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Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Interchangeability of V114 and Prevnar 13™ with Respect to Safety, Tolerability, and Immunogenicity in Healthy Infants (PNEU-DIRECTION)

Summary
EudraCT number	2018-001151-12
Trial protocol	Outside EU/EEA
Global end of trial date	14 Dec 2020

Results information
Results version number	v2(current)
This version publication date	14 Oct 2021
First version publication date	20 Jun 2021
Other versions	v1
Version creation reason

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

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Trial information

Top of page

Sponsor protocol code

V114-027

ISRCTN number

US NCT number

NCT03620162

WHO universal trial number (UTN)

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, United States, 07033

Public contact

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

Scientific contact

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

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

Yes

EMA paediatric investigation plan number(s)

EMEA-002215-PIP01-17

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

14 Dec 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

14 Dec 2020

Global end of trial reached?

Yes

Global end of trial date

14 Dec 2020

Was the trial ended prematurely?

Main objective of the trial

The goal of this study is to evaluate the safety, tolerability, and immunogenicity of the Pneumococcal Conjugate Vaccines (PCVs) V114 and Prevnar 13™ in healthy infants switched from Prevnar 13™ to V114 during the four-dose PCV immunization schedule.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Oct 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 487

Country: Number of subjects enrolled

Puerto Rico: 156

Country: Number of subjects enrolled

Thailand: 170

Country: Number of subjects enrolled

Turkey: 87

Worldwide total number of subjects

900

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

900

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Participants were screened at Study Day 1, prior to randomization.

Period 1 title

Period 1 (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer

Are arms mutually exclusive

Yes

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™

Arm description

Participants received a single 0.5 mL intramuscular (IM) injection of Prevnar 13™ on Day 1 (Vaccination 1), Month 2 (Vaccination 2), Month 4 (Vaccination 3) and Months 10-13 (Vaccination 4). Participants concomitantly received other licensed background paediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.

Arm type

Active comparator

Investigational medicinal product name

Prevnar 13™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Prevnar 13™ contains the pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each) and 6B (4.4 mcg) in each 0.5 mL dose given via IM injection.

Investigational medicinal product name

RotaTeq™

Investigational medicinal product code

Other name

V260; Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

RotaTeq™ live, pentavalent Rotavirus vaccine given as background treatment via oral solution.

Investigational medicinal product name

Pentacel™

Investigational medicinal product code

Other name

Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Pentacel™ Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine, given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

RECOMBIVAX HB™

Investigational medicinal product code

Other name

V232, HEPTAVAX™-II, HBVAXPRO; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

RECOMBIVAX HB™ Hepatitis B Vaccine (Recombinant), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

HIBERIX™

Investigational medicinal product code

Other name

Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

HIBERIX™ Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

M-M-R™ II

Investigational medicinal product code

Other name

V205C; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

M-M-R™ II (Measles, Mumps, and Rubella Virus Vaccine Live), given as background treatment via subcutaneous (SC) injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

VARIVAX™

Investigational medicinal product code

Other name

V210; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

VARIVAX™ Varicella Virus Vaccine Live, given as background treatment via SC injection in the opposite limb to V114 and Prevnar 13™ administration.

Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Arm description

Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1 (Vaccination 1), Month 2 (Vaccination 2), Month 4 (Vaccination 3) and a single 0.5 mL IM injection of V114 on Months 10-13 (Vaccination 4). Participants concomitantly received other licensed background paediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.

Arm type

Experimental

Investigational medicinal product name

Prevnar 13™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Prevnar 13™ contains the pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each) and 6B (4.4 mcg) in each 0.5 mL dose given via IM injection.

Investigational medicinal product name

RotaTeq™

Investigational medicinal product code

Other name

V260; Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

RotaTeq™ live, pentavalent Rotavirus vaccine given as background treatment via oral solution.

Investigational medicinal product name

V114

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

V114 contains the pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), and serotype 6B (4 mcg) in each 0.5 mL dose given via IM injection.

Investigational medicinal product name

M-M-R™ II

Investigational medicinal product code

Other name

V205C; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

M-M-R™ II (Measles, Mumps, and Rubella Virus Vaccine Live), given as background treatment via subcutaneous (SC) injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

HIBERIX™

Investigational medicinal product code

Other name

Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

HIBERIX™ Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

RECOMBIVAX HB™

Investigational medicinal product code

Other name

V232, HEPTAVAX™-II, HBVAXPRO; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

RECOMBIVAX HB™ Hepatitis B Vaccine (Recombinant), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

VARIVAX™

Investigational medicinal product code

Other name

V210; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

VARIVAX™ Varicella Virus Vaccine Live, given as background treatment via SC injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

Pentacel™

Investigational medicinal product code

Other name

Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Arm description

Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1 (Vaccination 1), Month 2 (Vaccination 2) and a single 0.5 mL IM injection of V114 on Month 4 (Vaccination 3) and Months 10-13 (Vaccination 4). Participants concomitantly received other licensed background paediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.

Arm type

Experimental

Investigational medicinal product name

RotaTeq™

Investigational medicinal product code

Other name

V260; Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

RotaTeq™ live, pentavalent Rotavirus vaccine given as background treatment via oral solution.

Investigational medicinal product name

V114

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Prevnar 13™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Prevnar 13™ contains the pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each) and 6B (4.4 mcg) in each 0.5 mL dose given via IM injection.

Investigational medicinal product name

VARIVAX™

Investigational medicinal product code

Other name

V210; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

VARIVAX™ Varicella Virus Vaccine Live, given as background treatment via SC injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

Pentacel™

Investigational medicinal product code

Other name

Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

M-M-R™ II

Investigational medicinal product code

Other name

V205C; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

M-M-R™ II (Measles, Mumps, and Rubella Virus Vaccine Live), given as background treatment via subcutaneous (SC) injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

HIBERIX™

Investigational medicinal product code

Other name

Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

HIBERIX™ Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

RECOMBIVAX HB™

Investigational medicinal product code

Other name

V232, HEPTAVAX™-II, HBVAXPRO; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

RECOMBIVAX HB™ Hepatitis B Vaccine (Recombinant), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Group 4: Prevnar 13™−V114−V114−V114

Arm description

Participants received a single 0.5 mL IM injection of Prevnar 13™ on Day 1 (Vaccination 1) and a single 0.5 mL IM injection of V114 on Month 2 (Vaccination 2), Month 4 (Vaccination 3) and Months 10-13 (Vaccination 4). Participants concomitantly received other licensed background paediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.

Arm type

Experimental

Investigational medicinal product name

Prevnar 13™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Prevnar 13™ contains the pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each) and 6B (4.4 mcg) in each 0.5 mL dose given via IM injection.

Investigational medicinal product name

V114

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

RotaTeq™

Investigational medicinal product code

Other name

V260; Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

RotaTeq™ live, pentavalent Rotavirus vaccine given as background treatment via oral solution.

Investigational medicinal product name

Pentacel™

Investigational medicinal product code

Other name

Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

RECOMBIVAX HB™

Investigational medicinal product code

Other name

V232, HEPTAVAX™-II, HBVAXPRO; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

RECOMBIVAX HB™ Hepatitis B Vaccine (Recombinant), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

HIBERIX™

Investigational medicinal product code

Other name

Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

HIBERIX™ Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

M-M-R™ II

Investigational medicinal product code

Other name

V205C; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

M-M-R™ II (Measles, Mumps, and Rubella Virus Vaccine Live), given as background treatment via subcutaneous (SC) injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

VARIVAX™

Investigational medicinal product code

Other name

V210; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

VARIVAX™ Varicella Virus Vaccine Live, given as background treatment via SC injection in the opposite limb to V114 and Prevnar 13™ administration.

