 781 (0.38%)
         occurrences all number
    0
    4
    Penile cyst
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Penile dermatitis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Vaginal discharge
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion
         subjects affected / exposed
    17 / 403 (4.22%)
    39 / 781 (4.99%)
         occurrences all number
    19
    44
    Asthma
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Brief resolved unexplained event
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Choking
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Cough
         subjects affected / exposed
    20 / 403 (4.96%)
    51 / 781 (6.53%)
         occurrences all number
    25
    58
    Dysphonia
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Epistaxis
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Hiccups
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Respiratory disorder
         subjects affected / exposed
    3 / 403 (0.74%)
    4 / 781 (0.51%)
         occurrences all number
    5
    4
    Respiratory symptom
         subjects affected / exposed
    17 / 403 (4.22%)
    31 / 781 (3.97%)
         occurrences all number
    20
    39
    Rhinitis allergic
         subjects affected / exposed
    2 / 403 (0.50%)
    3 / 781 (0.38%)
         occurrences all number
    2
    4
    Rhinorrhoea
         subjects affected / exposed
    12 / 403 (2.98%)
    25 / 781 (3.20%)
         occurrences all number
    14
    27
    Sneezing
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Snoring
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract irritation
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Wheezing
         subjects affected / exposed
    5 / 403 (1.24%)
    6 / 781 (0.77%)
         occurrences all number
    5
    6
    Respiration abnormal
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Breath holding
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Dependent personality disorder
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Emotional distress
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Insomnia
         subjects affected / exposed
    5 / 403 (1.24%)
    4 / 781 (0.51%)
         occurrences all number
    5
    4
    Irritability
         subjects affected / exposed
    330 / 403 (81.89%)
    713 / 781 (91.29%)
         occurrences all number
    345
    738
    Middle insomnia
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Selective eating disorder
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Sleep disorder
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Serum ferritin decreased
         subjects affected / exposed
    4 / 403 (0.99%)
    1 / 781 (0.13%)
         occurrences all number
    4
    1
    Blood lead increased
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Body temperature decreased
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Body temperature increased
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Breath sounds abnormal
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Cardiac murmur
         subjects affected / exposed
    2 / 403 (0.50%)
    2 / 781 (0.26%)
         occurrences all number
    2
    2
    Human rhinovirus test positive
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Occult blood positive
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Platelet count increased
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    SARS-CoV-2 test positive
         subjects affected / exposed
    2 / 403 (0.50%)
    2 / 781 (0.26%)
         occurrences all number
    2
    2
    Weight decreased
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Accidental exposure to product
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    2
    Accident at home
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Animal bite
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Arthropod bite
         subjects affected / exposed
    2 / 403 (0.50%)
    2 / 781 (0.26%)
         occurrences all number
    2
    2
    Contusion
         subjects affected / exposed
    1 / 403 (0.25%)
    5 / 781 (0.64%)
         occurrences all number
    1
    5
    Corneal abrasion
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Craniocerebral injury
         subjects affected / exposed
    1 / 403 (0.25%)
    3 / 781 (0.38%)
         occurrences all number
    1
    3
    Eyelid injury
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Fall
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Foreign body ingestion
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Head injury
         subjects affected / exposed
    1 / 403 (0.25%)
    4 / 781 (0.51%)
         occurrences all number
    1
    4
    Procedural pain
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Road traffic accident
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Scar
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Scrotal injury
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Skin laceration
         subjects affected / exposed
    0 / 403 (0.00%)
    4 / 781 (0.51%)
         occurrences all number
    0
    4
    Superficial injury of eye
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Thermal burn
