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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 Japanese Infants

Summary
EudraCT number	2019-003644-68
Trial protocol	Outside EU/EEA
Global end of trial date	09 Feb 2022

Results information
Results version number	v3(current)
This version publication date	25 Dec 2022
First version publication date	24 Jul 2022
Other versions	v1 , v2
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

V114-033

ISRCTN number

US NCT number

NCT04384107

WHO universal trial number (UTN)

Other trial identifiers

JAPIC-CTI: 205287

Sponsor organisation name

Merck Sharp & Dohme LLC

Sponsor organisation address

126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

01 Dec 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

01 Dec 2021

Global end of trial reached?

Yes

Global end of trial date

09 Feb 2022

Was the trial ended prematurely?

Main objective of the trial

The purpose of this clinical study is to evaluate the safety and immunogenicity of a 4-dose schedule (3-dose primary series followed by a toddler dose) of V114 compared with Pneumococcal 13-valent Conjugate Vaccine (PCV13). The hypotheses are that: 1) V114 is non-inferior to PCV13 for the 13 shared serotypes between V114 and PCV13 based on the response rates at 30 days following dose 3; 2) V114 is non-inferior to PCV13 for the 2 unique V114 serotypes based on the response rate of the 2 unique V114 serotypes at 30 days following dose 3; 3) V114 is non-inferior to PCV13 for the 13 shared serotypes between V114 and PCV13 based on anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) at 30 days following dose 3.

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

01 Jul 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Japan: 694

Worldwide total number of subjects

694

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

694

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study enrolled healthy Japanese infants at 2 to 6 months of age.

Screening details

694 infants were randomized in a 1:1 ratio with stratification into 3 categories by age category (2 months, 3 months and 4 to 6 months of age), to receive either V114 or PCV13.

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, Carer

Are arms mutually exclusive

Yes

V114

Arm description

Participants received single 0.5 mL subcutaneous injection of V114 administered at 2 to 6 months of age, and second and third dose is administered at an interval of ≥27 days from the prior dose. The fourth dose is administered at 12 to 15 months of age.

Arm type

Experimental

Investigational medicinal product name

V114

Investigational medicinal product code

Other name

Pneumococcal 15-valent Conjugate Vaccine, VAXNEUVANCE™

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

15-valent pneumococcal conjugate vaccine containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) present in Prevnar 13™ plus 2 additional serotypes (22F, 33F) in each 0.5 mL dose

PCV13

Arm description

Participants received a single 0.5 mL subcutaneous injection of PCV13 administered at 2 to 6 months of age, and second and third dose is administered at an interval of ≥27 days from the prior dose. The fourth dose is administered at 12 to 15 months of age.

Arm type

Experimental

Investigational medicinal product name

PCV13

Investigational medicinal product code

Other name

Prevnar 13™

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

13-valent pneumococcal conjugate vaccine containing 13 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	PCV13
Started	347	347
Dose 1	347	346
Dose 2	344	346
Dose 3	343	346
Dose 4	340	342
Completed	338	341
Not completed	9	6
Withdrawal By Parent/Guardian	8	6
Lost to follow-up	1	-

Baseline characteristics

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Reporting group title

V114

Reporting group description

Reporting group title

PCV13

Reporting group description

Reporting group values	V114	PCV13	Total
Number of subjects	347	347	694
Age Categorical
Units: Subjects
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	347	347	694
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	0	0	0
From 65-84 years	0	0	0
85 years and over	0	0	0
Age Continuous
Units: months
arithmetic mean (standard deviation)	2.4 ± 0.4	2.4 ± 0.4	-
Gender Categorical
Units: Subjects
Female	166	173	339
Male	181	174	355
Race
Units: Subjects
Asian	347	347	694
Ethnicity
Units: Subjects
Not Hispanic or Latino	347	347	694

End points

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Reporting group title

V114

Reporting group description

Reporting group title

PCV13

Reporting group description

Primary: Percentage of Participants with Solicited Injection-Site Adverse Events

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End point title

Percentage of Participants with Solicited Injection-Site Adverse Events

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 treatment, whether or not considered related to the study treatment. Following any injection with either V114 or PCV13 the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, induration, pain, and swelling. All randomized participants who received at least 1 dose of study vaccination were analyzed. One participant in the PCV13 group did not receive PCV13 and therefore was not included in the analysis for this end point.

End point type

Primary

End point timeframe

Day 1 to Day 14 post any vaccination, up to a total of 13.5 months

End point values	V114	PCV13
Number of subjects analysed	347	346
Units: Percentage of Participants
number (not applicable)
Injection site erythema	88.2	89.3
Injection site induration	81.0	81.2
Injection site pain	31.1	24.0
Injection site swelling	75.8	79.8

Injection site erythema

Comparison groups

V114 v PCV13

Number of subjects included in analysis

693

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

= 0.641

Method

Miettinen & Nurminen

Parameter type

Difference in Percent

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.9

upper limit

3.6

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.

Injection site induration

Comparison groups

V114 v PCV13

Number of subjects included in analysis

693

Analysis specification

Pre-specified

Analysis type

other ^[2]

P-value

= 0.937

Method

Miettinen & Nurminen

Parameter type

Difference in Percent

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

5.6

Notes
[2] - 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.

Injection site pain

Comparison groups

V114 v PCV13

Number of subjects included in analysis

693

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

= 0.036

Method

Miettinen & Nurminen

Parameter type

Difference in Percent

Point estimate

7.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

13.8

Notes
[3] - 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.