Group 5: V114−V114−V114−V114

Arm description

Participants received a single 0.5 mL IM injection of V114 on Day 1 (Vaccination 1), Month 2 (Vaccination 2), Month 4 (Vaccination 3) and Months 10-13 (Vaccination 4). Participants concomitantly received other licensed background paediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.

Arm type

Experimental

Investigational medicinal product name

V114

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

RotaTeq™

Investigational medicinal product code

Other name

V260; Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

RotaTeq™ live, pentavalent Rotavirus vaccine given as background treatment via oral solution.

Investigational medicinal product name

Pentacel™

Investigational medicinal product code

Other name

Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

RECOMBIVAX HB™

Investigational medicinal product code

Other name

V232, HEPTAVAX™-II, HBVAXPRO; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

RECOMBIVAX HB™ Hepatitis B Vaccine (Recombinant), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

HIBERIX™

Investigational medicinal product code

Other name

Trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

HIBERIX™ Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate), given as background treatment via IM injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

M-M-R™ II

Investigational medicinal product code

Other name

V205C; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

M-M-R™ II (Measles, Mumps, and Rubella Virus Vaccine Live), given as background treatment via subcutaneous (SC) injection in the opposite limb to V114 and Prevnar 13™ administration.

Investigational medicinal product name

VARIVAX™

Investigational medicinal product code

Other name

V210; trade names of the background vaccines may vary depending on where clinical supplies were sourced.

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

VARIVAX™ Varicella Virus Vaccine Live, given as background treatment via SC injection in the opposite limb to V114 and Prevnar 13™ administration.

Number of subjects in period 1	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114
Started	179	181	180	180	180
Vaccination 1 (V114 or Prevnar 13™)	179	181	178	179	179
Vaccination 2 (V114 or Prevnar 13™)	176	175	166	169	173
Vaccination 3 (V114 or Prevnar 13™)	175	174	161	167	173
Vaccination 4 (V114 or Prevnar 13™)	165	168	150	162	168
Completed	164	167	147	160	167
Not completed	15	14	33	20	13
Physician decision	4	-	1	-	2
Consent withdrawn by parent/guardian	9	8	25	17	9
Lost to follow-up	2	6	7	3	2

Baseline characteristics

Top of page

Reporting group title

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™

Reporting group description

Reporting group title

Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Reporting group description

Reporting group title

Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Reporting group description

Reporting group title

Group 4: Prevnar 13™−V114−V114−V114

Reporting group description

Reporting group title

Group 5: V114−V114−V114−V114

Reporting group description

Reporting group values	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114	Total
Number of subjects	179	181	180	180	180	900
Age Categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	179	181	180	180	180	900
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0
Age Continuous
Units: days
arithmetic mean (standard deviation)	63.0 ( 7.8 )	63.6 ( 8.4 )	62.7 ( 9.1 )	63.4 ( 9.3 )	64.0 ( 9.3 )	-
Gender Categorical
Units: Subjects
Female	76	91	85	86	88	426
Male	103	90	95	94	92	474
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic Or Latino	33	47	47	43	43	213
Not Hispanic Or Latino	146	134	133	136	137	686
Unknown Or Not Reported	0	0	0	1	0	1
Race (NIH/OMB)
Units: Subjects
American Indian Or Alaska Native	1	0	0	0	0	1
Asian	36	34	37	32	38	177
Black Or African American	8	11	3	3	9	34
More Than One Race	19	30	26	30	28	133
Native Hawaiian Or Other Pacific Islander	0	0	0	1	1	2
White	115	106	114	114	104	553

End points

Top of page

Reporting group title

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™

Reporting group description

Reporting group title

Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Reporting group description

Reporting group title

Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Reporting group description

Reporting group title

Group 4: Prevnar 13™−V114−V114−V114

Reporting group description

Reporting group title

Group 5: V114−V114−V114−V114

Reporting group description

Subject analysis set title

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Group 4: Prevnar 13™−V114−V114−V114

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Group 5: V114−V114−V114−V114

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 4: Prevnar 13™−V114−V114−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 5: V114−V114−V114−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 4: Prevnar 13™−V114−V114−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 5: V114−V114−V114−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 4: Prevnar 13™−V114−V114−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 5: V114−V114−V114−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 1 + Group 2

Subject analysis set type

Per protocol

Subject analysis set description

Group 1 participants who received a single 0.5 mL IM injection of Prevnar 13™ on Day 1 (Vaccination 1), Month 2 (Vaccination 2), Month 4 (Vaccination 3), Months 10-13 (Vaccination 4) and Group 2 participants who received a single 0.5 mL IM injection of Prevnar 13™ on Day 1 (Vaccination 1), Month 2 (Vaccination 2), Month 4 (Vaccination 3) and a single 0.5 mL IM injection of V114 on Months 10-13 (Vaccination 4), were combined across vaccination schedule. Group 1 plus Group 2 participants concomitantly received other licensed background paediatric vaccines as follows: RotaTeq™, Pentacel™, RECOMBIVAX HB™ on Day 1, Month 2, and on Month 4; HIBERIX™, M-M-R™ II, VARIVAX™ on Months 10-13.

Subject analysis set title

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 5: V114−V114−V114−V114

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Group 1 + Group 2

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Percentage of Participants With a Solicited Injection-site Adverse Event (AE)

Top of page

End point title

Percentage of Participants With a Solicited Injection-site Adverse Event (AE)

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Per protocol, the percentage of participants with solicited injection-site AEs was assessed for up to ~14 days after each vaccination. The solicited injection-site AEs assessed were erythema/redness, induration/hard lump, tenderness/pain and swelling. The analysis population included all randomized participants who got ≥1 dose of V114 or Prevnar 13™.

End point type

Primary

End point timeframe

Up to ~14 days after each vaccination

End point values	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114
Number of subjects analysed	179	181	178	179	179
Units: Percentage of Participants
number (not applicable)
Erythema/Redness	47.5	37.6	38.8	43.0	44.1
Induration/Hard lump	34.6	26.0	28.1	25.1	26.3
Tenderness/Pain	44.1	43.6	46.1	43.6	47.5
Swelling	22.9	18.8	24.7	20.7	22.9

Difference in Percentage: Erythema(Group 5 vs 1)

Comparison groups

Group 5: V114−V114−V114−V114 v Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

= 0.525

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-13.6

upper limit

Notes
[1] - Estimated differences, confidence intervals (CIs), and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Erythema(Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[2]

P-value

= 0.396

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-4.5

Confidence interval

level

95%

sides

2-sided

lower limit

-14.7

upper limit

5.8

Notes
[2] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Erythema(Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

= 0.097

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-18.8

upper limit

1.6

Notes
[3] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Erythema(Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[4]

P-value

= 0.057

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-9.9

Confidence interval

level

95%

sides

2-sided

lower limit

-19.9

upper limit

0.3

Notes
[4] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Induration(Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.085

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-8.4

Confidence interval

level

95%

sides

2-sided

lower limit

-17.8

upper limit

1.2

Notes
[5] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Induration(Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[6]

P-value

= 0.05

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-9.5

Confidence interval

level

95%

sides

2-sided

lower limit

-18.9

upper limit

Notes
[6] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Induration(Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[7]

P-value

= 0.183

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-6.5

Confidence interval

level

95%

sides

2-sided

lower limit

-16.1

upper limit

3.1

Notes
[7] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Induration(Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[8]

P-value

= 0.074

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-18.1

upper limit

0.8

Notes
[8] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Tenderness(Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[9]

P-value

= 0.525

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

13.6

Notes
[9] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Tenderness(Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[10]

P-value

= 0.915

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-10.8

upper limit

9.7

Notes
[10] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Tenderness(Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[11]

P-value

= 0.714

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

12.2

Notes
[11] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Tenderness(Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[12]

P-value

= 0.926

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-10.7

upper limit

9.7

Notes
[12] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Swelling(Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[13]

P-value

> 0.999

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

8.7

Notes
[13] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Swelling(Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[14]

P-value

= 0.609

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-10.8

upper limit

6.4

Notes
[14] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Swelling(Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[15]

P-value

= 0.688

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

10.7

Notes
[15] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Swelling(Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[16]

P-value

= 0.336

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-12.6

upper limit

4.3

Notes
[16] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Primary: Percentage of Participants with a Solicited Systemic AE

Top of page

End point title

Percentage of Participants with a Solicited Systemic AE

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Per protocol, the percentage of participants with solicited systemic AEs was assessed for up to ~14 days after each vaccination. The solicited systemic AEs assessed were appetite lost/decreased appetite, irritability, drowsiness/somnolence and hives or welts/urticaria. The analysis population included all randomized participants who got ≥1 dose of V114 or Prevnar 13™.