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Animal scratch
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Congenital, familial and genetic disorders
    Craniofacial deformity
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Brachycephaly
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Dacryostenosis congenital
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Hydrocele
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Kidney duplex
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Macrocephaly
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Plagiocephaly
         subjects affected / exposed
    3 / 403 (0.74%)
    3 / 781 (0.38%)
         occurrences all number
    3
    3
    Strabismus congenital
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Tethered oral tissue
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Developmental hip dysplasia
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Nervous system disorders
    Nystagmus
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Drooling
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Fine motor delay
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Infant irritability
         subjects affected / exposed
    2 / 403 (0.50%)
    2 / 781 (0.26%)
         occurrences all number
    2
    2
    Lethargy
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Movement disorder
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Myoclonus
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Petit mal epilepsy
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Speech disorder developmental
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Somnolence
         subjects affected / exposed
    319 / 403 (79.16%)
    681 / 781 (87.20%)
         occurrences all number
    322
    681
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 403 (0.99%)
    3 / 781 (0.38%)
         occurrences all number
    4
    3
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Thrombocytosis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Lymphadenopathy
         subjects affected / exposed
    20 / 403 (4.96%)
    20 / 781 (2.56%)
         occurrences all number
    23
    21
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    2 / 403 (0.50%)
    1 / 781 (0.13%)
         occurrences all number
    2
    1
    Conductive deafness
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Ear disorder
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Ear pain
         subjects affected / exposed
    5 / 403 (1.24%)
    9 / 781 (1.15%)
         occurrences all number
    5
    9
    Eustachian tube dysfunction
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Middle ear effusion
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Otorrhoea
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Tympanic membrane perforation
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Eye disorders
    Eye movement disorder
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Astigmatism
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Dacryostenosis acquired
         subjects affected / exposed
    1 / 403 (0.25%)
    3 / 781 (0.38%)
         occurrences all number
    1
    3
    Eczema eyelids
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Eye discharge
         subjects affected / exposed
    3 / 403 (0.74%)
    1 / 781 (0.13%)
         occurrences all number
    3
    1
    Eye swelling
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences all number
    2
    2
    Eyelid rash
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Ocular hyperaemia
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Pseudostrabismus
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Scleral discolouration
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Swelling of eyelid
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Eyelid oedema
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Mucous stools
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Abdominal distension
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain
         subjects affected / exposed
    0 / 403 (0.00%)
    3 / 781 (0.38%)
         occurrences all number
    0
    3
    Abnormal faeces
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Anal fissure
         subjects affected / exposed
    2 / 403 (0.50%)
    1 / 781 (0.13%)
         occurrences all number
    2
    1
    Aphthous ulcer
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    12 / 403 (2.98%)
    31 / 781 (3.97%)
         occurrences all number
    13
    32
    Diarrhoea
         subjects affected / exposed
    178 / 403 (44.17%)
    334 / 781 (42.77%)
         occurrences all number
    193
    350
    Dysphagia
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Faeces discoloured
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences all number
    1
    2
    Faeces hard
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Flatulence
         subjects affected / exposed
    1 / 403 (0.25%)
    4 / 781 (0.51%)
         occurrences all number
    1
    4
    Food protein-induced enterocolitis syndrome
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Frequent bowel movements
