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Clinical Trial Results:
A Phase 3, Randomized, Double-blind Trial to Evaluate the Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine in Pneumococcal Vaccine–naïve Adults 18 Years of age and Older

Summary
EudraCT number	2018-004279-11
Trial protocol	SE
Global end of trial date	16 Dec 2019

Results information
Results version number	v1(current)
This version publication date	17 Dec 2020
First version publication date	17 Dec 2020
Other versions

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

B7471007

ISRCTN number

US NCT number

NCT03760146

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.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?

Analysis stage

Final

Date of interim/final analysis

09 Apr 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 Dec 2019

Was the trial ended prematurely?

Main objective of the trial

• Safety: To describe the safety profile of 20-valent pneumococcal conjugate vaccine (20vPnC) in adults 18 years of age and older. • Immunogenicity: To demonstrate that the immune responses to the 13 serotypes in 13-valent pneumococcal conjugate vaccine (13vPnC) (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) induced by 20vPnC in adults 60 years of age and older are noninferior to the immune response induced by 13vPnC. • To demonstrate that the immune responses to the 7 additional serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) induced by 20vPnC in adults 60 years of age and older are noninferior to the immune response induced by 23-valent pneumococcal polysaccharide vaccine (PPSV23).

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

12 Dec 2018

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Sweden: 172

Country: Number of subjects enrolled

United States: 3730

Worldwide total number of subjects

3902

EEA total number of subjects

172

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)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

2881

From 65 to 84 years

1010

85 years and over

Subject disposition

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Recruitment details

This study was conducted from 12 December 2018 to 16 December 2019 in the United States and Sweden.

Screening details

A total of 3902 subjects aged greater than or equal to (>=) 18 years at baseline, were enrolled into the study. Out of these 3902 subjects, 3889 subjects received study vaccination.

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, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Cohort 1: 20vPnC/Saline

Arm description

Subjects aged 60 years and above were randomized to receive a single dose of 0.5 milliliter (mL) intramuscular injection of 20-valent pneumococcal vaccine (20vPnC) at Vaccination 1 (Day 1) and a single dose of 0.5 mL intramuscular injection of saline at Vaccination 2 (28 to 42 days after Vaccination 1).

Arm type

Experimental

Investigational medicinal product name

Saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a single 0.5 mL intramuscular injection of saline at Vaccination 2 (28 to 42 days after Vaccination 1).

Investigational medicinal product name

20vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a single 0.5 mL intramuscular injection of 20vPnC at Vaccination 1 (Day 1).

Cohort 1: 13vPnC/PPSV23

Arm description

Subjects aged 60 years and above were randomized to receive a single dose of 0.5 mL intramuscular injection of 13-valent pneumococcal vaccine (13vPnC) at Vaccination 1 (Day 1) and a single dose of 0.5 mL intramuscular injection of 23-valent pneumococcal polysaccharide vaccine (PPSV23) at Vaccination 2 (28 to 42 days after vaccination 1).

Arm type

Active comparator

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a single 0.5 mL intramuscular injection of 13vPnC at Vaccination 1 (Day 1)

Investigational medicinal product name

PPSV23

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL intramuscular injection of PPSV23 at Vaccination 2 (28 to 42 days after Vaccination2).

Cohort 2: 20vPnC

Arm description

Subjects aged 50 through 59 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 20vPnC (Day 1).

Arm type

Experimental

Investigational medicinal product name

20vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a single 0.5 mL intramuscular injection of 20vPnC (Day 1).

Cohort 2: 13vPnC

Arm description

Subjects aged 50 through 59 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 13vPnC (Day 1).

Arm type

Active comparator

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a single 0.5 mL intramuscular injection of 13vPnC (Day 1).

Cohort 3: 20vPnC

Arm description

Subjects aged 18 through 49 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 20vPnC (Day 1).

Arm type

Experimental

Investigational medicinal product name

20vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a single 0.5 mL intramuscular injection of 20vPnC (Day 1).

Cohort 3: 13vPnC

Arm description

Subjects aged 18 through 49 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 13vPnC (Day 1).

Arm type

Active comparator

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received a single 0.5 mL intramuscular injection of 13vPnC (Day 1).

Number of subjects in period 1	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23	Cohort 2: 20vPnC	Cohort 2: 13vPnC	Cohort 3: 20vPnC	Cohort 3: 13vPnC
Started	1514	1495	334	111	336	112
Vaccination 1	1507	1490	334	111	335	112
Vaccination 2	1461	1446	0 ^[1]	0 ^[2]	0 ^[3]	0 ^[4]
Evaluable-20 Immunogenicity	946 ^[5]	0 ^[6]	321 ^[7]	0 ^[8]	317 ^[9]	0 ^[10]
Evaluable 13-Matched Immunogenicity	1435	1420	0 ^[11]	0 ^[12]	0 ^[13]	0 ^[14]
Evaluable 7-Additional Immunogenicity	1433	1383 ^[15]	0 ^[16]	0 ^[17]	0 ^[18]	0 ^[19]
Safety Population	1507	1490	334	111	335	112
Completed	1418	1417	323	109	319	104
Not completed	96	78	11	2	17	8
Adverse event, serious fatal	1	-	-	-	-	-
Consent withdrawn by subject	19	20	1	-	1	-
Adverse event, non-fatal	11	8	-	-	-	-
No longer met eligibility criteria	3	9	-	-	1	-
Lost to follow-up	41	28	9	2	14	8
Protocol deviation	21	13	1	-	1	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[11] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[12] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[13] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[14] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[15] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[16] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[17] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[18] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.
[19] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.

Baseline characteristics

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Reporting group title

Cohort 1: 20vPnC/Saline

Reporting group description

Reporting group title

Cohort 1: 13vPnC/PPSV23

Reporting group description

Reporting group title

Cohort 2: 20vPnC

Reporting group description

Subjects aged 50 through 59 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 20vPnC (Day 1).

Reporting group title

Cohort 2: 13vPnC

Reporting group description

Subjects aged 50 through 59 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 13vPnC (Day 1).

Reporting group title

Cohort 3: 20vPnC

Reporting group description

Subjects aged 18 through 49 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 20vPnC (Day 1).

Reporting group title

Cohort 3: 13vPnC

Reporting group description

Subjects aged 18 through 49 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 13vPnC (Day 1).

Reporting group values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23	Cohort 2: 20vPnC	Cohort 2: 13vPnC	Cohort 3: 20vPnC	Cohort 3: 13vPnC	Total
Number of subjects	1514	1495	334	111	336	112	3902
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	996	992	334	111	336	112	2881
From 65-84 years	510	500	0	0	0	0	1010
85 years and over	8	3	0	0	0	0	11
Age Continuous
Units: Years
arithmetic mean (standard deviation)	64.6 ( 4.82 )	64.6 ( 4.83 )	54.9 ( 2.77 )	55.0 ( 3.11 )	34.0 ( 8.76 )	33.9 ( 8.03 )	-
Sex: Female, Male
Units: subjects
Female	900	880	195	69	214	77	2335
Male	614	615	139	42	122	35	1567
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	6	9	0	3	1	1	20
Asian	19	15	10	2	11	1	58
Native Hawaiian or Other Pacific Islander	1	1	0	0	3	1	6
Black or African American	179	212	35	15	34	7	482
White	1300	1240	278	90	275	101	3284
More than one race	7	9	6	1	8	1	32
Unknown or Not Reported	2	9	5	0	4	0	20
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	169	169	12	8	24	7	389
Not Hispanic or Latino	1329	1312	319	101	301	102	3464
Unknown or Not Reported	16	14	3	2	11	3	49

End points

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Reporting group title

Cohort 1: 20vPnC/Saline

Reporting group description

Reporting group title

Cohort 1: 13vPnC/PPSV23

Reporting group description

Reporting group title

Cohort 2: 20vPnC

Reporting group description

Subjects aged 50 through 59 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 20vPnC (Day 1).

Reporting group title

Cohort 2: 13vPnC

Reporting group description

Subjects aged 50 through 59 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 13vPnC (Day 1).

Reporting group title

Cohort 3: 20vPnC

Reporting group description

Subjects aged 18 through 49 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 20vPnC (Day 1).

Reporting group title

Cohort 3: 13vPnC

Reporting group description

Subjects aged 18 through 49 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 13vPnC (Day 1).

Subject analysis set title

Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants of 60-64 years of age who were enrolled in Cohort 1, received Vaccination 1 as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations.

Primary: Percentage of Subjects With Local Reactions Within 10 Days After Vaccination in All Cohorts

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End point title

Percentage of Subjects With Local Reactions Within 10 Days After Vaccination in All Cohorts ^[1]

End point description

Local reactions were recorded using an electronic diary. Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm) and severe (>10.0 cm). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity). Safety population included all subjects who received 1 dose of any of the following: 20vPnC, 13vPnC, PPSV23 or saline and had safety follow-up after any vaccination. Here, "Number of subjects analysed" =number of subjects with any electronic diary data after 20vPnC or 13vPnC.

