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    Clinical Trial Results:
    A Phase 3, Single-arm Trial to Evaluate the Safety and Immunogenicity of a 20-Valent Pneumococcal Conjugate Vaccine in Healthy Children 15 Months Through 17 Years of Age

    Summary
    EudraCT number
    		 2019-003308-11
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    06 Apr 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    06 Mar 2024
    First version publication date
    24 Sep 2022
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    B7471014
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04642079
    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 ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, 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
    07 Jul 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Apr 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To describe the safety profile of 20-valent pneumococcal conjugate (20vPnC). Cohort 1 (subjects aged >=15 to <24 months) and Cohort 2 (subjects aged >=2 to <5 years): To demonstrate that the serotype-specific immunoglobulin G (IgG) concentrations for the 7 additional serotypes 1 month after 20-valent pneumococcal conjugate (20vPnC) are superior to the corresponding IgG concentrations before 20vPnC. Cohort 3 (subjects aged >=5 to <10 years) and Cohort 4 (subjects aged >=10 to <18 years): To demonstrate that the serotype-specific opsonophagocytic activity (OPA) titers for the 7 additional serotypes 1 month after 20vPnC are superior to the corresponding OPA titers before 20vPnC.
    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 Council for 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
    04 Dec 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 839
    Worldwide total number of subjects
    839
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    210
    Children (2-11 years)
    473
    Adolescents (12-17 years)
    156
    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
    		 A total of 839 subjects were enrolled and assigned to receive a single dose of 20vPnC of which 8 subjects were not vaccinated and 831 were vaccinated with 20vPnC.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: 20vPnC: >=15 to <24 Months
    Arm description
    		 Subjects aged >=15 months to <24 months who have been previously vaccinated with at least 3 doses of 13vPnC, were administered a single dose of 0.5 millilitre (mL) 20vPnC intramuscularly on Day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    20-Valent Pneumococcal Conjugate Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered a single 0.5 mL dose of 20vPnC intramuscularly on Day 1.

    Arm title
    		 Cohort 2: 20vPnC: >=2 to <5 Years
    Arm description
    		 Subjects aged >=2 to <5 years who have been previously vaccinated with at least 3 doses of 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly on Day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    20-Valent Pneumococcal Conjugate Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered a single 0.5 mL dose of 20vPnC intramuscularly on Day 1.

    Arm title
    		 Cohort 3: 20vPnC: >=5 to <10 Years
    Arm description
    		 Subjects aged >=5 to <10 years regardless of previous vaccination status with 7vPnC or 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly into the left arm on Day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    20-Valent Pneumococcal Conjugate Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered a single 0.5 mL dose of 20vPnC intramuscularly on Day 1.

    Arm title
    		 Cohort 4: 20vPnC: >=10 to <18 Years
    Arm description
    		 Subjects aged >=10 to <18 years regardless of previous vaccination status with 7vPnC or 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly into the left arm on Day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    20-Valent Pneumococcal Conjugate Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered a single 0.5 mL dose of 20vPnC intramuscularly on Day 1.

    Number of subjects in period 1
    		Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Started
    210
    219
    203
    207
    Vaccinated
    209
    216
    201
    205
    Completed
    207
    210
    199
    203
    Not completed
    3
    9
    4
    4
         No longer meets eligibility criteria
    1
    -
    1
    1
         Not specified
    -
    -
    -
    1
         Lost to follow-up
    2
    5
    2
    -
         Consent withdrawn by parent/guardian/subject
    -
    4
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: 20vPnC: >=15 to <24 Months
    Reporting group description
    		 Subjects aged >=15 months to <24 months who have been previously vaccinated with at least 3 doses of 13vPnC, were administered a single dose of 0.5 millilitre (mL) 20vPnC intramuscularly on Day 1.

    Reporting group title
    Cohort 2: 20vPnC: >=2 to <5 Years
    Reporting group description
    		 Subjects aged >=2 to <5 years who have been previously vaccinated with at least 3 doses of 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly on Day 1.

    Reporting group title
    Cohort 3: 20vPnC: >=5 to <10 Years
    Reporting group description
    		 Subjects aged >=5 to <10 years regardless of previous vaccination status with 7vPnC or 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly into the left arm on Day 1.

    Reporting group title
    Cohort 4: 20vPnC: >=10 to <18 Years
    Reporting group description
    		 Subjects aged >=10 to <18 years regardless of previous vaccination status with 7vPnC or 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly into the left arm on Day 1.

    Reporting group values
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years Total
    Number of subjects
    		 210 219 203 207 839
    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-23months)
    		 210 0 0 0 210
        Children (2-11 years)
    		 0 219 203 51 473
        Adolescents (12-17 years)
    		 0 0 0 156 156
        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
    Age is reported in Months for 'Cohort 1: 20vPnC: >=15 to <24 Months'
    Units: years
        arithmetic mean (standard deviation)
    		 18.3 ( 2.67 ) 3.0 ( 0.82 ) 7.2 ( 1.38 ) 13.6 ( 2.32 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 93 111 94 91 389
        Male
    		 117 108 109 116 450
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 0 0 1
        Asian
    		 3 0 0 0 3
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 1 1
        Black or African American
    		 26 26 22 17 91
        White
    		 169 175 176 180 700
        More than one race
    		 10 14 5 9 38
        Unknown or Not Reported
    		 2 3 0 0 5
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 35 46 32 45 158
        Not Hispanic or Latino
    		 173 173 169 161 676
        Unknown or Not Reported
    		 2 0 2 1 5

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: 20vPnC: >=15 to <24 Months
    Reporting group description
    		 Subjects aged >=15 months to <24 months who have been previously vaccinated with at least 3 doses of 13vPnC, were administered a single dose of 0.5 millilitre (mL) 20vPnC intramuscularly on Day 1.

    Reporting group title
    Cohort 2: 20vPnC: >=2 to <5 Years
    Reporting group description
    		 Subjects aged >=2 to <5 years who have been previously vaccinated with at least 3 doses of 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly on Day 1.

    Reporting group title
    Cohort 3: 20vPnC: >=5 to <10 Years
    Reporting group description
    		 Subjects aged >=5 to <10 years regardless of previous vaccination status with 7vPnC or 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly into the left arm on Day 1.

    Reporting group title
    Cohort 4: 20vPnC: >=10 to <18 Years
    Reporting group description
    		 Subjects aged >=10 to <18 years regardless of previous vaccination status with 7vPnC or 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly into the left arm on Day 1.

    Primary: Percentage of Subjects Reporting Prompted Local Reactions Within 7 Days After Vaccination

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    End point title
    		 Percentage of Subjects Reporting Prompted Local Reactions Within 7 Days After Vaccination [1]
    End point description
    Local reactions included pain at injection site, redness and swelling recorded by parent’s/legal guardian’s of subjects in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. One measuring device unit =0.5 centimetre (cm). Redness and swelling were graded as mild: greater than (>) 0.0 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 (cohort 1) and did not interfere with activity (cohort 2-4); moderate: hurt if gently touched with crying (cohort 1) and interfered with daily activity (cohort 2-4) and; severe: limited limb movement (cohort 1) and prevented daily activity (cohort 2-4). 95 percent (%) confidence interval (CI) was based on Clopper and Pearson method. Safety population included all subjects who received 20vPnC and had safety follow-up after vaccination. Here, “Number of Subjects Analysed” signifies subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 7 days after vaccination
    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: No statistical analysis were performed.
    End point values
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    204
    215
    199
    205
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Any
    37.7 (31.1 to 44.8)
    39.1 (32.5 to 45.9)
    37.2 (30.5 to 44.3)
    15.1 (10.5 to 20.8)
        Redness: Mild
    30.4 (24.2 to 37.2)
    22.8 (17.4 to 29.0)
    16.6 (11.7 to 22.5)
    10.7 (6.8 to 15.8)
        Redness: Moderate
    7.4 (4.2 to 11.8)
    15.3 (10.8 to 20.9)
    18.6 (13.4 to 24.7)
    3.9 (1.7 to 7.5)
        Redness: Severe
    0 (0.0 to 1.8)
    0.9 (0.1 to 3.3)
    2.0 (0.6 to 5.1)
    0.5 (0.0 to 2.7)
        Swelling: Any
    22.1 (16.6 to 28.4)
    23.3 (17.8 to 29.5)
    27.1 (21.1 to 33.9)
    15.6 (10.9 to 21.3)
        Swelling: Mild
    15.7 (11.0 to 21.4)
    11.6 (7.7 to 16.7)
    10.6 (6.7 to 15.7)
    5.4 (2.7 to 9.4)
        Swelling: Moderate
    6.4 (3.4 to 10.7)
    11.2 (7.3 to 16.2)
    15.6 (10.8 to 21.4)
    10.2 (6.5 to 15.2)
        Swelling: Severe
    0 (0.0 to 1.8)
    0.5 (0.0 to 2.6)
    1.0 (0.1 to 3.6)
    0 (0.0 to 1.8)
        Pain at injection site: Any
    52.5 (45.4 to 59.5)
    66.0 (59.3 to 72.3)
    82.9 (77.0 to 87.9)
    82.0 (76.0 to 87.0)
        Pain at injection site: Mild
    41.7 (34.8 to 48.8)
    47.0 (40.2 to 53.9)
    56.8 (49.6 to 63.8)
    62.9 (55.9 to 69.6)
        Pain at the injection site: Moderate
    9.8 (6.1 to 14.7)
    17.7 (12.8 to 23.4)
    24.6 (18.8 to 31.2)
    17.6 (12.6 to 23.5)
        Pain at the injection site: Severe
    1.0 (0.1 to 3.5)
    1.4 (0.3 to 4.0)
    1.5 (0.3 to 4.3)
    1.5 (0.3 to 4.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Prompted Systemic Events Within 7 Days After Vaccination: Cohort 1