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    9 / 403 (2.23%)
    14 / 781 (1.79%)
         occurrences all number
    9
    14
    Gastrooesophageal reflux in neonate
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Gingival cyst
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Gingival disorder
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Haematochezia
         subjects affected / exposed
    1 / 403 (0.25%)
    5 / 781 (0.64%)
         occurrences all number
    1
    5
    Infantile colic
         subjects affected / exposed
    2 / 403 (0.50%)
    0 / 781 (0.00%)
         occurrences all number
    2
    0
    Infantile spitting up
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Oral mucosal eruption
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Protein-losing gastroenteropathy
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Regurgitation
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Retching
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Stomatitis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Teething
         subjects affected / exposed
    46 / 403 (11.41%)
    75 / 781 (9.60%)
         occurrences all number
    55
    84
    Toothache
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    159 / 403 (39.45%)
    317 / 781 (40.59%)
         occurrences all number
    174
    328
    Vomiting projectile
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Post-tussive vomiting
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Post inflammatory pigmentation change
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Acne
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Acne infantile
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Blood blister
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Dermatitis
         subjects affected / exposed
    2 / 403 (0.50%)
    9 / 781 (1.15%)
         occurrences all number
    2
    9
    Dermatitis atopic
         subjects affected / exposed
    3 / 403 (0.74%)
    8 / 781 (1.02%)
         occurrences all number
    3
    8
    Dermatitis contact
         subjects affected / exposed
    1 / 403 (0.25%)
    4 / 781 (0.51%)
         occurrences all number
    1
    4
    Dermatitis diaper
         subjects affected / exposed
    22 / 403 (5.46%)
    38 / 781 (4.87%)
         occurrences all number
    25
    41
    Dry skin
         subjects affected / exposed
    4 / 403 (0.99%)
    4 / 781 (0.51%)
         occurrences all number
    4
    4
    Ecchymosis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Eczema
         subjects affected / exposed
    10 / 403 (2.48%)
    16 / 781 (2.05%)
         occurrences all number
    10
    16
    Eczema infantile
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Erythema
         subjects affected / exposed
    1 / 403 (0.25%)
    7 / 781 (0.90%)
         occurrences all number
    1
    7
    Ingrowing nail
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Intertrigo
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Miliaria
         subjects affected / exposed
    3 / 403 (0.74%)
    1 / 781 (0.13%)
         occurrences all number
    3
    1
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Perioral dermatitis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Rash erythematous
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Rash macular
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences all number
    1
    2
    Rash maculo-papular
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Rash papular
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Seborrhoea
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Seborrhoeic dermatitis
         subjects affected / exposed
    4 / 403 (0.99%)
    3 / 781 (0.38%)
         occurrences all number
    4
    3
    Skin discolouration
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Skin exfoliation
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Skin fissures
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Skin irritation
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Umbilical erythema
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    3 / 403 (0.74%)
    5 / 781 (0.64%)
         occurrences all number
    4
    5
    Rash
         subjects affected / exposed
    106 / 403 (26.30%)
    216 / 781 (27.66%)
         occurrences all number
    117
    224
    Renal and urinary disorders
    Renal hypertrophy
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Single functional kidney
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Acquired plagiocephaly
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences all number
    1
    2
    Arthralgia
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Jaw clicking
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Joint noise
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Muscle tightness
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Muscular weakness
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    3
    Torticollis
         subjects affected / exposed
    2 / 403 (0.50%)
    3 / 781 (0.38%)
         occurrences all number
    2
    3
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences all number
    2
    3
    Abscess limb