End point type

Primary

End point timeframe

Up to ~14 days after each vaccination

End point values	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114
Number of subjects analysed	179	181	178	179	179
Units: Percentage of Participants
number (not applicable)
Appetite lost/Decreased Appetite	35.8	32.0	27.0	35.2	34.6
Irritability	67.6	60.8	62.9	68.2	70.4
Drowsiness/Somnolence	57.0	55.8	56.7	57.0	60.3
Hives/Urticaria	7.3	3.9	5.6	8.9	6.7

Difference in Percentage:Appetite lost(Group5 vs1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[17]

P-value

= 0.825

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-11

upper limit

8.8

Notes
[17] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage:Appetite lost(Group4 vs1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[18]

P-value

= 0.912

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-10.4

upper limit

9.3

Notes
[18] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage:Appetite lost(Group3 vs1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[19]

P-value

= 0.074

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-8.8

Confidence interval

level

95%

sides

2-sided

lower limit

-18.3

upper limit

0.9

Notes
[19] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage:Appetite lost(Group2 vs1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[20]

P-value

= 0.458

Method

Miettinen & Nurminen method

Parameter type

Percentage of Participants

Point estimate

-3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-13.4

upper limit

6.1

Notes
[20] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage:Irritability(Group 5 vs1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[21]

P-value

= 0.568

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6.8

upper limit

12.3

Notes
[21] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage:Irritability(Group 4 vs1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[22]

P-value

= 0.91

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-9.1

upper limit

10.2

Notes
[22] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage:Irritability(Group 3 vs1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[23]

P-value

= 0.354

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-14.5

upper limit

5.2

Notes
[23] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage:Irritability(Group 2 vs1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[24]

P-value

= 0.178

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-6.8

Confidence interval

level

95%

sides

2-sided

lower limit

-16.6

upper limit

3.1

Notes
[24] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Drowsiness(Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[25]

P-value

= 0.52

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6.8

upper limit

13.5

Notes
[25] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Drowsiness(Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[26]

P-value

> 0.999

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-10.2

upper limit

10.2

Notes
[26] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Drowsiness(Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[27]

P-value

= 0.963

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-10.5

upper limit

Notes
[27] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Drowsiness(Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[28]

P-value

= 0.821

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-11.4

upper limit

Notes
[28] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Hives(Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[29]

P-value

= 0.836

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

Notes
[29] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Hives(Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[30]

P-value

= 0.562

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

7.6

Notes
[30] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Hives(Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[31]

P-value

= 0.527

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

3.7

Notes
[31] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

Difference in Percentage: Hives(Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[32]

P-value

= 0.16

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-8.6

upper limit

1.5

Notes
[32] - Estimated differences, CIs, and p-values are calculated based on the Miettinen & Nurminen method and are provided in accordance with the statistical analysis plan.

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

Top of page

End point title

Percentage of Participants with a Vaccine-related Serious Adverse Event (SAE)

End point description

An SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgement. Relatedness of an SAE to the study vaccine was determined by the investigator. Per protocol, the percentage of participants with vaccine-related SAEs was assessed through 6 months following Vaccination 4. The analysis population included all randomized participants who got ≥1 dose of V114 or Prevnar 13™.

End point type

Primary

End point timeframe

Up to ~6 months after Vaccination 4 (up to ~19 months)

End point values	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114
Number of subjects analysed	179	181	178	179	179
Units: Percentage of Participants
number (not applicable)	0	0	0.6	0	0

Difference in Percentage (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[33]

Method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

2.1

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

Difference in Percentage (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[34]

Method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

2.1

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

Difference in Percentage (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[35]

Method

Parameter type

Difference in Percentage

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

3.1

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

Difference in Percentage (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[36]

Method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

2.1

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

Primary: Geometric Mean Concentration (GMC) of Anti-Pneumococcal Polysaccharide (PnP) Immunoglobulin G (IgG) For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

Top of page

End point title

Geometric Mean Concentration (GMC) of Anti-Pneumococcal Polysaccharide (PnP) Immunoglobulin G (IgG) For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

End point description

The GMC of anti-PnP serotype-specific IgG for 13 shared serotypes contained in V114 and Prevnar 13™ (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) was assessed using a pneumococcal electrochemiluminescence (PnECL) assay. Per protocol, 13 IgG serotypes in Groups 2, 3, 4 (experimental arms) were compared to Group 1 (comparator arm) at 30 days post Vaccination 4 as a pre-specified primary outcome analysis; 13 IgG serotypes in Group 5 (experimental arm) were compared to Group 1 (comparator arm) at 30 days post Vaccination 4, as a separate protocol-specified secondary outcome analysis and reported later in the record. Analysis population included all randomized participants who were compliant with the protocol, got scheduled dosing of V114 or Prevnar 13™, and had IgG GMC data available for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F or 23F in Groups 1, 2, 3, 4 or 5 at 30 Days post Vaccination 4.

