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    Clinical Trial Results:
    Immunogenicity and Safety Study of an Investigational Quadrivalent Meningococcal Conjugate Vaccine when Administered Concomitantly with Routine Pediatric Vaccines in Healthy Infants and Toddlers

    Summary
    EudraCT number
    		 2018-001473-24
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    22 Sep 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Jul 2024
    First version publication date
    14 Jul 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MET42
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03537508
    WHO universal trial number (UTN)
    		 U1111-1183-6361
    Other trial identifiers
    		 BB-IND: 14171
    Sponsors
    Sponsor organisation name
    Sanofi Pasteur Inc.
    Sponsor organisation address
    Discovery Drive, Swiftwater, PA, United States, 18370-0187
    Public contact
    Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001930-PIP01-16
    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
    08 Mar 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Sep 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    -To demonstrate the non-inferiority (NI) of the serum bactericidal assay using human complement (hSBA) vaccine seroresponse to meningococcal serogroups A, C, Y, and W following the administration of a 4-dose series of meningococcal polysaccharide (serogroups A, C, Y, and W) tetanus toxoid conjugate vaccine (MenACYW conjugate vaccine) compared to a 4-dose series of meningococcal (groups A, C, Y, and W-135) oligosaccharide diphtheria cross reacting material (CRM) 197 conjugate vaccine (MENVEO®) when given concomitantly with routine pediatric vaccines to infants and toddlers 6 weeks old to 15 months old. -To demonstrate the NI of the hSBA antibody response to meningococcal serogroups A, C, Y, and W following the administration of 3 doses in infancy of MenACYW conjugate vaccine compared to 3 doses in infancy of MENVEO when given concomitantly with routine pediatric vaccines to infants at 2, 4, and 6 months of age.
    Protection of trial subjects
    Vaccinations were performed by qualified and trained study personnel. Participants with allergy to any of the vaccine components were not vaccinated. After vaccination, participants were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment were also available on site in case of any immediate allergic reactions.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Apr 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Puerto Rico: 380
    Country: Number of subjects enrolled
    United States: 2247
    Worldwide total number of subjects
    2627
    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)
    2627
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted at 69 investigational sites in Puerto Rico and the United States. Healthy infants aged greater than or equal to (>=)42 to less than or equal to (<=)89 days were randomized in a 2:1 ratio to either Group 1: MenACYW conjugate vaccine and routine pediatric vaccines or Group 2: MENVEO and routine pediatric vaccines.

    Pre-assignment
    Screening details
    		 Each group was further randomized in a 2:1 ratio in 2 subgroups based on the time of analyses conducted in the 2nd year of life (30 days after the 12-month vaccinations [Groups 1a and 2a] or 30 days after the 15-month vaccinations [Groups 1b and 2b], respectively. A total of 2627 participants were enrolled in this 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
    		 Investigator, Monitor, Carer, Data analyst, Assessor, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group 1: MenACYW conjugate vaccine
    Arm description
    		 Group 1 was further randomized as Groups 1a and 1b based on the 4th dose timing, i.e. 12 to 15 months and 15 to 18 months respectively. Participants received MenACYW conjugate vaccine 0.5 milliliter (mL) as an intramuscular (IM) injection at 2, 4, 6, and 12 to 15 (Group 1a)/15-18 (Group 1b) months of age along with Pentacel® (diphtheria-tetanus-acellular pertussis [DTaP-IPV/Hib] vaccine) at 2, 4, 6 and 15 to 18 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine [PCV13] at 2, 4, 6, and 12 to 15 months of age; RotaTeq® (pentavalent rotavirus vaccine [RV5]) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 to 15 months of age. In addition to the above, Group 1b participants also received first dose of HAVRIX® (hepatitis A vaccine) at 15 to 18 months of age as a part of the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine
    Investigational medicinal product code
    Other name
    MenACYW conjugate vaccine
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received MenACYW conjugate vaccine at 2, 4, 6, and 12 to 15 (Group 1a)/15-18 (Group 1b) months of age.

    Investigational medicinal product name
    Diphtheria and Tetanus Toxoids and Acellular Pertussis Poliovirus and Hemophilus b Conjugate Vaccine
    Investigational medicinal product code
    Other name
    Pentacel
    Pharmaceutical forms
    Concentrate and solvent for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received Pentacel vaccine at 2, 4, 6, 15 to 18 months of age.

    Investigational medicinal product name
    Pneumococcal 13-valent Conjugate Vaccine
    Investigational medicinal product code
    Other name
    PREVNAR 13, PCV13
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received PREVNAR 13 vaccine at 2, 4, 6, and 12 to 15 months of age.

    Investigational medicinal product name
    Rotavirus Vaccine
    Investigational medicinal product code
    Other name
    RotaTeq
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received RotaTeq vaccine at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Hepatitis B Vaccine
    Investigational medicinal product code
    Other name
    ENGERIX-B
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received ENGERIX-B vaccine at 2 and 6 months of age.

    Investigational medicinal product name
    Measles, Mumps, and Rubella Virus Vaccine
    Investigational medicinal product code
    Other name
    M-M-R II
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received M-M-R II vaccine at 12 to 15 months of age.

    Investigational medicinal product name
    Varicella Virus Vaccine
    Investigational medicinal product code
    Other name
    VARIVAX
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received VARIVAX vaccine at 12 to 15 months of age.

    Investigational medicinal product name
    Hepatitis A vaccine
    Investigational medicinal product code
    Other name
    HAVRIX
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants in Group 1b received HAVRIX vaccine at 15 to 18 months of age as a part of this study. For Group 1a, it was administered after last study visit as per standard guidelines.

    Arm title
    		 Group 2: MENVEO
    Arm description
    		 Group 2 was further randomized as Groups 2a and 2b based on the timing of blood collection, i.e. 12 and 15 months respectively. Participants received MENVEO conjugate vaccine 0.5 mL as an IM injection at 2, 4, 6, and 12 months of age along with Pentacel (DTaP-IPV/Hib vaccine) at 2, 4, 6 and 15 to 18 months of age; PREVNAR 13 (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B (hepatitis B vaccine) at 2 and 6 months of age; M-M-R II (measles, mumps, and rubella vaccine) and VARIVAX (varicella vaccine) at 12 months of age. In addition, they also received first dose of HAVRIX (hepatitis A vaccine) at 15 to 18 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine
    Investigational medicinal product code
    Other name
    MENVEO
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received MENVEO vaccine at 2, 4, 6, and 12 months of age.

    Investigational medicinal product name
    Diphtheria and Tetanus Toxoids and Acellular Pertussis Poliovirus and Hemophilus b Conjugate Vaccine
    Investigational medicinal product code
    Other name
    Pentacel
    Pharmaceutical forms
    Concentrate and solvent for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received Pentacel vaccine at 2, 4, 6 and 15 to 18 months of age.

    Investigational medicinal product name
    Varicella Virus Vaccine
    Investigational medicinal product code
    Other name
    VARIVAX
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received VARIVAX vaccine at 12 months of age.

    Investigational medicinal product name
    Rotavirus Vaccine
    Investigational medicinal product code
    Other name
    RotaTeq
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received RotaTeq vaccine at 2, 4, and 6 months of age.

    Investigational medicinal product name
    Hepatitis B Vaccine
    Investigational medicinal product code
    Other name
    ENGERIX-B
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received ENGERIX-B vaccine at 2 and 6 months of age.