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Body tinea
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    3 / 403 (0.74%)
    13 / 781 (1.66%)
         occurrences all number
    3
    13
    Bronchitis
         subjects affected / exposed
    1 / 403 (0.25%)
    3 / 781 (0.38%)
         occurrences all number
    1
    3
    Bullous impetigo
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    COVID-19
         subjects affected / exposed
    5 / 403 (1.24%)
    6 / 781 (0.77%)
         occurrences all number
    5
    6
    Candida infection
         subjects affected / exposed
    0 / 403 (0.00%)
    5 / 781 (0.64%)
         occurrences all number
    0
    5
    Candida nappy rash
         subjects affected / exposed
    3 / 403 (0.74%)
    10 / 781 (1.28%)
         occurrences all number
    3
    11
    Cellulitis
         subjects affected / exposed
    2 / 403 (0.50%)
    2 / 781 (0.26%)
         occurrences all number
    2
    2
    Chronic sinusitis
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Conjunctivitis
         subjects affected / exposed
    15 / 403 (3.72%)
    17 / 781 (2.18%)
         occurrences all number
    17
    20
    Conjunctivitis bacterial
         subjects affected / exposed
    0 / 403 (0.00%)
    4 / 781 (0.51%)
         occurrences all number
    0
    4
    Conjunctivitis viral
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Coxsackie viral infection
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences all number
    1
    2
    Croup infectious
         subjects affected / exposed
    3 / 403 (0.74%)
    24 / 781 (3.07%)
         occurrences all number
    4
    25
    Cystitis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Dacryocystitis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Ear infection
         subjects affected / exposed
    0 / 403 (0.00%)
    4 / 781 (0.51%)
         occurrences all number
    0
    4
    Erythema infectiosum
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Exanthema subitum
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Eye infection
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    2
    0
    Folliculitis
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Fungal skin infection
         subjects affected / exposed
    0 / 403 (0.00%)
    3 / 781 (0.38%)
         occurrences all number
    0
    3
    Gastroenteritis
         subjects affected / exposed
    5 / 403 (1.24%)
    8 / 781 (1.02%)
         occurrences all number
    5
    8
    Gastroenteritis viral
         subjects affected / exposed
    1 / 403 (0.25%)
    9 / 781 (1.15%)
         occurrences all number
    1
    9
    Gastrointestinal viral infection
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Hand-foot-and-mouth disease
         subjects affected / exposed
    3 / 403 (0.74%)
    7 / 781 (0.90%)
         occurrences all number
    3
    7
    Impetigo
         subjects affected / exposed
    3 / 403 (0.74%)
    3 / 781 (0.38%)
         occurrences all number
    3
    4
    Bronchiolitis
         subjects affected / exposed
    13 / 403 (3.23%)
    30 / 781 (3.84%)
         occurrences all number
    16
    31
    Injection site cellulitis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Laryngotracheitis obstructive
         subjects affected / exposed
    2 / 403 (0.50%)
    2 / 781 (0.26%)
         occurrences all number
    2
    2
    Nail infection
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    18 / 403 (4.47%)
    40 / 781 (5.12%)
         occurrences all number
    20
    46
    Onychomycosis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Oral candidiasis
         subjects affected / exposed
    4 / 403 (0.99%)
    5 / 781 (0.64%)
         occurrences all number
    4
    5
    Oral viral infection
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Otitis externa
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Otitis media
         subjects affected / exposed
    29 / 403 (7.20%)
    47 / 781 (6.02%)
         occurrences all number
    37
    55
    Otitis media acute
         subjects affected / exposed
    23 / 403 (5.71%)
    33 / 781 (4.23%)
         occurrences all number
    28
    42
    Otitis media chronic
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 403 (0.00%)
    2 / 781 (0.26%)
         occurrences all number
    0
    2
    Paronychia
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Parvovirus infection
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Periorbital cellulitis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Pertussis
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Pharyngitis
         subjects affected / exposed
    1 / 403 (0.25%)
    5 / 781 (0.64%)
         occurrences all number
    1
    5
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 403 (0.00%)
    3 / 781 (0.38%)
         occurrences all number
    0
    3
    Pneumonia
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences all number
    1
    2
    Pustule
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Respiratory syncytial virus bronchiolitis
         subjects affected / exposed
    3 / 403 (0.74%)
    3 / 781 (0.38%)
         occurrences all number
    3
    3
    Respiratory syncytial virus infection
