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    Clinical Trial Results:
    A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Adults 50 Years of Age or Older (PNEU-AGE)

    Summary
    EudraCT number
    		 2018-004316-22
    Trial protocol
    		 ES  
    Global end of trial date
    02 Jul 2020

    Results information
    Results version number
    		 v2(current)
    This version publication date
    23 May 2021
    First version publication date
    10 Mar 2021
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    V114-019
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03950622
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 JAPIC-CTI: 194845, Study Acronym: PNEU-AGE
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Mar 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Mar 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jul 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to 1) evaluate the safety and tolerability of V114 and 2) to compare the immune responses of the 15 serotypes contained in V114 with V114 versus Prevnar 13™. The primary hypotheses are that 1) V114 is noninferior to Prevnar 13™ as measured by the serotype specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) for 13 shared serotypes at 30 days postvaccination and that 2) V114 is superior to Prevnar 13™ as measured by serotype-specific OPA GMTs for 2 unique serotypes in V114 at 30 days postvaccination.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Jun 2019
    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
    Canada: 188
    Country: Number of subjects enrolled
    Japan: 245
    Country: Number of subjects enrolled
    Spain: 100
    Country: Number of subjects enrolled
    Taiwan: 40
    Country: Number of subjects enrolled
    United States: 632
    Worldwide total number of subjects
    1205
    EEA total number of subjects
    100
    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)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    374
    From 65 to 84 years
    826
    85 years and over
    5

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 1200 participants were planned to be enrolled/randomized.

    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
    		 V114
    Arm description
    		 Participants received a single 0.5 mL intramuscular (IM) injection of V114 on Day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    V114
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F in each 0.5 mL dose.

    Arm title
    		 Prevnar 13™
    Arm description
    		 Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Prevnar 13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F in each 0.5 mL dose.

    Number of subjects in period 1
    		V114 Prevnar 13™
    Started
    604
    601
    Vaccinated
    602
    600
    Completed
    596
    594
    Not completed
    8
    7
         Adverse event, serious fatal
    1
    1
         Consent withdrawn by subject
    1
    -
         Physician decision
    1
    -
         Protocol Deviation
    -
    1
         Lost to follow-up
    5
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    V114
    Reporting group description
    		 Participants received a single 0.5 mL intramuscular (IM) injection of V114 on Day 1.

    Reporting group title
    Prevnar 13™
    Reporting group description
    		 Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.

    Reporting group values
    		 V114 Prevnar 13™ Total
    Number of subjects
    		 604 601 1205
    Age categorical
    Units: Participants
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 187 187 374
        From 65-84 years
    		 412 414 826
        85 years and over
    		 5 0 5
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 66.2 ( 7.7 ) 65.7 ( 7.4 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 359 332 691
        Male
    		 245 269 514
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 1
        Asian
    		 150 152 302
        Native Hawaiian or Other Pacific Islander
    		 1 0 1
        Black or African American
    		 36 37 73
        White
    		 410 407 817
        More than one race
    		 7 4 11
        Unknown or Not Reported
    		 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 135 129 264
        Not Hispanic or Latino
    		 469 471 940
        Unknown or Not Reported
    		 0 1 1

    End points

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    End points reporting groups
    Reporting group title
    V114
    Reporting group description
    		 Participants received a single 0.5 mL intramuscular (IM) injection of V114 on Day 1.

    Reporting group title
    Prevnar 13™
    Reporting group description
    		 Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1.