End point type

Primary

End point timeframe

30 Days after Vaccination 4 (Months 11-14)

End point values	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114
Number of subjects analysed	179	181	178	179	179
Units: µg/mL
geometric mean (confidence interval 95%)
Serotype 1 (n= 147, 151, 128, 139, 147)	2.02 (1.78 to 2.30)	1.69 (1.48 to 1.93)	1.89 (1.63 to 2.18)	1.68 (1.48 to 1.91)	1.46 (1.30 to 1.63)
Serotype 3 (n=148, 151, 128, 139, 147)	0.72 (0.64 to 0.82)	0.77 (0.68 to 0.87)	0.68 (0.61 to 0.77)	0.73 (0.66 to 0.82)	0.89 (0.79 to 0.99)
Serotype 4 (n=146, 151, 128, 139, 147)	1.51 (1.30 to 1.76)	1.33 (1.14 to 1.56)	1.27 (1.10 to 1.46)	1.23 (1.08 to 1.41)	1.35 (1.17 to 1.57)
Serotype 5 (n=147, 151, 128, 138, 147)	3.66 (3.18 to 4.20)	3.39 (2.91 to 3.94)	3.82 (3.23 to 4.51)	2.90 (2.50 to 3.38)	2.90 (2.50 to 3.35)
Serotype 6A (n=146, 151, 128, 139, 147)	6.42 (5.56 to 7.42)	7.16 (6.30 to 8.15)	7.16 (6.17 to 8.30)	5.17 (4.43 to 6.03)	4.43 (3.86 to 5.09)
Serotype 6B (n=146, 151, 128, 139, 147)	6.15 (5.36 to 7.07)	7.58 (6.61 to 8.68)	6.64 (5.73 to 7.69)	6.62 (5.75 to 7.62)	5.83 (5.09 to 6.68)
Serotype 7F (n=146, 151, 128, 139, 147)	5.10 (4.43 to 5.88)	5.69 (4.93 to 6.56)	5.06 (4.33 to 5.92)	3.98 (3.47 to 4.57)	3.43 (3.02 to 3.91)
Serotype 9V (n=147, 151, 128, 139, 147)	2.93 (2.56 to 3.34)	2.76 (2.41 to 3.16)	2.57 (2.22 to 2.97)	2.46 (2.19 to 2.78)	2.89 (2.56 to 3.26)
Serotype 14 (n=146, 151, 128, 139, 147)	7.62 (6.55 to 8.86)	10.59 (9.01 to 12.44)	10.91 (9.29 to 12.81)	7.87 (6.77 to 9.16)	6.57 (5.73 to 7.55)
Serotype 18C (n=147, 151, 128, 139, 147)	2.57 (2.21 to 2.99)	3.88 (3.38 to 4.45)	3.70 (3.20 to 4.29)	2.76 (2.42 to 3.15)	2.65 (2.34 to 3.01)
Serotype 19A (n=148, 151, 128, 139, 147)	5.92 (5.15 to 6.80)	5.52 (4.88 to 6.25)	5.20 (4.42 to 6.12)	4.95 (4.27 to 5.73)	4.66 (4.15 to 5.24)
Serotype 19F (n=148, 151, 128, 139, 147)	4.78 (4.22 to 5.42)	4.88 (4.33 to 5.51)	5.02 (4.40 to 5.73)	4.60 (4.00 to 5.28)	4.10 (3.66 to 4.59)
Serotype 23F (n=146, 150, 127, 138, 146)	2.89 (2.42 to 3.44)	2.72 (2.33 to 3.18)	2.29 (1.93 to 2.70)	2.22 (1.92 to 2.56)	2.11 (1.81 to 2.46)

GMC Ratio: Serotype 1 (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[37]

Method

Parameter type

GMC Ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.12

Notes
[37] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 1 (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[38]

Method

Parameter type

GMC Ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

Notes
[38] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 1 (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[39]

Method

Parameter type

GMC Ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

Notes
[39] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 3 (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[40]

Method

Parameter type

GMC Ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.19

Notes
[40] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 3 (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[41]

Method

Parameter type

GMC Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.12

Notes
[41] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 3 (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[42]

Method

Parameter type

GMC Ratio

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.25

Notes
[42] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 4 (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[43]

Method

Parameter type

GMC Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

Notes
[43] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 4 (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[44]

Method

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.03

Notes
[44] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 4 (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[45]

Method

Parameter type

GMC Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.08

Notes
[45] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 5 (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[46]

Method

Parameter type

GMC Ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.29

Notes
[46] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 5 (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[47]

Method

Parameter type

GMC Ratio

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.98

Notes
[47] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 5 (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[48]

Method

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.14

Notes
[48] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 6A (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[49]

Method

Parameter type

GMC Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

0.98

Notes
[49] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 6A (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[50]

Method

Parameter type

GMC Ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.37

Notes
[50] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 6B (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[51]

Method

Parameter type

GMC Ratio

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.31

Notes
[51] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 6A (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[52]

Method

Parameter type

GMC Ratio

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.36

Notes
[52] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 6B (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[53]

Method

Parameter type

GMC Ratio

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.32

Notes
[53] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 7F (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[54]

Method

Parameter type

GMC Ratio

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.95

Notes
[54] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 6B (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[55]

Method

Parameter type

GMC Ratio

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

1.49

Notes
[55] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 7F (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[56]

Method

Parameter type

GMC Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.21

Notes
[56] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 7F (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[57]

Method

Parameter type

GMC Ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.35

Notes
[57] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 9V (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[58]

Method

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.01

Notes
[58] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 9V (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[59]

Method

Parameter type

GMC Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.06

Notes
[59] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 9V (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[60]

Method

Parameter type

GMC Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.13

Notes
[60] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 14 (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[61]

Method

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.28

Notes
[61] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 14 (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[62]

Method

Parameter type

GMC Ratio

Point estimate

1.43

Confidence interval

level

95%

sides

2-sided

lower limit

1.15

upper limit

1.78

Notes
[62] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 14 (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[63]

Method

Parameter type

GMC Ratio

Point estimate

1.39

Confidence interval

level

95%

sides

2-sided

lower limit

1.13

upper limit

1.71

Notes
[63] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 18C (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[64]

Method

Parameter type

GMC Ratio

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.3

Notes
[64] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 18C (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[65]

Method

Parameter type

GMC Ratio

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

1.76

Notes
[65] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 18C (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[66]

Method

Parameter type

GMC Ratio

Point estimate

1.51

Confidence interval

level

95%

sides

2-sided

lower limit

1.25

upper limit

1.83

Notes
[66] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 19A (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[67]

Method

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.01

Notes
[67] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 19A (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[68]

Method

Parameter type

GMC Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.07

Notes
[68] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 19A (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[69]

Method

Parameter type

GMC Ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.13

Notes
[69] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 19F (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[70]

Method

Parameter type

GMC Ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.15

Notes
[70] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 19F (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[71]

Method

Parameter type

GMC Ratio

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.26

Notes
[71] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 19F (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[72]

Method

Parameter type

GMC Ratio

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.21

Notes
[72] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 23F (Group 4 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 4: Prevnar 13™−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[73]

Method

Parameter type

GMC Ratio

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

0.96

Notes
[73] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 23F (Group 3 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

other ^[74]

Method

Parameter type

GMC Ratio

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

0.99

Notes
[74] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 23F (Group 2 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Number of subjects included in analysis

360

Analysis specification

Pre-specified

Analysis type

other ^[75]

Method

Parameter type

GMC Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.17

Notes
[75] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

Secondary: Group 5 Versus Group 1 + Group 2: Percentage of Participants with anti-Hepatitis B Surface Antigen (HBsAg) ≥10 mIU/mL at 30 Days Post Vaccination 3

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End point title

Group 5 Versus Group 1 + Group 2: Percentage of Participants with anti-Hepatitis B Surface Antigen (HBsAg) ≥10 mIU/mL at 30 Days Post Vaccination 3

End point description

The concentration of anti-HBsAg was assessed using an enhanced chemiluminescence assay. The protocol-specified analysis of the percentage of participants with anti-HBsAg ≥10 mIU/mL at 30 days post vaccination 3 was conducted in participants combined across vaccine dosing schedules (Group 1 + Group 2) as well as in participants separated across vaccine dosing schedules (Group 1, Group 2). Per protocol, participants with anti-HBsAg ≥10 mIU/mL in Group 5 were compared to Group 1 + Group 2 at 30 days post Vaccination 3, as a pre-specified secondary outcome analysis. Analysis of participants with anti-HBsAg ≥10 mIU/mL was not planned to be reported in Group 3 and Group 4, per protocol. Analysis population included all randomized participants who were compliant with the protocol, got scheduled dosing of V114, Prevnar 13™ or background RECOMBIVAX HB™, and had anti-HBsAg ≥10 mIU/mL data available at 30 days post Vaccination 3.

End point type

Secondary

End point timeframe

30 Days after Vaccination 3 (Month 5)

End point values	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 5: V114−V114−V114−V114	Group 1 + Group 2
Number of subjects analysed	0 ^[76]	0 ^[77]	142	142	153	284
Units: Percentage of Participants
number (not applicable)			98.6	99.3	98.7	98.9

Notes
[76] - Analysis of participants with anti-HBsAg was not planned to be reported in Group 3 per protocol.
[77] - Analysis of participants with anti-HBsAg was not planned to be reported in Group 4 per protocol.

