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    Clinical Trial Results:
    A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE GIVEN AS A SERIES OF 2 INFANT DOSES AND 1 TODDLER DOSE IN HEALTHY INFANTS

    Summary
    EudraCT number
    		 2019-003306-27
    Trial protocol
    		 NO   CZ   EE   FI   PL   SK   DK   BE   NL   IT  
    Global end of trial date
    18 Feb 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Sep 2023
    First version publication date
    01 Sep 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    B7471012
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04546425
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer Inc., Pfizer ClinicalTrials.gov Call Center, 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002330-PIP01-18
    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
    20 Mar 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Feb 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Safety: To describe the safety profile of 20vPnC. Safety assessments included local reactions, systemic events and adverse events. Primary immunogenicity objectives for primary study population: Noninferiority (NI) of 20vPnC to 13vPnC based on IgG GMCs at 1 month after Dose 2 and 1 month after Dose 3; Percentage of subjects with predefined IgG concentrations 1 month after Dose 2; NI of percentage of subjects with prespecified antibody levels to specific concomitant vaccine antigens 1 month after Dose 3. Primary immunogenicity objectives for Russian Cohort: to describe IgG responses induced by 20vPnC (Percentages of participants with predefined IgG concentrations at 1 month after Dose 2; IgG GMCs at 1 month after Dose 2 and 1 month after Dose 3)
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Sep 2020
    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
    Australia: 2
    Country: Number of subjects enrolled
    Belgium: 15
    Country: Number of subjects enrolled
    Czechia: 72
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    Estonia: 78
    Country: Number of subjects enrolled
    Finland: 354
    Country: Number of subjects enrolled
    Italy: 72
    Country: Number of subjects enrolled
    Netherlands: 14
    Country: Number of subjects enrolled
    Norway: 14
    Country: Number of subjects enrolled
    Poland: 546
    Country: Number of subjects enrolled
    Slovakia: 34
    Country: Number of subjects enrolled
    Russian Federation: 51
    Worldwide total number of subjects
    1255
    EEA total number of subjects
    1202
    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)
    1255
    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
    		 -

    Pre-assignment
    Screening details
    		 For primary study population,1207 participants were enrolled & assigned to receive 3 doses of 20-valent pneumococcal conjugate vaccine (20vPnC) or 13vPnC of which 3 participants were not vaccinated, 1204 were vaccinated with 20vPnC or 13vPnC.Additional 51 Russian subjects were enrolled, all of which were vaccinated with 20vPnC or 13vPnC.

    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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 20vPnC: Primary Study Population
    Arm description
    		 Infants 42 to 112 days of age were enrolled to receive 3 doses of 0.5 mL 20vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 42 to 63 days later. Dose 3 was administered at 335 to 386 days of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    20-Valent Pneumococcal Conjugate Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL dose of 20vPnC intramuscularly on Visits 1, 2, and 4 with Dose 1, 2, 3 respectively.

    Arm title
    		 13vPnC: Primary Study Population
    Arm description
    		 Infants 42 to 112 days of age were enrolled to receive 3 doses of 0.5 mL 13vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 42 to 63 days later. Dose 3 was administered at 335 to 386 days of age.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    13-Valent Pneumococcal Conjugate Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL dose of 13vPnC intramuscularly on Visits 1, 2, and 4 with Dose 1, 2, 3 respectively.

    Arm title
    		 20vPnC: Russian Cohort
    Arm description
    		 Infants 42 to 70 days of age were enrolled to receive 3 doses of 0.5 mL 20vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 60 to 90 days later. Dose 3 was administered at 335 to 455 days of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    20-Valent Pneumococcal Conjugate Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL dose of 20vPnC intramuscularly on Visits 1, 2, and 4 with Dose 1, 2, 3 respectively.

    Arm title
    		 13vPnC: Russian Cohort
    Arm description
    		 Infants 42 to 70 days of age were enrolled to receive 3 doses of 0.5 mL 13vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 60 to 90 days later. Dose 3 was administered at 335 to 455 days of age.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    13-Valent Pneumococcal Conjugate Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL dose of 13vPnC intramuscularly on Visits 1, 2, and 4 with Dose 1, 2, 3 respectively.

    Number of subjects in period 1
    		20vPnC: Primary Study Population 13vPnC: Primary Study Population 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Started
    601
    603
    24
    27
    Dose 1
    601
    603
    24
    27
    Dose 2
    593
    598
    24
    27
    Dose 3
    588
    594
    22
    25
    Completed
    583
    590
    22
    25
    Not completed
    18
    13
    2
    2
         Adverse event, non-fatal
    3
    -
    -
    -
         Lost to follow-up
    5
    4
    -
    -
         Withdrawal by parent/guardian
    6
    5
    1
    1
         No Longer met eligibility criteria
    3
    3
    1
    1
         Protocol deviation
    1
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    20vPnC: Primary Study Population
    Reporting group description
    		 Infants 42 to 112 days of age were enrolled to receive 3 doses of 0.5 mL 20vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 42 to 63 days later. Dose 3 was administered at 335 to 386 days of age.

    Reporting group title
    13vPnC: Primary Study Population
    Reporting group description
    		 Infants 42 to 112 days of age were enrolled to receive 3 doses of 0.5 mL 13vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 42 to 63 days later. Dose 3 was administered at 335 to 386 days of age.

    Reporting group title
    20vPnC: Russian Cohort
    Reporting group description
    		 Infants 42 to 70 days of age were enrolled to receive 3 doses of 0.5 mL 20vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 60 to 90 days later. Dose 3 was administered at 335 to 455 days of age.

    Reporting group title
    13vPnC: Russian Cohort
    Reporting group description
    		 Infants 42 to 70 days of age were enrolled to receive 3 doses of 0.5 mL 13vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 60 to 90 days later. Dose 3 was administered at 335 to 455 days of age.

    Reporting group values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population 20vPnC: Russian Cohort 13vPnC: Russian Cohort Total
    Number of subjects
    		 601 603 24 27 1255
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 601 603 24 27 1255
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 0 0 0 0 0
        From 65-84 years
    		 0 0 0 0 0
        85 years and over
    		 0 0 0 0 0
    Age Continuous
    Units: Days
        arithmetic mean (standard deviation)
    		 69.2 ± 17.76 69.7 ± 18.32 64.2 ± 6.98 63.3 ± 6.21 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 302 292 16 12 622
        Male
    		 299 311 8 15 633
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 8 5 0 1 14
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 0 1 0 0 1
        White
    		 585 592 24 26 1227
        More than one race
    		 1 0 0 0 1
        Unknown or Not Reported
    		 7 5 0 0 12
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 1 0 0 5
        Not Hispanic or Latino
    		 577 586 22 25 1210
        Unknown or Not Reported
    		 20 16 2 2 40

    End points

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    End points reporting groups
    Reporting group title
    20vPnC: Primary Study Population
    Reporting group description
    		 Infants 42 to 112 days of age were enrolled to receive 3 doses of 0.5 mL 20vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 42 to 63 days later. Dose 3 was administered at 335 to 386 days of age.

    Reporting group title
    13vPnC: Primary Study Population
    Reporting group description
    		 Infants 42 to 112 days of age were enrolled to receive 3 doses of 0.5 mL 13vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 42 to 63 days later. Dose 3 was administered at 335 to 386 days of age.

    Reporting group title
    20vPnC: Russian Cohort
    Reporting group description
    		 Infants 42 to 70 days of age were enrolled to receive 3 doses of 0.5 mL 20vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 60 to 90 days later. Dose 3 was administered at 335 to 455 days of age.

    Reporting group title
    13vPnC: Russian Cohort
    Reporting group description
    		 Infants 42 to 70 days of age were enrolled to receive 3 doses of 0.5 mL 13vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 60 to 90 days later. Dose 3 was administered at 335 to 455 days of age.

    Primary: Percentage of Subjects With Local Reactions Within 7 Days After Dose 1: Primary Study Population

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    End point title
    		 Percentage of Subjects With Local Reactions Within 7 Days After Dose 1: Primary Study Population [1] [2]
    End point description
    Local reactions included redness, swelling and, pain at the injection site, recorded by parent’s/legal guardians of subjects in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild (greater than [>] 0 to 2.0 cm), moderate (> 2.0 to 7.0 cm) and severe (>7.0 cm). Pain at injection site was graded as mild (hurt if gently touched example, whimpered, winced, protested, or withdrew), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). 95 percent (%) confidence interval (CI) was based on Clopper and Pearson method.Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose. Here, “Number of subjects Analyzed” signifies the number of subjects with any e-diary data after Dose 1.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 1
    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: This endpoint was planned to be analysed only for the specified reporting arms
    [2] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    598
    603
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Mild
    20.7 (17.6 to 24.2)
    22.7 (19.4 to 26.3)
        Redness: Moderate
    4.5 (3.0 to 6.5)
    4.8 (3.2 to 6.8)
        Redness: Severe
    0 (0.0 to 0.6)
    0 (0.0 to 0.6)
        Swelling: Mild
    12.7 (10.1 to 15.6)
    12.9 (10.4 to 15.9)
        Swelling: Moderate
    8.7 (6.6 to 11.2)
    7.3 (5.4 to 9.7)
        Swelling: Severe
    0 (0.0 to 0.6)
    0 (0.0 to 0.6)
        Pain at Injection Site: Mild
    16.7 (13.8 to 20.0)
    17.9 (14.9 to 21.2)
        Pain at Injection Site: Moderate
    12.0 (9.5 to 14.9)
    11.4 (9.0 to 14.3)
        Pain at Injection Site: Severe
    0.3 (0.0 to 1.2)
    0 (0.0 to 0.6)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Local Reactions Within 7 Days After Dose 2: Primary Study Population

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    End point title
    		 Percentage of Subjects With Local Reactions Within 7 Days After Dose 2: Primary Study Population [3] [4]
    End point description
    Local reactions included redness, swelling and, pain at the injection site, recorded by parent’s/legal guardians of subjects in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0 to 2.0 cm), moderate (> 2.0 to 7.0 cm) and severe (>7.0 cm). Pain at injection site was graded as mild (hurt if gently touched example, whimpered, winced, protested, or withdrew), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). 95% CI was based on Clopper and Pearson method. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose. Here, “Number of Subjects Analyzed” signifies the number of subjects with any e-diary data after Dose 2.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 2
    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: This endpoint was planned to be analysed only for the specified reporting arms
    [4] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    592
    594
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Mild
    24.8 (21.4 to 28.5)
    22.9 (19.6 to 26.5)
        Redness: Moderate
    3.7 (2.3 to 5.6)
    5.1 (3.4 to 7.1)
        Redness: Severe
    0 (0.0 to 0.6)
    0.2 (0.0 to 0.9)
        Swelling: Mild
    13.7 (11.0 to 16.7)
    14.1 (11.4 to 17.2)
        Swelling: Moderate
    8.3 (6.2 to 10.8)
    6.2 (4.4 to 8.5)
        Swelling: Severe
    0 (0.0 to 0.6)
    0.2 (0.0 to 0.9)
        Pain at Injection Site: Mild
    13.3 (10.7 to 16.4)
    16.5 (13.6 to 19.7)
        Pain at Injection Site: Moderate
    9.3 (7.1 to 11.9)
    7.9 (5.9 to 10.4)
        Pain at Injection Site: Severe
    0.2 (0.0 to 0.9)
    0.2 (0.0 to 0.9)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Local Reactions Within 7 Days After Dose 3: Primary Study Population

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    End point title
    		 Percentage of Subjects With Local Reactions Within 7 Days After Dose 3: Primary Study Population [5] [6]
    End point description
    Local reactions included redness, swelling and, pain at the injection site, recorded by parent’s/legal guardians of subjects in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0 to 2.0 cm), moderate (> 2.0 to 7.0 cm) and severe (>7.0 cm). Pain at injection site was graded as mild (hurt if gently touched example, whimpered, winced, protested, or withdrew), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). 95% CI was based on Clopper and Pearson method.Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose. Here, “Number of Subjects Analyzed” signifies the number of subjects with any e-diary data after Dose 3.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 3
    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: This endpoint was planned to be analysed only for the specified reporting arms
    [6] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    580
    586
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Mild
    23.3 (19.9 to 26.9)
    25.1 (21.6 to 28.8)
        Redness: Moderate
    13.4 (10.8 to 16.5)
    8.5 (6.4 to 11.1)
        Redness: Severe
    0.2 (0.0 to 1.0)
    0.2 (0.0 to 0.9)
        Swelling: Mild
    17.8 (14.7 to 21.1)
    14.5 (11.8 to 17.6)
        Swelling: Moderate
    11.9 (9.4 to 14.8)
    9.7 (7.5 to 12.4)
        Swelling: Severe
    0.2 (0.0 to 1.0)
    0.3 (0.0 to 1.2)
        Pain at Injection Site: Mild
    24.7 (21.2 to 28.4)
    22.4 (19.0 to 25.9)
        Pain at Injection Site: Moderate
    17.4 (14.4 to 20.8)
    17.2 (14.3 to 20.5)
        Pain at Injection Site: Severe
    0.3 (0.0 to 1.2)
    0.3 (0.0 to 1.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Systemic Events Within 7 Days After Dose 1: Primary Study Population