Injection site swelling

Comparison groups

V114 v PCV13

Number of subjects included in analysis

693

Analysis specification

Pre-specified

Analysis type

other ^[4]

P-value

= 0.208

Method

Miettinen & Nurminen

Parameter type

Difference in Percent

Point estimate

-4

Confidence interval

level

95%

sides

2-sided

lower limit

-10.2

upper limit

2.2

Notes
[4] - 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.

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 any of the injections with either V114 or PCV13, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were decreased appetite, irritability, somnolence, and urticaria. All randomized participants who received at least 1 dose of study vaccination were analyzed. One participant in the PCV13 group did not receive PCV13 and therefore was not included in the analysis for this end point.

End point type

Primary

End point timeframe

Day 1 to Day 14 post any vaccination, up to a total of 13.5 months

End point values	V114	PCV13
Number of subjects analysed	347	346
Units: Percentage of Participants
number (not applicable)
Decreased appetite	23.9	24.3
Irritability	66.6	60.7
Somnolence	55.9	54.9
Urticaria	4.0	4.3

Decreased appetite

Comparison groups

V114 v PCV13

Number of subjects included in analysis

693

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.912

Method

Miettinen & Nurminen

Parameter type

Difference in Percent

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6.7

upper limit

Notes
[5] - 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.

Irritability

Comparison groups

V114 v PCV13

Number of subjects included in analysis

693

Analysis specification

Pre-specified

Analysis type

other ^[6]

P-value

= 0.108

Method

Miettinen & Nurminen

Parameter type

Difference in Percent

Point estimate

5.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

Notes
[6] - 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.

Somnolence

Comparison groups

V114 v PCV13

Number of subjects included in analysis

693

Analysis specification

Pre-specified

Analysis type

other ^[7]

P-value

= 0.792

Method

Miettinen & Nurminen

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-6.4

upper limit

8.4

Notes
[7] - 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.

Urticaria

Comparison groups

V114 v PCV13

Number of subjects included in analysis

693

Analysis specification

Pre-specified

Analysis type

other ^[8]

P-value

= 0.843

Method

Miettinen & Nurminen

Parameter type

Difference in Percent

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

2.8

Notes
[8] - 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.

Primary: Percentage of Participants with Vaccine-Related Serious Adverse Events

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End point title

Percentage of Participants with Vaccine-Related Serious Adverse Events

End point description

A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following dose 1 (with either V114 or PCV13) was reported. Vaccine-related SAEs were counted starting after vaccine dose 1 through completion of study. All randomized participants who received at least 1 dose of the relevant study vaccination for the timepoint of interest were analyzed. One participant in the PCV13 group did not receive PCV13 and therefore was not included in the analysis for this end point.

End point type

Primary

End point timeframe

~1 month after Dose 4 (Up to 14 months)

End point values	V114	PCV13
Number of subjects analysed	347	346
Units: Percentage of Participants
number (not applicable)	0.3	0.3

Vaccine-related SAEs

Statistical analysis description

Estimated differences and CIs are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Comparison groups

V114 v PCV13

Number of subjects included in analysis

693

Analysis specification

Pre-specified

Analysis type

other

Method

Miettinen & Nurminen

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

1.3

Primary: Percentage of Participants Meeting the Serotype Specific Immunoglobulin G Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 3

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End point title

Percentage of Participants Meeting the Serotype Specific Immunoglobulin G Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 3

End point description

The anti-pneumococcal polysaccharide (PnPs) serotype-specific immunoglobulin G (IgG) response rates (percentage of participants meeting serotype-specific IgG threshold value of ≥0.35 μg/mL for participants administered V114 versus participants administered PCV13) for the 15 serotypes contained in V114 were determined using an electrochemiluminescence assay. All randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity endpoint and who had sufficient data to perform the analyses were analyzed. One participant in the PCV13 group did not receive PCV13 and therefore was not included in the analysis for this end point. A value of '9999' indicates that data could not be calculated, as the analysis represents the difference between response rate to each serotype in recipients of V114 and lowest response (Serotype 3 at 97.7) in recipients of PCV13 for shared serotypes.

End point type

Primary

End point timeframe

30 Days after Dose 3, up to a total of 11 months

End point values	V114	PCV13
Number of subjects analysed	339	343
Units: Percentage of Participants
number (not applicable)
Serotype 1 (Shared) (n=339, 343)	99.7	100.0
Serotype 3 (Shared) (n=339, 343)	100.0	97.7
Serotype 4 (Shared) (n=339, 343)	100.0	100.0
Serotype 5 (Shared) (n=338, 343)	98.8	100.0
Serotype 6A (Shared) (n=339, 343)	99.1	100.0
Serotype 6B (Shared) (n=339, 343)	95.0	98.8
Serotype 7F (Shared) (n=339, 343)	99.7	100.0
Serotype 9V (Shared) (n=339, 343)	99.7	100.0
Serotype 14 (Shared) (n=339, 342)	99.4	99.7
Serotype 18C (Shared) (n=339, 343)	98.8	100.0
Serotype 19A (Shared) (n=339, 343)	99.7	100.0
Serotype 19F (Shared) (n=339, 343)	100.0	100.0
Serotype 23F (Shared) (n=338, 342)	97.9	99.7
Serotype 22F (Unique to V114) (n=339, 343)	99.7	9999
Serotype 33F (Unique to V114) (n=339, 343)	90.9	9999

Serotype 1

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.8

Notes
[9] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 3

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

4.5

Notes
[10] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 4

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[11] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 5

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-0.1

Notes
[12] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 6A

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

0.2

Notes
[13] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 6B

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6.9

upper limit

-1.3

Notes
[14] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 7F

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.8

Notes
[15] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 9V

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.8

Notes
[16] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 14

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

1.1

Notes
[17] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 18C

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-0.1

Notes
[18] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 19A

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.8

Notes
[19] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 19F

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[20] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 23F

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

-0.2

Notes
[21] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 22F

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

4.3

Notes
[22] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Serotype 33F

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

P-value

= 0.048

Method

Miettinen and Nurminen

Parameter type

Difference in Percent

Point estimate

-6.8

Confidence interval

level

95%

sides

2-sided

lower limit

-10.6

upper limit

-3.5

Notes
[23] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI and p-value based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age). A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (V114 - PCV13) being >-10 percentage points (1-sided p-value <0.025).

