A PHASE III, RANDOMISED, OPEN, CONTROLLED, MULTICENTRE, PRIMARY VACCINATION STUDY TO EVALUATE THE IMMUNOGENICITY AND PERSISTENCE OF 1 AND 2 DOSES OF MENINGOCOCCAL CONJUGATE VACCINE MENACWY-TT IN TODDLERS (AFTER 1 MONTH AND UP TO 5 YEARS) AND TO DEMONSTRATE NON-INFERIORITY OF CO-ADMINISTRATION OF MENACWY-TT AND 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE PREVENAR 13(REGISTERED) VERSUS SEPARATE ADMINISTRATION OF THE 2 VACCINES
Phase: PHASE3
Conditions: Infections, Meningococcal
Sponsor: Pfizer

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Clinical Study Protocol
Sponsor:
Pfizer, Inc.
235 East 42nd Street
New York, NY 10017, United States
Primary Study 
vaccine/product and number
Meningococcal serogroup A, C, W-135 and Y tetanus 
toxoid conjugate (MenACWY-TT) vaccine (Nimenrix®, 
PF-06866681)
Other Study vaccine/product
13-valent pneumococcal conjugate vaccine with diphtheria 
CRM197 as protein carrier (Prevenar 13®)
Study number and 
Abbreviated Title
C0921003 (MENACWY-TT-104; formerly GSK 116892)
EudraCT number
2013-001083-28
Date of protocol
Final Version 1: 24 April 2013
Date of protocol amendments
Amendment 1 Final: 02 July 2014
Amendment 2 Final: 25 January 2016
Amendment 3 Final: 09 May 2018
Title
Immunogenicity and safety study of 1 and 2 doses of
MenACWY-TT meningococcal vaccine (PF-06866681) in 
toddlers, persistence up to 5 years after vaccination and 
co-administration with pneumococcal vaccine Prevenar 
13®
Detailed Title
A Phase III, randomised, open, controlled, multicentre, 
primary vaccination study to evaluate the immunogenicity 
and persistence of 1 and 2 doses of meningococcal 
conjugate vaccine MenACWY-TT in toddlers (after 1 
month and up to 5 years) and to demonstrate non-
inferiority of co-administration of MenACWY-TT and 
13-valent pneumococcal conjugate vaccine Prevenar 13®
versus separate administration of the 2 vaccines.
This document contains confidential information belonging to Pfizer  Except as otherwise agreed to in writing, 
by accepting or reviewing this document, you agree to hold this information in confidence and not copy or 
disclose it to others (except where required by applicable law) or use it for unauthorized purposes.  In the 
event of any actual or suspected breach of this obligation, Pfizer must be promptly notified.

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PROTOCOL AMENDMENT 3 SPONSOR SIGNATORY APPROVAL
Study number and Abbreviated 
Title
C0921003 (MENACWY-TT-104; formerly GSK 116892)
EudraCT number
2013-001083-28
Date of protocol amendment
Amendment 2 Final: 25 January 2016
Amendment 3: 09 May 2018
Detailed Title 
A Phase III, randomised, open, controlled, multicentre, 
primary vaccination study to evaluate the 
immunogenicity and persistence of 1 and 2 doses of 
meningococcal conjugate vaccine MenACWY-TT in 
toddlers (after 1 month and up to 5 years) and to 
demonstrate non-inferiority of co-administration of 
MenACWY-TT and 13-valent pneumococcal conjugate 
vaccine Prevenar 13® versus separate administration of 
the 2 vaccines.
Sponsor signatory
 MD
Signature
Date
PPD
PPD

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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 3
09 May 2018
The single reference safety document 
(SRSD) was changed from core data 
sheet (CDS) to summary of product 
characteristics (SmPC).
Amendment 2
25 January 2016
Protocol amended to reflect 
sponsorship change to Pfizer 
following the acquisition of the GSK
meningococcal vaccine Nimenrix® by 
Pfizer on 01 October 2015.
Sponsor name updated throughout the 
protocol to Pfizer.
List of abbreviations and glossary of 
terms updated.
Information related to electronic SAE 
reports replaced by paper SAE reports 
throughout the protocol.
Sections updated / added  in line with 
standard Pfizer policy: 
- 1.1 Background
- 5.1 Regulatory and ethical 
considerations, including the informed 
consent process
- 5.5 Outline of study procedures
- 5.6.1 Informed consent
- 5.7 Biological sample handling and 
analysis
- 6.6 Warnings and precautions
- 6.8 Intercurrent medical conditions 
that may lead to elimination of a 
subject from ATP analysis
- 8.1.2 Definition of an adverse event
- 8.2 Detecting and recording adverse 
events, serious adverse events, NOCIs, 
and GBS
- 8.6 Subject card
- 9.2.1 Subject withdrawal from the 
study
-11.5 Posting of information on 
publicly available clinical trial 
registers and publication policy
-11.6 Provision of study results to 
investigators

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Document
Version Date
Summary of Changes and Rationale
-11.7 Reporting of Safety Issues and 
Serious Breaches of the Protocol or 
ICH GCP
Appendix A Laboratory Assays
Appendix B Clinical Laboratories
Amendment 1
02-July-2014
The Medicines Control Council 
(MCC) authorities requested that 
participants be screened for HIV 
testing prior to study enrolment in 
South Africa. to ensure that only HIV-
negative participants are enrolled. As 
such, HIV rapid test was added at 
Visit 1 only for subjects in South 
Africa. Subjects previously screened 
HIV positive will be excluded. 
Clinically healthy babies, who had not 
been previously tested for HIV, will 
be screened with 2 rapid HIV tests. If 
any test is positive, the participant will 
not be enrolled into the study and will 
be referred to referral networks for a 
confirmatory HIV test by PCR and to 
an appropriate health care provider. 
Any HIV-negative subjects with 
documented HIV negativity will not 
need to be re-tested, unless clinically 
indicated by the investigator.
The opsonophagocytic activity (OPA) 
of 13 pneumococcal serotypes will be 
tested at the Institute of Child Health 
in London. The testing of the 13 
serotypes was planned to be 
performed in two assay subsets: 
serotypes 1, 3, 4, 5, 6A and 6B would 
be tested in subset 3 and serotypes 7F, 
9V, 14, 18C, 19A, 19F and 23F would 
be tested in subset 4. Recently, the 
Institute however informed 
GlaxoSmithKline (GSK) on how the 
13 serotypes were divided into the 
cassettes used for OPA testing. 

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Document
Version Date
Summary of Changes and Rationale
Therefore, the serotypes to be tested in 
the subsets were re-distributed as 
follows: serotypes 3, 4, 6B, 14 and 
23F will be tested in subset 3 and 
serotypes 1, 5, 6A, 7F, 9V, 18C, 19A 
and 19F will be tested in subset 4. 
This will lead to faster results for OPA 
testing, without affecting the outcome 
of the study.
In the section on sequence of analyses, 
all references to sequence of reporting 
have been removed, as this 
information is redundant.
Original protocol
24 April 2013
Not applicable (NA)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities, institutional review boards/ independent ethics 
committees (IRBs/ECs), etc. 

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Protocol Amendment 3 Investigator Agreement
I agree:
To conduct the study in compliance with this protocol, any future protocol amendments or 
protocol administrative changes, with the terms of the clinical trial agreement and with any 
other study conduct procedures and/or study conduct documents provided by Pfizer.
To assume responsibility for the proper conduct of the study at this site.
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all applicable 
regulatory requirements. 
To ensure that all persons assisting me with the study are adequately informed about the 
investigational vaccine and other study-related duties and functions as described in the 
protocol.
To acquire the reference ranges for laboratory tests performed locally and, if required by 
local regulations, obtain the laboratory’s current certification or Quality Assurance procedure 
manual.
To ensure that no clinical samples (including serum samples) are retained onsite or elsewhere 
without the approval of Pfizer and the express written informed consent of the subject and/or 
the subject’s legally acceptable representative. 
To perform no other biological assays on the clinical samples except those described in the 
protocol or its amendment(s). 
To co-operate with a representative of Pfizer in the monitoring process of the study and in 
resolution of queries about the data.
That I have been informed that certain regulatory authorities require the sponsor to obtain 
and supply, as necessary, details about the investigator’s ownership interest in the sponsor or 
the investigational vaccine, and more generally about his/her financial ties with the sponsor. 
Pfizer will use and disclose the information solely for the purpose of complying with 
regulatory requirements.
Hence I:
Agree to supply Pfizer with any necessary information regarding ownership interest and 
financial ties (including those of my spouse and dependent children).
Agree to promptly update this information if any relevant changes occur during the course of 
the study and for one year following completion of the study. 
Agree that Pfizer may disclose any information it has about such ownership interests and 
financial ties to regulatory authorities.
Agree to provide Pfizer with an updated Curriculum Vitae and other documents required by 
regulatory agencies for this study.

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Study number and 
Abbreviated Title
C0921003 (MENACWY-TT-104; formerly GSK 
116892)
EudraCT number
2013-001083-28
Date of protocol Amendment
25 January 2016
Amendment 3: 09 May 2018
Detailed Title
A Phase III, randomised, open, controlled, multicentre, 
primary vaccination study to evaluate the 
immunogenicity and persistence of 1 and 2 doses of  
meningococcal conjugate vaccine MenACWY-TT in 
toddlers (after 1 month and up to 5 years) and to 
demonstrate non-inferiority of co-administration of 
MenACWY-TT and 13-valent pneumococcal conjugate 
vaccine Prevenar 13® versus separate administration of 
the 2 vaccines.
Investigator name
Signature
Date

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SYNOPSIS
Detailed Title
A Phase III, randomised, open, controlled, multicentre, primary 
vaccination study to evaluate the immunogenicity and persistence of 
1 and 2 doses of  meningococcal conjugate vaccine MenACWY-TT 
in toddlers (after 1 month and up to 5 years) and to demonstrate 
non-inferiority of co-administration of MenACWY-TT and 
13-valent pneumococcal conjugate vaccine Prevenar 13® versus 
separate administration of the 2 vaccines.
Indication
Active immunisation of individuals from 12 months of age against 
invasive meningococcal disease caused by Neisseria meningitidis
group A, C, W-135 and Y.
Rationale for the 
study and study 
design
Rationale for the study
Current data from clinical studies with the MenACWY-TT vaccine 
suggest that a single dose in toddlers provides sufficient protection. 
However, data on the possible advantage of administrating two 
vaccine doses are not available for toddlers around 12 months of 
age at the time of vaccination. The European Medicines Agency 
(EMA) requested GSK to conduct a study to evaluate the immediate 
and longer term antibody titres elicited by one or two doses of 
MenACWY-TT administered in children aged 12-23 months. This 
study was therefore designed to evaluate the immunogenicity of one 
and two doses of MenACWY-TT administered to unprimed 
toddlers during their second year of life.
Several European countries recommend a booster dose of a 
pneumococcal conjugate vaccine between 11 and 15 months of age.
This study will also be conducted to demonstrate that co-
administration of meningococcal vaccine MenACWY-TT with the 
booster dose of pneumococcal conjugate vaccine Prevenar 13 does 
not adversely impact the immunogenicity of either of the vaccines. 
The safety profile of both vaccines will also be evaluated.
Rationale for the study design
The study contains 4 study groups:

The ACWY1d group will receive 1 dose of MenACWY-TT 
at Visit 1. For this study group, 
Prevenar 13 is not considered as a study vaccine and has to 
be administered after Visit 2.

The ACWY2d group will receive 2 doses of MenACWY-TT 
2 months apart (at Visits 1 and 3). For this study group, 
Prevenar 13 is not considered as a study vaccine and has to 
be administered between the 2 doses of MenACWY-TT 
(after the Visit 2 blood sampling up to 30 days before the 

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second dose of MenACWY-TT) or after Visit 4.

The Co-ad group will receive 1 dose of MenACWY-TT and 
1 dose of Prevenar 13 at Visit 1.

The PCV-13 group will receive 1 dose of Prevenar 13 at 
Visit 1 and 1 dose of MenACWY-TT 2 months later 
(Visit 3).
The immunogenicity and long-term persistence of one and two 
doses of MenACWY-TT administered at toddler age will be 
evaluated in the ACWY1d and ACWY2d groups.
The data of the ACWY1d and ACWY2d groups after the first 
vaccine dose will be pooled (Pool1d group) and will be used as the 
control for the Co-ad group in terms of response to meningococcal 
antigens.
The data of the PCV-13 group will be used as the control for the 
Co-ad group in terms of response to pneumococcal antigens.
Objectives
Primary
Exploratory primary objectives

One month after administration of MenACWY-TT in the 
ACWY1d group and the ACWY2d group:

To evaluate the immunogenicity of MenACWY-TT vaccine 
after administration of 1 dose in groups ACWY1d and 
ACWY2d or 2 doses in group ACWY2d with respect to 
Serum Bactericidal Assay against Neisseria meningitidis 
serogroup A using rabbit complement (rSBA-MenA), 
rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres. 

One, three and five years after the last vaccination in the 
ACWY1d group and the ACWY2d group:

To evaluate the long-term persistence of the immune 
response induced by 1 or 2 doses of MenACWY-TT vaccine 
with respect to rSBA-MenA, rSBA-MenC, 
rSBA-MenW-135 and rSBA-MenY titres.
Confirmatory primary objectives
The confirmatory primary objectives will be assessed in a 
hierarchical manner according to the order presented below. The 
second confirmatory primary objective can only be considered as 
met if the statistical criteria for both that objective and the first 
confirmatory primary objective are met.

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
To demonstrate the non-inferiority of the immune response to 
meningococcal conjugate vaccine MenACWY-TT when 
co-administered with 13-valent pneumococcal vaccine 
Prevenar 13 versus meningococcal conjugate vaccine 
MenACWY-TT given alone one month after vaccination. 
Criterion for non-inferiority of meningococcal serogroups A, 
C, W-135 and Y:
Non-inferiority will be demonstrated for each serogroup 
separately if the lower limit of the two-sided standardized 
asymptotic 95% confidence interval (CI) for the group 
difference between the Co-ad group and the Pool1d group 
(Co-ad group minus Pool1d group) in the percentage of 
subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and 
rSBA-MenY titres ≥ 1:8 is greater than or equal to -10%. 

To demonstrate the non-inferiority of the immune response to 
13-valent pneumococcal vaccine Prevenar 13 when 
co-administered with meningococcal vaccine MenACWY-TT 
versus 13-valent pneumococcal vaccine Prevenar 13 given alone 
one month after vaccination 
Criterion for non-inferiority of pneumococcal serotypes 1, 3, 4, 
5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F:
Non-inferiority will be demonstrated for each serotype 
separately if the lower limit of the 95% CI of the Geometric 
Mean Concentration (GMC) ratio between the Co-ad group 
and the PCV-13 group (Co-ad group over PCV-13 group) is 
above 0.5.
Secondary
One month after administration of MenACWY-TT in the ACWY1d 
group and the ACWY2d group:

To evaluate the immunogenicity of MenACWY-TT vaccine 
after administration of 1 dose in groups ACWY1d and ACWY2d or 
2 doses in group ACWY2d with respect to SBA using human 
complement (hSBA-MenA, hSBA-MenC, 
hSBA-MenW-135 and hSBA-MenY) titres in a subset of subjects. 
One month after administration of MenACWY-TT in the Co-ad 
group and PCV-13 group:

To evaluate the immunogenicity of MenACWY-TT vaccine 
when administered as 1 dose with respect to rSBA-MenA, 
rSBA-MenC, rSBA-MenW-135, rSBA-MenY titres 

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One month after administration of Prevenar 13 in the Co-ad group 
and PCV-13 group:

To evaluate the immune response to 13-valent pneumococcal 
vaccine Prevenar 13, co-administered with MenACWY-TT 
vaccine and Prevenar 13 administered alone with respect to 
antibody concentrations and titres against pneumococcal 
serotype specific polysaccharides. 
One, three and five years after the last vaccination in the ACWY1d 
group and the ACWY2d group:

To evaluate the long-term persistence of the immune response
induced by 1 or 2 doses of MenACWY-TT vaccines with 
respect to hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and 
hSBA-MenY titres in a subset of subjects. 
One, three and five years after the last vaccination in the Co-ad 
group and PCV-13 group:

To evaluate the long-term persistence of the immune response 
induced by 1 dose of MenACWY-TT vaccine with respect to 
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY 
titres. 
After each vaccine administration:

To evaluate the safety and reactogenicity in terms of solicited 
symptoms, unsolicited symptoms, serious adverse events 
(SAEs) and New Onset of Chronic Illnesses (NOCI) following 
each study vaccine dose. 
One, three and five years after the last vaccination:

To evaluate the occurrence of SAEs related to study vaccine 
administration and any event related to lack of vaccine efficacy 
(i.e. meningococcal disease). 

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Study design

Experimental design: Phase III, open-label, randomised, 
controlled, multi-centric study with four parallel groups.

Duration of the study: 62 months for each subject 

Epoch 001: Primary starting at Visit 1 (Month 0) and ending 
at the phone contact (Month 9),

Epoch 002: Persistence Visit 5,

Epoch 003: Persistence Visit 6,

Epoch 004: Persistence Visit 7.

Study groups:
Synopsis Table 1
Study Groups and Epochs foreseen in the Study
Study groups
Number 
of 
subjects
Age (Min/Max)
Epochs
Epoch 
001
Epoch 
002
Epoch 
003
Epoch 004
ACWY1d 
200
12 months - 14 months
X
X
X
X
ACWY2d
200
12 months - 14 months
X
X
X
X
Co-ad
200
12 months  - 14 months
X
X
X
X
PCV-13 
200
12 months - 14 months
X
X
X
X
Synopsis Table 2
Study Groups and Treatment foreseen in the Study
Treatment name
Vaccine/Product name
Study Groups
ACWY1d 
ACWY2d 
Co-ad 
PCV-13 
MenACWY-TT
MenACWY-TT (pellet) 
X
X
X
X
NaCl (solution for vaccine reconstitution) 
X
X
X
X
PCV-13
Prevenar 13
X
X
*The lyophilised pellet of MenACWY-TT vaccine is to be reconstituted with the supplied saline diluent.

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
Control: active control.

Vaccination schedules:

Subjects in the ACWY1d group will 
receive one dose of MenACWY-TT 
at Visit 1. For this study group, 
Prevenar 13 is not considered as a 
study vaccine and has to be 
administered after Visit 2.

Subjects in the ACWY2d group will 
receive one dose of MenACWY-TT 
at Visit 1 and at Visit 3. For this 
study group, Prevenar 13 is not 
considered as a study vaccine and 
has to be administered between the 
2 doses of MenACWY-TT (after the 
Visit 2 blood sampling up to 30 
days before the second dose of 
MenACWY-TT) or after Visit 4.

Subjects in the Co-ad group will 
receive one dose of MenACWY-TT 
and one dose of Prevenar 13 at 
Visit 1.

Subjects in the PCV-13 group will 
receive one dose of Prevenar 13 at 
Visit 1 and one dose of MenACWY-
TT at Visit 3.

Treatment allocation: randomised

Blinding:
Synopsis Table 3
Blinding of Study Epochs
Study Epochs
Blinding
Epoch 001 
open
Epoch 002 
open
Epoch 003 
open
Epoch 004 
open

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
Sampling schedule:

Five blood samples will be taken from the subjects of the 
Co-ad and ACWY1d groups: at Visit 1, Visit 2, Visit 5, Visit 
6 and Visit 7.

Six blood samples will be taken from the subjects of the 
ACWY2d and PCV-13 groups: at Visit 1, Visit 2, Visit 4, 
Visit 5, Visit 6 and Visit 7.

Type of study: self-contained.

Data collection: Electronic Case Report Form (eCRF).
Number of subjects
The target enrolment will be approximately 800 subjects (200 in 
each of the study groups) to reach approximately 640 evaluable 
subjects for the statistical analysis up to Month 3, assuming 20% 
drop-out of subjects up to Visit 4.
Endpoints
Primary
Immunogenicity with respect to components of the study vaccines: 

Percentage of subjects with rSBA-MenA, rSBA-MenC, 
rSBA-MenW-135 and rSBA-MenY titres ≥ 1:8 one month 
after administration of 1 dose of MenACWY-TT in the 
ACWY1d, ACWY2d and Co-ad groups and one month after 
administration of 2 doses in the ACWY2d group. 

Percentage of subjects with rSBA-MenA, rSBA-MenC, 
rSBA-MenW-135 and rSBA-MenY titres ≥ 1:8, ≥ 1:128 and
geometric mean titres (GMTs) at Years 1, 3 and 5 in the 
ACWY1d and ACWY2d groups. 

Anti-pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 
18C, 19A, 19F and 23F geometric mean antibody 
concentrations one month after administration of
Prevenar 13 in the Co-ad and PCV-13 groups.
Secondary
Immunogenicity with respect to components of the study vaccines 
(on secondary readouts): 

Percentage of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW-135 and hSBA-MenY titres ≥ 1:4, ≥ 1:8 and
GMTs one month after administration of 1 dose of 
MenACWY-TT in a subset of subjects in the ACWY1d and 
ACWY2d groups and one month after administration of 2 
doses in the ACWY2d group.

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
Percentage of subjects with rSBA-MenA, rSBA-MenC, 
rSBA-MenW-135 and rSBA-MenY titres ≥ 1:8, ≥ 1:128 and
GMTs one month after administration of 1 dose of 
MenACWY-TT in the PCV-13 group.