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    End point title
    		 Percentage of Subjects With Systemic Events Within 7 Days After Dose 1: Primary Study Population [7] [8]
    End point description
    Systemic events:fever,decreased appetite,drowsiness/increased sleep & irritability, recorded by parents/legal guardians of subjects using e-diary. Fever: temperature >=38.0 degree C & categorized as >=38.0 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C & >40.0-degree C.Decreased appetite: mild (decreased interest in eating), moderate (decreased oral intake) & severe (refusal to feed).Drowsiness was graded as mild (increased/prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) & severe (disabling, not interested in usual daily activity).Irritability: mild (easily consolable), moderate (required increased attention) & severe (inconsolable, crying could not be comforted). 95% CI was based on Clopper & Pearson method. Safety analysis set: all subjects who received at least 1 dose of 20vPnC or 13vPnC & had safety data assessed after any dose. Here,“Number of Subjects Analyzed”:number of subjects with any e-diary data after Dose1
    End point type
    Primary
    End point timeframe
    Within 7 Days after Dose 1
    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: This endpoint was planned to be analysed only for the specified reporting arms.
    [8] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    598
    603
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever: >=38.0 degrees C to 38.4 degrees C
    7.5 (5.5 to 9.9)
    6.8 (4.9 to 9.1)
        Fever: >38.4 degrees C to 38.9 degrees C
    1.3 (0.6 to 2.6)
    1.3 (0.6 to 2.6)
        Fever: >38.9 degrees C to 40.0 degrees C
    0 (0.0 to 0.6)
    0.3 (0.0 to 1.2)
        Fever: >40.0 degrees C
    0 (0.0 to 0.6)
    0 (0.0 to 0.6)
        Decreased appetite: Mild
    16.2 (13.4 to 19.4)
    13.3 (10.7 to 16.2)
        Decreased appetite: Moderate
    7.5 (5.5 to 9.9)
    8.8 (6.7 to 11.3)
        Decreased appetite: Severe
    1.0 (0.4 to 2.2)
    0.5 (0.1 to 1.4)
        Drowsiness: Mild
    46.0 (41.9 to 50.1)
    48.6 (44.5 to 52.7)
        Drowsiness: Moderate
    14.4 (11.7 to 17.5)
    14.3 (11.6 to 17.3)
        Drowsiness: Severe
    0.8 (0.3 to 1.9)
    0.8 (0.3 to 1.9)
        Irritability: Mild
    17.6 (14.6 to 20.8)
    17.4 (14.5 to 20.7)
        Irritability: Moderate
    46.2 (42.1 to 50.2)
    46.4 (42.4 to 50.5)
        Irritability: Severe
    8.2 (6.1 to 10.7)
    8.6 (6.5 to 11.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Systemic Events Within 7 Days After Dose 2: Primary Study Population

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    End point title
    		 Percentage of Subjects With Systemic Events Within 7 Days After Dose 2: Primary Study Population [9] [10]
    End point description
    Systemic events:fever,decreased appetite,drowsiness/increased sleep & irritability, recorded by parents/legal guardians of subject's using e-diary. Fever: temperature >=38.0 degree C & categorized as >=38.0 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C & >40.0-degree C. Decreased appetite: mild (decreased interest in eating), moderate (decreased oral intake) & severe (refusal to feed).Drowsiness was graded as mild (increased/prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) & severe (disabling, not interested in usual daily activity).Irritability: mild (easily consolable), moderate (required increased attention) & severe (inconsolable, crying could not be comforted). 95% CI was based on Clopper & Pearson method. Safety analysis set: all subjects who received at least 1 dose of 20vPnC or 13vPnC & had safety data assessed after any dose. Here,“Number of Subjects Analyzed”: number of subjects with any e-diary data after Dose2
    End point type
    Primary
    End point timeframe
    Within 7 Days after Dose 2
    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: Only descriptive analysis was planned for this endpoint
    [10] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    592
    594
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever: >=38.0 degrees C to 38.4 degrees C
    11.7 (9.2 to 14.5)
    11.6 (9.2 to 14.5)
        Fever: >38.4 degrees C to 38.9 degrees C
    2.5 (1.4 to 4.1)
    2.0 (1.0 to 3.5)
        Fever: >38.9 degrees C to 40.0 degrees C
    0.7 (0.2 to 1.7)
    0.3 (0.0 to 1.2)
        Fever: >40.0 degrees C
    0 (0.0 to 0.6)
    0 (0.0 to 0.6)
        Decreased appetite: Mild
    13.5 (10.9 to 16.5)
    12.1 (9.6 to 15.0)
        Decreased appetite: Moderate
    10.1 (7.8 to 12.9)
    6.4 (4.6 to 8.7)
        Decreased appetite: Severe
    1.0 (0.4 to 2.2)
    0.8 (0.3 to 2.0)
        Drowsiness: Mild
    37.8 (33.9 to 41.9)
    37.0 (33.1 to 41.1)
        Drowsiness: Moderate
    13.2 (10.6 to 16.2)
    13.5 (10.8 to 16.5)
        Drowsiness: Severe
    0.3 (0.0 to 1.2)
    0.2 (0.0 to 0.9)
        Irritability: Mild
    22.8 (19.5 to 26.4)
    21.2 (18.0 to 24.7)
        Irritability: Moderate
    43.1 (39.0 to 47.2)
    40.6 (36.6 to 44.6)
        Irritability: Severe
    5.7 (4.0 to 7.9)
    6.6 (4.7 to 8.9)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Systemic Events Within 7 Days After Dose 3: Primary Study Population

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    End point title
    		 Percentage of Subjects With Systemic Events Within 7 Days After Dose 3: Primary Study Population [11] [12]
    End point description
    Systemic events:fever,decreased appetite,drowsiness/increased sleep & irritability, recorded by parents/legal guardians of subject's using e-diary. Fever: temperature >=38.0 degree C & categorized as >=38.0 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C & >40.0-degree C. Decreased appetite: mild (decreased interest in eating), moderate (decreased oral intake) & severe (refusal to feed).Drowsiness was graded as mild (increased/prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) & severe (disabling, not interested in usual daily activity).Irritability: mild (easily consolable), moderate (required increased attention) & severe (inconsolable, crying could not be comforted). 95% CI was based on Clopper & Pearson method. Safety analysis set: all subjects who received at least 1 dose of 20vPnC or 13vPnC & had safety data assessed after any dose. Here,“Number of Subjects Analyzed”: number of subjects with any e-diary data after Dose 3.
    End point type
    Primary
    End point timeframe
    Within 7 Days after Dose 3
    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: Only descriptive analysis was planned for this endpoint
    [12] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    580
    586
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever: >=38.0 degrees C to 38.4 degrees C
    13.4 (10.8 to 16.5)
    13.5 (10.8 to 16.5)
        Fever: >38.4 degrees C to 38.9 degrees C
    6.9 (5.0 to 9.3)
    7.0 (5.1 to 9.4)
        Fever: >38.9 degrees C to 40.0 degrees C
    3.6 (2.3 to 5.5)
    3.2 (2.0 to 5.0)
        Fever: >40.0 degrees C
    0.3 (0.0 to 1.2)
    0 (0.0 to 0.6)
        Decreased appetite: Mild
    20.0 (16.8 to 23.5)
    15.5 (12.7 to 18.7)
        Decreased appetite: Moderate
    17.1 (14.1 to 20.4)
    18.9 (15.8 to 22.4)
        Decreased appetite: Severe
    2.2 (1.2 to 3.8)
    2.0 (1.1 to 3.5)
        Drowsiness: Mild
    34.8 (30.9 to 38.9)
    32.8 (29.0 to 36.7)
        Drowsiness: Moderate
    15.3 (12.5 to 18.5)
    14.7 (11.9 to 17.8)
        Drowsiness: Severe
    0.7 (0.2 to 1.8)
    1.2 (0.5 to 2.4)
        Irritability: Mild
    23.4 (20.1 to 27.1)
    21.3 (18.1 to 24.9)
        Irritability: Moderate
    43.4 (39.4 to 47.6)
    45.4 (41.3 to 49.5)
        Irritability: Severe
    4.1 (2.7 to 6.1)
    4.1 (2.6 to 6.0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Serious Adverse Events (SAEs) From Dose 1 to 1 Month After Dose 3: Primary Study Population

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    End point title
    		 Percentage of Subjects With Serious Adverse Events (SAEs) From Dose 1 to 1 Month After Dose 3: Primary Study Population [13] [14]
    End point description
    An SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. 95% CI was based on the Clopper and Pearson method. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose.
    End point type
    Primary
    End point timeframe
    From Dose 1 to 1 month after Dose 3
    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: Only descriptive analysis was planned for this endpoint
    [14] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    601
    603
    Units: Percentage of subjects
        number (confidence interval 95%)
    5.7 (3.9 to 7.8)
    6.6 (4.8 to 8.9)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Adverse Events (AEs) From Dose 3 to 1 Month After Dose 3: Primary Study Population

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    End point title
    		 Percentage of Subjects With Adverse Events (AEs) From Dose 3 to 1 Month After Dose 3: Primary Study Population [15] [16]
    End point description
    An AE was any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment. 95% CI was based on the Clopper and Pearson method. AEs reported in this outcome measure excluded local reactions and systemic events collected from e-diary. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose. Here, “Number of Subjects Analyzed” signifies the number of subjects who received Dose 3.
    End point type
    Primary
    End point timeframe
    From Dose 3 to 1 month after Dose 3
    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: Only descriptive analysis was planned for this endpoint
    [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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    588
    594
    Units: Percentage of subjects
        number (confidence interval 95%)
    15.5 (12.6 to 18.7)
    16.5 (13.6 to 19.7)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Adverse Events (AEs) From Dose 1 to 1 Month After Dose 2: Primary Study Population

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    End point title
    		 Percentage of Subjects With Adverse Events (AEs) From Dose 1 to 1 Month After Dose 2: Primary Study Population [17] [18]
    End point description
    An AE was any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment. 95% CI was based on the Clopper and Pearson method. AEs reported in this outcome measure excluded local reactions and systemic events collected from e-diary. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose.
    End point type
    Primary
    End point timeframe
    From Dose 1 to 1 month after Dose 2
    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: Only descriptive analysis was planned for this endpoint
    [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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    601
    603
    Units: Percentage of subjects
        number (confidence interval 95%)
    13.8 (11.2 to 16.8)
    14.4 (11.7 to 17.5)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Dose 1 to 1 Month After Dose 3: Primary Study Population

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    End point title
    		 Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Dose 1 to 1 Month After Dose 3: Primary Study Population [19] [20]
    End point description
    An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or was otherwise long-lasting in its effects. 95% CI was based on the Clopper and Pearson method. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose.
    End point type
    Primary
    End point timeframe
    From Dose 1 to 1 month after Dose 3
    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 endpoint was planned to be analysed only for the specified reporting arms
    [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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    601
    603
    Units: Percentage of subjects
        number (confidence interval 95%)
    1.0 (0.4 to 2.2)
    1.0 (0.4 to 2.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Predefined Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After Dose 2: Primary Study Population

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    End point title
    		 Percentage of Subjects With Predefined Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After Dose 2: Primary Study Population [21]
    End point description
    Predefined IgG concentrations were as follows: for serotype 1, 3, 4, 6A, 7F, 9V, 14, 18C, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, 33F: >=0.35 microgram per mL (mcg/mL), for serotype 5: >=0.23 mcg/mL, for serotype 6B. >=0.10 mcg/mL and for serotype 19A: >=0.12 mcg/mL. 95% CI was based on the Clopper and Pearson method. Dose 2 evaluable immunogenicity population: eligible subjects 42-112 days of age at first vaccination, received first 2 doses as randomized, at least 1 valid immunogenicity results from blood collection (27 to 56 days after Dose 2),no other major protocol deviations. "Number of Subjects Analyzed"= subjects in Dose 2 evaluable immunogenicity population, "n"= subjects with valid IgG assay results for specified serotype.
    End point type
    Primary
    End point timeframe
    1 month after Dose 2
    Notes
    [21] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    567
    562
    Units: Percentage of subjects
    number (confidence interval 95%)
        Serotype 1, n=566, 562
    70.7 (66.7 to 74.4)
    84.2 (80.9 to 87.1)
        Serotype 3, n=566, 562
    58.0 (53.8 to 62.1)
    75.8 (72.0 to 79.3)
        Serotype 4, n=566, 562
    68.6 (64.5 to 72.4)
    79.5 (76.0 to 82.8)
        Serotype 5, n=566, 562
    63.4 (59.3 to 67.4)
    76.0 (72.2 to 79.5)
        Serotype 6A, n=566, 562
    59.5 (55.4 to 63.6)
    73.7 (69.8 to 77.3)
        Serotype 6B, n=564, 561
    20.7 (17.5 to 24.3)
    36.5 (32.5 to 40.7)
        Serotype 7F, n=566, 562
    87.6 (84.6 to 90.2)
    90.2 (87.5 to 92.5)
        Serotype 9V, n=566, 562
    60.2 (56.1 to 64.3)
    74.6 (70.7 to 78.1)
        Serotype 14, n=565, 562
    78.6 (75.0 to 81.9)
    81.9 (78.4 to 85.0)
        Serotype 18C, n=566, 562
    71.0 (67.1 to 74.7)
    76.5 (72.8 to 80.0)
        Serotype 19A, n=566, 562
    92.2 (89.7 to 94.3)
    94.0 (91.6 to 95.8)
        Serotype 19F, n=566, 562
    94.3 (92.1 to 96.1)
    95.7 (93.7 to 97.2)
        Serotype 23F, n=566, 562
    23.5 (20.1 to 27.2)
    41.8 (37.7 to 46.0)
        Serotype 8, n=567, 561
    96.5 (94.6 to 97.8)
    2.9 (1.6 to 4.6)
        Serotype 10A, n=567, 562
    28.9 (25.2 to 32.8)
    2.7 (1.5 to 4.4)
        Serotype 11A, n=567, 562
    94.2 (91.9 to 96.0)
    2.0 (1.0 to 3.5)
        Serotype 12F, n=567, 562
    30.3 (26.6 to 34.3)
    0.2 (0.0 to 1.0)
        Serotype 15B, n=566, 562
    94.3 (92.1 to 96.1)
    8.5 (6.4 to 11.2)
        Serotype 22F, n=567, 562
    94.4 (92.1 to 96.1)
    2.0 (1.0 to 3.5)
        Serotype 33F, n=566, 562
    46.8 (42.6 to 51.0)
    2.7 (1.5 to 4.4)
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 4: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [22]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16
         upper limit
    		 -5.9
    Notes
    [22] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 3: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [23]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -17.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.2
         upper limit
    		 -12.4
    Notes
    [23] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 5: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [24]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -12.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.8
         upper limit
    		 -7.2
    Notes
    [24] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 1: 2-Sided 95% CIs are calculated using the Miettinen and Nurminen method for the difference in proportions, expressed as a percentage.
    Comparison groups
    13vPnC: Primary Study Population v 20vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [25]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -13.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.3
         upper limit
    		 -8.7
    Notes
    [25] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 7F: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [26]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.3
         upper limit
    		 1.1
    Notes
    [26] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 6A: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [27]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -14.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.5
         upper limit
    		 -8.6
    Notes
    [27] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 9V: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [28]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -14.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.7
         upper limit
    		 -8.9
    Notes
    [28] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 6B: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [29]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -15.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21
         upper limit
    		 -10.6
    Notes
    [29] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 19A: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [30]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 1.3
    Notes
    [30] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 19F: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [31]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 1.2
    Notes
    [31] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 23F: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [32]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -18.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.6
         upper limit
    		 -12.9
    Notes
    [32] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 8: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [33]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    59.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 55.6
         upper limit
    		 64.1
    Notes
    [33] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC - lowest 13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 10A: 2-Sided 95% CI based on the Percent difference for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [34]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -7.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.1
         upper limit
    		 -2.1
    Notes
    [34] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC - lowest 13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 14: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [35]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.9
         upper limit
    		 1.4
    Notes
    [35] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 18C: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [36]
    Method
    Parameter type
    		 Percent Difference
    Point estimate
    -5.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.6
         upper limit
    		 -0.4
    Notes
    [36] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 11A: 2-Sided 95% CI based on the Percent difference for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [37]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    57.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 53.1
         upper limit
    		 61.9
    Notes
    [37] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC - lowest 13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 22F: 2-Sided 95% CI based on the Percent difference for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [38]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    57.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 53.3
         upper limit
    		 62.1
    Notes
    [38] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC - lowest 13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 33F: 2-Sided 95% CI based on the Percent difference for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [39]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    10.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.5
         upper limit
    		 16
    Notes
    [39] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC - lowest 13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 12F: 2-Sided 95% CI based on the Percent difference for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [40]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -6.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.7
         upper limit
    		 -0.7
    Notes
    [40] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC - lowest 13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 15B: 2-Sided 95% CI based on the Percent difference for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [41]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    57.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 53.3
         upper limit
    		 62.1
    Notes
    [41] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC - lowest 13vPnC) was greater than -10%.