    Investigational medicinal product name
    Measles, Mumps, and Rubella Virus Vaccine
    Investigational medicinal product code
    Other name
    M-M-R II
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received M-M-R II vaccine at 12 months of age.

    Investigational medicinal product name
    Hepatitis A vaccine
    Investigational medicinal product code
    Other name
    HAVRIX
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received HAVRIX vaccine at 15 to 18 months of age.

    Investigational medicinal product name
    Pneumococcal 13-valent Conjugate Vaccine
    Investigational medicinal product code
    Other name
    PREVNAR 13, PCV13
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received PREVNAR 13 vaccine at 2, 4, 6, and 12 months of age.

    Number of subjects in period 1
    		Group 1: MenACYW conjugate vaccine Group 2: MENVEO
    Started
    1746
    881
    Safety analysis set (SafAS)
    1727
    867
    Vaccinated at 2 months
    1727
    869
    Vaccinated at 4 months
    1619
    828
    Vaccinated at 6 months
    1543
    793
    Vaccinated at 12 months
    1411
    708
    Vaccinated at 15 months
    445 [1]
    644
    Completed
    1330
    623
    Not completed
    416
    258
         Adverse event, non-fatal
    2
    1
         Lost to follow-up
    86
    60
         Withdrawal by parent/guardian
    263
    149
         Protocol deviation
    65
    48
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only Group 1b participants were vaccinated

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group 1: MenACYW conjugate vaccine
    Reporting group description
    		 Group 1 was further randomized as Groups 1a and 1b based on the 4th dose timing, i.e. 12 to 15 months and 15 to 18 months respectively. Participants received MenACYW conjugate vaccine 0.5 milliliter (mL) as an intramuscular (IM) injection at 2, 4, 6, and 12 to 15 (Group 1a)/15-18 (Group 1b) months of age along with Pentacel® (diphtheria-tetanus-acellular pertussis [DTaP-IPV/Hib] vaccine) at 2, 4, 6 and 15 to 18 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine [PCV13] at 2, 4, 6, and 12 to 15 months of age; RotaTeq® (pentavalent rotavirus vaccine [RV5]) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 to 15 months of age. In addition to the above, Group 1b participants also received first dose of HAVRIX® (hepatitis A vaccine) at 15 to 18 months of age as a part of the study.

    Reporting group title
    Group 2: MENVEO
    Reporting group description
    		 Group 2 was further randomized as Groups 2a and 2b based on the timing of blood collection, i.e. 12 and 15 months respectively. Participants received MENVEO conjugate vaccine 0.5 mL as an IM injection at 2, 4, 6, and 12 months of age along with Pentacel (DTaP-IPV/Hib vaccine) at 2, 4, 6 and 15 to 18 months of age; PREVNAR 13 (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B (hepatitis B vaccine) at 2 and 6 months of age; M-M-R II (measles, mumps, and rubella vaccine) and VARIVAX (varicella vaccine) at 12 months of age. In addition, they also received first dose of HAVRIX (hepatitis A vaccine) at 15 to 18 months of age.

    Reporting group values
    		 Group 1: MenACYW conjugate vaccine Group 2: MENVEO Total
    Number of subjects
    		 1746 881
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: days
        arithmetic mean (standard deviation)
    		 65.3 ( 8.02 ) 65.3 ( 7.81 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 828 415 1243
        Male
    		 918 466 1384
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 11 3 14
        Asian
    		 15 10 25
        Black or African American
    		 204 99 303
        Native Hawaiian or Other Pacific Islander
    		 7 6 13
        White
    		 1428 722 2150
        Mixed Origin
    		 44 30 74
        Unknown
    		 19 6 25
        Not Reported
    		 18 5 23

    End points

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    End points reporting groups
    Reporting group title
    Group 1: MenACYW conjugate vaccine
    Reporting group description
    		 Group 1 was further randomized as Groups 1a and 1b based on the 4th dose timing, i.e. 12 to 15 months and 15 to 18 months respectively. Participants received MenACYW conjugate vaccine 0.5 milliliter (mL) as an intramuscular (IM) injection at 2, 4, 6, and 12 to 15 (Group 1a)/15-18 (Group 1b) months of age along with Pentacel® (diphtheria-tetanus-acellular pertussis [DTaP-IPV/Hib] vaccine) at 2, 4, 6 and 15 to 18 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine [PCV13] at 2, 4, 6, and 12 to 15 months of age; RotaTeq® (pentavalent rotavirus vaccine [RV5]) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 to 15 months of age. In addition to the above, Group 1b participants also received first dose of HAVRIX® (hepatitis A vaccine) at 15 to 18 months of age as a part of the study.

    Reporting group title
    Group 2: MENVEO
    Reporting group description
    		 Group 2 was further randomized as Groups 2a and 2b based on the timing of blood collection, i.e. 12 and 15 months respectively. Participants received MENVEO conjugate vaccine 0.5 mL as an IM injection at 2, 4, 6, and 12 months of age along with Pentacel (DTaP-IPV/Hib vaccine) at 2, 4, 6 and 15 to 18 months of age; PREVNAR 13 (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B (hepatitis B vaccine) at 2 and 6 months of age; M-M-R II (measles, mumps, and rubella vaccine) and VARIVAX (varicella vaccine) at 12 months of age. In addition, they also received first dose of HAVRIX (hepatitis A vaccine) at 15 to 18 months of age.

    Subject analysis set title
    Group 1a:MenACYW conjugate vaccine (post 12-month vaccination)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received MenACYW conjugate vaccine and routine vaccines at 2, 4, 6, and 12 to 15 months of age. The time of analyses as well as the collection of blood samples conducted in the 2nd year of life for this subgroup was 30 days after the 12-month vaccination.

    Subject analysis set title
    Group 1b:MenACYW conjugate vaccine(post 15-month vaccination)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received MenACYW conjugate vaccine at 2, 4, 6, and 15 to 18 months of age and routine vaccines at 2, 4, 6, 12 to 15 and 15 to 18 months of age. The time of analyses as well as the collection of blood samples conducted in the 2nd year of life for this subgroup was 30 days after the 15-month vaccination.

    Subject analysis set title
    Group 2a: MENVEO (post 12-month vaccination)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received MENVEO at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15 to 18 months of age. The time of analyses as well as the collection of blood samples conducted in the 2nd year of life for this subgroup was 30 days after the 12-month vaccination.

    Subject analysis set title
    Group 2b: MENVEO (post 15-month vaccination)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received MENVEO at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15 to 18 months of age. The time of analyses as well as the collection of blood samples conducted in the 2nd year of life for this subgroup was 30 days after the 15-month vaccination.