    Primary: Percentage of Participants with a Solicited Injection-site Adverse Event

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    End point title
    		 Percentage of Participants with a Solicited Injection-site Adverse Event
    End point description
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs consist of redness/erythema, swelling, and tenderness/pain. The analysis population included all randomized participants who received study vaccination and were included in the intervention group according to the intervention they received.
    End point type
    Primary
    End point timeframe
    Up to Day 5 postvaccination
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    602
    600
    Units: Percentage of Participants
    number (not applicable)
        Injection site erythema
    9.0
    11.3
        Injection site pain
    54.0
    42.3
        Injection site swelling
    12.5
    11.2
    Statistical analysis title
    		 Injection site redness/erythema
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    P-value
    		 = 0.175
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percent
    Point estimate
    -2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.8
         upper limit
    		 1.1
    Notes
    [1] - Estimated differences, confidence intervals (CIs), and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.
    Statistical analysis title
    		 Injection site tenderness/pain
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    P-value
    		 < 0.001
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percent
    Point estimate
    11.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6
         upper limit
    		 17.2
    Notes
    [2] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.
    Statistical analysis title
    		 Injection site swelling
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    P-value
    		 = 0.488
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percent
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 5
    Notes
    [3] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

    Primary: Percentage of Participants with Solicited Systemic Adverse Events

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    End point title
    		 Percentage of Participants with Solicited Systemic Adverse Events
    End point description
    An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following vaccination with V114 or Prevnar 13™, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. The analysis population included all randomized participants who received study vaccination and were included in the intervention group according to the intervention they received.
    End point type
    Primary
    End point timeframe
    Up to Day 14 postvaccination
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    602
    600
    Units: Percentage of Participants
    number (not applicable)
        Joint pain/arthralgia
    5.3
    5.5
        Tiredness/fatigue
    17.4
    17.3
        Headache
    11.6
    13.0
        Muscle pain/myalgia
    15.4
    12.0
    Statistical analysis title
    		 Joint pain/arthralgia
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    P-value
    		 = 0.888
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percent
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 2.4
    Notes
    [4] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.
    Statistical analysis title
    		 Tiredness/fatigue
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [5]
    P-value
    		 = 0.96
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percent
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.2
         upper limit
    		 4.4
    Notes
    [5] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.
    Statistical analysis title
    		 Headache
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [6]
    P-value
    		 = 0.469
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percent
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.1
         upper limit
    		 2.4
    Notes
    [6] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.
    Statistical analysis title
    		 Muscle pain/myalgia
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [7]
    P-value
    		 = 0.082
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percent
    Point estimate
    3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 7.4
    Notes
    [7] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

    Primary: Percentage of Participants with a Vaccine-related Serious Adverse Event

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    End point title
    		 Percentage of Participants with a Vaccine-related Serious Adverse Event
    End point description
    A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. SAEs that are reported to be at least possibly related by the investigator to study vaccination will be summarized. The analysis population included all randomized participants who received study vaccination and were included in the intervention group according to the intervention they received.
    End point type
    Primary
    End point timeframe
    Up to Month 6
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    602
    600
    Units: Percentage of Participants
        number (not applicable)
    0.0
    0.0
    Statistical analysis title
    		 Vaccine-related SAEs
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [8]
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percent
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.6
    Notes
    [8] - Estimated differences and CIs are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