End point type

Primary

End point timeframe

Within 10 days after 20vPnC or 13vPnC

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23	Cohort 2: 20vPnC	Cohort 2: 13vPnC	Cohort 3: 20vPnC	Cohort 3: 13vPnC
Number of subjects analysed	1505	1483	331	111	335	112
Units: percentage of subjects
number (confidence interval 95%)
Redness: Any	7.3 (6.0 to 8.7)	6.2 (5.0 to 7.6)	8.2 (5.4 to 11.6)	5.4 (2.0 to 11.4)	9.0 (6.1 to 12.5)	9.8 (5.0 to 16.9)
Redness: Mild	3.7 (2.8 to 4.8)	3.8 (2.9 to 4.9)	5.1 (3.0 to 8.1)	2.7 (0.6 to 7.7)	3.0 (1.4 to 5.4)	5.4 (2.0 to 11.3)
Redness: Moderate	2.8 (2.0 to 3.8)	2.2 (1.5 to 3.1)	2.7 (1.3 to 5.1)	2.7 (0.6 to 7.7)	5.4 (3.2 to 8.4)	4.5 (1.5 to 10.1)
Redness: Severe	0.8 (0.4 to 1.4)	0.2 (0.0 to 0.6)	0.3 (0.0 to 1.7)	0 (0.0 to 3.3)	0.6 (0.1 to 2.1)	0 (0.0 to 3.2)
Swelling: Any	7.5 (6.2 to 9.0)	8.0 (6.6 to 9.5)	8.8 (5.9 to 12.3)	10.8 (5.7 to 18.1)	11.6 (8.4 to 15.6)	12.5 (7.0 to 20.1)
Swelling: Mild	4.8 (3.8 to 6.0)	4.9 (3.8 to 6.1)	5.7 (3.5 to 8.8)	7.2 (3.2 to 13.7)	7.2 (4.6 to 10.5)	8.9 (4.4 to 15.8)
Swelling: Moderate	2.4 (1.7 to 3.3)	2.8 (2.0 to 3.8)	3.0 (1.5 to 5.5)	3.6 (1.0 to 9.0)	4.5 (2.5 to 7.3)	3.6 (1.0 to 8.9)
Swelling: Severe	0.3 (0.1 to 0.8)	0.3 (0.1 to 0.7)	0 (0.0 to 1.1)	0 (0.0 to 3.3)	0 (0.0 to 1.1)	0 (0.0 to 3.2)
Pain at the injection site: Any	55.4 (52.9 to 57.9)	54.1 (51.6 to 56.7)	72.5 (67.4 to 77.2)	69.4 (59.9 to 77.8)	81.2 (76.6 to 85.2)	82.1 (73.8 to 88.7)
Pain at the injection site: Mild	45.3 (42.8 to 47.9)	44.6 (42.1 to 47.2)	53.5 (47.9 to 58.9)	52.3 (42.6 to 61.8)	42.7 (37.3 to 48.2)	52.7 (43.0 to 62.2)
Pain at the injection site: Moderate	9.9 (8.4 to 11.5)	9.2 (7.7 to 10.8)	17.8 (13.9 to 22.4)	16.2 (9.9 to 24.4)	38.2 (33.0 to 43.6)	28.6 (20.4 to 37.9)
Pain at the injection site: Severe	0.2 (0.0 to 0.6)	0.3 (0.1 to 0.8)	1.2 (0.3 to 3.1)	0.9 (0.0 to 4.9)	0.3 (0.0 to 1.7)	0.9 (0.0 to 4.9)

No statistical analyses for this end point

Primary: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination in All Cohorts

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End point title

Percentage of Subjects With Systemic Events Within 7 Days After Vaccination in All Cohorts ^[2]

End point description

Systemic events fever, fatigue, headache, muscle pain and joint pain were recorded by using an electronic diary. Fever was defined as greater than or equal to (>=) 38.0 degree Celsius (C) and categorized to >=38.0 to 38.4 degree C, >38.4 to 38.9 degree C, >38.9 to 40.0 degree C and >40.0 degree C. Fatigue, headache, muscle pain and joint pain were graded as mild (did not interfere with activity), moderate (some interference with activity) and severe (prevented daily routine activity). Safety population included all subjects who received 1 dose of any of the following: 20vPnC, 13vPnC, PPSV23 or saline and had safety follow-up after any vaccination. Here, "Number of subjects analysed" =number of subjects with any electronic diary data after 20vPnC or 13vPnC.

End point type

Primary

End point timeframe

Within 7 days after 20vPnC or 13vPnC

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23	Cohort 2: 20vPnC	Cohort 2: 13vPnC	Cohort 3: 20vPnC	Cohort 3: 13vPnC
Number of subjects analysed	1505	1483	331	111	335	112
Units: percentage of subjects
number (confidence interval 95%)
Fever: >=38.0 degree C	0.9 (0.5 to 1.6)	0.8 (0.4 to 1.4)	1.5 (0.5 to 3.5)	0.9 (0.0 to 4.9)	1.2 (0.3 to 3.0)	1.8 (0.2 to 6.3)
Fever: >=38.0 degree C to 38.4 degree C	0.3 (0.1 to 0.7)	0.4 (0.1 to 0.9)	0.6 (0.1 to 2.2)	0.9 (0.0 to 4.9)	0.6 (0.1 to 2.1)	0 (0.0 to 3.2)
Fever: >38.4 degree C to 38.9 degree C	0.3 (0.1 to 0.7)	0.2 (0.0 to 0.6)	0.3 (0.0 to 1.7)	0 (0.0 to 3.3)	0.3 (0.0 to 1.7)	0 (0.0 to 3.2)
Fever: >38.9 degree C to 40.0 degree C	0.0 (0.0 to 0.4)	0 (0.0 to 0.2)	0.3 (0.0 to 1.7)	0 (0.0 to 3.3)	0.3 (0.0 to 1.7)	1.8 (0.2 to 6.3)
Fever: >40.0 degree C	0.3 (0.1 to 0.8)	0.2 (0.0 to 0.6)	0.3 (0.0 to 1.7)	0 (0.0 to 3.3)	0 (0.0 to 1.1)	0 (0.0 to 3.2)
Fatigue: Any	30.2 (27.9 to 32.6)	30.7 (28.3 to 33.1)	39.3 (34.0 to 44.8)	36.0 (27.1 to 45.7)	42.7 (37.3 to 48.2)	43.8 (34.4 to 53.4)
Fatigue: Mild	16.1 (14.3 to 18.1)	17.5 (15.6 to 19.6)	21.1 (16.9 to 25.9)	18.0 (11.4 to 26.4)	18.8 (14.8 to 23.4)	20.5 (13.5 to 29.2)
Fatigue: Moderate	12.8 (11.2 to 14.6)	11.9 (10.3 to 13.7)	17.2 (13.3 to 21.7)	15.3 (9.2 to 23.4)	22.1 (17.8 to 26.9)	19.6 (12.7 to 28.2)
Fatigue: Severe	1.2 (0.7 to 1.9)	1.2 (0.7 to 1.9)	0.9 (0.2 to 2.6)	2.7 (0.6 to 7.7)	1.8 (0.7 to 3.9)	3.6 (1.0 to 8.9)
Headache: Any	21.5 (19.5 to 23.7)	23.3 (21.1 to 25.5)	32.3 (27.3 to 37.7)	36.0 (27.1 to 45.7)	38.8 (33.6 to 44.3)	33.9 (25.3 to 43.5)
Headache: Mild	15.5 (13.7 to 17.4)	17.0 (15.1 to 19.0)	20.5 (16.3 to 25.3)	21.6 (14.4 to 30.4)	21.5 (17.2 to 26.3)	16.1 (9.8 to 24.2)
Headache: Moderate	5.4 (4.3 to 6.6)	5.9 (4.8 to 7.3)	10.9 (7.7 to 14.7)	13.5 (7.8 to 21.3)	14.6 (11.0 to 18.9)	17.0 (10.5 to 25.2)
Headache: Severe	0.7 (0.3 to 1.2)	0.3 (0.1 to 0.8)	0.9 (0.2 to 2.6)	0.9 (0.0 to 4.9)	2.7 (1.2 to 5.0)	0.9 (0.0 to 4.9)
Muscle pain: Any	39.1 (36.6 to 41.6)	37.3 (34.8 to 39.8)	49.8 (44.3 to 55.4)	49.5 (39.9 to 59.2)	66.6 (61.2 to 71.6)	74.1 (65.0 to 81.9)
Muscle pain: Mild	28.9 (26.6 to 31.3)	26.8 (24.6 to 29.2)	33.8 (28.8 to 39.2)	31.5 (23.0 to 41.0)	36.4 (31.3 to 41.8)	42.0 (32.7 to 51.7)
Muscle pain: Moderate	9.8 (8.3 to 11.4)	10.0 (8.5 to 11.6)	15.4 (11.7 to 19.8)	17.1 (10.6 to 25.4)	29.0 (24.2 to 34.1)	31.3 (22.8 to 40.7)
Muscle pain: Severe	0.4 (0.1 to 0.9)	0.5 (0.2 to 1.0)	0.6 (0.1 to 2.2)	0.9 (0.0 to 4.9)	1.2 (0.3 to 3.0)	0.9 (0.0 to 4.9)
Joint pain: Any	12.6 (11.0 to 14.4)	13.7 (12.0 to 15.5)	15.4 (11.7 to 19.8)	20.7 (13.6 to 29.5)	13.4 (10.0 to 17.6)	17.9 (11.3 to 26.2)
Joint pain: Mild	6.9 (5.7 to 8.3)	7.1 (5.9 to 8.6)	10.6 (7.5 to 14.4)	12.6 (7.1 to 20.3)	6.3 (3.9 to 9.4)	8.9 (4.4 to 15.8)
Joint pain: Moderate	5.4 (4.3 to 6.6)	6.3 (5.2 to 7.7)	4.8 (2.8 to 7.7)	7.2 (3.2 to 13.7)	7.2 (4.6 to 10.5)	8.0 (3.7 to 14.7)
Joint pain: Severe	0.3 (0.1 to 0.8)	0.2 (0.0 to 0.6)	0 (0.0 to 1.1)	0.9 (0.0 to 4.9)	0 (0.0 to 1.1)	0.9 (0.0 to 4.9)

No statistical analyses for this end point

Primary: Percentage of Subjects With Adverse Events (AEs) Within 1 Month After Vaccination in All Cohorts

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End point title

Percentage of Subjects With Adverse Events (AEs) Within 1 Month After Vaccination in All Cohorts ^[3]

End point description

An AE was any untoward medical occurrence in study subjects who received study vaccine without regard to possibility of causal relationship with the treatment. Safety population included all subjects who received 1 dose of any of the following: 20vPnC, 13vPnC, PPSV23 or saline and had safety follow-up after any vaccination.

End point type

Primary

End point timeframe

Within 1 month after 20vPnC or 13vPnC

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23	Cohort 2: 20vPnC	Cohort 2: 13vPnC	Cohort 3: 20vPnC	Cohort 3: 13vPnC
Number of subjects analysed	1507	1490	334	111	335	112
Units: percentage of subjects
number (confidence interval 95%)	9.8 (8.4 to 11.4)	11.1 (9.6 to 12.8)	10.2 (7.2 to 13.9)	8.1 (3.8 to 14.8)	15.2 (11.6 to 19.5)	11.6 (6.3 to 19.0)

No statistical analyses for this end point

Primary: Percentage of Subjects With Serious Adverse Events (SAEs) Within 6 Months After Vaccination in All Cohorts

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End point title

Percentage of Subjects With Serious Adverse Events (SAEs) Within 6 Months After Vaccination in All Cohorts ^[4]

End point description

An SAE was any untoward medical occurrence at any dose that results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect or that is considered to be an important medical event. Safety population included all subjects who received 1 dose of any of the following: 20vPnC, 13vPnC, PPSV23 or saline and had safety follow-up after any vaccination.