Primary: Geometric Mean Concentration of Serotype-Specific IgG for the 13 Shared Serotypes in V114 and PCV13 After Dose 3

Top of page

End point title

Geometric Mean Concentration of Serotype-Specific IgG for the 13 Shared Serotypes in V114 and PCV13 After Dose 3

End point description

The anti-PnPs serotype-specific IgG Geometric Mean Concentrations (GMCs) of participants administered V114 versus participants administered PCV13 for the 13 serotypes shared in V114 and PCV13 were determined using an electrochemiluminescence assay. All randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity endpoint and who had sufficient data to perform the analyses were analyzed. One participant in the PCV13 group did not receive PCV13 and therefore was not included in the analysis for this end point.

End point type

Primary

End point timeframe

30 Days after Dose 3, up to a total of 11 months

End point values	V114	PCV13
Number of subjects analysed	339	343
Units: μg/mL
geometric mean (confidence interval 95%)
Serotype 1 (Shared) (n=339, 343)	2.39 (2.19 to 2.62)	3.95 (3.61 to 4.32)
Serotype 3 (Shared) (n=339, 343)	2.63 (2.39 to 2.89)	1.42 (1.29 to 1.56)
Serotype 4 (Shared) (n=339, 343)	2.98 (2.71 to 3.27)	3.54 (3.23 to 3.89)
Serotype 5 (Shared) (n=338, 343)	2.59 (2.32 to 2.89)	3.35 (3.00 to 3.74)
Serotype 6A (Shared) (n=339, 343)	2.51 (2.26 to 2.79)	4.45 (4.00 to 4.94)
Serotype 6B (Shared) (n=339, 343)	2.46 (2.14 to 2.82)	4.17 (3.63 to 4.79)
Serotype 7F (Shared) (n=339, 343)	4.38 (3.95 to 4.85)	5.22 (4.71 to 5.78)
Serotype 9V (Shared) (n=339, 343)	3.09 (2.80 to 3.41)	3.55 (3.22 to 3.92)
Serotype 14 (Shared) (n=339, 342)	8.99 (7.96 to 10.14)	12.03 (10.66 to 13.57)
Serotype 18C (Shared) (n=339, 343)	2.85 (2.58 to 3.14)	3.85 (3.49 to 4.25)
Serotype 19A (Shared) (n=339, 343)	3.44 (3.14 to 3.77)	5.28 (4.82 to 5.79)
Serotype 19F (Shared) (n=339, 343)	4.24 (3.93 to 4.58)	5.65 (5.24 to 6.10)
Serotype 23F (Shared) (n=338, 342)	2.42 (2.15 to 2.72)	2.95 (2.62 to 3.32)

Serotype 1

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

0.67

Notes
[24] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PCV13) being >0.5 (1-sided p-value <0.025).

Serotype 3

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

1.85

Confidence interval

level

95%

sides

2-sided

lower limit

1.67

upper limit

2.05

Notes
[25] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PCV13) being >0.5 (1-sided p-value <0.025).

Serotype 4

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

0.93

Notes
[26] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Serotype 5

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[27]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

0.87

Notes
[27] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Serotype 6A

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[28]

P-value

= 0.019

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

0.63

Notes
[28] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Serotype 6B

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

P-value

= 0.015

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.59

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

0.68

Notes
[29] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Serotype 7F

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

0.94

Notes
[30] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Serotype 9V

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[31]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

0.97

Notes
[31] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Serotype 14

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[32]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

0.85

Notes
[32] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Serotype 18C

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[33]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

0.82

Notes
[33] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Serotype 19A

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[34]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

0.72

Notes
[34] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Serotype 19F

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[35]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

0.82

Notes
[35] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Serotype 23F

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[36]

P-value

< 0.001

Method

Linear model

Parameter type

GMC Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

0.93

Notes
[36] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors. A conclusion of non-inferiority of V114 to PCV13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (V114/PVC 13) being >0.5 (1-sided p-value <0.025).

Secondary: GMC of Serotype-Specific IgG for the 2 Unique V114 Serotypes After Dose 3

Top of page

End point title

GMC of Serotype-Specific IgG for the 2 Unique V114 Serotypes After Dose 3

End point description

The anti-PnPs serotype-specific IgG GMCs of participants administered V114 versus participants administered PCV13 for the 2 unique V114 serotypes was determined using an electrochemiluminescence assay. All randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity endpoint and who had sufficient data to perform the analyses were analyzed. One participant in the PCV13 group did not receive PCV13 and therefore was not included in the analysis for this end point.