    Primary: Groups 1a and 2a: Percentage of Participants With Vaccine Seroresponse Measured by hSBA at Day 30 Post 12-Month Vaccination

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    End point title
    		 Groups 1a and 2a: Percentage of Participants With Vaccine Seroresponse Measured by hSBA at Day 30 Post 12-Month Vaccination
    End point description
    Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. Vaccine seroresponse was defined as a post 4th dose (Day 30 after 12-month) hSBA titer >=1:16 for participants with pre 1st dose (Day 0 before 2-month) hSBA titer less than (<) 1:8, or at least a 4-fold increase in hSBA titer from pre-vaccination to post-vaccination for participants with pre-vaccination hSBA titer >=1:8. Analysis was performed on Per-Protocol Analysis Set 3 (PPAS3) (for 2nd year of life vaccination). PPAS3 included participants of Full Analysis set 3 (FAS3: a subset of all randomized participants who received >=1 dose of the study vaccine in the 2nd year of life [>=12 months of age] and had a valid post-vaccination serology result in the 2nd year of life) with no relevant protocol deviations. Only those participants with data collected are reported. Here, n=number of participants with data collected for each specific serogroup.
    End point type
    Primary
    End point timeframe
    Day 30 post 12-month vaccination (Month 13)
    End point values
    		 Group 1a:MenACYW conjugate vaccine (post 12-month vaccination) Group 2a: MENVEO (post 12-month vaccination)
    Number of subjects analysed
    540
    250
    Units: percentage of participants
    number (confidence interval 95%)
        Serogroup A (n=501, 223)
    79.4 (75.6 to 82.9)
    77.6 (71.5 to 82.9)
        Serogroup C (n=530, 238)
    97.0 (95.1 to 98.3)
    88.2 (83.4 to 92.0)
        Serogroup Y (n=523, 233)
    96.4 (94.4 to 97.8)
    92.3 (88.1 to 95.4)
        Serogroup W (n=540, 250)
    97.6 (95.9 to 98.7)
    96.4 (93.3 to 98.3)
    Statistical analysis title
    		 Statistical analysis for Serogroup A
    Statistical analysis description
    The overall non-inferiority was demonstrated if the lower limit of the 2-sided 95% confidence interval (CI) was >-10% for all 4 serogroups. 95% CI of the difference was calculated from the Wilson Score method without continuity correction.
    Comparison groups
    Group 1a:MenACYW conjugate vaccine (post 12-month vaccination) v Group 2a: MENVEO (post 12-month vaccination)
    Number of subjects included in analysis
    790
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    1.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.38
         upper limit
    		 8.64
    Statistical analysis title
    		 Statistical analysis for Serogroup C
    Statistical analysis description
    The overall non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI was >-10% for all 4 serogroups. 95% CI of the difference was calculated from the Wilson Score method without continuity correction.
    Comparison groups
    Group 1a:MenACYW conjugate vaccine (post 12-month vaccination) v Group 2a: MENVEO (post 12-month vaccination)
    Number of subjects included in analysis
    790
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    8.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.8
         upper limit
    		 13.6
    Statistical analysis title
    		 Statistical analysis for Serogroup Y
    Statistical analysis description
    The overall non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI was >-10% for all 4 serogroups. 95% CI of the difference was calculated from the Wilson Score method without continuity correction.
    Comparison groups
    Group 1a:MenACYW conjugate vaccine (post 12-month vaccination) v Group 2a: MENVEO (post 12-month vaccination)
    Number of subjects included in analysis
    790
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    4.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 8.44
    Statistical analysis title
    		 Statistical analysis for Serogroup W
    Statistical analysis description
    The overall non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI was >-10% for all 4 serogroups. 95% CI of the difference was calculated from the Wilson Score method without continuity correction.
    Comparison groups
    Group 1a:MenACYW conjugate vaccine (post 12-month vaccination) v Group 2a: MENVEO (post 12-month vaccination)
    Number of subjects included in analysis
    790
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.18
         upper limit
    		 4.45

    Primary: Groups 1 and 2: Percentage of Participants Who Achieved Antibody Titers >=1:8 by hSBA at Day 30 Post 6-Month Vaccination

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    End point title
    		 Groups 1 and 2: Percentage of Participants Who Achieved Antibody Titers >=1:8 by hSBA at Day 30 Post 6-Month Vaccination
    End point description
    Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. Analysis was performed on PPAS1 (for infant vaccination). PPAS1 included participants of FAS1 (subset of all randomized participants who received >=1 dose of the study vaccine in infancy [<12 months of age] and had a valid post-vaccination serology result in infancy) with no relevant protocol deviations during infancy. Only those participants with data collected are reported. Here, n=number of participants with data collected for each specific serogroup.
    End point type
    Primary
    End point timeframe
    Day 30 post 6-month vaccination (Month 7)
    End point values
    		 Group 1: MenACYW conjugate vaccine Group 2: MENVEO
    Number of subjects analysed
    883
    438
    Units: percentage of participants
    number (confidence interval 95%)
        Serogroup A (n=852, 409)
    77.9 (75.0 to 80.7)
    67.7 (63.0 to 72.2)
        Serogroup C (n=835, 421)
    99.0 (98.1 to 99.6)
    91.2 (88.1 to 93.7)
        Serogroup Y (n=861, 423)
    98.3 (97.1 to 99.0)
    91.7 (88.7 to 94.2)
        Serogroup W (n=883, 438)
    98.6 (97.6 to 99.3)
    92.9 (90.1 to 95.1)
    Statistical analysis title
    		 Statistical analysis for Serogroup A
    Statistical analysis description
    The overall non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI was >-10% for all 4 serogroups. 95% CI of the difference was calculated from the Wilson Score method without continuity correction.
    Comparison groups
    Group 1: MenACYW conjugate vaccine v Group 2: MENVEO
    Number of subjects included in analysis
    1321
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    10.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.98
         upper limit
    		 15.59
    Statistical analysis title
    		 Statistical analysis for Serogroup C
    Statistical analysis description
    The overall non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI was >-10% for all 4 serogroups. 95% CI of the difference was calculated from the Wilson Score method without continuity correction.
    Comparison groups
    Group 1: MenACYW conjugate vaccine v Group 2: MENVEO
    Number of subjects included in analysis
    1321
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    7.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.31
         upper limit
    		 10.96
    Statistical analysis title
    		 Statistical analysis for Serogroup Y
    Statistical analysis description
    The overall non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI was >-10% for all 4 serogroups. 95% CI of the difference was calculated from the Wilson Score method without continuity correction.
    Comparison groups
    Group 1: MenACYW conjugate vaccine v Group 2: MENVEO
    Number of subjects included in analysis
    1321
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    6.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.01
         upper limit
    		 9.62
    Statistical analysis title
    		 Statistical analysis for Serogroup W
    Statistical analysis description
    The overall non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI was >-10% for all 4 serogroups. 95% CI of the difference was calculated from the Wilson Score method without continuity correction.
    Comparison groups
    Group 1: MenACYW conjugate vaccine v Group 2: MENVEO
    Number of subjects included in analysis
    1321
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    5.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.44
         upper limit
    		 8.57

    Secondary: Groups 1 and 2: Percentage of Participants who Achieved Anti-Hepatitis B Antibody Concentrations >=10 Milli-International Units per Milliliter (mIU/mL) at Day 30 Post 6-Month Vaccination

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    End point title
    		 Groups 1 and 2: Percentage of Participants who Achieved Anti-Hepatitis B Antibody Concentrations >=10 Milli-International Units per Milliliter (mIU/mL) at Day 30 Post 6-Month Vaccination
    End point description
    Anti-Hepatitis B surface antibodies (HBsAg) were measured by the commercially available VITROS ECi/ECiQ immunodiagnostic system using chemiluminescence detection technology. The percentage of participants with an anti-HBsAg antibody titer >=10 mIU/mL was assessed. Analysis was performed on PPAS1 (for infant vaccination) which included participants of FAS1 with no relevant protocol deviations during infancy. Only those participants with data collected are reported.
    End point type
    Secondary
    End point timeframe
    Day 30 post 6-month vaccination (Month 7)
    End point values
    		 Group 1: MenACYW conjugate vaccine Group 2: MENVEO
    Number of subjects analysed
    765
    348
    Units: percentage of participants
        number (confidence interval 95%)
    98.6 (97.4 to 99.3)
    98.0 (95.9 to 99.2)
    No statistical analyses for this end point