End point type

Primary

End point timeframe

Within 6 months after 20vPnC or 13vPnC

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23	Cohort 2: 20vPnC	Cohort 2: 13vPnC	Cohort 3: 20vPnC	Cohort 3: 13vPnC
Number of subjects analysed	1507	1490	334	111	335	112
Units: percentage of subjects
number (confidence interval 95%)	2.4 (1.7 to 3.3)	1.9 (1.3 to 2.8)	0.3 (0.0 to 1.7)	0.9 (0.0 to 4.9)	0.6 (0.1 to 2.1)	0.9 (0.0 to 4.9)

No statistical analyses for this end point

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Conditions (NDCMCs) Within 6 Months After Vaccination in All Cohorts

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End point title

Percentage of Subjects With Newly Diagnosed Chronic Medical Conditions (NDCMCs) Within 6 Months After Vaccination in All Cohorts ^[5]

End point description

An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or was otherwise long-lasting in its effects. Safety population included all subjects who received 1 dose of any of the following: 20vPnC, 13vPnC, PPSV23 or saline and had safety follow-up after any vaccination.

End point type

Primary

End point timeframe

Within 6 months after 20vPnC or 13vPnC

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23	Cohort 2: 20vPnC	Cohort 2: 13vPnC	Cohort 3: 20vPnC	Cohort 3: 13vPnC
Number of subjects analysed	1507	1490	334	111	335	112
Units: percentage of subjects
number (confidence interval 95%)	2.3 (1.6 to 3.1)	2.3 (1.6 to 3.3)	1.5 (0.5 to 3.5)	0.9 (0.0 to 4.9)	1.5 (0.5 to 3.4)	1.8 (0.2 to 6.3)

No statistical analyses for this end point

Primary: Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the 13 Matched Serotypes at 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

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End point title

Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the 13 Matched Serotypes at 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population ^[6]

End point description

OPA GMTs were determined for serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. OPA titer was expressed as reciprocal of the highest serum dilution. OPA geometric mean and 2-sided 95% CIs were calculated. Evaluable 13-matched immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer for any of the 13 matched serotypes from the blood collection 27 to 49 days after Vaccination 1, had no other major protocol deviations. Here, "n" =subjects evaluable for this endpoint at specified rows.

End point type

Primary

End point timeframe

1 month after Vaccination 1

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23
Number of subjects analysed	1435	1420
Units: titer
geometric mean (confidence interval 95%)
Serotype 1 (n =1430, 1419)	123.4 (112.3 to 135.5)	153.8 (140.2 to 168.8)
Serotype 3 (n =1415, 1411)	40.7 (38.0 to 43.6)	47.8 (44.7 to 51.2)
Serotype 4 (n =1415, 1409)	508.7 (456.5 to 566.9)	626.9 (563.5 to 697.4)
Serotype 5 (n =1418, 1395)	91.6 (83.4 to 100.5)	109.7 (100.1 to 120.3)
Serotype 6A (n =1403, 1390)	889.0 (795.0 to 994.1)	1165.1 (1043.3 to 1301.0)
Serotype 6B (n =1413, 1401)	1115.2 (1003.1 to 1239.8)	1341.3 (1208.5 to 1488.8)
Serotype 7F (n =1409, 1391)	968.8 (887.0 to 1058.3)	1129.2 (1034.7 to 1232.4)
Serotype 9V (n =1399, 1391)	1455.5 (1317.5 to 1608.0)	1567.8 (1420.5 to 1730.5)
Serotype 14 (n =1418, 1408)	746.7 (679.0 to 821.2)	746.7 (679.8 to 820.1)
Serotype 18C (n =1420, 1403)	1252.6 (1123.1 to 1397.0)	1482.3 (1330.5 to 1651.5)
Serotype 19A (n =1420, 1398)	517.9 (472.2 to 568.0)	645.3 (588.9 to 707.1)
Serotype 19F (n =1421, 1403)	265.8 (240.2 to 294.1)	333.3 (301.5 to 368.3)
Serotype 23F (n =1424, 1409)	276.5 (242.5 to 315.2)	335.1 (294.4 to 381.4)

NI of 20vPnC to 13vPnC for 13 matched serotypes

Statistical analysis description

Serotype 1: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

Ratio of GMTs

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

0.9

Notes
[7] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the geometric mean ratio (GMR) for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 matched serotypes

Statistical analysis description

Serotype 3: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Parameter type

Ratio of GMTs

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

0.93

Notes
[8] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 matched serotypes

Statistical analysis description

Serotype 4: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

Method

Parameter type

Ratio of GMTs

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

0.93

Notes
[9] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 matched serotypes

Statistical analysis description

Serotype 5: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

Parameter type

Ratio of GMTs

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

0.94

Notes
[10] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 matched serotypes

Statistical analysis description

Serotype 6A: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

Method

Parameter type

Ratio of GMTs

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

0.88

Notes
[11] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 matched serotypes

Statistical analysis description

Serotype 6B: Geometric mean ratio (ratio of GMTs 20vPnC to 13vPnC) and 2-sided CIs were calculated by exponentiating the difference of LS means and the corresponding CIs based on a regression model with vaccine group, sex, smoking status, age at vaccination in years (continuous), and baseline log transformed OPA titers.

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

Method

Parameter type

Ratio of GMTs

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

0.95

Notes
[12] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 matched serotypes

Statistical analysis description

Serotype 7F: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

Method

Parameter type

Ratio of GMTs

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

0.96

Notes
[13] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 matched serotypes

Statistical analysis description

Serotype 9V: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

Method

Parameter type

Ratio of GMTs

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.05

Notes
[14] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 Matched Serotypes

Statistical analysis description

Serotype 14: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

Method

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.13

Notes
[15] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 Matched Serotypes

Statistical analysis description

Serotype 18C: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

Method

Parameter type

Ratio of GMTs

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

0.97

Notes
[16] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 Matched Serotypes

Statistical analysis description

Serotype 19A: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

Method

Parameter type

Ratio of GMTs

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

0.9

Notes
[17] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 Matched Serotypes

Statistical analysis description

Serotype 19F: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

Method

Parameter type

Ratio of GMTs

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

0.91

Notes
[18] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to 13vPnC for 13 Matched Serotypes

Statistical analysis description

Serotype 23F: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2855

Analysis specification

Pre-specified

Analysis type

^[19]

Method

Parameter type

Ratio of GMTs

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

0.91

Notes
[19] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

Primary: Pneumococcal OPA GMTs for the 7 Additional Serotypes at 1 Month After Vaccination 1 (20vPnC) or 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population (E7-AIP)

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End point title

Pneumococcal OPA GMTs for the 7 Additional Serotypes at 1 Month After Vaccination 1 (20vPnC) or 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population (E7-AIP) ^[20]

End point description

OPA GMTs were determined for serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. OPA titer was expressed as reciprocal of the highest serum dilution. OPA geometric mean and 2-sided 95% CIs were calculated. Evaluable 7-additional immunogenicity population: subjects who were enrolled in the appropriate cohort based on age, received 20vPnC if randomized to 20vPnC/saline group or received both vaccinations if randomized to 13vPnC/PPSV23 group, had at least 1 valid OPA titers for any of the 7 additional serotypes from the blood collection 27 to 49 days after Vaccination 1 or Vaccination 2 respectively, had no other major protocol deviations. Here, 'n' =subjects evaluable at specified rows.

End point type

Primary

End point timeframe

1 month after Vaccination 1 in “Cohort 1: 20vPnC/Saline”; 1 month after Vaccination 2 in “Cohort 1: 13vPnC/PPSV23”

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23
Number of subjects analysed	1433	1383
Units: titer
geometric mean (confidence interval 95%)
Serotype 8 (n =1374, 1319)	465.6 (422.5 to 513.1)	848.1 (769.1 to 935.2)
Serotype 10A (n =1310, 1263)	2007.6 (1808.0 to 2229.1)	1079.9 (972.1 to 1199.7)
Serotype 11A (n =1198, 1209)	4426.8 (3965.5 to 4941.8)	2534.9 (2276.8 to 2822.3)
Serotype 12F (n =1294, 1222)	2538.7 (2255.3 to 2857.7)	1716.6 (1521.8 to 1936.3)
Serotype 15B (n =1283, 1249)	2398.2 (2090.6 to 2751.2)	768.5 (669.7 to 881.9)
Serotype 22F (n =1274, 1227)	3666.2 (3244.4 to 4143.0)	1846.2 (1636.6 to 2082.6)
Serotype 33F (n =1157, 1201)	5125.9 (4611.3 to 5698.0)	3720.6 (3356.2 to 4124.6)

NI of 20vPnC to PPSV23 for 7 Additional Serotypes

Statistical analysis description

Serotype 8: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2816

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

Method

Parameter type

Ratio of GMTs

Point estimate

0.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

0.62

Notes
[21] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to PPSV23 for 7 Additional Serotypes

Statistical analysis description

Serotype 10A: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2816

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

Method

Parameter type

Ratio of GMTs

Point estimate

1.86

Confidence interval

level

95%

sides

2-sided

lower limit

1.63

upper limit

2.12

Notes
[22] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to PPSV23 for 7 Additional Serotypes

Statistical analysis description

Serotype 11A: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2816

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

Method

Parameter type

Ratio of GMTs

Point estimate

1.75

Confidence interval

level

95%

sides

2-sided

lower limit

1.52

upper limit

2.01

Notes
[23] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to PPSV23 for 7 Additional Serotypes

Statistical analysis description

Serotype 12F: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2816

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

Method

Parameter type

Ratio of GMTs

Point estimate

1.48

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

1.72

Notes
[24] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to PPSV23 for 7 Additional Serotypes

Statistical analysis description

Serotype 15B: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2816

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

Method

Parameter type

Ratio of GMTs

Point estimate

3.12

Confidence interval

level

95%

sides

2-sided

lower limit

2.62

upper limit

3.71

Notes
[25] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to PPSV23 for 7 Additional Serotypes