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    End point title
    		 Percentage of Subjects Reporting Prompted Systemic Events Within 7 Days After Vaccination: Cohort 1 [2] [3]
    End point description
    Systemic events for Cohort 1 were recorded by parents/legal guardians of subject’s using an e-diary. Fever was defined as temperature greater than or equal to (>=) 38.0 degree Celsius (C) and categorised as >=38.0 to 38.4 degree C, >38.4 to 38.9 degree C, >38.9 to 40.0 degree C and >40.0 degree C. Decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed). Drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity). Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). 95% CI was based on Clopper and Pearson method. Safety population included all subjects who received 20vPnC and had safety follow-up after vaccination. “Number of Subjects Analysed” = subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 7 days after vaccination
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was planned to be analysed only for the specified reporting arms.
    [3] - 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
    		 Cohort 1: 20vPnC: >=15 to <24 Months
    Number of subjects analysed
    204
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever: =>38.0 degree C
    11.8 (7.7 to 17.0)
        Fever: =>38.0 degree C to 38.4 degree C
    5.9 (3.1 to 10.0)
        Fever: >38.4 degree C to 38.9 degree C
    2.9 (1.1 to 6.3)
        Fever: >38.9 degree C to 40.0 degree C
    2.9 (1.1 to 6.3)
        Fever: >40.0 degree C
    0 (0.0 to 1.8)
        Decreased appetite: Any
    25.0 (19.2 to 31.5)
        Decreased appetite: Mild
    17.6 (12.7 to 23.6)
        Decreased appetite: Moderate
    6.4 (3.4 to 10.7)
        Decreased appetite: Severe
    1.0 (0.1 to 3.5)
        Drowsiness/increased sleep: Any
    41.7 (34.8 to 48.8)
        Drowsiness/increased sleep: Mild
    31.4 (25.1 to 38.2)
        Drowsiness/increased sleep: Moderate
    9.3 (5.7 to 14.2)
        Drowsiness/increased sleep: Severe
    1.0 (0.1 to 3.5)
        Irritability: Any
    61.8 (54.7 to 68.5)
        Irritability: Mild
    22.5 (17.0 to 28.9)
        Irritability: Moderate
    37.3 (30.6 to 44.3)
        Irritability: Severe
    2.0 (0.5 to 4.9)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Prompted Systemic Events Within 7 Days After Vaccination: Cohorts 2, 3 and 4

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    End point title
    		 Percentage of Subjects Reporting Prompted Systemic Events Within 7 Days After Vaccination: Cohorts 2, 3 and 4 [4] [5]
    End point description
    Systemic events for Cohort 2-4 included fever, fatigue, headache, muscle pain and joint pain, recorded by parents/legal guardians of subject’s using an e-diary. Fever was defined as temperature >=38.0 degree C and categorised as >=38.0 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C and >40.0 degree C. Fatigue, headache, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (prevents daily routine activity). 95% CI was based on Clopper and Pearson method. Safety population included all subjects who received 20vPnC and had safety follow-up after vaccination. “Number of Subjects Analysed” = subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 7 days after vaccination
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed.
    [5] - 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
    		 Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    215
    199
    205
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever: =>38.0 degree C
    3.3 (1.3 to 6.6)
    0.5 (0.0 to 2.8)
    0 (0.0 to 1.8)
        Fever: =>38.0 degree C to 38.4 degree C
    1.4 (0.3 to 4.0)
    0.5 (0.0 to 2.8)
    0 (0.0 to 1.8)
        Fever: 38.4 degree C to 38.9 degree C
    1.4 (0.3 to 4.0)
    0 (0.0 to 1.8)
    0 (0.0 to 1.8)
        Fever: 38.9 degree C to 40.0 degree C
    0.5 (0.0 to 2.6)
    0 (0.0 to 1.8)
    0 (0.0 to 1.8)
        Fever: =>40.0 degree C
    0 (0.0 to 1.7)
    0 (0.0 to 1.8)
    0 (0.0 to 1.8)
        Fatigue: Any
    37.2 (30.7 to 44.0)
    28.1 (22.0 to 34.9)
    27.8 (21.8 to 34.5)
        Fatigue: Mild
    21.9 (16.5 to 28.0)
    19.1 (13.9 to 25.3)
    15.6 (10.9 to 21.3)
        Fatigue: Moderate
    14.4 (10.0 to 19.8)
    8.5 (5.1 to 13.3)
    12.2 (8.0 to 17.5)
        Fatigue: Severe
    0.9 (0.1 to 3.3)
    0.5 (0.0 to 2.8)
    0 (0.0 to 1.8)
        Headache: Any
    5.6 (2.9 to 9.5)
    18.6 (13.4 to 24.7)
    29.3 (23.1 to 36.0)
        Headache: Mild
    3.3 (1.3 to 6.6)
    14.6 (10.0 to 20.3)
    20.0 (14.8 to 26.1)
        Headache: Moderate
    1.9 (0.5 to 4.7)
    3.0 (1.1 to 6.4)
    7.8 (4.5 to 12.4)
        Headache: Severe
    0.5 (0.0 to 2.6)
    1.0 (0.1 to 3.6)
    1.5 (0.3 to 4.2)
        Muscle pain: Any
    26.5 (20.7 to 32.9)
    39.2 (32.4 to 46.3)
    48.3 (41.3 to 55.4)
        Muscle pain: Mild
    17.7 (12.8 to 23.4)
    26.6 (20.6 to 33.3)
    34.6 (28.1 to 41.6)
        Muscle pain: Moderate
    8.4 (5.0 to 12.9)
    11.1 (7.1 to 16.3)
    13.2 (8.9 to 18.6)
        Muscle pain: Severe
    0.5 (0.0 to 2.6)
    1.5 (0.3 to 4.3)
    0.5 (0.0 to 2.7)
        Joint pain: Any
    3.7 (1.6 to 7.2)
    6.5 (3.5 to 10.9)
    8.3 (4.9 to 12.9)
        Joint pain: Mild
    2.3 (0.8 to 5.3)
    3.0 (1.1 to 6.4)
    3.4 (1.4 to 6.9)
        Joint pain: Moderate
    1.4 (0.3 to 4.0)
    3.0 (1.1 to 6.4)
    4.9 (2.4 to 8.8)
        Joint pain: Severe
    0 (0.0 to 1.7)
    0.5 (0.0 to 2.8)
    0 (0.0 to 1.8)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Adverse Events (AEs) up to 1 Month After Vaccination

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    End point title
    		 Percentage of Subjects Reporting Adverse Events (AEs) up to 1 Month After Vaccination [6]
    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. Safety population included all subjects who received 20vPnC and had safety follow-up after vaccination.
    End point type
    Primary
    End point timeframe
    From Day 1 of vaccination up to 1 month after vaccination
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed.
    End point values
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    209
    216
    201
    205
    Units: Percentage of subjects
        number (confidence interval 95%)
    23.9 (18.3 to 30.3)
    7.9 (4.7 to 12.3)
    6.5 (3.5 to 10.8)
    4.4 (2.0 to 8.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Serious Adverse Events (SAEs) up to 6 Months After Vaccination