    Primary: Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at Day 30

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    End point title
    		 Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at Day 30
    End point description
    Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) (estimated) and GMT ratios with 95% CIs were calculated using a constrained longitudinal data analysis (cLDA) model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMT ratios); within-group CIs were not calculated. OPA for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) were determined using a multiplexed opsonophagocytic assay (MOPA). The measure type of “number” presented in the data table below for serotype-specific OPA titer is the geometric mean. The analysis population included all randomized participants without protocol deviations, such as failure to receive study vaccine or receipt of prohibited medication prior to study vaccination.
    End point type
    Primary
    End point timeframe
    Day 30
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    602
    600
    Units: Titers
    number (not applicable)
        Serotype 1 (Shared) (n=598, 598)
    256.3
    322.6
        Serotype 3 (Shared) (n=598, 598)
    216.2
    135.1
        Serotype 4 (Shared) (n=598, 598)
    1125.6
    1661.6
        Serotype 5 (Shared) (n=598, 598)
    447.3
    563.5
        Serotype 6A (Shared) (n=596, 598)
    5407.2
    5424.5
        Serotype 6B (Shared) (n=598, 598)
    4011.7
    3258.2
        Serotype 7F (Shared) (n=597, 598)
    4617.3
    5880.6
        Serotype 9V (Shared) (n=598, 597)
    1817.3
    2232.9
        Serotype 14 (Shared) (n=598, 598)
    1999.3
    2656.7
        Serotype 18C (Shared) (n=598, 598)
    2757.7
    2583.7
        Serotype 19A (Shared) (n=598, 598)
    3194.3
    3979.8
        Serotype 19F (Shared) (n=598, 598)
    1695.1
    1917.8
        Serotype 23F (Shared) (n=598, 598)
    2045.4
    1740.4
        Serotype 22F (Unique to V114) (n=594, 586)
    2375.2
    74.6
        Serotype 33F (Unique to V114) (n=598, 597)
    7994.7
    1124.9
    Statistical analysis title
    		 Serotype 1 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [9]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 0.96
    Notes
    [9] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a constrained longitudinal data analysis (cLDA) model.
    Statistical analysis title
    		 Serotype 3 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [10]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.38
         upper limit
    		 1.85
    Notes
    [10] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 4 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [11]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 0.8
    Notes
    [11] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% CI of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 5 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [12]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.98
    Notes
    [12] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 6A (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [13]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.19
    Notes
    [13] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 6B (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [14]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 1.48
    Notes
    [14] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 7F (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [15]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 0.9
    Notes
    [15] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 9V (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [16]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 0.94
    Notes
    [16] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 14 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [17]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.89
    Notes
    [17] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 18C (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [18]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.26
    Notes
    [18] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 19A (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [19]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 0.93
    Notes
    [19] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 19F (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [20]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.02
    Notes
    [20] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 23F (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [21]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    1.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.44
    Notes
    [21] - The statistical criterion for noninferiority requires the lower bound of the 2-sided 95% confidence interval (CI) of the OPA GMT ratio (V114/ Prevnar 13™) to be greater than 0.5. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 22F (Unique to V114)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [22]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    31.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 25.35
         upper limit
    		 39.97
    Notes
    [22] - The statistical criterion for superiority requires the lower bound of the 2-sided 95% CI of the OPA GMT ratio [V114/ Prevnar 13™] to be greater than 2.0. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 33F (Unique to V114)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [23]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    7.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.07
         upper limit
    		 8.32
    Notes
    [23] - The statistical criterion for superiority requires the lower bound of the 2-sided 95% CI of the OPA GMT ratio [V114/ Prevnar 13™] to be greater than 2.0. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.

    Primary: Percentage of Participants with ≥4-Fold Rise in Serotype-specific OPA for 2 Unique V114 Serotypes

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    End point title
    		 Percentage of Participants with ≥4-Fold Rise in Serotype-specific OPA for 2 Unique V114 Serotypes
    End point description
    Activity for the serotypes contained in Prevnar 13™ and V114 was determined using a multiplexed opsonophagocytic assay (MOPA). The percentage of participants who had ≥4-fold rise in OPA titers were calculated from baseline (Day 1) to 30 days postvaccination (Day 30) for OPA responses for the 2 unique serotypes in V114. The observed response percentage (m/n) included: m=the number of participants with the indicated response divided by n=the number of participants contributing to the analysis. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the percentage point difference); within-group CIs were not calculated.
    End point type
    Primary
    End point timeframe
    Day 1 (Baseline) and Day 30
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    602
    600
    Units: Percentage of Participants
    number (not applicable)
        Serotype 22F (Unique to V114) (n=524, 498)
    71.4
    14.3
        Serotype 33F (Unique to V114)(n=578, 560)
    56.7
    6.3
    Statistical analysis title
    		 Serotype 22F (Unique to V114)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [24]
    P-value
    		 < 0.001
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Percentage Point Difference
    Point estimate
    57.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 52
         upper limit
    		 61.8
    Notes
    [24] - The statistical criterion for superiority requires the lower bound of the 2-sided 95% CI of the differences [V114 - Prevnar 13™] between the proportions of participants with a ≥4-fold rise from prevaccination [Day 1] to 30 days postvaccination [Day 30] to be greater than 0.1. Estimated difference, 95% CI, and p-value are based on the stratified Miettinen & Nurminen method.
    Statistical analysis title
    		 Serotype 33F (Unique to V114)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [25]
    P-value
    		 < 0.001
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Percentage Point Difference
    Point estimate
    50.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 45.9
         upper limit
    		 54.9
    Notes
    [25] - The statistical criterion for superiority requires the lower bound of the 2-sided 95% CI of the differences [V114 - Prevnar 13™] between the proportions of participants with a ≥4-fold rise from prevaccination [Day 1] to 30 days postvaccination [Day 30] to be greater than 0.1). Estimated difference, 95% CI, and p-value are based on the stratified Miettinen & Nurminen method.