    Secondary: Groups 1 and 2: Percentage of Participants who Achieved Anti-Polyribosyl-Ribitol (PRP) Antibody Concentrations >=0.15 and >=1.0 Microgram (mcg)/mL at Day 30 Post 6-Month Vaccination

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    End point title
    		 Groups 1 and 2: Percentage of Participants who Achieved Anti-Polyribosyl-Ribitol (PRP) Antibody Concentrations >=0.15 and >=1.0 Microgram (mcg)/mL at Day 30 Post 6-Month Vaccination
    End point description
    Anti-PRP concentrations were measured using a farr-type radioimmunoassay (RIA). The percentage of participants with an PRP antibody titer >=0.15 mcg/mL and >=1.0 mcg/mL were assessed. Analysis was performed on PPAS1 (for infant vaccination) which included participants of FAS1 with no relevant protocol deviations during infancy. Only those participants with data collected are reported.
    End point type
    Secondary
    End point timeframe
    Day 30 post 6-month vaccination (Month 7)
    End point values
    		 Group 1: MenACYW conjugate vaccine Group 2: MENVEO
    Number of subjects analysed
    882
    420
    Units: percentage of participants
    number (confidence interval 95%)
        >=0.15 mcg/mL
    99.0 (98.1 to 99.5)
    96.4 (94.2 to 98.0)
        >=1.0 mcg/mL
    91.3 (89.2 to 93.0)
    85.7 (82.0 to 88.9)
    No statistical analyses for this end point

    Secondary: Groups 1 and 2: Percentage of Participants who Achieved Anti-Poliovirus Antibody Titers >=1:8 at Day 30 Post 6-Month Vaccination

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    End point title
    		 Groups 1 and 2: Percentage of Participants who Achieved Anti-Poliovirus Antibody Titers >=1:8 at Day 30 Post 6-Month Vaccination
    End point description
    Anti-poliovirus types 1, 2, and 3 were measured by neutralization assay. The percentage of participants with anti-polio antibody titers >=1:8 were assessed. Analysis was performed on PPAS1 (for infant vaccination) which included participants of FAS1 with no relevant protocol deviations during infancy. Only those participants with data collected are reported. Here, n=number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    Day 30 post 6-month vaccination (Month 7)
    End point values
    		 Group 1: MenACYW conjugate vaccine Group 2: MENVEO
    Number of subjects analysed
    854
    415
    Units: percentage of participants
    number (confidence interval 95%)
        Anti-polio 1 (n=839, 412)
    100 (99.6 to 100)
    100 (99.1 to 100)
        Anti-polio 2 (n=838, 406)
    100 (99.6 to 100)
    100 (99.1 to 100)
        Anti-polio 3 (n=854, 415)
    100 (99.6 to 100)
    100 (99.1 to 100)
    No statistical analyses for this end point

    Secondary: Groups 1 and 2: Percentage of Participants who Achieved Anti-Rotavirus Immunoglobulin A (IgA) Antibody Concentrations >=3-Fold Rise at Day 30 Post 6-Month Vaccination

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    End point title
    		 Groups 1 and 2: Percentage of Participants who Achieved Anti-Rotavirus Immunoglobulin A (IgA) Antibody Concentrations >=3-Fold Rise at Day 30 Post 6-Month Vaccination
    End point description
    Anti-rotavirus IgA antibodies in human serum were measured by enzyme-linked immunosorbent assay (ELISA). The percentage of participants who achieved anti-rotavirus IgA Ab concentrations >=3-fold rise were assessed. Analysis was performed on PPAS1 (for infant vaccination) which included participants of FAS1 with no relevant protocol deviations during infancy. Only those participants with data collected are reported.
    End point type
    Secondary
    End point timeframe
    Day 30 post 6-month vaccination (Month 7)
    End point values
    		 Group 1: MenACYW conjugate vaccine Group 2: MENVEO
    Number of subjects analysed
    663
    321
    Units: percentage of participants
        number (confidence interval 95%)
    91.0 (88.5 to 93.0)
    92.8 (89.4 to 95.4)
    No statistical analyses for this end point

    Secondary: Groups 1 and 2: Geometric Mean Concentrations (GMCs) of Anti-Rotavirus IgA Antibodies at Day 30 Post 6-Month Vaccination

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    End point title
    		 Groups 1 and 2: Geometric Mean Concentrations (GMCs) of Anti-Rotavirus IgA Antibodies at Day 30 Post 6-Month Vaccination
    End point description
    GMCs of anti-rotavirus serum IgA antibodies were assessed using ELISA. Analysis was performed on PPAS1 (for infant vaccination) which included participants of FAS1 with no relevant protocol deviations during infancy. Only those participants with data collected are reported.
    End point type
    Secondary
    End point timeframe
    Day 30 post 6-month vaccination (Month 7)
    End point values
    		 Group 1: MenACYW conjugate vaccine Group 2: MENVEO
    Number of subjects analysed
    857
    403
    Units: U/mL
        geometric mean (confidence interval 95%)
    272 (244 to 303)
    308 (264 to 360)
    No statistical analyses for this end point

    Secondary: Groups 1 and 2: GMCs of Anti-Pertussis Antibodies at Day 30 Post 6-Month Vaccination

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    End point title
    		 Groups 1 and 2: GMCs of Anti-Pertussis Antibodies at Day 30 Post 6-Month Vaccination
    End point description
    GMCs of anti-pertussis antibodies (pertussis toxoid [PT], filamentous hemagglutinin adhesin [FHA], pertactin [PRN] and fimbriae types 2 and 3 [FIM]) were measured by electrochemiluminescent (ECL) assay. Analysis was performed on PPAS1 (for infant vaccination) which included participants of FAS1 with no relevant protocol deviations during infancy. Only those participants with data collected are reported.
    End point type
    Secondary
    End point timeframe
    Day 30 post 6-month vaccination (Month 7)
    End point values
    		 Group 1: MenACYW conjugate vaccine Group 2: MENVEO
    Number of subjects analysed
    906
    444
    Units: ELISA units/mL
    geometric mean (confidence interval 95%)
        Anti-PT
    75.8 (72.2 to 79.6)
    78.6 (72.8 to 84.9)
        Anti-FHA
    95.7 (90.9 to 101)
    98.6 (91.7 to 106)
        Anti-PRN
    39.4 (36.8 to 42.3)
    42.1 (37.9 to 46.6)
        Anti-FIM
    309 (291 to 330)
    311 (284 to 341)
    No statistical analyses for this end point

    Secondary: Groups 1 and 2: GMCs of Anti-Pneumococcal Antibodies at Day 30 Post 6-Month Vaccination