Statistical analysis description

Serotype 22F: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2816

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

Method

Parameter type

Ratio of GMTs

Point estimate

1.99

Confidence interval

level

95%

sides

2-sided

lower limit

1.7

upper limit

2.32

Notes
[26] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of 20vPnC to PPSV23 for 7 Additional Serotypes

Statistical analysis description

Serotype 33F: Geometric mean ratio (20vPnC/Saline vs 13vPnC/PPSV23) and the 2-sided 95% CI

Comparison groups

Cohort 1: 20vPnC/Saline v Cohort 1: 13vPnC/PPSV23

Number of subjects included in analysis

2816

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[27]

Method

Parameter type

Ratio of GMTs

Point estimate

1.38

Confidence interval

level

95%

sides

2-sided

lower limit

1.21

upper limit

1.57

Notes
[27] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

Secondary: Pneumococcal OPA GMTs for the 20 Vaccines Serotypes at 1 Month After 20vPnC Vaccination in Cohort 2, 50 Through 59 Years of Age and Cohort 1, Only 60 Through 64 Years of Age: Evaluable-20 Immunogenicity Population

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End point title

Pneumococcal OPA GMTs for the 20 Vaccines Serotypes at 1 Month After 20vPnC Vaccination in Cohort 2, 50 Through 59 Years of Age and Cohort 1, Only 60 Through 64 Years of Age: Evaluable-20 Immunogenicity Population ^[28]

End point description

OPA GMTs were determined for serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. OPA titer was expressed as reciprocal of the highest serum dilution. OPA geometric mean and 2-sided 95% CIs were calculated. Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received the vaccination as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations. Here, "n" =subjects evaluable for this endpoint at specified rows.

End point type

Secondary

End point timeframe

1 month after vaccination

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 2: 20vPnC	Cohort 1: 20vPnC/Saline (60-64 Years of Age)
Number of subjects analysed	321	946
Units: titer
geometric mean (confidence interval 95%)
Serotype 1 (n =320, 941)	135.9 (113.1 to 163.4)	131.8 (117.2 to 148.3)
Serotype 3 (n =318, 935)	43.3 (38.0 to 49.4)	40.9 (37.6 to 44.5)
Serotype 4 (n =318, 931)	633.3 (513.9 to 780.4)	577.9 (505.5 to 660.6)
Serotype 5 (n =313, 935)	84.6 (70.3 to 101.8)	96.5 (85.8 to 108.6)
Serotype 6A (n =318, 921)	1203.9 (968.1 to 1497.1)	997.1 (866.5 to 1147.5)
Serotype 6B (n =318, 933)	1502.7 (1228.2 to 1838.5)	1199.0 (1054.3 to 1363.4)
Serotype 7F (n =313, 924)	1047.0 (884.0 to 1240.2)	1173.0 (1052.9 to 1306.9)
Serotype 9V (n =312, 922)	1725.7 (1424.4 to 2090.6)	1687.9 (1493.7 to 1907.3)
Serotype 14 (n =313, 933)	926.2 (761.8 to 1126.0)	742.3 (655.8 to 840.2)
Serotype 18C (n =315, 937)	1805.0 (1459.6 to 2232.2)	1355.2 (1184.3 to 1550.7)
Serotype 19A (n =318, 932)	618.4 (519.9 to 735.5)	600.3 (537.5 to 670.6)
Serotype 19F (n =320, 937)	286.7 (236.0 to 348.2)	290.4 (256.4 to 329.0)
Serotype 23F (n =319, 937)	549.1 (425.4 to 708.9)	327.5 (278.2 to 385.6)
Serotype 8 (n =314, 901)	486.9 (400.6 to 591.9)	502.3 (442.8 to 569.8)
Serotype 10A (n =296, 857)	2520.4 (2076.0 to 3060.0)	2437.0 (2149.8 to 2762.5)
Serotype 11A (n =271, 796)	6416.9 (5131.9 to 8023.6)	5248.9 (4564.5 to 6035.9)
Serotype 12F (n =292, 855)	3445.1 (2807.8 to 4227.1)	3105.2 (2722.7 to 3541.4)
Serotype 15B (n =284, 830)	3355.9 (2582.0 to 4361.8)	2873.7 (2438.1 to 3387.1)
Serotype 22F (n =284, 835)	3808.1 (2998.2 to 4836.8)	4228.4 (3629.6 to 4926.0)
Serotype 33F (n =266, 765)	5571.3 (4495.7 to 6904.2)	5445.2 (4749.2 to 6243.2)

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 1: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

Method

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.26

Notes
[29] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 3: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

Method

Parameter type

Ratio of GMTs

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.22

Notes
[30] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 4: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[31]

Method

Parameter type

Ratio of GMTs

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.38

Notes
[31] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 5: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[32]

Method

Parameter type

Ratio of GMTs

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.07

Notes
[32] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 6A: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[33]

Method

Parameter type

Ratio of GMTs

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.53

Notes
[33] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 6B: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[34]

Method

Parameter type

Ratio of GMTs

Point estimate

1.25

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

1.56

Notes
[34] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 7F: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[35]

Method

Parameter type

Ratio of GMTs

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.07

Notes
[35] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 9V: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[36]

Method

Parameter type

Ratio of GMTs

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.26

Notes
[36] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 14: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[37]

Method

Parameter type

Ratio of GMTs

Point estimate

1.25

Confidence interval

level

95%

sides

2-sided

lower limit

1.01

upper limit

1.54

Notes
[37] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 18C: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[38]

Method

Parameter type

Ratio of GMTs

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

1.68

Notes
[38] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 19A: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[39]

Method

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.25

Notes
[39] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 19F: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[40]

Method

Parameter type

Ratio of GMTs

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.22

Notes
[40] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 23F: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[41]

Method

Parameter type

Ratio of GMTs

Point estimate

1.68

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

2.22

Notes
[41] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 8: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[42]

Method

Parameter type

Ratio of GMTs

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.2

Notes
[42] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 10A: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

Method

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.28

Notes
[43] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 11A: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[44]

Method

Parameter type

Ratio of GMTs

Point estimate

1.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.56

Notes
[44] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 12F: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[45]

Method

Parameter type

Ratio of GMTs

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.39

Notes
[45] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 15B: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[46]

Method

Parameter type

Ratio of GMTs

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.56

Notes
[46] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 22F: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[47]

Method

Parameter type

Ratio of GMTs

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.17

Notes
[47] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 2 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 33F: GMR (20vPnC Cohort 2 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 2: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1267

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

Method

Parameter type

Ratio of GMTs

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.3

Notes
[48] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

Secondary: Pneumococcal OPA GMTs for the 20 Vaccines Serotypes at 1 Month After 20vPnC Vaccination in Cohort 3, 18 Through 49 Years and Cohort 1, Only 60 Through 64 Years of Age: Evaluable-20 Immunogenicity Population

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End point title

Pneumococcal OPA GMTs for the 20 Vaccines Serotypes at 1 Month After 20vPnC Vaccination in Cohort 3, 18 Through 49 Years and Cohort 1, Only 60 Through 64 Years of Age: Evaluable-20 Immunogenicity Population ^[49]

End point description

End point type

Secondary

End point timeframe

1 month after vaccination

Notes
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 3: 20vPnC	Cohort 1: 20vPnC/Saline (60-64 Years of Age)
Number of subjects analysed	317	946
Units: titer
geometric mean (confidence interval 95%)
Serotype 1 (n =316, 941)	162.6 (135.1 to 195.6)	132.0 (117.7 to 148.1)
Serotype 3 (n =316, 935)	42.1 (36.9 to 48.1)	42.0 (38.7 to 45.7)
Serotype 4 (n =315, 931)	1966.7 (1599.5 to 2418.3)	594.5 (522.9 to 675.9)
Serotype 5 (n =317, 935)	107.9 (89.4 to 130.1)	96.9 (86.2 to 109.0)
Serotype 6A (n =315, 921)	3930.5 (3176.0 to 4864.4)	1022.8 (896.1 to 1167.4)
Serotype 6B (n =314, 933)	4260.0 (3461.3 to 5243.1)	1250.4 (1102.3 to 1418.4)
Serotype 7F (n =311, 924)	1872.8 (1564.2 to 2242.4)	1187.2 (1064.4 to 1324.2)
Serotype 9V (n =315, 922)	6041.4 (4962.5 to 7354.9)	1726.7 (1529.2 to 1949.7)
Serotype 14 (n =316, 933)	1848.4 (1514.7 to 2255.7)	772.8 (684.7 to 872.3)
Serotype 18C (n =312, 937)	4460.5 (3584.6 to 5550.4)	1395.3 (1220.9 to 1594.5)
Serotype 19A (n =312, 932)	1415.0 (1181.8 to 1694.2)	611.3 (547.8 to 682.3)
Serotype 19F (n =315, 937)	654.8 (538.2 to 796.8)	301.2 (266.7 to 340.1)
Serotype 23F (n =315, 937)	1559.2 (1208.1 to 2012.2)	324.5 (277.1 to 380.1)
Serotype 8 (n =306, 901)	867.0 (709.7 to 1059.2)	508.1 (448.8 to 575.3)
Serotype 10A (n =292, 857)	4157.3 (3410.9 to 5067.0)	2569.7 (2274.0 to 2903.7)
Serotype 11A (n =263, 796)	7169.3 (5735.7 to 8961.1)	5419.7 (4737.7 to 6199.7)
Serotype 12F (n =273, 855)	5875.4 (4719.8 to 7314.1)	3074.5 (2697.9 to 3503.7)
Serotype 15B (n =279, 830)	4601.0 (3487.9 to 6069.4)	3019.0 (2562.8 to 3556.4)
Serotype 22F (n =273, 835)	7568.2 (5927.4 to 9663.2)	4482.5 (3862.7 to 5201.8)
Serotype 33F (n =251, 765)	7976.9 (6341.7 to 10033.7)	5693.2 (4970.1 to 6521.5)

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 1: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[50]

Method

Parameter type

Ratio of GMTs

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

1.01

upper limit

1.5

Notes
[50] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 3: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[51]

Method

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.16

Notes
[51] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 4: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[52]

Method

Parameter type

Ratio of GMTs

Point estimate

3.31

Confidence interval

level

95%

sides

2-sided

lower limit

2.65

upper limit

4.13

Notes
[52] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 5: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[53]