Percentage of subjects with rSBA-MenA, rSBA-MenC, 
rSBA-MenW-135 and rSBA-MenY titres ≥ 1:128 and GMTs 
one month after administration of 1 dose of MenACWY-TT 
in the ACWY1d, ACWY2d and Co-ad groups. 

Percentage of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW-135 and hSBA-MenY titres ≥ 1:4, ≥1:8 and
GMTs at Years 1, 3 and 5 in a subset of subjects in the 
ACWY1d and ACWY2d groups.

Percentage of subjects with rSBA-MenA, rSBA-MenC, 
rSBA-MenW-135 and rSBA-MenY titres ≥ 1:8, ≥1:128 and
GMTs at Years 1, 3 and 5 in the Co-ad and PCV-13 groups. 

Percentage of subjects with anti-pneumococcal serotypes 1, 
3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F antibody 
concentrations ≥ 0.15 µg/ml, ≥ 0.26 µg/ml and ≥ 0.35 µg/ml 
one month after administration of Prevenar 13 in the Co-ad 
and PCV-13 groups.

Percentage of subjects with anti-pneumococcal serotypes 1, 
3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F OPA 
titres ≥ 1:8 and GMTs one month after administration of 
Prevenar 13 in the Co-ad and PCV-13 groups. 
Solicited local and general symptoms: 

Occurrence of each solicited local and general symptom 
within 4 days (Day 0 – Day 3) after each study vaccination. 
Unsolicited AEs:

Occurrence of unsolicited AEs within 31 days (Day 0 – Day 
30) after any study vaccination, according to the Medical 
Dictionary for Regulatory Activities (MedDRA) 
classification. 
SAEs: 

Occurrence of SAEs from Month 0 to Month 9. 

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SAEs related to study vaccine administration: 

Occurrence of SAEs related to study vaccine administration
and any event related to lack of vaccine efficacy (i.e. 
meningococcal disease) from the first receipt of study 
vaccine until study end. 
Occurrence of NOCI: 

Occurrence of NOCI (e.g. asthma, autoimmune disorders, 
type 1 diabetes, allergies) from Month 0 to Month 9. 

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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................21
1. INTRODUCTION ...............................................................................................................28
1.1. Background .............................................................................................................28
1.2. Rationale for the Study and Study Design ..............................................................29
1.2.1. Rationale for the Study...............................................................................29
1.2.2. Rationale for the Study Design...................................................................30
2. OBJECTIVES......................................................................................................................30
2.1. Primary Objective ...................................................................................................30
2.1.1. Exploratory Primary Objectives .................................................................30
2.1.2. Confirmatory Primary Objectives...............................................................31
2.2. Secondary Objectives..............................................................................................32
3. STUDY DESIGN OVERVIEW ..........................................................................................33
4. STUDY COHORT...............................................................................................................35
4.1. Number of Subjects/Centres....................................................................................35
4.2. Inclusion Criteria for Enrolment .............................................................................36
4.3. Exclusion Criteria for Enrolment ............................................................................36
5. CONDUCT OF THE STUDY.............................................................................................38
5.1. Regulatory and Ethical Considerations, including the Informed Consent 
Process.......................................................................................................................38
5.2. Subject Identification and Randomisation of Treatment.........................................39
5.2.1. Subject Identification..................................................................................39
5.2.2. Randomisation of Treatment ......................................................................39
5.2.2.1. Randomisation of Supplies........................................................39
5.2.2.2. Treatment Allocation to the Subject..........................................40
5.2.3. Allocation of Subjects to Assay Subsets ....................................................40
5.3. Method of Blinding .................................................................................................41
5.4. General Study Aspects ............................................................................................41
5.5. Outline of Study Procedures ...................................................................................41
5.6. Detailed description of Study Procedures ...............................................................48
5.6.1. Informed Consent .......................................................................................48

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5.6.2. Check Inclusion and Exclusion Criteria .....................................................48
5.6.3. Collect Demographic Data .........................................................................48
5.6.4. Medical History ..........................................................................................48
5.6.5. Vaccination History....................................................................................48
5.6.6. Physical Examination .................................................................................48
5.6.7. HIV Rapid Testing (Only in South Africa) (Amended 02 July 2014) .......48
5.6.8. Check Contraindications, Warnings and Precautions to Vaccination ........49
5.6.9. Assess Pre-vaccination Body Temperature ................................................49
5.6.10. Study Group and Treatment Number Allocation......................................49
5.6.11. Sampling...................................................................................................49
5.6.11.1. Blood Sampling for Immune Response Assessments.............49
5.6.12. Study Vaccine(S) Administration.............................................................50
5.6.13. Check and Record Concomitant Medication/Vaccination and 
Intercurrent Medical Conditions......................................................................50
5.6.14. Recording of AEs and SAEs.....................................................................50
5.6.15. Recording of NOCIs and GBS .................................................................51
5.6.16. Study Conclusion......................................................................................51
5.7. Biological Sample Handling and Analysis..............................................................51
5.7.1. Use of Specified Study Materials ...............................................................52
5.7.2. Biological Samples.....................................................................................52
5.7.3. Laboratory Assays ......................................................................................53
5.7.4. Biological Samples Evaluation...................................................................56
5.7.4.1. Immunological Read-outs .........................................................56
5.7.5. Immunological Correlates of Protection.....................................................58
6. STUDY VACCINES AND ADMINISTRATION..............................................................59
6.1. Description of Study Vaccines................................................................................59
6.2. Storage and Handling of Study Vaccines................................................................59
6.3. Dosage and Administration of Study Vaccines.......................................................60
6.4. Replacement of Unusable Vaccine Doses...............................................................60
6.5. Contraindications to Subsequent Vaccination.........................................................61
6.6. Warnings and Precautions.......................................................................................61
6.7. Concomitant Medication/Product and Concomitant Vaccination...........................62

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6.7.1. Recording of Concomitant Medications/Products and Concomitant 
Vaccination ......................................................................................................62
6.7.2. Concomitant Medications/Products/Vaccines that may lead to the 
Elimination of A Subject from ATP Analyses ................................................63
6.8. Intercurrent Medical Conditions that may lead to elimination of a Subject 
from ATP Analyses ...................................................................................................64
7. HEALTH ECONOMICS.....................................................................................................64
8. SAFETY ..............................................................................................................................64
8.1. Safety Definitions....................................................................................................64
8.1.1. Definition of an Adverse Event ..................................................................64
8.1.2. Definition of a Serious Adverse Event .......................................................65
8.1.3. Solicited Adverse Events............................................................................66
8.1.3.1. Solicited local (injection-site) adverse events...........................66
8.1.3.2. Solicited General Adverse Events.............................................67
8.1.4. Clinical Laboratory Parameters and Other Abnormal Assessments 
Qualifying as Adverse Events or Serious Adverse Events..............................67
8.1.5. Adverse events of Specific Interest ............................................................68
8.1.5.1. List of New Onset Chronic Illnesses.........................................68
8.2. Detecting and Recording Adverse Events, Serious Adverse Events, NOCIs 
and GBS.....................................................................................................................71
8.2.1. Time Period for Detecting and Recording Adverse Events aAnd 
Serious Adverse Events ...................................................................................71
8.2.2. Post-Study Adverse Events and Serious Adverse Events...........................77
8.2.3. Evaluation of Adverse Events and Serious Adverse Events ......................77
8.2.3.1. Active Questioning to Detect Adverse Events and Serious 
Adverse Events..................................................................................77
8.2.3.2. Assessment of Adverse Events .................................................77
8.2.3.3. Assessment of Outcomes ..........................................................80
8.2.3.4. Medically Attended Visits.........................................................81
8.3. Reporting of Serious Adverse Events and Other Events.........................................81
8.3.1. Prompt Reporting of Serious Adverse Events and Other Events ...............81
8.3.2. Completion and Transmission of SAE Reports..........................................81
8.3.3. Updating of SAE Information after Freezing of The Subject’s eCRF .......81
8.3.4. Regulatory Reporting Requirements for Serious Adverse Events .............82

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8.4. Follow-up of Adverse Events and Serious Adverse Events....................................82
8.4.1. Follow-up during The Study.......................................................................82
8.4.2. Follow-up after the Subject is Discharged from the Study.........................82
8.5. Treatment of Adverse Events..................................................................................83
8.6. Subject Card ............................................................................................................83
9. SUBJECT COMPLETION AND WITHDRAWAL ...........................................................83
9.1. Subject Completion.................................................................................................83
9.2. Subject Withdrawal.................................................................................................83
9.2.1. Subject Withdrawal from the Study ...........................................................83
9.2.2. Subject Withdrawal from Investigational Vaccine.....................................84
10. STATISTICAL METHODS..............................................................................................85
10.1. Primary Endpoints.................................................................................................85
10.2. Secondary Endpoints.............................................................................................85
10.3. Determination of Sample Size...............................................................................87
10.4. Study Cohorts/ Data sets to be Analysed ..............................................................90
10.4.1. Total Vaccinated Cohort...........................................................................90
10.4.2. According-To-Protocol Cohort for Safety................................................90
10.4.3. According-To-Protocol Cohort for Immunogenicity Post Dose 1 ...........90
10.4.4. According-To-Protocol for Immunogenicity Post Dose 2........................91
10.4.5. Total Cohort Year 1, 3 and 5 ....................................................................91
10.4.6. According-To-Protocol Cohort for Persistence Year 1, 3 and 5 ..............92
10.5. Derived and Transformed Data.............................................................................92
10.6. Analysis of Primary Vaccination ..........................................................................93
10.6.1. Demography .............................................................................................93
10.6.2. Analysis of Immunogenicity.....................................................................94
10.6.2.1. Within Group...........................................................................94
10.6.2.2. Between Group........................................................................95
10.6.3. Analysis of Safety.....................................................................................96
10.7. Analysis of Persistence..........................................................................................97
10.7.1. Demography .............................................................................................97
10.7.2. Analysis of Persistence.............................................................................97
10.7.3. Modelling Prediction ................................................................................98

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10.7.4. Analysis of Safety.....................................................................................98
10.8. Interpretation of Analyses .....................................................................................98
10.9. Conduct of Analyses .............................................................................................98
10.9.1. Sequence of Analyses (Amended 02 July 2014)......................................98
10.9.2. Statistical Considerations for Interim Analyses .......................................99
11. ADMINISTRATIVE MATTERS......................................................................................99
11.1. Remote Data Entry Instructions ............................................................................99
11.2. Study Monitoring ..................................................................................................99
11.3. Record Retention.................................................................................................100
11.4. Quality Assurance ...............................................................................................101
11.5. Posting of Information on Publicly Available Clinical Trial Registers and 
Publication Policy....................................................................................................101
11.6. Provision of Study Results to Investigators ........................................................103
11.7. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................103
12. COUNTRY SPECIFIC REQUIREMENTS ....................................................................103
13. REFERENCES ................................................................................................................103
LIST OF TABLES
Table 1.
Study Groups and Epochs Foreseen in the Study.....................................34
Table 2.
Study Groups and Treatment Foreseen in the Study ................................34
Table 3.
Blinding of Study Epochs.........................................................................35
Table 4.
Subsets (Amended 02 July 2014) .............................................................41
Table 5.
List of Study Procedures for Groups ACWY1d and Co-ad .....................42
Table 6.
List of study procedures for groups ACWY2d and PCV-13....................44
Table 7.
Intervals Between Study Visits for Groups ACWY1d and Co-ad ...........47
Table 8.
Intervals Between Study Visits for Groups ACWY2d and PCV-13........47
Table 9.
Biological samples (Amended 02 July 2014)...........................................52
Table 10.
Humoral Immunity (Antibody determination) (Amended 02 July 
2014).........................................................................................................53
Table 11.
Immunological Read-outs (Amended 02 July 2014)................................56
Table 12.
Study Vaccines .........................................................................................59
Table 13.
Dosage and Administration ......................................................................60

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Table 14.
Solicited local Adverse Events.................................................................67
Table 15.
Solicited General Adverse Events ............................................................67
Table 16.
List of Potential new onset of Chronic Illnesses ......................................68
Table 17.
Reporting Periods for Adverse Events, Serious Adverse Events, 
GBS and NOCIs for the ACWY1d and Co-ad Groups ............................73
Table 18.
Reporting Periods for Adverse Events, Serious Adverse Events, 
GBS and NOCIs for the ACWY2d and PCV-13 Groups.........................75
Table 19.
Intensity Scales for Solicited Symptoms in Infants/Toddlers...................77
Table 20.
Timeframes for Submitting Serious Adverse Event and Other 
Events Reports..........................................................................................81
Table 21.
Power to Show the Non-inferiority of the Co-ad Group Compared 
to the Pool1d Group..................................................................................87
Table 22.
Power to Show the Non-inferiority of the Co-ad Group Compared 
to the PCV-13 Group with respect to Prevenar 13 Antibody 
Concentrations..........................................................................................88
Table 23.
Summary of Power for the Confirmatory Primary Objectives.................89
Table 24.
Laboratories ............................................................................................108

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LIST OF ABBREVIATIONS
AE:
Adverse Event
ANCOVA:
Analysis of covariance
ATP:
According-To-Protocol
BAC:
Bactericidal Assay
CDC:
Centers for Disease Control and Prevention
CFU:
Colony-forming unit
CI:
Confidence interval
CRF:
Case report form
CRM197:
Cross-reactive material 197 (a non-toxic mutant form of 
Corynebacterium diphtheria toxin)
CSA:
Clinical Study Agreement
CSR:
Clinical Study Report
DIL:
Dilution
DT:
Diphtheria toxoid
DTP:
Diphtheria, Tetanus and Pertussis 
EC:
Ethics committee
eCRF:
electronic Case Report Form 
SmPC
summary of product characteristics
ELISA:
Enzyme-linked immunosorbent assay
EMA:
European Medicines Agency
ESFU:
Extended Safety Follow-Up
(e)TDF:
electronic Temperature excursion Decision Form
EU:
European Union
EudraCT:
European Clinical Trials Database
FDA:
Food and Drug Administration, United States of America
GBS:
Guillain-Barré Syndrome
GCP:
Good Clinical Practice
GMC:
Geometric Mean Concentration
GMT:
Geometric Mean Titre
GSK:
GlaxoSmithKline
Hib:
Haemophilus influenzae type b
HIV:
Human Immunodeficiency Virus
hSBA-MenA:
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup A (using human complement)
hSBA-MenC:
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup C (using human complement)
hSBA-MenW-135:
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup W-135 (using human complement)
hSBA-MenY:
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup Y (using human complement)
ICF:
Informed Consent Form
ICH:
International Conference on Harmonisation
IEC:
Independent Ethics Committee
IgG:
Immunoglobulin G

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IM:
Intramuscular
IMP:
Investigational Medicinal Product
IRB:
Institutional Review Board
IRT: 
Interactive Response Technology 
LAR:
Legally Acceptable Representative
LSLV:
Last Subject Last Visit
MedDRA:
Medical Dictionary for Regulatory Activities
MenA:
Neisseria meningitidis serogroup A
MenC:
Neisseria meningitidis serogroup C
MenW-135:
Neisseria meningitidis serogroup W
MenY:
Neisseria meningitidis serogroup Y
MMR:
Measles, Mumps and Rubella
MMRV:
Measles, Mumps, Rubella and Varicella
NA:
Not Applicable
NOCI:
New Onset of Chronic Illness
OPA:
Opsonophagocytic activity
OPS:
Opsonophagocytic assay
PCR:
Polymerase chain reaction
PCV:
Pneumococcal Conjugate Vaccine
PHE:
Public Health England
PI:
Prescribing Information
PS:
Polysaccharide
PSA:
Polysaccharide Neisseria meningitidis serogroup A
PSC:
Polysaccharide Neisseria meningitidis serogroup C
PSW-135:
Polysaccharide Neisseria meningitidis serogroup W-135
PSY:
Polysaccharide Neisseria meningitidis serogroup Y
RDE:
Remote Data Entry
rSBA-MenA:
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup A (using rabbit complement)
rSBA-MenC:
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup C (using rabbit complement)
rSBA-MenW-135:
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup W-135 (using rabbit complement)
rSBA-MenY:
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup Y (using rabbit complement)
SAE:
Serious Adverse Event
SBIR:
Randomisation system on the Internet
SDV:
Source Data Verification
SPM:
Study Procedures Manual
SRSD:
Single reference safety document
TT:
Tetanus Toxoid
UK:
United Kingdom
US; USA:
United States; United States of America

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GLOSSARY OF TERMS
Adverse event:
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use of a 
medicinal product, whether or not considered related to the 
medicinal product. 
An adverse event (AE) can therefore be any unfavourable and 
unintended sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product. For marketed 
medicinal products, this also includes failure to produce 
expected benefits (i.e. lack of efficacy), abuse or misuse.
Blinding:
A procedure in which one or more parties to the trial are kept 
unaware of the treatment assignment in order to reduce the 
risk of biased study outcomes. The level of blinding is 
maintained throughout the conduct of the trial, and only when 
the data are cleaned to an acceptable level of quality will 
appropriate personnel be unblinded or when required in case 
of a serious adverse event. In an open-label study, no blind is 
used. Both the investigator and the subject know the identity 
of the treatment assigned. 
Child in care:
A child who has been placed under the control or protection 
of an agency, organisation, institution or entity by the courts, 
the government or a government body, acting in accordance 
with powers conferred on them by law or regulation. The 
definition of a child in care can include a child cared for by 
foster parents or living in a care home or institution, provided 
that the arrangement falls within the definition above. The 
definition of a child in care does not include a child who is 
adopted or has an appointed legally acceptable representative.
Eligible:
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria.
Epoch:
An epoch is a self-contained set of consecutive timepoints or 
a single timepoint from a single protocol. Self-contained 
means that data collected for all subjects at all timepoints 
within that epoch permit drawing a complete conclusion to 
define or refine the targeted label of the product. Typical 
examples of epochs are primary vaccinations, boosters, yearly 
immunogenicity follow-ups, and surveillance periods for 
efficacy or safety.
Evaluable:
Meeting all eligibility criteria, complying with the procedures 
defined in the protocol, and, therefore, included in the
according-to-protocol (ATP) analysis (see Section 6.7.2 and 
Section 10.4 for details on criteria for evaluability).

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Immunological correlate of 
protection:
The defined humoral antibody response above which there is 
a high likelihood of protection in the absence of any host 
factors that might increase susceptibility to the infectious 
agent.
Investigational 
vaccine/product:
(Synonym of 
Investigational Medicinal 
Product)
A pharmaceutical form of an active ingredient or placebo 
being tested or used as a reference in a clinical trial, including 
a product with a marketing authorisation when used 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. 
Primary completion date:
The date that the final subject was examined or received an 
intervention for the purpose of final collection of data for the 
primary outcome, whether the clinical trial concluded 
according to the pre-specified protocol or was terminated.
Randomisation:
Process of random attribution of treatment to subjects in order 
to reduce bias of selection.
Self-contained study:
Study with objectives not linked to the data of another study.
Site Monitor:
An individual assigned by the sponsor who is responsible for 
assuring proper conduct of clinical studies at one or more 
investigational sites.
Solicited adverse event:
The presence/occurrence/intensity of these events is actively 
solicited from the subject or an observer during a specified 
post-vaccination follow-up period.
Subject:
Term used throughout the protocol to denote an individual 
who has been contacted in order to participate or participates 
in the clinical study, either as a recipient of the 
vaccine(s)/product(s) or as a control.
Subject number:
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study.
Summary of product 
characteristics
The European Union (EU) prescribing information for 
products registered via the centralized or mutual recognition 
procedure.
Treatment:
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or placebo 
intended to be administered to a subject, identified by a 
unique number, according to the study randomisation or 
treatment allocation.
Treatment number:
A number identifying a treatment to a subject, according to
the study randomisation or treatment allocation.
Unsolicited adverse event:
Any AE reported in addition to those solicited during the 
clinical study. Also any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse event.