Difference in Percentage (Group 5 vs Group 1+2)

Comparison groups

Group 5: V114−V114−V114−V114 v Group 1 + Group 2

Number of subjects included in analysis

437

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[78]

P-value

< 0.001

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

Notes
[78] - The statistical criterion for non-inferiority requires the lower bound of the 2-sided 95% CI for the difference in percentages (Group 5/Group 1+Group 2) to be >-10 percentage points.

Secondary: Group 5 Versus Group 1 + Group 2: Geometric Mean Titer (GMT) of Anti-Rotavirus Immunoglobulin A (IgA) at 30 Days Post Vaccination 3

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End point title

Group 5 Versus Group 1 + Group 2: Geometric Mean Titer (GMT) of Anti-Rotavirus Immunoglobulin A (IgA) at 30 Days Post Vaccination 3

End point description

The GMT of anti-rotavirus IgA was assessed using a serum IgA enzyme linked immunosorbent assay. The protocol specified analysis of anti-rotavirus IgA GMT at 30 days post vaccination 3 was conducted in participants combined across vaccine dosing schedules (Group 1 + Group 2) as well as in participants separated across vaccine dosing schedules (Group 1, Group 2). Per protocol, GMT of anti-rotavirus IgA in Group 5 was compared to Group 1 + Group 2 at 30 days post Vaccination 3, as a pre-specified secondary outcome analysis. Anti-rotavirus IgA GMT analysis was not planned to be reported in Group 3 and Group 4, per protocol. Analysis population included all randomized participants who were compliant with the protocol, got scheduled dosing of V114, Prevnar 13™ or background RotaTeq™, and had anti-rotavirus IgA GMT data available at 30 days post Vaccination 3.

End point type

Secondary

End point timeframe

30 Days after Vaccination 3 (Month 5)

End point values	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114	Group 1 + Group 2
Number of subjects analysed	147	143	0 ^[79]	0 ^[80]	152	290
Units: Titers
geometric mean (confidence interval 95%)	286.5 (218.1 to 376.2)	329.5 (254.9 to 426.1)	( to )	( to )	298.3 (228.2 to 390.0)	307.0 (254.7 to 369.9)

Notes
[79] - Anti-rotavirus IgA GMT analysis was not planned to be reported in Group 3, per protocol.
[80] - Anti-rotavirus IgA GMT analysis was not planned to be reported in Group 4, per protocol.

GMT Ratio (Group 5 vs Group 1+2)

Comparison groups

Group 5: V114−V114−V114−V114 v Group 1 + Group 2

Number of subjects included in analysis

442

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[81]

P-value

< 0.001

Method

ANCOVA

Parameter type

GMT Ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.34

Notes
[81] - The statistical criterion for non-inferiority requires the lower bound of the 2-sided 95% CI for the GMT ratio (Group 5/Group 1+Group 2) to be >0.5.

Secondary: GMC of Anti-PnP IgG for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

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End point title

GMC of Anti-PnP IgG for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

End point description

The concentration of anti-PnP serotype-specific IgG for 15 serotypes contained in V114 (13 serotypes shared with Prevnar 13™ [1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F] and 2 unique serotypes [22F, 33F]) was assessed using a PnECL assay. Per protocol, GMC of 15 IgG serotypes was assessed at 30 days post Vaccination 3. Analysis population included all randomized participants who were compliant with the protocol, got scheduled dosing of V114 or Prevnar 13™, and had IgG GMC data available for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 22F or 33F in Groups 1, 2, 3, 4 or 5 at 30 Days post Vaccination 3.

End point type

Secondary

End point timeframe

30 Days after Vaccination 3 (Month 5)

End point values	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114
Number of subjects analysed	179	181	178	179	179
Units: µg/mL
geometric mean (confidence interval 95%)
Serotype 1 (n=142, 142, 129, 138, 148)	1.93 (1.69 to 2.20)	1.99 (1.78 to 2.21)	1.86 (1.64 to 2.10)	1.35 (1.19 to 1.53)	1.27 (1.14 to 1.41)
Serotype 3 (n=142, 142, 129, 138, 147)	0.54 (0.47 to 0.61)	0.64 (0.56 to 0.73)	0.56 (0.49 to 0.63)	0.67 (0.60 to 0.76)	1.01 (0.91 to 1.12)
Serotype 4 (n=141, 139, 128, 137, 147)	1.39 (1.22 to 1.57)	1.47 (1.30 to 1.66)	1.34 (1.14 to 1.56)	1.07 (0.93 to 1.22)	1.40 (1.24 to 1.57)
Serotype 5 (n=141, 141, 128, 138, 148)	1.99 (1.69 to 2.34)	2.16 (1.87 to 2.49)	2.15 (1.83 to 2.52)	1.73 (1.50 to 1.99)	1.91 (1.67 to 2.18)
Serotype 6A (n=140, 140, 128, 138, 148)	3.07 (2.66 to 3.54)	3.22 (2.83 to 3.67)	3.26 (2.79 to 3.82)	2.05 (1.76 to 2.38)	1.82 (1.59 to 2.09)
Serotype 6B (n=138, 140, 127, 138, 147)	2.03 (1.66 to 2.49)	2.50 (2.10 to 2.99)	2.43 (2.05 to 2.88)	2.29 (1.91 to 2.76)	2.26 (1.87 to 2.73)
Serotype 7F (n=142, 142, 129, 138, 148)	3.36 (2.99 to 3.77)	3.54 (3.16 to 3.96)	3.52 (3.10 to 3.99)	2.61 (2.33 to 2.94)	2.41 (2.17 to 2.67)
Serotype 9V (n=143, 142, 128, 138, 148)	1.69 (1.48 to 1.94)	1.81 (1.60 to 2.05)	1.68 (1.44 to 1.97)	1.47 (1.28 to 1.67)	2.01 (1.80 to 2.24)
Serotype 14 (n=142, 142, 128, 138, 148)	6.57 (5.55 to 7.79)	6.18 (5.22 to 7.31)	9.32 (7.45 to 11.67)	6.71 (5.76 to 7.83)	5.50 (4.79 to 6.31)
Serotype 18C (n=142, 142, 129, 138, 148)	1.69 (1.46 to 1.95)	2.03 (1.81 to 2.28)	2.08 (1.81 to 2.38)	1.50 (1.33 to 1.71)	1.51 (1.34 to 1.72)
Serotype 19A (n=143, 142, 129, 138, 148)	2.17 (1.92 to 2.47)	2.46 (2.21 to 2.74)	2.25 (1.95 to 2.60)	1.64 (1.43 to 1.87)	1.63 (1.47 to 1.82)
Serotype 19F (n=143, 142, 128, 138, 148)	2.83 (2.51 to 3.18)	2.90 (2.61 to 3.23)	3.08 (2.72 to 3.48)	2.32 (2.06 to 2.62)	2.21 (2.00 to 2.46)
Serotype 23F (n=140, 140, 128, 135, 147)	1.32 (1.09 to 1.59)	1.72 (1.49 to 1.99)	1.22 (1.02 to 1.45)	1.33 (1.14 to 1.57)	1.46 (1.25 to 1.69)
Serotype 22F (n=138, 140, 128, 137, 148)	0.05 (0.04 to 0.05)	0.05 (0.04 to 0.06)	3.63 (2.91 to 4.52)	5.94 (5.13 to 6.88)	5.15 (4.52 to 5.87)
Serotype 33F (n=141, 139, 127, 137, 148)	0.05 (0.05 to 0.06)	0.05 (0.05 to 0.06)	0.28 (0.21 to 0.36)	0.89 (0.70 to 1.14)	2.22 (1.86 to 2.66)

No statistical analyses for this end point

Secondary: Percentage of Participants With Anti-PnP IgG Concentration ≥0.35 µg/mL for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

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End point title

Percentage of Participants With Anti-PnP IgG Concentration ≥0.35 µg/mL for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

End point description

The concentration of anti-PnP serotype-specific IgG for 15 serotypes contained in V114 (13 serotypes shared with Prevnar 13™ [1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F] and 2 unique serotypes [22F, 33F]) was assessed using a PnECL assay. Per protocol, percentage of participants with anti-PnP IgG concentrations ≥0.35 µg/mL was assessed at 30 days post Vaccination 3. Analysis population included all randomized participants who were compliant with the protocol, got scheduled dosing of V114 or Prevnar 13™, and had IgG concentration ≥0.35µg/mL data available for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 22F or 33F in Groups 1, 2, 3, 4 or 5 at 30 Days post Vaccination 3.