    Secondary: GMT of Serotype-specific OPA for Serotype 3 at Day 30

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    End point title
    		 GMT of Serotype-specific OPA for Serotype 3 at Day 30
    End point description
    Serotype-specific OPA GMTs (estimated) and GMT ratios with 95% CIs were calculated using a cLDA model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMT ratios); within-group CIs were not calculated. OPA for serotype 3 contained in Prevnar 13™ and V114 was determined using a MOPA. The measure type of “number” presented in the data table below for serotype-specific OPA titer is the geometric mean. The analysis population included all randomized participants without protocol deviations, such as failure to receive study vaccine or receipt of prohibited medication prior to study vaccination.
    End point type
    Secondary
    End point timeframe
    Day 30
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    598
    598
    Units: Titers
        number (not applicable)
    216.2
    135.1
    Statistical analysis title
    		 Serotype 3 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1196
    Analysis specification
    Pre-specified
    Analysis type
    		 [26]
    P-value
    		 < 0.001
    Method
    		 cLDA
    Parameter type
    		 GMT Ratio
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.38
         upper limit
    		 1.85
    Notes
    [26] - The statistical criterion for superiority requires the lower bound of the 2-sided 95% CI of the OPA GMT ratio [V114/ Prevnar 13™] to be greater than 1.2. GMT ratio, 95% CI, and p-value are estimated from a cLDA model.

    Secondary: Percentage of Participants with ≥4-Fold Rise in Serotype-specific OPA for Serotype 3 OPA Responses

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    End point title
    		 Percentage of Participants with ≥4-Fold Rise in Serotype-specific OPA for Serotype 3 OPA Responses
    End point description
    Activity for serotype 3 contained in Prevnar 13™ and V114 was determined using a MOPA. The observed response percentage of participants (m/n) who had ≥4-fold rise in OPA titers were calculated from baseline to postvaccination. n=Number of participants contributing to the analysis; m=Number of participants with the indicated response. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the percentage point difference); within-group CIs were not calculated.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Day 30
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    580
    576
    Units: Percentage of Participants
        number (not applicable)
    70.2
    58.7
    Statistical analysis title
    		 Serotype 3 (Shared) ≥4-Fold Rise in OPA
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1156
    Analysis specification
    Pre-specified
    Analysis type
    		 [27]
    P-value
    		 < 0.001
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Percentage Point Difference
    Point estimate
    11.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6
         upper limit
    		 16.9
    Notes
    [27] - The statistical criterion for superiority requires the lower bound of the 2-sided 95% CI of the difference(V114 - Prevnar 13™) between the proportions of participants with a ≥4-fold rise from prevaccination (Day 1) to 30 days postvaccination (Day 30) to be greater than 0. Estimated difference, 95% CI, and p-value are based on the stratified Miettinen & Nurminen method.