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TRADEMARKS
The following trademarks are used in the present protocol.
Note: In the body of the protocol (including the synopsis), the names of the vaccines will be 
written without the superscript symbol ™or ® and will be written in italics.
Trademarks of Pfizer
Generic description
Nimenrix®
Meningococcal serogroups A, C, W-135, 
Y polysaccharide tetanus toxoid conjugate 
vaccine
Prevenar 13®
13-valent pneumococcal conjugate 
vaccine with diphtheria CRM197 as 
protein carrier. Serotypes: 1, 3, 4, 5, 6A, 
6B, 7F, 9V, 14, 18C, 19A, 19F and 23F 

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1. INTRODUCTION
1.1. Background
Invasive meningococcal disease, including meningitis and meningococcal septicaemia, often 
follows invasive infection by Neisseria meningitidis (N. meningitidis - meningococcus) and 
is a major cause of death and morbidity throughout the world. The devastating disease 
caused by the bacteria is characterised by rapidly progressive sepsis which can be fatal within 
a few hours of onset leaving antibiotic treatment ineffective. Severe permanent sequelae 
(e.g. limb necrosis requiring amputation, hearing loss, chronic renal failure, neurological 
damage) can result after infection and the mortality rate is 7 - 19%, even with appropriate 
therapy [Kirsch, 1996; Anderson, 1998]. Mortality rates are generally highest in infants and 
young children [Harrison, 2001]. Meningococcal disease continues to be endemic in both 
industrialised (e.g. Europe and United States [US]) and developing countries. Epidemics 
regularly occur worldwide with the highest attack rates prevailing in the sub-Saharan 
countries [Harrison, 2009]. Older children, adolescents, and adults are more often affected 
during epidemics [CDC (Centers for Disease Control), 1995; Whalen, 1995].
N. meningitidis serogroups A, B, C, W-135 and Y are the most common causes of invasive 
meningococcal disease worldwide. The dominant serogroups which cause the disease are 
serogroup B followed by C in Europe and Latin America, serogroups B, C and Y in the US
and Canada, and serogroup A in Asia, Middle East and Africa. However, both disease 
incidence and serogroup distribution vary geographically and temporally [Harrison, 2009].
Meningococcal polysaccharide (PS) vaccines against meningococcal serogroups A, C, 
W-135 and Y (MenA, MenC, MenW-135 and MenY) have been effective in the control of 
epidemic meningococcal disease due to these serogroups, in the prevention of secondary 
cases of disease in household contacts as well as in the successful vaccination of high risk 
groups [Rosenstein, 1998]. However, the value of PS vaccines is limited because they elicit 
a T-cell-independent immune response, stimulate mature B lymphocytes, do not induce 
immunological memory and are not immunogenic in children below 2 years of age. The 
protection elicited is neither long-lasting nor characterised by an anamnestic response to 
subsequent challenge. Moreover, meningococcal PS vaccines do not significantly reduce 
nasopharyngeal colonisation and, accordingly, do not provide herd protection to the general 
population [Pollard, 2001; Balmer, 2004]. Of even greater concern is the observation that 
meningococcal PS vaccines may induce immunologic hyporesponsiveness, whereby the 
antibody response to subsequent doses of a PS vaccine is less than the response to the first 
dose [Richmond, 2000].
Polysaccharide antigens can however be made to induce T-cell responses and immunological 
memory by their covalent coupling to a carrier protein (conjugate vaccine). This principle 
was the key to the successful development of Haemophilus influenzae type b (Hib) conjugate 
vaccines that are immunogenic in young children and able to induce immunological memory. 
The other advantage of conjugate vaccines is their ability to reduce nasopharyngeal carriage 
[Maiden, 2002], allowing for significant indirect benefits through herd protection and 
reduced transmission [Ramsay, 2003]. 

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The data available after the introduction of meningococcal serogroup C conjugate vaccines in 
a mass vaccination programme in the United Kingdom (UK) have proven the effectiveness of 
conjugate vaccines in young children and indicated that primary vaccination in infants 
followed by a booster dose at toddler age was optimal for long-term protection 
[Trotter, 2004; Auckland, 2006].
Meningococcal serogroup C conjugate vaccines using a non-toxic mutant form of 
Corynebacterium diphtheriae toxin (CRM197) or tetanus toxoid (TT) carrier proteins have 
been developed and brought to the market in Europe, Canada, Australia and Latin America. 
At this time, three quadrivalent meningococcal conjugate vaccines have been licensed. 
MenACWY diphtheria toxoid (DT) conjugate vaccine (Menactra, Sanofi Pasteur Inc.) is 
authorised for active immunisation of persons aged 9 months to 55 years in the US and 
Canada [Menactra Prescribing Information, 2011], and for subjects aged 2 - 55 years in Gulf 
Cooperation States in the Middle East. MenACWY CRM197 conjugate vaccine (Menveo, 
GSK) is authorised for active immunisation of persons from 2 years of age in the European 
Union (EU) [Menveo Package Leaflet, 2012], from 11 years of age in Australia 
[Menveo Consumer Medicine Information, 2010], and from 2 to 55 years of age in the US 
and Canada [Menveo Prescribing Information, 2011; Menveo Product Monograph, 2011]. 
GlaxoSmithKline [GSK] Biologicals has developed a quadrivalent conjugate vaccine 
(MenACWY-TT) for the prevention of invasive infections with N. meningitidis serogroups 
A, C, Y, and W-135, using TT as the carrier. This vaccine has been shown to be 
immunogenic and well tolerated in individuals from 12 months of age [Baxter, 2011; 
Bermal, 2011; Knuf, 2010; Knuf, 2011; Memish, 2011; Ostergaard, 2009; Vesikari, 2011]. 
This MenACWY-TT conjugate vaccine (Nimenrix) has been licensed in the EU in April 
2012 for individuals 12 months of age and above [European Commission, 2012] and in 
Canada in March 2013 for individuals from 12 months of age up to 55 years of age.
Pfizer completed the acquisition of Nimenrix and Mencevax on 01 October 2015, and will 
therefore assume responsibility of sponsor for this study.
Please refer to the current summary of product characteristics (SmPC) for information 
regarding the pre-clinical and clinical studies and the potential risks and benefits of the 
MenACWY-TT vaccine. The SmPC is the single reference safety document (SRSD) for this 
study.
1.2. Rationale for the Study and Study Design
1.2.1. Rationale for the Study
Current data from clinical studies with the MenACWY-TT vaccine suggest that a single dose 
in toddlers provides sufficient protection. However, data on the possible advantage of 
administrating two vaccine doses are not available for toddlers around 12 months of age at 
the time of vaccination. The European Medicines Agency (EMA) requested GSK to conduct 
a study to evaluate the immediate and longer term antibody titres elicited by one or two doses 
of MenACWY-TT administered in children aged 12-23 months. This study was therefore 

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designed to evaluate the immunogenicity of one and two doses of MenACWY-TT 
administered to unprimed toddlers during their second year of life.
Countries with a vaccination schedule against pneumococcal disease recommend a booster 
dose of a pneumococcal conjugate vaccine between 11 and 15 months of age. This study 
will also be conducted to demonstrate that co-administration of meningococcal vaccine 
MenACWY-TT with the booster dose of pneumococcal conjugate vaccine Prevenar 13 does 
not adversely impact the immunogenicity of either of the vaccines. The safety profile of both 
vaccines will also be evaluated.
1.2.2. Rationale for the Study Design
The study contains 4 study groups:

The ACWY1d group will receive 1 dose of MenACWY-TT at Visit 1. For this study 
group, Prevenar 13 is not considered as a study vaccine and has to be administered after 
Visit 2.

The ACWY2d group will receive 2 doses of MenACWY-TT 2 months apart (at Visits 1 
and 3). For this study group, Prevenar 13 is not considered as a study vaccine and has to 
be administered between the 2 doses of MenACWY-TT (after the Visit 2 blood sampling 
up to 30 days before the second dose of MenACWY-TT) or after Visit 4.

The Co-ad group will receive 1 dose of MenACWY-TT and 1 dose of Prevenar 13 at 
Visit 1.

The PCV-13 group will receive 1 dose of Prevenar 13 at Visit 1 and 1 dose of 
MenACWY-TT 2 months later (Visit 3).
The immunogenicity and long-term persistence of one and two doses of MenACWY-TT 
administered at toddler age will be evaluated in the ACWY1d and ACWY2d groups.
The data of the ACWY1d and ACWY2d groups after the first vaccine dose will be pooled 
(Pool1d group) and will be used as the control for the Co-ad group in terms of response to 
meningococcal antigens.
The data of the PCV-13 group will be used as the control for the Co-ad group in terms of 
response to pneumococcal antigens. 
2. OBJECTIVES
2.1. Primary Objective
2.1.1. Exploratory Primary Objectives

One month after administration of MenACWY-TT in the ACWY1d group and the 
ACWY2d group:

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
To evaluate the immunogenicity of MenACWY-TT vaccine after administration of 1 
dose in groups ACWY1d and ACWY2d or 2 doses in group ACWY2d with respect to 
Serum Bactericidal Assay against Neisseria meningitidis serogroup A using rabbit 
complement (rSBA-MenA), rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres. 

One, three and five years after the last vaccination in the ACWY1d group and the 
ACWY2d group:

To evaluate the long-term persistence of the immune response induced by 1 or 2 
doses of MenACWY-TT vaccine with respect to rSBA-MenA, rSBA-MenC, 
rSBA-MenW-135 and rSBA-MenY titres 
Refer to Section 10.1 for the definition of the primary endpoints.
2.1.2. Confirmatory Primary Objectives
The confirmatory primary objectives will be assessed in a hierarchical manner according to 
the order presented below. The second confirmatory primary objective can only be 
considered as met if the statistical criteria for both that objective and the first confirmatory 
primary objective are met.

To demonstrate the non-inferiority of the immune response to meningococcal conjugate 
vaccine MenACWY-TT when co-administered with 13-valent pneumococcal vaccine 
Prevenar 13 versus meningococcal conjugate vaccine MenACWY-TT given alone one 
month after vaccination. 
Criterion for non-inferiority of meningococcal serogroups A, C, W-135 and Y:
Non-inferiority will be demonstrated for each serogroup separately if the lower limit of 
the two-sided standardized asymptotic 95% confidence interval (CI) for the group 
difference between the Co-ad group and the Pool1d group (Co-ad group minus Pool1d 
group) in the percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 
and rSBA-MenY titres ≥ 1:8 is greater than or equal to -10%. 

To demonstrate the non-inferiority of the immune response to 13-valent pneumococcal 
vaccine Prevenar 13 when co-administered with meningococcal vaccine MenACWY-TT 
versus 13-valent pneumococcal vaccine Prevenar 13 given alone one month after 
vaccination.
Criterion for non-inferiority of pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 
18C, 19A, 19F and 23F:
Non-inferiority will be demonstrated for each serotype separately if the lower limit of the
95% CI of the Geometric Mean Concentration (GMC) ratio between the Co-ad group 
and the PCV-13 group (Co-ad group over PCV-13 group) is above 0.5. 

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2.2. Secondary Objectives
One month after administration of MenACWY-TT in the ACWY1d group and the ACWY2d 
group:

To evaluate the immunogenicity of MenACWY-TT vaccine after administration of 1 
dose in groups ACWY1d and ACWY2d or 2 doses in group ACWY2d with respect to 
SBA using human complement (hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and 
hSBA-MenY) titres in a subset of subjects. 
One month after administration of MenACWY-TT in the Co-ad group and PCV-13 group:

To evaluate the immunogenicity of MenACWY-TT vaccine when administered as 1 dose 
with respect to rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY titres 
One month after administration of Prevenar 13 in the Co-ad group and PCV-13 group:

To evaluate the immune response to 13-valent pneumococcal vaccine Prevenar 13, 
co-administered with MenACWY-TT vaccine and Prevenar 13 administered alone with 
respect to antibody concentrations and titres against pneumococcal serotype specific 
polysaccharides. 
One, three and five years after the last vaccination in the ACWY1d group and the ACWY2d 
group:

To evaluate the long-term persistence of the immune response induced by 1 or 2 doses of 
MenACWY-TT vaccine with respect to hSBA-MenA, hSBA-MenC, hSBA-MenW-135 
and hSBA-MenY titres in a subset of subjects. 
One, three and five years after the last vaccination in the Co-ad group and PCV-13 group:

To evaluate the long-term persistence of the immune response induced by 1 dose of 
MenACWY-TT vaccine with respect to rSBA-MenA, rSBA-MenC, rSBA-MenW-135 
and rSBA-MenY titres. 
After each vaccine administration:

To evaluate the safety and reactogenicity in terms of solicited symptoms, unsolicited 
symptoms, serious adverse events (SAEs) and New Onset of Chronic Illnesses (NOCI) 
following each study vaccine dose. 
One, three and five years after the last vaccination:

To evaluate the occurrence of SAEs related to study vaccine administration and any event 
related to lack of vaccine efficacy (i.e. meningococcal disease). 
Refer to Section 10.2 for the definition of the secondary endpoints.

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3. STUDY DESIGN OVERVIEW
Enrolment of
800 toddlers
Randomisation
(1:1:1:1)
Co-ad 
group
ACWY2d 
group
Visit 1
Month 0
12-14 
Blood sampling
Vaccination
Visit 3
Month 2
14-16 
Vaccination 
(ACWY2d and 
PCV-13 group)
Visit 4
Month 3
15-17
Blood sampling
(ACWY2d and 
PCV-13 group)
Visit 5, 6, 7
Blood sampling 
at Year 1, 3 and 5
Epoch 001 
Epochs 002, 003 and 004
MenACWY-TT
MenACWY-TT
MenACWY-TT +
PCV-13
Visit 2
Month 1
13-15 
Blood sampling
PCV-13 
group
PCV-13
MenACWY-TT
Age (months)
Phone
Contact
Month 9
21-23 
MenACWY-TT
ACWY1d 
group
Visit 5 will take place at 12 months after the last study vaccine administration (see Table 7
and Table 8). The subjects in the Co-ad and the ACWY1d groups will be 24-26 months of 
age and the subjects in the ACWY2d and PCV-13 groups will be 26-28 months of age at this 
visit.
For the ACWY1d and ACWY2d groups, the booster dose of Prevenar 13 will be provided by 
GSK to complete the vaccination schedule according to the national vaccination schedule:
ACWY1d group: the booster dose of Prevenar 13 has to be administered after Visit 2. 
ACWY2d group: the booster dose of Prevenar 13 has to be administered between the 2 doses 
of MenACWY-TT (after the Visit 2 blood sampling up to 30 days before the second dose of 
MenACWY-TT) or after Visit 4.
These doses of Prevenar 13 are not considered as study vaccines.
Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns. Therefore, adherence to the study design requirements, including those specified 
in the outline of study procedures (Section 5.5), are essential and required for study conduct. 
Experimental design: Phase III, open-label, randomised, controlled, multi-centric study 
with four parallel groups.

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Duration of the study: 62 months for each subject 

Epoch 001: Primary starting at Visit 1 (Month 0) and ending at the phone contact 
(Month 9),

Epoch 002: Persistence Visit 5,

Epoch 003: Persistence Visit 6,

Epoch 004: Persistence Visit 7.
Study groups:
Table 1.
Study Groups and Epochs Foreseen in the Study
Study groups
Number 
of 
subjects
Age (Min/Max)
Epochs
Epoch 001
Epoch 002
Epoch 003
Epoch 004
ACWY1d 
200
12 months - 14 months
X
X
X
X
ACWY2d
200
12 months - 14 months
X
X
X
X
Co-ad
200
12 months  - 14 months
X
X
X
X
PCV-13 
200
12 months - 14 months
X
X
X
X
Table 2.
Study Groups and Treatment Foreseen in the Study
Treatment name
Vaccine/Product name
Study Groups
ACWY1d 
ACWY2d 
Co-ad 
PCV-13 
MenACWY-TT
MenACWY-TT (pellet) 
X
X
X
X
NaCl (solution for vaccine reconstitution) 
X
X
X
X
PCV-13
Prevenar 13
X
X
*The lyophilised pellet of MenACWY-TT vaccine is to be reconstituted with the supplied saline diluent.
Control: active control
Vaccination schedules:

Subjects in the ACWY1d group will receive one dose of MenACWY-TT at Visit 1. 
For this study group, Prevenar 13 is not considered as a study vaccine and has to be 
administered after Visit 2.

Subjects in the ACWY2d group will receive one dose of MenACWY-TT at Visit 1 
and at Visit 3. For this study group, Prevenar 13 is not considered as a study vaccine 
and has to be administered between the 2 doses of MenACWY-TT (after the Visit 2 
blood sampling up to 30 days before the second dose of MenACWY-TT) or after 
Visit 4.

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
Subjects in the Co-ad group will receive one dose of MenACWY-TT and one dose of 
Prevenar 13 at Visit 1.

Subjects in the PCV-13 group will receive one dose of Prevenar 13 at Visit 1 and one 
dose of MenACWY-TT at Visit 3.
Treatment allocation: randomised
Blinding:
Table 3.
Blinding of Study Epochs
Study Epochs
Blinding
Epoch 001 
open
Epoch 002 
open
Epoch 003 
open
Epoch 004 
open
Sampling schedule: 

Five blood samples will be taken from the subjects of the Co-ad and ACWY1d 
groups: at Visit 1, Visit 2, Visit 5, Visit 6 and Visit 7.

Six blood samples will be taken from the subjects of the ACWY2d and PCV-13 
groups: at Visit 1, Visit 2, Visit 4, Visit 5, Visit 6 and Visit 7.
Type of study: self-contained
Data collection: Electronic Case Report Form (eCRF)
4. STUDY COHORT
4.1. Number of Subjects/Centres
The target enrolment will be approximately 800 subjects (200 in each of the study groups) to 
reach approximately 640 evaluable subjects for the statistical analysis up to Month 3, 
assuming 20% drop-out of subjects up to Visit 4.
A 10% drop-out rate will be considered for each persistence visit.
Enrolment will be terminated when the target number of subjects has been enrolled. Refer to 
Section 10.3 for a detailed description of the criteria used in the estimation of sample size.
Overview of the Recruitment Plan
Approximately 800 subjects will be enrolled in this study 
In order to take advantage of greater rates of recruitment than anticipated in individual 
centres, an over-randomisation of approximately 20% will be prepared.

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The duration of the study will be approximately 62 months per subject.
Recruitment is anticipated to take 6 months.
The actual number of subjects enrolled versus the target number of subjects will be assessed 
on a continuous basis utilising an internet-based randomisation system (SBIR).
Local personnel are responsible for monitoring and direct implementation of the recruitment 
plan.
4.2. Inclusion Criteria for Enrolment
Deviations from inclusion criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.
All subjects must satisfy ALL the following criteria at study entry:
Subjects’ parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the 
investigator, can and will comply with the requirements of the protocol (eg, completion of 
the diary cards, return for follow-up visits). 
A male or female between, and including, 12 and 14 months of age at the time of the first 
vaccination. 
Written informed consent obtained from the parent(s)/LAR(s) of the subject. 
Healthy subjects as established by medical history and clinical examination before entering 
into the study. 
Vaccination records showing the completion of the full primary vaccination schedule with 
Prevenar 13 and Diphtheria, Tetanus and Pertussis (DTP) containing vaccine according to 
local recommendations at least 5 months before the study entry.
4.3. Exclusion Criteria for Enrolment
Deviations from exclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study:
Child in care
Please refer to the Glossary of Terms for the definition of child in care.

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Use of any investigational or non-registered product (drug or vaccine) other than the study 
vaccines within 30 days preceding the first dose of study vaccine or planned use during the 
study period. 
Chronic administration (defined as more than 14 days in total) of immunosuppressants or 
other immune-modifying drugs within six months prior to the first vaccine dose. For 
corticosteroids, this will mean prednisone 0.5 mg/kg/day, or equivalent. Inhaled and topical 
steroids are allowed. 
Planned administration/administration of a vaccine not foreseen by the study protocol within 
the period starting 30 days before and ending 30 days after the dose of vaccines, with the 
exception of a licensed inactivated influenza vaccine. Measles, Mumps Rubella (MMR) 
vaccine or Measles Mumps Rubella and Varicella (MMRV) vaccine can be co-administered 
with MenACWY-TT and/or Prevenar 13. A DTPa containing vaccine can be administered 
after the last blood sampling of epoch 001 (at Visit 2 or 4 depending on the group).
Concurrently participating in another clinical study, at any time during the study period, in 
which the subject has been or will be exposed to an investigational or a non-investigational 
vaccine/product (pharmaceutical product or device). 
Previous vaccination against Neisseria meningitidis. 
Previous booster vaccination against Streptococcus pneumoniae.
Previous booster vaccination against Corynebacterium diphtheriae, Clostridium tetani and 
Bordetella pertussis. 
History of meningococcal disease. 
Any confirmed or suspected immunosuppressive or immunodeficient condition (congenital 
or secondary), including human immunodeficiency virus (HIV) infection, based on medical 
history and physical examination (no laboratory testing required)*. 
* Note: With the exception of HIV rapid testing which will be done for subjects in South 
Africa. Refer to Section 5.6.7. (Amended 02 July 2014)
Family history of congenital or hereditary immunodeficiency. 
History of any reaction or hypersensitivity, including to diphtheria toxoid, likely to be 
exacerbated by any component of the vaccines. 
Major congenital defects or serious chronic illness. 
History of any neurological disorders or seizures, including Guillain-Barré syndrome (GBS). 
History of a simple, single febrile seizure is permitted. 

Acute disease and/or fever at the time of enrolment. 

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
Fever is defined as temperature 37.5°C/99.5°F for oral, axillary or tympanic route, 
or 38.0°C/100.4°F for rectal route. The preferred route for recording temperature in 
this study will be rectal.

Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory 
infection) without fever may be enrolled at the discretion of the investigator. 

Administration of immunoglobulins and/or any blood products within the 3 months 
preceding the first dose of study vaccine or planned administration during the study 
period. 
5. CONDUCT OF THE STUDY
5.1. Regulatory and Ethical Considerations, including the Informed Consent Process
The study will be conducted in accordance with all applicable regulatory requirements.
The study will be conducted in accordance with the ICH Guideline for Good Clinical 
Practice (GCP), all applicable subject privacy requirements and the guiding principles of the 
Declaration of Helsinki (World Medical Association 1996 & 2008) as well as the general 
principles set forth in the International Ethical Guidelines for Biomedical Research Involving 
Human Subjects (Council for International Organizations of Medical Sciences 2002). 
The study has been designed and will be conducted in accordance with the ICH Harmonised 
Tripartite Guideline for clinical investigation of medicinal products in the paediatric 
population (ICH E11) and all other applicable ethical guidelines.
Pfizer will obtain favourable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study in that country.
Conduct of the study includes, but is not limited to, the following:

Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
favourable opinion/approval of study protocol and any subsequent amendments.

Subject’s parent(s)/LAR(s) informed consent.