    Primary: Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal IgG Antibody 1 Month After Dose 2: Primary Study Population

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    End point title
    		 Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal IgG Antibody 1 Month After Dose 2: Primary Study Population [42]
    End point description
    Pneumococcal serotype-specific IgG concentration was measured for serum sample for 13vPnC serotype:1, 3, 4,5,6A,6B,7F,9V,14,18C,19A,19F,23F, 7 additional serotype:8, 10A, 11A, 12F, 15B, 22F, 33F.GMC & corresponding 2-sided 95% CIs were calculated by exponentiating mean logarithm of concentration, corresponding 2-sided 95% CIs (based on Student's t distribution).Assay result below LLOQ was set to 0.5×LLOQ.GMRs were reported in statistical analysis section & were calculated by exponentiating mean difference of logarithm of concentration & corresponding 2-sided 95% CIs (based on Student's t distribution).Dose 2 evaluable immunogenicity population:eligible subject 42-112 days of age at first vaccination,received 1st 2 doses as randomized,at least 1 valid immunogenicity result from blood collection (27-56 days after Dose2). "Number of Subject Analyzed"=subject in Dose 2 evaluable immunogenicity population, "n"= subject with valid IgG assay result for specified serotype.
    End point type
    Primary
    End point timeframe
    1 month after Dose 2
    Notes
    [42] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    567
    562
    Units: mcg/mL
    geometric mean (confidence interval 95%)
        Serotype 1, n=566, 562
    0.57 (0.52 to 0.62)
    0.93 (0.86 to 1.01)
        Serotype 3, n=566, 562
    0.41 (0.38 to 0.45)
    0.58 (0.54 to 0.63)
        Serotype 4, n=566, 562
    0.55 (0.50 to 0.61)
    0.92 (0.83 to 1.02)
        Serotype 5, n=566, 562
    0.34 (0.30 to 0.38)
    0.56 (0.50 to 0.62)
        Serotype 6A, n=566, 562
    0.45 (0.40 to 0.52)
    0.84 (0.73 to 0.95)
        Serotype 6B, n=564, 561
    0.03 (0.03 to 0.04)
    0.06 (0.05 to 0.07)
        Serotype 7F, n=566, 562
    1.02 (0.94 to 1.10)
    1.41 (1.30 to 1.53)
        Serotype 9V, n=566, 562
    0.45 (0.40 to 0.51)
    0.77 (0.68 to 0.87)
        Serotype 14, n=565, 562
    1.05 (0.94 to 1.18)
    1.28 (1.14 to 1.43)
        Serotype 18C, n=566, 562
    0.69 (0.62 to 0.77)
    0.87 (0.78 to 0.98)
        Serotype 19A, n=566, 562
    0.67 (0.61 to 0.74)
    1.13 (1.01 to 1.26)
        Serotype 19F, n=566, 562
    2.21 (2.04 to 2.40)
    3.06 (2.80 to 3.34)
        Serotype 23F, n=566, 562
    0.13 (0.12 to 0.15)
    0.25 (0.22 to 0.28)
        Serotype 8, n=567, 561
    1.62 (1.51 to 1.74)
    0.02 (0.02 to 0.02)
        Serotype 10A, n=567, 562
    0.16 (0.14 to 0.18)
    0.02 (0.02 to 0.02)
        Serotype 11A, n=567, 562
    1.62 (1.50 to 1.75)
    0.02 (0.02 to 0.02)
        Serotype 12F, n=567, 562
    0.15 (0.13 to 0.17)
    0.01 (0.01 to 0.01)
        Serotype 15B, n=566, 562
    3.33 (3.00 to 3.70)
    0.04 (0.04 to 0.04)
        Serotype 22F, n=567, 562
    2.25 (2.06 to 2.45)
    0.01 (0.01 to 0.01)
        Serotype 33F, n=566, 562
    0.31 (0.28 to 0.34)
    0.03 (0.02 to 0.03)
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 4: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [43]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 0.69
    Notes
    [43] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 3: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [44]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.79
    Notes
    [44] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 1: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [45]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 0.69
    Notes
    [45] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 9V: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [46]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 0.69
    Notes
    [46] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 7F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [47]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.8
    Notes
    [47] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 6B: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [48]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 0.61
    Notes
    [48] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 6A: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [49]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 0.65
    Notes
    [49] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 5: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [50]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 0.7
    Notes
    [50] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 12F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [51]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    2.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.08
         upper limit
    		 2.97
    Notes
    [51] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 15B: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [52]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    54.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 46.35
         upper limit
    		 64.3
    Notes
    [52] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 22F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [53]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    36.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 31.57
         upper limit
    		 42.89
    Notes
    [53] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 11A: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [54]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    26.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 22.95
         upper limit
    		 30.82
    Notes
    [54] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 10A: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [55]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    2.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.25
         upper limit
    		 3.17
    Notes
    [55] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 8: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [56]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    26.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 22.98
         upper limit
    		 30.67
    Notes
    [56] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 23F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [57]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.44
         upper limit
    		 0.62
    Notes
    [57] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 19F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [58]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.82
    Notes
    [58] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 19A: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [59]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 0.69
    Notes
    [59] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 33F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [60]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    5.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.27
         upper limit
    		 5.92
    Notes
    [60] - For the additional 7 serotypes, the compared results are from serotype 6B (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 14: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [61]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 0.96
    Notes
    [61] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 18C: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    		 [62]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 0.92
    Notes
    [62] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).

    Primary: GMC of Serotype-specific Pneumococcal IgG Antibody 1 Month After Dose 3: Primary Study Population

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    End point title
    		 GMC of Serotype-specific Pneumococcal IgG Antibody 1 Month After Dose 3: Primary Study Population [63]
    End point description
    Pneumococcal serotype-specific IgG concentrations were measured for serum samples for 13vPnC serotypes:1,3,4, 5,6A,6B,7F,9V,14,18C,19A,19F, 23F, 7additional serotype: 8, 10A, 11A, 12F, 15B, 22F,33F. GMC & corresponding 2-sided 95% CI were calculated by exponentiating mean logarithm of concentrations & corresponding 2-sided 95% CI (based on Student's t distribution).Assay result below LLOQ were set to 0.5×LLOQ.GMRs were reported in statistical analysis section & were calculated by exponentiating mean difference of logarithm of concentration & corresponding 2-sided 95% CI(based on Student's t distribution).Dose 3 evaluable immunogenicity population(EIP)=eligible subject 42-112 days of age at first vaccination,received all 3 dose as randomized with 335-386 day of age at Dose 3 atleast 1 valid immunogenicity results within 27-56 days after Dose 3,no major protocol deviation "Number of Subjects Analyzed"=subjects in Dose 3 EIP;"n"=subjects with valid IgG results for specified serotype.
    End point type
    Primary
    End point timeframe
    1 month after Dose 3
    Notes
    [63] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    497
    504
    Units: mcg/mL
    geometric mean (confidence interval 95%)
        Serotype 1, n=494, 502
    1.71 (1.58 to 1.84)
    2.53 (2.33 to 2.75)
        Serotype 3, n=494, 502
    0.72 (0.67 to 0.78)
    1.09 (1.01 to 1.17)
        Serotype 4, n=494, 502
    4.11 (3.77 to 4.48)
    5.36 (4.91 to 5.85)
        Serotype 5, n=494, 502
    1.74 (1.60 to 1.89)
    2.41 (2.21 to 2.64)
        Serotype 6A, n=494, 501
    7.75 (7.04 to 8.53)
    11.82 (10.66 to 13.11)
        Serotype 6B, n=494, 501
    2.64 (2.36 to 2.95)
    4.63 (4.09 to 5.25)
        Serotype 7F, n=494, 502
    3.61 (3.40 to 3.84)
    4.93 (4.63 to 5.24)
        Serotype 9V, n=494, 502
    3.68 (3.42 to 3.97)
    5.04 (4.67 to 5.43)
        Serotype 14, n=493, 501
    4.52 (4.08 to 5.00)
    5.66 (5.12 to 6.26)
        Serotype 18C, n=494, 502
    2.71 (2.52 to 2.93)
    3.61 (3.33 to 3.91)
        Serotype 19A, n=494, 502
    4.51 (4.11 to 4.94)
    5.49 (5.02 to 6.01)
        Serotype 19F, n=494, 502
    6.19 (5.68 to 6.75)
    8.08 (7.40 to 8.83)
        Serotype 23F, n=494, 502
    2.64 (2.40 to 2.91)
    4.40 (3.95 to 4.90)
        Serotype 8, n=495, 501
    3.57 (3.32 to 3.83)
    0.03 (0.03 to 0.03)
        Serotype 10A, n=495, 502
    4.86 (4.41 to 5.36)
    0.01 (0.01 to 0.01)
        Serotype 11A, n=495, 502
    3.74 (3.44 to 4.07)
    0.02 (0.01 to 0.02)
        Serotype 12F, n=495, 502
    1.86 (1.71 to 2.01)
    0.01 (0.01 to 0.01)
        Serotype 15B, n=495, 502
    13.09 (12.10 to 14.15)
    0.02 (0.02 to 0.03)
        Serotype 22F, n=495, 502
    9.27 (8.52 to 10.08)
    0.00 (0.00 to 0.00)
        Serotype 33F, n=495, 501
    6.37 (5.83 to 6.95)
    0.01 (0.01 to 0.01)
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 3: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [64]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 0.73
    Notes
    [64] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 1: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [65]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 0.75
    Notes
    [65] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 4: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [66]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 0.87
    Notes
    [66] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 5: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [67]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.81
    Notes
    [67] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 6A: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [68]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 0.75
    Notes
    [68] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 6B: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [69]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 0.67
    Notes
    [69] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 7F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [70]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 0.8
    Notes
    [70] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 14: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [71]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 0.92
    Notes
    [71] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 9V: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [72]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 0.81
    Notes
    [72] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 18C: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [73]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 0.84
    Notes
    [73] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 12F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [74]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 0.87
    Notes
    [74] - For the additional 7 serotypes, the compared results are from serotype 5 (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 11A: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [75]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    1.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.37
         upper limit
    		 1.75
    Notes
    [75] - For the additional 7 serotypes, the compared results are from serotype 5 (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 19A: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [76]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 0.93
    Notes
    [76] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 19F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [77]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 0.87
    Notes
    [77] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 23F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [78]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 0.69
    Notes
    [78] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 8: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [79]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    1.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.32
         upper limit
    		 1.66
    Notes
    [79] - For the additional 7 serotypes, the compared results are from serotype 5 (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 10A: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [80]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    2.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.77
         upper limit
    		 2.3
    Notes
    [80] - For the additional 7 serotypes, the compared results are from serotype 5 (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 15B: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [81]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    5.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.82
         upper limit
    		 6.1
    Notes
    [81] - For the additional 7 serotypes, the compared results are from serotype 5 (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 22F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [82]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    3.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.4
         upper limit
    		 4.34
    Notes
    [82] - For the additional 7 serotypes, the compared results are from serotype 5 (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 33F: 2-sided 95% CI was calculated by exponentiating the CI (based on the Student’s t distribution) for the mean difference of the logarithm of the concentrations.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [83]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    2.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.33
         upper limit
    		 2.99
    Notes
    [83] - For the additional 7 serotypes, the compared results are from serotype 5 (13vPnC serotype with the lowest GMC, not including serotype 3) in the 13vPnC group. Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/lowest 13vPnC) was greater than 0.5 (2-fold criterion).