    Secondary: Geometric Mean Concentration of Serotype-specific IgG at Day 30

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    End point title
    		 Geometric Mean Concentration of Serotype-specific IgG at Day 30
    End point description
    Serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) (estimated) and GMC ratios with 95% confidence intervals (CIs) were calculated using a cLDA model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMC ratios); within-group CIs were not calculated. IgG for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. The measure type of “number” presented in the data table below for serotype-specific IgG concentration is the geometric mean. The analysis population included all randomized participants without protocol deviations, such as failure to receive study vaccine or receipt of prohibited medication prior to study vaccination.
    End point type
    Secondary
    End point timeframe
    Day 30
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    602
    600
    Units: µg/mL
    number (not applicable)
        Serotype 1 (Shared) (n=598, 598)
    5.30
    7.34
        Serotype 3 (Shared) (n=598, 598)
    0.96
    0.64
        Serotype 4 (Shared) (n=598, 598)
    1.88
    2.62
        Serotype 5 (Shared) (n=598, 598)
    4.57
    5.56
        Serotype 6A (Shared) (n=598, 598)
    7.21
    7.01
        Serotype 6B (Shared) (n=598, 598)
    8.60
    6.19
        Serotype 7F (Shared) (n=598, 598)
    6.18
    8.09
        Serotype 9V (Shared) (n=598, 598)
    4.77
    5.52
        Serotype 14 (Shared) (n=598, 598)
    9.39
    12.30
        Serotype 18C (Shared) (n=598, 598)
    8.99
    10.00
        Serotype 19A (Shared) (n=598, 598)
    14.60
    17.38
        Serotype 19F (Shared) (n=598, 598)
    8.77
    9.70
        Serotype 23F (Shared) (n=598, 598)
    6.67
    6.13
        Serotype 22F (Unique to V114) (n=598, 598)
    3.44
    0.32
        Serotype 33F (Unique to V114) (n=598, 598)
    11.05
    1.23
    Statistical analysis title
    		 Serotype 1 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [28]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 0.83
    Notes
    [28] - GMC ratio and 95% CI are estimated from a constrained longitudinal data analysis (cLDA) model.
    Statistical analysis title
    		 Serotype 3 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [29]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.33
         upper limit
    		 1.71
    Notes
    [29] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 4 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [30]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 0.83
    Notes
    [30] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 5 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [31]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 0.96
    Notes
    [31] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 6A (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [32]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.21
    Notes
    [32] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 6B (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [33]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    1.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.17
         upper limit
    		 1.64
    Notes
    [33] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 7F (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [34]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 0.89
    Notes
    [34] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 9V (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [35]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1
    Notes
    [35] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 14 (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [36]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 0.89
    Notes
    [36] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 18C (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [37]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.05
    Notes
    [37] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 19A (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [38]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 0.97
    Notes
    [38] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 19F (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [39]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.05
    Notes
    [39] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 23F (Shared)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [40]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 1.28
    Notes
    [40] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 22F (Unique to V114)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [41]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    10.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.37
         upper limit
    		 12.03
    Notes
    [41] - GMC ratio and 95% CI are estimated from a cLDA model.
    Statistical analysis title
    		 Serotype 33F (Unique to V114)
    Comparison groups
    V114 v Prevnar 13™
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 [42]
    Method
    Parameter type
    		 GMC Ratio
    Point estimate
    8.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8
         upper limit
    		 10.07
    Notes
    [42] - GMC ratio and 95% CI are estimated from a cLDA model.