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    End point title
    		 Percentage of Subjects Reporting Serious Adverse Events (SAEs) up to 6 Months After Vaccination [7]
    End point description
    An SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalisation or prolongation of existing hospitalisation; 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 population included all subjects who received 20vPnC and had safety follow-up after vaccination.
    End point type
    Primary
    End point timeframe
    From Day 1 of vaccination up to 6 months after vaccination
    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: No statistical analysis were performed.
    End point values
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    209
    216
    201
    205
    Units: Percentage of subjects
        number (confidence interval 95%)
    0.5 (0.0 to 2.6)
    0 (0.0 to 1.7)
    0 (0.0 to 1.8)
    1.5 (0.3 to 4.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Newly Diagnosed Chronic Medical Conditions (NDCMCs) up to 6 Months After Vaccination

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    End point title
    		 Percentage of Subjects Reporting Newly Diagnosed Chronic Medical Conditions (NDCMCs) up to 6 Months After Vaccination [8]
    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 population included all subjects who received 20vPnC and had safety follow-up after vaccination.
    End point type
    Primary
    End point timeframe
    From Day 1 of vaccination up to 6 months after vaccination
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed.
    End point values
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    209
    216
    201
    205
    Units: Percentage of subjects
        number (confidence interval 95%)
    3.3 (1.4 to 6.8)
    0.5 (0.0 to 2.6)
    0.5 (0.0 to 2.7)
    1.0 (0.1 to 3.5)
    No statistical analyses for this end point

    Primary: Geometric Mean Fold Rises (GMFRs) of Pneumococcal Serotype-Specific Immunoglobulin G (IgG) Concentrations for the 7 Additional Serotypes From Before to 1 Month After 20vPnC Vaccination: Cohort 1 and 2

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    End point title
    		 Geometric Mean Fold Rises (GMFRs) of Pneumococcal Serotype-Specific Immunoglobulin G (IgG) Concentrations for the 7 Additional Serotypes From Before to 1 Month After 20vPnC Vaccination: Cohort 1 and 2 [9] [10]
    End point description
    Pneumococcal serotype-specific IgG concentrations were measured from serum samples for 7 additional 20vPnC serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. GMFR=geometric mean of fold rise from before vaccination on Day 1 to 1 month after vaccination with 20vPnC. GMFRs and corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of titres or fold rises and the corresponding CIs (based on Student t distribution). Superiority of IgG concentration 1 month after 20vPnC to before vaccination for each serotype was demonstrated if the 95% lower CI of GMFR was >1. Evaluable immunogenicity population (EIP) included all subjects who were eligible; received 20vPnC; at least 1 valid immunogenicity result from 1 month after vaccination collected within 27 to 56 days after vaccination for Cohorts 1-2; no other major protocol deviations. Number of Subjects Analysed=subjects included in the EIP and n=subjects with valid assay results at both timepoints for the specified serotype.
    End point type
    Primary
    End point timeframe
    Before vaccination to 1 month after vaccination
    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: This endpoint was planned to be analysed only for the specified reporting arms.
    [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
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years
    Number of subjects analysed
    190
    183
    Units: Fold rise
    geometric mean (confidence interval 95%)
        Serotype 8 (n=186, 178)
    113.4 (93.2 to 137.9)
    107.0 (86.1 to 133.0)
        Serotype 10A (n=188, 181)
    83.2 (69.1 to 100.2)
    106.7 (86.2 to 132.0)
        Serotype 11A (n=188, 182)
    62.7 (49.9 to 78.8)
    43.6 (33.2 to 57.1)
        Serotype 12F (n=188, 182)
    27.9 (22.9 to 34.1)
    36.6 (30.1 to 44.7)
        Serotype 15B (n=188, 180)
    52.1 (43.2 to 62.8)
    73.3 (58.7 to 91.5)
        Serotype 22F (n=188, 182)
    1847.7 (1481.3 to 2304.5)
    796.2 (577.1 to 1098.4)
        Serotype 33F (n=188, 182)
    113.5 (92.5 to 139.2)
    78.3 (61.6 to 99.5)
    No statistical analyses for this end point

    Primary: GMFRs of Pneumococcal Serotype-Specific Opsonophagocytic Activity (OPA) Titres for the 7 Additional Serotypes From Before to 1 Month After 20PnC Vaccination: Cohort 3 and 4

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    End point title
    		 GMFRs of Pneumococcal Serotype-Specific Opsonophagocytic Activity (OPA) Titres for the 7 Additional Serotypes From Before to 1 Month After 20PnC Vaccination: Cohort 3 and 4 [11] [12]
    End point description
    Pneumococcal serotype-specific OPA titers were measured from serum samples for 7 additional 20vPnC serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. GMFR was calculated as geometric mean of fold rise from before vaccination on Day 1 to 1 month after vaccination with 20vPnC. GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titres or fold rises and the corresponding CIs (based on the Student t distribution). Superiority of OPA titers 1 month after 20vPnC to before vaccination for each serotype was demonstrated if the 95% lower CI of the GMFR was >1. EIP included all subjects who were eligible; received 20vPnC; at least 1 valid immunogenicity result from 1 month after vaccination collected within 27 to 49 days after vaccination for Cohorts 3-4; no other major protocol deviations. Here, Number of Subjects Analysed=subjects included in the EIP and n=subjects with valid assay results at both timepoints for the specified serotype.
    End point type
    Primary
    End point timeframe
    Before vaccination to 1 month after vaccination
    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: This endpoint was planned to be analysed only for the specified reporting arms.
    [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
    		 Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    186
    198
    Units: Fold rise
    geometric mean (confidence interval 95%)
        Serotype 8 (n=153, 174)
    106.5 (79.9 to 142.0)
    86.3 (64.2 to 115.9)
        Serotype 10A (n=134, 142)
    30.6 (20.1 to 46.6)
    33.5 (22.3 to 50.1)
        Serotype 11A (n=136, 155)
    11.6 (7.6 to 17.7)
    14.9 (10.2 to 21.8)
        Serotype 12F (n=154, 164)
    463.6 (332.3 to 646.7)
    454.1 (333.3 to 618.7)
        Serotype 15B (n=142, 164)
    380.8 (228.3 to 635.2)
    499.0 (338.7 to 735.3)
        Serotype 22F (n=137, 168)
    128.5 (76.7 to 215.3)
    111.2 (67.1 to 184.3)
        Serotype 33F (n=144, 158)
    14.2 (10.9 to 18.4)
    11.5 (8.9 to 14.9)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Predefined Levels of Pneumococcal Serotype-Specific IgG Concentrations for the 7 Additional Serotypes at 1 Month After Vaccination in Cohort 1 Only

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    End point title
    		 Percentage of Subjects With Predefined Levels of Pneumococcal Serotype-Specific IgG Concentrations for the 7 Additional Serotypes at 1 Month After Vaccination in Cohort 1 Only [13]
    End point description
    Pneumococcal serotype-specific IgG concentrations were measured from serum samples for 7 additional 20vPnC serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. Percentage of subjects with predefined level (>=0.35 micrograms per millilitre (mcg/mL) of IgG concentration for the 7 additional 20vPnC serotypes was presented. 95% CI was based on Clopper and Pearson method. EIP included all subjects who were eligible; received 20vPnC; at least 1 valid immunogenicity result from 1 month after vaccination collected within 27 to 56 days after vaccination for Cohort 1; no other major protocol deviations. Here, “Number of Subjects Analysed” signifies subjects included in the EIP with valid assay results.
    End point type
    Secondary
    End point timeframe
    At 1 Month after vaccination
    Notes
    [13] - 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
    		 Cohort 1: 20vPnC: >=15 to <24 Months
    Number of subjects analysed
    190
    Units: Percentage of subjects
    number (confidence interval 95%)
        Serotype 8
    100.0 (98.1 to 100.0)
        Serotype 10A
    83.2 (77.1 to 88.2)
        Serotype 11A
    93.2 (88.6 to 96.3)
        Serotype 12F
    40.0 (33.0 to 47.3)
        Serotype 15B
    83.7 (77.6 to 88.6)
        Serotype 22F
    98.9 (96.2 to 99.9)
        Serotype 33F
    92.6 (87.9 to 95.9)
    No statistical analyses for this end point