End point type

Secondary

End point timeframe

30 Days after Vaccination 3 (Month 5)

End point values	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114
Number of subjects analysed	179	181	178	179	179
Units: Percentage of Participants
number (confidence interval 95%)
Serotype 1 (n=142, 142, 129, 138, 148)	97.9 (94.0 to 99.6)	100 (97.4 to 100.0)	99.2 (95.8 to 100.0)	97.8 (93.8 to 99.5)	96.6 (92.3 to 98.9)
Serotype 3 (n=142, 142, 129, 138, 147)	73.2 (65.2 to 80.3)	73.9 (65.9 to 80.9)	79.1 (71.0 to 85.7)	81.9 (74.4 to 87.9)	93.9 (88.7 to 97.2)
Serotype 4 (n=141, 139, 128, 137, 147)	97.9 (93.9 to 99.6)	98.6 (94.9 to 99.8)	93.0 (87.1 to 96.7)	94.2 (88.8 to 97.4)	96.6 (92.2 to 98.9)
Serotype 5 (n=141, 141, 128, 138, 148)	97.9 (93.9 to 99.6)	99.3 (96.1 to 100.0)	97.7 (93.3 to 99.5)	97.1 (92.7 to 99.2)	98.0 (94.2 to 99.6)
Serotype 6A (n=140, 140, 128, 138, 148)	99.3 (96.1 to 100.0)	99.3 (96.1 to 100.0)	99.2 (95.7 to 100.0)	97.1 (92.7 to 99.2)	98.6 (95.2 to 99.8)
Serotype 6B (n=138, 140, 127, 138, 147)	91.3 (85.3 to 95.4)	94.3 (89.1 to 97.5)	96.1 (91.1 to 98.7)	95.7 (90.8 to 98.4)	95.2 (90.4 to 98.1)
Serotype 7F (n=142, 142, 129, 138, 148)	100 (97.4 to 100.0)	100 (97.4 to 100)	100 (97.2 to 100.0)	100 (97.4 to 100.0)	100 (97.5 to 100.0)
Serotype 9V (n=143, 142, 128, 138, 148)	96.5 (92.0 to 98.9)	96.5 (92.0 to 98.8)	96.1 (91.1 to 98.7)	95.7 (90.8 to 98.4)	98.6 (95.2 to 99.8)
Serotype 14 (n=142, 142, 128, 138, 148)	98.6 (95.0 to 99.8)	98.6 (95.0 to 99.8)	96.9 (92.2 to 99.1)	100 (97.4 to 100.0)	98.6 (95.2 to 99.8)
Serotype 18C (n=142, 142, 129, 138, 148)	95.8 (91.0 to 98.4)	100 (97.4 to 100.0)	99.2 (95.8 to 100.0)	97.8 (93.8 to 99.5)	98.0 (94.2 to 99.6)
Serotype 19A (n=143, 142, 129, 138, 148)	99.3 (96.2 to 100.0)	100 (97.4 to 100.0)	98.4 (94.5 to 99.8)	97.1 (92.7 to 99.2)	97.3 (93.2 to 99.3)
Serotype 19F (n=143, 142, 128, 138, 148)	99.3 (96.2 to 100.0)	99.3 (96.1 to 100.0)	99.2 (95.7 to 100.0)	100 (97.4 to 100.0)	100 (97.5 to 100.0)
Serotype 23F (n=140, 140, 128, 135, 147)	91.4 (85.5 to 95.5)	97.9 (93.9 to 99.6)	90.6 (84.2 to 95.1)	92.6 (86.8 to 96.4)	94.6 (89.6 to 97.6)
Serotype 22F (n=138, 140, 128, 137, 148)	2.9 (0.8 to 7.3)	1.4 (0.2 to 5.1)	93.8 (88.1 to 97.3)	99.3 (96.0 to 100.0)	98.6 (95.2 to 99.8)
Serotype 33F (n=141, 139, 127, 137, 148)	2.1 (0.4 to 6.1)	2.2 (0.4 to 6.2)	39.4 (30.8 to 48.4)	75.9 (67.9 to 82.8)	93.2 (87.9 to 96.7)

No statistical analyses for this end point

Secondary: Group 5 Versus Group 1: GMC of Anti-PnP IgG For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

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End point title

Group 5 Versus Group 1: GMC of Anti-PnP IgG For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

End point description

The GMC of anti-PnP serotype-specific IgG for 13 shared serotypes contained in V114 and Prevnar 13™ (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) was assessed using a PnECL assay. Per protocol, GMC of 13 IgG serotypes was analysed by vaccine dosing schedules (Groups 1, 5). Per protocol, 13 IgG serotypes in Group 5 (experimental arm) were compared to Group 1 (comparator arm) at 30 days post Vaccination 4 as a pre-specified secondary outcome analysis; 13 IgG serotypes in Groups 2, 3, 4 (experimental arms) were compared to Group 1 (comparator arm) at 30 days post Vaccination 4, as a separate protocol-specified primary outcome analysis and reported earlier in the record. Analysis population included all randomized participants who were compliant with the protocol, got scheduled dosing of V114 or Prevnar 13™, and had IgG GMC data available for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F or 23F in Groups 5 or 1 at 30 Days post Vaccination 4.

End point type

Secondary

End point timeframe

30 Days after Vaccination 4 (Months 11-14)

End point values	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114
Number of subjects analysed	179	0 ^[82]	0 ^[83]	0 ^[84]	179
Units: µg/mL
geometric mean (confidence interval 95%)
Serotype 1 (n=147, 147)	2.02 (1.78 to 2.30)	( to )	( to )	( to )	1.46 (1.30 to 1.63)
Serotype 3 (n=148, 147)	0.72 (0.64 to 0.82)	( to )	( to )	( to )	0.89 (0.79 to 0.99)
Serotype 4 (n=146, 147)	1.51 (1.30 to 1.76)	( to )	( to )	( to )	1.35 (1.17 to 1.57)
Serotype 5 (n=147, 147)	3.66 (3.18 to 4.20)	( to )	( to )	( to )	2.90 (2.50 to 3.35)
Serotype 6A (n=146, 147)	6.42 (5.56 to 7.42)	( to )	( to )	( to )	4.43 (3.86 to 5.09)
Serotype 6B (n=146, 147)	6.15 (5.36 to 7.07)	( to )	( to )	( to )	5.83 (5.09 to 6.68)
Serotype 7F (n=146, 147)	5.10 (4.43 to 5.88)	( to )	( to )	( to )	3.43 (3.02 to 3.91)
Serotype 9V (n=147, 147)	2.93 (2.56 to 3.34)	( to )	( to )	( to )	2.89 (2.56 to 3.26)
Serotype 14 (n=146, 147)	7.62 (6.55 to 8.86)	( to )	( to )	( to )	6.57 (5.73 to 7.55)
Serotype 18C (n=147, 147)	2.57 (2.21 to 2.99)	( to )	( to )	( to )	2.65 (2.34 to 3.01)
Serotype 19A (n=148, 147)	5.92 (5.15 to 6.80)	( to )	( to )	( to )	4.66 (4.15 to 5.24)
Serotype 19F (n=148, 147)	4.78 (4.22 to 5.42)	( to )	( to )	( to )	4.10 (3.66 to 4.59)
Serotype 23F (n=146, 146)	2.89 (2.42 to 3.44)	( to )	( to )	( to )	2.11 (1.81 to 2.46)

Notes
[82] - Per protocol Group 2 was compared to Group 1 as a primary endpoint analysis and reported earlier.
[83] - Per protocol Group 3 was compared to Group 1 as a primary endpoint analysis and reported earlier.
[84] - Per protocol Group 4 was compared to Group 1 as a primary endpoint analysis and reported earlier.