    Secondary: Geometric Mean Fold Rise in Serotype-specific OPA

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    End point title
    		 Geometric Mean Fold Rise in Serotype-specific OPA
    End point description
    Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a Multiplexed Opsonophagocytic Assay. Geometric mean fold rise (GMFR) is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline. The analysis population included all randomized participants without protocol deviations, such as failure to receive study vaccine or receipt of prohibited medication prior to study vaccination.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Day 30
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    602
    600
    Units: Ratio
    geometric mean (confidence interval 95%)
        Serotype 1 (Shared) (n=583, 573)
    14.3 (12.5 to 16.4)
    18.7 (16.2 to 21.5)
        Serotype 3 (Shared) (n=580, 576)
    7.7 (7.0 to 8.6)
    5.2 (4.7 to 5.7)
        Serotype 4 (Shared) (n=586, 578)
    17.8 (15.7 to 20.3)
    24.4 (21.3 to 27.8)
        Serotype 5 (Shared) (n=588, 584)
    12.3 (10.7 to 14.2)
    15.3 (13.2 to 17.6)
        Serotype 6A (Shared) (n=545, 550)
    13.0 (11.4 to 14.9)
    13.3 (11.6 to 15.2)
        Serotype 6B (Shared) (n=579, 576)
    26.3 (22.4 to 30.8)
    21.6 (18.5 to 25.2)
        Serotype 7F (Shared) (n=566, 555)
    12.0 (10.3 to 13.9)
    14.1 (12.1 to 16.5)
        Serotype 9V (Shared) (n=578, 573)
    5.3 (4.8 to 6.0)
    6.3 (5.6 to 7.1)
        Serotype 14 (Shared) (n=579,576)
    6.2 (5.4 to 7.2)
    8.7 (7.5 to 10.0)
        Serotype 18C (Shared) (n=578,579)
    11.3 (10.0 to 12.9)
    10.4 (9.1 to 11.8)
        Serotype 19A (Shared) (n=581,575)
    10.9 (9.5 to 12.5)
    13.1 (11.4 to 15.1)
        Serotype 19F (Shared) (n=579,576)
    6.6 (5.9 to 7.5)
    7.4 (6.6 to 8.3)
        Serotype 23F (Shared) (n=555,555)
    16.2 (14.0 to 18.9)
    13.5 (11.5 to 15.9)
        Serotype 22F (Unique to V114) (n=524,498)
    28.3 (22.8 to 35.1)
    1.2 (1.0 to 1.4)
        Serotype 33F (Unique to V114)(n=578,560)
    7.4 (6.4 to 8.6)
    1.0 (1.0 to 1.2)
    No statistical analyses for this end point

    Secondary: Geometric Mean Fold Rise in Serotype-specific IgG

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    End point title
    		 Geometric Mean Fold Rise in Serotype-specific IgG
    End point description
    Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. Geometric mean fold rise (GMFR) is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline. The analysis population included all randomized participants without protocol deviations, such as failure to receive study vaccine or receipt of prohibited medication prior to study vaccination.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Day 30
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    602
    600
    Units: Ratio
    geometric mean (confidence interval 95%)
        Serotype 1 (Shared) (n=588,584)
    10.6 (9.4 to 12.0)
    14.7 (13.1 to 16.6)
        Serotype 3 (Shared) (n=588,582)
    6.8 (6.2 to 7.6)
    4.7 (4.2 to 5.1)
        Serotype 4 (Shared) (n=586,583)
    8.0 (7.2 to 9.0)
    11.2 (10.0 to 12.5)
        Serotype 5 (Shared) (n=588,584)
    4.7 (4.2 to 5.2)
    5.8 (5.2 to 6.5)
        Serotype 6A (Shared) (n=588,584)
    19.9 (17.6 to 22.6)
    19.7 (17.4 to 22.3)
        Serotype 6B (Shared) (n=588,582)
    19.1 (16.8 to 21.7)
    13.8 (12.3 to 15.6)
        Serotype 7F (Shared) (n=588,584)
    12.3 (10.9 to 13.9)
    15.8 (13.9 to 18.0)
        Serotype 9V (Shared) (n=588,584)
    9.9 (8.9 to 11.1)
    11.1 (9.9 to 12.4)
        Serotype 14 (Shared) (n=587,583)
    5.1 (4.5 to 5.7)
    7.2 (6.3 to 8.2)
        Serotype 18C (Shared) (n=588,583)
    12.8 (11.3 to 14.5)
    14.3 (12.6 to 16.2)
        Serotype 19A (Shared) (n=588,584)
    8.7 (7.8 to 9.8)
    10.6 (9.5 to 11.9)
        Serotype 19F (Shared) (n=583,580)
    10.9 (9.7 to 12.3)
    12.5 (11.1 to 14.0)
        Serotype 23F (Shared) (n=586,584)
    13.5 (11.9 to 15.3)
    12.2 (10.8 to 13.7)
        Serotype 22F (Unique to V114) (n=588,583)
    11.7 (10.3 to 13.3)
    1.1 (1.1 to 1.1)
        Serotype 33F (Unique to V114) (n=588,584)
    9.1 (8.0 to 10.2)
    1.0 (1.0 to 1.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer

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    End point title
    		 Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer
    End point description
    Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a multiplexed opsonophagocytic assay. The percentage of participants who had ≥4-fold rise in OPA titers were calculated from baseline to postvaccination. The analysis population included all randomized participants without protocol deviations, such as failure to receive study vaccine or receipt of prohibited medication prior to study vaccination.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Day 30
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    602
    600
    Units: Percentage of Participants
    number (confidence interval 95%)
        Serotype 1 (Shared) (n=583,573)
    75.1 (71.4 to 78.6)
    77.7 (74.0 to 81.0)
        Serotype 3 (Shared) (n=580,576)
    70.2 (66.3 to 73.9)
    58.7 (54.5 to 62.7)
        Serotype 4 (Shared) (n=586,578)
    79.5 (76.0 to 82.7)
    84.8 (81.6 to 87.6)
        Serotype 5 (Shared) (n=588,584)
    71.6 (67.8 to 75.2)
    75.3 (71.6 to 78.8)
        Serotype 6A (Shared) (n=545,550)
    76.5 (72.7 to 80.0)
    74.9 (71.1 to 78.5)
        Serotype 6B (Shared) (n=579,576)
    81.2 (77.7 to 84.3)
    79.2 (75.6 to 82.4)
        Serotype 7F (Shared) (n=566,555)
    66.4 (62.4 to 70.3)
    72.4 (68.5 to 76.1)
        Serotype 9V (Shared) (n=578,573)
    54.0 (49.8 to 58.1)
    60.0 (55.9 to 64.1)
        Serotype 14 (Shared) (n=579,576)
    52.2 (48.0 to 56.3)
    60.8 (56.6 to 64.8)
        Serotype 18C (Shared) (n=578,579)
    71.3 (67.4 to 74.9)
    69.1 (65.1 to 72.8)
        Serotype 19A (Shared) (n=581,575)
    70.6 (66.7 to 74.2)
    71.1 (67.2 to 74.8)
        Serotype 19F (Shared) (n=579,576)
    62.0 (57.9 to 66.0)
    65.1 (61.1 to 69.0)
        Serotype 23F (Shared) (n=555,555)
    75.0 (71.1 to 78.5)
    71.4 (67.4 to 75.1)
        Serotype 22F (Unique to V114) (n=524,498)
    71.4 (67.3 to 75.2)
    14.3 (11.3 to 17.6)
        Serotype 33F (Unique to V114) (n=578,560)
    56.7 (52.6 to 60.8)
    6.3 (4.4 to 8.6)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with ≥4-Fold Rise in Serotype-specific IgG Concentration