Method

Parameter type

Ratio of GMTs

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.36

Notes
[53] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 6A: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[54]

Method

Parameter type

Ratio of GMTs

Point estimate

3.84

Confidence interval

level

95%

sides

2-sided

lower limit

3.06

upper limit

4.83

Notes
[54] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 6B: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[55]

Method

Parameter type

Ratio of GMTs

Point estimate

3.41

Confidence interval

level

95%

sides

2-sided

lower limit

2.73

upper limit

4.26

Notes
[55] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 7F: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[56]

Method

Parameter type

Ratio of GMTs

Point estimate

1.58

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

1.91

Notes
[56] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 9V: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[57]

Method

Parameter type

Ratio of GMTs

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.83

upper limit

4.33

Notes
[57] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 14: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[58]

Method

Parameter type

Ratio of GMTs

Point estimate

2.39

Confidence interval

level

95%

sides

2-sided

lower limit

1.93

upper limit

2.96

Notes
[58] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 18C: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[59]

Method

Parameter type

Ratio of GMTs

Point estimate

3.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.53

upper limit

4.04

Notes
[59] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 19A: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[60]

Method

Parameter type

Ratio of GMTs

Point estimate

2.31

Confidence interval

level

95%

sides

2-sided

lower limit

1.91

upper limit

2.81

Notes
[60] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 19F: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[61]

Method

Parameter type

Ratio of GMTs

Point estimate

2.17

Confidence interval

level

95%

sides

2-sided

lower limit

1.76

upper limit

2.68

Notes
[61] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 23F: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[62]

Method

Parameter type

Ratio of GMTs

Point estimate

4.8

Confidence interval

level

95%

sides

2-sided

lower limit

3.65

upper limit

6.32

Notes
[62] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 8: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[63]

Method

Parameter type

Ratio of GMTs

Point estimate

1.71

Confidence interval

level

95%

sides

2-sided

lower limit

1.38

upper limit

2.12

Notes
[63] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 10A: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[64]

Method

Parameter type

Ratio of GMTs

Point estimate

1.62

Confidence interval

level

95%

sides

2-sided

lower limit

1.31

upper limit

Notes
[64] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 11A: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[65]

Method

Parameter type

Ratio of GMTs

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

1.68

Notes
[65] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 12F: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[66]

Method

Parameter type

Ratio of GMTs

Point estimate

1.91

Confidence interval

level

95%

sides

2-sided

lower limit

1.51

upper limit

2.41

Notes
[66] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 15B: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[67]

Method

Parameter type

Ratio of GMTs

Point estimate

1.52

Confidence interval

level

95%

sides

2-sided

lower limit

1.13

upper limit

2.05

Notes
[67] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 22F: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[68]

Method

Parameter type

Ratio of GMTs

Point estimate

1.69

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

2.2

Notes
[68] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

NI of Cohort 3 to Cohort 1 (60-64 yrs)

Statistical analysis description

Serotype 33F: GMR (20vPnC Cohort 3 vs 20vPnC Cohort 1 60-64 years of age) and the 2-sided 95% CI

Comparison groups

Cohort 3: 20vPnC v Cohort 1: 20vPnC/Saline (60-64 Years of Age)

Number of subjects included in analysis

1263

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[69]

Method

Parameter type

Ratio of GMTs

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

1.79

Notes
[69] - Noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

Secondary: Pneumococcal OPA Geometric Mean Fold Rises (GMFRs) for the 13 Matched Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

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End point title

Pneumococcal OPA Geometric Mean Fold Rises (GMFRs) for the 13 Matched Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population ^[70]

End point description

OPA GMFR is the ratio of OPA GMT, 1 month after vaccination to before vaccination OPA GMT. OPA GMFRs from before to 1 month after vaccination were calculated along with corresponding 2-sided 95% CIs for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. Evaluable 13-matched immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer for any of the 13 matched serotypes from the blood collection 27 to 49 days after Vaccination 1, had no other major protocol deviations. Here, "n" =subjects evaluable with OPA titers available at both timepoints at the specified row.

End point type

Secondary

End point timeframe

Before Vaccination 1 to 1 month after Vaccination 1

Notes
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23
Number of subjects analysed	1435	1420
Units: fold rise
geometric mean (confidence interval 95%)
Serotype 1 (n =1425, 1418)	12.6 (11.5 to 13.8)	15.4 (14.1 to 16.8)
Serotype 3 (n =1404, 1401)	4.8 (4.5 to 5.2)	5.8 (5.4 to 6.2)
Serotype 4 (n =1370, 1374)	31.2 (27.8 to 34.9)	39.3 (35.1 to 44.1)
Serotype 5 (n =1411, 1394)	6.1 (5.6 to 6.6)	7.2 (6.6 to 7.8)
Serotype 6A (n =1382,1371)	34.3 (30.7 to 38.3)	42.6 (38.2 to 47.5)
Serotype 6B (n =1360, 1360)	23.8 (21.3 to 26.6)	26.5 (23.7 to 29.6)
Serotype 7F (n =1367, 1355)	12.2 (11.1 to 13.3)	13.5 (12.3 to 14.8)
Serotype 9V (n =1317, 1294)	11.0 (9.9 to 12.2)	12.5 (11.3 to 13.9)
Serotype 14 (n =1370, 1366)	9.3 (8.3 to 10.3)	8.3 (7.4 to 9.2)
Serotype 18C (n =1407, 1396)	33.8 (30.0 to 38.1)	37.7 (33.5 to 42.5)
Serotype 19A (n =1400, 1379)	21.0 (19.0 to 23.3)	25.9 (23.3 to 28.8)
Serotype 19F (n =1405, 1397)	8.6 (7.9 to 9.5)	10.8 (9.8 to 11.9)
Serotype 23F (n =1409, 1402)	24.9 (22.0 to 28.1)	30.7 (27.1 to 34.7)

No statistical analyses for this end point

Secondary: Pneumococcal OPA GMFRs for the Additional 7 Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC) or From Before Vaccination 1 to 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population

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End point title

Pneumococcal OPA GMFRs for the Additional 7 Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC) or From Before Vaccination 1 to 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population ^[71]

End point description

OPA GMFR is the ratio of OPA GMT, 1 month after vaccination to before vaccination OPA GMT. OPA GMFRs from before to 1 month after vaccination were calculated along with corresponding 2-sided 95% CIs for pneumococcal serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F. Evaluable 7-additional immunogenicity population included subjects who were enrolled in appropriate cohort based on age, received 20vPnC if randomized to 20vPnC/saline group or received both vaccinations if randomized to 13vPnC/PPSV23 group, had at least 1 valid OPA titers for any of 7 additional serotypes from blood collection 27 to 49 days after Vaccination 1 or Vaccination 2 respectively, had no other major protocol deviations. Here, "n" =subjects evaluable with OPA titers available at both timepoints at specified row.

End point type

Secondary

End point timeframe

From before Vaccination 1 to 1 month after Vaccination 1 in “Cohort 1: 20vPnC/Saline” or From before Vaccination 1 to 1 month after Vaccination 2 in “Cohort 1: 13vPnC/PPSV23”

Notes
[71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23
Number of subjects analysed	1433	1383
Units: fold rise
geometric mean (confidence interval 95%)
Serotype 8 (n =1353, 1293)	22.1 (20.0 to 24.5)	40.4 (36.6 to 44.7)
Serotype 10A (n =1208, 1164)	18.5 (16.5 to 20.6)	10.1 (9.1 to 11.3)
Serotype 11A (n =973, 993)	9.3 (8.1 to 10.7)	6.0 (5.3 to 6.9)
Serotype 12F (n =1226, 1147)	72.4 (64.2 to 81.6)	47.3 (41.4 to 54.1)
Serotype 15B (n =1228, 1178)	55.4 (47.7 to 64.4)	18.2 (15.6 to 21.1)
Serotype 22F (n =1178, 1156)	78.5 (67.3 to 91.5)	37.9 (32.7 to 43.9)
Serotype 33F (n =1020, 1080)	7.5 (6.7 to 8.5)	5.7 (5.1 to 6.3)

No statistical analyses for this end point

Secondary: Pneumococcal OPA GMFRs for the 20 Vaccines Serotypes From Before Vaccination to 1 Month After Vaccination in Cohort 2 and 3: Evaluable-20 Immunogenicity Population

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End point title

Pneumococcal OPA GMFRs for the 20 Vaccines Serotypes From Before Vaccination to 1 Month After Vaccination in Cohort 2 and 3: Evaluable-20 Immunogenicity Population ^[72]

End point description

OPA GMFR is the ratio of OPA GMT, 1 month after vaccination to before vaccination OPA GMT. OPA GMFRs from before to 1 month after vaccination were calculated along with corresponding 2-sided 95% CIs for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received the vaccination as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations. Here, "n" =subjects evaluable with OPA titers available at both timepoints at the specified row.