End point type

Secondary

End point timeframe

30 days after Dose 3, up to a total of 11 months

End point values	V114	PCV13
Number of subjects analysed	339	343
Units: μg/mL
geometric mean (confidence interval 95%)
Serotype 22F (Unique to V114) (n=339, 343)	6.59 (5.95 to 7.30)	0.06 (0.06 to 0.07)
Serotype 33F (Unique to V114) (n=339, 337)	1.85 (1.60 to 2.14)	0.06 (0.05 to 0.07)

Serotype 22F

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

other ^[37]

Method

Parameter type

GMC Ratio

Point estimate

107.45

Confidence interval

level

95%

sides

2-sided

lower limit

96.18

upper limit

120.03

Notes
[37] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 33F

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

682

Analysis specification

Pre-specified

Analysis type

other ^[38]

Method

Parameter type

GMC Ratio

Point estimate

32.48

Confidence interval

level

95%

sides

2-sided

lower limit

27.72

upper limit

38.05

Notes
[38] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Secondary: Percentage of Participants Meeting the Serotype Specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 4

Top of page

End point title

Percentage of Participants Meeting the Serotype Specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 4

End point description

The anti-PnPs serotype-specific IgG response rates (percentage of participants meeting serotype-specific IgG threshold value of ≥0.35 μg/mL for participants administered V114 versus participants administered PCV13) for the 15 serotypes contained in V114 were determined using an electrochemiluminescence assay. All randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity endpoint and who had sufficient data to perform the analyses were analyzed. One participant in the PCV13 group did not receive PCV13 and therefore was not included in the analysis for this end point.

End point type

Secondary

End point timeframe

30 Days after Dose 4, up to a total of 14 months

End point values	V114	PCV13
Number of subjects analysed	333	334
Units: Percentage of Participants
number (not applicable)
Serotype 1 (Shared) (n=333, 334)	99.7	100.0
Serotype 3 (Shared) (n=333, 334)	100.0	96.7
Serotype 4 (Shared) (n=333, 334)	99.7	100.0
Serotype 5 (Shared) (n=333, 334)	100.0	100.0
Serotype 6A (Shared) (n=333, 334)	100.0	100.0
Serotype 6B (Shared) (n=333, 334)	100.0	100.0
Serotype 7F (Shared) (n=333, 334)	100.0	100.0
Serotype 9V (Shared) (n=333, 334)	100.0	100.0
Serotype 14 (Shared) (n=333, 334)	100.0	100.0
Serotype 18C (Shared) (n=333, 334)	100.0	100.0
Serotype 19A (Shared) (n=333, 334)	100.0	100.0
Serotype 19F (Shared) (n=333, 334)	100.0	100.0
Serotype 23F (Shared) (n=332, 334)	99.7	99.4
Serotype 22F (Unique to V114) (n=333, 327)	100.0	5.2
Serotype 33F (Unique to V114) (n=333, 313)	100.0	11.5

Serotype 1

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[39]

Method

Parameter type

Difference in Percent

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.8

Notes
[39] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 3

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[40]

Method

Parameter type

Difference in Percent

Point estimate

3.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

5.8

Notes
[40] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 4

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[41]

Method

Parameter type

Difference in Percent

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.8

Notes
[41] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 5

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[42]

Method

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[42] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 6A

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[43]

Method

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[43] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 6B

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[44]

Method

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[44] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 7F

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[45]

Method

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[45] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 9V

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[46]

Method

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[46] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 14

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[47]

Method

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[47] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 18C

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[48]

Method

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[48] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 19A

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[49]

Method

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[49] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 19F

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[50]

Method

Parameter type

Difference in Percent

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[50] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 23F

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[51]

Method

Parameter type

Difference in Percent

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.9

Notes
[51] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 22F

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[52]

Method

Parameter type

Difference in Percent

Point estimate

94.8

Confidence interval

level

95%

sides

2-sided

lower limit

91.8

upper limit

96.7

Notes
[52] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Serotype 33F

Statistical analysis description

Participants With IgG ≥0.35 μg/mL

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[53]

Method

Parameter type

Difference in Percent

Point estimate

88.5

Confidence interval

level

95%

sides

2-sided

lower limit

84.5

upper limit

91.6

Notes
[53] - The stratum-adjusted proportion difference using the Cochran-Mantel-Haenszel weight, and the corresponding 95% CI based on the method of Miettinen and Nurminen stratified by age category (2 months of age, ≥3 months of age).

Secondary: GMC of Serotype-Specific IgG for Each Serotype in V114 After Dose 4

Top of page

End point title

GMC of Serotype-Specific IgG for Each Serotype in V114 After Dose 4

End point description

The anti-PnPs serotype-specific IgG GMCs of participants administered V114 versus participants administered PCV13 for the 15 serotypes contained in V114 was determined using an electrochemiluminescence assay. All randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity endpoint and who had sufficient data to perform the analyses were analyzed. One participant in the PCV13 group did not receive PCV13 and therefore was not included in the analysis for this end point.