Subject’s assent form (if applicable, age dependent on local requirements)

Investigator reporting requirements as stated in the protocol.
Pfizer will provide full details of the above procedures to the investigator, either verbally, in 
writing, or both.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from the subject's legally acceptable representative(s)/parent(s) and the subject’s 
assent, when applicable, before any study-specific activity is performed, unless a waiver of 

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informed consent has been granted by an IRB/EC.  The investigator will retain the original of 
each subject's signed consent/assent document.
Pfizer will prepare a model Informed Consent Form (ICF) and assent which will embody the 
ICH GCP and Pfizer required elements. While it is strongly recommended that this model 
ICF and assent are to be followed as closely as possible, the informed consent/assent 
requirements given in this document are not intended to pre-empt any local regulations which 
require additional information to be disclosed for informed consent to be legally effective. 
Clinical judgement, local regulations and requirements should guide the final structure and 
content of the local version of the ICF/assent. 
The investigator has the final responsibility for the final presentation of the ICF/assent, 
respecting the mandatory requirements of local regulations. The ICF generated by the 
investigator with the assistance of the sponsor’s representative must be acceptable to Pfizer
and be approved (along with the protocol, and any other necessary documentation) by the 
IRB/IEC.
Whenever consent is obtained from a subject’s legally acceptable representative/parent(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/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.
5.2. Subject Identification and Randomisation of Treatment
5.2.1. Subject Identification
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study, according to the range of subject identification numbers 
allocated to each study centre.
5.2.2. Randomisation of Treatment
5.2.2.1. Randomisation of Supplies
The randomisation of supplies within blocks will be performed at GSK Biologicals using 
MATerial EXcellence (MATEX), a program developed for use in Statistical Analysis System 
(SAS®) (Cary, NC, USA) by GSK Biologicals. Entire blocks will be shipped to the study 
centres /warehouse(s).

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To allow GSK Biologicals to take advantage of greater rates of recruitment than anticipated 
at individual centres in this multi-centre study and to thus reduce the overall study 
recruitment period, an over-randomisation of supplies will be prepared. 
5.2.2.2. Treatment Allocation to the Subject
The treatment numbers will be allocated by dose. 
5.2.2.2.1. Study Group and Treatment Number Allocation
The target will be to enrol approximately 800 eligible subjects who will be randomly 
assigned to one of the four study groups in a (1: 1: 1: 1) ratio (approximately 200 subjects in 
each group).
Allocation of the subject to a study group at the investigator site will be performed using a 
randomisation system on the Internet (SBIR). The randomisation algorithm will use a 
minimisation procedure accounting for centre, country and number of doses of Prevenar 13
received before the study start (2 or 3 doses). Minimisation factors will have equal weight in 
the minimisation algorithm.
After obtaining the signed and dated ICF from the subject’s parent(s)/LAR(s) and having 
checked the eligibility of the subject, the site staff in charge of the vaccine administration 
will access SBIR. Upon providing the subject identification number, the randomisation 
system will determine the study group and will provide the treatment number to be used for 
the first dose. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen.
When SBIR is not available, please refer to the SBIR user guide or the Study Procedures 
Manual (SPM) for specific instructions.
5.2.2.2.2. Treatment Number Allocation for Subsequent Doses
For each dose subsequent to the first dose, the study staff in charge of the vaccine 
administration will access SBIR, provide the subject identification number, and the system 
will provide a treatment number consistent with the allocated study group.
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen.
5.2.3. Allocation of Subjects to Assay Subsets 
Table 4 presents the subsets which will be used for antibody determination.

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Table 4.
Subsets (Amended 02 July 2014)
Subset 
name
Description
Definition
Estimated 
number of 
subjects
Subset 1 
Groups ACWY1d and 
ACWY2d: hSBA-MenA and 
hSBA-MenC 
The first 50% of enrolled subjects within each 
country (according to their enrolment date) of 
groups ACWY1d and ACWY2d will be tested for 
hSBA-MenA and hSBA-MenC at all blood 
sampling timepoints planned for each group (i.e. 
Visits 1, 2, 5, 6 and 7 for the ACWY1d group and 
Visits 1, 2, 4, 5, 6 and 7 for the ACWY2d group).
200 
Subset 2 
Groups ACWY1d and 
ACWY2d: hSBA-MenW and 
hSBA-MenY 
The remaining 50% of enrolled subjects within 
each country (according to their enrolment date) of 
groups ACWY1d and ACWY2d will be tested for 
hSBA-MenW-135 and hSBA-MenY at all blood 
sampling timepoints planned for each group (i.e. 
Visits 1, 2, 5, 6 and 7 for the ACWY1d group and 
Visits 1, 2, 4, 5, 6 and 7 for the ACWY2d group).
200 
Subset 3 
Groups Co-ad and PCV-13: 
OPA 3, 4, 6B, 14, 23F
The first 50% of enrolled subjects within each 
country (according to their enrolment date) of 
groups Co-ad and PCV-13 will be tested for OPA 
for pneumococcal serotypes 3, 4, 6B, 14 and 23F
at Visits 1 and 2.
200 
Subset 4 
Groups Co-ad and PCV-13: 
OPA 1, 5, 6A, 7F, 9V, 18C, 
19A, 19F
The remaining 50% of enrolled subjects within 
each country (according to their enrolment date) of 
groups Co-ad and PCV-13 will be tested for OPA 
for pneumococcal serotypes 1, 5, 6A, 7F, 9V, 18C, 
19A and 19F at Visits 1 and 2.
200 
5.3. Method of Blinding
The study will be conducted in an open manner. The study cannot be double-blind due to 
differences in the external appearance of the vaccine vials and the difference in the 
vaccination schedules in each of the four study groups.
The laboratory in charge of the laboratory testing will be blinded to the treatment, and codes 
will be used to link the subject and study (without any link to the treatment attributed to the 
subject) to each sample.
5.4. General Study Aspects
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects.
5.5. Outline of Study Procedures
An outline of the schedule of assessments to be performed in subjects during the course of 
the study is provided in Table 5 for the ACWY1d and Co-ad groups and in Table 6 for the 
ACWY2d and PCV-13 groups.

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Table 5.
List of Study Procedures for Groups ACWY1d and Co-ad
Age
12-14 
months
13-15 
months
21-23
months
24-26 
months
48-50
months
72-74 months
Epoch
001
002
003
004
Type of contact
Visit 1
Visit 2
Phone 
contact
Visit 5 
Visit 6 
Visit 7 
Timepoints
Month 0
Month 1
Month 9
Year 1
Year 3
Year 5
Sampling timepoints
Pre-
Vacc 
Month 1 
Post-Vacc 
ESFU 
Y1 Post-
Vacc 
Y3 Post-
Vacc 
Y5 Post-Vacc 
Informed consent
●
Informed assent (according to local 
requirement)
X
X
Informed consent for HIV testing #  
(Amended 02 July 2014) 
O
HIV testing # (Amended 02 July 2014) 
O
Demography
●
Inclusion/exclusion criteria
●
Medical history
●
Check medical history since last visit 
done
●
●
Vaccination history 1
●
Physical examination
O
Check contraindications
O
Check warnings and precautions
O
Pre-vaccination body temperature
●
Study group and treatment number 
allocation
O
Recording of administered treatment 
number
●
Blood sampling for antibody 
determination (approx. 5 ml)
●
●
●
●
●
Vaccine administration: MenACWY-
TT in group ACWY1d; MenACWY-
TT and Prevenar 13 in group Co-ad
●
Record timing related to 
reconstitution and vaccination of 
MenACWY-TT
●
Observation of subjects for 30 
minutes after vaccination
O
Record any concomitant 
medication/vaccination 2
●
●
●
●
●
●
Record any intercurrent medical 
conditions 3
●
●
●
●
●
Distribution of diary cards
O
Recording of solicited adverse events 
(Days 0–3)
●
Recording of non-serious adverse 
events within 30 days post-
vaccination
●
●
Return of diary cards
O
Diary card transcription by 
investigator
O

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Table 5.
List of Study Procedures for Groups ACWY1d and Co-ad
Age
12-14 
months
13-15 
months
21-23
months
24-26 
months
48-50
months
72-74 months
Epoch
001
002
003
004
Type of contact
Visit 1
Visit 2
Phone 
contact
Visit 5 
Visit 6 
Visit 7 
Timepoints
Month 0
Month 1
Month 9
Year 1
Year 3
Year 5
Sampling timepoints
Pre-
Vacc 
Month 1 
Post-Vacc 
ESFU 
Y1 Post-
Vacc 
Y3 Post-
Vacc 
Y5 Post-Vacc 
Recording of serious adverse events 4
●
●
●
Recording of SAEs related to study 
vaccine administration and any event 
related to lack of vaccine efficacy 4
● 
● 
● 
●
●
●
Recording of SAEs related to study 
participation5
●
●
●
●
●
●
Reporting of Guillain-Barré 
syndrome6
●
●
●
Reporting of New Onset of Chronic 
Illnesses 7
●
●
●
Study Conclusion 8
●
Note: The double-line border following Month 1 and 9 and Year 1 and 3 indicates the analyses which will be 
performed on all data (i.e. data that are as clean as possible) obtained up to Month 1 and 9 and Year 1 
and 3.
Vacc: vaccination, ESFU: Extended Safety Follow-Up.
● is used to indicate a study procedure that requires documentation in the individual eCRF.
O is used to indicate a study procedure that does not require documentation in the individual eCRF.
X Informed assent: as applicable according to local requirement, verbal or signed informed assent should be 
obtained at Visit 6 or Visit 7.
# HIV rapid testing is mandatory only for subjects from South Africa, prior to their enrolment in the study. If 
source documentation shows that the subject is HIV negative based on previous testing at other facilities, 
no additional HIV rapid testing is needed, unless clinically indicated by the investigator. Refer to 
Section 5.6.7. (Amended 02 July 2014).
1
All vaccines administered since birth have to be recorded.
2
Up to Visit 2, all non-study vaccines administered within 30 days preceding the study vaccine and any 
medications/non-study vaccinations taken on Days 0-30 following vaccination (day of vaccination is 
considered Day 0) will be recorded. Throughout the whole study, any investigational or non-registered 
medication or vaccine, any meningococcal vaccine, any pneumococcal vaccine and any medication to treat 
SAEs that are required to be reported per protocol will be recorded.
3
These conditions include: any confirmed or suspected condition that has the capability of altering the 
subject’s immune response (e.g. intercurrent lymphopenia, the occurrence of meningococcal or 
pneumococcal disease, any confirmed or suspected immunosuppressive or immunodeficient condition and 
diagnosis of serious chronic illness) throughout the study. Report using the Non-Serious Adverse Events
and Intercurrent Medical Conditions eCRF form.
4
Occurrences of meningococcal or pneumococcal diseases should be reported as SAEs and documented in 
the AE report in the eCRF.
5 
This will also include SAE(s) leading to the withdrawal of the subject from the study.
6
In the event of Guillain-Barré Syndrome (GBS) subjects’ parents/LARs should be contacted to obtain 
clinical details as outlined in the ‘Potential immune mediated disorders: standard questionnaires and list of 
preferred terms’. All occurrences of GBS have to be reported as SAEs.
7 
New Onset of Chronic Illnesses (NOCIs) (e.g. auto-immune disorders, allergies, type 1 diabetes, asthma) 
will be recorded until the ESFU phone contact and will be reported either as an AE or as an SAE as 
appropriate.
8
To be completed for all subjects who are enrolled in the study.

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Table 6.
List of study procedures for groups ACWY2d and PCV-13
Age
12-14 
months
13-15 
months
14-16 
months
15-17 
months
21-23 
months
26-28 
months
50-52
months
74-76 months
Epoch
001
002
003
004
Type of contact
Visit 1
Visit 2
Visit 3 Visit 4 Phone 
contact
Visit 5 
Visit 6 
Visit 7
Timepoints
Month 
0
Month 
1
Month 
2
Month 
3
Month 
9
Year 1
Year 3
Year 5
Sampling timepoints
Pre-
Vacc 
Month 
1 Post-
Vacc 
Month 
2 Post-
Vacc 
Month 
3 Post-
Vacc 
ESFU Y1 Post-
Vacc 
Y3 Post-
Vacc 
Y5 Post-Vacc 
Informed consent
●
Informed assent (according 
to local requirement)
X
X
Demography
●
Informed consent for HIV 
testing # (Amended 02 
July 2014)
O 
HIV testing # (Amended 
02 July 2014)
O 
Inclusion/exclusion criteria 
●
Medical history 
●
Check medical history 
since last visit done
●
●
Vaccination history 1
●
Physical examination 
O
Check contraindications 
O
O
Check warnings and 
precautions 
O
O
Pre-vaccination body 
temperature 
●
●
Study group and treatment 
number allocation 
O
Treatment number 
allocation for subsequent 
doses 
O
Recording of administered 
treatment number 
●
●
Blood sampling for 
antibody determination 
(approx. 5 ml) 
●
●
●
●
●
●
Vaccine administration:
MenACWY-TT in group 
ACWY2d and Prevenar 
13 in group PCV-13
●

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Table 6.
List of study procedures for groups ACWY2d and PCV-13
Age
12-14 
months
13-15 
months
14-16 
months
15-17 
months
21-23 
months
26-28 
months
50-52
months
74-76 months
Epoch
001
002
003
004
Type of contact
Visit 1
Visit 2
Visit 3 Visit 4 Phone 
contact
Visit 5 
Visit 6 
Visit 7
Timepoints
Month 
0
Month 
1
Month 
2
Month 
3
Month 
9
Year 1
Year 3
Year 5
Sampling timepoints
Pre-
Vacc 
Month 
1 Post-
Vacc 
Month 
2 Post-
Vacc 
Month 
3 Post-
Vacc 
ESFU Y1 Post-
Vacc 
Y3 Post-
Vacc 
Y5 Post-Vacc 
Vaccine administration 
(MenACWY-TT in groups 
ACWY2d and PCV13)
●
Record timing related to 
reconstitution and 
vaccination of 
MenACWY-TT 
●2
●
Observation of subjects for 
30 minutes after 
vaccination 
O
O
Record any concomitant 
medication/vaccination 3
●
●
●
●
●
●
●
●
Record any intercurrent 
medical conditions 4
●
●
●
●
●
●
●
Distribution of diary cards 
O
O
Recording of solicited 
adverse events (Days 0–3) 
●
●
Recording of non-serious 
adverse events within 30 
days post-vaccination 
●
●
●
●
Return of diary cards 
O
O
Diary card transcription by 
investigator 
O
O
Recording of serious 
adverse events 5
●
●
●
●
●
Recording of SAEs related 
to study vaccine 
administration and any 
event related to lack of 
vaccine efficacy 5
● 
● 
● 
● 
● 
●
●
●
Recording of SAEs related 
to study participation 6
●
●
●
●
●
●
●
●
Reporting of Guillain-
Barré syndrome 7
●
●
●
●
●

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Table 6.
List of study procedures for groups ACWY2d and PCV-13
Age
12-14 
months
13-15 
months
14-16 
months
15-17 
months
21-23 
months
26-28 
months
50-52
months
74-76 months
Epoch
001
002
003
004
Type of contact
Visit 1
Visit 2
Visit 3 Visit 4 Phone 
contact
Visit 5 
Visit 6 
Visit 7
Timepoints
Month 
0
Month 
1
Month 
2
Month 
3
Month 
9
Year 1
Year 3
Year 5
Sampling timepoints
Pre-
Vacc 
Month 
1 Post-
Vacc 
Month 
2 Post-
Vacc 
Month 
3 Post-
Vacc 
ESFU Y1 Post-
Vacc 
Y3 Post-
Vacc 
Y5 Post-Vacc 
Reporting of New Onset of 
Chronic Illnesses 8
●
●
●
●
●
Study Conclusion 9
●
Note: The double-line border following Month 3 and 9 and Year 1 and 3 indicates the analyses which will be 
performed on all data (i.e. data that are as clean as possible) obtained up to Month 3 and 9 and Year 1 
and 3.
Vacc: vaccination, ESFU: Extended Safety Follow-Up.
● is used to indicate a study procedure that requires documentation in the individual eCRF.
○ is used to indicate a study procedure that does not require documentation in the individual eCRF.
X Informed assent: as applicable according to local requirement, verbal or signed informed assent should be 
obtained at Visit 6 or Visit 7.
# HIV rapid testing is mandatory only for subjects from South Africa, prior to their enrolment in the study. If 
source documentation shows that the subject is HIV negative based on previous testing at other facilities, 
no additional HIV rapid testing is needed, unless clinically indicated by the investigator. Refer to 
Section 5.6.7. (Amended 02 July 2014).
1
All vaccines administered since birth have to be recorded.
2
Only for group ACWY2d.
3 
Up to Visit 4, all non-study vaccines administered during the period starting 30 days preceding the first 
dose of study vaccine and ending 30 days after the last dose of study vaccine and any medications taken 
from the day of each vaccination until 30 days later will be recorded. Throughout the whole study, any 
investigational or non-registered medication or vaccine, any meningococcal vaccine, any pneumococcal 
vaccine and any medication to treat SAEs that are required to be reported per protocol will be recorded.
4
These conditions include: any confirmed or suspected condition that has the capability of altering the 
subject’s immune response (e.g. intercurrent lymphopenia, the occurrence of meningococcal or 
pneumococcal disease, any confirmed or suspected immunosuppressive or immunodeficient condition and 
diagnosis of serious chronic illness) throughout the study. Report using the Non-Serious Adverse Events 
and Intercurrent Medical Conditions eCRF form.
5
Occurrences of meningococcal or pneumococcal diseases should be reported as SAEs and documented in 
the AE report in the eCRF.
6
This will also include SAE(s) leading to the withdrawal of the subject from the study.
7
In the event of Guillain-Barré Syndrome (GBS) subjects’ parents/LARs should be contacted to obtain 
clinical details as outlined in the ‘Potential immune mediated disorders: standard questionnaires and list of 
preferred terms’. All occurrences of GBS have to be reported as SAEs.
8
New Onset of Chronic Illnesses (NOCIs) (e.g. auto-immune disorders, allergies, type 1 diabetes, asthma) 
will be recorded until the ESFU phone contact and will be reported either as an AE or as an SAE as 
appropriate.
9
To be completed for all subjects who are enrolled in the study.

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It is the investigator’s responsibility to ensure that the intervals between visits are strictly 
followed. These intervals determine each subject’s evaluability in the according-to-protocol 
(ATP) analyses.
The intervals between study visits are presented in Table 7 for the ACWY1d and Co-ad 
groups and in Table 8 for the ACWY2d and PCV-13 groups. Visits refer to the day of 
vaccination.
Table 7.
Intervals Between Study Visits for Groups ACWY1d and Co-ad
Interval
Optimal length of interval
Allowed interval 1,2
Date of birth first vaccination
12-14 months
12-14 months
Visit 1 Visit 2 
30 days
21 - 48 days
Visit 1 Phone contact 
270 days
270 - 300 days
Visit 1 Visit 5 
12 months
44 - 60 weeks
Visit 1 Visit 6 
36 months
148 - 164 weeks
Visit 1 Visit 7 
60 months
252 - 268 weeks
1
Whenever possible the investigator should arrange study visits within this interval.
2
Subjects will not be eligible for inclusion in the ATP cohort for analysis of immunogenicity or persistence 
Year 1, 3 or 5 if they make the study visit outside this interval (see Section 10.4 for more details). 
If a subject returns for the Visit 2 blood draw prior to completion of the 31-day safety follow-up period, the 
subject should continue to record this information on the diary card until 31 days post-vaccination and mail 
the diary card to the site. The investigator will make an attempt to obtain this information as soon as 
possible after the 31-day follow-up period if it is not mailed in.
Table 8.
Intervals Between Study Visits for Groups ACWY2d and PCV-13
Interval
Optimal length of interval
Allowed interval 1,2
Date of birth first vaccination
12-14 months
12-14 months
Visit 1 Visit 2 
30 days
21 days - 48 days
Visit 1 Visit 3 
60 days
60 days - 90 days
Visit 3 Visit 4 
30 days
21 days  - 48 days
Visit 1 Phone contact 
270 days
270 - 300 days
Visit 3 Visit 5 
12 months
44 - 60 weeks
Visit 3 Visit 6 
36 months
148 - 164 weeks
Visit 3 Visit 7 
60 months
252 - 268 weeks
1
Whenever possible the investigator should arrange study visits within this interval.
2
Subjects will not be eligible for inclusion in the ATP cohort for analysis of immunogenicity or persistence 
Year 1, 3 or 5 f they make the study visit outside this interval (see Section 10.4 for more details). 
If a subject returns for the Visit 2 blood draw prior to completion of the 31-day safety follow-up period, the 
subject should continue to record this information on the diary card until 31 days post-vaccination and mail 
the diary card to the site. The investigator will make an attempt to obtain this information as soon as 
possible after the 31-day follow-up period if it is not mailed in.

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5.6. Detailed description of Study Procedures
5.6.1. Informed Consent
The signed informed consent of the subject’s parent(s)/LAR(s) must be obtained before study 
participation. For children in South Africa, a signed informed consent of the subject’s 
parent(s)/LAR(s) for HIV testing must be obtained before HIV rapid test is performed
(Amended 02 July 2014).
The informed assent of the subject below the age of consent (i.e., minor) should be obtained 
in addition to the signed informed consent by his/her parent(s)/LAR(s) according to local 
rules and regulations.
Refer to Section 5.1 for the requirements on how to obtain informed consent.
5.6.2. Check Inclusion and Exclusion Criteria
Check all inclusion and exclusion criteria as described in Section 4.2 and Section 4.3 before 
enrolment. 
5.6.3. Collect Demographic Data
Record demographic data such as date of birth, gender and race/ethnicity in the subject’s 
eCRF.
5.6.4. Medical History
Obtain the subject’s medical history by interview and/or review of the subject’s medical 
records and record any pre-existing conditions or signs and/or symptoms present in a subject 
prior to the first study vaccination in the eCRF.
5.6.5. Vaccination History
Vaccination history of any vaccines received since birth has to be recorded as shown on the 
subject’s vaccination record. 
5.6.6. Physical Examination 
Perform a physical examination of the subject, including assessment of length and weight, at 
the first vaccination visit. 
Treatment of any abnormality observed during physical examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate health 
care provider. 
5.6.7. HIV Rapid Testing (Only in South Africa) (Amended 02 July 2014)
HIV rapid testing will be performed prior to enrolment for children in South Africa, to ensure 
that only HIV-negative subjects are enrolled in the study. Participants who were previously 
screened HIV positive will be excluded. Any HIV-negative subjects with documented HIV
negativity will not need to be re-tested, unless clinically indicated by the investigator.