    Primary: Percentage of Subjects With Predefined Antibody Levels for Concomitant Vaccine Antigens 1 Month After Dose 3: Primary Study Population

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    End point title
    		 Percentage of Subjects With Predefined Antibody Levels for Concomitant Vaccine Antigens 1 Month After Dose 3: Primary Study Population [84]
    End point description
    Diphtheria & tetanus toxoids:concentration(conc) of antibody(AB)(in international units[IU]) to diphtheria & tetanus toxoid(prespecified level>=0.1 IU/mL); Pertussis antigens-pertussis toxin (PT),filamentous hemagglutinin (FHA),pertactin (PRN):prespecified level>=observed antipertussis AB concentration achieved by 95% of 13vPnC recipient; HBsAg prespecified level >=10 milli-IU per mL (mIU/mL); Poliovirus strains (types 1, 2, and 3): prespecified level: >=1:8; Haemophilus influenzae type b(Hib): prespecified level>=0.15 mcg/mL polyribosylribitol phosphate (anti-PRP) in mcg/mL.Dose3 EIP=eligible subject 42-112 day(D) of age at 1st vaccine,received 3 dose as randomized with 335-386 D of age at Dose3,1 valid immunogenicity result within 27-56 D after Dose3.n=subjects in Dose3 EIP.Concomitant vaccine response was assessed from subset of randomly selected study subjects.
    End point type
    Primary
    End point timeframe
    1 month after Dose 3
    Notes
    [84] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    497
    504
    Units: Percentage of subjects
    number (confidence interval 95%)
        Diphtheria toxoid, n=494, 498
    99.6 (98.5 to 100.0)
    99.8 (98.9 to 100.0)
        Tetanus toxoid, n=494, 498
    99.4 (98.2 to 99.9)
    100.0 (99.3 to 100.0)
        Pertussis: PT, n=494, 498
    92.9 (90.3 to 95.0)
    95.2 (92.9 to 96.9)
        Pertussis: FHA, n=494, 498
    95.3 (93.1 to 97.0)
    95.2 (92.9 to 96.9)
        Pertussis: PRN, n=494, 498
    96.8 (94.8 to 98.1)
    95.2 (92.9 to 96.9)
        Hepatitis B, n=173, 178
    100.0 (97.9 to 100.0)
    98.9 (96.0 to 99.9)
        Poliovirus: Type 1, n=81, 89
    100.0 (95.5 to 100.0)
    100.0 (95.9 to 100.0)
        Poliovirus: Type 2, n=81, 89
    100.0 (95.5 to 100.0)
    100.0 (95.9 to 100.0)
        Poliovirus: Type 3, n=81, 89
    100.0 (95.5 to 100.0)
    100.0 (95.9 to 100.0)
        Haemophilus influenzae type b, n=185, 169
    100.0 (98.0 to 100.0)
    100.0 (97.8 to 100.0)
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    PT: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [85]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.3
         upper limit
    		 0.7
    Notes
    [85] - Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Tetanus: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnc - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [86]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 0.2
    Notes
    [86] - Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Diphtheria: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnc - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [87]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.8
    Notes
    [87] - Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC -13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Poliovirus Type 1: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnc - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [88]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 4.2
    Notes
    [88] - Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC -13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Poliovirus Type 2: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnc - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [89]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 4.2
    Notes
    [89] - Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Poliovirus Type 3: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnc - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [90]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 4.2
    Notes
    [90] - Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Hepatitis B: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnc - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [91]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 4
    Notes
    [91] - Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Hib: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnc - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [92]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 2.2
    Notes
    [92] - Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    FHA: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [93]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.6
         upper limit
    		 2.9
    Notes
    [93] - Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    PRN: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [94]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 4.2
    Notes
    [94] - Noninferiority was declared if the lower bound of the 2-sided 95% CIs for the percentage differences (20vPnC-13vPnC) was greater than -10%.

    Primary: GMC of Measles Virus Antibody 1 Month After Dose 3: Primary Study Population

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    End point title
    		 GMC of Measles Virus Antibody 1 Month After Dose 3: Primary Study Population [95]
    End point description
    Pre-specified vaccine antigen (measles) was administered concomitantly with 20vPnC or 13vPnC at Dose 3 and responses measured 1 month after Dose 3. Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ in the analysis. GMCs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student’s t distribution). The immune responses were only measured on random subset of subjects. Dose 3 evaluable immunogenicity population = eligible subjects 42-112 days of age at first vaccination, received all 3 doses as randomized with 335-386 days of age at Dose 3, at least 1 valid immunogenicity results from blood collection within 27 to 56 days after Dose 3, no major protocol deviations. Here, "Number of Subjects Analyzed"= subjects in Dose 3 evaluable immunogenicity population, received measles vaccine and had valid assay results measle vaccine antigen.
    End point type
    Primary
    End point timeframe
    1 month after Dose 3
    Notes
    [95] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    128
    132
    Units: Arbitrary units per milliliter
        geometric mean (confidence interval 95%)
    228.63 (186.34 to 280.52)
    216.72 (174.92 to 268.52)
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Measles: GMR and 2-sided 95% CIs were calculated by exponentiating the mean differences of the logarithms of the concentrations (20vPnC − 13vPnC) and the corresponding CIs (based on the Student's t distribution).
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    260
    Analysis specification
    Pre-specified
    Analysis type
    		 [96]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.42
    Notes
    [96] - Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).

    Primary: GMC of Rubella Virus Antibody 1 Month After Dose 3: Primary Study Population

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    End point title
    		 GMC of Rubella Virus Antibody 1 Month After Dose 3: Primary Study Population [97]
    End point description
    Pre-specified vaccine antigen (rubella) was administered concomitantly with 20vPnC or 13vPnC at Dose 3 and responses measured 1 month after Dose 3. Assay results below LLOQ were set to 0.5*LLOQ in the analysis. GMCs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student’s t distribution). The immune responses were only measured on random subset of subjects. Dose 3 evaluable immunogenicity population = eligible subjects 42-112 days of age at first vaccination, received all 3 doses as randomized with 335-386 days of age at Dose 3, at least 1 valid immunogenicity results from blood collection within 27 to 56 days after Dose 3, no major protocol deviations. Here, "Number of Subjects Analyzed"= subjects in Dose 3 evaluable immunogenicity population, received rubella vaccine and had valid assay results rubella vaccine antigen.
    End point type
    Primary
    End point timeframe
    1 month after Dose 3
    Notes
    [97] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    128
    132
    Units: International units per milliliter
        geometric mean (confidence interval 95%)
    31.81 (25.54 to 39.62)
    38.20 (32.10 to 45.45)
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Rubella: GMR and 2-sided 95% CIs were calculated by exponentiating the mean differences of the logarithms of the concentrations (20vPnC − 13vPnC) and the corresponding CIs (based on the Student's t distribution).
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    260
    Analysis specification
    Pre-specified
    Analysis type
    		 [98]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.1
    Notes
    [98] - Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).

    Primary: GMC of Mumps Virus Antibody 1 Month After Dose 3: Primary Study Population

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    End point title
    		 GMC of Mumps Virus Antibody 1 Month After Dose 3: Primary Study Population [99]
    End point description
    Pre-specified vaccine antigen (mumps) was administered concomitantly with 20vPnC or 13vPnC at Dose 3 and responses measured 1 month after Dose 3. Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. GMCs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student’s t distribution). The immune responses were only measured on random subset of subjects.Dose 3 evaluable immunogenicity population = eligible subjects 42-112 days of age at first vaccination, received all 3 doses as randomized with 335-386 days of age at Dose 3, at least 1 valid immunogenicity results from blood collection within 27 to 56 days after Dose 3, no major protocol deviations. Here, "Number of Subjects Analyzed"= subjects in Dose 3 evaluable immunogenicity population, received mumps vaccine and had valid assay results mumps vaccine antigen.
    End point type
    Primary
    End point timeframe
    1 month after Dose 3
    Notes
    [99] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    128
    133
    Units: Arbitrary units per milliliter
        geometric mean (confidence interval 95%)
    36.81 (29.12 to 46.54)
    35.25 (28.14 to 44.17)
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Mumps: GMR and 2-sided 95% CIs were calculated by exponentiating the mean differences of the logarithms of the concentrations (20vPnC − 13vPnC) and the corresponding CIs (based on the Student's t distribution).
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    		 [100]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.44
    Notes
    [100] - Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).

    Primary: Percentage of Subjects With Local Reactions Within 7 Days After Dose 1: Russian Cohort

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    End point title
    		 Percentage of Subjects With Local Reactions Within 7 Days After Dose 1: Russian Cohort [101] [102]
    End point description
    Local reactions included redness, swelling and, pain at the injection site, recorded by parent’s/legal guardians of subjects in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0 to 2.0 cm), moderate (> 2.0 to 7.0 cm) and severe (>7.0 cm). Pain at injection site was graded as mild (hurt if gently touched example, whimpered, winced, protested, or withdrew), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). 95% CI was based on Clopper and Pearson method. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose.Here, “Number of subjects Analyzed” signifies number of subjects with any e-diary data after Dose 1
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 1
    Notes
    [101] - 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 endpoint was planned to be analysed only for the specified reporting arms
    [102] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    24
    27
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Mild
    4.2 (0.1 to 21.1)
    7.4 (0.9 to 24.3)
        Redness: Moderate
    4.2 (0.1 to 21.1)
    3.7 (0.1 to 19.0)
        Redness: Severe
    0 (0.0 to 14.2)
    0 (0.0 to 12.8)
        Swelling: Mild
    0 (0.0 to 14.2)
    0 (0.0 to 12.8)
        Swelling: Moderate
    4.2 (0.1 to 21.1)
    0 (0.0 to 12.8)
        Swelling: Severe
    0 (0.0 to 14.2)
    0 (0.0 to 12.8)
        Pain at Injection Site: Mild
    8.3 (1.0 to 27.0)
    7.4 (0.9 to 24.3)
        Pain at Injection Site: Moderate
    0 (0.0 to 14.2)
    3.7 (0.1 to 19.0)
        Pain at Injection Site: Severe
    0 (0.0 to 14.2)
    0 (0.0 to 12.8)
    No statistical analyses for this end point

    Primary: GMC of Varicella Virus Antibody 1 Month After Dose 3: Primary Study Population

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    End point title
    		 GMC of Varicella Virus Antibody 1 Month After Dose 3: Primary Study Population [103]
    End point description
    Pre-specified vaccine antigen (varicella) was administered concomitantly with 20vPnC or 13vPnC at Dose 3 and responses measured 1 month after Dose 3. Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ in the analysis. GMCs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student’s t distribution). The immune responses were only measured on random subset of subjects. Dose 3 evaluable immunogenicity population = eligible subjects 42-112 days of age at first vaccination, received all 3 doses as randomized with 335-386 days of age at Dose 3, at least 1 valid immunogenicity results from blood collection within 27 to 56 days after Dose 3, no major protocol deviations. Here, "Number of Subjects Analyzed"= subjects in Dose 3 evaluable immunogenicity population, received varicella vaccine and had valid assay results varicella vaccine antigen.
    End point type
    Primary
    End point timeframe
    1 month after Dose 3
    Notes
    [103] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    128
    132
    Units: Milli-international units per milliliter
        geometric mean (confidence interval 95%)
    195.58 (165.14 to 231.62)
    157.60 (133.57 to 185.95)
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Varicella: GMR and 2-sided 95% CIs were calculated by exponentiating the mean differences of the logarithms of the concentrations (20vPnC − 13vPnC) and the corresponding CIs (based on the Student's t distribution).
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    260
    Analysis specification
    Pre-specified
    Analysis type
    		 [104]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    1.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.57
    Notes
    [104] - Noninferiority was declared if the lower bound of the 2-sided 95% CI for the GMR (20vPnC/13vPnC) was greater than 0.5 (2-fold criterion).

    Primary: Percentage of Subjects With Local Reactions Within 7 Days After Dose 2: Russian Cohort

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    End point title
    		 Percentage of Subjects With Local Reactions Within 7 Days After Dose 2: Russian Cohort [105] [106]
    End point description
    Local reactions included redness, swelling and, pain at the injection site, recorded by parent’s/legal guardians of subjects in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0 to 2.0 cm), moderate (> 2.0 to 7.0 cm) and severe (>7.0 cm). Pain at injection site was graded as mild (hurt if gently touched example, whimpered, winced, protested, or withdrew), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). 95% CI was based on Clopper and Pearson method. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose. Here, “Number of Subjects Analyzed” signifies the number of subjects with any e-diary data after Dose 2.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 2
    Notes
    [105] - 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 endpoint was planned to be analysed only for the specified reporting arms
    [106] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    23
    27
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Mild
    0 (0.0 to 14.8)
    3.7 (0.1 to 19.0)
        Redness: Moderate
    4.3 (0.1 to 21.9)
    0 (0.0 to 12.8)
        Redness: Severe
    0 (0.0 to 14.8)
    0 (0.0 to 12.8)
        Swelling: Mild
    0 (0.0 to 14.8)
    7.4 (0.9 to 24.3)
        Swelling: Moderate
    8.7 (1.1 to 28.0)
    0 (0.0 to 12.8)
        Swelling: Severe
    0 (0.0 to 14.8)
    0 (0.0 to 12.8)
        Pain at Injection Site: Mild
    8.7 (1.1 to 28.0)
    7.4 (0.9 to 24.3)
        Pain at Injection Site: Moderate
    4.3 (0.1 to 21.9)
    0 (0.0 to 12.8)
        Pain at Injection Site: Severe
    0 (0.0 to 14.8)
    0 (0.0 to 12.8)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Local Reactions Within 7 Days After Dose 3: Russian Cohort

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    End point title
    		 Percentage of Subjects With Local Reactions Within 7 Days After Dose 3: Russian Cohort [107] [108]
    End point description
    Local reactions included redness, swelling and, pain at the injection site, recorded by parent’s/legal guardians of subjects in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0 to 2.0 cm), moderate (> 2.0 to 7.0 cm) and severe (>7.0 cm). Pain at injection site was graded as mild (hurt if gently touched example, whimpered, winced, protested, or withdrew), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). 95% CI was based on Clopper and Pearson method. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose. Here, “Number of Subjects Analyzed” signifies the number of subjects with any e-diary data after Dose 3.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 3
    Notes
    [107] - 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 endpoint was planned to be analysed only for the specified reporting arms
    [108] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    22
    25
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Mild
    0 (0.0 to 15.4)
    4.0 (0.1 to 20.4)
        Redness: Moderate
    4.5 (0.1 to 22.8)
    0 (0.0 to 13.7)
        Redness: Severe
    0 (0.0 to 15.4)
    4.0 (0.1 to 4.0)
        Swelling: Mild
    0 (0.0 to 15.4)
    0 (0.0 to 13.7)
        Swelling: Moderate
    9.1 (1.1 to 29.2)
    0 (0.0 to 13.7)
        Swelling: Severe
    0 (0.0 to 15.4)
    4.0 (0.1 to 20.4)
        Pain at Injection Site: Mild
    13.6 (2.9 to 34.9)
    8.0 (1.0 to 26.0)
        Pain at Injection Site: Moderate
    0 (0.0 to 15.4)
    0 (0.0 to 13.7)
        Pain at Injection Site: Severe
    0 (0.0 to 15.4)
    0 (0.0 to 13.7)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Systemic Events Within 7 Days After Dose 1: Russian cohort