    Secondary: Geometric Mean Concentrations (GMCs) of Pneumococcal Serotype-Specific IgG for the 20vPnC Serotypes Before and 1 Month After Vaccination

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    End point title
    		 Geometric Mean Concentrations (GMCs) of Pneumococcal Serotype-Specific IgG for the 20vPnC Serotypes Before and 1 Month After Vaccination
    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 20vPnC serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. GMCs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). EIP included all subjects who were eligible; received 20vPnC; at least 1 valid immunogenicity result from 1 month after vaccination collected within 27 to 56 days or within 27 to 49 days after vaccination for Cohorts 1-2 or Cohorts 3-4, respectively; no other major protocol deviations. Here, “Number of Subjects Analysed” signifies subjects included in the EIP and n=subjects with valid IgG concentrations at the specified timepoint.
    End point type
    Secondary
    End point timeframe
    Before vaccination (Vacc.) and 1 month after vaccination (1M after Vacc.)
    End point values
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    190
    183
    186
    198
    Units: Micrograms per millilitre
    geometric mean (confidence interval 95%)
        Before Vacc.,Serotype 1 (n=189,183,186,198)
    0.43 (0.37 to 0.49)
    0.20 (0.17 to 0.24)
    0.12 (0.10 to 0.14)
    0.09 (0.08 to 0.11)
        1M after Vacc.,Serotype 1 (n=190,183,186,198)
    1.46 (1.28 to 1.67)
    4.21 (3.62 to 4.90)
    5.86 (5.15 to 6.67)
    4.04 (3.32 to 4.93)
        Before Vacc.,Serotype 3 (n=189,183,186,198)
    0.14 (0.12 to 0.16)
    0.08 (0.06 to 0.10)
    0.22 (0.17 to 0.30)
    0.15 (0.11 to 0.20)
        1M after Vacc.,Serotype 3 (n=190,183,186,198)
    0.54 (0.47 to 0.61)
    1.21 (1.04 to 1.42)
    1.32 (1.16 to 1.50)
    0.62 (0.52 to 0.76)
        Before Vacc.,Serotype 4 (n=189,183,186,198)
    0.61 (0.52 to 0.72)
    0.30 (0.25 to 0.37)
    0.13 (0.11 to 0.16)
    0.12 (0.10 to 0.15)
        1M after Vacc.,Serotype 4 (n=190, 183, 186, 198)
    2.59 (2.27 to 2.96)
    8.37 (7.28 to 9.62)
    9.76 (8.54 to 11.15)
    6.37 (5.39 to 7.53)
        Before Vacc.,Serotype 5 (n=189,183,186,198)
    0.43 (0.36 to 0.50)
    0.18 (0.15 to 0.22)
    0.07 (0.06 to 0.08)
    0.04 (0.03 to 0.06)
        1M after Vacc.,Serotype 5 (n=190,183,186,198)
    1.53 (1.32 to 1.77)
    5.09 (4.32 to 5.99)
    7.50 (6.52 to 8.63)
    2.58 (1.88 to 3.53)
        Before Vacc.,Serotype 6A (n=188,183,184,195)
    1.61 (1.38 to 1.88)
    0.71 (0.58 to 0.88)
    0.50 (0.39 to 0.65)
    0.28 (0.22 to 0.37)
        1M after Vacc.,Serotype 6A (n=190,183,186,198)
    7.59 (6.67 to 8.63)
    31.99 (27.85 to 36.75)
    46.28 (39.90 to 53.67)
    20.03 (15.39 to 26.07)
        Before Vacc.,Serotype 6B (n=188,183,182,195)
    0.85 (0.71 to 1.02)
    0.52 (0.42 to 0.63)
    0.26 (0.20 to 0.32)
    0.40 (0.31 to 0.51)
        1M after Vacc.,Serotype 6B (n=190,183,186,198)
    4.27 (3.69 to 4.94)
    17.78 (15.43 to 20.48)
    32.45 (27.90 to 37.74)
    38.82 (31.49 to 47.86)
        Before Vacc.,Serotype 7F (n=189,183,186,198)
    1.17 (1.03 to 1.33)
    0.51 (0.44 to 0.60)
    0.18 (0.16 to 0.21)
    0.11 (0.08 to 0.14)
        1M after Vacc.,Serotype 7F (n=190,183,186,198)
    3.53 (3.16 to 3.94)
    6.42 (5.69 to 7.24)
    7.92 (7.03 to 8.93)
    3.19 (2.65 to 3.85)
        Before Vacc.,Serotype 9V (n=189,183,186,198)
    0.71 (0.61 to 0.83)
    0.35 (0.28 to 0.42)
    0.14 (0.11 to 0.17)
    0.14 (0.11 to 0.18)
        1M after Vacc.,Serotype 9V (n=190,183,186,198)
    2.70 (2.35 to 3.09)
    7.94 (6.83 to 9.24)
    10.86 (9.41 to 12.54)
    7.67 (6.52 to 9.02)
        Before Vacc.,Serotype 14 (n=188,183,186,198)
    1.53 (1.31 to 1.79)
    0.66 (0.53 to 0.81)
    0.42 (0.33 to 0.53)
    0.29 (0.23 to 0.37)
        1M after Vacc.,Serotype 14 (n=189,183,186,198)
    4.42 (3.82 to 5.12)
    14.60 (12.44 to 17.13)
    28.54 (24.77 to 32.89)
    28.17 (23.90 to 33.21)
        Before Vacc.,Serotype 18C (n=189,183,186,198)
    0.65 (0.55 to 0.76)
    0.26 (0.21 to 0.32)
    0.12 (0.09 to 0.14)
    0.13 (0.11 to 0.17)
        1M after Vacc.,Serotype 18C (n=190,183,186,198)
    2.69 (2.32 to 3.12)
    7.07 (6.01 to 8.32)
    10.83 (9.53 to 12.30)
    8.61 (7.34 to 10.10)
        Before Vacc.,Serotype 19A (n=189,183,186,198)
    0.47 (0.38 to 0.58)
    0.52 (0.40 to 0.68)
    0.78 (0.58 to 1.04)
    0.55 (0.43 to 0.70)
        1M after Vacc.,Serotype 19A (n=189,183,186,197)
    3.29 (2.89 to 3.76)
    12.48 (10.76 to 14.48)
    13.65 (11.96 to 15.59)
    8.89 (7.29 to 10.84)
        Before Vacc.,Serotype 19F (n=189,183,186,198)
    0.80 (0.67 to 0.94)
    0.56 (0.44 to 0.71)
    0.96 (0.70 to 1.32)
    0.82 (0.63 to 1.06)
        1M after Vacc.,Serotype 19F (n=190,183,186,198)
    4.16 (3.61 to 4.79)
    12.50 (10.48 to 14.91)
    14.62 (12.32 to 17.36)
    6.55 (5.60 to 7.66)
        Before Vacc.,Serotype 23F (n=189,183,186,198)
    0.96 (0.79 to 1.18)
    0.90 (0.71 to 1.15)
    0.82 (0.64 to 1.06)
    0.61 (0.48 to 0.78)
        1M after Vacc.,Serotype 23F (n=190,183,186,198)
    5.35 (4.55 to 6.30)
    16.18 (13.75 to 19.04)
    22.69 (19.40 to 26.53)
    19.16 (16.31 to 22.51)
        Before Vacc.,Serotype 8 (n=186,179,185,196)
    0.04 (0.03 to 0.05)
    0.05 (0.04 to 0.06)
    0.08 (0.07 to 0.10)
    0.16 (0.12 to 0.20)
        1M after Vacc.,Serotype 8 (n=190,182,186,198)
    4.66 (4.17 to 5.22)
    5.08 (4.45 to 5.80)
    4.65 (4.05 to 5.34)
    4.26 (3.67 to 4.94)
        Before Vacc.,Serotype 10A (n=188,183,186,198)
    0.01 (0.01 to 0.02)
    0.03 (0.02 to 0.03)
    0.07 (0.06 to 0.09)
    0.15 (0.12 to 0.19)
        1M after Vacc.,Serotype 10A (n=190,181,186,198)
    1.23 (1.02 to 1.48)
    2.76 (2.28 to 3.34)
    3.98 (3.25 to 4.88)
    5.35 (4.20 to 6.81)
        Before Vacc.,Serotype 11A (n=188,183,186,198)
    0.03 (0.02 to 0.03)
    0.06 (0.04 to 0.08)
    0.12 (0.09 to 0.16)
    0.30 (0.23 to 0.38)
        1M after Vacc.,Serotype 11A (n=190,182,186,198)
    1.61 (1.40 to 1.86)
    2.64 (2.25 to 3.09)
    2.80 (2.35 to 3.33)
    3.13 (2.60 to 3.77)
        Before Vacc.,Serotype 12F (n=188,183,186,198)
    0.01 (0.01 to 0.01)
    0.01 (0.01 to 0.01)
    0.01 (0.01 to 0.01)
    0.01 (0.01 to 0.01)
        1M after Vacc.,Serotype 12F (n=190,182,186,198)
    0.22 (0.18 to 0.27)
    0.38 (0.31 to 0.46)
    0.36 (0.29 to 0.44)
    0.28 (0.22 to 0.34)
        Before Vacc.,Serotype 15B (n=188,182,186,198)
    0.02 (0.02 to 0.03)
    0.05 (0.04 to 0.07)
    0.20 (0.15 to 0.27)
    0.35 (0.27 to 0.45)
        1M after Vacc.,Serotype 15B (n=190,181,186,198)
    1.17 (0.97 to 1.40)
    3.96 (3.12 to 5.03)
    10.74 (8.49 to 13.60)
    18.79 (15.16 to 23.28)
        Before Vacc.,Serotype 22F (n=188,183,186,198)
    0.01 (0.00 to 0.01)
    0.02 (0.01 to 0.02)
    0.08 (0.06 to 0.11)
    0.14 (0.11 to 0.19)
        1M after Vacc.,Serotype 22F (n=190,182,186,198)
    9.57 (8.12 to 11.29)
    12.46 (10.82 to 14.35)
    15.68 (13.45 to 18.29)
    12.36 (10.38 to 14.72)
        Before Vacc.,Serotype 33F (n=188,183,185,196)
    0.02 (0.01 to 0.02)
    0.04 (0.03 to 0.05)
    0.10 (0.08 to 0.12)
    0.18 (0.14 to 0.22)
        1M after Vacc.,Serotype 33F (n=190,182,185,197)
    1.91 (1.60 to 2.27)
    3.16 (2.63 to 3.79)
    3.87 (3.24 to 4.61)
    3.93 (3.25 to 4.75)
    No statistical analyses for this end point