End point type

Secondary

End point timeframe

30 Days after Dose 4, up to a total of 14 months

End point values	V114	PCV13
Number of subjects analysed	333	334
Units: μg/mL
geometric mean (confidence interval 95%)
Serotype 1 (Shared) (n=333, 334)	2.74 (2.47 to 3.04)	5.19 (4.68 to 5.77)
Serotype 3 (Shared) (n=333, 334)	2.18 (1.97 to 2.41)	1.28 (1.15 to 1.41)
Serotype 4 (Shared) (n=333, 334)	2.91 (2.57 to 3.30)	3.18 (2.81 to 3.59)
Serotype 5 (Shared) (n=333, 334)	4.43 (3.96 to 4.95)	6.65 (5.95 to 7.43)
Serotype 6A (Shared) (n=333, 334)	6.05 (5.36 to 6.81)	9.41 (8.35 to 10.60)
Serotype 6B (Shared) (n=333, 334)	8.03 (7.12 to 9.05)	10.88 (9.66 to 12.26)
Serotype 7F (Shared) (n=333, 334)	5.80 (5.15 to 6.54)	7.15 (6.35 to 8.05)
Serotype 9V (Shared) (n=333, 334)	4.27 (3.79 to 4.81)	5.18 (4.60 to 5.83)
Serotype 14 (Shared) (n=333, 334)	9.51 (8.45 to 10.69)	11.26 (10.02 to 12.66)
Serotype 18C (Shared) (n=333, 334)	5.21 (4.60 to 5.89)	5.21 (4.61 to 5.90)
Serotype 19A (Shared) (n=333, 334)	6.88 (6.20 to 7.63)	8.37 (7.55 to 9.28)
Serotype 19F (Shared) (n=333, 334)	6.53 (5.89 to 7.22)	7.76 (7.01 to 8.58)
Serotype 23F (Shared) (n=332, 334)	3.75 (3.26 to 4.31)	6.22 (5.42 to 7.15)
Serotype 22F (Unique to V114) (n=333, 327)	11.42 (10.31 to 12.66)	0.13 (0.12 to 0.15)
Serotype 33F (Unique to V114) (n=333, 313)	6.14 (5.48 to 6.89)	0.14 (0.12 to 0.15)

Serotype 1

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[54]

Method

Parameter type

GMC Ratio

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

0.59

Notes
[54] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 3

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[55]

Method

Parameter type

GMC Ratio

Point estimate

1.71

Confidence interval

level

95%

sides

2-sided

lower limit

1.53

upper limit

1.9

Notes
[55] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 4

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[56]

Method

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.05

Notes
[56] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 5

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[57]

Method

Parameter type

GMC Ratio

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

0.75

Notes
[57] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 6A

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[58]

Method

Parameter type

GMC Ratio

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

0.73

Notes
[58] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 6B

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[59]

Method

Parameter type

GMC Ratio

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

0.84

Notes
[59] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 7F

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[60]

Method

Parameter type

GMC Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

0.92

Notes
[60] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 9V

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[61]

Method

Parameter type

GMC Ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

0.94

Notes
[61] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 14

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[62]

Method

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

0.96

Notes
[62] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 18C

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[63]

Method

Parameter type

GMC Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.14

Notes
[63] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 19A

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[64]

Method

Parameter type

GMC Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

0.92

Notes
[64] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 19F

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[65]

Method

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

0.94

Notes
[65] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 23F

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[66]

Method

Parameter type

GMC Ratio

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

0.7

Notes
[66] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 22F

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[67]

Method

Parameter type

GMC Ratio

Point estimate

86.74

Confidence interval

level

95%

sides

2-sided

lower limit

77.61

upper limit

96.95

Notes
[67] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 33F

Statistical analysis description

IgG GMC Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

667

Analysis specification

Pre-specified

Analysis type

other ^[68]

Method

Parameter type

GMC Ratio

Point estimate

45.44

Confidence interval

level

95%

sides

2-sided

lower limit

40.07

upper limit

51.54

Notes
[68] - Based on a linear model with natural log-transformed IgG concentrations as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Secondary: Geometric Mean Titer of Serotype-Specific Opsonophagocytic Activity for Each Serotype in V114 After Dose 3

Top of page

End point title

Geometric Mean Titer of Serotype-Specific Opsonophagocytic Activity for Each Serotype in V114 After Dose 3

End point description

The anti-PnPs serotype-specific opsonophagocytic activity (OPA) and geometric mean titers (GMTs) of participants administered V114 versus participants administered PCV13 for the 15 serotypes contained in V114 was determined using a multiplexed opsonophagocytic assay. All randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity endpoint and who had sufficient data to perform the analyses were analyzed. One participant in the PCV13 group did not receive PCV13 and therefore was not included in the analysis for this end point.

End point type

Secondary

End point timeframe

30 Days after Dose 3, up to a total of 11 months

End point values	V114	PCV13
Number of subjects analysed	337	340
Units: Titer
geometric mean (confidence interval 95%)
Serotype 1 (Shared) (n=336, 340)	211.51 (180.48 to 247.86)	322.44 (275.23 to 377.76)
Serotype 3 (Shared) (n=333, 336)	660.68 (586.60 to 744.11)	471.43 (418.48 to 531.08)
Serotype 4 (Shared) (n=334, 338)	3984.87 (3537.66 to 4488.62)	4118.16 (3656.82 to 4637.70)
Serotype 5 (Shared) (n=336, 339)	1241.69 (1098.82 to 1403.14)	1358.43 (1202.35 to 1534.79)
Serotype 6A (Shared) (n=334, 336)	9124.96 (7894.53 to 10547.16)	11956.64 (10340.85 to 13824.91)
Serotype 6B (Shared) (n=334, 338)	8416.19 (7243.92 to 9778.18)	10421.94 (8972.87 to 12105.02)
Serotype 7F (Shared) (n=334, 338)	22324.41 (19365.68 to 25735.19)	27396.28 (23771.84 to 31573.33)
Serotype 9V (Shared) (n=334, 338)	2725.29 (2399.27 to 3095.62)	3338.40 (2939.75 to 3791.11)
Serotype 14 (Shared) (n=334, 339)	14175.13 (12024.73 to 16710.08)	12288.35 (10433.90 to 14472.40)
Serotype 18C (Shared) (n=334, 339)	3698.24 (3346.73 to 4086.66)	3705.21 (3353.84 to 4093.39)
Serotype 19A (Shared) (n=335, 339)	2709.90 (2418.02 to 3037.02)	3961.10 (3535.23 to 4438.26)
Serotype 19F (Shared) (n=334, 339)	2371.39 (2141.38 to 2624.87)	2541.27 (2297.18 to 2811.29)
Serotype 23F (Shared) (n=334, 340)	11861.63 (10118.30 to 13905.32)	18957.26 (16186.86 to 22201.82)
Serotype 22F (Unique to V114) (n=333, 333)	5575.08 (4769.68 to 6516.47)	9.95 (8.51 to 11.63)
Serotype 33F (Unique to V114) (n=333, 334)	23888.79 (17632.59 to 32364.75)	121.79 (89.73 to 165.32)