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    End point title
    		 Percentage of Subjects With Systemic Events Within 7 Days After Dose 1: Russian cohort [109] [110]
    End point description
    Systemic events:fever,decreased appetite,drowsiness/increased sleep & irritability, recorded by parents/legal guardians of subject's using e-diary.Fever: temperature >=38.0 degree C & categorized as >=38.0 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C & >40.0-degree C. Decreased appetite:mild (decreased interest in eating), moderate (decreased oral intake) & severe (refusal to feed).Drowsiness was graded as mild (increased/prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) & severe (disabling, not interested in usual daily activity).Irritability: mild (easily consolable), moderate (required increased attention) & severe (inconsolable, crying could not be comforted).95% CI was based on Clopper & Pearson method. Safety analysis set:all subjects who received at least 1 dose of 20vPnC or 13vPnC & had safety data assessed after any dose.Here, “Number of subjects Analyzed” signifies number of subjects with any e-diary data after Dose 1.
    End point type
    Primary
    End point timeframe
    Within 7 Days after Dose 1
    Notes
    [109] - 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 endpoint was planned to be analysed only for the specified reporting arms
    [110] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    24
    27
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever: >=38.0 degrees C to 38.4 degrees C
    4.2 (0.1 to 21.1)
    0 (0.0 to 12.8)
        Fever: >38.4 degrees C to 38.9 degrees C
    0 (0.0 to 14.2)
    0 (0.0 to 12.8)
        Fever: >38.9 degrees C to 40.0 degrees C
    0 (0.0 to 14.2)
    0 (0.0 to 12.8)
        Fever: >40.0 degrees C
    0 (0.0 to 14.2)
    0 (0.0 to 12.8)
        Decreased appetite: Mild
    16.7 (4.7 to 37.4)
    14.8 (4.2 to 33.7)
        Decreased appetite: Moderate
    0 (0.0 to 14.2)
    3.7 (0.1 to 19.0)
        Decreased appetite: Severe
    0 (0.0 to 14.2)
    0 (0.0 to 12.8)
        Drowsiness: Mild
    20.8 (7.1 to 42.2)
    18.5 (6.3 to 38.1)
        Drowsiness: Moderate
    8.3 (1.0 to 27.0)
    11.1 (2.4 to 29.2)
        Drowsiness: Severe
    0 (0.0 to 14.2)
    0 (0.0 to 12.8)
        Irritability: Mild
    12.5 (2.7 to 32.4)
    7.4 (0.9 to 24.3)
        Irritability: Moderate
    8.3 (1.0 to 27.0)
    14.8 (4.2 to 33.7)
        Irritability: Severe
    4.2 (0.1 to 21.1)
    0 (0.0 to 12.8)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Systemic Events Within 7 Days After Dose 2: Russian cohort

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    End point title
    		 Percentage of Subjects With Systemic Events Within 7 Days After Dose 2: Russian cohort [111] [112]
    End point description
    Systemic events: fever, decreased appetite, drowsiness/increased sleep & irritability, recorded by parents/legal guardians of participant’s using e-diary. Fever: temperature >=38.0 degree C & categorized as >=38.0 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C & >40.0-degree C. Decreased appetite: mild (decreased interest in eating), moderate (decreased oral intake) & severe (refusal to feed).Drowsiness was graded as mild (increased/prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) & severe (disabling, not interested in usual daily activity).Irritability: mild (easily consolable), moderate (required increased attention) & severe (inconsolable, crying could not be comforted). 95% CI was based on Clopper & Pearson method. Safety analysis set: all subjects who received at least 1 dose of 20vPnC or 13vPnC & had safety data assessed after any dose.Here,“Number of Subjects Analyzed”: number of subjects with any e-diary data after Dose 2
    End point type
    Primary
    End point timeframe
    Within 7 Days after Dose 2
    Notes
    [111] - 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 endpoint was planned to be analysed only for the specified reporting arms
    [112] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    23
    27
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever: >=38.0 degrees C to 38.4 degrees C
    0 (0.0 to 14.8)
    11.1 (2.4 to 29.2)
        Fever: >38.4 degrees C to 38.9 degrees C
    4.3 (0.1 to 21.9)
    0 (0.0 to 12.8)
        Fever: >38.9 degrees C to 40.0 degrees C
    0 (0.0 to 14.8)
    0 (0.0 to 12.8)
        Fever: >40.0 degrees C
    0 (0.0 to 14.8)
    0 (0.0 to 12.8)
        Decreased appetite: Mild
    4.3 (0.1 to 21.9)
    7.4 (0.9 to 24.3)
        Decreased appetite: Moderate
    4.3 (0.1 to 21.9)
    3.7 (0.1 to 19.0)
        Decreased appetite: Severe
    0 (0.0 to 14.8)
    0 (0.0 to 12.8)
        Drowsiness: Mild
    4.3 (0.1 to 21.9)
    3.7 (0.1 to 19.0)
        Drowsiness: Moderate
    0 (0.0 to 14.8)
    3.7 (0.1 to 19.0)
        Drowsiness: Severe
    0 (0.0 to 14.8)
    0 (0.0 to 12.8)
        Irritability: Mild
    13.0 (2.8 to 33.6)
    22.2 (8.6 to 42.3)
        Irritability: Moderate
    4.3 (0.1 to 21.9)
    18.5 (6.3 to 38.1)
        Irritability: Severe
    0 (0.0 to 14.8)
    3.7 (0.1 to 19.0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Systemic Events Within 7 Days After Dose 3: Russian cohort

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    End point title
    		 Percentage of Subjects With Systemic Events Within 7 Days After Dose 3: Russian cohort [113] [114]
    End point description
    Systemic events: fever, decreased appetite, drowsiness/increased sleep & irritability, recorded by parents/legal guardians of subjects using e-diary. Fever: temperature >=38.0 degree C & categorized as >=38.0 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C & >40.0-degree C. Decreased appetite: mild (decreased interest in eating), moderate (decreased oral intake) & severe (refusal to feed).Drowsiness was graded as mild (increased/prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) & severe (disabling, not interested in usual daily activity).Irritability: mild (easily consolable), moderate (required increased attention) & severe (inconsolable, crying could not be comforted). 95% CI was based on Clopper & Pearson method. Safety analysis set:all subjects who received at least 1 dose of 20vPnC or 13vPnC & had safety data assessed after any dose.Here,“Number of Subjects Analyzed”: number of subjects with any e-diary data after Dose 3
    End point type
    Primary
    End point timeframe
    Within 7 Days after Dose 3
    Notes
    [113] - 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 endpoint was planned to be analysed only for the specified reporting arms
    [114] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    22
    25
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever: >=38.0 degrees C to 38.4 degrees C
    0 (0.0 to 15.4)
    0 (0.0 to 13.7)
        Fever: >38.4 degrees C to 38.9 degrees C
    0 (0.0 to 15.4)
    4.0 (0.1 to 20.4)
        Fever: >38.9 degrees C to 40.0 degrees C
    4.5 (0.1 to 22.8)
    0 (0.0 to 13.7)
        Fever: >40.0 degrees C
    0 (0.0 to 15.4)
    0 (0.0 to 13.7)
        Decreased appetite: Mild
    9.1 (1.1 to 29.2)
    8.0 (1.0 to 26.0)
        Decreased appetite: Moderate
    9.1 (1.1 to 29.2)
    0 (0.0 to 13.7)
        Decreased appetite: Severe
    0 (0.0 to 15.4)
    0 (0.0 to 13.7)
        Drowsiness: Mild
    13.6 (2.9 to 34.9)
    20.0 (6.8 to 40.7)
        Drowsiness: Moderate
    0 (0.0 to 15.4)
    4.0 (0.1 to 20.4)
        Drowsiness: Severe
    0 (0.0 to 15.4)
    0 (0.0 to 13.7)
        Irritability: Mild
    27.3 (10.7 to 50.2)
    16.0 (4.5 to 36.1)
        Irritability: Moderate
    9.1 (1.1 to 29.2)
    8.0 (1.0 to 26.0)
        Irritability: Severe
    0 (0.0 to 15.4)
    0 (0.0 to 13.7)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With SAEs From Dose 1 to 1 month after Dose 3: Russian cohort

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    End point title
    		 Percentage of Subjects With SAEs From Dose 1 to 1 month after Dose 3: Russian cohort [115] [116]
    End point description
    An SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. 95% CI was based on the Clopper and Pearson method. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose.
    End point type
    Primary
    End point timeframe
    From Dose 1 to 1 month after Dose 3
    Notes
    [115] - 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: Only descriptive analysis was planned for this endpoint
    [116] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    24
    27
    Units: Percentage of subjects
        number (confidence interval 95%)
    0 (0 to 0)
    0 (0 to 0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With AEs From Dose 1 to 1 Month After Dose 2: Russian Cohort

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    End point title
    		 Percentage of Subjects With AEs From Dose 1 to 1 Month After Dose 2: Russian Cohort [117] [118]
    End point description
    An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. 95% CI was based on the Clopper and Pearson method. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose.
    End point type
    Primary
    End point timeframe
    From Dose 1 to 1 month after Dose 2
    Notes
    [117] - 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 endpoint was planned to be analysed only for the specified reporting arms
    [118] - 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: Only descriptive analysis was planned for this endpoint
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    24
    27
    Units: Percentage of subjects
        number (confidence interval 95%)
    8.3 (1.0 to 27.0)
    3.7 (0.1 to 19.0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With AEs From Dose 3 to 1 Month After Dose 3: Russian Cohort

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    End point title
    		 Percentage of Subjects With AEs From Dose 3 to 1 Month After Dose 3: Russian Cohort [119] [120]
    End point description
    An AE was any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment. 95% CI was based on the Clopper and Pearson method. AEs reported in this outcome measure excluded local reactions and systemic events. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose. Here, “Number of Subjects Analyzed” signifies the number of subjects who received Dose 3.
    End point type
    Primary
    End point timeframe
    From Dose 3 to 1 month after Dose 3
    Notes
    [119] - 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: Only descriptive analysis was planned for this endpoint.
    [120] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    22
    25
    Units: Percentage of subjects
        number (confidence interval 95%)
    4.5 (0.1 to 22.8)
    0 (0.0 to 13.7)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Predefined Pneumococcal IgG Antibody 1 Month After Dose 2: Russian Cohort

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    End point title
    		 Percentage of Subjects With Predefined Pneumococcal IgG Antibody 1 Month After Dose 2: Russian Cohort [121] [122]
    End point description
    Predefined IgG concentrations were as follows: for serotype 1, 3, 4, 6A, 7F, 9V, 14, 18C, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, 33F: >=0.35 microgram per mL (mcg/mL), for serotype 5: >=0.23 mcg/mL, for serotype 6B. >=0.10 mcg/mL and for serotype 19A: >=0.12 mcg/mL. 95% CI was based on the Clopper and Pearson method. Dose 2 evaluable immunogenicity population: eligible subjects 42-70 days of age at first vaccination, received first 2 doses as randomized, at least 1 valid immunogenicity results within 27 to 56 days after Dose 2, no other major protocol deviations. "Number of Subjects Analyzed"= subjects with valid IgG assay results for specified serotype.
    End point type
    Primary
    End point timeframe
    1 month after Dose 2
    Notes
    [121] - 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: Only descriptive analysis was planned for this endpoint
    [122] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    24
    27
    Units: Percentage of subjects
    number (confidence interval 95%)
        Serotype 1
    70.8 (48.9 to 87.4)
    77.8 (57.7 to 91.4)
        Serotype 3
    37.5 (18.8 to 59.4)
    59.3 (38.8 to 77.6)
        Serotype 4
    75.0 (53.3 to 90.2)
    74.1 (53.7 to 88.9)
        Serotype 5
    66.7 (44.7 to 84.4)
    81.5 (61.9 to 93.7)
        Serotype 6A
    54.2 (32.8 to 74.4)
    81.5 (61.9 to 93.7)
        Serotype 6B
    20.8 (7.1 to 42.2)
    59.3 (38.8 to 77.6)
        Serotype 7F
    95.8 (78.9 to 99.9)
    92.6 (75.7 to 99.1)
        Serotype 9V
    41.7 (22.1 to 63.4)
    81.5 (61.9 to 93.7)
        Serotype 14
    83.3 (62.6 to 95.3)
    85.2 (66.3 to 95.8)
        Serotype 18C
    66.7 (44.7 to 84.4)
    81.5 (61.9 to 93.7)
        Serotype 19A
    87.5 (67.6 to 97.3)
    92.6 (75.7 to 99.1)
        Serotype 19F
    79.2 (57.8 to 92.9)
    96.3 (81.0 to 99.9)
        Serotype 23F
    37.5 (18.8 to 59.4)
    70.4 (49.8 to 86.2)
        Serotype 8
    75.0 (53.3 to 90.2)
    33.3 (16.5 to 54.0)
        Serotype 10A
    41.7 (22.1 to 63.4)
    18.5 (6.3 to 38.1)
        Serotype 11A
    83.3 (62.6 to 95.3)
    18.5 (6.3 to 38.1)
        Serotype 12F
    12.5 (2.7 to 32.4)
    14.8 (4.2 to 33.7)
        Serotype 15B
    66.7 (44.7 to 84.4)
    33.3 (16.5 to 54.0)
        Serotype 22F
    66.7 (44.7 to 84.4)
    14.8 (4.2 to 33.7)
        Serotype 33F
    45.8 (25.6 to 67.2)
    25.9 (11.1 to 46.3)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With NDCMC From Dose 1 to 1 Month After Dose 3: Russian Cohort