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    End point title
    		 Groups 1 and 2: GMCs of Anti-Pneumococcal Antibodies at Day 30 Post 6-Month Vaccination
    End point description
    GMCs of anti-pneumococcal antibodies was assessed by pneumococcal capsular polysaccharide (PnPS) IgG ECL assay which is used to quantitate the amount of anti-streptococcus pneumoniae PS (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) antibodies in human serum. Analysis was performed on PPAS1 (for infant vaccination) which included participants of FAS1 with no relevant protocol deviations during infancy. Only those participants with data collected are reported. Here, n=number of participants with data collected for each serotype.
    End point type
    Secondary
    End point timeframe
    Day 30 post 6-month vaccination (Month 7)
    End point values
    		 Group 1: MenACYW conjugate vaccine Group 2: MENVEO
    Number of subjects analysed
    874
    420
    Units: mcg/mL
    geometric mean (confidence interval 95%)
        Serotype 1 (n=872, 420)
    2.26 (2.13 to 2.40)
    1.93 (1.77 to 2.12)
        Serotype 3 (n=869, 412)
    0.607 (0.577 to 0.638)
    0.544 (0.505 to 0.585)
        Serotype 4 (n=872, 420)
    1.46 (1.40 to 1.53)
    1.33 (1.24 to 1.42)
        Serotype 5 (n=873, 420)
    1.54 (1.46 to 1.63)
    1.26 (1.15 to 1.37)
        Serotype 6A (n=874, 420)
    4.01 (3.82 to 4.22)
    3.34 (3.09 to 3.62)
        Serotype 6B (n=874, 420)
    2.47 (2.29 to 2.67)
    1.97 (1.75 to 2.21)
        Serotype 7F (n=874, 419)
    3.48 (3.32 to 3.64)
    3.40 (3.18 to 3.63)
        Serotype 9V (n=873, 420)
    1.88 (1.78 to 1.99)
    1.61 (1.48 to 1.74)
        Serotype 14 (n=872, 420)
    6.95 (6.53 to 7.41)
    7.17 (6.58 to 7.81)
        Serotype 18C (n=874, 420)
    1.95 (1.86 to 2.04)
    1.82 (1.69 to 1.96)
        Serotype 19A (n=874, 420)
    2.21 (2.10 to 2.32)
    2.00 (1.86 to 2.14)
        Serotype 19F (n=874, 420)
    3.36 (3.21 to 3.52)
    2.98 (2.77 to 3.21)
        Serotype 23F (n=872, 420)
    1.59 (1.49 to 1.69)
    1.30 (1.18 to 1.44)
    No statistical analyses for this end point

    Secondary: Groups 1a and 2a: Percentage of Participants who Achieved Vaccine Response for Measles, Mumps and Rubella (MMR) Antibodies at Day 30 Post 12-Month Vaccination

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    End point title
    		 Groups 1a and 2a: Percentage of Participants who Achieved Vaccine Response for Measles, Mumps and Rubella (MMR) Antibodies at Day 30 Post 12-Month Vaccination
    End point description
    Vaccine response against anti-measles and anti-rubella antibodies were measured by bulk IgG enzyme immunoassay and anti-mumps antibodies were assessed by ELISA. Percentage of participants with anti-measles, anti-mumps, anti-rubella antibody concentration that met the respective mentioned criterion are reported: measles: >=255 mIU/mL; mumps: >=10 antibody units per milliliter and rubella: >=10 IU/mL. Analysis was performed on PPAS3 (for 2nd year of life vaccination) which included participants of FAS3 with no relevant protocol deviations. Only those participants with data collected are reported. Here, n=number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    Day 30 post 12-month vaccination (Month 13)
    End point values
    		 Group 1a:MenACYW conjugate vaccine (post 12-month vaccination) Group 2a: MENVEO (post 12-month vaccination)
    Number of subjects analysed
    662
    301
    Units: percentage of participants
    number (confidence interval 95%)
        Anti-measles (n=662, 301)
    97.6 (96.1 to 98.6)
    97.3 (94.8 to 98.8)
        Anti-mumps (n=660, 301)
    95.5 (93.6 to 96.9)
    97.7 (95.3 to 99.1)
        Anti-rubella (n=662, 301)
    97.9 (96.5 to 98.8)
    98.0 (95.7 to 99.3)
    No statistical analyses for this end point

    Secondary: Groups 1a and 2a: Percentage of Participants who Achieved Vaccine Response for Varicella Antibodies at Day 30 Post 12-Month Vaccination

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    End point title
    		 Groups 1a and 2a: Percentage of Participants who Achieved Vaccine Response for Varicella Antibodies at Day 30 Post 12-Month Vaccination
    End point description
    Vaccine response against anti-varicella antibodies were measured by glycoprotein (gp) ELISA. Percentage of participants with anti-varicella antibody concentration >=5 antibody (Ab) gpELISA units/mL are reported. Analysis was performed on PPAS3 (for 2nd year of life vaccination) which included participants of FAS3 with no relevant protocol deviations. Only those participants with data collected are reported.
    End point type
    Secondary
    End point timeframe
    Day 30 post 12-month vaccination (Month 13)
    End point values
    		 Group 1a:MenACYW conjugate vaccine (post 12-month vaccination) Group 2a: MENVEO (post 12-month vaccination)
    Number of subjects analysed
    662
    301
    Units: percentage of participants
        number (confidence interval 95%)
    96.4 (94.7 to 97.7)
    94.7 (91.5 to 96.9)
    No statistical analyses for this end point

    Secondary: Groups 1a and 2a: GMCs of Anti-Pneumococcal Antibodies at Day 30 Post 12-Month Vaccination

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    End point title
    		 Groups 1a and 2a: GMCs of Anti-Pneumococcal Antibodies at Day 30 Post 12-Month Vaccination
    End point description
    GMCs of anti-pneumococcal antibodies was assessed by PnPS IgG ECL assay which is used to quantitate the amount of anti-streptococcus pneumoniae PS (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) antibodies in human serum. Analysis was performed on PPAS3 (for 2nd year of life vaccination) which included participants of FAS3 with no relevant protocol deviations. Only those participants with data collected are reported. Here, n=number of participants with data collected for each specific serogroup.
    End point type
    Secondary
    End point timeframe
    Day 30 post 12-month vaccination (Month 13)
    End point values
    		 Group 1a:MenACYW conjugate vaccine (post 12-month vaccination) Group 2a: MENVEO (post 12-month vaccination)
    Number of subjects analysed
    653
    300
    Units: mcg/mL
    geometric mean (confidence interval 95%)
        Serotype 1 (n=652, 299)
    3.81 (3.56 to 4.08)
    3.44 (3.12 to 3.81)
        Serotype 3 (n=651, 299)
    0.771 (0.728 to 0.817)
    0.751 (0.690 to 0.818)
        Serotype 4 (n=652, 299)
    2.08 (1.95 to 2.22)
    2.00 (1.83 to 2.18)
        Serotype 5 (n=652, 300)
    2.70 (2.53 to 2.88)
    2.46 (2.25 to 2.69)
        Serotype 6A (n=652, 300)
    9.65 (9.09 to 10.2)
    9.51 (8.72 to 10.4)
        Serotype 6B (n=649, 300)
    7.41 (6.92 to 7.93)
    6.37 (5.77 to 7.03)
        Serotype 7F (n=652, 298)
    5.40 (5.08 to 5.73)
    6.04 (5.56 to 6.55)
        Serotype 9V (n=652, 299)
    3.53 (3.31 to 3.77)
    3.62 (3.30 to 3.96)
        Serotype 14 (n=653, 300)
    7.80 (7.26 to 8.38)
    9.20 (8.37 to 10.1)
        Serotype 18C (n=652, 300)
    2.60 (2.44 to 2.78)
    2.92 (2.68 to 3.19)
        Serotype 19A (n=649, 300)
    6.19 (5.82 to 6.59)
    5.86 (5.32 to 6.45)
        Serotype 19F (n=652, 300)
    6.49 (6.11 to 6.90)
    6.01 (5.45 to 6.62)
        Serotype 23F (n=652, 300)
    3.88 (3.60 to 4.17)
    3.41 (3.09 to 3.78)
    No statistical analyses for this end point