    Secondary: GMFRs of Pneumococcal Serotype-Specific IgG Concentrations for the 13vPnC Serotypes From Before to 1 Month After Vaccination: Cohort 1 and 2

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    End point title
    		 GMFRs of Pneumococcal Serotype-Specific IgG Concentrations for the 13vPnC Serotypes From Before to 1 Month After Vaccination: Cohort 1 and 2 [14]
    End point description
    Pneumococcal serotype-specific IgG concentrations were measured from serum samples for 13vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. GMFR was calculated as geometric mean of fold rise from before vaccination on Day 1 to 1 month after vaccination with 20vPnC. GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titres or fold rises and the corresponding CIs (based on the Student t distribution). EIP included all subjects who were eligible; received 20vPnC; at least 1 valid immunogenicity result from 1 month after vaccination collected within 27 to 56 days after vaccination for Cohorts 1-2; no other major protocol deviations. Here, “Number of Subjects Analysed” signifies subjects included in the EIP and n=subjects with valid assay results at both timepoints for the specified serotype.
    End point type
    Secondary
    End point timeframe
    Before vaccination to 1 month after vaccination
    Notes
    [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
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years
    Number of subjects analysed
    190
    183
    Units: Fold-rise
    geometric mean (confidence interval 95%)
        Serotype 1 (n=189, 183)
    3.4 (3.0 to 3.9)
    20.6 (17.2 to 24.7)
        Serotype 3 (n=189, 183)
    3.9 (3.4 to 4.5)
    14.9 (12.4 to 17.9)
        Serotype 4 (n=189, 183)
    4.3 (3.7 to 5.0)
    27.6 (22.7 to 33.5)
        Serotype 5 (n=189, 183)
    3.6 (3.1 to 4.2)
    28.2 (23.0 to 34.6)
        Serotype 6A (n=188, 183)
    4.8 (4.1 to 5.6)
    44.9 (35.8 to 56.3)
        Serotype 6B (n=188, 183)
    5.0 (4.3 to 5.9)
    34.5 (28.3 to 42.0)
        Serotype 7F (n=189, 183)
    3.0 (2.7 to 3.4)
    12.5 (10.5 to 14.9)
        Serotype 9V (n=189, 183)
    3.8 (3.3 to 4.4)
    23.0 (19.0 to 27.8)
        Serotype 14 (n=187, 183)
    2.9 (2.5 to 3.3)
    22.2 (18.0 to 27.4)
        Serotype 18C (n=189, 183)
    4.2 (3.6 to 4.9)
    27.2 (22.5 to 32.9)
        Serotype 19A (n=188, 183)
    6.9 (5.7 to 8.4)
    24.1 (19.0 to 30.6)
        Serotype 19F (n=189, 183)
    5.2 (4.4 to 6.3)
    22.3 (17.2 to 28.8)
        Serotype 23F (n=189, 183)
    5.6 (4.8 to 6.6)
    17.9 (14.6 to 21.9)
    No statistical analyses for this end point

    Secondary: GMFRs of Pneumococcal Serotype-Specific IgG Concentrations for the 20vPnC Serotypes From Before to 1 Month After Vaccination: Cohort 3 and 4

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    End point title
    		 GMFRs of Pneumococcal Serotype-Specific IgG Concentrations for the 20vPnC Serotypes From Before to 1 Month After Vaccination: Cohort 3 and 4 [15]
    End point description
    Pneumococcal serotype-specific IgG concentrations were measured from serum samples for 13vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F; and 7 additional 20vPnC serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. GMFR was calculated as geometric mean of fold rise from before vaccination on Day 1 to 1 month after vaccination with 20vPnC. GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titres or fold rises and the corresponding CIs (based on the Student t distribution). EIP included all subjects who were eligible; received 20vPnC; at least 1 valid immunogenicity result from 1 month after vaccination collected within 27 to 49 days after vaccination for Cohorts 3-4; no other major protocol deviations. Here, “Number of Subjects Analysed” signifies subjects included in the EIP and n= subjects with valid assay results at both timepoints for the specified serotype.
    End point type
    Secondary
    End point timeframe
    Before vaccination to 1 month after vaccination
    Notes
    [15] - 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
    		 Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    186
    198
    Units: Fold-rise
    geometric mean (confidence interval 95%)
        Serotype: 1 (n=186, 198)
    49.4 (41.6 to 58.6)
    44.2 (37.0 to 52.9)
        Serotype: 3 (n=186, 198)
    5.9 (4.6 to 7.5)
    4.3 (3.5 to 5.2)
        Serotype: 4 (n=186, 198)
    74.1 (61.4 to 89.4)
    52.0 (42.3 to 64.0)
        Serotype: 5 (n=186, 198)
    107.0 (89.4 to 128.2)
    59.3 (47.6 to 73.9)
        Serotype: 6A (n=184, 195)
    91.9 (67.7 to 124.9)
    72.5 (54.9 to 95.7)
        Serotype: 6B (n=182, 195)
    127.9 (101.0 to 162.0)
    99.5 (77.1 to 128.3)
        Serotype: 7F (n=186, 198)
    42.9 (36.1 to 51.1)
    30.0 (24.0 to 37.6)
        Serotype: 9V (n=186, 198)
    80.3 (64.3 to 100.3)
    54.2 (42.7 to 68.9)
        Serotype: 14 (n=186, 198)
    68.4 (53.4 to 87.7)
    96.7 (76.6 to 122.1)
        Serotype: 18C (n=186, 198)
    93.7 (76.9 to 114.1)
    64.5 (52.3 to 79.4)
        Serotype: 19A (n=186, 197)
    17.6 (13.2 to 23.4)
    16.2 (13.1 to 20.0)
        Serotype: 19F (n=186, 198)
    15.2 (10.5 to 22.0)
    8.0 (6.0 to 10.7)
        Serotype: 23F (n=186, 198)
    27.6 (21.0 to 36.3)
    31.4 (23.8 to 41.5)
        Serotype: 8 (n=185, 196)
    55.2 (44.8 to 67.9)
    27.3 (21.9 to 33.9)
        Serotype: 10A (n=186, 198)
    54.8 (44.4 to 67.7)
    35.9 (29.3 to 43.9)
        Serotype: 11A (n=186, 198)
    23.6 (18.6 to 29.9)
    10.5 (8.5 to 12.9)
        Serotype: 12F (n=186, 198)
    31.9 (26.7 to 38.3)
    21.4 (17.6 to 26.0)
        Serotype: 15B (n=186, 198)
    52.6 (41.3 to 66.9)
    53.8 (43.1 to 67.1)
        Serotype: 22F (n=186, 198)
    187.7 (134.6 to 261.7)
    86.2 (64.9 to 114.4)
        Serotype: 33F (n=184, 195)
    39.3 (31.6 to 49.0)
    22.4 (18.2 to 27.6)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With >=4-fold Rise in Pneumococcal Serotype-Specific OPA Titres for the 7 Additional Serotypes From Before to 1 Month After Vaccination: Cohorts 2, 3, and 4 Only