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    End point title
    		 Percentage of Subjects With NDCMC From Dose 1 to 1 Month After Dose 3: Russian Cohort [123] [124]
    End point description
    An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or was otherwise long-lasting in its effects. 95% CI was based on the Clopper and Pearson method. Safety analysis set included all subjects who received at least 1 dose of 20vPnC or 13vPnC and had safety data assessed after any dose.
    End point type
    Primary
    End point timeframe
    From Dose 1 to 1 month after Dose 3
    Notes
    [123] - 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: Only descriptive analysis was planned for this endpoint
    [124] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    24
    27
    Units: Percentage of subjects
        number (confidence interval 95%)
    0 (0 to 0)
    0 (0 to 0)
    No statistical analyses for this end point

    Primary: GMC of Serotype-specific Pneumococcal IgG Antibody 1 Month After Dose 2: Russian Cohort

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    End point title
    		 GMC of Serotype-specific Pneumococcal IgG Antibody 1 Month After Dose 2: Russian Cohort [125] [126]
    End point description
    Pneumococcal serotype-specific IgG concentrations were measured for serum samples for 13vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F and 7 additional serotypes: 8, 10A, 11A, 12F, 15B, 22F, 33F. Assay results below the LLOQ were set to 0.5 × LLOQ. GMC & corresponding 2-sided 95% CIs were calculated by exponentiating mean logarithm of concentration, corresponding 2-sided 95% CIs (based on Student's t distribution). Dose 2 evaluable immunogenicity population: eligible subjects 42-70days of age at first vaccination, received first 2 doses as randomized, at least 1 valid immunogenicity results within 27 to 56 days after Dose 2, no other major protocol deviations. "Number of Subjects Analyzed"= subjects with valid IgG assay results for specified serotype.
    End point type
    Primary
    End point timeframe
    1 month after Dose 2
    Notes
    [125] - 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: Only descriptive analysis was planned for this endpoint
    [126] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    24
    27
    Units: mcg/mL
    geometric mean (confidence interval 95%)
        Serotype 1
    0.76 (0.49 to 1.19)
    1.04 (0.64 to 1.69)
        Serotype 3
    0.28 (0.19 to 0.42)
    0.47 (0.31 to 0.72)
        Serotype 4
    0.67 (0.45 to 1.00)
    1.00 (0.58 to 1.71)
        Serotype 5
    0.53 (0.31 to 0.92)
    0.75 (0.40 to 1.40)
        Serotype 6A
    0.45 (0.20 to 1.03)
    1.57 (0.80 to 3.10)
        Serotype 6B
    0.07 (0.03 to 0.16)
    0.27 (0.12 to 0.63)
        Serotype 7F
    1.06 (0.68 to 1.65)
    1.89 (1.32 to 2.71)
        Serotype 9V
    0.44 (0.23 to 0.84)
    1.22 (0.73 to 2.06)
        Serotype 14
    1.56 (0.88 to 2.75)
    2.66 (1.46 to 4.86)
        Serotype 18C
    0.94 (0.46 to 1.91)
    0.94 (0.50 to 1.78)
        Serotype 19A
    1.15 (0.47 to 2.82)
    1.21 (0.59 to 2.49)
        Serotype 19F
    1.51 (0.84 to 2.72)
    3.32 (2.03 to 5.44)
        Serotype 23F
    0.25 (0.11 to 0.55)
    0.73 (0.37 to 1.42)
        Serotype 8
    0.79 (0.37 to 1.69)
    0.07 (0.03 to 0.18)
        Serotype 10A
    0.31 (0.10 to 0.94)
    0.04 (0.01 to 0.10)
        Serotype 11A
    0.83 (0.43 to 1.60)
    0.04 (0.02 to 0.09)
        Serotype 12F
    0.06 (0.03 to 0.11)
    0.02 (0.01 to 0.04)
        Serotype 15B
    1.19 (0.46 to 3.05)
    0.16 (0.05 to 0.50)
        Serotype 22F
    0.48 (0.16 to 1.47)
    0.02 (0.01 to 0.06)
        Serotype 33F
    0.40 (0.18 to 0.88)
    0.07 (0.03 to 0.16)
    No statistical analyses for this end point

    Primary: GMC of Serotype-specific Pneumococcal IgG Antibody 1 Month After Dose 3: Russian Cohort

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    End point title
    		 GMC of Serotype-specific Pneumococcal IgG Antibody 1 Month After Dose 3: Russian Cohort [127] [128]
    End point description
    Pneumococcal serotype-specific IgG concentrations were measured for serum samples for 13vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F and additional serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. Assay results below the LLOQ were set to 0.5 × LLOQ. GMC & corresponding 2-sided 95% CIs were calculated by exponentiating mean logarithm of concentration, corresponding 2-sided 95% CIs (based on Student's t distribution). Dose 3 evaluable immunogenicity population = eligible subjects 42-70 days of age at first vaccination, received all 3 doses as randomized with 335-455 days of age at Dose 3, at least 1 valid immunogenicity results from blood collection within 27 to 56 days after Dose 3, no major protocol deviations.Here, “Number of Subjects Analyzed” signifies the subjects with valid IgG assay result for specified serotype.
    End point type
    Primary
    End point timeframe
    1 month after Dose 3
    Notes
    [127] - 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: Only descriptive analysis was planned for this endpoint
    [128] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    22
    24
    Units: mcg/mL
    geometric mean (confidence interval 95%)
        Serotype 1
    1.61 (0.93 to 2.78)
    1.65 (0.94 to 2.90)
        Serotype 3
    0.84 (0.44 to 1.60)
    0.57 (0.32 to 1.01)
        Serotype 4
    3.05 (1.50 to 6.20)
    3.04 (1.72 to 5.36)
        Serotype 5
    1.50 (0.80 to 2.82)
    1.72 (0.90 to 3.29)
        Serotype 6A
    6.63 (2.96 to 14.86)
    5.63 (2.96 to 10.72)
        Serotype 6B
    1.94 (0.82 to 4.56)
    1.49 (0.67 to 3.32)
        Serotype 7F
    3.53 (1.97 to 6.33)
    4.14 (2.73 to 6.26)
        Serotype 9V
    2.32 (1.28 to 4.19)
    2.27 (1.19 to 4.35)
        Serotype 14
    4.01 (1.64 to 9.77)
    5.06 (3.04 to 8.40)
        Serotype 18C
    2.60 (1.24 to 5.44)
    2.64 (1.49 to 4.69)
        Serotype 19A
    4.81 (2.07 to 11.16)
    2.69 (1.12 to 6.45)
        Serotype 19F
    4.97 (2.30 to 10.76)
    4.58 (2.36 to 8.90)
        Serotype 23F
    3.52 (1.68 to 7.38)
    2.96 (1.33 to 6.56)
        Serotype 8
    1.33 (0.50 to 3.56)
    0.09 (0.04 to 0.24)
        Serotype 10A
    1.99 (0.63 to 6.29)
    0.03 (0.01 to 0.09)
        Serotype 11A
    1.50 (0.58 to 3.87)
    0.06 (0.02 to 0.16)
        Serotype 12F
    0.17 (0.05 to 0.56)
    0.02 (0.01 to 0.03)
        Serotype 15B
    4.90 (1.67 to 14.37)
    0.07 (0.03 to 0.20)
        Serotype 22F
    1.52 (0.38 to 6.03)
    0.02 (0.01 to 0.08)
        Serotype 33F
    1.38 (0.53 to 3.59)
    0.04 (0.02 to 0.10)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Predefined Pneumococcal IgG Antibody 1 Month After Dose 3: Primary Study Population

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    End point title
    		 Percentage of Subjects With Predefined Pneumococcal IgG Antibody 1 Month After Dose 3: Primary Study Population [129]
    End point description
    Predefined IgG concentrations were as follows: for serotype 1, 3, 4, 6A, 7F, 9V, 14, 18C, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, 33F: >=0.35 microgram per mL (mcg/mL), for serotype 5: >=0.23 mcg/mL, for serotype 6B. >=0.10 mcg/mL and for serotype 19A: >=0.12 mcg/mL. 95% CI was based on the Clopper and Pearson method.Dose 3 evaluable immunogenicity population = eligible subjects 42-112 days of age at first vaccination, received all 3 doses as randomized with 335-386 days of age at Dose 3, at least 1 valid immunogenicity results from blood collection within 27 to 56 days after Dose 3, no major protocol deviations. "Number of Subjects Analyzed"= subjects in Dose 3 evaluable immunogenicity population; "n"= subjects with valid IgG results for specified serotype.
    End point type
    Secondary
    End point timeframe
    1 Month after Dose 3
    Notes
    [129] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    497
    504
    Units: Percentage of subjects
    number (confidence interval 95%)
        Serotype 1, n=494, 502
    97.2 (95.3 to 98.4)
    98.2 (96.6 to 99.2)
        Serotype 3, n=494, 502
    82.6 (79.0 to 85.8)
    93.2 (90.7 to 95.3)
        Serotype 4, n=494, 502
    99.2 (97.9 to 99.8)
    99.2 (98.0 to 99.8)
        Serotype 5, n=494, 502
    98.4 (96.8 to 99.3)
    98.0 (96.4 to 99.0)
        Serotype 6A, n=494, 501
    98.8 (97.4 to 99.6)
    98.8 (97.4 to 99.6)
        Serotype 6B, n=494, 501
    98.4 (96.8 to 99.3)
    97.6 (95.9 to 98.8)
        Serotype 7F, n=494, 502
    99.6 (98.5 to 100.0)
    100.0 (99.3 to 100.0)
        Serotype 9V, n=494, 502
    99.2 (97.9 to 99.8)
    98.8 (97.4 to 99.6)
        Serotype 14, n=493, 501
    96.6 (94.5 to 98.0)
    98.0 (96.4 to 99.0)
        Serotype 18C, n=494, 502
    99.2 (97.9 to 99.8)
    98.2 (96.6 to 99.2)
        Serotype 19A, n=494, 502
    99.6 (98.5 to 100.0)
    99.6 (98.6 to 100.0)
        Serotype 19F, n=494, 502
    99.6 (98.5 to 100.0)
    99.4 (98.3 to 99.9)
        Serotype 23F, n=494, 502
    96.4 (94.3 to 97.8)
    97.2 (95.4 to 98.5)
        Serotype 8, n=495, 501
    99.2 (97.9 to 99.8)
    3.6 (2.1 to 5.6)
        Serotype 10A, n=495, 502
    97.8 (96.1 to 98.9)
    1.6 (0.7 to 3.1)
        Serotype 11A, n=495, 502
    98.4 (96.8 to 99.3)
    4.6 (2.9 to 6.8)
        Serotype 12F, n=495, 502
    96.6 (94.6 to 98.0)
    0.2 (0.0 to 1.1)
        Serotype 15B, n=495, 502
    99.4 (98.2 to 99.9)
    4.8 (3.1 to 7.0)
        Serotype 22F, n=495, 502
    99.2 (97.9 to 99.8)
    1.4 (0.6 to 2.9)
        Serotype 33F, n=495, 501
    98.6 (97.1 to 99.4)
    1.8 (0.8 to 3.4)
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 4: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [130]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 1.3
    Notes
    [130] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 3: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [131]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -10.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.7
         upper limit
    		 -6.7
    Notes
    [131] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 1: 2-Sided 95% CIs are calculated using the Miettinen and Nurminen method for the difference in proportions, expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [132]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 0.9
    Notes
    [132] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 5: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [133]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 2.2
    Notes
    [133] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 6A: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [134]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 1.5
    Notes
    [134] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 6B: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [135]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 2.7
    Notes
    [135] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 14: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [136]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.7
         upper limit
    		 0.6
    Notes
    [136] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 9V: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [137]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1.9
    Notes
    [137] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 7F: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [138]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 0.4
    Notes
    [138] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 18C: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [139]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 2.7
    Notes
    [139] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 19A: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [140]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 1.1
    Notes
    [140] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 19F: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [141]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 1.4
    Notes
    [141] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 23F: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [142]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.2
         upper limit
    		 1.4
    Notes
    [142] - Comparison for the 13 matched serotypes for 20vPnC is to the corresponding serotype in 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 8: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [143]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 3.9
    Notes
    [143] - For the additional 7 serotypes, the compared results are from serotype 23F(13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 10A: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [144]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 2.7
    Notes
    [144] - For the additional 7 serotypes, the compared results are from serotype 23F(13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 11A: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [145]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 3.2
    Notes
    [145] - For the additional 7 serotypes, the compared results are from serotype 23F (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 12F: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [146]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 1.6
    Notes
    [146] - For the additional 7 serotypes, the compared results are from serotype 23F (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 15B: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [147]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 4.1
    Notes
    [147] - For the additional 7 serotypes, the compared results are from serotype 23F (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 22F: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [148]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 3.9
    Notes
    [148] - For the additional 7 serotypes, the compared results are from serotype 23F(13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group.
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Serotype 33F: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1001
    Analysis specification
    Pre-specified
    Analysis type
    		 [149]
    Method
    Parameter type
    		 Percent difference
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 3.4
    Notes
    [149] - For the additional 7 serotypes, the compared results are from serotype 23F (13vPnC serotype with the lowest percentage, not including serotype 3) in the 13vPnC group.