End point type

Secondary

End point timeframe

Before vaccination to 1 month after vaccination

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 2: 20vPnC	Cohort 3: 20vPnC
Number of subjects analysed	321	317
Units: Fold rise
geometric mean (confidence interval 95%)
Serotype 1 (n =319, 315)	14.4 (12.0 to 17.3)	18.6 (16.0 to 21.8)
Serotype 3 (n =317, 312)	5.1 (4.4 to 5.9)	4.8 (4.2 to 5.5)
Serotype 4 (n =304, 302)	43.4 (34.4 to 54.9)	131.8 (106.4 to 163.4)
Serotype 5 (n =312,315)	5.9 (5.0 to 7.0)	7.9 (6.7 to 9.4)
Serotype 6A (n =312, 305)	50.3 (40.2 to 63.0)	146.5 (120.6 to 178.0)
Serotype 6B (n =299, 286)	31.7 (25.3 to 39.7)	70.3 (55.7 to 88.7)
Serotype 7F (n =300, 284)	12.8 (10.7 to 15.4)	19.7 (16.1 to 24.3)
Serotype 9V (n =288, 281)	12.1 (9.9 to 14.7)	35.1 (27.9 to 44.2)
Serotype 14 (n =300, 291)	10.4 (8.3 to 13.0)	14.6 (11.3 to 18.9)
Serotype 18C (n =308, 299)	48.3 (37.9 to 61.5)	111.8 (86.8 to 143.8)
Serotype 19A (n =310, 299)	23.6 (19.2 to 29.1)	39.1 (30.9 to 49.6)
Serotype 19F (n =316, 310)	9.2 (7.6 to 11.3)	17.8 (14.7 to 21.6)
Serotype 23F (n =313, 309)	47.8 (37.2 to 61.3)	118.2 (92.7 to 150.7)
Serotype 8 (n =310, 300)	23.9 (19.3 to 29.6)	34.6 (27.8 to 43.0)
Serotype 10A (n =273, 260)	17.9 (14.2 to 22.6)	22.7 (17.8 to 29.0)
Serotype 11A (n =213, 220)	10.4 (7.7 to 14.2)	5.2 (3.9 to 6.9)
Serotype 12F (n =279, 252)	107.3 (85.8 to 134.1)	171.1 (135.1 to 216.8)
Serotype 15B (n =263, 248)	72.1 (51.9 to 100.1)	65.0 (44.8 to 94.4)
Serotype 22F (n =256, 241)	63.5 (44.8 to 90.1)	69.3 (48.4 to 99.4)
Serotype 33F (n =233, 213)	9.1 (7.1 to 11.7)	7.5 (5.8 to 9.7)

No statistical analyses for this end point

Secondary: Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers to the 13 Matched Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

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End point title

Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers to the 13 Matched Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population ^[73]

End point description

Percentage of subjects with a >=4-fold rise in serotype-specific pneumococcal OPA titers from before vaccination to 1 month after vaccination along with corresponding 2-sided 95% CIs were calculated for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. Evaluable 13-matched immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer for any of the 13 matched serotypes from the blood collection 27 to 49 days after Vaccination 1, had no other major protocol deviations. Here, "n" =subjects evaluable for this endpoint at specified rows.

End point type

Secondary

End point timeframe

Before Vaccination 1 to 1 month after Vaccination 1

Notes
[73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23
Number of subjects analysed	1435	1420
Units: percentage of subjects
number (confidence interval 95%)
Serotype 1 (n =1425, 1418)	72.1 (69.7 to 74.4)	74.8 (72.4 to 77.0)
Serotype 3 (n =1404, 1401)	56.1 (53.4 to 58.7)	61.7 (59.1 to 64.2)
Serotype 4 (n =1370, 1374)	75.5 (73.2 to 77.8)	79.6 (77.4 to 81.7)
Serotype 5 (n =1411, 1394)	55.6 (52.9 to 58.2)	60.6 (58.0 to 63.2)
Serotype 6A (n =1382, 1371)	80.5 (78.3 to 82.5)	84.0 (82.0 to 85.9)
Serotype 6B (n =1360, 1360)	75.7 (73.3 to 77.9)	77.6 (75.3 to 79.8)
Serotype 7F (n =1367, 1355)	71.8 (69.3 to 74.1)	72.3 (69.8 to 74.6)
Serotype 9V (n =1317, 1294)	67.7 (65.1 to 70.3)	69.3 (66.7 to 71.8)
Serotype 14 (n =1370, 1366)	58.2 (55.5 to 60.8)	54.0 (51.3 to 56.6)
Serotype 18C (n =1407, 1396)	77.7 (75.4 to 79.8)	79.6 (77.4 to 81.7)
Serotype 19A (n =1400, 1379)	73.6 (71.3 to 75.9)	77.5 (75.2 to 79.7)
Serotype 19F (n =1405, 1397)	63.6 (61.1 to 66.2)	66.9 (64.4 to 69.4)
Serotype 23F (n =1409, 1402)	70.6 (68.2 to 73.0)	74.4 (72.0 to 76.7)

No statistical analyses for this end point

Secondary: Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers for the 7 Additional Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1(20vPnC) or From Before Vaccination 1 to 1 Month After Vaccination 2(PPSV23) in Cohort 1:E7-AIP

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End point title

Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers for the 7 Additional Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1(20vPnC) or From Before Vaccination 1 to 1 Month After Vaccination 2(PPSV23) in Cohort 1:E7-AIP ^[74]

End point description

Percentage of subjects with a >=4-fold rise in serotype-specific pneumococcal OPA titers from before vaccination to 1 month after vaccination along with corresponding 2-sided 95% CIs were calculated for pneumococcal serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F. E7-AIP included subjects who were enrolled in appropriate cohort based on age, received 20vPnC if randomized to 20vPnC/saline group or received both vaccinations if randomized to 13vPnC/PPSV23 group, had at least 1 valid OPA titers for any of 7 additional serotypes from blood collection 27 to 49 days after Vaccination 1 or Vaccination 2 respectively, had no other major protocol deviations. Here, "n" =subjects evaluable for this endpoint at specified rows.

End point type

Secondary

End point timeframe

Before Vaccination 1 to 1 month after Vaccination 1 for “Cohort 1: 20vPnC/Saline”; Before Vaccination 1 to 1 month after Vaccination 2 for “Cohort 1: 13vPnC/PPSV23”

Notes
[74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23
Number of subjects analysed	1433	1383
Units: percentage of subjects
number (confidence interval 95%)
Serotype 8 (n =1353, 1293)	77.8 (75.5 to 80.0)	86.8 (84.8 to 88.6)
Serotype 10A (n =1208, 1164)	75.5 (73.0 to 77.9)	65.6 (62.8 to 68.4)
Serotype 11A (n =973, 993)	59.2 (56.0 to 62.3)	51.9 (48.7 to 55.0)
Serotype 12F (n =1226, 1147)	87.4 (85.5 to 89.2)	80.6 (78.1 to 82.8)
Serotype 15B (n =1228, 1178)	77.8 (75.3 to 80.1)	63.8 (61.0 to 66.6)
Serotype 22F (n =1178, 1156)	82.7 (80.4 to 84.8)	76.8 (74.3 to 79.2)
Serotype 33F (n =1020, 1080)	60.1 (57.0 to 63.1)	55.5 (52.4 to 58.5)

No statistical analyses for this end point

Secondary: Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers for the 20 Vaccines Serotypes From Before Vaccination to 1 Month After Vaccination in Cohort 2 and 3: Evaluable-20 Immunogenicity Population

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End point title

Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers for the 20 Vaccines Serotypes From Before Vaccination to 1 Month After Vaccination in Cohort 2 and 3: Evaluable-20 Immunogenicity Population ^[75]

End point description

Percentage of subjects with a >=4-fold rise in serotype-specific pneumococcal OPA titers from before vaccination to 1 month after vaccination along with corresponding 2-sided 95% CIs were calculated for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received the vaccination as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations. Here, "n" =subjects evaluable for this endpoint at specified rows.

End point type

Secondary

End point timeframe

Before vaccination to 1 month after vaccination

Notes
[75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 2: 20vPnC	Cohort 3: 20vPnC
Number of subjects analysed	321	317
Units: Percentage of subjects
number (confidence interval 95%)
Serotype 1 (n =319, 315)	74.9 (69.8 to 79.6)	86.0 (81.7 to 89.7)
Serotype 3 (n =317,312)	59.0 (53.4 to 64.5)	56.7 (51.0 to 62.3)
Serotype 4 (n =304,302)	84.2 (79.6 to 88.1)	91.4 (87.6 to 94.3)
Serotype 5 (n =312, 315)	54.8 (49.1 to 60.4)	64.8 (59.2 to 70.0)
Serotype 6A (n =312, 305)	85.9 (81.5 to 89.6)	96.7 (94.1 to 98.4)
Serotype 6B (n =299, 286)	78.9 (73.9 to 83.4)	89.2 (85.0 to 92.5)
Serotype 7F (n =300, 284)	73.0 (67.6 to 77.9)	76.1 (70.7 to 80.9)
Serotype 9V (n =288, 281)	73.6 (68.1 to 78.6)	84.0 (79.2 to 88.1)
Serotype 14 (n =300, 291)	62.3 (56.6 to 67.8)	62.2 (56.4 to 67.8)
Serotype 18C (n =308, 299)	82.5 (77.8 to 86.5)	87.3 (83.0 to 90.8)
Serotype 19A (n =310, 299)	80.0 (75.1 to 84.3)	82.6 (77.8 to 86.7)
Serotype 19F (n =316, 310)	64.2 (58.7 to 69.5)	78.4 (73.4 to 82.8)
Serotype 23F (n =313, 309)	81.2 (76.4 to 85.3)	87.7 (83.5 to 91.1)
Serotype 8 (n =310, 300)	79.4 (74.4 to 83.7)	83.0 (78.3 to 87.1)
Serotype 10A (n =273, 260)	78.8 (73.4 to 83.5)	78.8 (73.4 to 83.6)
Serotype 11A (n =213, 220)	61.0 (54.1 to 67.6)	47.3 (40.5 to 54.1)
Serotype 12F (n =279, 252)	93.2 (89.6 to 95.9)	93.7 (89.9 to 96.3)
Serotype 15B (n =263, 248)	82.5 (77.4 to 86.9)	73.4 (67.4 to 78.8)
Serotype 22 F (n =256, 241)	80.5 (75.1 to 85.1)	83.8 (78.5 to 88.2)
Serotype 33F (n =233, 213)	63.9 (57.4 to 70.1)	60.6 (53.7 to 67.2)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Pneumococcal OPA Titers >= Lower Limit of Quantitation (LLOQ) for the 13 Matched Serotypes at 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

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End point title

Percentage of Subjects With Pneumococcal OPA Titers >= Lower Limit of Quantitation (LLOQ) for the 13 Matched Serotypes at 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population ^[76]

End point description

The percentage of subjects with OPA titers >=LLOQ along with corresponding 2-sided 95% CIs were calculated 1 month after vaccination for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. Evaluable 13-matched immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received Vaccination 1 as randomized, had at least 1 valid OPA titer for any of the 13 matched serotypes from the blood collection 27 to 49 days after Vaccination 1, had no other major protocol deviations. Here, "n" =subjects evaluable for this endpoint at specified rows.