Serotype 1

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[69]

Method

Parameter type

GMT Ratio

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

0.78

Notes
[69] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 3

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[70]

Method

Parameter type

GMT Ratio

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

1.59

Notes
[70] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 4

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[71]

Method

Parameter type

GMT Ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.1

Notes
[71] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 5

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[72]

Method

Parameter type

GMT Ratio

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.04

Notes
[72] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 6A

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[73]

Method

Parameter type

GMT Ratio

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

0.89

Notes
[73] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 7F

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[74]

Method

Parameter type

GMC Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

0.95

Notes
[74] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 6B

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[75]

Method

Parameter type

GMC Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

0.95

Notes
[75] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 9V

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[76]

Method

Parameter type

GMT Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

0.94

Notes
[76] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 14

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[77]

Method

Parameter type

GMT Ratio

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.38

Notes
[77] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 18C

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[78]

Method

Parameter type

GMT Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.11

Notes
[78] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 19A

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[79]

Method

Parameter type

GMT Ratio

Point estimate

0.68

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

0.77

Notes
[79] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 19F

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[80]

Method

Parameter type

GMT Ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.04

Notes
[80] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 23F

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[81]

Method

Parameter type

GMT Ratio

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

0.74

Notes
[81] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 22F

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[82]

Method

Parameter type

GMT Ratio

Point estimate

560.46

Confidence interval

level

95%

sides

2-sided

lower limit

474.05

upper limit

662.63

Notes
[82] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 33F

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

677

Analysis specification

Pre-specified

Analysis type

other ^[83]

Method

Parameter type

GMT Ratio

Point estimate

196.14

Confidence interval

level

95%

sides

2-sided

lower limit

141.85

upper limit

271.21

Notes
[83] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Secondary: GMT of Serotype-Specific OPA for Each Serotype in V114 After Dose 4

Top of page

End point title

GMT of Serotype-Specific OPA for Each Serotype in V114 After Dose 4

End point description

The anti-PnPs serotype-specific opsonophagocytic activity (OPA) and geometric mean titers (GMTs) of participants administered V114 versus participants administered PCV13 for the 15 serotypes contained in V114 was determined using a multiplexed opsonophagocytic assay. The first 50% of all participants with sufficient serum volume after dose 3 to evaluate OPA responses were analyzed. One participant in the PCV13 group did not receive PCV13 and therefore was not included in the analysis for this end point.

End point type

Secondary

End point timeframe

30 Days after Dose 4, up to a total of 14 months

End point values	V114	PCV13
Number of subjects analysed	157	156
Units: Titer
geometric mean (confidence interval 95%)
Serotype 1 (Shared) (n=156, 156)	453.42 (327.21 to 628.32)	854.50 (616.64 to 1184.10)
Serotype 3 (Shared) (n=150, 146)	1444.00 (1166.36 to 1787.72)	893.97 (720.25 to 1109.58)
Serotype 4 (Shared) (n=153, 152)	4531.52 (3592.99 to 5715.21)	6264.94 (4957.63 to 7916.97)
Serotype 5 (Shared) (n=157, 154)	1853.08 (1439.01 to 2386.30)	2151.95 (1669.81 to 2773.30)
Serotype 6A (Shared) (n=152, 152)	12553.06 (10072.11 to 15645.13)	17476.24 (13999.28 to 21816.75)
Serotype 6B (Shared) (n=153, 153)	9218.64 (7346.96 to 11567.14)	14041.53 (11171.79 to 17648.42)
Serotype 7F (Shared) (n=155, 155)	15451.96 (12500.49 to 19100.31)	18039.04 (14593.41 to 22298.22)
Serotype 9V (Shared) (n=152, 154)	3259.24 (2548.05 to 4168.93)	5050.89 (3957.89 to 6445.73)
Serotype 14 (Shared) (n=154, 155)	8486.72 (6720.27 to 10717.49)	5719.04 (4521.91 to 7233.08)
Serotype 18C (Shared) (n=153, 153)	7027.62 (5704.70 to 8657.32)	5903.86 (4785.06 to 7284.24)
Serotype 19A (Shared) (n=155, 156)	8441.43 (6620.55 to 10763.11)	10834.58 (8499.57 to 13811.07)
Serotype 19F (Shared) (n=153, 156)	4716.70 (3863.66 to 5758.07)	3829.62 (3138.93 to 4672.28)
Serotype 23F (Shared) (n=153, 153)	11319.82 (8635.69 to 14838.22)	30686.58 (23314.40 to 40389.89)
Serotype 22F (Unique to V114) (n=156, 144)	5561.71 (3730.30 to 8292.26)	35.68 (23.67 to 53.79)
Serotype 33F (Unique to V114) (n=154, 152)	19899.34 (14204.44 to 27877.46)	1183.52 (844.22 to 1659.18)