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The test will be conducted on a sample of whole blood by finger stick. Clinically healthy 
babies will be screened with 2 rapid HIV tests. If any test is positive participant will not be 
enrolled into the study and will be referred to referral networks for a confirmatory HIV test 
by PCR and to appropriate health care provider for treatment and supportive services.
Positive HIV results should be presented by the investigator/designee in person to the 
parent(s)/LAR(s). General information about the retesting and available treatment must be 
presented to the parent(s).
HIV informed consent and HIV test results should be recorded in the subject’ source 
documents but will not be recorded in the eCRF.
5.6.8. Check Contraindications, Warnings and Precautions to Vaccination 
Contraindications, warnings and precautions to vaccination must be checked at the beginning 
of each vaccination visit. Refer to Section 6.5 and Section 6.6 for more details. 
5.6.9. Assess Pre-vaccination Body Temperature
The axillary, rectal, oral or tympanic body temperature of all subjects needs to be measured 
prior to any study vaccine administration. The preferred route for recording temperature in 
this study will be rectal. If the subject has fever [fever is defined as rectal temperature 
38°C/axillary temperature 37.5°C/oral temperature 37.5°C/tympanic temperature on oral 
setting 37.5°C/tympanic temperature on rectal setting 38°C] on the day of vaccination, the 
vaccination visit will be rescheduled within the allowed interval for this visit (see Table 7 for 
the ACWY1d and Co-ad groups and Table 8 for the ACWY2d and PCV-13 groups).
5.6.10. Study Group and Treatment Number Allocation
Study group and treatment number allocation will be performed as described in Section 5.2.2. 
The number of each administered treatment must be recorded in the eCRF.
5.6.11. Sampling
Refer to the Module on Biospecimen Management in the SPM for detailed instructions for 
the collection, handling and processing of the samples.
5.6.11.1. Blood Sampling for Immune Response Assessments 
Blood samples will be taken during certain study visits as specified in Section 5.5 List of 
Study Procedures.
A volume of approximately 5 mL of whole blood (to provide approximately 1.8 mL of 
serum) should be drawn from all subjects for antibody determination at each pre-defined 
timepoint. After centrifugation, serum samples should be kept at approximately 
-20°C/ -4°F or below until shipment. Refer to the SPM for more details on sample storage 
conditions.

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5.6.12. Study Vaccine(S) Administration
After completing the prerequisite procedures prior to vaccination, the study vaccine(s)
(MenACWY-TT and/or Prevenar 13) will be administered intramuscularly (IM) in the 
anterolateral thigh (left side for MenACWY-TT and right side for Prevenar 13). If the 
deltoid muscle size is adequate, the vaccine can be administered into the deltoid.
Note: To comply with the national immunization schedule, subjects in the ACWY1d and 
ACWY2d groups will receive the booster dose of Prevenar 13 as follows:

ACWY1d group: the booster dose of Prevenar 13 has to be administered after Visit 2. 

ACWY2d group: the booster dose of Prevenar 13 has to be administered between the 
2 doses of MenACWY-TT (after the Visit 2 blood sampling up to 30 days before the 
second dose of MenACWY-TT) or after Visit 4.
These doses of Prevenar 13 will be considered as non-investigational vaccines and 
should be administered according to the Summary of Product Characteristics.
Refer to Section 6.3 for detailed description of the vaccines administration procedure. If 
the investigator or delegate determines that the subject’s health on the day of vaccination 
temporarily precludes vaccine administration, the visit will be rescheduled within the 
allowed interval for this visit (refer to Table 7 for the ACWY1d and Co-ad groups and to 
Table 8 for the ACWY2d and PCV-13 groups).
The timing related to reconstitution and vaccination of MenACWY-TT will be recorded in 
the eCRF.
The subjects will be observed closely for at least 30 minutes following the administration of 
the vaccine(s), with appropriate medical treatment readily available in case of anaphylaxis.
5.6.13. Check and Record Concomitant Medication/Vaccination and Intercurrent 
Medical Conditions 
Concomitant medication/vaccination must be checked and recorded in the eCRF as described 
in Section 6.7.
Intercurrent medical conditions must be checked and recorded in the eCRF as described in 
Section 6.8.
5.6.14. Recording of AEs and SAEs
Refer to Section 8.2 for procedures for the investigator to record adverse events (AEs) and
SAEs. Refer to Section 8.3 for guidelines on how to submit SAE reports to Pfizer.
The subjects’ parent(s)/LAR(s) will be instructed to contact the investigator immediately 
should the subjects manifest any signs or symptoms they perceive as serious. 

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
At each vaccination visit, diary cards will be provided to the subject’s parent(s)/LAR(s). 
The subject’s parent(s)/LAR(s) will record body (rectal) temperature and any solicited 
local/general AEs (i.e. on the day of vaccination and during the next three days) or any 
unsolicited AEs (i.e. on the day of vaccination and during the next 30 days occurring 
after vaccination). The subject’s parent(s)/LAR(s) will be instructed to return the 
completed diary card to the investigator at the next study visit.

Collect and verify completed diary cards during discussion with the subject’s 
parent(s)/LAR(s) on Visit 2 for the ACWY1d and Co-ad groups and Visits 2 and 4 for the 
ACWY2d and PCV-13 groups.

Any unreturned diary cards will be sought from the subject’s parent(s)/LAR(s) through 
telephone call(s) or any other convenient procedure. The investigator will transcribe the 
collected information into the eCRF in English.
5.6.15. Recording of NOCIs and GBS
Please refer to Section 8.2 for procedures for the investigator to record GBS and NOCIs. 
Refer to Section 8.3 for guidelines on how to report GBS and NOCIs.
In the event of GBS, subject’s parent(s)/LAR(s) should be contacted to obtain clinical details 
as outlined in the ‘Potential immune mediated disorders: standard questionnaires and list of 
preferred terms’. All occurrences of GBS have to be reported as SAE(s).
NOCIs (e.g. auto-immune disorders, asthma, type 1 diabetes, allergies) will be reported as 
AE or SAE as appropriate
5.6.16. Study Conclusion
The investigator will:

review data collected to ensure accuracy and completeness

complete the Study Conclusion screen in the eCRF.
5.7. Biological Sample Handling and Analysis
Refer to the SPM for details on biospecimen management (handling, storage and shipment).
See Section 5.6.11.1 for a brief description of the procedure for collection, preparation and 
storage of serum samples.
Samples will not be labelled with information that directly identifies the subject but will be 
coded with the identification number for the subject (subject number). 
Under the following circumstances, additional testing on the samples may be performed by 
Pfizer outside the scope of this protocol:

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
Collected samples may be used in other assays, for test improvement or development 
of analytical methods related to the study vaccines and its constituents or the disease 
under study. 

Collected samples may be used for purposes related to the quality assurance of data 
generated linked to the study vaccines or the disease under study, such as for 
maintenance of assays described in this protocol and comparison between analytical 
methods and/or laboratories.
Information on further investigations and their rationale can be obtained from Pfizer. 
Any sample testing will be done in line with the consent of the individual subject’s 
parent(s)/LAR(s). 
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s). 
If additional testing is performed, the marker priority ranking given in Section 5.7.4 may be 
changed.
Collected samples will be stored for a maximum of 15 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed and 
agreed with Pfizer.
5.7.1. Use of Specified Study Materials
When materials are provided by Pfizer or designee, it is MANDATORY that all clinical 
samples (including serum samples) be collected and stored exclusively using those materials 
in the appropriate manner. The use of other materials could result in the exclusion of the 
subject from the ATP analysis (See Section 10.4 for the definition of study cohorts/ data sets 
to be analysed). The investigator must ensure that his/her personnel and the laboratory(ies) 
under his/her supervision comply with this requirement. Refer to the Module on Clinical 
Trial Supplies in the SPM.
5.7.2. Biological Samples
Table 9 presents the biological samples to be collected in the study.
Table 9.
Biological samples (Amended 02 July 2014)
Sample type
Quantity
Unit
Time point
Whole venous
blood
Approximately 
0.05 (two drops)
ml
Children in South Africa only, for HIV rapid test1
Visit 1 (Pre-Vacc)

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Table 9.
Biological samples (Amended 02 July 2014)
Sample type
Quantity
Unit
Time point
Whole venous 
blood 
Approximately 5
ml
Groups ACWY1d and Co-ad:
Visit 1 (Pre-Vacc), Visit 2 (Month 1 Post-Vacc), Visit 5 (Y1 
Post-Vacc), Visit 6 (Y3 Post-Vacc) and Visit 7 (Y5 Post-Vacc)
Groups ACWY2d and PCV-13: 
Visit 1 (Pre-Vacc), Visit 2 (Month 1 Post-Vacc), Visit 4 (Month 
3 Post-Vacc), Visit 5 (Y1 Post-Vacc), Visit 6 (Y3 Post-Vacc) 
and Visit 7 (Y5 Post-Vacc)
1 If source documentation shows that the subject is HIV negative based on previous testing at other facilities, no 
additional HIV rapid testing is needed, unless clinically indicated by the investigator. Refer to Section 5.6.7.
5.7.3. Laboratory Assays
Please refer to APPENDIX A for a detailed description of the assays performed in the study. 
Please refer to APPENDIX B for the address of the clinical laboratories used for sample 
analysis.
Approximately 5 mL of blood (to provide approximately 1.8 mL of serum) will be collected 
from the subjects of the ACWY1d and Co-ad groups at Visits 1, 2, 5, 6 and 7 and from 
subjects of the ACWY2d and PCV-13 groups at Visits 1, 2, 4, 5, 6 and 7. A summary of the 
laboratory assays to be performed on the blood samples is presented in Table 10.
Table 10.
Humoral Immunity (Antibody determination) (Amended 02 July 2014)
System
Component
Method
Kit / 
Manufacturer
Cut-
off
Unit
Laboratory*
Humoral Neisseria meningitidis 
Serogroup A L10 3125 Ab 
Serum 
Bactericidal 
Assay using 
rabbit 
complement
NA 
8 
1/dilution PHE
Humoral Neisseria meningitidis 
Serogroup C L3v C11 Ab
Serum 
Bactericidal 
Assay using 
rabbit 
complement
NA 
8 
1/dilution PHE
Humoral Neisseria meningitidis 
Serogroup W L3v 
MP01240070 Ab 
Serum 
Bactericidal 
Assay using 
rabbit 
complement
NA 
8 
1/dilution PHE
Humoral Neisseria meningitidis 
Serogroup Y L3v S1975 
Ab 
Serum 
Bactericidal 
Assay using 
rabbit 
complement
NA 
8 
1/dilution PHE
Humoral Neisseria meningitidis 
Serogroup A L10 3125 Ab 
BAC using 
human 
complement
NA 
4 
1/DIL 
Neomed

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Table 10.
Humoral Immunity (Antibody determination) (Amended 02 July 2014)
System
Component
Method
Kit / 
Manufacturer
Cut-
off
Unit
Laboratory*
Humoral Neisseria meningitidis 
Serogroup C L3v C11 Ab 
BAC using 
human
complement
NA 
4 
1/DIL 
Neomed
Humoral Neisseria meningitidis 
Serogroup W L3v 
MP01240070 Ab 
BAC using 
human 
complement
NA 
4 
1/DIL 
Neomed
Humoral Neisseria meningitidis 
Serogroup Y L3v S1975 
Ab 
BAC using 
human 
complement
NA 
4 
1/DIL 
Neomed
Humoral Streptococcus 
pneumoniae.Polysaccharide 
01 Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
03 Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
04 Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
05 Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
06A Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
06B Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
07F Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
09V Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
14 Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
18C Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
19A Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
19F Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health
Humoral Streptococcus 
pneumoniae.Polysaccharide 
23F Ab.IgG 
Enzyme Linked 
Immuno Sorbent 
Assay 
NA 
0.15 µg/ml 
Institute of Child 
Health

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Table 10.
Humoral Immunity (Antibody determination) (Amended 02 July 2014)
System
Component
Method
Kit / 
Manufacturer
Cut-
off
Unit
Laboratory*
Humoral Streptococcus pneumoniae 
Serotype 01/37 Brugmann 
Hospital Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 03/1 Statens 
Serum Institut Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 04/2656 
Brugmann Hospital Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 05 Ambrose-
Statens Serum Institut Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 06A Centers for 
Disease Control Ab
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 06B/DS2212/94 
Centers for Disease Control 
Ab
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 07F/46 Brugmann 
Hospital Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 09V/112 161/95 
Statens Serum Institut Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 14/58 Brugmann 
Hospital Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 18C/4593/40 
Statens Serum Institut Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 19A/DB18 
Kansanterveyslaitos 
Folkhalsoinstitutet Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 19F/2737 
Brugmann Hospital Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
Humoral Streptococcus pneumoniae 
Serotype 23F Mac-Statens 
Serum Institut Ab 
OPS 
NA 
8 
1/DIL 
Institute of Child 
Health
* Refer to APPENDIX B for the laboratory addresses.
BAC: Bactericidal Assay; DIL: Dilution; NA: Not applicable; OPS: Opsonophagocytic Assay; 
PHE: Public Health England

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5.7.4. Biological Samples Evaluation
5.7.4.1. Immunological Read-outs
Table 11 presents the immunological read-outs.
Table 11.
Immunological Read-outs (Amended 02 July 2014)
Blood sampling timepoint
Group/
Subset*
No. 
subjects
Component
Type of contact 
and timepoint
Sampling 
timepoint
Visit 1 (Month 0)
Pre-Vacc
Co-ad
PCV-13
400
rSBA-MenA
rSBA-MenC
rSBA-MenW-135
rSBA-MenY
ELISA for pneumococcal serotypes 1, 3, 4, 5, 
6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F
Visit 1 (Month 0)
Pre-Vacc
ACWY1d
ACWY2d
400
rSBA-MenA
rSBA-MenC
rSBA-MenW-135
rSBA-MenY
Visit 1 (Month 0)
Pre-Vacc
Subset 1
200
hSBA-MenA, hSBA-MenC
Visit 1 (Month 0)
Pre-Vacc
Subset 2
200
hSBA-MenW-135, hSBA-MenY
Visit 1 (Month 0)
Pre-Vacc
Subset 3
200
OPA for pneumococcal serotypes 3, 4, 6B, 14 
and 23F
Visit 1 (Month 0)
Pre-Vacc
Subset 4
200
OPA for pneumococcal serotypes 1, 5, 6A, 7F, 
9V, 18C, 19A and 19F
Visit 2 (Month 1)
Mth 1 Post-
Vacc
Co-ad
200
rSBA-MenA
rSBA-MenC
rSBA-MenW-135
rSBA-MenY
ELISA for pneumococcal serotypes 1, 3, 4, 5, 
6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F
Visit 2 (Month 1)
Mth 1 Post-
Vacc
PCV-13
200
ELISA for pneumococcal serotypes 1, 3, 4, 5, 
6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F
Visit 2 (Month 1)
Mth 1 Post-
Vacc
ACWY1d
ACWY2d
400
rSBA-MenA
rSBA-MenC
rSBA-MenW-135
rSBA-MenY
Visit 2 (Month 1)
Mth 1 Post-
Vacc
Subset 1
200
hSBA-MenA, hSBA-MenC
Visit 2 (Month 1)
Mth 1 Post-
Vacc
Subset 2
200
hSBA-MenW-135, hSBA-MenY
Visit 2 (Month 1)
Mth 1 Post-
Vacc
Subset 3
200
OPA for pneumococcal serotypes 3, 4, 6B, 14 
and 23F
Visit 2 (Month 1)
Mth 1 Post-
Vacc
Subset 4
200
OPA for pneumococcal serotypes 1, 5, 6A, 7F, 
9V, 18C, 19A and 19F
Visit 4 (Month 3)
Mth 3 Post-
Vacc
PCV-13
ACWY2d
400
rSBA-MenA
rSBA-MenC
rSBA-MenW-135
rSBA-MenY

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Table 11.
Immunological Read-outs (Amended 02 July 2014)
Blood sampling timepoint
Group/
Subset*
No. 
subjects
Component
Type of contact 
and timepoint
Sampling 
timepoint
Visit 4 (Month 3)
Mth 3 Post-
Vacc
Subset 1
(Group 
ACWY2d 
only)
100
hSBA-MenA, hSBA-MenC
Visit 4 (Month 3)
Mth 3 Post-
Vacc
Subset 2
(Group 
ACWY2d 
only)
100
hSBA-MenW-135, hSBA-MenY
Visit 5 (Year 1)
Y 1 Post-Vacc
All
576
rSBA-MenA
rSBA-MenC
rSBA-MenW-135
rSBA-MenY
Visit 5 (Year 1)
Y 1 Post-Vacc
Subset 1
144
hSBA-MenA, hSBA-MenC
Visit 5 (Year 1)
Y 1 Post-Vacc
Subset 2
144
hSBA-MenW-135, hSBA-MenY
Visit 6 (Year 3)
Y 3 Post-Vacc
All
516
rSBA-MenA
rSBA-MenC
rSBA-MenW-135
rSBA-MenY
Visit 6 (Year 3)
Y 3 Post-Vacc
Subset 1
129
hSBA-MenA, hSBA-MenC
Visit 6 (Year 3)
Y 3 Post-Vacc
Subset 2
129
hSBA-MenW-135, hSBA-MenY
Visit 7 (Year 5)
Y5 Post-Vacc
All
468
rSBA-MenA
rSBA-MenC
rSBA-MenW-135
rSBA-MenY
Visit 7 (Year 5)
Y5 Post-Vacc
Subset 1
117
hSBA-MenA, hSBA-MenC
Visit 7 (Year 5)
Y5 Post-Vacc
Subset 2
117
hSBA-MenW-135, hSBA-MenY
Refer to Section 5.2.3 for the definition of the subsets and method of selection.
In case of insufficient blood sample volume to perform assays for all antibodies, the samples 
will be analysed according to following priority ranking:
rSBA-MenC > rSBA-MenA > rSBA-MenW-135 > rSBA-MenY > ELISA for pneumococcal 
serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F > hSBA-MenC > hSBA-
MenA > hSBA-MenW-135 > hSBA-MenY > OPA for pneumococcal serotypes 1, 3, 4, 5, 
6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

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5.7.5. Immunological Correlates of Protection
Antibodies against N. meningitidis serogroups A, C, W-135 and Y
Bactericidal antibodies are recognised as surrogate markers of protection. An rSBA cut-off 
of 1:8 was shown to be the most consistent with observed efficacy at 4 weeks post 
vaccination with the meningococcal serogroup C conjugate vaccine in post-licensure efficacy 
estimates in the UK [Andrews, 2003]. The established correlate of protection for the 
hSBA-MenC assay using human serum as the exogenous complement source is 1:4 
[Goldschneider, 1969; Borrow, 2005]. Even though no correlate of protection has been 
established for serogroups A, W-135 and Y, it is common practice to extend the 1:8 cut-off 
for rSBA-MenA, rSBA-MenW-135 and rSBA-MenY and the 1:4 cut-off for hSBA-MenA, 
hSBA-MenW-135 and hSBA-MenW-135 [CDC, 2006].
Antibodies against S. pneumonia serotypes
No immunological correlate of protection has been clearly established so far for the 
pneumococcal antigens. Individual immunology assay results will however be 
communicated to the study investigator as soon as they become available and in any case no 
later than 12 months after Last Subject Last Visit (LSLV of the study).
Communication of individual immunogenicity assay results to study investigator
The immunological assay results will be communicated to the investigator.
The following thresholds will be considered at one month after the dose of MenACWY-TT 
in the ACWY1d, Co-ad and PCV-13 groups and at one month after the second dose of 
MenACWY-TT in the ACWY2d group:
rSBA-MenC < 1:8,
hSBA-MenC < 1:4.
Although no correlate of protection is established for N. meningitidis serogroups A, W-135 
and Y, individual serology assay results for SBA testing using rabbit and human complement 
for these 3 antigens will also be provided to the study investigator according to the same 
threshold.
Investigators will be provided with immunogenicity results for subjects identified as 
non-responders shortly after the database on the data collected up to Visit 4 has been frozen. 
Immunogenicity results of all subjects will be provided when the individual listings of the 
statistical report have been released after the analysis of the data collected up to Visit 4.
For the study subjects identified as non-responders, it remains the responsibility of the study 
investigator in charge of the subject’s clinical management to determine the medical need for 
re-vaccination and to re-vaccinate the subjects as per local/regional practices.

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6. STUDY VACCINES AND ADMINISTRATION
6.1. Description of Study Vaccines
The MenACWY-TT candidate vaccine to be used has been developed and manufactured by 
GSK Biologicals. The MenACWY-TT vaccine was acquired by Pfizer on 01 October 2015. 
The Quality Control Standards and Requirements for the candidate vaccine are described in 
separate Quality Assurance documents (eg, release protocols, certificate of analysis) and the 
required approvals have been obtained. 
The vaccines are labelled and packed according to applicable regulatory requirements.
Commercial vaccines are assumed to comply with the specifications given in the 
manufacturer’s Summary of Product Characteristics.
Table 12 presents the description of the study vaccines.
Table 12.
Study Vaccines
Treatment 
name
Vaccine/product 
name
Formulation
Presentation
Volume to be 
administered*
Number of 
doses
MenACWY-
TT
MenACWY-TT 
PSA=5μg TT; 
PSC=5μg TT; 
PSW₁₃₅=5μg TT; 
PsY=5μg TT; 
TT~=44μg 
Lyophilised, 
white pellet to be 
reconstituted 
with saline 
diluent 
0.5 ml
1 dose for the 
ACWY1d, 
Co-ad and 
PCV-13 groups 
and 2 doses for 
the ACWY2d 
group
NaCl 
NaCl=150mM 
Liquid form in 
prefilled syringe 
PCV-13
Prevenar 13
2.2 μg of each 
pneumococcal PS 
for serotypes 1, 3, 
4, 5, 6A, 7F, 9V, 
14, 18C, 19A, 19F, 
23F and 4.4 μg for 
serotype 6B 
conjugated to 
CRM197 carrier 
protein. 0.125 mg 
aluminium as 
aluminium 
phosphate 
Suspension in 
pre-filled syringe 
0.5 ml
1 dose for the 
Co-ad and 
PCV-13 groups
*Refer to the SPM for the volume after reconstitution.
6.2. Storage and Handling of Study Vaccines
The study vaccines must be stored at the respective label storage temperature conditions in a 
safe and locked place. Access to the storage space should be limited to authorized study 
personnel. The storage conditions will be assessed during pre-study activities under the 
responsibility of the sponsor study contact. The storage temperature should be continuously 
monitored with calibrated (if not validated) temperature monitoring device(s) and recorded. 

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Refer to the Module on Clinical Trial Supplies in the SPM for more details on storage of the 
study vaccines.
Temperature excursions must be reported in degree Celsius.  
Any temperature excursion outside the range of 0.0 to +8.0C (for +2 to +8°C/+36 to +46°F 
label storage condition) impacting investigational medicinal products (IMPs) must be 
reported in the appropriate (electronic) temperature excursion decision form ([e]TDF). The 
impacted IMPs must not be used and must be stored in quarantine at label temperature 
conditions until usage approval has been obtained from the sponsor.
In case of temperature excursion below +2.0°C down to 0.0°C impacting IMP(s) there is no 
need to report in (e)TDF, but adequate actions must be taken to restore the +2 to +8°C/+36 to 
+46°F label storage temperature conditions. The impacted IMP(s) may still be administered, 
but the site should avoid re-occurrence of such temperature excursion. Refer to the Module 
on Clinical Trial Supplies in the SPM for more details on actions to take.
Refer to the Module on Clinical Trial Supplies in the SPM for details and instructions on the 
temperature excursion reporting and usage decision process, packaging and accountability of 
the study vaccines.
6.3. Dosage and Administration of Study Vaccines
The lyophilised white pellet of the MenACWY-TT vaccine is to be reconstituted with the 
supplied saline diluent to obtain 0.5 ml for administration. 
Refer to the Module on Clinical Trial Supplies in the SPM for details on the reconstitution 
and administration of study vaccines.
Table 13.
Dosage and Administration
Type of contact and 
timepoint
Volume to be 
administered
Study 
Group
Treatment 
name
Route 1
Site 2
Side
Visit 1 (Month 0)
0.5 ml
ACWY1d
ACWY2d
Co-ad 
MenACWY-TT 
IM
Anterolateral 
thigh or Deltoid
Left
Visit 1 (Month 0)
0.5 ml
Co-ad
PCV-13
PCV-13 
IM
Anterolateral 
thigh or Deltoid
Right
Visit 3 (Month 2)
0.5 ml
ACWY2d
PCV-13 
MenACWY-TT 
IM
Anterolateral 
thigh or Deltoid
Left
1 Intramuscular (IM).
2 The deltoid muscle can be used if the muscle mass is appropriate.
6.4. Replacement of Unusable Vaccine Doses
In addition to the vaccine doses provided for the planned number of subjects (including over-
randomisation when applicable), at least 20% additional vaccine doses will be supplied to 
replace those that are unusable. 

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6.5. Contraindications to Subsequent Vaccination
The following events constitute absolute contraindications to further administration of
MenACWY-TT. If any of these events occur during the study, the subject must not receive 
additional doses of vaccine but may continue other study procedures at the discretion of the 
investigator (see Section 8.4). 
Anaphylaxis following the administration of vaccine(s).
Hypersensitivity to the active substances or any of the excipients contained in the vaccine.
The following events constitute contraindications to administration of MenACWY-TT or 
Prevenar 13 at that point in time; if any of these events occur at the time scheduled for 
vaccination, the subject may be vaccinated at a later date, within the time window specified 
in the protocol (see Section 5.5), or the subject may be withdrawn at the discretion of the 
investigator (see Section 8.4). 
Acute disease and/or fever at the time of vaccination. 

Fever is defined as temperature 37.5°C/99.5°F for oral, axillary or tympanic route, 
or 38.0°C/100.4°F for rectal route. The preferred route for recording temperature in 
this study will be rectal.

Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory 
infection) without fever can be administered all vaccines.
6.6. Warnings and Precautions
As with all injectable vaccines, appropriate medical treatment and supervision should always 
be readily available in case of a rare anaphylactic reaction following the administration of the 
study vaccines.
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic 
response to the needle injection. It is important that procedures are in place to avoid injury 
from faints.
MenACWY-TT
MenACWY-TT should under no circumstances be administered intravascularly, 
intradermally or subcutaneously.
MenACWY-TT should be given with caution to individuals with thrombocytopenia or any 
coagulation disorder since bleeding may occur following an intramuscular administration to 
these subjects.
Refer to the SRSD (ie, SmPC).

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Prevenar 13
Prevenar 13 should not be administered intravascularly.
Prevenar 13 should not be given as an intramuscular injection to individuals with 
thrombocytopenia or any coagulation disorder that would contraindicate intramuscular 
injection, but may be given subcutaneously if the potential benefit clearly outweighs the 
risks.
Refer to the approved product package insert.
6.7. Concomitant Medication/Product and Concomitant Vaccination
At each study visit/contact, the investigator should question the subject’s parent(s)/LAR(s) 
about any medication/product taken and vaccination received by the subject.
6.7.1. Recording of Concomitant Medications/Products and Concomitant Vaccination
The following concomitant medications/products/vaccines must be recorded in the eCRF or 
SAE report if administered during the indicated recording period:
All concomitant medications/products, except vitamins and dietary supplements, 
administered within 30 days following each dose of study vaccine.
Any concomitant vaccination administered in the period starting 30 days before the first dose 
of study vaccine and ending 30 days after the last dose of study vaccine.
Prophylactic medication (i.e. medication administered in the absence of ANY symptom and 
in anticipation of a reaction to the vaccination).
Eg, an anti-pyretic is considered to be prophylactic when it is given in the absence of 
fever and any other symptom, to prevent fever from occurring [fever is defined as rectal 
temperature 38°C/axillary temperature 37.5°C/oral temperature 37.5°C/tympanic 
temperature on oral setting 37.5°C/tympanic temperature on rectal setting 38°C].
Any concomitant medications/products/vaccines listed in Section 6.7.2.
Any concomitant medication/product/vaccine relevant to a SAE* or administered at any time 
during the study period for the treatment of a SAE*.
* SAEs that are required to be reported per protocol.
Any antipyretic administered in the period starting 6 hours before vaccination and ending 
12 hours after vaccination.

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6.7.2. Concomitant Medications/Products/Vaccines that may lead to the Elimination of 
A Subject from ATP Analyses
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the subject from the study but may determine a subject’s evaluability in the 
ATP analysis. See Section 10.4 for study cohorts/ data sets to be analysed.
Any investigational or non-registered product (drug or vaccine) other than the study 
vaccine(s) used during the study period. 
Immunosuppressants or other immune-modifying drugs administered chronically (i.e. more 
than 14 days) during the study period. For corticosteroids, this will mean prednisone 
0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.
i.
A vaccine not foreseen by the study protocol administered during the period starting 
from 30 days before each dose of study vaccine(s) and ending 30 days after*, with the 
exception of: 

inactivated influenza vaccine can be administered at any time during the study;

MMR or MMRV vaccine can be co-administered with MenACWY-TT or Prevenar
13. If MMR or MMRV are not co-administered with MenACWY-TT or Prevenar 13, 
the vaccine can be administered outside of the period starting from 30 days before 
and ending 30 days after each dose of study vaccine(s).

A DTP containing vaccine has to be administered after the blood sampling: 
o
at Visit 2 in the Co-ad group and the ACWY1d groups,
o
at Visit 4 in the ACWY2d and PCV-13 groups.
* In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a 
pandemic) is organised by the public health authorities, outside the routine immunisation 
program, the time period described above can be reduced if necessary for that vaccine 
provided it is licensed and used according to its Summary of Product Characteristics or 
Prescribing Information (PI) and according to the local governmental 
recommendations.
Any meningococcal or pneumococcal vaccine administered during the study period not 
foreseen by the protocol with the exception of the booster dose of Prevenar 13 in the 
ACWY1d and ACWY2d groups.
Immunoglobulins and/or any blood products administered during the study period.

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6.8. Intercurrent Medical Conditions that may lead to elimination of a Subject from 
ATP Analyses
At each study visit subsequent to the first vaccination/the vaccination visit, it must be 
verified if the subject has experienced or is experiencing any intercurrent medical condition. 
The presence of these conditions will not require withdrawal of the subject from the study 
but may determine a subject’s evaluability in the ATP analysis. If it is the case, the 
condition(s) must be recorded in the eCRF.
Subjects may be eliminated from the ATP cohort for immunogenicity post dose 1, ATP 
cohort for immunogenicity post dose 2 or ATP cohort for persistence Year 1, 3 or 5 if, during 
the study, they incur a condition that has the capability of altering their immune response, 
e.g.:
Occurrence of meningococcal disease.*
Occurrence of pneumococcal disease.*
Any confirmed or suspected HIV infection based on medical history and physical 
examination (no laboratory testing required).
Any confirmed or suspected immunosuppressive or immunodeficient condition based on 
medical history and physical examination (no laboratory testing required).
Diagnosis of any serious chronic illness.
or if they are confirmed to have an alteration of their initial immune status.
* event to be reported as an SAE.
7. HEALTH ECONOMICS
Not applicable.
8. SAFETY
The investigator or site staff is/are responsible for the detection, documentation and reporting 
of events meeting the criteria and definition of an adverse event (AE) or serious adverse 
event (SAE) as provided in this protocol. 
Each subject’s parent(s)/LAR(s) will be instructed to contact the investigator immediately 
should the subject manifest any signs or symptoms they perceive as serious.
8.1. Safety Definitions
8.1.1. Definition of an Adverse Event
An AE is any untoward medical occurrence in a clinical investigation subject, temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product.

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An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a medicinal product. For marketed medicinal products, this also includes failure to 
produce expected benefits (i.e. lack of efficacy), abuse or misuse. 
Examples of an AE include:

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after investigational vaccine(s)/product(s) 
administration even though they may have been present prior to the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
investigational vaccine(s)/product(s) or a concurrent medication (overdose per se should 
not be reported as an AE/SAE).

Signs, symptoms temporally associated with vaccine administration.
Pre- or post-treatment events that occur as a result of protocol-mandated procedures 
(i.e. invasive procedures, modification of subject’s previous therapeutic regimen).
AEs to be recorded as solicited AEs are described in Section 8.1.3. All other AEs will be 
recorded as UNSOLICITED AEs.
Examples of an AE DO NOT include:

Medical or surgical procedures (e.g. endoscopy, appendectomy); the condition that leads 
to the procedure is an AE/SAE.

Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 

Pre-existing conditions or signs and/or symptoms present in a subject prior to the first 
study vaccination. These events will be recorded in the medical history section of the 
eCRF.
8.1.2. Definition of a Serious Adverse Event 
A serious adverse event is any untoward medical occurrence that:
a.
Results in death,

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b. Is life-threatening,
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which 
the subject was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, had it been more severe.
c.
Requires hospitalisation or prolongation of existing hospitalisation,
Note: In general, hospitalisation signifies that the subject has been admitted at the 
hospital or emergency ward for observation and/or treatment that would not have been 
appropriate in the physician’s office or in an out-patient setting. Complications that 
occur during hospitalisation are also considered AEs. If a complication prolongs 
hospitalisation or fulfils any other serious criteria, the event will also be considered 
serious. When in doubt as to whether ‘hospitalisation’ occurred or was necessary, the 
AE should be considered serious.
Hospitalisation for elective treatment of a pre-existing condition (known or diagnosed 
prior to informed consent signature) that did not worsen from baseline is NOT 
considered an AE.
d. Results in disability/incapacity.
Note: The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. This definition is not intended to include experiences of relatively 
minor medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhoea, influenza like illness, and accidental trauma (e.g. sprained ankle) which may 
interfere or prevent everyday life functions but do not constitute a substantial disruption.
e.
Lack of efficacy.
Medical or scientific judgement should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalisation but may jeopardise the subject or may 
require medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition. These should also be considered serious. Examples of such events are 
invasive or malignant cancers, intensive treatment in an emergency room or at home for 
allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalisation.
8.1.3. Solicited Adverse Events
A 4-day follow-up (Days 0-3) of solicited local and general symptoms will be performed 
after the study vaccine(s) administration.
8.1.3.1. Solicited local (injection-site) adverse events
The following local (injection-site) AEs will be solicited:

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Table 14.
Solicited local Adverse Events
Pain at injection site
Redness at injection site
Swelling at injection site
For subjects of the Co-ad and PCV-13 groups: 
If the parent(s)/LAR(s) observe any large injection site reactions (defined as swelling with a 
diameter > 50 mm, noticeable diffuse swelling or noticeable increase of limb circumference) 
following the dose of Prevenar 13, they will be asked to contact the study personnel and to 
bring the child as soon as possible to the study site for evaluation. The investigator will 
record detailed information, describing the adverse event on a large injection site reaction 
screen in the eCRF.
8.1.3.2. Solicited General Adverse Events
The following general AEs will be solicited:
Table 15.
Solicited General Adverse Events
Drowsiness
Fever
Irritability/Fussiness
Loss of appetite
Fever is defined as rectal temperature 38°C/axillary temperature 37.5°C/oral temperature 37.5°C/tympanic 
temperature on oral setting 37.5°C/tympanic temperature on rectal setting 38°C. 
Note: Temperature will be recorded in the evening. Should additional temperature 
measurements be performed at other times of day, the highest temperature will be recorded in 
the eCRF.
8.1.4. Clinical Laboratory Parameters and Other Abnormal Assessments Qualifying as 
Adverse Events or Serious Adverse Events 
In absence of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, haematology, 
urinalysis) or other abnormal assessments (e.g. medical imaging) that are judged by the 
investigator to be clinically significant will be recorded as AE or SAE if they meet the 
definition of an AE or SAE (refer to Section 8.1.1 and Section 8.1.2).  Clinically significant 
abnormal laboratory findings or other abnormal assessments that are present at baseline and 
significantly worsen following the start of the study will also be reported as AEs or SAEs. 
However, clinically significant abnormal laboratory findings or other abnormal assessments 
that are associated with the disease being studied, unless judged by the investigator as more 
severe than expected for the subject’s condition, or that are present or detected at the start of 
the study and do not worsen, will not be reported as AEs or SAEs.

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The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant.
8.1.5. Adverse events of Specific Interest
AEs of specific interest for safety monitoring include the occurrence of:
NOCIs such as autoimmune disorders, asthma, type 1 diabetes and allergies. Refer to 
Section 8.1.5.1 for a non-exhaustive list of illnesses that can be recorded as NOCI.
GBS (to be reported as an SAE).
Meningococcal and pneumococcal disease (to be reported as an SAE).
See Section 8.2 and Section 8.3 for information on recording and reporting of these events.
8.1.5.1. List of New Onset Chronic Illnesses
Table 16 presents a non-exhaustive list of illnesses that can be recorded as NOCIs.
Table 16.
List of Potential new onset of Chronic Illnesses
Disease/Disorder
Blood autoimmune disorders
Anaemia haemolytic autoimmune
Antiphospholipid syndrome
Cold type haemolytic anaemia
Coombs positive haemolytic anaemia
Idiopathic thrombocytopenic purpura
Pernicious anaemia
Warm type haemolytic anaemia
Autoimmune thrombocytopenia
Evan’s syndrome
Autoimmune neutropenia
Thrombocytopenias
Endocrine autoimmune disorder
Basedow’s disease
Insulin autoimmune syndrome
Polyglandular autoimmune syndrome type I
Polyglandular autoimmune syndrome type II
Autoimmune thyroiditis
Diabetic mastopathy
Lymphocytic hypophysitis
Polyglandular autoimmune syndrome type III
Endocrine symptoms
Hyperthyroidism
Hypothyroidism
Goiter
Hepatic autoimmune disorder
Autoimmune hepatitis
Biliary cirrhosis primary

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Table 16.
List of Potential new onset of Chronic Illnesses
Disease/Disorder
Muscular autoimmune disorder
Myasthenia gravis
Myasthenia gravis neonatal
Polymyalgia
Polypyalgia rheumatica
Polymyositis
Ocular myasthenia
Myasthenia gravis crisis
Lupus erythematosus and associated conditions
Lupoid hepatic cirrhosis
Lupus encephalitis
Lupus nephritis
SLE arthritis
Systemic lupus erythematosus
Systemic lupus erythematosus rash
Lupus-like syndrome
Cutaneous lupus erythematosus
Lupus pneumonitis
Neonatal lupus erythematosus
Lupus vasculitis
Pericarditis lupus
Lupus endocarditis
Peritonitis lupus
Neuropsychiatric lupus
Autoimmune disorders NEC
Ankylosis spondylitis
Cryoglobulinaemia
Gastritis atrophic
Goodpasture’s syndrome
Keratoconjunctivitis sicca
Keratoderma blenorrhagica
Mixed connective tissue disease
Reiter’s syndrome
Sicca syndrome
Sjogren’s syndrome
Sympathetic ophtalmia
Leukoencephalomyelitis
Toxic oil syndrome
Cryofibrinogenaemia
Encephalitis allergic
Nephritis autoimmune
Acute haemorrhagic leukoencephalitis
Autoimmune disorder
Rheumatoid arthritis and associated conditions
Felty’s syndrome
Rheumatoid arthritis
Rheumatoid lung
Rheumatoid vasculitis
Rheumatoid nodule
Juvenile arthritis
Laryngeal rheumatoid arthritis

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Table 16.
List of Potential new onset of Chronic Illnesses
Disease/Disorder
Scleroderma and associated disorders
CREST syndrome
Morphoea
Scleroderma
Systemic sclerosis
Systemic sclerosis pulmonary
Scleroderma renal crisis
Skin autommune disorders NEC
Benign familial pemphigus
Dermatitis herpetiformis
Dermatomyosistis
Eosinophilic fasciitis
Herpes gestationis
Linear IgA disease
Pemphigoid
Pemphigus
Vitiligo
Acute and chronic thyroiditis
Thyroiditis
Thyroiditis acute
Thyroiditis chronic
Thyroiditis subacute
Autoimmune thyroiditis
Optic neuritis
Optic neuritis
Optic neuritis retrobulbar
Vision blurred
Blindness
Visual acuity reduced
Visual evoked potential abnormaly
Multiple sclerosis
Multiple sclerosis
Demyelineting disorder
Gait disturbances
Muscle weakness
Paraesthesias
(Cognitive impairment)
(Nuclear magnetic resonance imaging brain abnormal)
Transverse myelitis
Myelitis Transverse
Muscle weakness
Low back pain
Paraesthesias and dysaesthesias
Paralysis
(Urinary retention)
(Neurogenic bladder)
Guillain-Barre syndrome
Guillain-Barre syndrome
Muscle weakness
Paraesthesias and dysaesthesias
Diabetes mellitus insulin-dependent
Diabetes mellitus
Diabetes mellitus (incl. subtypes)
Glucose metabolism disorders (incl. diabetes mellitus)
Uveitis
Uveitis
Eye pain
Eye redness
Photophobia

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Table 16.
List of Potential new onset of Chronic Illnesses
Disease/Disorder
Glomerulonephritis
Lupus nephritis
Proteinuria
Haematuria
Glomerular filtration rate decreased
(Hypoproteinemia)
(Oedema)
Blood urea increased
Blood creatinine increase
Inflammatory bowel disease
Inflammatory bowel disease
Crohn’s disease
Crohn’s disease
Ulcerative colitis
Ulcerative colitis
Rectal bleeding
Coeliac disease
Coeliac disease
Sarcoidosis
Sarcoidosis
Angiotensin converting enzyme increased
Asthma
Asthma
Allergies
Immune system disorders
Allergic conditions
Auto immunity analyses
Asthmatic crisis
Asthmatic crisis
8.2. Detecting and Recording Adverse Events, Serious Adverse Events, NOCIs and GBS
8.2.1. Time Period for Detecting and Recording Adverse Events aAnd Serious Adverse 
Events
All AEs starting within 30 days following administration of each dose of study vaccine must 
be recorded into the appropriate section of the eCRF, irrespective of intensity or whether or 
not they are considered vaccination-related.
The time period for collecting and recording SAEs will begin at the first receipt of study 
vaccine and will end at the extended safety follow-up (ESFU) phone contact (Month 9) for 
each subject. See Section 8.3 for instructions on reporting of SAEs.
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from the 
time of the first receipt of study vaccine.
SAEs that are related to the investigational vaccine/product and any event related to lack of 
vaccine efficacy will be collected and recorded from the time of the first receipt of study 
vaccine until the subject is discharged from the study.
In addition to the above-mentioned reporting requirements and in order to fulfil international 
reporting obligations, SAEs that are related to study participation (i.e. protocol-mandated 
procedures, invasive tests, a change from existing therapy) will be collected and recorded 
from the time the subject consents to participate in the study until she/he is discharged from 
the study.