End point type

Secondary

End point timeframe

1 month after Vaccination 1

Notes
[76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23
Number of subjects analysed	1435	1420
Units: Percentage of subjects
number (confidence interval 95%)
Serotype 1 (n =1430, 1419)	85.0 (83.0 to 86.8)	87.9 (86.1 to 89.5)
Serotype 3 (n =1415, 1411)	84.2 (82.2 to 86.0)	87.0 (85.2 to 88.7)
Serotype 4 (n =1415, 1409)	91.1 (89.5 to 92.5)	92.1 (90.5 to 93.4)
Serotype 5 (n =1418, 1395)	71.9 (69.5 to 74.3)	76.0 (73.7 to 78.2)
Serotype 6A (n =1403, 1390)	88.9 (87.1 to 90.5)	90.9 (89.2 to 92.3)
Serotype 6B (n =1413, 1401)	90.5 (88.9 to 92.0)	91.6 (90.0 to 93.0)
Serotype 7F (n =1409, 1391)	89.1 (87.3 to 90.7)	91.3 (89.7 to 92.7)
Serotype 9V (n =1399, 1391)	89.1 (87.4 to 90.7)	90.3 (88.6 to 91.8)
Serotype 14 (n =1418, 1408)	91.6 (90.0 to 93.0)	93.5 (92.1 to 94.8)
Serotype 18C (n =1420, 1403)	93.8 (92.4 to 95.0)	94.7 (93.4 to 95.8)
Serotype 19A (n =1420, 1398)	96.3 (95.2 to 97.3)	96.6 (95.5 to 97.5)
Serotype 19F (n =1421, 1403)	80.3 (78.1 to 82.3)	81.5 (79.3 to 83.5)
Serotype 23F (n =1424, 1409)	82.1 (80.0 to 84.1)	83.7 (81.6 to 85.6)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Pneumococcal OPA Titers >=LLOQ for the 7 Additional Serotypes at 1 Month After Vaccination 1 (20vPnC) or 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population

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End point title

Percentage of Subjects With Pneumococcal OPA Titers >=LLOQ for the 7 Additional Serotypes at 1 Month After Vaccination 1 (20vPnC) or 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population ^[77]

End point description

The percentage of subjects with OPA titers >=LLOQ along with corresponding 2-sided 95% CIs were calculated 1 month after vaccination for pneumococcal serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F. E7-AIP included subjects who were enrolled in appropriate cohort based on age, received 20vPnC if randomized to 20vPnC/saline group or received both vaccinations if randomized to 13vPnC/PPSV23 group, had at least 1 valid OPA titers for any of 7 additional serotypes from blood collection 27 to 49 days after Vaccination 1 or Vaccination 2 respectively, had no other major protocol deviations. Here, "n" =subjects evaluable for this endpoint at specified rows.

End point type

Secondary

End point timeframe

1 month after Vaccination 1 in “Cohort 1: 20vPnC/Saline” or 1 month after Vaccination 2 in “Cohort 1: 13vPnC/PPSV23”

Notes
[77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23
Number of subjects analysed	1433	1383
Units: Percentage of subjects
number (confidence interval 95%)
Serotype 8 (n =1374, 1319)	92.9 (91.5 to 94.2)	96.6 (95.5 to 97.5)
Serotype 10A (n =1310, 1263)	95.6 (94.3 to 96.6)	88.9 (87.1 to 90.6)
Serotype 11A (n =1198, 1209)	97.7 (96.6 to 98.4)	95.4 (94.0 to 96.5)
Serotype 12F (n =1294, 1222)	95.7 (94.4 to 96.7)	89.3 (87.4 to 91.0)
Serotype 15B (n =1283, 1249)	94.1 (92.6 to 95.3)	83.3 (81.1 to 85.3)
Serotype 22F (n =1274, 1227)	98.6 (97.8 to 99.2)	94.5 (93.0 to 95.7)
Serotype 33F (n =1157, 1201)	96.4 (95.1 to 97.4)	92.8 (91.2 to 94.2)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Pneumococcal OPA Titers >=LLOQ for the 20 Vaccines Serotypes at 1 Month After Vaccination (20vPnC) in Cohort 2 and 3: Evaluable-20 Immunogenicity Population

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End point title

Percentage of Subjects With Pneumococcal OPA Titers >=LLOQ for the 20 Vaccines Serotypes at 1 Month After Vaccination (20vPnC) in Cohort 2 and 3: Evaluable-20 Immunogenicity Population ^[78]

End point description

The percentage of subjects with OPA titers >=LLOQ along with corresponding 2-sided 95% CIs were calculated 1 month after vaccination for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. Data for this outcome measure were planned to be analyzed for the 20vPnC groups of Cohorts 2 and 3 only. Evaluable-20 immunogenicity population included subjects who were enrolled in the appropriate cohort based on age, received the vaccination as randomized, had at least 1 valid OPA titer from the blood collection 27 to 49 days after 20vPnC, had no other major protocol deviations. Here, "n" =subjects evaluable for this endpoint at specified rows.

End point type

Secondary

End point timeframe

1 month after vaccination

Notes
[78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analyzed for reporting arms “Cohort 1: 20vPnC/Saline” and “Cohort 1: 13vPnC/PPSV23” only.

End point values	Cohort 2: 20vPnC	Cohort 3: 20vPnC
Number of subjects analysed	321	317
Units: Percentage of subjects
number (confidence interval 95%)
Serotype 1 (n =320, 316)	87.2 (83.0 to 90.6)	92.1 (88.5 to 94.8)
Serotype 3 (n =318, 316)	87.4 (83.3 to 90.9)	89.9 (86.0 to 93.0)
Serotype 4 (n =318, 315)	94.0 (90.8 to 96.4)	98.1 (95.9 to 99.3)
Serotype 5 (n =313, 317)	72.8 (67.6 to 77.7)	81.1 (76.3 to 85.2)
Serotype 6A (n =318, 315)	91.8 (88.2 to 94.6)	99.7 (98.2 to 100.0)
Serotype 6B (n =318, 314)	95.3 (92.3 to 97.3)	99.0 (97.2 to 99.8)
Serotype 7F (n =313, 311)	92.7 (89.2 to 95.3)	93.9 (90.6 to 96.3)
Serotype 9V (n =312, 315)	92.6 (89.1 to 95.3)	99.0 (97.2 to 99.8)
Serotype 14 (n =313, 316)	94.9 (91.8 to 97.1)	99.1 (97.3 to 99.8)
Serotype 18C (n =315, 312)	97.5 (95.1 to 98.9)	98.1 (95.9 to 99.3)
Serotype 19A (n =318, 312)	98.7 (96.8 to 99.7)	99.7 (98.2 to 100.0)
Serotype 19F (n =320, 315)	81.9 (77.2 to 85.9)	95.2 (92.3 to 97.3)
Serotype 23F (n =319, 315)	89.3 (85.4 to 92.5)	96.5 (93.8 to 98.2)
Serotype 8 (n =314, 306)	92.4 (88.8 to 95.0)	95.8 (92.8 to 97.7)
Serotype 10A (n =296, 292)	98.3 (96.1 to 99.4)	100.0 (98.7 to 100.0)
Serotype 11A (n =271, 263)	97.0 (94.3 to 98.7)	99.6 (97.9 to 100.0)
Serotype 12F (n =292, 273)	97.9 (95.6 to 99.2)	98.5 (96.3 to 99.6)
Serotype 15B (n =284, 279)	95.8 (92.7 to 97.8)	96.8 (94.0 to 98.5)
Serotype 22F (n =284, 273)	98.2 (95.9 to 99.4)	99.6 (98.0 to 100.0)
Serotype 33F (n =266, 251)	95.9 (92.7 to 97.9)	99.6 (97.8 to 100.0)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Local reactions: within 10 days after Vaccination 1 (systematic assessment), Systemic events: within 7 days after Vaccination 1 (systematic assessment), Non serious AEs: up to 1 month after Vaccination 1, SAEs: up to 6 months after Vaccination 1

Adverse event reporting additional description

Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 subject and as non-serious in another subject or 1 subject may have experienced both serious and non-serious event during study. Safety population was used for the analysis.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

22.1

Reporting group title

Cohort 1: 20vPnC/Saline

Reporting group description

Reporting group title

Cohort 1: 13vPnC/PPSV23

Reporting group description

Reporting group title

Cohort 2: 20vPnC

Reporting group description

Subjects aged 50 through 59 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 20vPnC (Day 1).

Reporting group title

Cohort 2: 13vPnC

Reporting group description

Subjects aged 50 through 59 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 13vPnC (Day 1).

Reporting group title

Cohort 3: 20vPnC

Reporting group description

Subjects aged 18 through 49 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 20vPnC (Day 1).

Reporting group title

Cohort 3: 13vPnC

Reporting group description

Subjects aged 18 through 49 years were randomized to receive a single dose of 0.5 mL intramuscular injection of 13vPnC (Day 1).