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    End point title
    		 Percentage of Subjects With >=4-fold Rise in Pneumococcal Serotype-Specific OPA Titres for the 7 Additional Serotypes From Before to 1 Month After Vaccination: Cohorts 2, 3, and 4 Only [16]
    End point description
    Pneumococcal serotype-specific OPA titres were measured from serum samples for 7 additional 20vPnC serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. Percentage of subjects with >=4 fold rise in serotype-specific OPA titres from before vaccination to 1 month after vaccination with 20vPnC and the associated 2-sided 95% CI based on the Clopper and Pearson method was presented. EIP included all subjects who were eligible; received 20vPnC; at least 1 valid immunogenicity result from 1 month after vaccination collected within 27 to 56 days or 27 to 49 days after vaccination for Cohort 2 or Cohorts 3-4, respectively; no other major protocol deviations. Here, “Number of Subjects Analysed” signifies subjects included in the EIP and n=subjects with valid assay results at both timepoints for the specified serotype.
    End point type
    Secondary
    End point timeframe
    Before vaccination to 1 month after vaccination
    Notes
    [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
    		 Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    183
    186
    198
    Units: Percentage of subjects
    number (confidence interval 95%)
        Serotype: 8 (n=74, 153, 174)
    93.2 (84.9 to 97.8)
    92.2 (86.7 to 95.9)
    89.1 (83.5 to 93.3)
        Serotype: 10A (n=73, 134, 142)
    84.9 (74.6 to 92.2)
    80.6 (72.9 to 86.9)
    81.7 (74.3 to 87.7)
        Serotype: 11A (n=52, 136, 155)
    86.5 (74.2 to 94.4)
    66.2 (57.6 to 74.1)
    62.6 (54.5 to 70.2)
        Serotype: 12F (n=74, 154, 164)
    94.6 (86.7 to 98.5)
    96.8 (92.6 to 98.9)
    94.5 (89.8 to 97.5)
        Serotype: 15B (n=76, 142, 164)
    88.2 (78.7 to 94.4)
    89.4 (83.2 to 94.0)
    93.9 (89.1 to 97.0)
        Serotype: 22F (n=68, 137, 168)
    86.8 (76.4 to 93.8)
    87.6 (80.9 to 92.6)
    81.0 (74.2 to 86.6)
        Serotype: 33F (n=73, 144, 158)
    71.2 (59.4 to 81.2)
    79.9 (72.4 to 86.1)
    75.3 (67.8 to 81.8)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers (GMTs) of Pneumococcal Serotype-Specific OPA Titers for the 20vPnC Serotypes Before and 1 Month After Vaccination

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    End point title
    		 Geometric Mean Titers (GMTs) of Pneumococcal Serotype-Specific OPA Titers for the 20vPnC Serotypes Before and 1 Month After Vaccination
    End point description
    Pneumococcal serotype-specific OPA titres were measured from serum samples for 13vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F; and 7 additional 20vPnC serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. GMTs and 2-sided CIs were calculated by exponentiating the mean logarithm of the titres and the corresponding CIs (based on the Student t distribution). EIP included all subjects who were eligible; received 20vPnC; at least 1 valid immunogenicity result from 1 month after vaccination collected within 27 to 56 days or 27 to 49 days after vaccination for Cohorts 1-2 or Cohorts 3-4,respectively; no other major protocol deviations. Here, “Number of Subjects Analysed” signifies subjects included in the EIP and n=subjects with valid OPA titres at the specified timepoint.
    End point type
    Secondary
    End point timeframe
    Before vaccination (Vacc.) and 1 month after vaccination (1M after Vacc.)
    End point values
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    190
    183
    186
    198
    Units: Titer
    geometric mean (confidence interval 95%)
        Before Vacc., Serotype 1 (n=46, 47, 93, 96)
    14 (11 to 18)
    12 (10 to 14)
    10 (9 to 11)
    11 (9 to 12)
        1M after Vacc.Serotype 1 (n=44,46, 93, 96)
    57 (39 to 84)
    360 (272 to 476)
    548 (455 to 660)
    396 (302 to 519)
        Before Vacc., Serotype 3 (n=46, 47, 94, 95)
    21 (15 to 29)
    15 (11 to 22)
    29 (22 to 40)
    19 (14 to 24)
        1M after Vacc.Serotype 3 (n=44, 46, 92, 94)
    80 (62 to 103)
    150 (116 to 195)
    155 (135 to 178)
    105 (88 to 124)
        Before Vacc., Serotype: 4 (n=41, 45, 82, 86)
    42 (24 to 75)
    34 (19 to 62)
    43 (27 to 67)
    34 (22 to 51)
        1M after Vacc.Serotype 4 (n=43, 44, 88, 93)
    563 (342 to 927)
    1729 (1188 to 2516)
    2328 (1942 to 2789)
    2290 (1822 to 2878)
        Before Vacc., Serotype: 5 (n=46,47, 94, 96)
    18 (16 to 21)
    17 (15 to 20)
    15 (15 to 15)
    15 (15 to 16)
        1M after Vacc.Serotype 5, (n=44, 46, 92, 96)
    51 (38 to 68)
    198 (143 to 276)
    385 (324 to 458)
    216 (159 to 294)
        Before Vacc., Serotype: 6A (n=46, 47, 90, 91)
    137 (77 to 243)
    96 (55 to 168)
    74 (51 to 106)
    64 (44 to 91)
        1M after Vacc.Serotype 6A (n=43, 46, 92, 96)
    1707 (1144 to 2547)
    5283 (3954 to 7060)
    8268 (6617 to 10331)
    9434 (7616 to 11686)
        Before Vacc., Serotype: 6B (n=44, 43, 78, 90)
    110 (67 to 182)
    126 (72 to 219)
    156 (99 to 244)
    237 (155 to 363)
        1M after Vacc.Serotype 6B (n=44, 46, 90, 93)
    943 (611 to 1455)
    3273 (2390 to 4482)
    6569 (5367 to 8040)
    10085 (8263 to 12309)
        Before Vacc., Serotype 7F (n=41, 45, 81, 86)
    705 (492 to 1010)
    996 (748 to 1327)
    541 (410 to 713)
    516 (381 to 698)
        1M after Vacc.Serotype 7F (n=42, 44, 87, 93)
    2635 (2105 to 3297)
    3409 (2552 to 4556)
    3981 (3446 to 4598)
    3326 (2878 to 3843)
        Before Vacc., Serotype: 9V (n=39, 45, 84, 92)
    649 (350 to 1204)
    323 (202 to 515)
    410 (289 to 580)
    469 (330 to 667)
        1M after Vacc.Serotype 9V (n=43, 44, 87, 93)
    7686 (5718 to 10332)
    7210 (4781 to 10876)
    11717 (9262 to 14823)
    9627 (7492 to 12369)
        Before Vacc., Serotype: 14 (n=46, 44, 90, 92)
    242 (151 to 387)
    300 (186 to 484)
    246 (172 to 353)
    97 (65 to 145)
        1M after Vacc.Serotype 14 (n=44, 46, 93, 96)
    1018 (748 to 1385)
    2506 (1932 to 3249)
    4610 (3688 to 5762)
    3925 (3153 to 4885)
        Before Vacc., Serotype: 18C (n=38, 44, 76, 87)
    300 (147 to 613)
    139 (69 to 277)
    152 (89 to 261)
    73 (45 to 119)
        1M after Vacc.Serotype 18C (n=43, 44, 87, 93)
    3749 (2740 to 5131)
    5344 (3809 to 7498)
    6766 (5585 to 8197)
    3617 (2816 to 4645)
        Before Vacc., Serotype: 19A (n=40, 47, 86, 90)
    138 (71 to 271)
    84 (45 to 156)
    117 (76 to 181)
    66 (44 to 100)
        1M after Vacc.Serotype: 19A (n=43, 44, 88, 93)
    1708 (1192 to 2448)
    2640 (1943 to 3587)
    2162 (1786 to 2618)
    2212 (1801 to 2717)
        Before Vacc., Serotype: 19F (n=45, 47, 94, 93)
    44 (31 to 61)
    44 (31 to 61)
    91 (66 to 125)
    57 (44 to 73)
        1M after Vacc.Serotype 19F (n=44, 46, 92, 96)
    267 (169 to 421)
    928 (618 to 1394)
    1095 (810 to 1479)
    551 (401 to 757)
        Before Vacc., Serotype 23F (n=41, 46, 87, 92)
    139 (67 to 288)
    206 (108 to 394)
    87 (53 to 145)
    46 (29 to 73)
        1M after Vacc.Serotype 23F (n=43, 44, 88, 93)
    1936 (1385 to 2707)
    2493 (1757 to 3539)
    2213 (1751 to 2797)
    1842 (1391 to 2439)
        Before Vacc., Serotype: 8 (n=86, 82, 164, 185)
    30 (24 to 39)
    39 (29 to 54)
    34 (28 to 42)
    35 (28 to 43)
        1M after Vacc.Serotyp 8 (n=85, 80, 175, 187)
    4758 (3763 to 6016)
    4428 (3467 to 5654)
    3870 (3302 to 4535)
    3125 (2680 to 3642)
        Before Vacc., Serotype: 10A (n=84, 82, 158, 168)
    92 (60 to 141)
    275 (160 to 472)
    745 (519 to 1071)
    554 (395 to 777)
        1M after Vacc.Serotype 10A (n=86, 78, 159, 171)
    10626 (7825 to 14429)
    14345 (10473 to 19649)
    21102 (17238 to 25833)
    17417 (14301 to 21214)
        Before Vacc., Serotype 11A (n=68, 60, 147, 165)
    88 (60 to 127)
    436 (237 to 800)
    1347 (962 to 1887)
    765 (543 to 1076)
        1M after Vacc.Serotype: 11A (n=84, 78, 172, 186)
    13350 (10540 to 16910)
    14093 (9904 to 20054)
    16882 (13650 to 20880)
    11677 (9751 to 13982)
        Serotype: 12F (n=92, 86, 174, 182)
    38 (29 to 50)
    37 (27 to 50)
    48 (38 to 60)
    46 (36 to 59)
        1M after Vacc.Serotype: 12F (n=84, 76, 164, 180)
    16924 (13400 to 21376)
    13257 (9463 to 18572)
    23860 (19002 to 29959)
    20250 (16861 to 24320)
        Before Vacc., Serotype: 15B (n=94, 84, 163, 187)
    30 (21 to 45)
    111 (63 to 197)
    79 (54 to 115)
    45 (33 to 61)
        1M after Vacc.Serotype: 15B (n=86, 80, 163, 174)
    22951 (17380 to 30307)
    27095 (19557 to 37538)
    25729 (19647 to 33695)
    21496 (16697 to 27672)
        Before Vacc., Serotype: 22F (n=87, 80, 161, 184)
    21 (13 to 33)
    104 (55 to 194)
    259 (170 to 394)
    243 (161 to 366)
        1M after Vacc.Serotype 22F (n=81, 74, 158, 179)
    22464 (16840 to 29967)
    25573 (18096 to 36141)
    33615 (26198 to 43130)
    27922 (22622 to 34463)
        Before Vacc., Serotype: 33F (n=91, 85, 170, 177)
    1154 (861 to 1548)
    2179 (1694 to 2804)
    3334 (2847 to 3905)
    2895 (2448 to 3424)
        1M after Vacc.Serotype 33F (n=81, 76, 155, 171)
    23431 (17375 to 31598)
    28076 (19255 to 40938)
    45921 (36768 to 57353)
    32363 (26219 to 39946)
    No statistical analyses for this end point