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    End point title
    		 Percentage of Participants with ≥4-Fold Rise in Serotype-specific IgG Concentration
    End point description
    Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. The percentage of participants who had ≥4-fold rise in IgG concentration are calculated from baseline to postvaccination. The analysis population included all randomized participants without protocol deviations, such as failure to receive study vaccine or receipt of prohibited medication prior to study vaccination.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Day 30
    End point values
    		 V114 Prevnar 13™
    Number of subjects analysed
    602
    600
    Units: Percentage of Participants
    number (confidence interval 95%)
        Serotype 1 (Shared) (n=588,584)
    73.1 (69.4 to 76.7)
    78.4 (74.9 to 81.7)
        Serotype 3 (Shared) (n=588,582)
    61.6 (57.5 to 65.5)
    51.4 (47.2 to 55.5)
        Serotype 4 (Shared) (n=586,583)
    65.0 (61.0 to 68.9)
    76.0 (72.3 to 79.4)
        Serotype 5 (Shared) (n=588,584)
    45.1 (41.0 to 49.2)
    53.4 (49.3 to 57.5)
        Serotype 6A (Shared) (n=588,584)
    83.5 (80.3 to 86.4)
    83.4 (80.1 to 86.3)
        Serotype 6B (Shared) (n=588,582)
    82.8 (79.5 to 85.8)
    77.5 (73.9 to 80.8)
        Serotype 7F (Shared) (n=588,584)
    73.5 (69.7 to 77.0)
    78.6 (75.0 to 81.9)
        Serotype 9V (Shared) (n=588,584)
    69.6 (65.7 to 73.3)
    75.5 (71.8 to 79.0)
        Serotype 14 (Shared) (n=587,583)
    49.4 (45.3 to 53.5)
    59.5 (55.4 to 63.5)
        Serotype 18C (Shared) (n=588,583)
    73.1 (69.4 to 76.7)
    76.3 (72.7 to 79.7)
        Serotype 19A (Shared) (n=588,584)
    67.2 (63.2 to 71.0)
    71.2 (67.4 to 74.9)
        Serotype 19F (Shared) (n=583,580)
    69.5 (65.6 to 73.2)
    75.5 (71.8 to 79.0)
        Serotype 23F (Shared) (n=586,584)
    74.9 (71.2 to 78.4)
    74.3 (70.6 to 77.8)
        Serotype 22F (Unique to V114) (n=588,583)
    71.4 (67.6 to 75.0)
    1.7 (0.8 to 3.1)
        Serotype 33F (Unique to V114) (n=588,584)
    66.5 (62.5 to 70.3)
    1.7 (0.8 to 3.1)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Non-serious adverse events: Up to 14 days after vaccination; Serious adverse events and all-cause mortality: Up to ~Month 6 (Up to 194 days after vaccination).
    Adverse event reporting additional description
    The analysis population for adverse events and serious adverse events: all randomized participants who received study vaccination and were included in the intervention group according to the intervention they received. All randomized participants were included in the number of deaths (all causes).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    V114
    Reporting group description
    		 -

    Reporting group title
    PCV13
    Reporting group description
    		 -

    Serious adverse events
    		 V114 PCV13
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 602 (1.50%)
    13 / 600 (2.17%)
         number of deaths (all causes)
    1
    1
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 602 (0.17%)
    0 / 600 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer stage II
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Meniscus injury
         subjects affected / exposed
    1 / 602 (0.17%)
    0 / 600 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    1 / 602 (0.17%)
    0 / 600 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 602 (0.17%)
    0 / 600 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    1 / 602 (0.17%)
    0 / 600 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal disorders
    Incarcerated umbilical hernia
         subjects affected / exposed
    1 / 602 (0.17%)
    0 / 600 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis ulcerative
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Ureterolithiasis
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 602 (0.17%)
    0 / 600 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 602 (0.17%)
    0 / 600 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    1 / 602 (0.17%)
    0 / 600 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 602 (0.00%)
    1 / 600 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 V114 PCV13
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    395 / 602 (65.61%)
    336 / 600 (56.00%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    70 / 602 (11.63%)
    78 / 600 (13.00%)
         occurrences all number
    93
    105
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    105 / 602 (17.44%)
    104 / 600 (17.33%)
         occurrences all number
    144
    140
    Injection site erythema
         subjects affected / exposed
    60 / 602 (9.97%)
    73 / 600 (12.17%)
         occurrences all number
    62
    77
    Injection site pain
         subjects affected / exposed
    327 / 602 (54.32%)
    257 / 600 (42.83%)
         occurrences all number
    367
    294
    Injection site swelling
         subjects affected / exposed
    76 / 602 (12.62%)
    73 / 600 (12.17%)
         occurrences all number
    79
    78
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    32 / 602 (5.32%)
    33 / 600 (5.50%)
         occurrences all number
    38
    39
    Myalgia
         subjects affected / exposed
    93 / 602 (15.45%)
    72 / 600 (12.00%)
         occurrences all number
    111
    85

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Apr 2020
    Amendment 01- Revisions were made to include assessment of superiority for Serotype 3 and to include a revised statistical criterion for assessment of superiority for serotypes 22F and 33F. to make it a more stringent test.

    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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