GMC Ratio: Serotype 1 (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[85]

Method

Parameter type

GMC Ratio

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

0.86

Notes
[85] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 3 (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[86]

Method

Parameter type

GMC Ratio

Point estimate

1.22

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

1.44

Notes
[86] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 4 (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[87]

Method

Parameter type

GMC Ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.1

Notes
[87] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 5 (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[88]

Method

Parameter type

GMC Ratio

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.97

Notes
[88] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 6A (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[89]

Method

Parameter type

GMC Ratio

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

0.84

Notes
[89] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 6B (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[90]

Method

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.15

Notes
[90] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 7F (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[91]

Method

Parameter type

GMC Ratio

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

0.82

Notes
[91] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 9V (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[92]

Method

Parameter type

GMC Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.18

Notes
[92] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 14 (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[93]

Method

Parameter type

GMC Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.07

Notes
[93] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 18C (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[94]

Method

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.25

Notes
[94] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 19A (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[95]

Method

Parameter type

GMC Ratio

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

0.95

Notes
[95] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 19F (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[96]

Method

Parameter type

GMC Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.02

Notes
[96] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

GMC Ratio: Serotype 23F (Group 5 vs 1)

Comparison groups

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™ v Group 5: V114−V114−V114−V114

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

other ^[97]

Method

Parameter type

GMC Ratio

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

0.91

Notes
[97] - GMC ratio and CI are estimated from a serotype-specific ANCOVA model utilizing the natural log-transformed antibody concentration as the response and vaccination group and stratification factor as covariates.

Adverse events

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Timeframe for reporting adverse events

Non-serious AEs (NSAEs): Up to ~14 days after each vaccination; SAEs and all-cause mortality: Up to ~6 months after Vaccination 4 (up to ~19 months)

Adverse event reporting additional description

Safety was analyzed by the vaccine dosing schedules (Groups 1, 2, 3, 4, 5), from the first vaccination of a participant. All-cause mortality was analyzed in all randomized participants; SAEs and NSAEs were analyzed in all randomized participants who received at least dose of study vaccination V114 or Prevnar 13™.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114

Reporting group description

Reporting group title

Group 3: Prevnar 13™−Prevnar 13™−V114−V114

Reporting group description

Reporting group title

Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™

Reporting group description

Reporting group title

Group 4: Prevnar 13™−V114−V114−V114

Reporting group description

Reporting group title

Group 5: V114−V114−V114−V114

Reporting group description

Serious adverse events	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114
Total subjects affected by serious adverse events
subjects affected / exposed	24 / 181 (13.26%)	15 / 178 (8.43%)	21 / 179 (11.73%)	18 / 179 (10.06%)	21 / 179 (11.73%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hair follicle tumour benign
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Foreign body ingestion
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Humerus fracture
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Subdural haemorrhage
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Nervous system disorders
Epilepsy
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile convulsion
subjects affected / exposed	1 / 181 (0.55%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	2 / 181 (1.10%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
General disorders and administration site conditions
Complication associated with device
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Pyrexia
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Gastrointestinal disorders
Enteritis
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	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
Respiratory, thoracic and mediastinal disorders
Asphyxia
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Aspiration
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Hypoxia
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Interstitial lung disease
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Upper airway obstruction
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Musculoskeletal and connective tissue disorders
Synovitis
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Infections and infestations
Adenoviral upper respiratory infection
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Adenovirus infection
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Arthritis bacterial
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Bacteraemia
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Bacterial infection
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	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
Bronchiolitis
subjects affected / exposed	6 / 181 (3.31%)	3 / 178 (1.69%)	6 / 179 (3.35%)	3 / 179 (1.68%)	8 / 179 (4.47%)
occurrences causally related to treatment / all	0 / 6	0 / 3	0 / 6	0 / 3	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	2 / 179 (1.12%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Conjunctivitis
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Croup infectious
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	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
Exanthema subitum
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	2 / 181 (1.10%)	1 / 178 (0.56%)	4 / 179 (2.23%)	0 / 179 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 4	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Herpangina
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Influenza
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	3 / 179 (1.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mycoplasma infection
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Osteomyelitis
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Otitis media acute
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Periorbital cellulitis
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Pharyngitis
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	1 / 179 (0.56%)	1 / 179 (0.56%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngotonsillitis
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	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
Pneumonia
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	2 / 179 (1.12%)	2 / 179 (1.12%)	2 / 179 (1.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Pneumonia influenzal
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Pneumonia respiratory syncytial viral
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Pneumonia viral
subjects affected / exposed	1 / 181 (0.55%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	2 / 181 (1.10%)	1 / 178 (0.56%)	2 / 179 (1.12%)	3 / 179 (1.68%)	3 / 179 (1.68%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	1 / 179 (0.56%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Skin bacterial infection
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Upper respiratory tract infection
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Urinary tract infection
subjects affected / exposed	2 / 181 (1.10%)	0 / 178 (0.00%)	1 / 179 (0.56%)	2 / 179 (1.12%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection bacterial
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Viral infection
subjects affected / exposed	1 / 181 (0.55%)	1 / 178 (0.56%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral pharyngitis
subjects affected / exposed	1 / 181 (0.55%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Viral rash
subjects affected / exposed	0 / 181 (0.00%)	1 / 178 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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
Viral upper respiratory tract infection
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	0 / 179 (0.00%)	0 / 179 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	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
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 181 (0.00%)	0 / 178 (0.00%)	1 / 179 (0.56%)	0 / 179 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	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