    Secondary: GMFRs of Pneumococcal Serotype-Specific OPA Titres for the 20vPnC Serotypes From Before to 1 Month After Vaccination: Cohorts 1 and 2

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    End point title
    		 GMFRs of Pneumococcal Serotype-Specific OPA Titres for the 20vPnC Serotypes From Before to 1 Month After Vaccination: Cohorts 1 and 2 [17]
    End point description
    Pneumococcal serotype-specific OPA titres were measured from serum samples for 13vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F; and 7 additional 20vPnC serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. GMFR was calculated as geometric mean of fold rise from before vaccination on Day 1 to 1 month after vaccination with 20vPnC. GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titres or fold rises and the corresponding CIs (based on the Student t distribution). EIP included all subjects who were eligible; received 20vPnC; at least 1 valid immunogenicity result from 1 month after vaccination collected within 27 to 56 days after vaccination for Cohorts 1-2; no other major protocol deviations. Here, 'Number of Subjects Analysed' signifies subjects included in the EIP and n=subjects with valid assay results at both timepoints for the specified serotype.
    End point type
    Secondary
    End point timeframe
    Before vaccination to 1 month after vaccination
    Notes
    [17] - 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
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years
    Number of subjects analysed
    190
    183
    Units: Fold rise
    geometric mean (confidence interval 95%)
        Serotype 1 (n=42, 46)
    4.1 (2.9 to 6.0)
    29.8 (21.2 to 41.9)
        Serotype 3 (n=42, 46)
    3.7 (2.6 to 5.3)
    9.6 (7.1 to 13.1)
        Serotype 4 (n=40, 41)
    13.2 (7.0 to 25.0)
    50.0 (26.7 to 93.6)
        Serotype 5 (n=42, 46)
    2.8 (2.0 to 3.8)
    11.4 (8.2 to 16.0)
        Serotype 6A (n=41, 46)
    12.7 (8.1 to 20.0)
    52.9 (30.8 to 90.9)
        Serotype 6B (n=40, 42)
    7.8 (4.6 to 13.2)
    24.4 (14.4 to 41.2)
        Serotype 7F (n=39, 41)
    3.6 (2.5 to 5.2)
    3.6 (2.7 to 4.8)
        Serotype 9V (n=38, 42)
    11.5 (6.2 to 21.3)
    23.1 (14.7 to 36.5)
        Serotype 14 (n=42, 43)
    3.9 (2.5 to 6.1)
    8.3 (5.1 to 13.4)
        Serotype 18C (n=38, 40)
    12.7 (6.6 to 24.5)
    40.6 (20.7 to 79.6)
        Serotype 19A (n=39, 43)
    11.1 (6.2 to 19.8)
    33.5 (17.3 to 65.0)
        Serotype 19F (n=41, 46)
    5.7 (3.3 to 9.7)
    21.0 (13.0 to 33.9)
        Serotype 23F (n=40, 42)
    12.5 (6.7 to 23.6)
    10.7 (6.2 to 18.5)
        Serotype 8 (n=76, 74)
    155.9 (110.4 to 220.2)
    105.4 (67.6 to 164.3)
        Serotype 10A (n=76, 73)
    121.7 (74.7 to 198.4)
    53.3 (28.7 to 99.0)
        Serotype 11A (n=60, 52)
    161.4 (115.7 to 225.2)
    34.7 (17.1 to 70.4)
        Serotype 12F (n=81, 74)
    437.2 (307.0 to 622.7)
    319.9 (193.9 to 527.9)
        Serotype 15B (n=84, 76)
    717.6 (449.8 to 1144.6)
    294.4 (149.1 to 581.3)
        Serotype 22F (n=74, 68)
    983.6 (580.9 to 1665.5)
    224.6 (104.9 to 480.9)
        Serotype 33F (n=78, 73)
    18.8 (13.1 to 27.2)
    12.4 (7.4 to 20.7)
    No statistical analyses for this end point

    Secondary: GMFRs of Pneumococcal Serotype-Specific OPA Titres for the 13vPnC Serotypes From Before to 1 Month After Vaccination: Cohorts 3 and 4