    Secondary: Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Activity (OPA) 1 Month After Dose 2: Primary Study Population

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    End point title
    		 Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Activity (OPA) 1 Month After Dose 2: Primary Study Population [150]
    End point description
    OPA titers for the 20 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, and 33F) were determined in randomly selected subsets of subjects at 1 month after Dose 2. Results were expressed as OPA titers. GMTs and 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs based on the Student's t distribution. Dose 2 evaluable immunogenicity population: eligible subjects 42-112 days of age at first vaccination, received first 2 doses as randomized, at least 1 valid immunogenicity results within 27 to 56 days after Dose 2, no other major protocol deviations. "Number of Subjects Analyzed"= subjects in Dose 2 evaluable immunogenicity population, "n"= subjects with valid OPA assay results for specified serotype.
    End point type
    Secondary
    End point timeframe
    1 month after Dose 2
    Notes
    [150] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    567
    562
    Units: Titers
    geometric mean (confidence interval 95%)
        Serotype 1, n=113, 107
    14 (12 to 16)
    23 (19 to 28)
        Serotype 3, n=114, 102
    31 (26 to 36)
    40 (34 to 47)
        Serotype 4, n=113, 112
    333 (270 to 413)
    391 (314 to 486)
        Serotype 5, n=112, 102
    21 (18 to 23)
    27 (23 to 31)
        Serotype 6A, n=112, 100
    347 (273 to 441)
    409 (318 to 527)
        Serotype 6B, n=106, 97
    54 (42 to 71)
    105 (76 to 144)
        Serotype 7F, n=114, 111
    858 (736 to 1000)
    895 (781 to 1027)
        Serotype 9V, n=567, 112
    233 (182 to 298)
    285 (228 to 358)
        Serotype 14, n=111, 101
    287 (215 to 383)
    360 (264 to 489)
        Serotype 18C, n=114, 112
    588 (467 to 741)
    719 (590 to 876)
        Serotype 19A, n=115, 111
    57 (43 to 75)
    91 (69 to 121)
        Serotype 19F, n=114, 103
    97 (81 to 116)
    117 (94 to 146)
        Serotype 23F, n=105, 108
    59 (42 to 84)
    68 (48 to 96)
        Serotype 8, n=103, 115
    164 (133 to 203)
    17 (15 to 18)
        Serotype 10A, n=109, 115
    855 (610 to 1199)
    39 (34 to 44)
        Serotype 11A, n=105, 116
    327 (253 to 423)
    49 (47 to 51)
        Serotype 12F, n=96, 116
    4788 (3779 to 6067)
    26 (23 to 28)
        Serotype 15B, n=104, 117
    846 (605 to 1183)
    17 (15 to 19)
        Serotype 22F, n=104, 117
    4444 (3666 to 5386)
    10 (9 to 11)
        Serotype 33F, n=102, 115
    2373 (1759 to 3202)
    178 (163 to 195)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Activity (OPA) 1 Month After Dose 3: Primary Study Population

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    End point title
    		 Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Activity (OPA) 1 Month After Dose 3: Primary Study Population [151]
    End point description
    OPA titers for the 20 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, and 33F) were determined in randomly selected subsets of subjects at 1 month after Dose 3. Results were expressed as OPA titers. GMTs and 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs based on the Student's t distribution. Dose 3 evaluable immunogenicity population = eligible subjects 42-112 days of age at first vaccination, received all 3 doses as randomized with 335-386 days of age at Dose 3, at least 1 valid immunogenicity results from blood collection within 27 to 56 days after Dose 3, no major protocol deviations. "Number of Subjects Analyzed"= subjects in Dose 3 evaluable immunogenicity population; "n"= subjects with valid assay results for specified OPA serotype.
    End point type
    Secondary
    End point timeframe
    1 Month after Dose 3
    Notes
    [151] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    497
    504
    Units: Titers
    geometric mean (confidence interval 95%)
        Serotype 1, n=104, 97
    54 (43 to 69)
    101 (79 to 129)
        Serotype 3, n=105, 98
    99 (84 to 117)
    129 (111 to 150)
        Serotype 4, n=99, 100
    904 (752 to 1086)
    992 (777 to 1266)
        Serotype 5, n=106, 98
    60 (50 to 72)
    82 (66 to 101)
        Serotype 6A, n=105, 96
    1101 (897 to 1350)
    1304 (1018 to 1671)
        Serotype 6B, n=102, 96
    537 (408 to 706)
    864 (664 to 1125)
        Serotype 7F, n=100, 103
    1811 (1553 to 2112)
    2197 (1905 to 2533)
        Serotype 9V, n=97, 99
    3254 (2596 to 4079)
    4544 (3681 to 5610)
        Serotype 14, n=105, 95
    738 (606 to 899)
    926 (751 to 1142)
        Serotype 18C, n=98, 102
    1296 (1048 to 1602)
    1870 (1489 to 2348)
        Serotype 19A, n=99, 100
    754 (627 to 907)
    707 (558 to 896)
        Serotype 19F, n=105, 97
    183 (140 to 237)
    258 (192 to 347)
        Serotype 23F, n=100, 101
    697 (530 to 917)
    975 (734 to 1296)
        Serotype 8, n=92, 105
    1398 (1088 to 1796)
    31 (25 to 39)
        Serotype 10A, n=91, 107
    3403 (2600 to 4455)
    69 (52 to 91)
        Serotype 11A, n=87, 92
    2966 (2212 to 3978)
    66 (51 to 85)
        Serotype 12F, n=88, 108
    5501 (4499 to 6725)
    29 (25 to 35)
        Serotype 15B, n=91, 504
    2676 (1948 to 3677)
    23 (18 to 30)
        Serotype 22F, n=83, 103
    6523 (4848 to 8777)
    17 (13 to 24)
        Serotype 33F, n=72, 99
    11315 (8107 to 15794)
    708 (545 to 920)
    No statistical analyses for this end point

    Secondary: Geometric Mean Fold Rise (GMFRs) of IgG Concentrations From Before Dose 3 to 1 Month After Dose 3: Primary Study Population

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    End point title
    		 Geometric Mean Fold Rise (GMFRs) of IgG Concentrations From Before Dose 3 to 1 Month After Dose 3: Primary Study Population [152]
    End point description
    20vPnC serotypes included: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student's t distribution). Dose 3 evaluable immunogenicity population = eligible subjects 42-112 days of age at first vaccination, received all 3 doses as randomized with 335-386 days of age at Dose 3, at least 1 valid immunogenicity results from blood collection within 27 to 56 days after Dose 3, no major protocol deviations. "Number of Subjects Analyzed"= subjects in Dose 3 evaluable immunogenicity population; "n"= subjects with valid IgG assay results for specified serotype at both timepoints
    End point type
    Secondary
    End point timeframe
    1 month after Dose 3
    Notes
    [152] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    497
    504
    Units: Fold rise
    geometric mean (confidence interval 95%)
        Serotype 1, n=482, 495
    13.9 (12.7 to 15.3)
    13.9 (12.8 to 15.1)
        Serotype 3, n=482, 495
    13.7 (12.4 to 15.1)
    15.2 (13.9 to 16.7)
        Serotype 4, n=482, 495
    29.8 (27.0 to 32.9)
    27.7 (25.0 to 30.6)
        Serotype 5, n=482, 495
    14.0 (12.9 to 15.2)
    13.6 (12.6 to 14.7)
        Serotype 6A, n=482, 493
    26.9 (24.2 to 30.0)
    28.7 (25.9 to 31.7)
        Serotype 6B, n=481, 493
    36.8 (33.3 to 40.6)
    40.2 (36.8 to 44.0)
        Serotype 7F, n=482, 495
    8.5 (7.9 to 9.2)
    9.3 (8.6 to 10.0)
        Serotype 9V, n=482, 495
    22.5 (20.4 to 24.7)
    19.9 (18.3 to 21.6)
        Serotype 14, n=480, 494
    9.7 (8.7 to 10.8)
    8.4 (7.6 to 9.4)
        Serotype 18C, n=482, 495
    15.8 (14.5 to 17.1)
    17.0 (15.7 to 18.4)
        Serotype 19A, n=481, 495
    39.3 (34.6 to 44.7)
    40.7 (36.4 to 45.5)
        Serotype 19F, n=482, 495
    20.5 (18.4 to 22.9)
    21.4 (19.4 to 23.7)
        Serotype 23F, n=482, 495
    32.3 (29.2 to 35.7)
    38.3 (34.7 to 42.4)
        Serotype 8, n=483, 493
    12.7 (11.6 to 13.9)
    1.4 (1.3 to 1.5)
        Serotype 10A, n=484, 495
    14.8 (13.3 to 16.4)
    1.1 (1.0 to 1.2)
        Serotype 11A, n=484, 495
    13.8 (12.4 to 15.3)
    1.1 (1.0 to 1.2)
        Serotype 12F, n=484, 495
    16.5 (15.0 to 18.0)
    1.0 (1.0 to 1.1)
        Serotype 15B, n=484, 495
    13.4 (11.9 to 15.1)
    1.3 (1.2 to 1.4)
        Serotype 22F, n=484, 495
    12.8 (11.5 to 14.3)
    1.3 (1.1 to 1.4)
        Serotype 33F, n=484, 494
    12.9 (11.6 to 14.3)
    1.1 (1.0 to 1.2)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Predefined Antibody Levels for Concomitant Vaccine Antigens 1 Month After Dose 2: Primary Study Population

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    End point title
    		 Percentage of Subjects With Predefined Antibody Levels for Concomitant Vaccine Antigens 1 Month After Dose 2: Primary Study Population [153]
    End point description
    Diphtheria & tetanus toxoids:concentration(conc) of antibody(AB)(in international units[IU]) to diphtheria & tetanus toxoid(prespecified level>=0.1 IU/mL); Pertussis antigens-pertussis toxin (PT),filamentous hemagglutinin (FHA),pertactin (PRN):prespecified level>=observed antipertussis AB concentration achieved by 95% of 13vPnC recipient; HBsAg prespecified level >=10 milli-IU per mL (mIU/mL); Poliovirus strains (types 1, 2, and 3): prespecified level: >=1:8; Haemophilus influenzae type b(Hib): prespecified level>=0.15 mcg/mL polyribosylribitol phosphate (anti-PRP) in mcg/mL.Dose3 EIP=eligible subject 42-112 day(D) of age at 1st vaccine,received 2 dose as randomized,1 valid immunogenicity result within 27-56 D after Dose2."Number of Subjects Analyzed"=subjects in Dose 3 evaluable immunogenicity population; Concomitant vaccine response was assessed from subset of randomly selected study subjects.
    End point type
    Secondary
    End point timeframe
    1 month after Dose 2
    Notes
    [153] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Primary Study Population 13vPnC: Primary Study Population
    Number of subjects analysed
    567
    562
    Units: Percentage of subjects
    number (confidence interval 95%)
        Diphtheria toxoid, n=170, 179
    85.0 (79.3 to 89.6)
    89.5 (84.4 to 93.4)
        Tetanus toxoid, n=191, 197
    95.5 (91.6 to 97.9)
    98.5 (95.7 to 99.7)
        Pertussis: PT, n=189, 190
    94.5 (90.4 to 97.2)
    95.0 (91.0 to 97.6)
        Pertussis: FHA, n=187, 190
    93.5 (89.1 to 96.5)
    95.0 (91.0 to 97.6)
        Pertussis: PRN, n=187, 190
    93.5 (89.1 to 96.5)
    95.0 (91.0 to 97.6)
        Poliovirus: Type 1, n=91, 102
    94.8 (88.3 to 98.3)
    98.1 (93.2 to 99.8)
        Poliovirus: Type 2, n=85, 95
    88.5 (80.4 to 94.1)
    91.3 (84.2 to 96.0)
        Poliovirus: Type 3, n=92, 104
    95.8 (89.7 to 98.9)
    100.0 (96.5 to 100.0)
        Haemophilus influenzae type b, n=207, 193
    100.0 (98.2 to 100.0)
    100.0 (98.1 to 100.0)
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Diphtheria: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnC - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -4.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.2
         upper limit
    		 2.1
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Tetanus: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnC - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 0.4
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    PT: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnC - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.2
         upper limit
    		 4.1
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    FHA: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnC - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.4
         upper limit
    		 3.3
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    PRN: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnC - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.4
         upper limit
    		 3.3
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Poliovirus Type 1: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnC - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 2.2
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Poliovirus Type 2: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnC - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -2.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.8
         upper limit
    		 5.8
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Poliovirus Type 3: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnC - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Percent difference
    Point estimate
    -4.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.2
         upper limit
    		 -0.5
    Statistical analysis title
    		 20vPnC Versus 13vPnC
    Statistical analysis description
    Hib: 2-Sided 95% CI based on the Miettinen and Nurminen method for the difference in proportions (20vPnC - 13vPnC) expressed as a percentage.
    Comparison groups
    20vPnC: Primary Study Population v 13vPnC: Primary Study Population
    Number of subjects included in analysis
    1129
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Percent difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 2

    Secondary: Percentage of Subjects With Predefined Pneumococcal IgG Antibody 1 Month After Dose 3: Russian Cohort

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    End point title
    		 Percentage of Subjects With Predefined Pneumococcal IgG Antibody 1 Month After Dose 3: Russian Cohort [154]
    End point description
    Predefined IgG concentrations were as follows: for serotype 1, 3, 4, 6A, 7F, 9V, 14, 18C, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, 33F: >=0.35 microgram per mL (mcg/mL), for serotype 5: >=0.23 mcg/mL, for serotype 6B. >=0.10 mcg/mL and for serotype 19A: >=0.12 mcg/mL. 95% CI was based on the Clopper and Pearson method. Dose 3 evaluable immunogenicity population = eligible subjects 42-70 days of age at first vaccination, received all 3 doses as randomized with 335-455 days of age at Dose 3, at least 1 valid immunogenicity results from blood collection within 27 to 56 days after Dose 3, no major protocol deviations. "Number of Subjects Analyzed"= subjects in Dose 3 evaluable immunogenicity population.
    End point type
    Secondary
    End point timeframe
    1 Month after Dose 3
    Notes
    [154] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    22
    24
    Units: Percentage of subjects
    number (confidence interval 95%)
        Serotype 1
    90.9 (70.8 to 98.9)
    83.3 (62.6 to 95.3)
        Serotype 3
    68.2 (45.1 to 86.1)
    50.0 (29.1 to 70.9)
        Serotype 4
    95.5 (77.2 to 99.9)
    100.0 (85.8 to 100.0)
        Serotype 5
    90.9 (70.8 to 98.9)
    91.7 (73.0 to 99.0)
        Serotype 6A
    95.5 (77.2 to 99.9)
    100.0 (85.8 to 100.0)
        Serotype 6B
    90.9 (70.8 to 98.9)
    91.7 (73.0 to 99.0)
        Serotype 7F
    95.5 (77.2 to 99.0)
    100.0 (85.8 to 100.0)
        Serotype 9V
    100.0 (84.6 to 100.0)
    83.3 (62.6 to 95.3)
        Serotype 14
    90.9 (70.8 to 98.9)
    100.0 (85.8 to 100.0)
        Serotype 18C
    90.9 (70.8 to 98.9)
    95.8 (78.9 to 99.9)
        Serotype 19A
    100.0 (84.6 to 100.0)
    95.8 (78.9 to 99.9)
        Serotype 19F
    100.0 (84.6 to 100.0)
    91.7 (73.0 to 99.0)
        Serotype 23F
    90.9 (70.8 to 98.9)
    79.2 (57.8 to 92.9)
        Serotype 8
    68.2 (45.1 to 86.1)
    25.0 (9.8 to 46.7)
        Serotype 10A
    68.2 (45.1 to 86.1)
    16.7 (4.7 to 37.4)
        Serotype 11A
    77.3 (54.6 to 92.2)
    20.8 (7.1 to 42.2)
        Serotype 12F
    36.4 (17.2 to 59.3)
    4.2 (0.1 to 21.1)
        Serotype 15B
    90.9 (70.8 to 98.9)
    20.8 (7.1 to 42.2)
        Serotype 22F
    63.6 (40.7 to 82.8)
    12.5 (2.7 to 32.4)
        Serotype 33F
    72.7 (49.8 to 89.3)
    20.8 (7.1 to 42.2)
    No statistical analyses for this end point

