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Clinical Trial Results:
A phase 3 open label trial to assess the safety, tolerability, and immunogenicity of 13-valent pneumococcal conjugate vaccine in infants and young children in China who are naive to pneumococcal vaccination

Summary
EudraCT number	2019-000926-23
Trial protocol	Outside EU/EEA
Global end of trial date	13 Oct 2023

Results information
Results version number	v1(current)
This version publication date	11 Apr 2024
First version publication date	11 Apr 2024
Other versions

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

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Trial information

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Sponsor protocol code

B1851178

ISRCTN number

US NCT number

NCT03574389

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

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

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

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

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

31 Mar 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

13 Oct 2023

Was the trial ended prematurely?

Main objective of the trial

To assess the immune responses to the 13 pneumococcal serotypes induced by 13vPnC in infants and children 7 months to <6 years of age (Cohorts 2, 3, and 4) compared to immune responses in infants 6 weeks to 2 months of age (Cohort 1). To evaluate the safety profile of 13vPnC in infants and children 7 months to <6 years of age (Cohorts 2, 3, and 4) as measured by the incidence rates of local reactions, systemic events (including the use of antipyretic medication, and adverse events (AEs).

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Jun 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

China: 932

Worldwide total number of subjects

932

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)

726

Children (2-11 years)

206

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study presents results following completion of all vaccinations, including data from 6-month follow-up after the last study vaccination. This study was conducted in China.

Screening details

A total of 986 subjects were screened in this study, of whom 936 subjects were enrolled or randomized, and 932 of 936 subjects were vaccinated.

Period 1 title

Vaccination Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort 1: 13vPnC

Arm description

Subjects vaccinated with 4 doses of 13vPnC (13-valent Pneumococcal Conjugate) vaccine (single intramuscular injection): Vaccination 1 (Visit 1): 42 to 56 days of age; Vaccination 2 (Visit 2): 42 to 70 days after Visit 1; Vaccination 3 (Visit 3): 42 to 70 days after Visit 2; Vaccination 4: 365 to 455 days of age.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 13-valent pneumococcal conjugate vaccine intramuscularly into a left limb (left anterolateral thigh muscle or deltoid of the left arm).

Cohort 2: 13vPnC

Arm description

Subjects vaccinated with 3 doses of 13vPnC (single intramuscular injection): Vaccination 1 (Visit 1): 7 to <12 months of age; Vaccination 2 (Visit 2): at least 28 days after Visit 1; Vaccination 3: 365 days to <450 days of age and at least 56 days after Visit 2.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 13-valent pneumococcal conjugate vaccine intramuscularly into a left limb (left anterolateral thigh muscle or deltoid of the left arm).

Cohort 2: Hib Vaccine

Arm description

Subjects vaccinated with 2 doses of Hib (Haemophilus influenzae type B) Vaccine (single intramuscular injection): Vaccination 1 (Visit 1): 7 to <12 months of age; Vaccination 2: at least 28 days after Visit 1.

Arm type

Active comparator

Investigational medicinal product name

Hib vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

A 0.5 mL dose of Hib vaccine was administered intramuscularly into a left limb (left anterolateral thigh muscle or deltoid of the left arm).

Cohort 3: 13vPnC

Arm description

Subjects vaccinated with 2 doses of 13vPnC (single intramuscular injection): Vaccination 1 (Visit 1): >=1 to <2 years of age; Vaccination 2: at least 56 days after Visit 1.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 13-valent pneumococcal conjugate vaccine intramuscularly into a left limb (left anterolateral thigh muscle or deltoid of the left arm).

Cohort 3: Hib Vaccine

Arm description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=1 to <2 years of age.

Arm type

Active comparator

Investigational medicinal product name

Hib vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

A 0.5 mL dose of Hib vaccine was administered intramuscularly into a left limb (left anterolateral thigh muscle or deltoid of the left arm).

Cohort 4: 13vPnC

Arm description

Subjects vaccinated with 1 dose of 13vPnC (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 13-valent pneumococcal conjugate vaccine administered intramuscularly into a left limb (left anterolateral thigh muscle or deltoid of the left arm).

Cohort 4: Hib Vaccine

Arm description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Arm type

Active comparator

Investigational medicinal product name

Hib vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

A 0.5 mL dose of Hib vaccine was administered intramuscularly into a left limb (left anterolateral thigh muscle or deltoid of the left arm).

Number of subjects in period 1	Cohort 1: 13vPnC	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine
Started	125	236	117	165	83	138	68
Vaccination 1	125	236	117	165	83	138	68
Vaccination 2	114	219	107	146	0 ^[1]	0 ^[2]	0 ^[3]
Vaccination 3	111	214	0 ^[4]	0 ^[5]	0 ^[6]	0 ^[7]	0 ^[8]
Vaccination 4	92	0 ^[9]	0 ^[10]	0 ^[11]	0 ^[12]	0 ^[13]	0 ^[14]
Completed	90	214	107	146	83	138	68
Not completed	35	22	10	19	0	0	0
Noncompliance With Investigational Product	3	-	-	-	-	-	-
Adverse event	-	1	-	-	-	-	-
Withdrawal by Parent/guardian	26	21	10	19	-	-	-
Unspecified	6	-	-	-	-	-	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[11] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[12] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[13] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.
[14] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Not all participants received all vaccines.

Period 2 title

Follow-up Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort 1: 13vPnC

Arm description

Subjects vaccinated with 4 doses of 13vPnC (single intramuscular injection): Vaccination 1 (Visit 1): 42 to 56 days of age; Vaccination 2 (Visit 2): 42 to 70 days after Visit 1; Vaccination 3 (Visit 3): 42 to 70 days after Visit 2; Vaccination 4: 365 to 455 days of age.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort 2: 13vPnC

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort 2: Hib Vaccine

Arm description

Subjects vaccinated with 2 doses of Hib Vaccine (single intramuscular injection): Vaccination 1 (Visit 1): 7 to <12 months of age; Vaccination 2: at least 28 days after Visit 1.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort 3: 13vPnC

Arm description

Subjects vaccinated with 2 doses of 13vPnC (single intramuscular injection): Vaccination 1 (Visit 1): >=1 to <2 years of age; Vaccination 2: at least 56 days after Visit 1.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort 3: Hib Vaccine

Arm description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=1 to <2 years of age.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort 4: 13vPnC

Arm description

Subjects vaccinated with 1 dose of 13vPnC (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort 4: Hib Vaccine

Arm description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	Cohort 1: 13vPnC	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine
Started	90	214	107	146	83	138	68
Completed	89	201	98	137	76	131	67
Not completed	1	13	9	9	7	7	1
Withdrawal by Parent/guardian	1	13	9	9	7	7	1

Baseline characteristics

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Reporting group title

Cohort 1: 13vPnC

Reporting group description

Reporting group title

Cohort 2: 13vPnC

Reporting group description

Reporting group title

Cohort 2: Hib Vaccine

Reporting group description

Reporting group title

Cohort 3: 13vPnC

Reporting group description

Subjects vaccinated with 2 doses of 13vPnC (single intramuscular injection): Vaccination 1 (Visit 1): >=1 to <2 years of age; Vaccination 2: at least 56 days after Visit 1.

Reporting group title

Cohort 3: Hib Vaccine

Reporting group description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=1 to <2 years of age.

Reporting group title

Cohort 4: 13vPnC

Reporting group description

Subjects vaccinated with 1 dose of 13vPnC (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Reporting group title

Cohort 4: Hib Vaccine

Reporting group description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Reporting group values	Cohort 1: 13vPnC	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine	Total
Number of subjects	125	236	117	165	83	138	68	932
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	125	236	117	162	78	0	0	718
Children (2-11 years)	0	0	0	3	5	138	68	214
Adolescents (12-17 years)	0	0	0	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0	0
Age Continuous
The ages of subjects in Cohort 3 and 4 were counted in different 'Unit of Measures' from Cohort 1 and 2, and thus they were reported in separated 'Baseline Measures'. Cohort 1 and 2 were reported here. "0" signifies data was measured in years for subjects in this Cohort.
Units: days
arithmetic mean (standard deviation)	49.1 ± 3.78	286.0 ± 41.06	285.9 ± 40.40	0 ± 0	0 ± 0	0 ± 0	0 ± 0	-
Sex: Female, Male
Units: Subjects
Female	59	115	50	83	36	56	37	436
Male	66	121	67	82	47	82	31	496
Race
Units: Subjects
Asian	125	236	117	165	83	138	68	932
Ethnicity
Units: Subjects
Non-Hispanic/Non-Latino	125	236	117	165	83	138	68	932
Age Continuous
The ages of subjects in Cohort 1 and 2 were counted in different 'Unit of Measures' from Cohort 3 and 4, and thus they were reported in separated 'Baseline Measures'. Cohort 3 and 4 were reported here. "0" signifies data was measured in days for subjects in this Cohort.
Units: Years
arithmetic mean (standard deviation)	0 ± 0	0 ± 0	0 ± 0	1.5 ± 0.27	1.6 ± 0.30	3.3 ± 1.11	3.3 ± 1.04	-

End points

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Reporting group title

Cohort 1: 13vPnC

Reporting group description

Reporting group title

Cohort 2: 13vPnC

Reporting group description

Reporting group title

Cohort 2: Hib Vaccine

Reporting group description

Reporting group title

Cohort 3: 13vPnC

Reporting group description

Subjects vaccinated with 2 doses of 13vPnC (single intramuscular injection): Vaccination 1 (Visit 1): >=1 to <2 years of age; Vaccination 2: at least 56 days after Visit 1.