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Occurrences of NOCIs (New Onset of Chronic Illnesses, e.g. autoimmune disorders, asthma, 
type 1 diabetes and allergies) will be reported from administration of the first dose of study 
vaccine until the ESFU phone contact (Month 9) and will be reported either as an AE or as an 
SAE as appropriate.
Occurrences of GBS will be reported from administration of the first dose of study vaccine
until the ESFU phone contact (Month 9). Clinical details should be obtained as outlined in 
the ‘Potential immune mediated disorders: standard questionnaires and list of preferred 
terms’. All occurrences of GBS have to be reported as SAE.
Occurrences of meningococcal and pneumococcal disease will be reported from the time the 
subject enters the study until the end of the study (Visit 7). Meningococcal and 
pneumococcal disease will be reported as SAE.
An overview of the protocol-required reporting periods for AEs, SAEs, GBS and NOCIs is 
given in Table 17 for the ACWY1d and Co-ad groups and in Table 18 for the ACWY2d and 
PCV-13 groups. 

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Table 17.
Reporting Periods for Adverse Events, Serious Adverse Events, GBS and NOCIs for the ACWY1d and Co-ad 
Groups
Event
ICF 
signed*
Vacc
3 d 
post-Vacc
30 d 
post-Vacc
ESFU
Study 
Conclusion
Day 0
Day 3
Day 30
Month 9
Year 1
Year 3
Year 5 
Solicited local and general AEs
Unsolicited AEs
AEs/SAEs leading to 
withdrawal from the study
SAEs**
SAEs** related to the 
investigational vaccine/product 
and any event related to lack of 
vaccine efficacy
SAEs related to study 
participation 
GBS#

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Table 17.
Reporting Periods for Adverse Events, Serious Adverse Events, GBS and NOCIs for the ACWY1d and Co-ad 
Groups
Event
ICF 
signed*
Vacc
3 d 
post-Vacc
30 d 
post-Vacc
ESFU
Study 
Conclusion
Day 0
Day 3
Day 30
Month 9
Year 1
Year 3
Year 5 
NOCIs§
Vacc: vaccination; Post-Vacc: post-vaccination
* Information on consent will be encoded in the eCRF.
**Occurrences of meningococcal and pneumococcal disease should be reported as SAEs and in the AE report in the eCRF.
#In the event of GBS, subject’s parents/LARs should be contacted to obtain the clinical details as outlined in the ‘Potential immune mediated disorders: standard 
questionnaires and list of preferred terms’. All occurrences of GBS have to be reported as SAEs.
§ NOCIs (New Onset of Chronic Illnesses, e.g. autoimmune disorders, asthma, type 1 diabetes and allergies) will be reported until the ESFU (Extended Safety 
Follow-Up) phone contact (Month 9) and will be reported either as an AE or as an SAE as appropriate. 

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Table 18.
Reporting Periods for Adverse Events, Serious Adverse Events, GBS and NOCIs for the ACWY2d and PCV-13 
Groups
Event
ICF 
signed*
Vacc1
3 d
post-
Vacc1
30 d 
post-
Vacc1
Vacc2
3 d
post-Vacc2
30 d
post-Vacc2
ESFU
Study 
Conclusion
Day 0
Day 3
Day 30
Day 0
Day 3
Day 30
Month 
9
Year 1
Year 3
Year 5
Solicited local 
and general AEs
Unsolicited AEs
AEs/SAEs 
leading to 
withdrawal from 
the study
SAEs**
SAEs** related to 
the 
investigational 
vaccine/product
and any event 
related to lack of 
vaccine efficacy
SAEs related to 
study 
participation
GBS#

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Table 18.
Reporting Periods for Adverse Events, Serious Adverse Events, GBS and NOCIs for the ACWY2d and PCV-13 
Groups
Event
ICF 
signed*
Vacc1
3 d
post-
Vacc1
30 d 
post-
Vacc1
Vacc2
3 d
post-Vacc2
30 d
post-Vacc2
ESFU
Study 
Conclusion
Day 0
Day 3
Day 30
Day 0
Day 3
Day 30
Month 
9
Year 1
Year 3
Year 5
NOCI§
Vacc1: vaccination 1; Post-Vacc1: post-vaccination 1, Vacc2: vaccination 2; Post-Vacc2: post-vaccination 2.
* Information on consent will be encoded in the eCRF. 
**Occurrences of meningococcal and pneumococcal disease should be reported as SAEs and documented in the AE report in the eCRF.
#In the event of GBS, subject’s parents/LARs should be contacted to obtain the clinical details as outlined in the ‘Potential immune mediated disorders: standard 
questionnaires and list of preferred terms’. All occurrences of GBS have to be reported as SAEs. 
§ NOCIs (New Onset of Chronic Illnesses, e.g. autoimmune disorders, asthma, type 1 diabetes and allergies) will be reported until the ESFU (Extended Safety 
Follow-Up) phone contact (Month 9) and will be reported either as an AE or as an SAE as appropriate. 

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8.2.2. Post-Study Adverse Events and Serious Adverse Events
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE reporting 
period defined in Table 17 and Table 18. Investigators are not obligated to actively seek AEs 
or SAEs in former study participants. However, if the investigator learns of any SAE at any 
time after a subject has been discharged from the study, and he/she considers the event 
reasonably related to the investigational vaccine/product, the investigator will promptly 
report the SAEs to Pfizer.
8.2.3. Evaluation of Adverse Events and Serious Adverse Events
8.2.3.1. Active Questioning to Detect Adverse Events and Serious Adverse Events
As a consistent method of collecting AEs, the subject’s parent(s)/LAR(s) should be asked a 
non-leading question such as:
‘Has your child acted differently or felt different in any way since receiving the vaccine or 
since the last visit?’
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative to 
the event. The investigator will then record all relevant information regarding an AE/SAE in 
the eCRF. The investigator is not allowed to send photocopies of the subject’s medical 
records to Pfizer instead of appropriately completing the SAE form and AE CRF. However, 
there may be instances when copies of medical records for certain cases are requested by 
Pfizer. In this instance, all subject identifiers will be blinded on the copies of the medical 
records prior to submission to Pfizer.
The investigator will attempt to establish a diagnosis pertaining to the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms.
8.2.3.2. Assessment of Adverse Events
8.2.3.2.1. Assessment of Intensity
The intensity of the following solicited AEs will be assessed as described:
Table 19.
Intensity Scales for Solicited Symptoms in Infants/Toddlers
Adverse Event
Intensity grade
Parameter
Pain at injection site
0
None
1
Mild: Minor reaction to touch
2
Moderate: Cries/protests on touch
3
Severe: Cries when limb is moved/spontaneously painful
Redness at injection site
Record greatest surface diameter in mm
Swelling at injection site
Record greatest surface diameter in mm
Fever*
Record temperature in °C/°F

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Table 19.
Intensity Scales for Solicited Symptoms in Infants/Toddlers
Adverse Event
Intensity grade
Parameter
Irritability/Fussiness
0
Behaviour as usual
1
Mild: Crying more than usual/no effect on normal activity
2
Moderate: Crying more than usual/interferes with normal 
activity
3
Severe: Crying that cannot be comforted/prevents normal 
activity
Drowsiness
0
Behaviour as usual
1
Mild: Drowsiness easily tolerated
2
Moderate: Drowsiness that interferes with normal activity
3
Severe: Drowsiness that prevents normal activity
Loss of appetite
0
Appetite as usual
1
Mild: Eating less than usual/no effect on normal activity
2
Moderate: Eating less than usual/interferes with normal 
activity
3
Severe: Not eating at all
*Fever is defined as rectal temperature 38°C/axillary temperature 37.5°C/oral temperature 37.5°C/tympanic 
temperature on oral setting 37.5°C/tympanic temperature on rectal setting 38°C.
The maximum intensity of local injection site redness/swelling will be scored as follows:
0
:
None
1
:
> 0 - ≤ 10 mm
2
:
> 10 - ≤ 30 mm
3
:
> 30 mm
The maximum intensity of fever will be scored as follows:
Oral/Axillary/Tympanic 
temperature on oral setting
Rectal/Tympanic temperature on 
rectal setting
0
:
< 37.5°C
< 38.0°C
1
:
≥ 37.5°C - ≤ 38.5°C
≥38.0°C - ≤ 39.0°C
2
:
> 38.5°C - ≤ 39.5°C
> 39.0°C - ≤ 40.0°C
3
:
> 39.5°C
> 40.0°C
The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgement.

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The intensity should be assigned to one of the following categories:
1 (mild)
=
An AE which is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities.
2 (moderate)
=
An AE which is sufficiently discomforting to interfere with normal 
everyday activities.
3 (severe)
=
An AE which prevents normal, everyday activities (in a young child, 
such an AE would, for example, prevent attendance at 
school/kindergarten/a day-care centre and would cause the 
parent(s)/LAR(s) to seek medical advice.)
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. Grade 3 is a 
category used for rating the intensity of an event; and both AEs and SAEs can be assessed as 
Grade 3. An event is defined as ‘serious’ when it meets one of the pre-defined outcomes as 
described in Section 8.1.2.
8.2.3.2.2. Assessment of Causality
The investigator is obligated to assess the relationship between investigational 
vaccine/product and the occurrence of each unsolicited AE (including SAEs) and for general 
solicited AEs. The investigator will use clinical judgement to determine the relationship. 
Alternative plausible causes, such as natural history of the underlying diseases, concomitant 
therapy, other risk factors, and the temporal relationship of the event to the investigational 
vaccine/product will be considered and investigated. The investigator will also consult the 
SRSD and/or PI for marketed products to determine his/her assessment.
There may be situations when a SAE has occurred and the investigator has minimal 
information to include in the initial report to Pfizer. However, it is very important that the 
investigator always makes an assessment of causality for every event prior to submission of 
the SAE report to Pfizer. The investigator may change his/her opinion of causality in light of 
follow-up information and update the SAE information accordingly. The causality 
assessment is one of the criteria used when determining regulatory reporting requirements.
In case of concomitant administration of multiple vaccines/products, it may not be possible to 
determine the causal relationship of general AEs to the individual vaccines administered. 
The investigator should, therefore, assess whether the AE could be causally related to 
vaccination rather than to the individual vaccines.
All solicited local (injection site) reactions will be considered causally related to vaccination. 
Causality of all other AEs should be assessed by the investigator using the following 
question:
Is there a reasonable possibility that the AE may have been caused by the investigational 
vaccine/product?

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YES
:
There is a reasonable possibility that the vaccine(s) contributed to the AE. 
NO
:
There is no reasonable possibility that the AE is causally related to the 
administration of the study vaccine(s). There are other, more likely causes 
and administration of the study vaccine(s) is not suspected to have 
contributed to the AE.
If an event meets the criteria to be determined as ‘serious’ (see Section 8.1.2), additional 
examinations/tests will be performed by the investigator in order to determine ALL possible 
contributing factors for each SAE.
Possible contributing factors include:
Medical history.
Other medication.
Protocol required procedure.
Other procedure not required by the protocol.
Lack of efficacy of the vaccine(s), if applicable.
Erroneous administration.
Other cause (specify).
8.2.3.3. Assessment of Outcomes
The investigator will assess the outcome of all unsolicited AEs (including SAEs) recorded 
during the study as:
Recovered/resolved.
Recovering/resolving.
Not recovered/not resolved.
Recovered with sequelae/resolved with sequelae.
Fatal (SAEs only).

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8.2.3.4. Medically Attended Visits
For each solicited and unsolicited symptom the subject experiences, the subject’s 
parent(s)/LAR(s) will be asked if the subject received medical attention defined as 
hospitalisation, or an otherwise unscheduled visit to or from medical personnel for any 
reason, including emergency room visits. This information will be recorded in the eCRF. 
8.3. Reporting of Serious Adverse Events and Other Events
8.3.1. Prompt Reporting of Serious Adverse Events and Other Events
SAEs that occur in the time period defined in Section 8.2 will be reported promptly within 
the timeframes described in Table 20, once the investigator determines that the event meets 
the protocol definition of a SAE.
Cases of GBS and meningococcal or pneumococcal disease must be reported within 24 hours 
to Pfizer regardless of seriousness.
Table 20.
Timeframes for Submitting Serious Adverse Event and Other Events 
Reports
Type of Event
Initial Reports
Follow-up of Relevant Information on a 
Previous Report
Timeframe
Documents
Timeframe
Documents
SAEs
24 hours*
Paper SAE report
24 hours*
Paper SAE report
GBS 
24 hours*
Paper SAE report
24 hours*
Paper SAE report
Meningococcal or 
pneumococcal disease
24 hours*
Paper SAE report
24 hours*
Paper SAE report
* Timeframe allowed after receipt or awareness of the information.
8.3.2. Completion and Transmission of SAE Reports
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator (or designate) must complete the information in the paper SAE report WITHIN 
24 HOURS. The SAE report will always be completed as thoroughly as possible with all 
available details of the event. Even if the investigator does not have all information 
regarding a SAE, the report should still be completed within 24 hours. Once additional 
relevant information is received, the report should be updated WITHIN 24 HOURS.
The investigator will always provide an assessment of causality at the time of the initial 
report.
8.3.3. Updating of SAE Information after Freezing of The Subject’s eCRF
When additional SAE information is received after freezing of the subject’s eCRF, new or 
updated information should be recorded on a paper report, with all changes signed and dated 
by the investigator. The updated report should be faxed to Pfizer within the designated 
reporting time frames specified in Table 20.

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8.3.4. Regulatory Reporting Requirements for Serious Adverse Events
The investigator will promptly report all SAEs to Pfizer in accordance with the procedures 
detailed in Section 8.3.1. Pfizer has a legal responsibility to promptly notify, as appropriate, 
both the local regulatory authority and other regulatory agencies about the safety of a product 
under clinical investigation. Prompt notification of SAEs by the investigator to Pfizer is 
essential so that legal obligations and ethical responsibilities towards the safety of other 
subjects are met.
Investigator safety reports are prepared according to the current Pfizer policy and are 
forwarded to investigators as necessary. An investigator safety report is prepared for a 
SAE(s) that is both attributable to the investigational vaccine/product and unexpected. The 
purpose of the report is to fulfil specific regulatory and GCP requirements, regarding the 
product under investigation.
8.4. Follow-up of Adverse Events and Serious Adverse Events
8.4.1. Follow-up during The Study
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject and provide additional relevant information on the subject’s condition to Pfizer
(within 24 hours for SAEs; refer to Table 20).
All SAEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until the end 
of the study.
All AEs documented at a previous visit/contact and designated as not recovered/not resolved 
or recovering/resolving will be reviewed at subsequent visits/contacts until 30 days after the 
last vaccination.
NOCIs and GBS documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until the 
ESFU phone contact (Month 9).
8.4.2. Follow-up after the Subject is Discharged from the Study
The investigator will follow subjects:
with SAEs or subjects withdrawn from the study as a result of an AE, until the event has 
resolved, subsided, stabilised, disappeared, or until the event is otherwise explained, or the 
subject is lost to follow-up. 
with other non-serious AEs, e.g. NOCIs, until the ESFU phone contact (Month 9) or they are 
lost to follow-up. 
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to Pfizer using a paper SAE report.

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Pfizer may request that the investigator performs or arranges the conduct of additional 
clinical examinations/tests and/or evaluations to elucidate as fully as possible the nature 
and/or causality of the AE or SAE. The investigator is obliged to assist. If a subject dies 
during participation in the study or during a recognised follow-up period, Pfizer will be 
provided with any available post-mortem findings, including histopathology.
8.5. Treatment of Adverse Events
Treatment of any AE is at the sole discretion of the investigator and according to current 
good medical practice. Any medication administered for the treatment of an AE should be 
recorded in the subject’s eCRF (refer to Section 6.7).
8.6. Subject Card
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 compound identifiers, subject study numbers, 
contact information for the investigational site, and contact details for a contact center in the 
event that the investigational 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 investigational 
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 investigational 
site and the study team are not available.  It is therefore intended to augment, but not replace, 
the established communication pathways between the investigational 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 investigational site.
Subjects’ parent(s)/LAR(s) must be instructed to keep subject cards in their possession at all 
times.
9. SUBJECT COMPLETION AND WITHDRAWAL
9.1. Subject Completion
A subject who returns for the concluding visit/is available for the concluding contact 
foreseen in the protocol is considered to have completed the study.
9.2. Subject Withdrawal
Withdrawals will not be replaced.
9.2.1. Subject Withdrawal from the Study
From an analysis perspective, a ‘withdrawal’ from the study refers to any subject who did not 
come back for the concluding visit/was not available for the concluding contact foreseen in 
the protocol. 

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All data collected until the date of withdrawal/last contact of the subject will be used for the 
analysis.
A subject is considered a ‘withdrawal’ from the study when no study procedure has occurred, 
no follow-up has been performed and no further information has been collected for this 
subject from the date of withdrawal/last contact.
Investigators will make an attempt to contact those subjects who do not return for scheduled 
visits or follow-up. Lost to follow-up is defined by the inability to reach the subject after a 
minimum of 2 documented phone calls, faxes, or e-mails as well as lack of response by the 
subject to 1 registered mail letter.  All attempts should be documented in the subject’s 
medical records.  
Information relative to the withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by the 
subject’s parent(s) or LAR(s), or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal:
Serious adverse event.
Non-serious adverse event.
Protocol violation (specify).
Consent withdrawal, not due to an adverse event.*
Moved from the study area.
Lost to follow-up.
Other (specify).
*In case a subject is withdrawn from the study because he/she/the subject’s parent(s) has 
withdrawn consent, the investigator will document the reason for withdrawal of consent, if 
specified by the subject, in the CRF.
Subjects who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from subjects who are withdrawn for other reasons. Investigators will follow 
subjects who are withdrawn from the study as result of a SAE/AE until resolution of the 
event (see Section 8.4.2).
9.2.2. Subject Withdrawal from Investigational Vaccine
A ‘withdrawal’ from the investigational vaccine refers to any subject who does not receive 
the complete treatment, i.e. when no further planned dose is administered from the date of 
withdrawal. A subject withdrawn from the investigational vaccine may not necessarily be 
withdrawn from the study as further study procedures or follow-up may be performed (safety 
or immunogenicity) if planned in the study protocol. 

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Information relative to premature discontinuation of the investigational vaccine will be 
documented on the Vaccine Administration screen of the eCRF. The investigator will 
document whether the decision to discontinue further vaccination/treatment was made by the 
subject’s parent(s) or LAR(s), or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal:
Serious adverse event.
Non-serious adverse event.
Other (specify).
10. STATISTICAL METHODS
10.1. Primary Endpoints
Immunogenicity with respect to components of the study vaccines: 

Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and 
rSBA-MenY titres ≥ 1:8 one month after administration of 1 dose of MenACWY-TT 
in the ACWY1d, ACWY2d and Co-ad groups and one month after administration of 
2 doses in the ACWY2d group. 

Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and 
rSBA-MenY titres ≥ 1:8, ≥ 1:128 and geometric mean titres (GMTs) at Years 1, 3 and 
5 in the ACWY1d and ACWY2d groups. 

Anti-pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F 
geometric mean antibody concentrations one month after administration of 
Prevenar 13 in the Co-ad and PCV-13 groups.
10.2. Secondary Endpoints
Immunogenicity with respect to components of the study vaccines (on secondary readouts):

Percentage of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and 
hSBA-MenY titres ≥ 1:4, ≥ 1:8 and GMTs one month after administration of 1 dose 
of MenACWY-TT in a subset of subjects in the ACWY1d and ACWY2d groups and 
one month after administration of 2 doses in the ACWY2d group.

Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and 
rSBA-MenY titres ≥ 1:8, ≥ 1:128 and GMTs one month after administration of 1 dose 
of MenACWY-TT in the PCV-13 group. 

Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and 
rSBA-MenY titres ≥ 1:128 and GMTs one month after administration of 1 dose of 
MenACWY-TT in the ACWY1d, ACWY2d and Co-ad groups.

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
Percentage of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and 
hSBA-MenY titres ≥ 1:4, ≥1:8 and GMTs at Years 1, 3 and 5 in a subset of subjects 
in the ACWY1d and ACWY2d groups. 

Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and 
rSBA-MenY titres ≥ 1:8, ≥1:128 and GMTs at Years 1, 3 and 5 in the Co-ad and 
PCV-13 groups. 

Percentage of subjects with anti-pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 
14, 18C, 19A, 19F and 23F antibody concentrations ≥ 0.15 µg/ml, ≥ 0.26 µg/ml and 
≥ 0.35 µg/ml one month after administration of Prevenar 13 in the Co-ad and 
PCV-13 groups. 