Serotype 1

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[84]

Method

Parameter type

GMT Ratio

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

0.75

Notes
[84] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 3

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[85]

Method

Parameter type

GMT Ratio

Point estimate

1.62

Confidence interval

level

95%

sides

2-sided

lower limit

1.28

upper limit

2.03

Notes
[85] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 4

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[86]

Method

Parameter type

GMT Ratio

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

0.93

Notes
[86] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 5

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[87]

Method

Parameter type

GMT Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

1.13

Notes
[87] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 6A

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[88]

Method

Parameter type

GMT Ratio

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

0.91

Notes
[88] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 6B

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[89]

Method

Parameter type

GMT Ratio

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

0.83

Notes
[89] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 7F

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[90]

Method

Parameter type

GMT Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.07

Notes
[90] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 9V

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[91]

Method

Parameter type

GMT Ratio

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

0.84

Notes
[91] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 14

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[92]

Method

Parameter type

GMT Ratio

Point estimate

1.48

Confidence interval

level

95%

sides

2-sided

lower limit

1.16

upper limit

1.9

Notes
[92] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 18C

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[93]

Method

Parameter type

GMT Ratio

Point estimate

1.19

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.48

Notes
[93] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 19A

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[94]

Method

Parameter type

GMT Ratio

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.01

Notes
[94] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 19F

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[95]

Method

Parameter type

GMT Ratio

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

1.52

Notes
[95] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 23F

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[96]

Method

Parameter type

GMT Ratio

Point estimate

0.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.28

upper limit

0.49

Notes
[96] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 22F

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[97]

Method

Parameter type

GMT Ratio

Point estimate

155.88

Confidence interval

level

95%

sides

2-sided

lower limit

101.84

upper limit

238.59

Notes
[97] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Serotype 33F

Statistical analysis description

OPA GMT Ratio

Comparison groups

V114 v PCV13

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

other ^[98]

Method

Parameter type

GMT Ratio

Point estimate

16.81

Confidence interval

level

95%

sides

2-sided

lower limit

11.74

upper limit

24.08

Notes
[98] - Based on a linear model with natural log-transformed OPA titers as response variable, and vaccination group and age category (2 months of age, ≥3 months of age) as factors.

Adverse events

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Timeframe for reporting adverse events

Non-serious adverse events: Up to 14 days after each vaccination, up to a total of 13.5 months; Serious adverse events: Approximately 1 month after Dose 4 (Up to 14 months); All-cause mortality: Up to 17 months

Adverse event reporting additional description

The analysis population for deaths (all-causes) included all randomized participants (N=347, N=347). The analysis population for AEs included all randomized participants who received at least 1 dose of study vaccination. One participant in the PCV13 group did not receive PCV13.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

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	24 / 347 (6.92%)	23 / 346 (6.65%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Congenital, familial and genetic disorders
Hamartoma
subjects affected / exposed	1 / 347 (0.29%)	0 / 346 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Kawasaki's disease
subjects affected / exposed	1 / 347 (0.29%)	2 / 346 (0.58%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Febrile convulsion
subjects affected / exposed	1 / 347 (0.29%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 347 (0.29%)	0 / 346 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Food allergy
subjects affected / exposed	3 / 347 (0.86%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Milk allergy
subjects affected / exposed	1 / 347 (0.29%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Intussusception
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
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
Asthma
subjects affected / exposed	0 / 347 (0.00%)	2 / 346 (0.58%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract inflammation
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
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
Compartment syndrome
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Adenovirus infection
subjects affected / exposed	1 / 347 (0.29%)	0 / 346 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	1 / 347 (0.29%)	2 / 346 (0.58%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 347 (0.29%)	2 / 346 (0.58%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
COVID-19
subjects affected / exposed	1 / 347 (0.29%)	0 / 346 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	1 / 347 (0.29%)	0 / 346 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis norovirus
subjects affected / exposed	1 / 347 (0.29%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	1 / 347 (0.29%)	0 / 346 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphadenitis bacterial
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nephritis bacterial
subjects affected / exposed	1 / 347 (0.29%)	0 / 346 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	3 / 347 (0.86%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia respiratory syncytial viral
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus bronchitis
subjects affected / exposed	1 / 347 (0.29%)	2 / 346 (0.58%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	4 / 347 (1.15%)	3 / 346 (0.87%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	4 / 347 (1.15%)	1 / 346 (0.29%)
occurrences causally related to treatment / all	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	1 / 347 (0.29%)	0 / 346 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral pharyngitis
subjects affected / exposed	1 / 347 (0.29%)	0 / 346 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral rash
subjects affected / exposed	0 / 347 (0.00%)	1 / 346 (0.29%)
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	340 / 347 (97.98%)	340 / 346 (98.27%)
Nervous system disorders
Somnolence
subjects affected / exposed	194 / 347 (55.91%)	190 / 346 (54.91%)
occurrences all number	430	399
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	306 / 347 (88.18%)	309 / 346 (89.31%)
occurrences all number	878	929
Injection site induration
subjects affected / exposed	281 / 347 (80.98%)	281 / 346 (81.21%)
occurrences all number	813	787
Injection site pain
subjects affected / exposed	108 / 347 (31.12%)	83 / 346 (23.99%)
occurrences all number	178	134
Injection site swelling
subjects affected / exposed	263 / 347 (75.79%)	276 / 346 (79.77%)
occurrences all number	670	688
Pyrexia
subjects affected / exposed	227 / 347 (65.42%)	252 / 346 (72.83%)
occurrences all number	544	610
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	35 / 347 (10.09%)	20 / 346 (5.78%)
occurrences all number	43	22
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
subjects affected / exposed	10 / 347 (2.88%)	21 / 346 (6.07%)
occurrences all number	12	23
Skin and subcutaneous tissue disorders
Eczema infantile
subjects affected / exposed	18 / 347 (5.19%)	16 / 346 (4.62%)
occurrences all number	19	16
Erythema
subjects affected / exposed	33 / 347 (9.51%)	31 / 346 (8.96%)
occurrences all number	44	42
Rash
subjects affected / exposed	17 / 347 (4.90%)	18 / 346 (5.20%)
occurrences all number	21	22
Skin induration
subjects affected / exposed	23 / 347 (6.63%)	18 / 346 (5.20%)
occurrences all number	29	22
Psychiatric disorders
Irritability
subjects affected / exposed	231 / 347 (66.57%)	210 / 346 (60.69%)
occurrences all number	522	500
Infections and infestations
Nasopharyngitis
subjects affected / exposed	32 / 347 (9.22%)	37 / 346 (10.69%)
occurrences all number	34	39
Upper respiratory tract infection
subjects affected / exposed	20 / 347 (5.76%)	22 / 346 (6.36%)
occurrences all number	23	29
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	83 / 347 (23.92%)	84 / 346 (24.28%)
occurrences all number	132	117