Reporting group title

Cohort 3: Hib Vaccine

Reporting group description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=1 to <2 years of age.

Reporting group title

Cohort 4: 13vPnC

Reporting group description

Subjects vaccinated with 1 dose of 13vPnC (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Reporting group title

Cohort 4: Hib Vaccine

Reporting group description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Reporting group title

Cohort 1: 13vPnC

Reporting group description

Reporting group title

Cohort 2: 13vPnC

Reporting group description

Reporting group title

Cohort 2: Hib Vaccine

Reporting group description

Subjects vaccinated with 2 doses of Hib Vaccine (single intramuscular injection): Vaccination 1 (Visit 1): 7 to <12 months of age; Vaccination 2: at least 28 days after Visit 1.

Reporting group title

Cohort 3: 13vPnC

Reporting group description

Subjects vaccinated with 2 doses of 13vPnC (single intramuscular injection): Vaccination 1 (Visit 1): >=1 to <2 years of age; Vaccination 2: at least 56 days after Visit 1.

Reporting group title

Cohort 3: Hib Vaccine

Reporting group description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=1 to <2 years of age.

Reporting group title

Cohort 4: 13vPnC

Reporting group description

Subjects vaccinated with 1 dose of 13vPnC (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Reporting group title

Cohort 4: Hib Vaccine

Reporting group description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Subject analysis set title

Cohort 1: Infant Series

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects vaccinated with 3 infant series doses of 13vPnC (single intramuscular injection): Vaccination 1: 42 to 56 days of age; Vaccination 2: 42 to 70 days after Visit 1;Vaccination 3: 42 to 70 days after Visit 2.

Subject analysis set title

Cohort 1: Toddler Dose

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects vaccinated with 4 doses of 13vPnC (single intramuscular injection):Vaccination 1 (Visit 1): 42 to 56 days of age;Vaccination 2 (Visit 2): 42 to 70 days after Visit 1;Vaccination 3 (Visit 3): 42 to 70 days after Visit 2; Vaccination 4: 365 to 455 days of age.

Primary: The Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for Each of the Pneumococcal Serotypes Measured in Cohorts 2, 3 and 4 Compared to IgG GMCs Measured in Cohort 1

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End point title

The Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for Each of the Pneumococcal Serotypes Measured in Cohorts 2, 3 and 4 Compared to IgG GMCs Measured in Cohort 1 ^[1] ^[2]

End point description

Serotype-specific IgG concentrations to the 13 pneumococcal serotypes(1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F, and 23F)were determined in all subjects from blood samples taken 1 month after the infant series in Cohort 1 and the last dose 13vPnC in Cohorts 2, 3, 4.GMC and corresponding 2-sided 95%confidence intervals(CI)were evaluated.Geometric means were calculated using all subjects with available data for the specified blood draw.Evaluable analysis set included all subjects evaluable for the study at randomization;received all study vaccinations for Cohort 2-4,received all 3 infant series doses for Cohort 1;had blood drawn for assay testing within 27-56 days after third vaccination,visit 3,visit 2 and visit 1 for Cohort 1,2,3 and 4,respectively and the sample from this blood drawn provided at least 1 valid and determinate assay result;received no prohibited vaccine;had no major protocol violation."Number of Subjects Analyzed" =the number of subjects who were evaluable for this endpoint.

End point type

Primary

End point timeframe

Cohort 1: 1 month after the third dose of 13vPnC (infant series dose). Cohort 2, 3, 4: 1 month after the last dose of 13vPnC

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 2: 13vPnC	Cohort 3: 13vPnC	Cohort 4: 13vPnC	Cohort 1: Infant Series
Number of subjects analysed	176	127	131	72
Units: microgram/milliliter (mcg/mL)
geometric mean (confidence interval 95%)
Serotype 1	3.75 (3.26 to 4.32)	4.38 (3.75 to 5.11)	4.40 (3.76 to 5.14)	5.40 (4.43 to 6.58)
Serotype 3	1.19 (1.08 to 1.32)	1.32 (1.16 to 1.51)	1.12 (0.97 to 1.29)	0.63 (0.54 to 0.75)
Serotype 4	2.97 (2.60 to 3.40)	4.04 (3.48 to 4.68)	4.47 (3.92 to 5.10)	3.96 (3.24 to 4.84)
Serotype 5	3.07 (2.73 to 3.46)	2.57 (2.26 to 2.92)	2.92 (2.57 to 3.32)	3.50 (2.91 to 4.19)
Serotype 6A	3.12 (2.74 to 3.57)	3.19 (2.69 to 3.78)	3.39 (2.80 to 4.09)	5.35 (4.44 to 6.44)
Serotype 6B	2.20 (1.91 to 2.54)	2.47 (2.06 to 2.96)	2.96 (2.44 to 3.59)	4.62 (3.76 to 5.69)
Serotype 7F	5.73 (5.10 to 6.44)	7.87 (6.90 to 8.96)	7.08 (6.19 to 8.10)	7.14 (6.00 to 8.50)
Serotype 9V	2.24 (1.99 to 2.51)	3.31 (2.90 to 3.77)	3.68 (3.22 to 4.21)	3.66 (2.99 to 4.50)
Serotype 14	10.89 (9.59 to 12.35)	9.79 (8.40 to 11.41)	6.94 (5.53 to 8.70)	15.09 (11.39 to 20.00)
Serotype 18C	2.25 (1.98 to 2.57)	3.88 (3.25 to 4.64)	5.60 (4.74 to 6.62)	4.94 (4.11 to 5.94)
Serotype 19A	3.62 (3.30 to 3.97)	5.55 (4.86 to 6.34)	11.62 (9.75 to 13.86)	3.44 (2.85 to 4.16)
Serotype 19F	4.50 (3.98 to 5.09)	5.04 (4.28 to 5.92)	5.44 (4.46 to 6.64)	4.95 (3.91 to 6.26)
Serotype 23F	2.04 (1.76 to 2.37)	2.26 (1.90 to 2.67)	2.80 (2.33 to 3.36)	4.36 (3.23 to 5.88)

No statistical analyses for this end point

Primary: Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 2

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End point title

Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 2 ^[3] ^[4]

End point description

Local reactions (redness, swelling, and tenderness) at the site of the investigational product injection were monitored daily for 7 days after each vaccination. Temperature were collected at bedtime daily for 7 days and at any time during the 7 days that fever is suspected. Fever is defined as temperature of greater than or equal to 38.0 degree Celsius (100.4ºF). Other systemic events (decreased appetite, drowsiness and irritability) were recorded for 7 days after each investigational product vaccination. The safety population included all subjects who received at least 1 dose of the investigational product.99999 indicates data could not be calculated as no subjects received vaccination 3 for Cohort 2 Hib vaccine. 'n' = subjects evaluable for specified rows.

End point type

Primary

End point timeframe

Day 1 to Day 7 after vaccination 1, 2 and 3

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine
Number of subjects analysed	236	117
Units: Subjects
Local Reactions- Vaccination 1 (n=236, 117)	66	18
Local Reactions- Vaccination 2 (n=219,107)	20	14
Local Reactions- Vaccination 3 (n=194,0)	4	99999
Systemic Events- Vaccination 1 (n=236,117)	23	7
Systemic Events- Vaccination 2 (n=219,107)	23	5
Systemic Events- Vaccination 3 (n=194,0)	1	99999

No statistical analyses for this end point

Primary: Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 3

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End point title

Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 3 ^[5] ^[6]

End point description

Local reactions (redness, swelling, and tenderness) at the site of the investigational product injection were monitored daily for 7 days after each vaccination. Temperature were collected at bedtime daily for 7 days and at any time during the 7 days that fever is suspected. Fever is defined as temperature of greater than or equal to 38.0ºC (100.4ºF). Other systemic events (decreased appetite, drowsiness and irritability) were recorded for 7 days after each investigational product vaccination. The safety population included all subjects who received at least 1 dose of the investigational product. 99999 indicates data could not be calculated as no subjects received vaccination 2 for Cohort 3 Hib vaccine. 'n' = subjects evaluable for specified rows.

End point type

Primary

End point timeframe

Day 1 to Day 7 after vaccination 1 and 2

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine
Number of subjects analysed	164	83
Units: Subjects
Local Reactions- Vaccination 1 (n=164,83)	45	10
Local Reactions- Vaccination 2 (n=146,0)	9	99999
Systemic Events- Vaccination 1 (n=164,83)	26	7
Systemic Events- Vaccination 2 (n=146,0)	4	99999

No statistical analyses for this end point

Primary: Number of Subjects With Adverse Events (AE) From the Signing of the Informed Consent Document (ICD) to 1 Month After the Last Vaccination in Cohorts 2, 3, 4

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End point title

Number of Subjects With Adverse Events (AE) From the Signing of the Informed Consent Document (ICD) to 1 Month After the Last Vaccination in Cohorts 2, 3, 4 ^[7] ^[8]

End point description

An AE was any untoward medical occurrence in a study subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage.The safety population included all subjects who received at least 1 dose of the investigational product.

End point type

Primary

End point timeframe

From the signing of ICD to 1 month after the last vaccination (13vPnC or Hib) in Cohort 2, 3 and 4

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine
Number of subjects analysed	236	117	165	83	138	68
Units: Subjects	76	29	21	1	11	1

No statistical analyses for this end point

Primary: Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 4

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End point title

Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 4 ^[9] ^[10]

End point description

Local reactions (redness, swelling, and tenderness) at the site of the investigational product injection were monitored daily for 7 days after each vaccination. Temperature were collected at bedtime daily for 7 days and at any time during the 7 days that fever is suspected. Fever is defined as temperature of greater than or equal to 38.0ºC (100.4ºF). Other systemic events (fatigue, headache, vomiting, diarrhea, muscle pain and joint pain) were recorded for 7 days after each investigational product vaccination. The safety population included all subjects who received at least 1 dose of the investigational product. 'n' = subjects evaluable for specified rows.

End point type

Primary

End point timeframe

Within 7 Days After Vaccination 1

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine
Number of subjects analysed	138	68
Units: Subjects
Local Reactions- Vaccination 1 (n=138,67)	48	21
Systemic Events- Vaccination 1 (n=138,68)	17	10

No statistical analyses for this end point

Primary: Number of Subjects With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From 1 Month to 6 Months After the Last Vaccination in Cohorts 2, 3, 4

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End point title

Number of Subjects With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From 1 Month to 6 Months After the Last Vaccination in Cohorts 2, 3, 4 ^[11] ^[12]

End point description

Number of subjects with NDCMCs from 1 month after the last study vaccination (13vPnC or Hib vaccine) to 6 months after the last study vaccination in Cohorts 2, 3, and 4. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects.The safety population included all subjects who received at least 1 dose of the investigational product.

End point type

Primary

End point timeframe

From 1 month after last vaccination to 6 months after the last vaccination in Cohorts 2,3,4

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine
Number of subjects analysed	236	117	165	83	138	68
Units: Subjects	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Number of Subjects With SAE From the Signing of the ICD to 6 Months After the Last Vaccination in Cohorts 2, 3, 4

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End point title

Number of Subjects With SAE From the Signing of the ICD to 6 Months After the Last Vaccination in Cohorts 2, 3, 4 ^[13] ^[14]

End point description

An SAE was any untoward medical occurrence at any dose that resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect or considered to be an important medical event.The safety population included all subjects who received at least 1 dose of the investigational product.

End point type

Primary

End point timeframe

From the signing of ICD to 6 months after the last vaccination (13vPnC or Hib) in Cohorts 2, 3 and 4

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine
Number of subjects analysed	236	117	165	83	138	68
Units: Subjects	5	1	2	0	2	1

No statistical analyses for this end point

Secondary: The Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for Each of the Pneumococcal Serotypes Measured in Cohorts 2, 3 and 4 Compared to IgG GMTs Measured in Cohort 1

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End point title

The Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for Each of the Pneumococcal Serotypes Measured in Cohorts 2, 3 and 4 Compared to IgG GMTs Measured in Cohort 1 ^[15]

End point description

Serotype-specific OPA titers to the 13 pneumococcal serotypes(1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F,23F)were determined in randomly selected subset of subjects receiving 13vPnC from the blood samples taken 1 month after the infant series in Cohort 1 and the last 13vPnC vaccination in each of the 3 cohorts.GMT and corresponding 2-sided 95%CI were evaluated.GMs were calculated using all subjects with available data for the specified blood draw.Evaluable analysis set included all subjects evaluable for the study at randomization; received all study vaccinations for Cohort 2-4,received all 3 infant series doses for Cohort1;had blood draw for assay testing within 27-56 days after third vaccination for Cohort 1,visit 3 for Cohort 2,visit 2 for Cohort 3,visit 1 for Cohort 4 and the sample from this blood drawn provided at least 1 valid and determinate assay result; received no prohibited vaccine;had no major protocol violation."Number of Subjects Analyzed"=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Cohort 1: 1 month after the third dose of 13vPnC. Cohort 2, 3, 4: 1 month after the last dose of 13vPnC

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 2: 13vPnC	Cohort 3: 13vPnC	Cohort 4: 13vPnC	Cohort 1: Infant Series
Number of subjects analysed	87	78	71	37
Units: Titers
geometric mean (confidence interval 95%)
Serotype 1	142.7 (103.4 to 196.9)	93.3 (70.1 to 124.1)	40.9 (31.3 to 53.4)	201.7 (134.8 to 301.8)
Serotype 3	249.0 (205.7 to 301.5)	332.3 (273.3 to 404.1)	244.8 (192.0 to 312.1)	112.9 (82.5 to 154.4)
Serotype 4	2172.2 (1740.7 to 2710.7)	2682.8 (2210.4 to 3256.2)	4236.3 (3489.6 to 5142.8)	1857.8 (1264.8 to 2728.8)
Serotype 5	286.3 (214.5 to 382.0)	164.5 (131.5 to 205.7)	79.3 (57.7 to 109.0)	645.9 (452.6 to 921.8)
Serotype 6A	6042.7 (4830.2 to 7559.6)	7661.8 (6116.0 to 9598.4)	5849.3 (4364.0 to 7840.2)	5996.2 (4337.5 to 8289.3)
Serotype 6B	2181.6 (1350.1 to 3525.2)	4986.3 (3717.6 to 6687.9)	3775.2 (2825.1 to 5044.9)	2331.6 (1481.3 to 3670.0)
Serotype 7F	10234.6 (8612.2 to 12162.8)	14963.5 (12367.6 to 18104.4)	17107.3 (13842.7 to 21141.8)	10413.4 (7373.1 to 14707.3)
Serotype 9V	4154.1 (3358.6 to 5138.0)	7220.1 (5620.9 to 9274.2)	10533.5 (7811.9 to 14203.4)	5386.5 (3634.0 to 7984.3)
Serotype 14	4108.0 (3342.6 to 5048.8)	6885.4 (5642.6 to 8402.0)	7504.5 (5718.2 to 9848.9)	2859.4 (1688.9 to 4899.3)
Serotype 18C	1486.6 (1124.6 to 1965.2)	1890.4 (1429.0 to 2500.6)	2111.9 (1630.6 to 2735.2)	2677.9 (2000.3 to 3585.0)
Serotype 19A	2611.3 (2071.6 to 3291.6)	3560.0 (2867.8 to 4419.1)	3055.1 (2154.1 to 4333.1)	1677.3 (1159.9 to 2425.5)
Serotype 19F	1158.4 (937.0 to 1432.1)	1854.0 (1520.3 to 2260.8)	1629.7 (1292.9 to 2054.2)	744.4 (506.7 to 1093.6)
Serotype 23F	5640.0 (3590.5 to 8859.4)	6693.6 (4464.2 to 10036.4)	4234.7 (2916.1 to 6149.5)	3833.2 (2216.2 to 6630.1)

No statistical analyses for this end point

Secondary: The Serotype-Specific IgG GMCs for Each of the Pneumococcal Serotypes in Cohorts 2, 3, 4 Vaccinated With 13 vPnC Compared to Cohorts 2, 3 and 4 Vaccinated With Hib Vaccine

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End point title

The Serotype-Specific IgG GMCs for Each of the Pneumococcal Serotypes in Cohorts 2, 3, 4 Vaccinated With 13 vPnC Compared to Cohorts 2, 3 and 4 Vaccinated With Hib Vaccine ^[16]

End point description

Serotype-specific IgG concentrations to the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in all subjects from the blood samples taken before vaccination (BV) and 1 month after vaccination (1MAV) in each of the 3 cohorts. GMC and corresponding 2-sided 95% CI were evaluated. GMs were calculated using all subjects with available data for the specified blood draw. Evaluable analysis set included all subjects evaluable for the study at randomization; received all study vaccinations for Cohort 2-4; had blood drawn for assay testing within 27-56 days after visit 3 for Cohort 2, visit 2 for Cohort 3 and visit 1 for Cohort 4 and the sample from this blood drawn provided at least 1 valid and determinate assay result; received no prohibited vaccine; had no major protocol violation.Here "Number of Subjects Analyzed" signifies the number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Cohort 2, 3, 4: Before Vaccination and 1 Month After the Last Dose

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine
Number of subjects analysed	176	72	127	77	131	67
Units: mcg/mL
geometric mean (confidence interval 95%)
Serotype 1- BV (n=176,72,126,77,131,67)	0.02 (0.01 to 0.02)	0.02 (0.01 to 0.03)	0.07 (0.05 to 0.09)	0.07 (0.05 to 0.10)	0.18 (0.14 to 0.22)	0.21 (0.15 to 0.28)
Serotype 1 - 1MAV (n=176,72,127,77,131,67)	3.75 (3.26 to 4.32)	0.04 (0.03 to 0.06)	4.38 (3.75 to 5.11)	0.07 (0.04 to 0.11)	4.40 (3.76 to 5.14)	0.16 (0.12 to 0.23)
Serotype 3 - BV (n=176,72,125,77,131,67)	0.03 (0.03 to 0.04)	0.03 (0.02 to 0.04)	0.07 (0.05 to 0.09)	0.07 (0.05 to 0.09)	0.14 (0.10 to 0.18)	0.13 (0.08 to 0.22)
Serotype 3 - 1MAV (n=176,72,127,77,131,67)	1.19 (1.08 to 1.32)	0.04 (0.03 to 0.05)	1.32 (1.16 to 1.51)	0.09 (0.06 to 0.13)	1.12 (0.97 to 1.29)	0.12 (0.07 to 0.20)
Serotype 4 - BV (n=176,72,127,77,131,67)	0.01 (0.01 to 0.01)	0.01 (0.01 to 0.01)	0.03 (0.02 to 0.04)	0.04 (0.03 to 0.06)	0.07 (0.05 to 0.10)	0.07 (0.05 to 0.11)
Serotype 4 - 1MAV (n=176,72,127,77,131,67)	2.97 (2.60 to 3.40)	0.02 (0.01 to 0.02)	4.04 (3.48 to 4.68)	0.03 (0.02 to 0.05)	4.47 (3.92 to 5.10)	0.06 (0.04 to 0.08)
Serotype 5 - BV (n=176,72,127,77,131,67)	0.38 (0.34 to 0.43)	0.36 (0.31 to 0.42)	0.69 (0.60 to 0.78)	0.63 (0.54 to 0.74)	1.04 (0.92 to 1.17)	0.97 (0.83 to 1.13)
Serotype 5 - 1MAV (n=176,72,127,77,131,67)	3.07 (2.73 to 3.46)	0.51 (0.43 to 0.61)	2.57 (2.26 to 2.92)	0.74 (0.62 to 0.88)	2.92 (2.57 to 3.32)	0.89 (0.73 to 1.07)
Serotype 6A - BV (n=174,72,127,77,129,67)	0.15 (0.13 to 0.18)	0.16 (0.13 to 0.20)	0.30 (0.26 to 0.35)	0.36 (0.30 to 0.42)	0.79 (0.68 to 0.93)	0.79 (0.64 to 0.97)
Serotype 6A - 1MAV (n=176,72,127,76,129,67)	3.12 (2.74 to 3.57)	0.20 (0.15 to 0.26)	3.19 (2.69 to 3.78)	0.42 (0.34 to 0.51)	3.39 (2.80 to 4.09)	0.80 (0.65 to 0.98)
Serotype 6B - BV (n=176,72,127,77,131,67)	0.15 (0.12 to 0.17)	0.15 (0.11 to 0.19)	0.30 (0.26 to 0.35)	0.35 (0.30 to 0.41)	0.80 (0.69 to 0.94)	0.70 (0.58 to 0.84)
Serotype 6B - 1MAV (n=176,72,127,77,131,67)	2.20 (1.91 to 2.54)	0.21 (0.16 to 0.26)	2.47 (2.06 to 2.96)	0.38 (0.32 to 0.46)	2.96 (2.44 to 3.59)	0.62 (0.49 to 0.79)
Serotype 7F - BV (n=175,72,127,76,130,64)	0.03 (0.03 to 0.04)	0.03 (0.02 to 0.04)	0.10 (0.08 to 0.12)	0.11 (0.08 to 0.15)	0.25 (0.21 to 0.31)	0.25 (0.18 to 0.33)
Serotype 7F - 1MAV (n=176,71,127,76,131,67)	5.73 (5.10 to 6.44)	0.05 (0.03 to 0.07)	7.87 (6.90 to 8.96)	0.13 (0.09 to 0.20)	7.08 (6.19 to 8.10)	0.21 (0.16 to 0.29)
Serotype 9V - BV (n=176,72,126,77,131,67)	0.13 (0.11 to 0.16)	0.16 (0.12 to 0.22)	0.25 (0.20 to 0.31)	0.27 (0.23 to 0.33)	0.55 (0.47 to 0.65)	0.41 (0.31 to 0.55)
Serotype 9V - 1MAV (n=176,72,127,76,131,67)	2.24 (1.99 to 2.51)	0.20 (0.14 to 0.27)	3.31 (2.90 to 3.77)	0.34 (0.26 to 0.43)	3.68 (3.22 to 4.21)	0.45 (0.37 to 0.54)
Serotype 14 - BV (n=175,72,127,77,130,67)	0.03 (0.02 to 0.04)	0.02 (0.02 to 0.03)	0.03 (0.03 to 0.05)	0.05 (0.03 to 0.09)	0.19 (0.12 to 0.29)	0.20 (0.11 to 0.36)
Serotype 14 - 1MAV (n=176,72,127,77,131,67)	10.89 (9.59 to 12.35)	0.02 (0.02 to 0.03)	9.79 (8.40 to 11.41)	0.07 (0.04 to 0.11)	6.94 (5.53 to 8.70)	0.20 (0.11 to 0.36)
Serotype 18C - BV (n=176,72,127,77,130,67)	0.01 (0.01 to 0.01)	0.01 (0.01 to 0.02)	0.04 (0.03 to 0.06)	0.05 (0.04 to 0.08)	0.20 (0.15 to 0.27)	0.20 (0.12 to 0.29)
Serotype 18C - 1MAV (n=176,72,127,77,131,66)	2.25 (1.98 to 2.57)	0.02 (0.01 to 0.03)	3.88 (3.25 to 4.64)	0.07 (0.04 to 0.12)	5.60 (4.74 to 6.62)	0.18 (0.11 to 0.29)
Serotype 19A - BV (n=176,72,127,77,131,67)	0.36 (0.31 to 0.41)	0.38 (0.31 to 0.46)	0.65 (0.55 to 0.76)	0.69 (0.58 to 0.83)	1.72 (1.46 to 2.02)	1.44 (1.13 to 1.83)
Serotype 19A -1MAV (n=176,72,127,77,131,67)	3.62 (3.30 to 3.97)	0.50 (0.41 to 0.60)	5.55 (4.86 to 6.34)	0.88 (0.71 to 1.10)	11.62 (9.75 to 13.86)	1.33 (1.04 to 1.70)
Serotype 19F - BV (n=173,72,127,77,131,67)	0.08 (0.07 to 0.11)	0.11 (0.08 to 0.16)	0.23 (0.18 to 0.29)	0.23 (0.17 to 0.31)	0.62 (0.49 to 0.78)	0.57 (0.41 to 0.80)
Serotype 19F - 1MAV (n=176,72,127,77,131,67)	4.50 (3.98 to 5.09)	0.13 (0.09 to 0.19)	5.04 (4.28 to 5.92)	0.27 (0.18 to 0.39)	5.44 (4.46 to 6.64)	0.53 (0.38 to 0.73)
Serotype 23F - BV (n=176,72,126,76,131,67)	0.11 (0.10 to 0.13)	0.11 (0.09 to 0.14)	0.19 (0.17 to 0.23)	0.22 (0.19 to 0.26)	0.54 (0.46 to 0.64)	0.45 (0.35 to 0.57)
Serotype 23F - 1MAV (n=176,71,127,77,131,67)	2.04 (1.76 to 2.37)	0.17 (0.14 to 0.21)	2.26 (1.90 to 2.67)	0.27 (0.22 to 0.34)	2.80 (2.33 to 3.36)	0.44 (0.34 to 0.56)

No statistical analyses for this end point

Secondary: The Serotype-Specific OPA GMT for Each of the Pneumococcal Serotypes in Cohorts 2, 3, 4 Vaccinated With 13 vPnC Compared to Cohorts 2, 3 and 4 Vaccinated With Hib Vaccine

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End point title

The Serotype-Specific OPA GMT for Each of the Pneumococcal Serotypes in Cohorts 2, 3, 4 Vaccinated With 13 vPnC Compared to Cohorts 2, 3 and 4 Vaccinated With Hib Vaccine ^[17]

End point description

Serotype-Specific OPA titers to the 13 pneumococcal serotypes (1, 3, 4, 5,6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in a randomly selected subset of subjects receiving 13vPnC and approximately Hib vaccine from the blood samples taken before vaccination and 1 month after the last 13vPnC/Hib vaccination in each of the 3 cohorts.Evaluable analysis set included all subjects evaluable for the study at randomization; received all study vaccinations for Cohort 2-4; had blood drawn for assay testing within 27-56 days after visit 3 for Cohort 2, visit 2 for Cohort 3 and visit 1 for Cohort 4 and the sample from this blood draw provided at least 1 valid and determinate assay result; received no prohibited vaccine; had no major protocol violation.Here "Number of Subjects Analyzed" signifies the number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Cohort 2, 3, 4: Before Vaccination and 1 Month After the Last Dose

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine
Number of subjects analysed	87	34	78	42	71	36
Units: Titers
geometric mean (confidence interval 95%)
Serotype 1 - Before Vaccination	4.1 (3.9 to 4.4)	4.2 (3.8 to 4.6)	4.0 (4.0 to 4.0)	4.2 (3.8 to 4.7)	4.6 (4.2 to 5.0)	5.5 (4.5 to 6.7)
Serotype 1 - 1 Month After the Last Dose	142.7 (103.4 to 196.9)	4.9 (3.6 to 6.8)	93.3 (70.1 to 124.1)	4.8 (3.8 to 6.0)	40.9 (31.3 to 53.4)	4.4 (3.8 to 5.1)
Serotype 3 - Before Vaccination	5.8 (5.0 to 6.7)	6.7 (4.5 to 10.0)	11.9 (8.6 to 16.5)	11.3 (6.9 to 18.5)	27.1 (19.2 to 38.4)	40.0 (22.7 to 70.7)
Serotype 3 - 1 Month After the Last Dose	249.0 (205.7 to 301.5)	7.4 (4.9 to 11.3)	332.3 (273.3 to 404.1)	13.4 (7.7 to 23.4)	244.8 (192.0 to 312.1)	28.4 (16.2 to 49.7)
Serotype 4 - Before Vaccination	5.5 (4.3 to 6.9)	5.0 (3.6 to 6.9)	6.3 (4.8 to 8.3)	9.5 (5.6 to 16.2)	23.4 (13.8 to 39.7)	15.9 (8.4 to 30.1)
Serotype 4 - 1 Month After the Last Dose	2172.2 (1740.7 to 2710.7)	10.3 (5.2 to 20.3)	2682.8 (2210.4 to 3256.2)	10.6 (5.7 to 19.6)	4236.3 (3489.6 to 5142.8)	19.2 (10.0 to 36.6)
Serotype 5 - Before Vaccination	4.3 (3.8 to 4.9)	4.0 (4.0 to 4.0)	4.2 (3.9 to 4.4)	4.1 (3.9 to 4.4)	4.7 (4.1 to 5.3)	4.2 (3.9 to 4.6)
Serotype 5 - 1 Month After the Last Dose	286.3 (214.5 to 382.0)	6.2 (4.0 to 9.7)	164.5 (131.5 to 205.7)	5.1 (3.6 to 7.2)	79.3 (57.7 to 109.0)	4.8 (4.0 to 5.8)
Serotype 6A - Before Vaccination	5.0 (4.1 to 6.3)	4.0 (4.0 to 4.0)	6.9 (4.9 to 9.8)	8.2 (4.7 to 14.3)	45.5 (26.5 to 78.0)	137.4 (63.3 to 297.9)
Serotype 6A - 1 Month After the Last Dose	6042.7 (4830.2 to 7559.6)	5.9 (4.0 to 8.8)	7661.8 (6116.0 to 9598.4)	17.8 (8.1 to 39.1)	5849.3 (4364.0 to 7840.2)	101.8 (45.7 to 226.8)
Serotype 6B - Before Vaccination	5.1 (4.1 to 6.4)	4.0 (4.0 to 4.0)	8.2 (5.5 to 12.2)	9.7 (5.6 to 16.8)	53.6 (30.4 to 94.5)	94.9 (43.0 to 209.3)
Serotype 6B - 1 Month After the Last Dose	2181.6 (1350.1 to 3525.2)	5.7 (3.8 to 8.6)	4986.3 (3717.6 to 6687.9)	20.2 (9.3 to 43.8)	3775.2 (2825.1 to 5044.9)	117.7 (51.9 to 267.1)
Serotype 7F - Before Vaccination	63.0 (35.8 to 111.0)	29.6 (12.4 to 70.4)	195.8 (114.5 to 334.9)	432.7 (213.8 to 875.8)	1155.2 (852.6 to 1565.2)	892.7 (515.3 to 1546.5)
Serotype 7F - 1 Month After the Last Dose	10234.6 (8612.2 to 12162.8)	94.0 (37.2 to 237.3)	14963.5 (12367.6 to 18104.4)	707.1 (361.9 to 1381.6)	17107.3 (13842.7 to 21141.8)	1090.7 (696.2 to 1708.8)
Serotype 9V - Before Vaccination	9.3 (6.3 to 13.8)	11.3 (5.9 to 21.5)	59.5 (34.1 to 103.7)	74.5 (31.0 to 179.0)	458.9 (280.9 to 749.8)	850.2 (469.4 to 1539.9)
Serotype 9V - 1 Month After the Last Dose	4154.1 (3358.6 to 5138.0)	20.6 (9.1 to 46.8)	7220.1 (5620.9 to 9274.2)	154.3 (69.9 to 340.9)	10533.5 (7811.9 to 14203.4)	795.1 (472.6 to 1337.6)
Serotype 14 - Before Vaccination	9.8 (6.5 to 14.7)	12.7 (6.2 to 26.3)	30.0 (16.1 to 56.1)	19.1 (8.5 to 43.0)	132.6 (64.8 to 271.5)	210.6 (87.7 to 505.5)
Serotype 14 - 1 Month After the Last Dose	4108.0 (3342.6 to 5048.8)	26.6 (11.4 to 62.3)	6885.4 (5642.6 to 8402.0)	39.0 (16.3 to 93.2)	7504.5 (5718.2 to 9848.9)	294.9 (126.5 to 687.1)
Serotype 18C - Before Vaccination	4.3 (3.8 to 4.9)	4.4 (3.8 to 5.1)	6.1 (5.0 to 7.4)	6.3 (4.4 to 8.9)	12.7 (8.4 to 19.1)	20.3 (10.0 to 41.3)
Serotype 18C - 1 Month After the Last Dose	1486.6 (1124.6 to 1965.2)	6.5 (4.1 to 10.3)	1890.4 (1429.0 to 2500.6)	7.9 (4.8 to 13.1)	2111.9 (1630.6 to 2735.2)	24.6 (12.1 to 50.1)
Serotype 19A - Before Vaccination	5.3 (4.5 to 6.3)	5.8 (4.1 to 8.1)	11.1 (7.8 to 15.8)	13.8 (7.8 to 24.3)	60.3 (37.6 to 96.7)	52.0 (24.2 to 111.6)
Serotype 19A - 1 Month After the Last Dose	2611.3 (2071.6 to 3291.6)	6.4 (4.6 to 8.9)	3560.0 (2867.8 to 4419.1)	15.5 (8.6 to 28.2)	3055.1 (2154.1 to 4333.1)	54.3 (27.6 to 107.1)
Serotype 19F - Before Vaccination	4.3 (3.9 to 4.8)	4.6 (3.7 to 5.7)	6.2 (4.9 to 7.8)	6.1 (4.5 to 8.3)	24.7 (15.7 to 38.9)	38.5 (18.1 to 81.8)
Serotype 19F - 1 Month After the Last Dose	1158.4 (937.0 to 1432.1)	5.9 (4.1 to 8.6)	1854.0 (1520.3 to 2260.8)	9.5 (5.6 to 16.2)	1629.7 (1292.9 to 2054.2)	41.1 (19.4 to 86.8)
Serotype 23F - Before Vaccination	5.1 (4.1 to 6.3)	4.7 (3.4 to 6.4)	15.0 (8.8 to 25.6)	11.1 (5.6 to 22.0)	106.0 (59.5 to 188.9)	70.5 (29.5 to 168.3)
Serotype 23F - 1 Month After the Last Dose	5640.0 (3950.5 to 8859.4)	20.2 (8.5 to 47.7)	6693.6 (4464.2 to 10036.4)	19.4 (8.8 to 42.8)	4234.7 (2916.1 to 6149.5)	97.2 (40.8 to 231.2)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Pneumococcal Serotype-Specific IgG Concentration >=0.35 mcg/mL for 1 Month After the Last Vaccination in Cohorts 2,3,4 (13vPnC and Hib Vaccine) and 1 Month After the Infant Series in Cohort 1 (13vPnC)

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End point title

Percentage of Subjects Achieving Pneumococcal Serotype-Specific IgG Concentration >=0.35 mcg/mL for 1 Month After the Last Vaccination in Cohorts 2,3,4 (13vPnC and Hib Vaccine) and 1 Month After the Infant Series in Cohort 1 (13vPnC) ^[18]

End point description

Serotype-specific IgG concentrations to the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in all subjects from the blood samples taken 1 month after the infant series in Cohort 1 and the last dose of vaccination (13vPnC or Hib vaccine) in Cohorts 2, 3, 4. Evaluable analysis set included all subjects evaluable for the study at randomization; received all study vaccinations for Cohort 2-4, received all 3 infant series doses for Cohort 1; had blood draw for assay testing within 27-56 days after 3rd vaccination for Cohort 1, visit 3 for Cohort 2, visit 2 for Cohort 3 and visit 1 for Cohort 4 and the sample from this blood draw provided at least 1 valid and determinate assay result; received no prohibited vaccine; had no major protocol violation.Here "Number of Subjects Analyzed" signifies the number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Cohort 1: 1 month after the third dose (infant series) of 13vPnC. Cohorts 2, 3, 4: 1 month after the last dose of 13vPnC and Hib Vaccine

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine	Cohort 1: Infant Series
Number of subjects analysed	176	72	127	77	131	67	72
Units: Percentage of Subjects
number (confidence interval 95%)
Serotype 1 (n=176,72,127,77,131,67,72)	99.4 (96.9 to 100.0)	4.2 (0.9 to 11.7)	97.6 (93.3 to 99.5)	10.4 (4.6 to 19.4)	99.2 (95.8 to 100.0)	23.9 (14.3 to 35.9)	100.0 (95.0 to 100.0)
Serotype 3 (n=176,72,127,77,131,67,72)	97.7 (94.3 to 99.4)	4.2 (0.9 to 11.7)	94.5 (89.0 to 97.8)	11.7 (5.5 to 21.0)	98.5 (94.6 to 99.8)	19.4 (10.8 to 30.9)	83.3 (72.7 to 91.1)
Serotype 4 (n=176,72,127,77,131,67,72)	99.4 (96.9 to 100.0)	5.6 (1.5 to 13.6)	97.6 (93.3 to 99.5)	6.5 (2.1 to 14.5)	99.2 (95.8 to 100.0)	4.5 (0.9 to 12.5)	100.0 (95.0 to 100.0)
Serotype 5 (n=176,72,127,77,131,67,72)	100.0 (97.9 to 100.0)	69.4 (57.5 to 79.8)	100.0 (97.1 to 100.0)	85.7 (75.9 to 92.6)	99.2 (95.8 to 100.0)	88.1 (77.8 to 94.7)	100.0 (95.0 to 100.0)
Serotype 6A (n=176,72,127,76,129,67,72)	97.7 (94.3 to 99.4)	33.3 (22.7 to 45.4)	97.6 (93.3 to 99.5)	56.6 (44.7 to 67.9)	100.0 (97.2 to 100.0)	86.6 (76.0 to 93.7)	100.0 (95.0 to 100.0)
Serotype 6B (n=176,72,127,77,131,67,72)	96.0 (92.0 to 98.4)	23.6 (14.4 to 35.1)	97.6 (93.3 to 99.5)	50.6 (39.0 to 62.2)	99.2 (95.8 to 100.0)	77.6 (65.8 to 86.9)	100.0 (95.0 to 100.0)
Serotype 7F (n=176,71,127,76,131,67,72)	99.4 (96.9 to 100.0)	4.2 (0.9 to 11.9)	98.4 (94.4 to 99.8)	21.1 (12.5 to 31.9)	99.2 (95.8 to 100.0)	37.3 (25.8 to 50.0)	100.0 (95.0 to 100.0)
Serotype 9V (n=176,72,127,76,131,67,72)	98.3 (95.1 to 99.6)	31.9 (21.4 to 44.0)	99.2 (95.7 to 100.0)	40.8 (29.6 to 52.7)	100.0 (97.2 to 100.0)	59.7 (47.0 to 71.5)	100.0 (95.0 to 100.0)
Serotype 14 (n=176,72,127,77,131,67,72)	99.4 (96.9 to 100.0)	6.9 (2.3 to 15.5)	98.4 (94.4 to 99.8)	22.1 (13.4 to 33.0)	100.0 (97.2 to 100.0)	41.8 (29.8 to 54.5)	97.2 (90.3 to 99.7)
Serotype 18C (n=176,72,127,77,131,66,72)	97.7 (94.3 to 99.4)	5.6 (1.5 to 13.6)	98.4 (94.4 to 99.8)	15.6 (8.3 to 25.6)	100.0 (97.2 to 100.0)	40.9 (29.0 to 53.7)	100.0 (95.0 to 100.0)
Serotype 19A (n=176,72,127,77,131,67,72)	100.0 (97.9 to 100.0)	63.9 (51.7 to 74.9)	100.0 (97.1 to 100.0)	90.9 (82.2 to 96.3)	100.0 (97.2 to 100.0)	94.0 (85.4 to 98.3)	100.0 (95.0 to 100.0)
Serotype 19F (n=176,72,127,77,131,67,72)	98.9 (96.0 to 99.9)	29.2 (19.0 to 41.1)	97.6 (93.3 to 99.5)	44.2 (32.8 to 55.9)	100.0 (97.2 to 100.0)	70.1 (57.7 to 80.7)	98.6 (92.5 to 100.0)
Serotype 23F (n=176,71,127,77,131,67,72)	95.5 (91.2 to 98.0)	14.1 (7.0 to 24.4)	97.6 (93.3 to 99.5)	26.0 (16.6 to 37.2)	96.9 (92.4 to 99.2)	52.2 (39.7 to 64.6)	95.8 (88.3 to 99.1)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal OPA titer >=Lower Limit of Quantitation (LLOQ) for 1 Month After the Last Vaccination in Cohorts 2,3,4 (13vPnC and Hib Vaccine) and 1 Month After the Infant Series in Cohort 1 (13vPnC)

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End point title

Percentage of Subjects Achieving Serotype-Specific Pneumococcal OPA titer >=Lower Limit of Quantitation (LLOQ) for 1 Month After the Last Vaccination in Cohorts 2,3,4 (13vPnC and Hib Vaccine) and 1 Month After the Infant Series in Cohort 1 (13vPnC) ^[19]

End point description

Serotype-specific OPA titers to the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in a randomly selected subset of about 50 subjects receiving 13vPnC from the blood samples taken 1 month after the infant series in Cohort 1 and the last vaccination (13vPnC or Hib vaccine) in each of the 3 cohorts. Evaluable analysis set included all subjects evaluable for the study at randomization; received all study vaccinations for Cohort 2-4, received all 3 infant series doses for Cohort 1; had blood draw for assay testing within 27-56 days after 3rd vaccination for Cohort 1, visit 3 for Cohort 2, visit 2 for Cohort 3 and visit 1 for Cohort 4 and the sample from this blood draw provided at least 1 valid and determinate assay result; received no prohibited vaccine; had no major protocol violation.Here "Number of Subjects Analyzed" signifies the number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Cohort 1: 1 month after the 3rd dose (infant series) of 13vPnC. Cohorts 2, 3, 4: 1 month after the last dose of 13vPnC and Hib Vaccine

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 3: 13vPnC	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine	Cohort 1: Infant Series
Number of subjects analysed	87	34	78	42	71	36	37
Units: Percentage of Subjects
number (confidence interval 95%)
Serotype 1	96.6 (90.3 to 99.3)	5.9 (0.7 to 19.7)	96.2 (89.2 to 99.2)	7.1 (1.5 to 19.5)	95.8 (88.1 to 99.1)	5.6 (0.7 to 18.7)	100.0 (90.5 to 100.0)
Serotype 3	100.0 (95.8 to 100.0)	29.4 (15.1 to 47.5)	100.0 (95.4 to 100.0)	38.1 (23.6 to 54.4)	100.0 (94.9 to 100.0)	80.6 (64.0 to 91.8)	100.0 (90.5 to 100.0)
Serotype 4	100.0 (95.8 to 100.0)	23.5 (10.7 to 41.2)	100.0 (95.4 to 100.0)	23.8 (12.1 to 39.5)	100.0 (94.9 to 100.0)	55.6 (38.1 to 72.1)	100.0 (90.5 to 100.0)
Serotype 5	100.0 (95.8 to 100.0)	14.7 (5.0 to 31.1)	100.0 (95.4 to 100.0)	4.8 (0.6 to 16.2)	98.6 (92.4 to 100.0)	11.1 (3.1 to 26.1)	100.0 (90.5 to 100.0)
Serotype 6A	100.0 (95.8 to 100.0)	14.7 (5.0 to 31.1)	100.0 (95.4 to 100.0)	31.0 (17.6 to 47.1)	100.0 (94.9 to 100.0)	80.6 (64.0 to 91.8)	100.0 (90.5 to 100.0)
Serotype 6B	94.3 (87.1 to 98.1)	11.8 (3.3 to 27.5)	98.7 (93.1 to 100.0)	35.7 (21.6 to 52.0)	100.0 (94.9 to 100.0)	80.6 (64.0 to 91.8)	100.0 (90.5 to 100.0)
Serotype 7F	100.0 (95.8 to 100.0)	61.8 (43.6 to 77.8)	100.0 (95.4 to 100.0)	90.5 (77.4 to 97.3)	100.0 (94.9 to 100.0)	100.0 (90.3 to 100.0)	100.0 (90.5 to 100.0)
Serotype 9V	100.0 (95.8 to 100.0)	41.2 (24.6 to 59.3)	100.0 (95.4 to 100.0)	76.2 (60.5 to 87.9)	100.0 (94.9 to 100.0)	97.2 (85.5 to 99.9)	100.0 (90.5 to 100.0)
Serotype 14	100.0 (95.8 to 100.0)	41.2 (24.6 to 59.3)	100.0 (95.4 to 100.0)	45.2 (29.8 to 61.3)	100.0 (94.9 to 100.0)	83.3 (67.2 to 93.6)	100.0 (90.5 to 100.0)
Serotype 18C	98.9 (93.8 to 100)	14.7 (5.0 to 31.1)	98.7 (93.1 to 100.0)	21.4 (10.3 to 36.8)	100.0 (94.9 to 100.0)	52.8 (35.5 to 69.6)	100.0 (90.5 to 100.0)
Serotype 19A	100.0 (95.8 to 100.0)	26.5 (12.9 to 44.4)	100.0 (95.4 to 100.0)	47.6 (32.0 to 63.6)	100.0 (94.9 to 100.0)	83.3 (67.2 to 93.6)	100.0 (90.5 to 100.0)
Serotype 19F	100.0 (95.8 to 100.0)	17.6 (6.8 to 34.5)	100.0 (95.4 to 100.0)	26.2 (13.9 to 42.0)	100.0 (94.9 to 100.0)	63.9 (46.2 to 79.2)	97.3 (85.8 to 99.9)
Serotype 23F	95.4 (88.6 to 98.7)	35.3 (19.7 to 53.5)	96.2 (89.2 to 99.2)	33.3 (19.6 to 49.5)	97.2 (90.2 to 99.7)	72.2 (54.8 to 85.8)	97.3 (85.8 to 99.9)

No statistical analyses for this end point

Secondary: Number of Subjects with AE From the Signing of the ICD to 1 Month After the Infant Series in Cohort 1

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End point title

Number of Subjects with AE From the Signing of the ICD to 1 Month After the Infant Series in Cohort 1

End point description

An AE was any untoward medical occurrence in a study subjects administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. The safety population included all subjects who received at least 1 dose of the investigational product.

End point type

Secondary

End point timeframe

From the signing of ICD to 1 month after the third dose (infant series) of 13vPnC in Cohort 1

End point values	Cohort 1: Infant Series
Number of subjects analysed	125
Units: Subjects	14

No statistical analyses for this end point

Secondary: Number of Subjects With NDCMCs From 1 Month After Vaccination 3 to Vaccination 4 in Cohort 1

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End point title

Number of Subjects With NDCMCs From 1 Month After Vaccination 3 to Vaccination 4 in Cohort 1

End point description

Number of subjects with NDCMCs from 1 month after vaccination 3 to vaccination 4 in Cohort 1. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. The safety population included all subjects who received at least 1 dose of the investigational product.

End point type

Secondary

End point timeframe

From 1 month after Vaccination 3 to Vaccination 4

End point values	Cohort 1: Infant Series
Number of subjects analysed	125
Units: Subjects	0

No statistical analyses for this end point

Secondary: Number of Subjects With AE From Toddler Dose Until 1 Month After the Toddler Dose in Cohort 1

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End point title

Number of Subjects With AE From Toddler Dose Until 1 Month After the Toddler Dose in Cohort 1

End point description

Number of subjects With AEs from vaccination 4 to 1 month after vaccination 4 in Cohort 1. An AE was any untoward medical occurrence in a study subjects administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. The safety population included all subjects who received at least 1 dose of the investigational product.

End point type

Secondary

End point timeframe

From Vaccination 4 (toddler dose) to 1 month after vaccination 4 in Cohort 1

End point values	Cohort 1: Toddler Dose
Number of subjects analysed	90
Units: Subjects	5

No statistical analyses for this end point

Secondary: Number of Subjects With NDCMCs From 1 Month to 6 Months After the Toddler Dose in Cohort 1

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End point title

Number of Subjects With NDCMCs From 1 Month to 6 Months After the Toddler Dose in Cohort 1

End point description

Number of subjects With NDCMCs from 1 month after vaccination 4 to 6 months after vaccination 4 in Cohort 1. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. The safety population included all subjects who received at least 1 dose of the investigational product.

End point type

Secondary

End point timeframe

From 1 month to 6 months (5 months) after Vaccination 4 in Cohort 1

End point values	Cohort 1: Toddler Dose
Number of subjects analysed	90
Units: Subjects	0

No statistical analyses for this end point

Secondary: Number of Subjects With SAE From the Signing of the ICD to 6 Months After the Toddler Dose in Cohort 1

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End point title

Number of Subjects With SAE From the Signing of the ICD to 6 Months After the Toddler Dose in Cohort 1 ^[20]

End point description

Number of subjects With SAEs from the signing of the ICD to 6 months after vaccination 4. An SAE was any untoward medical occurrence at any dose that resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect or considered to be an important medical event. The safety population included all subjects who received at least 1 dose of the investigational product.

End point type

Secondary

End point timeframe

From the signing of the ICD to 6 Months After the Vaccination 4

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are reported for the arms specified

End point values	Cohort 1: 13vPnC
Number of subjects analysed	125
Units: Subjects	9

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Local reactions/systemic events: Day 1 to 7 after each dose.Non-SAE-Cohort 1:from ICD signing to 1 month after Vaccination 4;Cohorts 2,3,4:from ICD signing to 1 month after last vaccination.SAE: From ICD signing to 6 months after last vaccination.

Adverse event reporting additional description

Same event may appear as non-SAE and SAE, what is presented are distinct events. Event may be SAE in 1 subject and as Non-SAE in another subject or 1 subject may have experienced both SAE and Non-SAE during study. Safety population. Local reactions and systemic events were assessed by systematic collection and AEs by non-systematic collection.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Cohort 3: Hib Vaccine

Reporting group description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=1 to <2 years of age.

Reporting group title

Cohort 4: 13vPnC

Reporting group description

Subjects vaccinated with 1 dose of 13vPnC (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Reporting group title

Cohort 4: Hib Vaccine

Reporting group description

Subjects vaccinated with 1 dose of Hib vaccine (single intramuscular injection): Vaccination 1: >=2 to <6 years of age.

Reporting group title

Cohort 3: 13vPnC

Reporting group description

Subjects vaccinated with 2 doses of 13vPnC (single intramuscular injection): Vaccination 1 (Visit 1): >=1 to <2 years of age; Vaccination 2: at least 56 days after Visit 1.

Reporting group title

Cohort 2: 13vPnC

Reporting group description

Reporting group title

Cohort 2: Hib Vaccine

Reporting group description

Subjects vaccinated with 2 doses of Hib Vaccine (single intramuscular injection): Vaccination 1 (Visit 1): 7 to <12 months of age; Vaccination 2: at least 28 days after Visit 1.

Reporting group title

Cohort 1: 13vPnC

Reporting group description

Serious adverse events	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine	Cohort 3: 13vPnC	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 1: 13vPnC
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 83 (0.00%)	2 / 138 (1.45%)	1 / 68 (1.47%)	2 / 165 (1.21%)	5 / 236 (2.12%)	1 / 117 (0.85%)	9 / 125 (7.20%)
number of deaths (all causes)	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0
Nervous system disorders
Febrile convulsion
subjects affected / exposed	0 / 83 (0.00%)	0 / 138 (0.00%)	0 / 68 (0.00%)	1 / 165 (0.61%)	0 / 236 (0.00%)	0 / 117 (0.00%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Toxic encephalopathy
subjects affected / exposed	0 / 83 (0.00%)	0 / 138 (0.00%)	0 / 68 (0.00%)	1 / 165 (0.61%)	0 / 236 (0.00%)	0 / 117 (0.00%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
subjects affected / exposed	0 / 83 (0.00%)	0 / 138 (0.00%)	1 / 68 (1.47%)	0 / 165 (0.00%)	0 / 236 (0.00%)	0 / 117 (0.00%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 83 (0.00%)	0 / 138 (0.00%)	0 / 68 (0.00%)	0 / 165 (0.00%)	3 / 236 (1.27%)	0 / 117 (0.00%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	3 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 83 (0.00%)	0 / 138 (0.00%)	0 / 68 (0.00%)	0 / 165 (0.00%)	0 / 236 (0.00%)	0 / 117 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sleep apnoea syndrome
subjects affected / exposed	0 / 83 (0.00%)	1 / 138 (0.72%)	0 / 68 (0.00%)	0 / 165 (0.00%)	0 / 236 (0.00%)	0 / 117 (0.00%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Lower respiratory tract infection bacterial
subjects affected / exposed	0 / 83 (0.00%)	0 / 138 (0.00%)	0 / 68 (0.00%)	0 / 165 (0.00%)	0 / 236 (0.00%)	0 / 117 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media
subjects affected / exposed	0 / 83 (0.00%)	1 / 138 (0.72%)	0 / 68 (0.00%)	0 / 165 (0.00%)	0 / 236 (0.00%)	0 / 117 (0.00%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 83 (0.00%)	1 / 138 (0.72%)	1 / 68 (1.47%)	1 / 165 (0.61%)	1 / 236 (0.42%)	0 / 117 (0.00%)	7 / 125 (5.60%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 1	0 / 1	0 / 0	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infections
subjects affected / exposed	0 / 83 (0.00%)	0 / 138 (0.00%)	0 / 68 (0.00%)	0 / 165 (0.00%)	1 / 236 (0.42%)	1 / 117 (0.85%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0

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

Non-serious adverse events	Cohort 3: Hib Vaccine	Cohort 4: 13vPnC	Cohort 4: Hib Vaccine	Cohort 3: 13vPnC	Cohort 2: 13vPnC	Cohort 2: Hib Vaccine	Cohort 1: 13vPnC
Total subjects affected by non serious adverse events
subjects affected / exposed	25 / 83 (30.12%)	58 / 138 (42.03%)	28 / 68 (41.18%)	88 / 165 (53.33%)	177 / 236 (75.00%)	74 / 117 (63.25%)	0 / 125 (0.00%)
General disorders and administration site conditions
Fatigue
alternative assessment type: Systematic
subjects affected / exposed	0 / 83 (0.00%)	7 / 138 (5.07%)	6 / 68 (8.82%)	0 / 165 (0.00%)	0 / 236 (0.00%)	0 / 117 (0.00%)	0 / 125 (0.00%)
occurrences all number	0	7	6	0	0	0	0
Swelling
alternative assessment type: Systematic
subjects affected / exposed	3 / 83 (3.61%)	27 / 138 (19.57%)	16 / 68 (23.53%)	21 / 165 (12.73%)	38 / 236 (16.10%)	5 / 117 (4.27%)	0 / 125 (0.00%)
occurrences all number	3	27	16	23	42	5	0
Tenderness
alternative assessment type: Systematic
subjects affected / exposed	3 / 83 (3.61%)	26 / 138 (18.84%)	15 / 68 (22.06%)	18 / 165 (10.91%)	18 / 236 (7.63%)	2 / 117 (1.71%)	0 / 125 (0.00%)
occurrences all number	3	26	15	21	20	2	0
Pyrexia (Fever)
alternative assessment type: Systematic
subjects affected / exposed	16 / 83 (19.28%)	20 / 138 (14.49%)	16 / 68 (23.53%)	55 / 165 (33.33%)	121 / 236 (51.27%)	37 / 117 (31.62%)	0 / 125 (0.00%)
occurrences all number	16	20	16	63	146	40	0
Pyrexia
subjects affected / exposed	0 / 83 (0.00%)	0 / 138 (0.00%)	0 / 68 (0.00%)	0 / 165 (0.00%)	31 / 236 (13.14%)	13 / 117 (11.11%)	0 / 125 (0.00%)
occurrences all number	0	0	0	0	31	13	0
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
subjects affected / exposed	0 / 83 (0.00%)	0 / 138 (0.00%)	0 / 68 (0.00%)	0 / 165 (0.00%)	22 / 236 (9.32%)	9 / 117 (7.69%)	0 / 125 (0.00%)
occurrences all number	0	0	0	0	25	9	0
Cough
subjects affected / exposed	0 / 83 (0.00%)	0 / 138 (0.00%)	0 / 68 (0.00%)	0 / 165 (0.00%)	22 / 236 (9.32%)	6 / 117 (5.13%)	0 / 125 (0.00%)
occurrences all number	0	0	0	0	22	6	0
Skin and subcutaneous tissue disorders
Erythemas
alternative assessment type: Systematic
subjects affected / exposed	10 / 83 (12.05%)	36 / 138 (26.09%)	15 / 68 (22.06%)	42 / 165 (25.45%)	68 / 236 (28.81%)	27 / 117 (23.08%)	0 / 125 (0.00%)
occurrences all number	10	36	15	46	79	32	0
Metabolism and nutrition disorders
Decreased appetite
alternative assessment type: Systematic
subjects affected / exposed	3 / 83 (3.61%)	0 / 138 (0.00%)	0 / 68 (0.00%)	13 / 165 (7.88%)	0 / 236 (0.00%)	0 / 117 (0.00%)	0 / 125 (0.00%)
occurrences all number	3	0	0	13	0	0	0

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Were there any global substantial amendments to the protocol? Yes

07 Feb 2019

Protocol amendment 2: Updated Protocol Summary, Section 1.2,Section 3.4, Section 7.5.1, Section 7.5.2, Section 9.4: Added the enrollment of additional 280 subjects from country CDCs. To provide additional data in the event that only subjects recruited at municipal and county level CDCs should be included in vaccine clinical studies.

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 open label trial to assess the safety, tolerability, and immunogenicity of 13-valent pneumococcal conjugate vaccine in infants and young children in China who are naive to pneumococcal vaccination

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: The Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for Each of the Pneumococcal Serotypes Measured in Cohorts 2, 3 and 4 Compared to IgG GMCs Measured in Cohort 1

Primary: The Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for Each of the Pneumococcal Serotypes Measured in Cohorts 2, 3 and 4 Compared to IgG GMCs Measured in Cohort 1

Primary: Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 2

Primary: Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 2

Primary: Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 3

Primary: Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 3

Primary: Number of Subjects With Adverse Events (AE) From the Signing of the Informed Consent Document (ICD) to 1 Month After the Last Vaccination in Cohorts 2, 3, 4

Primary: Number of Subjects With Adverse Events (AE) From the Signing of the Informed Consent Document (ICD) to 1 Month After the Last Vaccination in Cohorts 2, 3, 4

Primary: Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 4

Primary: Number of Subjects With Local Reactions and Systemic Events Within 7 Days After Each Vaccination in Cohort 4

Primary: Number of Subjects With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From 1 Month to 6 Months After the Last Vaccination in Cohorts 2, 3, 4

Primary: Number of Subjects With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From 1 Month to 6 Months After the Last Vaccination in Cohorts 2, 3, 4

Primary: Number of Subjects With SAE From the Signing of the ICD to 6 Months After the Last Vaccination in Cohorts 2, 3, 4

Primary: Number of Subjects With SAE From the Signing of the ICD to 6 Months After the Last Vaccination in Cohorts 2, 3, 4

Secondary: The Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for Each of the Pneumococcal Serotypes Measured in Cohorts 2, 3 and 4 Compared to IgG GMTs Measured in Cohort 1

Secondary: The Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for Each of the Pneumococcal Serotypes Measured in Cohorts 2, 3 and 4 Compared to IgG GMTs Measured in Cohort 1

Secondary: The Serotype-Specific IgG GMCs for Each of the Pneumococcal Serotypes in Cohorts 2, 3, 4 Vaccinated With 13 vPnC Compared to Cohorts 2, 3 and 4 Vaccinated With Hib Vaccine

Secondary: The Serotype-Specific IgG GMCs for Each of the Pneumococcal Serotypes in Cohorts 2, 3, 4 Vaccinated With 13 vPnC Compared to Cohorts 2, 3 and 4 Vaccinated With Hib Vaccine

Secondary: The Serotype-Specific OPA GMT for Each of the Pneumococcal Serotypes in Cohorts 2, 3, 4 Vaccinated With 13 vPnC Compared to Cohorts 2, 3 and 4 Vaccinated With Hib Vaccine

Secondary: The Serotype-Specific OPA GMT for Each of the Pneumococcal Serotypes in Cohorts 2, 3, 4 Vaccinated With 13 vPnC Compared to Cohorts 2, 3 and 4 Vaccinated With Hib Vaccine

Secondary: Percentage of Subjects Achieving Pneumococcal Serotype-Specific IgG Concentration >=0.35 mcg/mL for 1 Month After the Last Vaccination in Cohorts 2,3,4 (13vPnC and Hib Vaccine) and 1 Month After the Infant Series in Cohort 1 (13vPnC)

Secondary: Percentage of Subjects Achieving Pneumococcal Serotype-Specific IgG Concentration >=0.35 mcg/mL for 1 Month After the Last Vaccination in Cohorts 2,3,4 (13vPnC and Hib Vaccine) and 1 Month After the Infant Series in Cohort 1 (13vPnC)

Secondary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal OPA titer >=Lower Limit of Quantitation (LLOQ) for 1 Month After the Last Vaccination in Cohorts 2,3,4 (13vPnC and Hib Vaccine) and 1 Month After the Infant Series in Cohort 1 (13vPnC)

Secondary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal OPA titer >=Lower Limit of Quantitation (LLOQ) for 1 Month After the Last Vaccination in Cohorts 2,3,4 (13vPnC and Hib Vaccine) and 1 Month After the Infant Series in Cohort 1 (13vPnC)

Secondary: Number of Subjects with AE From the Signing of the ICD to 1 Month After the Infant Series in Cohort 1

Secondary: Number of Subjects with AE From the Signing of the ICD to 1 Month After the Infant Series in Cohort 1

Secondary: Number of Subjects With NDCMCs From 1 Month After Vaccination 3 to Vaccination 4 in Cohort 1

Secondary: Number of Subjects With NDCMCs From 1 Month After Vaccination 3 to Vaccination 4 in Cohort 1

Secondary: Number of Subjects With AE From Toddler Dose Until 1 Month After the Toddler Dose in Cohort 1

Secondary: Number of Subjects With AE From Toddler Dose Until 1 Month After the Toddler Dose in Cohort 1

Secondary: Number of Subjects With NDCMCs From 1 Month to 6 Months After the Toddler Dose in Cohort 1

Secondary: Number of Subjects With NDCMCs From 1 Month to 6 Months After the Toddler Dose in Cohort 1

Secondary: Number of Subjects With SAE From the Signing of the ICD to 6 Months After the Toddler Dose in Cohort 1

Secondary: Number of Subjects With SAE From the Signing of the ICD to 6 Months After the Toddler Dose in Cohort 1

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A phase 3 open label trial to assess the safety, tolerability, and immunogenicity of 13-valent pneumococcal conjugate vaccine in infants and young children in China who are naive to pneumococcal vaccination