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Group 2: Prevnar 13™−Prevnar 13™−Prevnar 13™−V114	Group 3: Prevnar 13™−Prevnar 13™−V114−V114	Group 1: Prevnar 13™−Prevnar 13™−Prevnar 13™−Prevnar 13™	Group 4: Prevnar 13™−V114−V114−V114	Group 5: V114−V114−V114−V114
Total subjects affected by non serious adverse events
subjects affected / exposed	161 / 181 (88.95%)	160 / 178 (89.89%)	164 / 179 (91.62%)	163 / 179 (91.06%)	160 / 179 (89.39%)
Nervous system disorders
Somnolence
subjects affected / exposed	101 / 181 (55.80%)	101 / 178 (56.74%)	102 / 179 (56.98%)	102 / 179 (56.98%)	108 / 179 (60.34%)
occurrences all number	241	207	285	248	237
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	68 / 181 (37.57%)	69 / 178 (38.76%)	85 / 179 (47.49%)	77 / 179 (43.02%)	79 / 179 (44.13%)
occurrences all number	108	109	137	130	142
Injection site induration
subjects affected / exposed	47 / 181 (25.97%)	50 / 178 (28.09%)	62 / 179 (34.64%)	45 / 179 (25.14%)	47 / 179 (26.26%)
occurrences all number	83	84	106	75	86
Injection site pain
subjects affected / exposed	79 / 181 (43.65%)	82 / 178 (46.07%)	79 / 179 (44.13%)	78 / 179 (43.58%)	85 / 179 (47.49%)
occurrences all number	140	165	158	156	170
Injection site swelling
subjects affected / exposed	34 / 181 (18.78%)	44 / 178 (24.72%)	41 / 179 (22.91%)	37 / 179 (20.67%)	41 / 179 (22.91%)
occurrences all number	55	63	58	59	71
Pyrexia
subjects affected / exposed	66 / 181 (36.46%)	52 / 178 (29.21%)	53 / 179 (29.61%)	49 / 179 (27.37%)	49 / 179 (27.37%)
occurrences all number	94	77	83	78	68
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	11 / 181 (6.08%)	11 / 178 (6.18%)	15 / 179 (8.38%)	10 / 179 (5.59%)	10 / 179 (5.59%)
occurrences all number	12	12	20	10	12
Vomiting
subjects affected / exposed	11 / 181 (6.08%)	4 / 178 (2.25%)	8 / 179 (4.47%)	11 / 179 (6.15%)	11 / 179 (6.15%)
occurrences all number	12	4	11	13	11
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	12 / 181 (6.63%)	10 / 178 (5.62%)	17 / 179 (9.50%)	18 / 179 (10.06%)	17 / 179 (9.50%)
occurrences all number	14	13	17	20	17
Nasal congestion
subjects affected / exposed	15 / 181 (8.29%)	12 / 178 (6.74%)	24 / 179 (13.41%)	12 / 179 (6.70%)	14 / 179 (7.82%)
occurrences all number	18	14	25	16	15
Rhinorrhoea
subjects affected / exposed	3 / 181 (1.66%)	4 / 178 (2.25%)	6 / 179 (3.35%)	16 / 179 (8.94%)	6 / 179 (3.35%)
occurrences all number	3	4	6	16	6
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	7 / 181 (3.87%)	10 / 178 (5.62%)	13 / 179 (7.26%)	16 / 179 (8.94%)	12 / 179 (6.70%)
occurrences all number	9	14	16	20	20
Psychiatric disorders
Irritability
subjects affected / exposed	110 / 181 (60.77%)	112 / 178 (62.92%)	121 / 179 (67.60%)	122 / 179 (68.16%)	126 / 179 (70.39%)
occurrences all number	362	378	430	376	434
Infections and infestations
Nasopharyngitis
subjects affected / exposed	11 / 181 (6.08%)	13 / 178 (7.30%)	10 / 179 (5.59%)	8 / 179 (4.47%)	10 / 179 (5.59%)
occurrences all number	12	14	12	8	12
Upper respiratory tract infection
subjects affected / exposed	9 / 181 (4.97%)	9 / 178 (5.06%)	14 / 179 (7.82%)	12 / 179 (6.70%)	14 / 179 (7.82%)
occurrences all number	10	11	14	13	14
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	58 / 181 (32.04%)	48 / 178 (26.97%)	64 / 179 (35.75%)	63 / 179 (35.20%)	62 / 179 (34.64%)
occurrences all number	95	77	150	90	121

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Interchangeability of V114 and Prevnar 13™ with Respect to Safety, Tolerability, and Immunogenicity in Healthy Infants (PNEU-DIRECTION)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With a Solicited Injection-site Adverse Event (AE)

Primary: Percentage of Participants With a Solicited Injection-site Adverse Event (AE)

Primary: Percentage of Participants with a Solicited Systemic AE

Primary: Percentage of Participants with a Solicited Systemic AE

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

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

Primary: Geometric Mean Concentration (GMC) of Anti-Pneumococcal Polysaccharide (PnP) Immunoglobulin G (IgG) For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

Primary: Geometric Mean Concentration (GMC) of Anti-Pneumococcal Polysaccharide (PnP) Immunoglobulin G (IgG) For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

Secondary: Group 5 Versus Group 1 + Group 2: Percentage of Participants with anti-Hepatitis B Surface Antigen (HBsAg) ≥10 mIU/mL at 30 Days Post Vaccination 3

Secondary: Group 5 Versus Group 1 + Group 2: Percentage of Participants with anti-Hepatitis B Surface Antigen (HBsAg) ≥10 mIU/mL at 30 Days Post Vaccination 3

Secondary: Group 5 Versus Group 1 + Group 2: Geometric Mean Titer (GMT) of Anti-Rotavirus Immunoglobulin A (IgA) at 30 Days Post Vaccination 3

Secondary: Group 5 Versus Group 1 + Group 2: Geometric Mean Titer (GMT) of Anti-Rotavirus Immunoglobulin A (IgA) at 30 Days Post Vaccination 3

Secondary: GMC of Anti-PnP IgG for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

Secondary: GMC of Anti-PnP IgG for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

Secondary: Percentage of Participants With Anti-PnP IgG Concentration ≥0.35 µg/mL for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

Secondary: Percentage of Participants With Anti-PnP IgG Concentration ≥0.35 µg/mL for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

Secondary: Group 5 Versus Group 1: GMC of Anti-PnP IgG For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

Secondary: Group 5 Versus Group 1: GMC of Anti-PnP IgG For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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

Clinical trials

Clinical Trial Results: A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Interchangeability of V114 and Prevnar 13™ with Respect to Safety, Tolerability, and Immunogenicity in Healthy Infants (PNEU-DIRECTION)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With a Solicited Injection-site Adverse Event (AE)

Primary: Percentage of Participants With a Solicited Injection-site Adverse Event (AE)

Primary: Percentage of Participants with a Solicited Systemic AE

Primary: Percentage of Participants with a Solicited Systemic AE

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

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

Primary: Geometric Mean Concentration (GMC) of Anti-Pneumococcal Polysaccharide (PnP) Immunoglobulin G (IgG) For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

Primary: Geometric Mean Concentration (GMC) of Anti-Pneumococcal Polysaccharide (PnP) Immunoglobulin G (IgG) For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

Secondary: Group 5 Versus Group 1 + Group 2: Percentage of Participants with anti-Hepatitis B Surface Antigen (HBsAg) ≥10 mIU/mL at 30 Days Post Vaccination 3

Secondary: Group 5 Versus Group 1 + Group 2: Percentage of Participants with anti-Hepatitis B Surface Antigen (HBsAg) ≥10 mIU/mL at 30 Days Post Vaccination 3

Secondary: Group 5 Versus Group 1 + Group 2: Geometric Mean Titer (GMT) of Anti-Rotavirus Immunoglobulin A (IgA) at 30 Days Post Vaccination 3

Secondary: Group 5 Versus Group 1 + Group 2: Geometric Mean Titer (GMT) of Anti-Rotavirus Immunoglobulin A (IgA) at 30 Days Post Vaccination 3

Secondary: GMC of Anti-PnP IgG for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

Secondary: GMC of Anti-PnP IgG for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

Secondary: Percentage of Participants With Anti-PnP IgG Concentration ≥0.35 µg/mL for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

Secondary: Percentage of Participants With Anti-PnP IgG Concentration ≥0.35 µg/mL for 15 Serotypes Contained in V114 at 30 Days Post Vaccination 3

Secondary: Group 5 Versus Group 1: GMC of Anti-PnP IgG For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

Secondary: Group 5 Versus Group 1: GMC of Anti-PnP IgG For 13 Shared Serotypes Contained in V114 and Prevnar 13™ at 30 Days Post Vaccination 4

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Interchangeability of V114 and Prevnar 13™ with Respect to Safety, Tolerability, and Immunogenicity in Healthy Infants (PNEU-DIRECTION)