More information

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Were there any global substantial amendments to the protocol? Yes

25 Aug 2020

Amendment 01: Primary reason for amendment was to change the primary objectives for the evaluation of this study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

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 Japanese Infants

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with Solicited Injection-Site Adverse Events

Primary: Percentage of Participants with Solicited Injection-Site Adverse Events

Primary: Percentage of Participants with Solicited Systemic Adverse Events

Primary: Percentage of Participants with Solicited Systemic Adverse Events

Primary: Percentage of Participants with Vaccine-Related Serious Adverse Events

Primary: Percentage of Participants with Vaccine-Related Serious Adverse Events

Primary: Percentage of Participants Meeting the Serotype Specific Immunoglobulin G Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 3

Primary: Percentage of Participants Meeting the Serotype Specific Immunoglobulin G Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 3

Primary: Geometric Mean Concentration of Serotype-Specific IgG for the 13 Shared Serotypes in V114 and PCV13 After Dose 3

Primary: Geometric Mean Concentration of Serotype-Specific IgG for the 13 Shared Serotypes in V114 and PCV13 After Dose 3

Secondary: GMC of Serotype-Specific IgG for the 2 Unique V114 Serotypes After Dose 3

Secondary: GMC of Serotype-Specific IgG for the 2 Unique V114 Serotypes After Dose 3

Secondary: Percentage of Participants Meeting the Serotype Specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 4

Secondary: Percentage of Participants Meeting the Serotype Specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 4

Secondary: GMC of Serotype-Specific IgG for Each Serotype in V114 After Dose 4

Secondary: GMC of Serotype-Specific IgG for Each Serotype in V114 After Dose 4

Secondary: Geometric Mean Titer of Serotype-Specific Opsonophagocytic Activity for Each Serotype in V114 After Dose 3

Secondary: Geometric Mean Titer of Serotype-Specific Opsonophagocytic Activity for Each Serotype in V114 After Dose 3

Secondary: GMT of Serotype-Specific OPA for Each Serotype in V114 After Dose 4

Secondary: GMT of Serotype-Specific OPA for Each Serotype in V114 After Dose 4

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

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 Japanese Infants

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with Solicited Injection-Site Adverse Events

Primary: Percentage of Participants with Solicited Injection-Site Adverse Events

Primary: Percentage of Participants with Solicited Systemic Adverse Events

Primary: Percentage of Participants with Solicited Systemic Adverse Events

Primary: Percentage of Participants with Vaccine-Related Serious Adverse Events

Primary: Percentage of Participants with Vaccine-Related Serious Adverse Events

Primary: Percentage of Participants Meeting the Serotype Specific Immunoglobulin G Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 3

Primary: Percentage of Participants Meeting the Serotype Specific Immunoglobulin G Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 3

Primary: Geometric Mean Concentration of Serotype-Specific IgG for the 13 Shared Serotypes in V114 and PCV13 After Dose 3

Primary: Geometric Mean Concentration of Serotype-Specific IgG for the 13 Shared Serotypes in V114 and PCV13 After Dose 3

Secondary: GMC of Serotype-Specific IgG for the 2 Unique V114 Serotypes After Dose 3

Secondary: GMC of Serotype-Specific IgG for the 2 Unique V114 Serotypes After Dose 3

Secondary: Percentage of Participants Meeting the Serotype Specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 4

Secondary: Percentage of Participants Meeting the Serotype Specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 4

Secondary: GMC of Serotype-Specific IgG for Each Serotype in V114 After Dose 4

Secondary: GMC of Serotype-Specific IgG for Each Serotype in V114 After Dose 4

Secondary: Geometric Mean Titer of Serotype-Specific Opsonophagocytic Activity for Each Serotype in V114 After Dose 3

Secondary: Geometric Mean Titer of Serotype-Specific Opsonophagocytic Activity for Each Serotype in V114 After Dose 3

Secondary: GMT of Serotype-Specific OPA for Each Serotype in V114 After Dose 4

Secondary: GMT of Serotype-Specific OPA for Each Serotype in V114 After Dose 4

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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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 Japanese Infants