    Secondary: GMTs of Serotype-specific OPA 1 Month After Dose 2: Russian Cohort

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    End point title
    		 GMTs of Serotype-specific OPA 1 Month After Dose 2: Russian Cohort [155]
    End point description
    OPA titers for the 20 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, and 33F) were determined in randomly selected subsets of subjects at 1 month after Dose 2. Results were expressed as OPA titers. GMTs and 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs based on the Student's t distribution. Dose 2 evaluable immunogenicity population: eligible subjects 42-70 days of age at first vaccination, received first 2 doses as randomized, at least 1 valid immunogenicity results from blood collection (27 to 56 days after Dose 2), no other major protocol deviations. "Number of Subjects Analyzed"= subjects in Dose 2 evaluable immunogenicity population, "n"= subjects with valid OPA assay results for specified serotype.
    End point type
    Secondary
    End point timeframe
    1 month after Dose 2
    Notes
    [155] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    24
    27
    Units: Titers
    geometric mean (confidence interval 95%)
        Serotype 1, n=8, 9
    17 (7 to 40)
    33 (10 to 105)
        Serotype 3, n=8, 9
    79 (42 to 149)
    31 (13 to 73)
        Serotype 4, n=8, 9
    166 (38 to 736)
    163 (32 to 840)
        Serotype 5, n=8, 9
    28 (11 to 76)
    31 (14 to 71)
        Serotype 6A, n=8, 9
    222 (32 to 1553)
    247 (60 to 1011)
        Serotype 6B, n=7, 8
    314 (27 to 3584)
    216 (39 to 1186)
        Serotype 7F, n=8, 9
    809 (481 to 1361)
    717 (246 to 2084)
        Serotype 9V, n=8, 9
    218 (70 to 676)
    293 (85 to 1008)
        Serotype 14, n=7, 9
    984 (492 to 1970)
    247 (69 to 886)
        Serotype 18C, n=8, 9
    968 (403 to 2326)
    268 (43 to 1655)
        Serotype 19A, n=7, 9
    314 (68 to 1443)
    31 (8 to 118)
        Serotype 19F, n=8, 9
    120 (27 to 529)
    230 (48 to 1097)
        Serotype 23F, n=8, 9
    35 (6 to 196)
    56 (9 to 346)
        Serotype 8, n=7, 9
    203 (19 to 2155)
    38 (9 to 161)
        Serotype 10A, n=6, 5
    559 (50 to 6233)
    232 (8 to 6478)
        Serotype 11A, n=6, 7
    3537 (863 to 14497)
    2717 (470 to 15716)
        Serotype 12F, n=7, 9
    698 (77 to 6301)
    198 (41 to 960)
        Serotype 15B, n=7, 8
    142 (9 to 2269)
    242 (18 to 3267)
        Serotype 22F, n=7, 8
    413 (32 to 5406)
    499 (28 to 8837)
        Serotype 33F, n=7, 9
    3508 (349 to 35250)
    3961 (706 to 22238)
    No statistical analyses for this end point

    Secondary: GMTs of Serotype-specific OPA 1 Month After Dose 3: Russian Cohort

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    End point title
    		 GMTs of Serotype-specific OPA 1 Month After Dose 3: Russian Cohort [156]
    End point description
    OPA titers for the 20 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, and 33F) were determined in randomly selected subsets of subjects at 1 month after Dose 3. Results were expressed as OPA titers. GMTs and 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs based on the Student's t distribution. Dose 3 evaluable immunogenicity population = eligible subjects 42-70 days of age at first vaccination, received all 3 doses as randomized with 335-455 days of age at Dose 3, at least 1 valid immunogenicity results from blood collection within 27 to 56 days after Dose 3, no major protocol deviations. "Number of Subjects Analyzed"= subjects in Dose 3 evaluable immunogenicity population; "n"= subjects with valid OPA assay results for specified serotype.
    End point type
    Secondary
    End point timeframe
    1 Month after Dose 3
    Notes
    [156] - 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 endpoint was planned to be analysed only for the specified reporting arms
    End point values
    		 20vPnC: Russian Cohort 13vPnC: Russian Cohort
    Number of subjects analysed
    22
    24
    Units: Titers
    geometric mean (confidence interval 95%)
        Serotype 1, n=8, 9
    85 (17 to 421)
    93 (22 to 394)
        Serotype 3, n=8, 9
    126 (41 to 383)
    107 (37 to 309)
        Serotype 4, n=8, 8
    310 (86 to 1123)
    429 (38 to 4863)
        Serotype 5, n=8, 9
    116 (28 to 476)
    108 (26 to 456)
        Serotype 6A, n=7, 9
    2922 (311 to 27459)
    1580 (393 to 6351)
        Serotype 6B, n=7, 7
    4417 (998 to 19951)
    1397 (150 to 12967)
        Serotype 7F, n=8, 8
    1039 (509 to 2122)
    1411 (373 to 5340)
        Serotype 9V, n=8, 7
    1574 (369 to 6711)
    1067 (150 to 7583)
        Serotype 14, n=7, 9
    1151 (321 to 4132)
    628 (137 to 2890)
        Serotype 18C, n=8, 8
    583 (149 to 2284)
    973 (89 to 10606)
        Serotype 19A, n=8, 7
    652 (131 to 3234)
    435 (14 to 13833)
        Serotype 19F, n=7, 9
    1570 (239 to 10337)
    701 (124 to 3958)
        Serotype 23F, n=8, 8
    152 (24 to 966)
    410 (22 to 7594)
        Serotype 8, n=4, 6
    368 (11 to 12078)
    149 (9 to 2337)
        Serotype 10A, n=4, 6
    2851 (1309 to 6210)
    117 (15 to 916)
        Serotype 11A, n=4, 4
    7137 (1036 to 49164)
    1789 (36 to 89068)
        Serotype 12F, n=4, 7
    757 (15 to 37522)
    241 (16 to 3734)
        Serotype 15B, n=5, 7
    822 (42 to 16070)
    147 (10 to 2214)
        Serotype 22F, n=4, 7
    1983 (390 to 10085)
    1635 (165 to 16157)
        Serotype 33F, n=3, 7
    5903 (53 to 657862)
    3619 (948 to 13817)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Local reactions & Systemic events [systematic assessment (SA)]: Within 7 days after Dose 1,2, or 3; SAEs(non-SA): From Dose 1 up to 1 month after Dose 3 & other AEs (non-SAE): From Dose 1 up to 1 month after Dose 2 & from Dose 3 up to 1 month after Dose 3
    Adverse event reporting additional description
    Same event may appear as both SAE & non-SAE.However, what is presented are distinct events.Event may be classified as serious in 1 subject & non-serious in another, or 1 subject may have experienced both during study.Safety analysis set evaluated. MedDRA 25.0 was used for primary cohorts and 26.0 was used for Russian cohort.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    20vPnC: Primary Study Population
    Reporting group description
    		 Infants 42 to 112 days of age were enrolled to receive 3 doses of 0.5 mL 20vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 42 to 63 days later. Dose 3 was administered at 11 to 12 months of age.

    Reporting group title
    13vPnC: Russian Cohort
    Reporting group description
    		 Infants 42 to 70 days of age were enrolled to receive 3 doses of 0.5 mL 13vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 60 to 90 days later. Dose 3 was administered at 28 to 42 days after Dose 2.

    Reporting group title
    20vPnC: Russian Cohort
    Reporting group description
    		 Infants 42 to 70 days of age were enrolled to receive 3 doses of 0.5 mL 20vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 60 to 90 days later. Dose 3 was administered at 28 to 42 days after Dose 2

    Reporting group title
    13vPnC: Primary Study Population
    Reporting group description
    		 Infants 42 to 112 days of age were enrolled to receive 3 doses of 0.5 mL 13vPnC intramuscularly. Dose 1 was given at enrollment and Dose 2 was given 42 to 63 days later. Dose 3 was administered at 11 to 12 months of age.

    Serious adverse events
    		 20vPnC: Primary Study Population 13vPnC: Russian Cohort 20vPnC: Russian Cohort 13vPnC: Primary Study Population
    Total subjects affected by serious adverse events
         subjects affected / exposed
    34 / 601 (5.66%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    40 / 603 (6.63%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign salivary gland neoplasm
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Inflammation
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchial hyperreactivity
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Foreign body aspiration
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thermal burn
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Aorticopulmonary septal defect
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchogenic cyst
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Febrile convulsion
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial pressure increased
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotonia
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thymus enlargement
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenitis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Urticaria
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis atopic
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephritis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vesicoureteric reflux
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacterial infection
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchiolitis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    2 / 601 (0.33%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    2 / 603 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema infectiosum
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    2 / 603 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    4 / 601 (0.67%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    5 / 603 (0.83%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection viral
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal infection
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    2 / 601 (0.33%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    2 / 603 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal viral infection
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpangina
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    2 / 603 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral candidiasis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis enteroviral
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    3 / 603 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    4 / 601 (0.67%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    4 / 603 (0.66%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchiolitis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    2 / 601 (0.33%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    3 / 601 (0.50%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Underweight
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    1 / 601 (0.17%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 603 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Poor feeding infant
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 603 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Feeding disorder
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    0 / 601 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    3 / 603 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 20vPnC: Primary Study Population 13vPnC: Russian Cohort 20vPnC: Russian Cohort 13vPnC: Primary Study Population
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    589 / 601 (98.00%)
    20 / 27 (74.07%)
    17 / 24 (70.83%)
    593 / 603 (98.34%)
    Nervous system disorders
    Hypersomnia (INCREASED SLEEP)
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
    alternative assessment type: Systematic
         subjects affected / exposed
    495 / 601 (82.36%)
    11 / 27 (40.74%)
    8 / 24 (33.33%)
    512 / 603 (84.91%)
         occurrences all number
    965
    16
    11
    970
    General disorders and administration site conditions
    Injection site erythema (REDNESS)
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
    alternative assessment type: Systematic
         subjects affected / exposed
    331 / 601 (55.07%)
    4 / 27 (14.81%)
    3 / 24 (12.50%)
    333 / 603 (55.22%)
         occurrences all number
    534
    6
    4
    531
    Injection site pain (PAIN)
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
    alternative assessment type: Systematic
         subjects affected / exposed
    343 / 601 (57.07%)
    6 / 27 (22.22%)
    7 / 24 (29.17%)
    347 / 603 (57.55%)
         occurrences all number
    555
    7
    8
    557
    Injection site swelling (SWELLING)
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
    alternative assessment type: Systematic
         subjects affected / exposed
    260 / 601 (43.26%)
    3 / 27 (11.11%)
    4 / 24 (16.67%)
    251 / 603 (41.63%)
         occurrences all number
    431
    3
    5
    388
    Pyrexia (FEVER)
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
    alternative assessment type: Systematic
         subjects affected / exposed
    212 / 601 (35.27%)
    4 / 27 (14.81%)
    2 / 24 (8.33%)
    214 / 603 (35.49%)
         occurrences all number
    282
    4
    3
    273
    Psychiatric disorders
    Irritability (IRRITABILITY)
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
    alternative assessment type: Systematic
         subjects affected / exposed
    553 / 601 (92.01%)
    15 / 27 (55.56%)
    13 / 24 (54.17%)
    556 / 603 (92.21%)
         occurrences all number
    1266
    24
    18
    1258
    Infections and infestations
    Upper respiratory tract infection
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
         subjects affected / exposed
    21 / 601 (3.49%)
    0 / 27 (0.00%)
    1 / 24 (4.17%)
    35 / 603 (5.80%)
         occurrences all number
    21
    0
    1
    40
    Metabolism and nutrition disorders
    Decreased appetite (DECREASED APPETITE)
    Additional description: MedDRA 26.0 was used for Russian Cohorts.
    alternative assessment type: Systematic
         subjects affected / exposed
    345 / 601 (57.40%)
    8 / 27 (29.63%)
    9 / 24 (37.50%)
    323 / 603 (53.57%)
         occurrences all number
    522
    10
    10
    465

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jun 2021
    amendment 2:Added noninferiority of IgG GMCs and the percentage of participants with predefined thresholds after 2 infant doses as primary immunogenicity objectives and moved objective for IgG percentage of participants with predefined thresholds after toddler dose to secondary objective, based on Scientific Advice from CHMP. The statistical sections for these objectives were updated accordingly. Added country-specific appendix for Russian cohort to add approximately 60 participants and address comments from a national agency on schedule, concomitant vaccines and other study aspects, including management of Russian cohort data. Made updates throughout the protocol on managing the Russian cohort.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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