Serious adverse events	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23	Cohort 2: 20vPnC	Cohort 2: 13vPnC	Cohort 3: 20vPnC	Cohort 3: 13vPnC
Total subjects affected by serious adverse events
subjects affected / exposed	36 / 1507 (2.39%)	29 / 1490 (1.95%)	1 / 334 (0.30%)	1 / 111 (0.90%)	2 / 335 (0.60%)	1 / 112 (0.89%)
number of deaths (all causes)	1	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Glioblastoma multiforme
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to peritoneum
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic carcinoma
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	2 / 1507 (0.13%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transitional cell carcinoma
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hernia
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	2 / 1507 (0.13%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	1 / 335 (0.30%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Completed suicide
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device malfunction
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood pressure increased
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gun shot wound
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Heat exhaustion
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle rupture
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural haematuria
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stress fracture
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	1 / 335 (0.30%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 1507 (0.07%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 1507 (0.00%)	2 / 1490 (0.13%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	3 / 1507 (0.20%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Silent myocardial infarction
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic encephalopathy
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 1507 (0.07%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Blood loss anaemia
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Colitis
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Biloma
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	2 / 1507 (0.13%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
End stage renal disease
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	0 / 1507 (0.00%)	0 / 1490 (0.00%)	1 / 334 (0.30%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ureteric obstruction
subjects affected / exposed	0 / 1507 (0.00%)	0 / 1490 (0.00%)	1 / 334 (0.30%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neck mass
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	2 / 1507 (0.13%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	2 / 1507 (0.13%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis infective
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	2 / 1507 (0.13%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Kidney infection
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin bacterial infection
subjects affected / exposed	0 / 1507 (0.00%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	1 / 111 (0.90%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes simplex meningitis
subjects affected / exposed	0 / 1507 (0.00%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 1507 (0.07%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 1507 (0.00%)	1 / 1490 (0.07%)	0 / 334 (0.00%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Cohort 1: 20vPnC/Saline	Cohort 1: 13vPnC/PPSV23	Cohort 2: 20vPnC	Cohort 2: 13vPnC	Cohort 3: 20vPnC	Cohort 3: 13vPnC
Total subjects affected by non serious adverse events
subjects affected / exposed	1074 / 1507 (71.27%)	1063 / 1490 (71.34%)	281 / 334 (84.13%)	91 / 111 (81.98%)	302 / 335 (90.15%)	107 / 112 (95.54%)
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 1507 (0.00%)	0 / 1490 (0.00%)	4 / 334 (1.20%)	0 / 111 (0.00%)	0 / 335 (0.00%)	0 / 112 (0.00%)
occurrences all number	0	0	4	0	0	0
Nervous system disorders
Headache (HEADACHE)
subjects affected / exposed	324 / 1507 (21.50%)	345 / 1490 (23.15%)	107 / 334 (32.04%)	40 / 111 (36.04%)	130 / 335 (38.81%)	38 / 112 (33.93%)
occurrences all number	324	345	107	40	130	38
General disorders and administration site conditions
Fatigue (FATIGUE)
subjects affected / exposed	454 / 1507 (30.13%)	455 / 1490 (30.54%)	130 / 334 (38.92%)	40 / 111 (36.04%)	143 / 335 (42.69%)	49 / 112 (43.75%)
occurrences all number	454	455	130	40	143	49
Injection site erythema (REDNESS)
subjects affected / exposed	110 / 1507 (7.30%)	92 / 1490 (6.17%)	27 / 334 (8.08%)	6 / 111 (5.41%)	30 / 335 (8.96%)	11 / 112 (9.82%)
occurrences all number	110	92	27	6	30	11
Injection site pain (PAIN)
subjects affected / exposed	834 / 1507 (55.34%)	803 / 1490 (53.89%)	240 / 334 (71.86%)	77 / 111 (69.37%)	272 / 335 (81.19%)	92 / 112 (82.14%)
occurrences all number	834	803	240	77	272	92
Injection site swelling (SWELLING)
subjects affected / exposed	113 / 1507 (7.50%)	118 / 1490 (7.92%)	29 / 334 (8.68%)	12 / 111 (10.81%)	39 / 335 (11.64%)	14 / 112 (12.50%)
occurrences all number	113	118	29	12	39	14
Pyrexia (FEVER)
subjects affected / exposed	0 / 1507 (0.00%)	0 / 1490 (0.00%)	5 / 334 (1.50%)	1 / 111 (0.90%)	4 / 335 (1.19%)	2 / 112 (1.79%)
occurrences all number	0	0	5	1	4	2
Musculoskeletal and connective tissue disorders
Arthralgia (JOINT PAIN)
subjects affected / exposed	190 / 1507 (12.61%)	203 / 1490 (13.62%)	51 / 334 (15.27%)	23 / 111 (20.72%)	45 / 335 (13.43%)	20 / 112 (17.86%)
occurrences all number	190	203	51	23	45	20
Myalgia (MUSCLE PAIN)
subjects affected / exposed	588 / 1507 (39.02%)	553 / 1490 (37.11%)	165 / 334 (49.40%)	55 / 111 (49.55%)	223 / 335 (66.57%)	83 / 112 (74.11%)
occurrences all number	588	553	165	55	223	83
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	0 / 1507 (0.00%)	0 / 1490 (0.00%)	4 / 334 (1.20%)	3 / 111 (2.70%)	7 / 335 (2.09%)	1 / 112 (0.89%)
occurrences all number	0	0	4	3	7	1
Influenza
subjects affected / exposed	0 / 1507 (0.00%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	7 / 335 (2.09%)	1 / 112 (0.89%)
occurrences all number	0	0	0	0	7	1
Nasopharyngitis
subjects affected / exposed	0 / 1507 (0.00%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	6 / 335 (1.79%)	2 / 112 (1.79%)
occurrences all number	0	0	0	0	6	2
Urinary tract infection
subjects affected / exposed	0 / 1507 (0.00%)	0 / 1490 (0.00%)	0 / 334 (0.00%)	0 / 111 (0.00%)	1 / 335 (0.30%)	2 / 112 (1.79%)
occurrences all number	0	0	0	0	1	2

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Were there any global substantial amendments to the protocol? Yes

25 Sep 2018

1. Revised the scope of clinical assessment, allowing for physical examination based on medical history. 2. Added instruction for the investigator to contact the sponsor or designee for SAEs occurring within 30 days after vaccination

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, Randomized, Double-blind Trial to Evaluate the Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine in Pneumococcal Vaccine–naïve Adults 18 Years of age and Older

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects With Local Reactions Within 10 Days After Vaccination in All Cohorts

Primary: Percentage of Subjects With Local Reactions Within 10 Days After Vaccination in All Cohorts

Primary: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination in All Cohorts

Primary: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination in All Cohorts

Primary: Percentage of Subjects With Adverse Events (AEs) Within 1 Month After Vaccination in All Cohorts

Primary: Percentage of Subjects With Adverse Events (AEs) Within 1 Month After Vaccination in All Cohorts

Primary: Percentage of Subjects With Serious Adverse Events (SAEs) Within 6 Months After Vaccination in All Cohorts

Primary: Percentage of Subjects With Serious Adverse Events (SAEs) Within 6 Months After Vaccination in All Cohorts

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Conditions (NDCMCs) Within 6 Months After Vaccination in All Cohorts

Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Conditions (NDCMCs) Within 6 Months After Vaccination in All Cohorts

Primary: Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the 13 Matched Serotypes at 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

Primary: Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the 13 Matched Serotypes at 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

Primary: Pneumococcal OPA GMTs for the 7 Additional Serotypes at 1 Month After Vaccination 1 (20vPnC) or 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population (E7-AIP)

Primary: Pneumococcal OPA GMTs for the 7 Additional Serotypes at 1 Month After Vaccination 1 (20vPnC) or 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population (E7-AIP)

Secondary: Pneumococcal OPA GMTs for the 20 Vaccines Serotypes at 1 Month After 20vPnC Vaccination in Cohort 2, 50 Through 59 Years of Age and Cohort 1, Only 60 Through 64 Years of Age: Evaluable-20 Immunogenicity Population

Secondary: Pneumococcal OPA GMTs for the 20 Vaccines Serotypes at 1 Month After 20vPnC Vaccination in Cohort 2, 50 Through 59 Years of Age and Cohort 1, Only 60 Through 64 Years of Age: Evaluable-20 Immunogenicity Population

Secondary: Pneumococcal OPA GMTs for the 20 Vaccines Serotypes at 1 Month After 20vPnC Vaccination in Cohort 3, 18 Through 49 Years and Cohort 1, Only 60 Through 64 Years of Age: Evaluable-20 Immunogenicity Population

Secondary: Pneumococcal OPA GMTs for the 20 Vaccines Serotypes at 1 Month After 20vPnC Vaccination in Cohort 3, 18 Through 49 Years and Cohort 1, Only 60 Through 64 Years of Age: Evaluable-20 Immunogenicity Population

Secondary: Pneumococcal OPA Geometric Mean Fold Rises (GMFRs) for the 13 Matched Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

Secondary: Pneumococcal OPA Geometric Mean Fold Rises (GMFRs) for the 13 Matched Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

Secondary: Pneumococcal OPA GMFRs for the Additional 7 Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC) or From Before Vaccination 1 to 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population

Secondary: Pneumococcal OPA GMFRs for the Additional 7 Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC) or From Before Vaccination 1 to 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population

Secondary: Pneumococcal OPA GMFRs for the 20 Vaccines Serotypes From Before Vaccination to 1 Month After Vaccination in Cohort 2 and 3: Evaluable-20 Immunogenicity Population

Secondary: Pneumococcal OPA GMFRs for the 20 Vaccines Serotypes From Before Vaccination to 1 Month After Vaccination in Cohort 2 and 3: Evaluable-20 Immunogenicity Population

Secondary: Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers to the 13 Matched Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

Secondary: Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers to the 13 Matched Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

Secondary: Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers for the 7 Additional Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1(20vPnC) or From Before Vaccination 1 to 1 Month After Vaccination 2(PPSV23) in Cohort 1:E7-AIP

Secondary: Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers for the 7 Additional Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1(20vPnC) or From Before Vaccination 1 to 1 Month After Vaccination 2(PPSV23) in Cohort 1:E7-AIP

Secondary: Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers for the 20 Vaccines Serotypes From Before Vaccination to 1 Month After Vaccination in Cohort 2 and 3: Evaluable-20 Immunogenicity Population

Secondary: Percentage of Subjects With >=4-Fold Rise in Pneumococcal OPA Titers for the 20 Vaccines Serotypes From Before Vaccination to 1 Month After Vaccination in Cohort 2 and 3: Evaluable-20 Immunogenicity Population

Secondary: Percentage of Subjects With Pneumococcal OPA Titers >= Lower Limit of Quantitation (LLOQ) for the 13 Matched Serotypes at 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

Secondary: Percentage of Subjects With Pneumococcal OPA Titers >= Lower Limit of Quantitation (LLOQ) for the 13 Matched Serotypes at 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population

Secondary: Percentage of Subjects With Pneumococcal OPA Titers >=LLOQ for the 7 Additional Serotypes at 1 Month After Vaccination 1 (20vPnC) or 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population

Secondary: Percentage of Subjects With Pneumococcal OPA Titers >=LLOQ for the 7 Additional Serotypes at 1 Month After Vaccination 1 (20vPnC) or 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population

Secondary: Percentage of Subjects With Pneumococcal OPA Titers >=LLOQ for the 20 Vaccines Serotypes at 1 Month After Vaccination (20vPnC) in Cohort 2 and 3: Evaluable-20 Immunogenicity Population

Secondary: Percentage of Subjects With Pneumococcal OPA Titers >=LLOQ for the 20 Vaccines Serotypes at 1 Month After Vaccination (20vPnC) in Cohort 2 and 3: Evaluable-20 Immunogenicity Population

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Randomized, Double-blind Trial to Evaluate the Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine in Pneumococcal Vaccine–naïve Adults 18 Years of age and Older