         subjects affected / exposed
    3 / 403 (0.74%)
    9 / 781 (1.15%)
         occurrences all number
    3
    9
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences all number
    1
    2
    Rhinitis
         subjects affected / exposed
    0 / 403 (0.00%)
    5 / 781 (0.64%)
         occurrences all number
    0
    5
    Roseola
         subjects affected / exposed
    1 / 403 (0.25%)
    2 / 781 (0.26%)
         occurrences all number
    1
    2
    Rotavirus infection
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Sinusitis
         subjects affected / exposed
    6 / 403 (1.49%)
    6 / 781 (0.77%)
         occurrences all number
    6
    6
    Skin candida
         subjects affected / exposed
    3 / 403 (0.74%)
    5 / 781 (0.64%)
         occurrences all number
    3
    5
    Skin infection
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Suspected COVID-19
         subjects affected / exposed
    1 / 403 (0.25%)
    4 / 781 (0.51%)
         occurrences all number
    1
    4
    Tinea cruris
         subjects affected / exposed
    1 / 403 (0.25%)
    1 / 781 (0.13%)
         occurrences all number
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    62 / 403 (15.38%)
    125 / 781 (16.01%)
         occurrences all number
    79
    149
    Urinary tract infection
         subjects affected / exposed
    2 / 403 (0.50%)
    4 / 781 (0.51%)
         occurrences all number
    2
    4
    Viral infection
         subjects affected / exposed
    7 / 403 (1.74%)
    13 / 781 (1.66%)
         occurrences all number
    7
    14
    Viral pharyngitis
         subjects affected / exposed
    1 / 403 (0.25%)
    3 / 781 (0.38%)
         occurrences all number
    1
    3
    Viral rash
         subjects affected / exposed
    1 / 403 (0.25%)
    3 / 781 (0.38%)
         occurrences all number
    1
    3
    Viral upper respiratory tract infection
         subjects affected / exposed
    12 / 403 (2.98%)
    16 / 781 (2.05%)
         occurrences all number
    12
    17
    Wound infection
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    2 / 403 (0.50%)
    1 / 781 (0.13%)
         occurrences all number
    2
    1
    Metabolism and nutrition disorders
    Breast milk substitute intolerance
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Decreased appetite
         subjects affected / exposed
    2 / 403 (0.50%)
    4 / 781 (0.51%)
         occurrences all number
    2
    4
    Feeding disorder
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Food intolerance
         subjects affected / exposed
    0 / 403 (0.00%)
    1 / 781 (0.13%)
         occurrences all number
    0
    1
    Hypophagia
         subjects affected / exposed
    216 / 403 (53.60%)
    543 / 781 (69.53%)
         occurrences all number
    217
    544
    Iron deficiency
         subjects affected / exposed
    1 / 403 (0.25%)
    3 / 781 (0.38%)
         occurrences all number
    1
    3
    Milk soy protein intolerance
         subjects affected / exposed
    1 / 403 (0.25%)
    0 / 781 (0.00%)
         occurrences all number
    1
    0
    Weight gain poor
         subjects affected / exposed
    0 / 403 (0.00%)
    3 / 781 (0.38%)
         occurrences all number
    0
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Nov 2018
    The protocol was amended to revise the endpoints and success criteria based on using the strain M10713, for evaluating immune responses to the NHBA antigen.
    10 Apr 2020
    The protocol was amended to outline measures that were applicable during special circumstances (e.g., COVID-19 pandemic). The purpose of the amendment was to protect subject’s welfare, and ensure the potential benefit to the subject and promote data integrity.
    09 Dec 2021
    The protocol was amended to update the criteria for the primary and key secondary immunogenicity objectives and the total number of enrolled subjects was revised to 1200.
    24 Oct 2022
    The protocol was amended to shorten the safety follow-up period to 6 months in subjects who had not reached the 6-month safety follow-up after the last dose, at the time this amendment took effect.
    19 Dec 2023
    The protocol was amended to align with the update of CDC’s ACIP for the US NIP (National Immunization Program). According to this ACIP update, the 20-valent pneumococcal conjugate vaccine (PCV20) was listed as one of the recommended vaccines for the immunization of pneumococcal disease in children in U.S while PCV13 was no longer recommended for full series of pneumococcal vaccination. Children who received 3 PCV13 doses before 12 months but had not received their fourth booster dose, had the option to receive PCV20 or PCV13. Therefore, to incorporate the ACIP recommendations, subjects who had not reached their visit 5 at the time when this protocol amendment became effective had the option to receive either PCV13 or PCV20 based on the investigator judgment and/or parent’s preference.

    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
    For support, Contact us.
    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.

    European Medicines Agency © 1995-Fri Mar 27 14:03:55 CET 2026 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA