A PHASE 4, RANDOMIZED, OPEN-LABEL TRIAL TO DESCRIBE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF 13- VALENT PNEUMOCOCCAL CONJUGATE VACCINE FORMULATED IN MULTIDOSE VIALS WHEN GIVEN WITH ROUTINE PEDIATRIC VACCINES IN HEALTHY INFANTS IN INDIA
Phase: PHASE4
Conditions: Vaccines
Sponsor: Pfizer

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A PHASE 4, RANDOMIZED, OPEN-LABEL TRIAL TO DESCRIBE 
THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF 
13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE 
FORMULATED IN MULTIDOSE VIALS WHEN GIVEN WITH 
ROUTINE PEDIATRIC VACCINES IN HEALTHY INFANTS IN INDIA
Investigational Product Number:
PF-06414256
Investigational Product Name:
13-valent Pneumococcal Conjugate Vaccine
United States (US) Investigational New 
Drug (IND) Number:
N/A
European Clinical Trials Database 
(EudraCT) Number:
2016-005134-29
Protocol Number:
B4671004
Phase:
4
 
 
 

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Document History
Document
Version Date
Summary of Changes and 
Rationale
Original protocol
10 January 2017
Not applicable (N/A)
Protocol Amendment 1
14 February 2017
Clarification added that this 
study is defined as a 
postauthorization safety study.
Corrections made to the 
Secondary Objective and Data 
Analysis/Statistical Methods 
sections.
Clarification added that OPA 
will be determined in all 
subjects for each blood 
sample collected 1 month after 
the infant series and 1 month 
after the toddler dose, where 
sufficient sera are available.
References have been altered 
to match the AMA style of 
formatting.
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).

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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................6
APPENDICES ...........................................................................................................................6
PROTOCOL SUMMARY.........................................................................................................7
Background ......................................................................................................................7
Primary Objective and Endpoints ....................................................................................7
Study Design ....................................................................................................................8
Approximate Duration of Subject Participation...............................................................8
Approximate Duration of the Study.................................................................................8
Approximate Number of Subjects....................................................................................8
SCHEDULE OF ACTIVITIES..................................................................................................9
1. INTRODUCTION ...............................................................................................................10
1.1. Indication.................................................................................................................10
1.2. Background and Rationale ......................................................................................10
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................12
3. STUDY DESIGN.................................................................................................................14
3.1. Approximate Duration of Subject Participation......................................................14
3.2. Approximate Duration of the Study........................................................................14
3.3. Approximate Number of Subjects...........................................................................14
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................14
4.1. Inclusion Criteria.....................................................................................................15
4.2. Exclusion Criteria....................................................................................................15
4.3. Criteria for Temporarily Delaying Vaccine Administration...................................16
4.4. Subject Replacement...............................................................................................16
4.5. Sponsor’s Qualified Medical Personnel..................................................................16
5. INVESTIGATIONAL PRODUCTS ...................................................................................17
5.1. Allocation to Investigational Product......................................................................17
5.2. Subject Compliance.................................................................................................17
5.3. Investigational Product Supplies.............................................................................17
5.3.1. Dosage Form(s) and Packaging..................................................................17
5.3.2. Concomitant Study Vaccines......................................................................18
5.4. Concomitant Medication(s)/Treatment(s)...............................................................18

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5.4.1. Prior Treatment...........................................................................................18
5.4.2. Prohibited Vaccines and Medications ........................................................18
5.4.3. Permitted Vaccines and Medications..........................................................19
5.5. Preparation and Dispensing.....................................................................................19
5.6. Administration.........................................................................................................19
5.7. Investigational Product Storage ..............................................................................20
5.8. Investigational Product Accountability...................................................................21
5.8.1. Destruction of Investigational Product Supplies ........................................21
6. STUDY PROCEDURES .....................................................................................................21
6.1. Study Period ............................................................................................................21
6.1.1. Infant Series (6, 10, and 14 Weeks of Age)................................................21
6.1.1.1. Visit 1 (42 to 72 Days of Age) ..................................................21
6.1.1.2. Visit 2 (28 to 42 Days After Visit 1).........................................22
6.1.1.3. Visit 3 (28 to 42 Days After Visit 2).........................................24
6.1.2. Post–Infant Series Visit (18 Weeks of Age)...............................................25
6.1.2.1. Visit 4 (28 to 42 Days After Visit 3).........................................25
6.1.3. Toddler Dose (12 Months of Age)..............................................................25
6.1.3.1. Visit 5 (365 to 420 Days of Age) ..............................................25
6.1.4. Post–Toddler Dose Visit (13 Months of Age)............................................26
6.1.4.1. Visit 6 (28 to 42 Days After Visit 5).........................................26
6.1.5. Unscheduled Visits.....................................................................................27
6.2. Subject Withdrawal.................................................................................................27
7. ASSESSMENTS..................................................................................................................29
7.1. Safety Assessments .................................................................................................29
7.1.1. Electronic Diary..........................................................................................29
7.1.2. Local Reactions ..........................................................................................30
7.1.3. Systemic Events and Fever.........................................................................30
7.2. Biological Samples..................................................................................................31
7.3. Immunogenicity ......................................................................................................32
8. ADVERSE EVENT REPORTING......................................................................................32
8.1. Requirements...........................................................................................................32
8.1.1. Additional Details on Recording Adverse Events on the CRF...................34

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8.1.2. Eliciting Adverse Event Information..........................................................34
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the 
Subject Withdrawal section)............................................................................34
8.1.4. Time Period for Collecting AE/SAE Information......................................34
8.1.4.1. Reporting SAEs to Pfizer Safety...............................................34
8.1.4.2. Recording Nonserious AEs and SAEs on the CRF...................35
8.1.5. Causality Assessment .................................................................................35
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ..................35
8.2. Definitions...............................................................................................................35
8.2.1. Adverse Events...........................................................................................35
8.2.2. Abnormal Test Findings .............................................................................36
8.2.3. Serious Adverse Events ..............................................................................37
8.2.4. Hospitalization............................................................................................38
8.3. Severity Assessment................................................................................................39
8.4. Special Situations ....................................................................................................39
8.4.1. Protocol-Specified Serious Adverse Events...............................................39
8.4.2. Potential Cases of Drug-Induced Liver Injury............................................39
8.4.3. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................41
8.4.3.1. Exposure During Pregnancy......................................................41
8.4.3.2. Exposure During Breastfeeding ................................................43
8.4.3.3. Occupational Exposure .............................................................43
8.4.4. Medication Errors and Lack of Efficacy ....................................................43
8.4.4.1. Medication Errors......................................................................43
8.4.4.2. Lack of Efficacy........................................................................44
8.5. Medical Device Complaint Reporting Requirements .............................................44
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................44
9.1. Sample Size Determination.....................................................................................45
9.2. Efficacy Analysis ....................................................................................................46
9.2.1. Analysis of the Primary Endpoints.............................................................46
9.2.2. Analysis of the Secondary Endpoints.........................................................46
9.3. Analysis of Demographic Characteristics...............................................................47
9.4. Safety Analysis........................................................................................................47

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9.5. Interim Analysis ......................................................................................................48
9.6. Data Monitoring Committee ...................................................................................48
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................48
11. DATA HANDLING AND RECORD KEEPING .............................................................49
11.1. Case Report Forms/Electronic Data Record .........................................................49
11.2. Record Retention...................................................................................................49
12. ETHICS..............................................................................................................................50
12.1. Institutional Review Board/Ethics Committee......................................................50
12.2. Ethical Conduct of the Study ................................................................................50
12.3. Subject Information and Consent..........................................................................50
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................51
13. DEFINITION OF END OF TRIAL...................................................................................52
13.1. End of Trial in All Participating Countries ...........................................................52
14. SPONSOR DISCONTINUATION CRITERIA ................................................................52
15. PUBLICATION OF STUDY RESULTS..........................................................................52
15.1. Communication of Results by Pfizer ....................................................................52
15.2. Publications by Investigators ................................................................................53
16. REFERENCES ..................................................................................................................54
LIST OF TABLES
Table 1.
Schedule of Activities.............................................................................................9
Table 2.
Study Vaccination Schedule.................................................................................14
Table 3.
Local Reaction Grading Scale ..............................................................................30
Table 4.
Grading Scale for Fever and Systemic Events .....................................................31
Table 5.
Probability of Detection of at Least 1 Adverse Event in the Infant Series...........45
Table 6.
Half-Width of the 95% Confidence Interval for Geometric Mean 
Concentration, by Serotype ..................................................................................45
APPENDICES
Appendix 1. Abbreviations......................................................................................................58

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PROTOCOL SUMMARY
Background
Diseases caused by Streptococcus pneumoniae are a major public health problem affecting 
all age groups worldwide. Pfizer has entered into an agreement with Gavi, the Vaccine 
Alliance, to improve access to Prevenar (13-valent pneumococcal conjugate vaccine;
13vPnC) in countries that are supported by Gavi where individuals are at high risk of 
pneumococcal disease. To best supply 13vPnC for this program, Pfizer developed a 
multidose formulation of Prevenar 13 (4 doses per vial), which requires 2-phenoxyethanol 
(2-PE) as a preservative in order to prevent microbial growth. Currently, 2-PE is the 
preservative used in a number of commercially available vaccines. The multidose vial 
(MDV) occupies less cold-chain capacity than an equivalent number of doses presented in a
single-dose prefilled syringe (PFS) that contains the 13vPnC formulation without 
preservative. In a study in the Gambia, the 13vPnC MDV formulation, with 2-PE as 
preservative, demonstrated immunogenicity and safety profiles comparable to those of the 
approved formulation of 13vPnC without 2-PE.
This study is being conducted to assess the safety, tolerability, and immunogenicity of the 
13vPnC MDV formulation in infants and toddlers in India in response to a request from the 
Subject Expert Committee (SEC) and the Drugs Controller General of India (DCGI) 
following a no objection certificate (NOC) to the marketing authorization of the MDV 
13vPnC+2-PE formulation in India.
Primary Objective and Endpoints
To describe the safety profile of 13vPnC with 2-PE in the MDV group and without 2-PE in 
the PFS group.

Incidence of local reactions and systemic events at the following time periods in the 
MDV group and in the PFS group:
o
Within the 7 days after the first dose of the infant series.
o
Within the 7 days after the second dose of the infant series.
o
Within the 7 days after the third dose of the infant series.
o
Within the 7 days after the toddler dose.

Incidence of adverse events (AEs) in the MDV group and in the PFS group from the first 
dose up to 1 month after the infant series.

Incidence of AEs in the MDV group and in the PFS group from the toddler dose up to 
1 month after the toddler dose.

Incidence of serious adverse events (SAEs) in the MDV group and in the PFS group from 
the first dose up to 1 month after the toddler dose.

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
Incidence of newly diagnosed chronic medical conditions in the MDV group and in the 
PFS group from 1 month after the infant series up to the toddler dose.
Study Design
This is a randomized, open-label study in which subjects will receive either 13vPnC with 
2-PE from an MDV or 13vPnC without 2-PE in a PFS. 
Subjects will be randomized in a 1:1 ratio to 1 of the 2 groups. 
Subjects will be vaccinated in a 3-dose infant series followed by a toddler dose.
Subjects will have 2 blood draws of up to 5 mL at approximately 1 month after the infant 
series and 1 month after the toddler dose. 
Approximate Duration of Subject Participation
Each subject is expected to participate from the first vaccination at 6 weeks of age to a 
post– toddler dose blood draw.  The total duration of subject participation is therefore up to 
approximately 14 months.
Approximate Duration of the Study
This study is anticipated to last approximately 20 months, assuming a 6-month recruitment 
period. The total duration may differ depending on the actual enrollment rate.  The end of the 
study is the last visit of the last subject, which is scheduled 1 month after the toddler dose.
Approximate Number of Subjects
Approximately 300 subjects (150 subjects per group) will be randomized in this study at 
approximately 8 sites. The number of subjects enrolled at each site may vary based on 
enrollment capabilities of each site and the final number of sites.

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SCHEDULE OF ACTIVITIES
The schedule of activities table (Table 1) provides an overview of the protocol visits and 
procedures.  Refer to the Study Procedures and Assessments sections of the protocol for 
detailed information on each procedure and assessment required for compliance with the 
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed on the 
schedule of activities table, in order to conduct evaluations or assessments required to protect 
the well-being of the subject.
Table 1.
Schedule of Activities
Visit Number
1
2
3
4
5
6
Visit ID
6-Week 
Visit
10-Week 
Visit
14-Week 
Visit
18-Week 
Visit
12-Month 
Visit
13-Month 
Visit
Visit Windowa
42 to 72 
Days of 
Age
28 to 42 
Days After 
Visit 1
28 to 42 
Days After 
Visit 2
28 to 42 
Days After
Visit 3
365 to 420
Days of 
Age
28 to 42 
Days After 
Visit 5
Informed consent
x
Review inclusion/exclusion 
criteria
x
Demography
x
Medical history, physical 
examination
x
Weigh subject
x
Axillary temperature
x
x
x
x
Randomization
x
13vPnC administration & 
30-minute observation
x
x
x
x
DTP-Hib-HBV 
administration
x
x
x
Rotavirus vaccine 
administration
x
x
x
Hepatitis A virus vaccine 
administration
x
Provide parent with e-diary, 
caliper, thermometer, as 
appropriate for visit
x
x
x
x
Review e-diary data
x
x
x
x
Confirm continued eligibility
x
x
x
x
AE collection as appropriate 
for visit
x
x
x
x
x
x
Obtain blood sample
x
x
Abbreviations:  DTP-Hib-HBV = diphtheria, tetanus, and pertussis; Haemophilus influenzae type b; and 
hepatitis B virus vaccine; e-diary = electronic diary. 
a.
Visit windows are included in this protocol so that subjects in this study all have their vaccinations and 
blood draws within a broadly uniform time frame. However, because of the population under study, it is 
recognized that it may not always be possible to adhere to these windows (for example, because of subject 
illness).

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1. INTRODUCTION
Diseases caused by Streptococcus pneumoniae are a major public health problem affecting 
all age groups worldwide. Pfizer has entered into an agreement with Gavi, the Vaccine 
Alliance, to improve access to Prevenar 13(13-valent pneumococcal conjugate vaccine;
13vPnC) in the countries that are supported by Gavi where individuals are at high risk of 
pneumococcal disease. Gavi is a global health partnership between the private and public 
sectors that aims to increase access to immunization in developing countries.  To best supply 
13vPnC for this program, Pfizer developed a multidose formulation of Prevenar 13 (4 doses 
per vial), which requires 2-phenoxyethanol (2-PE) as a preservative in order to prevent 
microbial growth. Currently, 2-PE is the preservative used in a number of commercially 
available vaccines, eg, diphtheria, tetanus, and acellular pertussis vaccine (DTaP; Daptacel); 
tetanus, low-dose diphtheria, and low-dose acellular pertussis vaccine (Tdap; Adacel); 
diphtheria, tetanus, and acellular pertussis; inactivated poliovirus; and Haemophilus 
influenzae type b vaccine (DTaP-IPV-Hib; Pentacel); and inactivated poliovirus vaccine 
(IPV; Ipol). The multidose vial (MDV) occupies less cold-chain capacity than an equivalent 
number of doses presented in a single-dose prefilled syringe (PFS) that contains the 13vPnC 
formulation without preservative.
1.1. Indication
Prevenar 13 is licensed in India for active immunization for the prevention of disease caused 
by S pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F (including 
sepsis, meningitis, bacteremia, pneumonia, and acute otitis media) in infants and children 
from 6 weeks to 5 years of age and for active immunization for the prevention of pneumonia 
and invasive disease caused by S pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 
19A, 19F, and 23F in adults 50 years of age and older.
The MDV 13vPnC+2-PE formulation is also licensed in India for the above indication.
1.2. Background and Rationale
Infections caused by S pneumoniae are a major cause of morbidity and mortality all over the 
world.  Pneumonia, febrile bacteremia, and meningitis are the most common manifestations 
of invasive pneumococcal disease (IPD).  Pneumococcal meningitis is a severe disease with 
high mortality and high incidence of neurologic sequelae.1  S pneumoniae also causes
noninvasive pneumococcal disease, including otitis media, sinusitis, bronchitis, and 
nonbacteremic pneumonia.  Of the estimated 8.8 million global annual deaths among 
children <5 years of age in 2008, the World Health Organization (WHO) estimated that 
476,000 (333,000-529,000) were caused by pneumococcal infections. Disease rates and 
mortality are higher in developing than in industrialized settings, with the majority of deaths 
occurring in Africa and Asia. Development of pneumococcal resistance to commonly used 
antibiotics such as penicillins, macrolides, cephalosporins, and cotrimoxazole is a serious 
problem in some parts of the world. However, following the introduction of large-scale 
pneumococcal immunization, a reduction in the circulation of drug-resistant strains has been 
observed.2

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Before the introduction of the 7-valent pneumococcal conjugate vaccine (7vPnC), marketed 
as Prevenar/Prevnar, the incidence of IPD in the United States was approximately 
96/100,000 cases in children less than 5 years of age, with higher rates in children less than 
2 years of age.3  The ability of 7vPnC to prevent vaccine serotype–related pediatric IPD, 
pneumonia, and otitis media initially reported in controlled clinical trials4,5,6 was 
subsequently established in clinical practice following the incorporation of 7vPnC into the 
routine childhood vaccination schedule in the United States and other
countries.7,8,9,10,11,12,13,14,15,16  Vaccination of children has also been shown to reduce IPD 
incidences among unimmunized adult populations in some countries.17,18
After the introduction of 7vPnC, the Active Bacterial Core surveillance (ABCs) data have 
shown a small but statistically significant increase in pneumococcal disease due to 
nonvaccine serogroups/serotypes in both infants and adults.10,17,19  Serotypes 19A, 3, 15, 22F, 
33F, and 35 have been isolated, with 19A being the most prevalent in children below 5 years 
of age.19  To expand the serotype coverage, Pfizer developed 13vPnC. The efficacy of 
13vPnC against vaccine-type IPD has been demonstrated in all ages in a number of national 
surveillances of pneumococcal disease in countries that have implemented widespread 
13vPnC immunization.20,21,22,23,24,25,26,27,28,29,30 The efficacy of 13vPnC against vaccine-type 
community-acquired pneumonia (including nonbacteremic) and IPD in adults aged 65 years 
is supported by the findings from the Community-Acquired Pneumonia Immunization Trial 
in Adults (CAPiTA).31
13vPnC is licensed in the European Union and other European countries, the United States, 
and other countries globally, including India, as Prevenar 13/Prevnar 13.  It contains 
polysaccharides from the 7 serotypes included in 7vPnC and an additional 6 serotypes (1, 3, 
5, 6A, 7F, and 19A), all conjugated to cross-reactive material 197 (CRM197).  It has been 
shown that the 6 additional serotypes in 13vPnC increase coverage for IPD prevention in 
children <5 years of age to 74% to 88% globally.32  Importantly, the additional serotypes in 
13vPnC are associated with a high percentage of pneumococcal disease in the developing 
world.33,34 Vaccines are often presented as single-dose vials or PFSs; however, MDV
formulations are commonly used in developing countries.  In single-dose vaccine 
formulations, each dose remains sealed and protected until it is ready for administration, 
decreasing chances for wastage and contamination.  Because each dose needs its own 
container, single-dose formulations occupy a greater volume per dose than MDVs with 
regard to supply-chain storage and medical waste disposal.35,36  This issue is a significant 
problem when storage space and transport space are limited.  The advantage of MDVs is that 
they allow the vaccine to occupy less cold-chain capacity than single-dose PFSs, therefore 
reducing cold-chain and storage costs.  Unlike single-dose PFSs that are discarded 
immediately after single use, MDVs are used more than once.  As the vaccine vial is 
punctured more than once, a preservative not present in the single-dose PFS is required to 
prevent microbial growth.
The preservative 2-PE is added to 13vPnC in MDVs.  This preservative is a phenolic 
derivative used in vaccine production. It was studied at high concentrations in animal studies 
and did not result in adverse events (AEs).37,38  Furthermore, a study published by Khandke 
et al39 demonstrated that 2-PE at 5.0 mg per dose in the Prevenar 13 multidose formulation 

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met the antimicrobial effectiveness requirements of the European Pharmacopoeia.  Currently, 
2-PE is the preservative used in a number of commercially available vaccines, eg, diphtheria 
and tetanus toxoids and acellular pertussis vaccine adsorbed (Daptacel; Infanrix) and 
hepatitis A inactivated and hepatitis B (recombinant) vaccine (Twinrix).40
In the open-label, randomized study in healthy infants in the Gambia (Study B4671001), the 
13vPnC MDV formulation, with 2-PE as preservative, demonstrated immunogenicity and 
safety profiles comparable to those of the approved formulation of 13vPnC without 2-PE. In 
the Gambia study, the 13vPnC MDV formulation was given to healthy infants at 8, 12, and 
16 weeks of age and compared to Prevenar 13 without added preservative. Pneumococcal 
immune responses were compared using noninferiority criteria, including the percentage of 
subjects with serum antipolysaccharide serotype-specific immunoglobulin G (IgG)
concentration 0.35 μg/mL and the comparison of IgG geometric mean concentrations 
(GMCs) 1 month after the infant series. In addition, opsonophagocytic activity (OPA)
geometric mean titers (GMTs) between groups receiving Prevenar 13 with or without 2-PE 
were compared. Noninferiority for the proportion of subjects achieving an IgG concentration 
0.35 μg/mL was demonstrated for all 13 serotypes. Additionally, all 13 serotypes met the 
predefined noninferiority criterion for IgG GMCs. OPA GMTs were similar in both groups, 
except for serotype 3, for which the OPA GMT was lower, and serotype 18C, for which it 
was higher, in the group that received Prevenar 13 with 2-PE.
This study is being conducted in response to a request from the Subject Expert Committee 
(SEC) and the Drugs Controller General of India (DCGI) following a no objection certificate 
(NOC) to the marketing authorization of the MDV 13vPnC+2-PE formulation in India. This 
study will describe the safety, tolerability, and immunogenicity of 13vPnC with 2-PE
presented in MDVs in infants and toddlers in India. This study is defined as a 
postauthorization safety study (PASS).
Additional information for 13vPnC with 2-PE (MDV) and 13vPnC without 2-PE (PFS) may 
be found in the single reference safety document (SRSD), which for this study is the local 
package label.
2. STUDY OBJECTIVES AND ENDPOINTS
Primary 
Objective
Primary Endpoints
To describe the 
safety profile of 
13vPnC with 2-PE 
in the MDV group
and without 2-PE in 
the PFS group.

Incidence of local reactions and systemic events at the following 
time periods in the MDV group and in the PFS group:
o
Within the 7 days after the first dose of the infant series.
o
Within the 7 days after the second dose of the infant series.
o
Within the 7 days after the third dose of the infant series.
o
Within the 7 days after the toddler dose.

Incidence of AEs in the MDV group and in the PFS group from the 
first dose up to 1 month after the infant series.

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
Incidence of AEs in the MDV group and in the PFS group from the 
toddler dose up to 1 month after the toddler dose.

Incidence of serious adverse events (SAEs) in the MDV group and 
in the PFS group from the first dose up to 1 month after the toddler 
dose.

Incidence of newly diagnosed chronic medical conditions in the 
MDV group and in the PFS group from 1 month after the infant 
series up to the toddler dose.
Secondary 
Objective
Secondary Endpoints
To describe the 
pneumococcal 
immune responses 
induced by 13vPnC 
with 2-PE in the 
MDV group and in 
the PFS group.

The proportion of subjects with IgG concentrations equal to or 
above the defined threshold for each of the pneumococcal 
serotypes measured.
o
1 month after the infant series in the MDV group and in the 
PFS group.
o
1 month after the toddler dose in the MDV group and in the 
PFS group.

The serotype-specific IgG GMC for each of the pneumococcal 
serotypes measured
o
1 month after the infant series in the MDV group and in the 
PFS group.
o
1 month after the toddler dose in the MDV group and in the 
PFS group.

The serotype-specific OPA GMT for each of the pneumococcal 
serotypes measured
o
1 month after the infant series in the MDV group and in the 
PFS group.
o
1 month after the toddler dose in the MDV group and in the 
PFS group.

The proportion of subjects achieving a serotype-specific OPA titer 
the lower limit of quantitation (LLOQ) for each of the 
pneumococcal serotypes measured
o
1 month after the infant series in the MDV group and in the 
PFS group.
o
1 month after the toddler dose in the MDV group and in the 
PFS group.

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3. STUDY DESIGN
This is a randomized, open-label study in which subjects will receive either 13vPnC with 
2-PE from an MDV or 13vPnC without 2-PE in a PFS (see Table 2).
Subjects will be randomized in a 1:1 ratio to 1 of the 2 groups.
Subjects will be vaccinated in a 3-dose infant series followed by a toddler dose.
Subjects will have 2 blood draws of up to 5 mL at approximately 1 month after the infant 
series and approximately 1 month after the toddler dose.
Table 2.
Study Vaccination Schedule
Randomization 
Group
Visit 1
6 Weeks
Visit 2
10 Weeks
Visit 3
14 Weeks
Visit 5
12 Months 
Group 1:
MDV  
MDV
DTP-Hib-HBV
Rotavirus vaccine
MDV
DTP-Hib-HBV
Rotavirus vaccine
MDV
DTP-Hib-HBV
Rotavirus vaccine
MDV
Hepatitis A virus 
vaccine
Group 2:
PFS 
PFS
DTP-Hib-HBV
Rotavirus vaccine
PFS
DTP-Hib-HBV
Rotavirus vaccine
PFS
DTP-Hib-HBV
Rotavirus vaccine
PFS
Hepatitis A virus 
vaccine
Abbreviations: DTP-Hib-HBV = diphtheria, tetanus, and pertussis; Haemophilus influenzae type b; and 
hepatitis B virus vaccine; MDV = multidose vial; PFS = prefilled syringe.
3.1. Approximate Duration of Subject Participation
Each subject is expected to participate from the first vaccination at 6 weeks of age to a 
post–toddler dose blood draw.  The total duration of subject participation is therefore up to 
approximately 14 months.
3.2. Approximate Duration of the Study
This study is anticipated to last approximately 20 months, assuming a 6-month recruitment 
period. The total duration may differ depending on the actual enrollment rate.  The end of the 
study is the last visit of the last subject, which is scheduled 1 month after the toddler dose.
3.3. Approximate Number of Subjects
Approximately 300 subjects (150 subjects per group) will be randomized in this study at 
approximately 8 sites. The number of subjects enrolled at each site may vary based on 
enrollment capabilities of each site and the final number of sites.
4. SUBJECT ELIGIBILITY CRITERIA
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate.  All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol.

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Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.
4.1. Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document indicating that the
parent(s)/legal guardian(s) has/have been informed of all pertinent aspects of the study.
2. Parent(s)/legal guardian(s)/caregiver(s) willing and able to comply with scheduled visits, 
treatment plan, and other study procedures.
3. Aged 6 weeks (42 to 72 days) at the time of vaccination. (The day of birth is considered 
Day 0.)
4. Available for the entire study period and whose parent(s)/legal guardian(s)/caregiver(s)
can be reached by telephone.
5. Healthy infant as determined by medical history, physical examination, and judgment of 
the investigator.
6. Weight of 3.0 kg or greater at the time of vaccination.
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Infant who is a direct descendant (child, grandchild) of

Investigator site staff members directly involved in the conduct of the study, or

Site staff members otherwise supervised by the investigator, or

Pfizer employees directly involved in the conduct of the study.
2. Participation in other studies involving investigational drug(s) within 28 days prior to 
study entry and/or during study participation. Participation in purely observational studies 
is acceptable.
3. Previous vaccination with licensed or investigational pneumococcal conjugate vaccine.
4. A previous anaphylactic reaction to any vaccine or vaccine-related component.
5. Contraindication to vaccination with pneumococcal conjugate vaccine, or any other 
vaccine or vaccine component. Bleeding diathesis or condition associated with 
prolonged bleeding time that would contraindicate intramuscular injection.

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6. Known or suspected immune deficiency or suppression, including known human 
immunodeficiency virus infection.
7. Major known congenital malformation or serious chronic disorder.
8. Significant neurological disorder or history of seizure including febrile seizure, or 
significant stable or evolving disorders such as cerebral palsy, encephalopathy, 
hydrocephalus, or other significant disorders.  Does not include resolving syndromes due 
to birth trauma such as Erb’s palsy.
9. Other acute or chronic medical condition including recent laboratory abnormality that 
may increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study.
10. Receipt of blood products or gamma globulin (including hepatitis B immunoglobulin and 
monoclonal antibodies, eg, Synagis).
4.3. Criteria for Temporarily Delaying Vaccine Administration
The following conditions are temporary or self-limiting and a subject may be vaccinated 
once the condition(s) has/have resolved and no other exclusion criteria are met:
1. Current febrile illness (axillary temperature greater than or equal to 38.0°C [100.4°F]) or 
other acute illness within 48 hours before investigational product administration.
2. Subject is less than 5 days into a course of antibiotic therapy for other acute illness.
4.4. Subject Replacement
Subjects whose parent/legal guardian signed the informed consent document but are 
discontinued or withdrawn from the study before randomization will be replaced with 
additional subjects.
4.5. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study. The contact number can also be used by investigator
staff if they are seeking advice on medical questions or problems; however, it should be used
only in the event that the established communication pathways between the investigator site 

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and the study team are not available. It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study. The contact 
number is not intended for use by the subject directly, and if a subject calls that number, he 
or she will be directed back to the investigator site.
5. INVESTIGATIONAL PRODUCTS
For the purposes of this study, and per International Council for Harmonisation (ICH)
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33).
For this study, the investigational products are 13vPnC with 2-PE in MDVs and 13vPnC 
without 2-PE in PFSs.
5.1. Allocation to Investigational Product
The investigator’s knowledge of the investigational product should not influence the decision 
to randomize a particular subject or affect the order in which subjects are randomized.
Allocation of subjects to vaccine groups will proceed through the use of an interactive 
response technology (IRT) system (interactive web-based response [IWR]).  The site 
personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the subject number. The site personnel will then be provided with a 
vaccine assignment, randomization number, and dispensable unit (DU) or container number 
when investigational product is being supplied via the IRT system.  The IRT system will 
provide a confirmation report containing the subject number, randomization number, and DU 
or container number assigned. The confirmation report must be stored in the site’s files.
The study-specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system.
5.2. Subject Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
5.3. Investigational Product Supplies
5.3.1. Dosage Form(s) and Packaging
13vPnC will be provided to the study site by the sponsor in MDVs and single-dose PFSs.
13vPnC contains saccharides from pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 
18C, 19A, 19F, and 23F individually conjugated to nontoxic diphtheria toxin CRM197.  The 

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vaccine is formulated to contain 2.2 g of each saccharide, except for 4.4 g of 6B, per 
0.5-mL dose.  The vaccine is formulated with 5 mM succinate buffer, 0.02% polysorbate 80, 
and 0.125 mg of aluminum as aluminum phosphate, per 0.5-mL dose.
13vPnC MDVs will also contain 4 mg of 2-PE per 0.5-mL dose. Four (4) doses of 13vPnC 
(2.0 mL) will be contained within each MDV. For the purposes of this study, only a single 
0.5-mL dose will be administered from each of the MDVs.
5.3.2. Concomitant Study Vaccines
The following mandatory vaccines will be administered concomitantly with the 
investigational product as detailed in the schedule of activities: 

DTP-Hib-HBV

Rotavirus vaccine

Hepatitis A virus vaccine
DTP-Hib-HBV will be administered intramuscularly at 6, 10, and 14 weeks of age.
Rotavirus vaccine will be administered orally at 6, 10, and 14 weeks of age.
Hepatitis A virus vaccine will be administered intramuscularly at 12 months of age.
The SRSD for DTP-Hib-HBV, rotavirus vaccine, or hepatitis A virus vaccine is the local 
package insert.
5.4. Concomitant Medication(s)/Treatment(s)
5.4.1. Prior Treatment
Vaccines given at birth or before enrollment, including bacillus Calmette-Guerin (BCG) 
vaccine, hepatitis B virus (HBV) vaccine, or polio vaccine, may be given as per local 
recommendations.
All vaccinations received from birth until enrollment into the study will be recorded on the 
case report form (CRF).
5.4.2. Prohibited Vaccines and Medications
No pneumococcal vaccines (licensed or investigational) other than those described in this 
study may be given prior to or during the study.
Local anesthetic cream should not be used at the site of investigational product 
administration.
Prophylactic use of antipyretic and other pain medications to prevent symptoms that might 
occur as a result of study vaccine administration should be discouraged; however, it is 

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recognized that use of antipyretic medication is a matter of parental choice and local clinical 
practice.
5.4.3. Permitted Vaccines and Medications
In addition to the mandatory vaccines given concomitantly with the investigational product, 
other vaccines, including polio vaccine, may be administered as per local recommendations 
at any time. Vaccines concomitantly administered with the investigational product must be 
given in a different limb from that used to administer 13vPnC. All vaccinations received 
during the study will be recorded on the CRF.
Topical and inhaled corticosteroids are permitted during the course of the study.
Local anesthetic cream may be applied before the blood draws.
Antipyretic and other pain medications to treat symptoms are permitted.
Any medications, except those listed in Section 5.3.2, are permitted.
Details of any medication(s) given will not be collected in the CRF.
5.5. Preparation and Dispensing
Only qualified personnel should dispense the investigational products.
See the Investigational Product Manual (IP manual) or equivalent for instructions on how to 
prepare the investigational product for administration.  Investigational product should be 
prepared and dispensed by an appropriately qualified and experienced member of the study 
staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacy 
assistant/technician, or pharmacist) as allowed by local, state, and institutional guidance.
5.6. Administration
Subjects will receive 1 dose of 13vPnC at each vaccination visit (Visits 1, 2, 3, and 5) in 
accordance with the study’s schedule of activities.
13vPnC should be administered intramuscularly by injecting 0.5 mL into the anterolateral 
thigh muscle of the left leg at the vaccination visits.
For the purposes of this study, only a single 0.5-mL dose will be administered from each of 
the MDVs.
For DTP-Hib-HBV, rotavirus vaccine, and hepatitis A virus vaccine, dosage 
recommendations in the appropriate locally approved labeling should be followed.
Concomitant vaccines must be given in a different limb from that used to administer 13vPnC.
Standard vaccination practices must be observed and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 

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hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance.
Investigational product administration details will be recorded on the CRF.
5.7. Investigational Product Storage
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products and other mandatory study vaccines, including DTP-Hib-HBV, 
rotavirus vaccine, and hepatitis A virus vaccine, are stored in a secured area with controlled 
access under required storage conditions and in accordance with applicable regulatory 
requirements.
Investigational products should be stored in their original containers and in accordance with 
the labels.
Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products).  This should 
be captured from the time of investigational product receipt throughout the study.  Even for 
continuous-monitoring systems, a log or site procedure that ensures active evaluation for 
excursions should be available.  The intent is to ensure that the minimum and maximum 
temperature is checked each business day to confirm that no excursion occurred since the last 
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all nonworking days upon return to normal operations.  The operation of the 
temperature-monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure they are maintained in working order.
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery. The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer.
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion. Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation. Specific details regarding information the site should report 
for each excursion will be provided to the site.

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Receipt of materials, door opening and closing, and other routine handling operations where 
the products are briefly out of the temperature range described in the labeling are not 
considered excursions.
5.8. Investigational Product Accountability
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record.
5.8.1. Destruction of Investigational Product Supplies
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site). If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
6. STUDY PROCEDURES
6.1. Study Period
Visit windows are included in this protocol so that subjects in this study all have their 
vaccinations and blood draws within a broadly uniform time frame. However, because of the 
population under study, it is recognized that it may not always be possible to adhere to these 
windows (for example, because of subject illness).
6.1.1. Infant Series (6, 10, and 14 Weeks of Age)
6.1.1.1. Visit 1 (42 to 72 Days of Age)

Obtain informed consent per local requirements from the subject’s parent(s)/legal 
guardian(s) before performing study-specific procedures.

Record the subject’s demographic information (including date of birth, sex, and 
ethnicity).

Obtain and record the subject’s medical history including prior vaccinations.

Perform a physical examination evaluating any clinically significant abnormalities within 
the following body systems: general appearance; skin; head, eyes, ears, nose, and throat; 
heart; lungs; abdomen; extremities; neurological; musculoskeletal; and lymph nodes; 
including worsening of medical history conditions.

Weigh the subject.

Ensure that all inclusion criteria, none of the exclusion criteria, and none of the temporary 
delay criteria are met.

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
On the day of vaccination, prior to vaccination, measure and record the subject’s axillary 
temperature.

After all entry criteria are confirmed, the subject will be randomized into 1 of the 2 
vaccine groups using an IRT system (IWR), or equivalent system. An appropriate site 
staff member will use the IRT system to obtain the subject’s investigational product DU 
or container number.

Administer a single 0.5-mL intramuscular injection of 13vPnC from either an MDV or a 
PFS into the anterolateral thigh muscle of the left leg.

Administer a single intramuscular dose of DTP-Hib-HBV into a different limb from that
used to administer 13vPnC, according to local clinical practice.

Administer a single dose of rotavirus vaccine according to local clinical practice.

Observe the subject for at least 30 minutes after vaccination for any significant acute 
reactions.  Any AEs noted during the observation period should be recorded in the 
subject’s source documents and on the AE section of the CRF.

Issue a caliper and a digital thermometer to the parent(s)/legal guardian(s)/caregiver(s) 
and provide instructions on their use.

Issue a subject electronic diary (e-diary) to the parent(s)/legal guardian(s)/caregiver(s). 
Provide instruction on its completion for 7 days (Day 1 through Day 7, where Day 1 is 
the day of vaccination).

Ask the parent(s)/legal guardian(s)/caregiver(s) to contact the investigator immediately if 
any significant illness or hospitalization occurs during the study period, or if the subject 
experiences a large (>14 caliper units) local reaction.

Schedule an appointment with the parent(s)/legal guardian(s)/caregiver(s) for the next 
study visit.

Remind the parent(s)/legal guardian(s)/caregiver(s) to bring the e-diary to the next study 
visit.

The investigator or an authorized designee completes the source documents, completes 
the CRF, and updates the investigational product accountability records.
6.1.1.2. Visit 2 (28 to 42 Days After Visit 1)

Review the subject’s e-diary data and follow up on any ongoing local reactions or 
systemic events.

Based on clinical evaluation, determine whether any AEs or SAEs have occurred since 
the last study visit and record them on the CRF.

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
Review AEs that were ongoing from the previous visit and record their end dates or 
confirm that they are still ongoing.

Ensure that the subject continues to be eligible for the study and meets none of the 
withdrawal criteria (Section 6.2).

On the day of vaccination, prior to vaccination, measure and record the subject’s axillary 
temperature.

Ensure that the subject does not meet any of the temporary delay criteria (Section 4.3).

An appropriate site staff member will use the IRT system to obtain the subject’s 
investigational product DU or container number.

Administer a single 0.5-mL intramuscular injection of 13vPnC from an MDV or a PFS 
into the anterolateral thigh muscle of the left leg.

Administer a single intramuscular dose of DTP-Hib-HBV into a different limb from that
used to administer 13vPnC, according to local clinical practice.

Administer a single dose of rotavirus vaccine according to local clinical practice.

Observe the subject for at least 30 minutes after vaccination for any significant acute 
reactions.  Any AE noted during the observation period should be recorded on the source 
documents and on the AE section of the CRF.

Issue a caliper and a digital thermometer (if necessary) to the parent(s)/legal 
guardian(s)/caregiver(s) and provide instructions on their use.

Issue a subject e-diary (if necessary) to the parent(s)/legal guardian(s)/caregiver(s).  
Provide instruction on its completion for 7 days (Day 1 through Day 7, where Day 1 is 
the day of vaccination).

Ask the parent(s)/legal guardian(s)/caregiver(s) to contact the investigator immediately if 
any significant illness or hospitalization occurs during the study period, or if the subject 
experiences a large (>14 caliper units) local reaction.

Schedule an appointment with the parent(s)/legal guardian(s)/caregiver(s) for the next 
study visit.

Remind the parent(s)/legal guardian(s)/caregiver(s) to bring the e-diary to the next study 
visit.

The investigator or an authorized designee completes the source documents, completes 
the CRF, and updates the investigational product accountability records.

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6.1.1.3. Visit 3 (28 to 42 Days After Visit 2)

Review the subject’s e-diary and follow up on any ongoing local reactions or systemic
events.

Based on clinical evaluation, determine whether any AEs or SAEs have occurred since 
the last study visit and record them on the CRF.

Review AEs that were ongoing from the previous visit and record their end dates or 
confirm that they are still ongoing.

Ensure that the subject continues to be eligible for the study and meets none of the 
withdrawal criteria (Section 6.2).

On the day of vaccination, prior to vaccination, measure and record the subject’s axillary 
temperature.

Ensure that the subject does not meet any of the temporary delay criteria (Section 4.3).

An appropriate site staff member will use the IRT system to obtain the subject’s 
investigational product DU or container number.

Administer a single 0.5-mL intramuscular injection of 13vPnC from an MDV or a PFS 
into the anterolateral thigh muscle of the left leg.

Administer a single intramuscular dose of DTP-Hib-HBV into a different limb from that 
used to administer 13vPnC, according to local clinical practice.

Administer a single dose of rotavirus vaccine according to local clinical practice.

Observe the subject for at least 30 minutes after vaccination for any significant acute 
reactions.  Any AE noted during the observation period should be recorded on the source 
documents and on the AE section of the CRF.

Issue a caliper and a digital thermometer (if necessary) to the parent(s)/legal 
guardian(s)/caregiver(s) and provide instructions on their use.

Issue a subject e-diary (if necessary) to the parent(s)/legal guardian(s)/caregiver(s). 
Provide instruction on its completion for 7 days (Day 1 through Day 7, where Day 1 is 
the day of vaccination).

Ask the parent(s)/legal guardian(s)/caregiver(s) to contact the investigator immediately if 
any significant illness or hospitalization occurs during the study period, or if the subject 
experiences a large (>14 caliper units) local reaction.

Schedule an appointment with the parent(s)/legal guardian(s)/caregiver(s) for the next 
study visit.

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
Remind the parent(s)/legal guardian(s)/caregiver(s) to bring the e-diary to the next study 
visit.

The investigator or an authorized designee completes the source documents, completes 
the CRF, and updates the investigational product accountability records.
6.1.2. Post–Infant Series Visit (18 Weeks of Age)
6.1.2.1. Visit 4 (28 to 42 Days After Visit 3)

Collect the subject’s e-diary.

Review the subject’s e-diary data and follow up on any ongoing local reactions or 
systemic events.

Based on clinical evaluation, determine whether any AEs or SAEs have occurred since 
the last study visit and record them on the CRF.

Review AEs that were ongoing from the previous visit and record their end dates or 
confirm that they are still ongoing.

Ensure that the subject continues to be eligible for the study and meets none of the 
withdrawal criteria (Section 6.2).

Collect an approximately 5-mL blood sample.

Schedule an appointment with the parent(s)/legal guardian(s)/caregiver(s) for the next 
study visit.

The investigator or an authorized designee completes the source documents, and 
completes the CRF.
6.1.3. Toddler Dose (12 Months of Age)
6.1.3.1. Visit 5 (365 to 420 Days of Age)

Based on clinical evaluation, determine whether SAEs or newly diagnosed chronic 
medical conditions have occurred since the last study visit and record them on the CRF.

Review AEs that were ongoing from the previous visit and record their end dates or 
confirm that they are still ongoing.

On the day of vaccination, prior to vaccination, measure and record the subject’s axillary 
temperature.

Ensure that the subject continues to be eligible for the study and meets none of the 
withdrawal criteria (Section 6.2).

Ensure that the subject does not meet any of the temporary delay criteria (Section 4.3).

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
An appropriate site staff member will use the IRT system to obtain the subject’s 
investigational product DU or container number.

Administer a single 0.5-mL intramuscular injection of 13vPnC from an MDV or a PFS 
into the anterolateral thigh muscle of the left leg.

Administer a single dose of hepatitis A virus vaccine into a different limb from that used
to administer 13vPnC, according to local clinical practice.

Observe the subject for at least 30 minutes after vaccination for any significant acute 
reactions.  Any AE noted during the observation period should be recorded on the source 
documents and on the AE section of the CRF.

Issue a caliper and a digital thermometer to the parent(s)/legal guardian(s)/caregiver(s)
and provide instructions on their use.

Issue a subject e-diary to the parent(s)/legal guardian(s)/caregiver(s).  Provide instruction 
on its completion for 7 days (Day 1 through Day 7, where Day 1 is the day of 
vaccination).

Ask the parent(s)/legal guardian(s)/caregiver(s) to contact the investigator immediately if 
any significant illness or hospitalization occurs during the study period, or if the subject 
experiences a large (>14 caliper units) local reaction.

Schedule an appointment with the parent(s)/legal guardian(s)/caregiver(s) for the next 
study visit.

Remind the parent(s)/legal guardian(s)/caregiver(s) to bring the e-diary to the next study 
visit.

The investigator or an authorized designee completes the source documents, completes 
the CRF, and updates the investigational product accountability records.
6.1.4. Post–Toddler Dose Visit (13 Months of Age)
6.1.4.1. Visit 6 (28 to 42 Days After Visit 5)

Collect the subject’s e-diary.

Review the subject’s e-diary data and follow up on any ongoing local reactions or 
systemic events.

Based on clinical evaluation, determine whether any AEs or SAEs have occurred since 
the last study visit and record them on the CRF.

Review AEs that were ongoing from the previous visit and record their end dates or 
confirm that they are still ongoing.

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
Collect a blood sample (approximately 5 mL).

The investigator or an authorized designee completes the source documents, and 
completes the CRF.
6.1.5. Unscheduled Visits
If a local reaction at the pneumococcal injection site is greater than 14 caliper units (7.0 cm), 
a study site visit will be required to assess the extent of the reaction.  The subject’s 
parent(s)/legal guardian(s)/caregiver(s) should contact the study personnel to arrange for an 
additional visit to the study site for assessment by the investigator or a medically qualified 
member of the investigator’s staff, who will:

Measure axillary temperature.

Measure the minimum and maximum diameter of the redness or swelling in centimeters.

Assess pain at the injection site (tenderness) in accordance with the criteria provided in 
Section 7.1.2.

Complete the CRF.

If applicable, remind the subject’s parent(s)/legal guardian(s)/caregiver(s) to enter an end 
date of the reaction in the e-diary.
For the purpose of assessments performed during unscheduled visits, a medically qualified 
member of study staff is a study physician or a study nurse, as applicable to the investigator’s 
local practice.
6.2. Subject Withdrawal
An investigator and/or sponsor can withdraw a subject from the study if deemed appropriate.  
In addition, if a subject fails to continue to meet the inclusion criteria, new information 
becomes available that would exclude the subject, or the subject develops a condition or 
situation that would meet exclusion criteria, the subject may be considered for withdrawal.
Reasons why a subject may discontinue or be withdrawn from the study include, but are not 
limited to, failure to meet entrance criteria (screening failure), AE, death, protocol violation, 
lost to follow-up, no longer willing to participate in the study, study terminated by sponsor, 
investigator declined further study participation, or any other reason.  Subjects who have 
received the investigational product will not be replaced regardless of the reason for 
withdrawal.
Lost to follow-up:
All reasonable efforts must be made to locate subjects to determine and report their ongoing
status. Lost to follow-up is defined by the inability to reach the subject’s parent(s)/legal 
guardian(s)/caregiver(s) after a minimum of 2 documented phone calls, faxes, or emails as 

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well as lack of response by the subject’s parent(s)/legal guardian(s)/caregiver(s) to 
1 registered mail letter. All attempts should be documented in the subject’s medical records.
If it is determined that the subject has died, the site will use locally permissible methods to 
obtain the date and cause of death. The site staff and representative will consult publicly 
available sources, such as public health registries and databases, in order to obtain updated 
contact information. If, after all attempts, the subject remains lost to follow-up, then the 
last-known-alive date as determined by the investigator should be reported and documented 
in the subject’s medical records.
The subject’s parent(s)/legal guardian(s) may withdraw the subject from the study at any 
time at their own request, or the subject may be withdrawn at any time at the discretion of the 
investigator or sponsor for safety (see also the Withdrawal From the Study Due to Adverse 
Events section) or behavioral reasons, or the inability of the subject to comply with the 
protocol-required schedule of study visits or procedures at a given study site.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject’s parent(s)/legal guardian(s)/caregiver(s). All attempts to contact the subject’s
parent(s)/legal guardian(s)/caregiver(s) and information received during contact attempts 
must be documented in the subject’s medical record.  In any circumstance, every effort 
should be made to document subject outcome, if possible.  The investigator should inquire 
about the reason for withdrawal, request that the subject return for a final visit, if applicable, 
and follow up with the subject’s parent(s)/legal guardian(s)/caregiver(s) regarding any 
unresolved AEs.
If the subject’s parent(s)/legal guardian(s) withdraw(s) the child from the study, and also 
withdraw(s) consent for disclosure of future information, no further evaluations should be 
performed, and no additional data should be collected.  The sponsor may retain and continue 
to use any data collected before such withdrawal of consent.
Withdrawal of consent:
Subjects whose parent(s)/legal guardian(s) request(s) to discontinue receipt of investigational 
product will remain in the study and must continue to be followed for protocol-specified 
follow-up procedures.  The only exception to this is when a subject’s parent(s)/legal 
guardian(s) specifically withdraw(s) consent for any further contact with him or her or 
persons previously authorized by the subject’s parent(s)/legal guardian(s) to provide this 
information.  Subject’s parent(s)/legal guardian(s) should notify the investigator in writing of 
the decision to withdraw consent from future follow-up, whenever possible.  The withdrawal 
of consent should be explained in detail in the medical records by the investigator, as to 
whether the withdrawal is only from further receipt of investigational product or also from 
study procedures and/or posttreatment study follow-up.  In the event that vital status (whether 
the subject is alive or dead) is being measured, publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law.

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7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the subject. When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible. The 
study team will be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
7.1. Safety Assessments
Safety parameters will be assessed as described in the schedule of activities, and below.
A medical history and physical examination including measurement of vital signs will be 
performed on all subjects at Visit 1.  Significant medical history and observations from the 
physical examination will be documented in the CRF.
The safety parameters include e-diary reports of local reactions at the 13vPnC injection site 
and systemic events that occur in the 7 days after investigational product administration.
These prospectively collected occurrences of local reactions and systemic events are graded 
as described in Section 7.1.
Acute reactions within the first 30 minutes after investigational product administration will 
be assessed and documented in the AE CRF.
In addition, AEs and SAEs are collected, recorded, and reported as defined in Section 8.
7.1.1. Electronic Diary
Subject’s parent(s)/legal guardian(s)/caregiver(s) will be required to use an e-diary, based on 
appropriate technology, and will be asked to monitor and record local reactions and systemic 
events for 7 days following vaccination (Day 1 through Day 7, where Day 1 is the day of 
vaccination). The e-diary allows recording of these assessments only within a fixed time 
window, thus providing the accurate representation of the subject’s experience at that time.  
Local reactions and systemic events will be collected in the e-diary in the evening daily 
during the e-diary reporting period.
Data on local reactions and systemic events reported on the e-diary will be transferred 
electronically to a third-party vendor, where they will be available for review by investigators 
and the Pfizer clinicians at all times via an internet-based portal.

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At intervals agreed to by the vendor and Pfizer, these data will be transferred electronically 
into Pfizer's database for analysis and reporting.  These data do not need to be reported by the
investigator in the CRF as AEs.
Investigators (or appropriately qualified designee) are required to review the e-diary data 
online at frequent intervals as part of the ongoing safety review. The investigator or designee 
must contact the subject’s parent(s)/legal guardian(s)/caregiver(s) in order to obtain stop 
dates for any ongoing local reactions or systemic events on the last day that the e-diary was 
completed.  The stop dates should be documented in the source documents and the 
information entered in the CRF.
7.1.2. Local Reactions
Redness and swelling will be measured and recorded in caliper units (range: 1 to 14) for the 
first 7 days following vaccination (Days 1 to 7), and then categorized using the scale shown 
in Table 3. The measurements will then be recorded in the e-diary.
A caliper will be given to the subject’s parent(s)/legal guardian(s)/caregiver(s) with 
instructions for measuring both redness and swelling at the injection site.  Each caliper unit is 
equivalent to 0.5 cm.  The parent(s)/legal guardian(s)/caregiver(s) will be asked to measure 
the largest diameters of the local reaction.  Where a caliper measurement is between 2 values, 
the higher value should be reported.  At the time of entry into the e-diary, the parent(s)/legal 
guardian(s)/caregiver(s) should record the maximum severity of the reaction since the 
previous entry into the e-diary.
Table 3.
Local Reaction Grading Scale
GRADE 1
mild
GRADE 2
moderate
GRADE 3a
severe
Redness
1 to 4 caliper units
(or measuring device units)
=
0.5 to 2.0 cm
5 to 14 caliper units
(or measuring device units)
=
2.5 to 7.0 cm
>14 caliper units
(or measuring device units)
=
>7.0 cm
Swelling
1 to 4 caliper units
(or measuring device units)
=
0.5 to 2.0 cm
5 to 14 caliper units
(or measuring device units)
=
2.5 to 7.0 cm
>14 caliper units
(or measuring device units)
=
>7.0 cm
Pain at injection site
(tenderness)
Hurts if gently touched
(eg, whimpers, winces, 
protests, or withdraws)
Hurts if gently touched 
(with crying)
Causes limitation of limb 
movement
a.
Local reactions >14 caliper units (>7.0 cm) should be assessed by the study site.
7.1.3. Systemic Events and Fever
The e-diary will be used to record the presence of systemic events (loss of or decreased 
appetite, drowsiness, and irritability) daily for 7 days (Day 1 to Day 7) after each vaccination, 
using the grading scale in Table 4.

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A digital thermometer will be given to the subject’s parent(s)/legal guardian(s) with 
instructions on how to measure the child’s axillary temperature at home.  Axillary 
temperature will be collected at evening bedtime daily for 7 days (Day 1 to Day 7) after each 
vaccination, and at any time during the 7 days when fever is suspected.  The highest 
temperature for each day will be recorded in the e-diary.
Fever is defined as a temperature of 38.0C (100.4F).
Temperature will be measured and recorded to 1 decimal place and then categorized 
according to the scale for fever (see Table 4).
Table 4.
Grading Scale for Fever and Systemic Events
Fever
38.0°C to 38.4°C
100.4°F to 101.1°F
38.5°C to 38.9°C
101.2°F to 102.0°F
39.0°C to 40.0°C
102.1°F to 104.0°F
>40.0°C
>104.0°F  
Systemic Events
GRADE 1
Mild
GRADE 2
Moderate
GRADE 3
Severe
Decreased appetite 
(loss of appetite) 
Decreased interest in 
eating 
Decreased oral 
intake
Refusal to feed
Drowsiness
(increased sleep)
Increased or 
prolonged sleeping 
bouts
Slightly subdued;
interfering with daily 
activity
Disabling; not 
interested in usual 
daily activity
Irritability 
(fussiness)
(synonymous with 
restless sleep; 
decreased sleep)
Easily consolable
Requiring 
increased attention
Inconsolable;
crying cannot be 
comforted
7.2. Biological Samples
Serum samples will be used only for scientific research.  Each sample will be labeled with a 
code so that the laboratory personnel testing the samples will not know the subject’s identity. 
Samples that remain after performing assays outlined in the protocol may be stored by Pfizer. 
Unless a time limitation is required by local regulations or ethical requirements, the samples 
will be stored for up to 15 years after the end of the study and then destroyed.  If allowed by 
the informed consent document, stored samples may be used for additional testing to better 
understand the immune responses to the vaccine(s) under study in this protocol, to inform the 
development of other products, and/or for vaccine-related assay work supporting vaccine 
programs.  No testing of the subject’s genetic material will be performed.
The subject’s parent(s)/legal guardian(s) may request that the child’s samples, if still 
identifiable, be destroyed at any time; however, any data already collected from those 
samples will still be used for this research.  The biological samples may be shared with other 
researchers as long as confidentiality is maintained and no testing of the subject’s genetic 
material is performed.

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7.3. Immunogenicity
Serotype-specific IgG concentrations to the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 
7F, 9V, 14, 18C, 19A, 19F, and 23F) will be determined in all subjects from the blood 
sample taken 1 month after the infant series and 1 month after the toddler dose of 13vPnC.
To support the clinical development of Pfizer’s pneumococcal conjugate vaccines, a high-
throughput, multiplex direct Luminex-based immunoassay (dLIA) platform has been 
developed to replace the WHO standardized enzyme-linked immunosorbent assay (ELISA) 
platform.  Pfizer’s 13-plex dLIA was validated using immunized human serum that contains 
IgG antibodies against the Prevnar 13 serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 
19F, and 23F.  There are several advantages to using a multiplex assay approach over the 
WHO reference ELISA for testing clinical samples. While both measure pneumococcal 
serotype-specific IgG antibodies, the Luminex-based assay is performed in a multiplex 
format, which generates more results in a shorter period of time, requires less serum, and 
generates less laboratory waste compared to ELISA. In addition, in part because of its 
multiplex format, Pfizer’s 13-plex pneumococcal dLIA platform accommodates 143 tests on 
a single assay plate, while the ELISA platform would require 36 assay plates to achieve the 
same number of tests.
An examination of the percentage of vaccine responders reaching IgG concentrations 
0.35 g/mL is historically based on the WHO reference ELISA, and the WHO Expert 
Committee has provided guidance on acceptable bridging strategies for manufacturers that 
use an alternative assay platform for clinical evaluations. To bridge the validated 13-plex 
dLIA to the WHO ELISA platform, a comprehensive bridging study was performed using 
residual serum from pivotal Prevnar 13 studies. On the basis of the bridging data submitted 
to, and approved by, the US Food and Drug Administration (FDA), an IgG threshold level of 
0.35 g/mL using the 13-plex dLIA platform is appropriate for serotypes 1, 3, 4, 5, 6A, 7F, 
9V, 14, 18C, 19F, and 23F, while lower threshold values for the 13-plex dLIA platform are 
justified for serotypes 5 (0.23 g/mL), 6B (0.10 g/mL), and 19A (0.12 g/mL) in order to 
maintain the same proportion of vaccine responders reported using the ELISA platform.
Serotype-specific OPA assays for the 13 pneumococcal serotypes will be performed in all 
subjects from the blood samples taken 1 month after the infant series and 1 month after the 
toddler dose of 13vPnC, where sufficient sera are available. Results will be reported as 
antibody titers.
8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report Form 
to Pfizer Safety.  These requirements are delineated for 3 types of events: (1) SAEs; (2) 
nonserious AEs; and (3) exposure to the investigational product under study during 
pregnancy or breastfeeding, and occupational exposure.

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Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study during 
pregnancy or breastfeeding, 
and occupational exposure
All (regardless of whether 
associated with an AE), except 
occupational exposure
Exposure during pregnancy, 
exposure via breastfeeding, 
occupational exposure 
(regardless of whether 
associated with an AE)
All observed or volunteered events regardless of vaccine group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this will include 
a description of the event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality.  Any information relevant to 
the event, such as concomitant medications and illnesses, must be provided.  In the case of a 
subject death, a summary of available autopsy findings must be submitted as soon as possible 
to Pfizer Safety.  Any pertinent additional information must be reported on the CT SAE 
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to 
be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 

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investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.1.1. Additional Details on Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  It 
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study subject’s parent(s)/legal guardian(s)/caregiver(s).  In addition, each 
study subject’s parent(s)/legal guardian(s)/caregiver(s) will be questioned about the 
occurrence of AEs in a nonleading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Subject 
Withdrawal section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF.
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above.
8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each subject begins from the time the subject’s parent(s)/legal 
guardian(s)/caregiver(s) provide(s) informed consent, which is obtained before the subject’s 
participation in the study (ie, before undergoing any study-related procedure and/or receiving 
investigational product), through and including Visit 4 and from Visit 5 to Visit 6.
Between Visit 4 and Visit 5, only newly diagnosed chronic medical conditions and SAEs will 
be reported. In addition, end dates will be reported for any events ongoing from the previous 
visit.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 

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investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
8.1.4.2. Recording Nonserious AEs and SAEs on the CRF
During the active collection period, both nonserious AEs and SAEs are recorded on the CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable.  An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the investigational product caused the event, then 
the event will be handled as “related to investigational product” for reporting purposes, as 
defined by the sponsor.  If the investigator's causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records.
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
8.2. Definitions
8.2.1. Adverse Events
An AE is 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.  Examples of AEs include, but are not limited to:

Abnormal test findings;

Clinically significant signs and symptoms;

Changes in physical examination findings;

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
Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or

Test result leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
recording as an AE.

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8.2.3. Serious Adverse Events
An SAE is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
Medical device complaints may meet the SAE reporting requirement criteria (see the Medical 
Device Complaint Reporting Requirements section).  An incident is any malfunction (ie, the 
failure of a device to meet its performance specifications or to perform as intended; 
performance specifications include all claims made in the labeling for the device) that, 
directly or indirectly, might lead to or might have led to the death of a subject, or user, or of 
other persons, or to a serious deterioration in their state of health.
A serious injury that can cause a serious deterioration in state of health can include:

A life-threatening illness, even if temporary in nature;

A permanent impairment of a body function or permanent damage to a body 
structure; 

A condition necessitating medical or surgical intervention to prevent the above 
2 bulleted items;

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Examples: clinically relevant increase in the duration of a surgical procedure; a 
condition that requires hospitalization or significant prolongation of existing 
hospitalization;

Any indirect harm as a consequence of an incorrect diagnostic or in vitro diagnostic 
device test results when used within the manufacturer’s instructions for use;

Fetal distress, fetal death, or any congenital abnormality or birth defects.
8.2.4. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE.  Examples include:

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of a persistent pretreatment laboratory abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

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
Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE.
8.3. Severity Assessment
GRADE If required on the AE page of the CRF, the investigator will use the adjectives 
MILD, MODERATE, SEVERE, or LIFE-THREATENING to describe the 
maximum intensity of the AE. For purposes of consistency, these intensity grades 
are defined as follows:
1
MILD
Does not interfere with subject's usual function.
2
MODERATE
Interferes to some extent with subject's usual function.
3
SEVERE
Interferes significantly with subject's usual function.
4
LIFE-
THREATENING
Life-threatening consequences; urgent intervention indicated.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database.
8.4.2. Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some subjects, transaminase elevations are a harbinger of a more 

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serious potential outcome.  These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI).  Subjects who experience a transaminase elevation above 3 times the upper limit of 
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” 
or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a subject 
presents with clinical signs/symptoms, such LFT results should be managed and followed as 
described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions.  Subjects who present with the 
following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law) 
cases to definitively determine the etiology of the abnormal laboratory values:

Subjects with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available;

For subjects with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:
o
Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
o
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.

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The subject should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl 
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase, and acetaminophen drug and/or protein adduct levels.  
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a coformulated product in prescription or over-the-counter medications), 
recreational drug, or supplement (herbal) use and consumption, family history, sexual 
history, travel history, history of contact with a jaundiced person, surgery, blood transfusion, 
history of liver or allergic disease, and potential occupational exposure to chemicals, should 
be collected.  Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging
(eg, biliary tract) may be warranted.
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
8.4.3. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.3.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an EDP occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).

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
A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy.
If a subject or subject’s partner becomes or is found to be pregnant during the subject’s 
treatment with the investigational product, the investigator must report this information to 
Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, regardless of 
whether an SAE has occurred.  In addition, the investigator must submit information 
regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a subject 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) to Pfizer Safety using the EDP supplemental form.  This must be done irrespective 
of whether an AE has occurred and within 24 hours of awareness of the exposure.  The 
information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows:

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product.
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the subject with the Pregnant Partner Release of Information Form 
to deliver to his partner.  The investigator must document in the source documents that the 

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subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.3.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.3.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a subject enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.4.4. Medication Errors and Lack of Efficacy
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors and lack of efficacy.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
Medication errors and lack of 
efficacy
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
8.4.4.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength.
Medication errors include:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.

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
The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

The administration of investigational product that has undergone temperature 
excursion from the specified storage range, unless it is determined by the sponsor that 
the investigational product under question is acceptable for use.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4.4.2. Lack of Efficacy
Lack of efficacy in an approved indication should be reported as an SAE to Pfizer Safety.
8.5. Medical Device Complaint Reporting Requirements
All medical device complaints, regardless of whether the medical device complaint is 
associated with an AE, will be recorded on the applicable pages within the CRF.  This 
includes potential incidents or malfunctions associated with the use of a medical device 
product.  An incident or malfunction is an event that might have led to death or serious 
deterioration in health, or if it occurred again might lead to death or serious deterioration in 
health.
Pfizer is to be notified of all medical device complaints within 24 hours of the investigator’s 
awareness of the event.
9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.

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9.1. Sample Size Determination
Sample size is justified by the probability of detection of AEs and the precision of estimates 
of GMCs. The sample size of 150 per group offers reasonable detection probability of AEs 
commonly seen in other studies, and provides reasonable width of the confidence interval 
(CI) around the GMC.
The primary endpoints include the incidence of AEs in the MDV group.  AE incidences were 
obtained from infant series data from a related Pfizer study, B4671001. The incidences from 
the 2 vaccine groups, MDV and PFS, were combined.  The combined sample size was 500.  
The probability of detecting at least 1 indicated event is presented in Table 5.  Incidences are 
sorted in descending order.
Table 5.
Probability of Detection of at Least 1 Adverse Event in the Infant Series
Incidence After Combining 
MDV and PFS
(n=500 in Study B4671001)
Proposed Sample 
Size for MDV in 
Study B4671004
Probability of at 
Least 1 Indicated 
AE
Any AE
50.0%
150
100.0%
Any related AE
0.6%
150
59.5%
Any SAE
0.2%
150
25.9%
Abbreviations: MDV = multidose vial; PFS = prefilled syringe.
For the immunogenicity comparison of the MDV and PFS groups, 2-sided 95% CIs 
comparing the groups will be compiled, but no formal noninferiority criteria are specified.
Precision for GMCs is quantified by dividing the upper limit of the 95% CI by the GMC.
Standard deviations (SDs) of each serotype’s assays, in log scale, were derived from 
Table 21 in the B4671001 clinical study report (CSR). Assay SDs were obtained for both 
MDV and PFS intervals.  
  
 
 
 
 
 
CCI
CCI

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9.2. Efficacy Analysis
9.2.1. Analysis of the Primary Endpoints
Not applicable.
9.2.2. Analysis of the Secondary Endpoints
The proportions of subjects with IgG ≥the defined threshold will be accompanied by 2-sided 
95% CIs.  The Clopper-Pearson method will be used.
GMCs will be obtained by log transformation of concentrations, averaging the transformed 
values, then exponentiating the results.  95% confidence will also be obtained for CIs.  The 
CIs will be calculated in the log scale with reference to the appropriate t-distribution.  Then 
the lower and upper limits will be exponentiated.
Empirical reverse cumulative distribution curves (RCDCs) will be compiled for each 
serotype at each blood sampling time point.
Two (2)-sided 95% CIs comparing the 2 vaccine groups will also be compiled in order to 
quantify the differences between the 2 vaccine groups.  For the proportions of subjects with 
IgG ≥the defined threshold for each of the pneumococcal serotypes measured, the 2-sided 
95% CI on MDV minus PFS will be compiled using the method of Chan and Zhang.42 For 
the GMC, the 2-sided 95% CI on MDV minus PFS will be compiled, using the log 
concentrations, as a 2-sample CI on the difference between means. The t-distribution will be
used.  The lower and upper limits will be exponentiated, so the results will describe the ratio 
of MDV to PFS.
Assay results below the limit of quantification will be set to the limit of detection before 
analysis.  Missing data will not be replaced or imputed.
Two (2) analysis populations will be defined for the infant immunogenicity analyses: infant 
evaluable and infant all-available immunogenicity. To be included in the infant evaluable 
immunogenicity population, the subject must
1. have been eligible,
CCI

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2. have received 3 doses of vaccine, 
3. have post–Dose 3 blood drawn within the prespecified time frame, 
4. have at least 1 valid and determinate post–Dose 3 assay result, and 
5. have no other major protocol violations. 
To be included in the infant all-available immunogenicity population, a subject must have at 
least 1 valid and determinate assay result after Dose 3. 
Two (2) analysis populations will be defined for the toddler immunogenicity analyses: 
toddler evaluable and toddler all-available immunogenicity. To be included in the toddler 
evaluable immunogenicity population, the subject must
1. have been eligible,
2. have received 3 doses of vaccine in the infant series and 1 toddler dose, 
3. have post–Dose 4 blood drawn within the prespecified time frame, 
4. have at least 1 valid and determinate post–Dose 4 assay result, and 
5. have no other major protocol violations.
To be included in the toddler all-available immunogenicity population, a subject must have at 
least 1 valid and determinate assay result after Dose 4.
A subject could be evaluable (or all-available) in the infant series and all-available 
(or evaluable) for the toddler dose.
The primary immunogenicity populations for the infant and toddler analyses will be their 
respective evaluable populations.
Subjects in these populations will be assigned to their randomized vaccination regimen.
9.3. Analysis of Demographic Characteristics
The demographic characteristics that will be summarized using descriptive statistics include 
sex, ethnicity, and age at each vaccination.
9.4. Safety Analysis
Local injection site reactions, systemic events, and AEs will be summarized by vaccine 
group and by vaccination.
The proportions of subjects with local reactions at the injection site and systemic events 
reported on any day within the 7-day period after each vaccination will be estimated for each 
vaccine group.  Local reactions will not be compiled for concurrent vaccinations.

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Local reactions and systemic events that persist beyond Day 7 will be listed in the CSR.
AEs will be categorized according to the Medical Dictionary for Regulatory Activities 
(MedDRA).  AEs within 1 month after vaccination will be summarized by vaccine group for 
each vaccination separately.  AEs will also be summarized from the first dose up to 1 month 
after the infant series.
SAEs will be summarized from the first dose up to 1 month after the toddler dose.
Newly diagnosed chronic medical conditions will be summarized from 1 month after the 
infant series up to the toddler dose.
All safety analyses will be performed on the safety population, which will include any 
subject with at least 1 vaccination.  Subjects will be assigned to the vaccine actually received.  
If a subject receives different vaccines at different time points, then local reactions, systemic 
events, and AEs immediately following the vaccination will be assigned to the vaccine most 
recently received.  Compilation of AEs or SAEs from the first infant dose up to the toddler 
dose will be assigned to the vaccine received.  If a subject receives both vaccines during the 
infant series, then the subject will be assigned to the randomized vaccine group.
9.5. Interim Analysis
No formal interim analysis will be conducted for this study. However, as this is an 
open-label study, the sponsor may conduct unblinded reviews of the data during the course 
of the study for the purpose of safety assessment or to support clinical development. This 
includes compilation of results of the infant series before completion of the toddler dose.
9.6. Data Monitoring Committee
This study will not use a data monitoring committee.
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate.  The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification.  This
verification may also occur after study completion.
During study conduct and/or after study completion, the investigator site may be subject to 
review by the institutional review board (IRB)/ethics committee (EC), and/or to quality 
assurance audits performed by Pfizer, or companies working with or on behalf of Pfizer, 
and/or to inspection by appropriate regulatory authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer or its 

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agent, whenever feasible, to be present during the inspection.  The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study 
data and the subject's medical records.  The investigator will promptly provide copies of the 
inspection findings to Pfizer or its agent.  Before response submission to the regulatory 
authorities, the investigator will provide Pfizer or its agents with an opportunity to review 
and comment on responses to any such findings.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry.
In most cases, the source documents are the hospital or the physician subject chart.  In these 
cases, data collected on the CRFs must match the data in those charts.
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
informed consent documents, copies of all CRFs, safety reporting forms, source documents, 
and detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports).  The records should 

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be retained by the investigator according to the ICH guidelines, according to local 
regulations, or as specified in the clinical study agreement (CSA), whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer.
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg,
recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki.
12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where
required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study subjects. The investigator
site will maintain a confidential list of subjects who participated in the study, linking each 
subject’s numerical code to his or her actual identity.  In case of data transfer, Pfizer will 

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maintain high standards of confidentiality and protection of subjects’ personal data consistent 
with applicable privacy laws.
The informed consent documents and any subject recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws.
The informed consent documents used during the informed consent process and any subject 
recruitment materials must be reviewed and approved by Pfizer, approved by the IRB/EC
before use, and available for inspection.
The investigator must ensure that each study subject, or parent(s) or legal guardian(s) if a 
minor, is fully informed about the nature and objectives of the study and possible risks 
associated with participation.
Whenever consent is obtained from a subject’s parent(s) or legal guardian(s), the subject’s 
assent (affirmative agreement) must subsequently be obtained when the subject has the 
capacity to provide assent, as determined by the IRB/EC.  If the investigator determines that 
a subject’s decisional capacity is so limited he/she cannot reasonably be consulted, then, as 
permitted by the IRB/EC and consistent with local regulatory and legal requirements, the 
subject’s assent may be waived with source documentation of the reason assent was not 
obtained.  If the study subject does not provide his or her own consent, the source documents
must record why the subject did not provide consent (eg, minor, decisionally impaired adult), 
how the investigator determined that the person signing the consent was the subject’s legally 
acceptable representative, the consent signer’s relationship to the study subject (eg, parent, 
spouse), and that the subject’s assent was obtained or waived.  If assent is obtained verbally,
it must be documented in the source documents.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject's parent(s) or legal guardian(s) before any study-specific activity is 
performed. The investigator will retain the original of each subject's signed consent
document.
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.

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13. DEFINITION OF END OF TRIAL
13.1. End of Trial in All Participating Countries
End of trial in all participating countries is defined as the last subject last visit (LSLV).
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of 
13vPnC at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) within approximately 30 days.  As directed by Pfizer, all study materials must 
be collected and all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.

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www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication. However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section.
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.

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16. REFERENCES
1. Reinert RR.  Pneumococcal conjugate vaccines—a European perspective. Int J Med 
Microbiol. 2004;294(5):277-294.
2. Pneumococcal vaccines WHO position paper--2012. Wkly Epidemiol Rec.
2012;87(14):129-44.
3. Whitney CG, Farley MM, Hadler J, et al.  Decline in invasive pneumococcal disease after 
the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 
2003;348(18):1737-1746.
4. Black S, Shinefield H, Fireman B, et al.  Efficacy, safety and immunogenicity of 
heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J. 
2000;19(3):187-195.
5. Black SB, Shinefield HR, Ling S, et al.  Effectiveness of heptavalent pneumococcal 
conjugate vaccine in children younger than five years of age for prevention of 
pneumonia. Pediatr Infect Dis J. 2002;21(9):810-815.
6. Eskola J, Kilpi T, Palmu A, et al.  Efficacy of a pneumococcal conjugate vaccine against 
acute otitis media. N Engl J Med. 2001;344(6):403-409.
7. Black S, Shinefield H, Baxter R, et al.  Postlicensure surveillance for pneumococcal 
invasive disease after use of heptavalent pneumococcal conjugate vaccine in Northern 
California Kaiser Permanente. Pediatr Infect Dis J. 2004;23(6):485-489.
8. Black SB, Shinefield HR, Hansen J, Elvin L, Laufer D, Malinoski F.  Postlicensure 
evaluation of the effectiveness of seven valent pneumococcal conjugate vaccine. 
Pediatr Infect Dis J. 2001;20(12):1105-1107. 
9. Bruce MG, Deeks SL, Zulz T, et al.  International circumpolar surveillance system for 
invasive pneumococcal disease, 1999–2005. Emerg Infect Dis. 2008;14(1):25-33.
10. Byington CL, Samore MH, Stoddard GJ, et al.  Temporal trends of invasive disease due 
to Streptococcus pneumoniae among children in the intermountain west: emergence of 
nonvaccine serogroups. Clin Infect Dis. 2005;41(1):21-29. 
11. Center KJ.  Prevenar vaccination: review of the global data, 2006. Vaccine. 
2007;25(16):3085-3089. 
12. Kellner JD, Vanderkooi OG, MacDonald J, Church DL, Tyrrell GJ, Scheifele DW.  
Changing epidemiology of invasive pneumococcal disease in Canada, 1998–2007: update 
from the Calgary-Area Streptococcus pneumoniae Research (CASPER) study. Clin Infect 
Dis. 2009;49(2):205-212. 

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13. Pilishvili T, Lexau C, Farley MM, et al.  Active Bacterial Core Surveillance/Emerging 
Infections Program Network. Sustained reductions in invasive pneumococcal disease in 
the era of conjugate vaccine. J Infect Dis. 2010;201(1):32-41. 
14. Rückinger S, van der Linden M, Reinert RR, von Kries R, Burckhardt F, Siedler A.  
Reduction in the incidence of invasive pneumococcal disease after general vaccination 
with 7-valent pneumococcal conjugate vaccine in Germany. Vaccine. 
2009;27(31):4136-4141. 
15. Talbot TR, Poehling KA, Hartert TV, et al. Elimination of racial differences in invasive 
pneumococcal disease in young children after introduction of the conjugate 
pneumococcal vaccine. Pediatr Infect Dis J. 2004;23(8):726-731.
16. Whitney CG, Farley MM, Hadler J, et al.  Decline in invasive pneumococcal disease after 
the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 
2003;348(18):1737-1746.
17. Centers for Disease Control and Prevention.  Direct and indirect effects of routine 
vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of 
invasive pneumococcal disease – United States, 1998–2003. MMWR Morb Mortal Wkly 
Rep. 2005;54(36):893-897.
18. McIntosh ED, Conway P, Willingham J, Hollingsworth R, Lloyd A.  Pneumococcal 
pneumonia in the UK – how herd immunity affects the cost-effectiveness of 7-valent 
pneumococcal conjugate vaccine (PCV). Vaccine. 2005;23(14):1739-1745.
19. Hicks L, Harrison L, Flannery B, et al.  Incidence of pneumococcal disease due to non-
pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of 
widespread PCV7 vaccination, 1998-2004. J Infect Dis. 2007;196(9):1346-1354.
20. Regev-Yochay G, Paran Y, Bishara J, et al. Early impact of PCV7/PCV13 sequential 
introduction to the national pediatric immunization plan, on adult invasive pneumococcal 
disease: a nationwide surveillance study. Vaccine. 2015;33(9):1135-1142.
21. Demczuk WH, Martin I, Griffith A, et al. Serotype distribution of invasive Streptococcus 
pneumoniae in Canada after the introduction of the 13-valent pneumococcal conjugate 
vaccine, 2010-2012. Can J Microbiol. 2013;59(12):778-788.
22. Wei SH, Chiang CS, Chiu CH, Chou P, Lin TY. Pediatric invasive pneumococcal disease 
in Taiwan following a national catch-up program with the 13-valent pneumococcal 
conjugate vaccine. Pediatr Infect Dis J. 2015;34(3):e71-e77.
23. Andrews NJ, Waight PA, Burbidge P, et al. Serotype-specific effectiveness and correlates 
of protection for the 13-valent pneumococcal conjugate vaccine: a postlicensure indirect 
cohort study. Lancet Infect Dis. 2014;14(9):839-846.

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24. Waight PA, Andrews NJ, Ladhani SN, Sheppard CL, Slack MP, Miller E. Effect of the 
13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England 
and Wales 4 years after its introduction: an observational cohort study. Lancet Infect Dis.
2015;15(5):535-543.
25. Harboe ZB, Dalby T, Weinberger DM, et al. Impact of 13-valent pneumococcal 
conjugate vaccination in invasive pneumococcal disease incidence and mortality. 
Clin Infect Dis. 2014;59(8):1066-1073.
26. Ben-Shimol S, Greenberg D, Givon-Lavi N, et al. Early impact of sequential introduction 
of 7-valent and 13-valent pneumococcal conjugate vaccine on IPD in Israeli children <5 
years: an active prospective nationwide surveillance. Vaccine. 2014;32(27):3452-3459.
27. Kaplan SL, Barson WJ, Lin PL, et al. Early trends for invasive pneumococcal infections 
in children after the introduction of the 13-valent pneumococcal conjugate vaccine. 
Pediatr Infect Dis J. 2013;32(3):203-207.
28. Moore MR, Link-Gelles R, Schaffner W, et al. Effect of use of 13-valent pneumococcal 
conjugate vaccine in children on invasive pneumococcal disease in children and adults in 
the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis.
2015;15(3):301-309.
29. Iroh Tam PY, Madoff LC, Coombes B, Pelton SI. Invasive pneumococcal disease after 
implementation of 13-valent conjugate vaccine. Pediatrics. 2014;134(2):210-217.
30. Steens A, Bergsaker MA, Aaberge IS, Ronning K, Vestrheim DF. Prompt effect of 
replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the 
epidemiology of invasive pneumococcal disease in Norway. Vaccine.
2013;31(52):6232-6238.
31. Bonten MJ, Huijts SM, Bolkenbaas M, et al. Polysaccharide conjugate vaccine against 
pneumococcal pneumonia in adults. N Engl J Med. 2015;372(12):1114-1125.
32. Johnson HL, Deloria-Knoll M, Levine OS, et al.  Systematic evaluation of serotypes 
causing invasive pneumococcal disease among children under five: the Pneumococcal 
Global Serotype Project.  PLoS Med. 2010;7(10):e1000348.
33. Dinleyici EC, Yargic ZA.  Current knowledge regarding the investigational 13-valent 
pneumococcal conjugate vaccine.  Expert Rev Vaccines. 2009;8(8):977-986.
34. Hausdorff WP.  The roles of pneumococcal serotypes 1 and 5 in paediatric invasive 
disease. Vaccine. 2007;25(13):2406-2412. 
35. Lee BY, Norman BA, Assi TM, et al. Single versus multi-dose vaccine vials: an 
economic computational model. Vaccine. 2010;28(32):5292-5300.

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36. Parmar D, Baruwa EM, Zuber P, Kone S.  Impact of wastage on single and multi-dose 
vaccine vials: implications for introducing pneumococcal vaccines in developing 
countries. Hum Vaccin. 2010;6(3):270-278.
37. Rowe RC, Sheskey PJ, Quinn ME. Phenoxyethanol. In: Handbook of Pharmaceutical 
Excipients. 6th edition. London, UK: Pharmaceutical Press; Washington, DC: American 
Pharmaceutical Association; 2009:488.
38. Bian CX, Jiang SD, Yang JY, et al.  Effect of 2-phenoxyethanol on potency of Sabin 
inactivated poliomyelitis vaccine and its safety [in Chinese]. Zhonghua Shi Yan He Lin
Chuang Bing Du Xue Za Zhi. 2007;21(1):44-46.
39. Khandke L, Yang C, Krylova K, Jansen KU, Rashidbaigi A.  Preservative of choice for 
Prev(e)nar 13 in a multi-dose formulation. Vaccine. 2011;29(41):7144-7153.
40. Meyer BK, Ni A, Hu B, Shi L.  Antimicrobial preservative use in parenteral products: 
past and present. J Pharm Sci. 2007;96(12):3155-3167.
41. World Health Organization.  Expert Committee on Biological Standardization, 19-23 Oct 
2009: Recommendations to Assure the Quality, Safety and Efficacy of Pneumococcal 
Conjugate Vaccines.  Geneva, Switzerland: World Health Organization; 2009: 
Replacement of TRS 927, Annex 2.
42. Chan ISF, Zhang Z.  Test-based exact confidence intervals for the difference of two 
binomial proportions. Biometrics. 1999;55(4):1202-1209.

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Appendix 1. Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
2-PE
2-phenoxyethanol
7vPnC
7-valent pneumococcal conjugate vaccine
13vPnC
13-valent pneumococcal conjugate vaccine
ABCs
Active Bacterial Core surveillance
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BCG
bacillus Calmette-Guerin 
CAPiTA
Community-Acquired Pneumonia Immunization Trial in Adults
CI
confidence interval
CK
creatine kinase
CRF
case report form
CRM197
cross-reactive material 197 
CSA
clinical study agreement
CSR
clinical study report
CT
clinical trial
DCGI
Drugs Controller General of India
DILI
drug-induced liver injury
dLIA
direct Luminex-based immunoassay
DTaP
diphtheria, tetanus, and acellular pertussis vaccine 
DTaP-IPV-Hib
diphtheria, tetanus, and acellular pertussis; inactivated poliovirus; 
and Haemophilus influenzae type b vaccine 
DTP-Hib-HBV 
diphtheria, tetanus, and pertussis; Haemophilus influenzae type b; 
and hepatitis B virus vaccine
DU
dispensable unit
EC
ethics committee
e-diary
electronic diary
EDP
exposure during pregnancy
ELISA
enzyme-linked immunosorbent assay
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration (United States)
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMC
geometric mean concentration
GMT
geometric mean titer 
HBV
hepatitis B virus
ICH
International Council for Harmonisation

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Abbreviation
Term
ID
identification
IgG
immunoglobulin G
IND
investigational new drug application
INR
international normalized ratio
IP
investigational product
IPD
invasive pneumococcal disease
IPV
inactivated poliovirus vaccine
IRB
institutional review board
IRT
interactive response technology
IWR
interactive web-based response
LFT
liver function test
LLOQ
lower limit of quantitation
LSLV
last subject last visit 
MDV
multidose vial
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
NOC
no objection certificate
OPA
opsonophagocytic activity
PASS
postauthorization safety study
PCD
primary completion date
PFS
prefilled syringe
PI
principal investigator
PT
prothrombin time
RCDC
reverse cumulative distribution curve
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SEC
subject expert committee
SRSD
single reference safety document
TBili
total bilirubin
Tdap
tetanus, low-dose diphtheria, and low-dose acellular pertussis 
vaccine
ULN
upper limit of normal
US
United States
WHO
World Health Organization

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