    Secondary: Groups 1b and 2b: Percentage of Participants who Achieved Anti-PRP Antibody Concentrations >=1.0 mcg/mL at Day 30 Post 15-Month Vaccination

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    End point title
    		 Groups 1b and 2b: Percentage of Participants who Achieved Anti-PRP Antibody Concentrations >=1.0 mcg/mL at Day 30 Post 15-Month Vaccination
    End point description
    Anti-PRP concentrations were measured using a farr-type RIA. The percentage of participants with an PRP antibody titers >=1.0 mcg/mL were assessed. Analysis was performed on PPAS3 (for 2nd year of life vaccination) which included participants of FAS3 with no relevant protocol deviations. Only those participants with data collected are reported.
    End point type
    Secondary
    End point timeframe
    Day 30 post 15-month vaccination (Month 16)
    End point values
    		 Group 1b:MenACYW conjugate vaccine(post 15-month vaccination) Group 2b: MENVEO (post 15-month vaccination)
    Number of subjects analysed
    297
    125
    Units: percentage of participants
        number (confidence interval 95%)
    98.3 (96.1 to 99.5)
    98.4 (94.3 to 99.8)
    No statistical analyses for this end point

    Secondary: Groups 1b and 2b: Percentage of Participants who Achieved Anti-Poliovirus Antibody Titers >=1:8 at Day 30 Post 15-Month Vaccination

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    End point title
    		 Groups 1b and 2b: Percentage of Participants who Achieved Anti-Poliovirus Antibody Titers >=1:8 at Day 30 Post 15-Month Vaccination
    End point description
    Anti-poliovirus types 1, 2, and 3 were measured by neutralization assay. The percentage of participants with anti-polio antibody titers >=1:8 are assessed. Analysis was performed on PPAS3 (for 2nd year of life vaccination) which included participants of FAS3 with no relevant protocol deviations. Only those participants with data collected are reported. Here, n=number of participants with data collected for each specified category.
    End point type
    Secondary
    End point timeframe
    Day 30 post 15-month vaccination (Month 16)
    End point values
    		 Group 1b:MenACYW conjugate vaccine(post 15-month vaccination) Group 2b: MENVEO (post 15-month vaccination)
    Number of subjects analysed
    291
    122
    Units: percentage of participants
    number (confidence interval 95%)
        Anti-polio 1 (n=286, 122)
    100 (98.7 to 100)
    100 (97.0 to 100)
        Anti-polio 2 (n=291, 122)
    100 (98.7 to 100)
    100 (97.0 to 100)
        Anti-polio 3 (n=289, 122)
    100 (98.7 to 100)
    100 (97.0 to 100)
    No statistical analyses for this end point

    Secondary: Groups 1b and 2b: Percentage of Participants who Achieved Vaccine Response for Anti-Pertussis Antibodies at Day 30 Post 15-Month Vaccination

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    End point title
    		 Groups 1b and 2b: Percentage of Participants who Achieved Vaccine Response for Anti-Pertussis Antibodies at Day 30 Post 15-Month Vaccination
    End point description
    Vaccine response was defined as: if the pre-booster (4th) vaccination concentration was <lower limit of quantification (LLOQ), then the post-booster (4th) vaccination concentration should be >= 4 times LLOQ. The LLOQ was equal to 2.00 EU/mL. Analysis was performed on PPAS3 (for 2nd year of life vaccination) which included participants of FAS3 with no relevant protocol deviations. Only those participants with data collected are reported.
    End point type
    Secondary
    End point timeframe
    Day 30 post 15-month vaccination (Month 16)
    End point values
    		 Group 1b:MenACYW conjugate vaccine(post 15-month vaccination) Group 2b: MENVEO (post 15-month vaccination)
    Number of subjects analysed
    273
    121
    Units: percentage of participants
    number (confidence interval 95%)
        Anti-PT
    98.5 (96.3 to 99.6)
    98.3 (94.2 to 99.8)
        Anti-FHA
    96.7 (93.8 to 98.5)
    96.7 (91.8 to 99.1)
        Anti-PRN
    96.3 (93.4 to 98.2)
    97.5 (92.9 to 99.5)
        Anti-FIM
    98.2 (95.8 to 99.4)
    97.5 (92.9 to 99.5)
    No statistical analyses for this end point

    Secondary: Groups 1a and 2a: Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Measured by hSBA at Day 30 Post 6-Month Vaccination and Day 0 Before 12-Month Vaccination

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    End point title
    		 Groups 1a and 2a: Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Measured by hSBA at Day 30 Post 6-Month Vaccination and Day 0 Before 12-Month Vaccination
    End point description
    GMTs of antibody against meningococcal serogroups A, C, Y, and W were measured by hSBA. Analysis was performed on PPAS2 (for immunogenicity persistence evaluation). PPAS2 included participants of FAS2 (subset of all randomized participants who received >=1 dose of the study vaccine in infancy [at Visit 1 to 3, < 12 months of age] and had a valid pre-vaccination serology result at Visit 5 before the 12-month vaccinations for Subgroups 1a and 2a or at Visit 6 before the 15-month vaccinations for Subgroups 1b and 2b) with no relevant protocol deviations during infancy and for whom a pre-dose serology sample at Visit 5 for Subgroups 1a and 2a before the 12-month vaccinations or Visit 6 for Subgroups 1b and 2b before the 15-month vaccinations was not withdrawn. Only those participants with data collected are reported. Here, n=number of participants with data collected for each specified category; 3rd dose is 6-month vaccination and 4th dose is 12-month vaccination.
    End point type
    Secondary
    End point timeframe
    Day 30 post 6-month vaccination (Month 7) and Day 0 before 12-month vaccination (Month 12)
    End point values
    		 Group 1a:MenACYW conjugate vaccine (post 12-month vaccination) Group 2a: MENVEO (post 12-month vaccination)
    Number of subjects analysed
    644
    329
    Units: titer
    geometric mean (confidence interval 95%)
        Serogroup A: Day 30 post 3rd dose (n=547, 258)
    24.9 (21.6 to 28.6)
    16.3 (13.5 to 19.6)
        Serogroup A: Day 0 before 4th dose (n=627, 321)
    9.33 (8.45 to 10.3)
    6.43 (5.64 to 7.33)
        Serogroup C: Day 30 post 3rd dose (n=542, 268)
    365 (325 to 411)
    51.4 (42.9 to 61.5)
        Serogroup C: Day 0 before 4th dose (n=637, 324)
    57.8 (51.5 to 64.8)
    4.82 (4.22 to 5.50)
        Serogroup Y: Day 30 post 3rd dose (n=558, 270)
    83.0 (75.0 to 91.8)
    42.9 (36.7 to 50.0)
        Serogroup Y: Day 0 before 4th dose (n=633, 327)
    42.9 (39.3 to 46.7)
    10.4 (9.15 to 11.9)
        Serogroup W: Day 30 post 3rd dose (n=571, 277)
    92.8 (84.8 to 102)
    51.4 (43.9 to 60.0)
        Serogroup W: Day 0 before 4th dose (n=644, 329)
    57.8 (52.7 to 63.3)
    9.27 (8.15 to 10.5)
    No statistical analyses for this end point