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    End point title
    		 GMFRs of Pneumococcal Serotype-Specific OPA Titres for the 13vPnC Serotypes From Before to 1 Month After Vaccination: Cohorts 3 and 4 [18]
    End point description
    Pneumococcal serotype-specific OPA titres were measured for 13vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. GMFR was calculated as geometric mean of fold rise from before vaccination on Day 1 to 1 month after vaccination with 20vPnC. GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titres or fold rises and the corresponding CIs (based on the Student t distribution). EIP included all subjects who were eligible; received 20vPnC; at least 1 valid immunogenicity result from 1 month after vaccination collected within 27 to 49 days after vaccination for Cohorts 3-4; no other major protocol deviations. Here, “Number of Subjects Analysed” signifies subjects included in the EIP and n=subjects with valid assay results at both timepoints for the specified serotype.
    End point type
    Secondary
    End point timeframe
    Before vaccination to 1 month after vaccination
    Notes
    [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
    		 Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Number of subjects analysed
    186
    198
    Units: Fold rise
    geometric mean (confidence interval 95%)
        Serotype 1 (n=91, 96)
    55.2 (45.1 to 67.4)
    37.3 (28.7 to 48.6)
        Serotype 3 (n=91, 93)
    5.3 (3.9 to 7.2)
    5.8 (4.5 to 7.5)
        Serotype 4 (n=80, 86)
    50.2 (31.6 to 79.5)
    65.6 (41.4 to 103.7)
        Serotype 5 (n=91, 96)
    26.7 (22.4 to 31.8)
    14.4 (10.5 to 19.6)
        Serotype 6A (n=87, 91)
    110.3 (68.7 to 177.1)
    147.9 (96.0 to 228.0)
        Serotype 6B (n=73, 87)
    38.8 (22.7 to 66.3)
    42.0 (26.1 to 67.6)
        Serotype 7F (n=78, 86)
    7.0 (5.3 to 9.3)
    6.2 (4.4 to 8.8)
        Serotype 9V (n=82, 92)
    28.9 (19.7 to 42.5)
    20.4 (13.4 to 31.0)
        Serotype 14 (n=88, 92)
    18.1 (12.2 to 26.8)
    38.9 (25.1 to 60.3)
        Serotype 18C (n=74, 87)
    46.2 (26.8 to 79.6)
    47.3 (28.7 to 78.0)
        Serotype 19A (n=84, 90)
    17.5 (10.8 to 28.3)
    33.1 (20.7 to 53.1)
        Serotype 19F (n=91, 93)
    11.7 (7.4 to 18.5)
    10.0 (6.7 to 15.0)
        Serotype 23F (n=85, 92)
    26.9 (16.3 to 44.5)
    39.4 (23.7 to 65.7)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Local reactions and systemic events (systematic assessment): within 7 days after vaccination; SAEs (non-systematic assessment): from Day1 up to 6 months after vaccination and other AEs (non-systematic assessment): from Day1 up to 1 month after vaccination
    Adverse event reporting additional description
    The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Cohort 1: 20vPnC: >=15 to <24 Months
    Reporting group description
    		 Subjects aged >=15 months to <24 months who have been previously vaccinated with at least 3 doses of 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly on Day 1.

    Reporting group title
    Cohort 2: 20vPnC: >=2 to <5 Years
    Reporting group description
    		 Subjects aged >=2 to <5 years who have been previously vaccinated with at least 3 doses of 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly on Day 1.

    Reporting group title
    Cohort 3: 20vPnC: >=5 to <10 Years
    Reporting group description
    		 Subjects aged >=5 to <10 years regardless of previous vaccination status with 7vPnC or 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly into the left arm on Day 1.

    Reporting group title
    Cohort 4: 20vPnC: >=10 to <18 Years
    Reporting group description
    		 Subjects aged >=10 to <18 years regardless of previous vaccination status with 7vPnC or 13vPnC, were administered a single dose of 0.5 mL 20vPnC intramuscularly into the left arm on Day 1.

    Serious adverse events
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 209 (0.96%)
    0 / 216 (0.00%)
    0 / 201 (0.00%)
    3 / 205 (1.46%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 209 (0.00%)
    0 / 216 (0.00%)
    0 / 201 (0.00%)
    1 / 205 (0.49%)
         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
    Injury, poisoning and procedural complications
    Near drowning
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 216 (0.00%)
    0 / 201 (0.00%)
    0 / 205 (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
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 209 (0.00%)
    0 / 216 (0.00%)
    0 / 201 (0.00%)
    1 / 205 (0.49%)
         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
    Febrile convulsion
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 216 (0.00%)
    0 / 201 (0.00%)
    0 / 205 (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
    Appendicitis
         subjects affected / exposed
    0 / 209 (0.00%)
    0 / 216 (0.00%)
    0 / 201 (0.00%)
    1 / 205 (0.49%)
         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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1: 20vPnC: >=15 to <24 Months Cohort 2: 20vPnC: >=2 to <5 Years Cohort 3: 20vPnC: >=5 to <10 Years Cohort 4: 20vPnC: >=10 to <18 Years
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    173 / 209 (82.78%)
    163 / 216 (75.46%)
    178 / 201 (88.56%)
    186 / 205 (90.73%)
    Nervous system disorders
    Headache (HEADACHE)
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 209 (0.00%)
    12 / 216 (5.56%)
    37 / 201 (18.41%)
    60 / 205 (29.27%)
         occurrences all number
    0
    13
    45
    75
    Hypersomnia (INCREASED SLEEP)
    alternative assessment type: Systematic
         subjects affected / exposed
    85 / 209 (40.67%)
    0 / 216 (0.00%)
    0 / 201 (0.00%)
    0 / 205 (0.00%)
         occurrences all number
    104
    0
    0
    0
    General disorders and administration site conditions
    Injection site erythema (REDNESS)
    alternative assessment type: Systematic
         subjects affected / exposed
    77 / 209 (36.84%)
    84 / 216 (38.89%)
    74 / 201 (36.82%)
    31 / 205 (15.12%)
         occurrences all number
    84
    86
    79
    32
    Injection site pain (PAIN)
    alternative assessment type: Systematic
         subjects affected / exposed
    107 / 209 (51.20%)
    142 / 216 (65.74%)
    165 / 201 (82.09%)
    168 / 205 (81.95%)
         occurrences all number
    115
    157
    178
    175
    Injection site swelling (SWELLING)
    alternative assessment type: Systematic
         subjects affected / exposed
    45 / 209 (21.53%)
    50 / 216 (23.15%)
    54 / 201 (26.87%)
    32 / 205 (15.61%)
         occurrences all number
    51
    54
    57
    34
    Pyrexia (FEVER)
    alternative assessment type: Systematic
         subjects affected / exposed
    24 / 209 (11.48%)
    7 / 216 (3.24%)
    1 / 201 (0.50%)
    0 / 205 (0.00%)
         occurrences all number
    25
    9
    1
    0
    Fatigue (FATIGUE)
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 209 (0.00%)
    80 / 216 (37.04%)
    56 / 201 (27.86%)
    57 / 205 (27.80%)
         occurrences all number
    0
    98
    76
    66
    Psychiatric disorders
    Irritability (IRRITABILITY)
    alternative assessment type: Systematic
         subjects affected / exposed
    126 / 209 (60.29%)
    0 / 216 (0.00%)
    0 / 201 (0.00%)
    0 / 205 (0.00%)
         occurrences all number
    170
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia (JOINT PAIN)
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 209 (0.00%)
    8 / 216 (3.70%)
    13 / 201 (6.47%)
    17 / 205 (8.29%)
         occurrences all number
    0
    9
    14
    17
    Myalgia (MUSCLE PAIN)
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 209 (0.00%)
    57 / 216 (26.39%)
    78 / 201 (38.81%)
    99 / 205 (48.29%)
         occurrences all number
    0
    63
    86
    108
    Metabolism and nutrition disorders
    Decreased appetite (DECREASED APPETITE)
    alternative assessment type: Systematic
         subjects affected / exposed
    51 / 209 (24.40%)
    0 / 216 (0.00%)
    0 / 201 (0.00%)
    0 / 205 (0.00%)
         occurrences all number
    72
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Oct 2021
    -To be consistent with the European PIP modification approved in August 2021 added 2 secondary immunogenicity endpoints. -Added 2 exploratory immunogenicity endpoints for additional description of the immune response. - Clarified that the primary immunogenicity endpoints and the additional secondary endpoints are addressing consistencies with the approved European PIP modification.

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

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

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