    Secondary: Groups 1a and 2a: Percentage of Participants Who Achieved Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W at Day 30 Post 6-Month Vaccination and Day 0 Before 12-Month Vaccination

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    End point title
    		 Groups 1a and 2a: Percentage of Participants Who Achieved Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W at Day 30 Post 6-Month Vaccination and Day 0 Before 12-Month Vaccination
    End point description
    Antibody titers of Meningococcal Serogroups A, C, Y, and W were measured by hSBA assay. Analysis was performed on PPAS2 (for immunogenicity persistence evaluation) which included participants of FAS2 with no relevant protocol deviations during infancy and for whom a pre-dose serology sample at Visit 5 for Subgroups 1a and 2a before the 12-month vaccinations or Visit 6 for Subgroups 1b and 2b before the 15-month vaccinations was not withdrawn. Only those participants with data collected are reported. Here, n=number of participants with data collected at each specified category, 3rd dose is 6-month vaccination, 4th dose is 12-month vaccination D0 is Day 0 and D30 is Day 30.
    End point type
    Secondary
    End point timeframe
    Day 30 post 6-month vaccination (Month 7) and Day 0 before 12-month vaccination (Month 12)
    End point values
    		 Group 1a:MenACYW conjugate vaccine (post 12-month vaccination) Group 2a: MENVEO (post 12-month vaccination)
    Number of subjects analysed
    644
    329
    Units: percentage of participants
    number (confidence interval 95%)
        Serogroup A: D30 post 3rd dose:>=1:4 (n=547,258)
    87.0 (83.9 to 89.7)
    84.9 (79.9 to 89.0)
        Serogroup A: D30 post 3rd dose:>=1:8 (n=547,258)
    77.3 (73.6 to 80.8)
    70.2 (64.2 to 75.7)
        Serogroup A:D0 before 4th dose:>=1:4(n=627,321)
    82.5 (79.2 to 85.4)
    66.4 (60.9 to 71.5)
        Serogroup A:D0 before 4th dose:>=1:8(n=627,321)
    59.0 (55.0 to 62.9)
    47.0 (41.5 to 52.7)
        Serogroup C: D30 post 3rd dose:>=1:4 (n=542,268)
    99.3 (98.1 to 99.8)
    93.7 (90.0 to 96.3)
        Serogroup C: D30 post 3rd dose:>=1:8 (n=542,268)
    99.1 (97.9 to 99.7)
    91.0 (87.0 to 94.2)
        Serogroup C:D0 before 4th dose:>=1:4(n=637,324)
    95.4 (93.5 to 96.9)
    49.1 (43.5 to 54.7)
        Serogroup C:D0 before 4th dose:>=1:8(n=637,324)
    92.9 (90.7 to 94.8)
    34.0 (28.8 to 39.4)
        Serogroup Y: D30 post 3rd dose:>=1:4 (n=558,270)
    99.1 (97.9 to 99.7)
    96.3 (93.3 to 98.2)
        Serogroup Y: D30 post 3rd dose:>=1:8 (n=558,270)
    98.6 (97.2 to 99.4)
    92.2 (88.4 to 95.1)
        Serogroup Y:D0 before 4th dose:>=1:4(n=633,327)
    99.2 (98.2 to 99.7)
    83.5 (79.0 to 87.3)
        Serogroup Y:D0 before 4th dose:>=1:8(n=633,327)
    96.8 (95.2 to 98.1)
    69.1 (63.8 to 74.1)
        Serogroup W: D30 post 3rd dose:>=1:4 (n=571,277)
    99.8 (99.0 to 100)
    97.5 (94.9 to 99.0)
        Serogroup W: D30 post 3rd dose:>=1:8 (n=571,277)
    98.8 (97.5 to 99.5)
    94.2 (90.8 to 96.7)
        Serogroup W:D0 before 4th dose:>=1:4(n=644,329)
    98.9 (97.8 to 99.6)
    82.7 (78.1 to 86.6)
        Serogroup W:D0 before 4th dose:>=1:8(n=644,329)
    97.2 (95.6 to 98.3)
    62.0 (56.5 to 67.3)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From start of study (Day 0) up to end of study (last point of contact [which included the 6-month safety follow up]), approximately 65 months
    Adverse event reporting additional description
    Analysis was performed on SafAS which was defined as those participants who received at least 1 dose of the study vaccines and had any safety data available.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Group 2
    Reporting group description
    		 Group 2 was further randomized as Groups 2a and 2b based on the timing of blood collection, i.e. 12 and 15 months respectively. Participants received MENVEO conjugate vaccine 0.5 mL as an IM injection at 2, 4, 6, and 12 months of age along with Pentacel (DTaP-IPV/Hib vaccine) at 2, 4, 6 and 15 to 18 months of age; PREVNAR 13 (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B (hepatitis B vaccine) at 2 and 6 months of age; M-M-R II (measles, mumps, and rubella vaccine) and VARIVAX (varicella vaccine) at 12 months of age. In addition, they also received first dose of HAVRIX (hepatitis A vaccine) at 15 to 18 months of age.

    Reporting group title
    Group 1
    Reporting group description
    		 Group 1 was further randomized as Groups 1a and 1b based on the 4th dose timing, i.e. 12 to 15 months and 15- 18 months respectively. Participants received MenACYW conjugate vaccine 0.5 mL as an IM injection at 2, 4, 6, and 12 to 15 (Group 1a)/15-18 (Group 1b) months of age along with Pentacel (diphtheria-tetanus-acellular pertussis [DTaP-IPV/Hib] vaccine) at 2, 4, 6 and 15 to 18 months of age; PREVNAR 13 (pneumococcal 13-valent conjugate vaccine [PCV13] at 2, 4, 6, and 12 to 15 months of age; RotaTeq (pentavalent rotavirus vaccine [RV5]) at 2, 4, and 6 months of age; ENGERIX-B (hepatitis B vaccine) at 2 and 6 months of age; M-M-R II (measles, mumps, and rubella vaccine) and VARIVAX (varicella vaccine) at 12 to 15 months of age. In addition to the above, Group 1b participants also received first dose of HAVRIX (hepatitis A vaccine) at 15 to 18 months of age as a part of the study.

    Serious adverse events
    		 Group 2 Group 1
    Total subjects affected by serious adverse events
         subjects affected / exposed
    38 / 867 (4.38%)
    99 / 1727 (5.73%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Glioma
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         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
    Craniocerebral Injury
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur Fracture
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post Vaccination Fever
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head Injury
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper Limb Fracture
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural Haematoma
         subjects affected / exposed
    0 / 867 (0.00%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skull Fractured Base
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         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 / 867 (0.00%)
    3 / 1727 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Congenital Absence Of Bile Ducts
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Talipes
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urachal Abnormality
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyloric Stenosis
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac Arrest
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid Haemorrhage
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure Like Phenomena
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 867 (0.12%)
    3 / 1727 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile Convulsion
         subjects affected / exposed
    3 / 867 (0.35%)
    8 / 1727 (0.46%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infantile Spasms
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Coagulopathy
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sandifer's Syndrome
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    0 / 867 (0.00%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (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 / 867 (0.00%)
    1 / 1727 (0.06%)
         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
    Apnoea
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute Respiratory Failure
         subjects affected / exposed
    1 / 867 (0.12%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Distress
         subjects affected / exposed
    3 / 867 (0.35%)
    4 / 1727 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         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
    0 / 867 (0.00%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess Neck
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenovirus Infection
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial Pyelonephritis
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bordetella Infection
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    4 / 867 (0.46%)
    15 / 1727 (0.87%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Covid-19
         subjects affected / exposed
    1 / 867 (0.12%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Croup Infectious
         subjects affected / exposed
    0 / 867 (0.00%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eczema Coxsackium
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia Urinary Tract Infection
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Exanthema Subitum
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 867 (0.35%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis Norovirus
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis Viral
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal Viral Infection
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impetigo
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         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 / 867 (0.12%)
    4 / 1727 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis Media
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis Media Acute
         subjects affected / exposed
    1 / 867 (0.12%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parainfluenzae Virus Infection
         subjects affected / exposed
    0 / 867 (0.00%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perirectal Abscess
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis Streptococcal
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral Infection
         subjects affected / exposed
    1 / 867 (0.12%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    3 / 867 (0.35%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 867 (0.00%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic Viral Infection
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic Infection
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal Scalded Skin Syndrome
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin Bacterial Infection
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 867 (0.23%)
    6 / 1727 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Mycoplasmal
         subjects affected / exposed
    1 / 867 (0.12%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Viral
         subjects affected / exposed
    0 / 867 (0.00%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 867 (0.00%)
    3 / 1727 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis Acute
         subjects affected / exposed
    0 / 867 (0.00%)
    2 / 1727 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Syncytial Virus Bronchiolitis
         subjects affected / exposed
    4 / 867 (0.46%)
    9 / 1727 (0.52%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Syncytial Virus Infection
         subjects affected / exposed
    6 / 867 (0.69%)
    7 / 1727 (0.41%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus Infection
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Roseola
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 867 (0.00%)
    1 / 1727 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Type 1 Diabetes Mellitus
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ketoacidosis
         subjects affected / exposed
    1 / 867 (0.12%)
    0 / 1727 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    4 / 867 (0.46%)
    3 / 1727 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Group 2 Group 1
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    746 / 867 (86.04%)
    1471 / 1727 (85.18%)
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    507 / 867 (58.48%)
    975 / 1727 (56.46%)
         occurrences all number
    1273
    2319
    General disorders and administration site conditions
    Injection Site Bruising
         subjects affected / exposed
    88 / 867 (10.15%)
    185 / 1727 (10.71%)
         occurrences all number
    158
    380
    Injection Site Erythema
         subjects affected / exposed
    409 / 867 (47.17%)
    806 / 1727 (46.67%)
         occurrences all number
    2054
    3898
    Injection Site Pain
         subjects affected / exposed
    637 / 867 (73.47%)
    1201 / 1727 (69.54%)
         occurrences all number
    5053
    9341
    Injection Site Swelling
         subjects affected / exposed
    323 / 867 (37.25%)
    632 / 1727 (36.60%)
         occurrences all number
    1491
    2651
    Pyrexia
         subjects affected / exposed
    312 / 867 (35.99%)
    580 / 1727 (33.58%)
         occurrences all number
    512
    912
    Crying
         subjects affected / exposed
    541 / 867 (62.40%)
    1023 / 1727 (59.24%)
         occurrences all number
    1303
    2366
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    196 / 867 (22.61%)
    417 / 1727 (24.15%)
         occurrences all number
    276
    607
    Teething
         subjects affected / exposed
    62 / 867 (7.15%)
    106 / 1727 (6.14%)
         occurrences all number
    73
    124
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    598 / 867 (68.97%)
    1154 / 1727 (66.82%)
         occurrences all number
    1694
    3082
    Infections and infestations
    Otitis Media
         subjects affected / exposed
    48 / 867 (5.54%)
    79 / 1727 (4.57%)
         occurrences all number
    64
    91
    Nasopharyngitis
         subjects affected / exposed
    50 / 867 (5.77%)
    96 / 1727 (5.56%)
         occurrences all number
    62
    105
    Upper Respiratory Tract Infection
         subjects affected / exposed
    130 / 867 (14.99%)
    214 / 1727 (12.39%)
         occurrences all number
    162
    264
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    388 / 867 (44.75%)
    704 / 1727 (40.76%)
         occurrences all number
    732
    1246

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Mar 2018
    Updated cover page details and number of participants to be enrolled. Clarified how participants were randomized. Clarified that the 4th dose of Pentacel for Subgroup 1a was to be administered outside of the study by the study site personnel/Investigator. Modified existing primary objective; added an additional primary objective and added endpoint for rotavirus following Center for Biologics Evaluation and Research (CBER) protocol review received on 11 January 2018, also modified secondary objectives. Updated measles, mumps, and rubella endpoints with assay limits. Following CBER review/feedback; it was clarified that subgroup analyses was to be performed, presented in statistical analysis plan, an additional immunogenicity objective was added, planned sample size was updated, safety analysis after all 4 doses to observational objectives was included, power calculation was updated. Added and modified observational endpoints to correspond with observational objectives. Clarified exclusion criterion. Updated wording for statistical methods and hypothesis analysis to match the changes from objectives and endpoints. Updated the time window for Visits 02 and 03, and the age at Visit 03. in all tables. Deleted non-clinical safety section. Clarified visit procedure. Updated study calendar and randomization information. Added explanation of the role of the Sponsor’s Safety Management Team. Updated text to reflect regulatory changes. Added new references for adverse events of special interest. Clarified safety and per protocol anlayses sets.
    25 Jan 2019
    Updated cover page details. Updated secondary and observational objectives and modified an inclusion criterion following CBER’s comments. Modified an exclusion criterion. Product composition details modified. Mistake in value corrected. Added maternal immunization history as a study procedure. Wordings modified for clarity wherever necessary. Clarification added defining study vaccines. Modified definitions of analyses sets and updated package inserts.
    02 Jun 2021
    Updated cover page details and study period. During the study conduct, rather high attrition rate was noted especially during the Coronavirus Disease-2019 (COVID-19) pandemic year of 2020 which led the study team to increase the sample size for maintaining an acceptable overall power of primary and powered secondary hypotheses. Main factors of attrition were the visits outside of time windows, no blood draws performed at some visits and routine pediatric vaccines administration outside of the time window. No safety concerns were identified. Sample size was updated. The immunogenicity objectives initially listed as observational objectives were placed under secondary objectives. Added latest information on vaccine approval. Updated name of team member, the total number of participants to align with the updated sample size and study calendar. Minor changes to improve the clarity. A new section on a conditional sensitivity analysis was added to document the impact of COVID-19 pandemic situation on the study conduct.
    26 Jan 2022
    Cover page details updated. Updated the table on “History of Protocol Versions”. Updated secondary endpoints and sensitivity analysis due to COVID-19 pandemic post feedback from CBER. Typo corrected in hypotheses section.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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