Percentage of subjects with anti-pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 
14, 18C, 19A, 19F and 23F OPA titres ≥ 1:8 and GMTs one month after 
administration of Prevenar 13 in the Co-ad and PCV-13 groups. 
Solicited local and general symptoms:

Occurrence of each solicited local and general symptom within 4 days (Day 0 – Day 
3) after each study vaccination. 
Unsolicited AEs:

Occurrence of unsolicited AEs within 31 days (Day 0 – Day 30) after any study 
vaccination, according to the Medical Dictionary for Regulatory Activities 
(MedDRA) classification. 
SAEs: 

Occurrence of SAEs from Month 0 to Month 9. 
SAEs related to study vaccine administration: 

Occurrence of SAEs related to study vaccine administration and any event related to 
lack of vaccine efficacy (i.e. meningococcal disease) from the first receipt of study 
vaccine until study end.
Occurrence of NOCI: 

Occurrence of NOCI (e.g. asthma, autoimmune disorders, type 1 diabetes, allergies) 
from Month 0 to Month 9. 

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10.3. Determination of Sample Size
The target sample size is 640 evaluable subjects (160 in the 4 study groups) for the statistical 
analysis of epoch 001. Considering that approximately 20% of the enrolled subjects might 
withdraw or not be evaluable for immunogenicity post-vaccination, the target sample size to 
be enrolled is 800 subjects (200 in each study group).
Moreover, assuming 10% drop-out for each persistence visit:
Around 576 subjects will be evaluable at Visit 5 (144 in each study group);
Around 516 subjects will be evaluable at Visit 6 (129 in each study group);
Around 468 subjects will be evaluable at Visit 7 (117 in each study group).
The co-primary confirmatory objectives will be assessed in a hierarchical manner according 
to the order presented below. A co-primary objective can only be met if the statistical 
criteria for that objective are met as well as the statistical criteria for all previous co-primary 
objectives. Therefore, the multiplicity of objectives does not require an alpha adjustment. 
However, it impacts the beta as the last objective can only be reached if the last and all 
previous objectives are met simultaneously.
Confirmatory primary objective 1: To demonstrate non-inferiority of  meningococcal 
conjugate vaccine MenACWY-TT when co-administered with 13-valent pneumococcal 
vaccine Prevenar 13 versus meningococcal conjugate vaccine MenACWY-TT given alone.
Criterion for non-inferiority of the meningococcal serogroups A, C, W-135 and Y.
Non-inferiority will be demonstrated for each serogroup separately if the lower limit of the 
two-sided standardized asymptotic 95% CI for the group difference between the Co-ad group 
and the Pool1d group (Co-ad group minus Pool1d group ) in the percentage of subjects with 
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY ≥ 1:8 is greater than or equal 
to -10%.
Table 21.
Power to Show the Non-inferiority of the Co-ad Group Compared to the 
Pool1d Group
Endpoint
H0 (group difference 
in expected % of 
subjects with rSBA 
titre 1:8, Co-ad –
Pool1d group)
Ha
Reference** rate in 
both groups used 
for HA
*
N = 160 subjects in 
Co-ad group and 320 
subjects in Pool1d group
rSBA-MenA 
µ<-10%
µ-10%
98.4%
<0.01%
rSBA-MenC 
µ<-10%
µ-10%
97.3%
0.12%
rSBA-MenW-135 µ<-10%
µ-10%
98.4%
<0.01%
rSBA-MenY 
µ<-10%
µ-10%
97.3%
0.12%

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Table 21.
Power to Show the Non-inferiority of the Co-ad Group Compared to the 
Pool1d Group
Endpoint
H0 (group difference 
in expected % of 
subjects with rSBA 
titre 1:8, Co-ad –
Pool1d group)
Ha
Reference** rate in 
both groups used 
for HA
*
N = 160 subjects in 
Co-ad group and 320 
subjects in Pool1d group
Global Beta to show non-inferiority
<0.26%
Global power to show non-inferiority
99.74%
* PASS 2005, 1-sided equivalence test on 2 proportions (non-inferiority), alpha=0.025 one sided, power under 
different proportions in each group.
H0: group difference in expected % of subjects with rSBA titre < -(P Co-ad – P Pool1d < -10%).
Ha: group difference in expected % of subjects with rSBA titre -.
** Reference: rSBA tested at GSK laboratory for study 109835 (MENACWY-TT-040) which involved subjects 
12 to 23 months of age.
Confirmatory primary objective 2: To demonstrate non-inferiority of  13-valent 
pneumococcal vaccine Prevenar 13 when co-administered with meningococcal vaccine 
MenACWY-TT versus 13-valent pneumococcal vaccine Prevenar 13 given alone.
Criterion for non-inferiority of the pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 
18C, 19A, 19F and 23F: 
Non-inferiority will be demonstrated for each serotype separately if the lower limit of the 
95% CI of the GMC ratio between the Co-ad group and the PCV-13 group (Co-ad group over 
PCV-13 group) is above 0.5.
Table 22.
Power to Show the Non-inferiority of the Co-ad Group Compared to the 
PCV-13 Group with respect to Prevenar 13 Antibody Concentrations
Endpoint:
Standard 
Deviation**
Margin ()
* (1:1)
N=160 vs. 160
strepto-1
0.314
0.5
<0.01%
strepto-3
0.255
0.5
<0.01%
strepto-4
0.356
0.5
<0.01%
strepto-5
0.302
0.5
<0.01%
strepto-6A
0.366
0.5
<0.01%
strepto-6B
0.547
0.5
0.15%
strepto-7F
0.280
0.5
<0.01%
strepto-9V
0.412
0.5
<0.01%
strepto-14
0.486
0.5
0.02%
strepto-18C
0.372
0.5
<0.01%
strepto-19A
0.278
0.5
<0.01%
strepto-19F
0.315
0.5
<0.01%
strepto-23F
0.549
0.5
0.16%

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Table 22.
Power to Show the Non-inferiority of the Co-ad Group Compared to the 
PCV-13 Group with respect to Prevenar 13 Antibody Concentrations
Endpoint:
Standard 
Deviation**
Margin ()
* (1:1)
N=160 vs. 160
Global Beta to show non-inferiority
<0.43%
Global power to show non-inferiority
99.57%
* Pass 2005: Non inferiority test of 2 independent means (non-inferiority using differences of Log10
transformed GMCs), = 2.5% one sided, power under assumption of equal Log10(GMC)s and standard 
deviations in both groups.
H0: expected value for the group difference in log10 transformed titres, co-ad group minus PCV-13 group, is 
< Log10() 
Ha: expected value for the group difference in log10 transformed titre is Log10().
** Reference: 101858 (HIB-MENCY-TT-005) for serogroups 6B and 19F, 107005 (10PN-PD-DIT-011) for 
serogroups 4, 9V, 14, 18C and 23F and 113948 (DTPA-HBV-IPV-124 PRI) for serogroups 1, 3, 5, 6A, 7F and 
19A. 
The global power to meet all primary confirmatory objectives considering a sample size of 
640 evaluable subjects in total will be at least 99.31% (see Table 23).
Table 23.
Summary of Power for the Confirmatory Primary Objectives
Objective
Endpoint
β
1
rSBA-MenA 
<0.01%
1
rSBA-MenC 
0.12%
1
rSBA-MenW-135 
<0.01%
1
rSBA-MenY 
0.12%
2
Strepto-1 ELISA
<0.01%
2
strepto-3 ELISA
<0.01%
2
strepto-4 ELISA
<0.01%
2
strepto-5 ELISA
<0.01%
2
strepto-6A ELISA
<0.01%
2
strepto-6B ELISA
0.15%
2
strepto-7F ELISA
<0.01%
2
strepto-9V ELISA
<0.01%
2
strepto-14 ELISA
0.02%
2
strepto-18C ELISA
<0.01%
2
strepto-19A ELISA
<0.01%
2
strepto-19F ELISA
<0.01%
2
strepto-23F ELISA
0.16%
Global Beta to show non-inferiority
<0.69%
Global power to show non-inferiority
99.31%
Global beta is conservatively computed as the sum of all individual beta. The objectives will be assessed in a 
hierarchical way and the second objective can only be met if the first objective is met.

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10.4. Study Cohorts/ Data sets to be Analysed
10.4.1. Total Vaccinated Cohort
The Total Vaccinated Cohort will include all subjects vaccinated with at least one dose of 
study vaccine:
A safety analysis based on the Total Vaccinated Cohort will include all subjects with at least 
one vaccine dose administration documented.
An immunogenicity analysis based on the Total Vaccinated Cohort will include all 
vaccinated subjects for whom immunogenicity results are available.
The Total Vaccinated Cohort analysis will be performed per treatment actually administered 
(at dose 1).
10.4.2. According-To-Protocol Cohort for Safety
The ATP cohort for analysis of safety will include all vaccinated and eligible subjects:

who meet all inclusion criteria and no exclusion criteria for the study,

who have received at least one dose of study vaccine according to their random 
assignment,

for whom administration site and route of study vaccine is known and according to 
protocol,

who have not received the booster dose of Prevenar 13 outside the defined timeline 
(if administered, for groups ACWY1d and ACWY2d only),

who have not received a vaccine forbidden in the protocol (subjects who received a 
vaccine not foreseen by the study protocol from 30 days before until 30 days after the 
administration of one [or more] of the study vaccine doses will be eliminated from the 
ATP cohort for safety if the vaccine not foreseen by the protocol was administered before 
the corresponding post-vaccination blood sample),

who have not received a meningococcal or pneumococcal vaccine not foreseen in the 
protocol with the exception of the booster dose of Prevenar 13 in the ACWY1d and 
ACWY2d groups.
10.4.3. According-To-Protocol Cohort for Immunogenicity Post Dose 1
The ATP cohort for immunogenicity post dose 1 will include all evaluable subjects (i.e. those 
meeting all eligibility criteria, complying with the procedures defined in the protocol and 
with no elimination criteria during the study) from the ATP cohort for safety:

who received all study vaccines at Month 0,

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
for whom assay results are available for antibodies against at least one study vaccine 
antigen component at Visit 2,

who comply with the procedures and intervals defined in the protocol:
o
Date of birth to Vaccination 1 (Visit 1): 12-14 months,
o
Vaccination 1(Visit 1) to Blood sample of Visit 2: 21-48 days.

with no concomitant infection which may influence immune response,

who were not administered a vaccine not foreseen by the study protocol before the 
corresponding post-vaccination blood sample.
10.4.4. According-To-Protocol for Immunogenicity Post Dose 2
The ATP cohort for immunogenicity post dose 2 will include all evaluable subjects (i.e. those 
meeting all eligibility criteria, complying with the procedures defined in the protocol and 
with no elimination criteria during the study) from the ACWY2d and PCV-13 groups in the 
ATP cohort for safety:

who received all study vaccines at Month 0 and Month 2,

for whom assay results are available for antibodies against at least one study vaccine 
antigen component at Visit 4,

who comply with the procedures and intervals defined in the protocol:
o
Date of birth to Vaccination 1 (Visit 1): 12-14 months,
o
Vaccination 1 (Visit 1) to Vaccination 2 (Visit 3): 60 to 90 days,
o
Vaccination 2 (Visit 3) to Blood sample of Visit 4: 21-48 days.

with no concomitant infection which may influence immune response,

who were not administered a vaccine not foreseen by the study protocol before the 
post-dose 2 blood sample.
10.4.5. Total Cohort Year 1, 3 and 5
The Total Cohort Year 1, 3 and 5 will include all subjects who received at least one dose of 
any study vaccine from whom data concerning persistence endpoint measures are available at 
Year 1, 3 or 5.

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10.4.6. According-To-Protocol Cohort for Persistence Year 1, 3 and 5
The ATP cohort for persistence at Year 1, 3 and 5 will include all evaluable subjects: 

who meet all eligibility criteria,

who have received the complete primary vaccination with MenACWY-TT according 
to their random assignment,

who have assay results available for at least one antigen tested at the Year considered
(i.e. Year 1, 3 or 5),

who comply with the procedures and intervals defined in the protocol (refer to 
Section 5.5),

who did not receive a product leading to elimination from an ATP analysis as listed in 
Section 6.7.2,

who did not present with a medical condition leading to elimination from an ATP 
analysis as listed in Section 6.8,

who were not excluded from the ATP cohort for immunogenicity (post-dose 1 for the 
ACWY1d and Co-ad groups; post-dose 2 for the ACWY2d and PCV-13 groups) and 
from the previous ATP cohorts for persistence (for Years 3 and 5 only), unless the 
reason for exclusion was either non-compliance with the protocol-defined serum 
sampling windows or lack of availability of immunogenicity results at the previous 
time point.
10.5. Derived and Transformed Data
The analyses will be performed per treatment actually administered.
Immunogenicity
The cut-off value is defined by the laboratory before the analysis and is described in 
Section 5.7.3.
The Geometric mean titre (GMT)/Geometric mean concentration (GMC) calculations are 
performed by taking the anti-log of the mean of the log titre transformations. Antibody titres 
below the cut-off of the assay will be given an arbitrary value of half the cut-off for the 
purpose of GMT/GMC calculation.
Handling of missing data: for a given subject and a given immunogenicity measurement, 
missing or non-evaluable measurements will not be replaced.

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Safety and Reactogenicity
For a given subject and the analysis of solicited symptoms within 4 days post-vaccination, 
missing or non-evaluable measurements will not be replaced. Therefore, the analysis of the 
solicited symptoms based on the Total Vaccinated cohort will include only vaccinated 
subjects for doses with documented safety data (i.e. symptom screen completed). More 
specifically, the following rules will be used:

Subjects who documented the absence of a solicited symptom after one dose will be 
considered not having that symptom after that dose;

Subjects who documented the presence of a solicited symptom and fully or partially 
recorded daily measurement over the solicited period will be included in the 
summaries at that dose and classified according to their maximum observed daily 
recording over the solicited period;

Subjects who documented the presence of a solicited symptom after one dose without 
having recorded any daily measurement will be assigned to the lowest intensity 
category at that dose (i.e. 37.5°C for fever or grade 1 for other symptoms);

Doses without symptom sheets documented will be excluded.
In case the number of subjects who documented the presence of a solicited symptom after 
one dose without having recorded any daily measurement exceeds 1%, a sensitivity analysis 
will be carried out to assess the impact of assigning the lowest intensity for the symptom.
For analysis of unsolicited AEs, such as SAEs or AEs by primary Medical Dictionary for 
Regulatory Activities (MedDRA) term, and for the analysis of concomitant medications, all 
vaccinated subjects will be considered. Subjects who did not report the event or the 
concomitant medication will be considered as subjects without the event or the concomitant 
medication.
10.6. Analysis of Primary Vaccination
10.6.1. Demography
Demographic characteristics (age [in months] at vaccination, gender and geographic 
ancestry) of each study cohort will be tabulated per group.
The mean age at vaccination (in months and with the range and standard deviation) as a 
whole and per group will be calculated.
The distribution of subjects enrolled among the study sites will be tabulated as a whole and 
per group.
The demography analyses will be performed overall, by country and by the number of doses 
of Prevenar 13 received before the study (2 or 3 doses).

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10.6.2. Analysis of Immunogenicity
The primary analysis of immunogenicity will be performed on the ATP cohort for 
immunogenicity. At post dose 1, the analysis will be done on the ATP cohort for 
immunogenicity post dose 1. At post dose 2, the analysis will be done on the ATP cohort for 
immunogenicity post dose 2. 
A second analysis on the Total Vaccinated Cohort will be performed to support the ATP
analysis if:

the percentage of subjects enrolled in groups Co-ad or ACWY1d with serological 
results at Visit 2 excluded from the ATP cohort for immunogenicity post dose 1 is 
more than 5% or,

the percentage of subjects enrolled in groups ACWY2d or PCV-13 with serological 
results at Visit 4 excluded from the ATP cohort for immunogenicity post dose 2 is 
more than 5%.
In addition to the overall analyses, the immunogenicity analyses on the ATP cohort for 
immunogenicity post dose 1 and on the ATP cohort for immunogenicity post dose 2 will be 
performed by country and by the number of doses of Prevenar 13 received before the study 
(2 or 3 doses).
10.6.2.1. Within Group
For the ACWY1d, ACWY2d, Co-ad and PCV-13 groups, at each timepoint that data on 
meningococcal antibody titres, pneumococcal antibody concentrations or pneumococcal 
antibody titres are available:
Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY 
titres 1:8 and 1:128 will be calculated.
Percentage of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY 
titres 1:4 and 1:8 will be calculated.
Percentage of subjects with anti-pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 
19A, 19F and 23F antibody concentrations 0.15 g/ml, 0.26 g/ml and 0.35 g/ml will 
be calculated.
Percentage of subjects with anti-pneumococcal serotype 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 
19A, 19F and 23F OPA titres 1:8 will be calculated.
GMTs and GMCs with 95% CI will be calculated.
The distribution of antibody concentrations and titres will also be tabulated and evaluated 
using reverse cumulative curves.
These analyses will be done on the ATP cohort for immunogenicity adapted per timepoint.

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10.6.2.2. Between Group
Confirmatory Primary Objective
Non-inferiority of meningococcal conjugate vaccine MenACWY-TT when co-administered 
with 13-valent pneumococcal vaccine, Prevenar 13, versus meningococcal conjugate vaccine 
MenACWY-TT given alone one month after vaccination. 
Two-sided standardized asymptotic 95% CI of the group difference between the Co-ad and 
the Pool1d group (Co-ad group minus Pool1d group) will be computed for the percentage of 
subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titre 1:8 
(Visit 2).
It can be concluded (for each serogroup separately) that co-administration of MenACWY-TT 
and Prevenar 13 is non-inferior to administration of MenACWY-TT alone if the lower limit 
of the CI of the difference is greater than or equal to -10%.
Non-inferiority of 13-valent pneumococcal vaccine, Prevenar 13, when co-administered with 
meningococcal vaccine MenACWY-TT versus 13-valent pneumococcal vaccine, Prevenar 
13, given alone one month after vaccination.
95% CI of the GMC ratio between the Co-ad and the PCV-13 group (Co-ad group over 
PCV-13 group) will be computed for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 
18C, 19A, 19F and 23F (Visit 2). This will be performed using an ANCOVA model on the 
logarithm10 transformation of the concentrations using the pre-vaccination logarithm10
transformation of the concentrations, the country, the number of doses of Prevenar 13
received before the study (2 or 3 doses) and the vaccine group as covariates.
It can be concluded (for each serotype separately) that co-administration of Prevenar 13 and 
MenACWY-TT is non-inferior to administration of Prevenar 13 alone if the lower limit of 
the CI of the GMC ratio is above 0.5.
Exploratory Analysis
An exploratory evaluation of the comparability of the immune response to each 
pneumococcal serotype at one month after administration of Prevenar 13 will be done 
through:
Computation of the asymptotic standardised 95% CI on the difference between the 
percentages of subjects with concentrations and OPA titres above proposed cut-offs between 
groups Co-ad and (minus) PCV-13 (Visit 2).
Computation of the 95% CI of the GMC and GMT ratios between the Co-ad and (over) the 
PCV-13 group (Visit 2). This will be performed using an ANCOVA model on the 
logarithm10 transformation of the concentrations using the pre-vaccination logarithm10
transformation of the concentrations or titres, the country, the number of doses of 
Prevenar 13 received before the study (2 or 3 doses) and the vaccine group as covariates. 

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An exploratory evaluation of the comparability of the immune response to each 
meningococcal serogroup at one month after the first dose of MenACWY-TT and at one 
month after the second dose of MenACWY-TT will be done through:
Computation of the asymptotic standardised 95% CI on the difference between the 
percentage of subjects with rSBA and hSBA titres above proposed cut-offs between the 
ACWY2d group (after second dose of MenACWY-TT, Visit 4) and (minus) the ACWY1d 
group (Visit 2).
Computation of the 95% CI of the rSBA and hSBA GMT ratios between the ACWY2d group 
(after second dose of MenACWY-TT, Visit 4) and (over) ACWY1d group (Visit 2). This 
will be performed using an ANCOVA model on the logarithm10 transformation of the titres 
using the pre-vaccination logarithm10 transformation of the titres, the country, the number of 
doses of Prevenar 13 received before the study (2 or 3 doses) and the vaccine group as 
covariates.
These analyses will be performed on the ATP cohort for immunogenicity adapted per 
timepoint.
10.6.3. Analysis of Safety
The primary analysis will be performed on the Total Vaccinated Cohort. If, for any vaccine 
group, more than 5% of the enrolled subjects are eliminated from the ATP cohort for safety, 
a second analysis will be performed on the ATP cohort for safety to support the analyses of 
the Total Vaccinated Cohort.
All percentages/proportions described below will be tabulated with exact 95% CI.
The percentage of subjects with at least one local AE (solicited and unsolicited), with at least 
one general AE (solicited and unsolicited) and with any AE during the 4-day solicited 
follow-up period will be tabulated. The same calculations will be performed for symptoms 
rated as grade 3 and for symptoms related to vaccination.
The percentage of subjects reporting each individual solicited local (any grade, grade 3 and 
medical advice) and general (any grade, grade 3, related, grade 3 and related, and medical 
advice) AE during the 4-day follow-up period (Day 0 - Day 3) after vaccination will be 
tabulated. 
Occurrence of fever will also be reported per 0.5°C cumulative increments.
The percentage of subjects using concomitant medication (any medication, any antipyretic, 
any antipyretic taken prophylactically, respectively) during the 4-day and 31-day follow-up 
periods (Day 0 – Day 3 and Day 0 – Day 30, respectively) after each vaccination will be 
summarised.

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The verbatim reports of unsolicited symptoms will be reviewed by the clinical development 
manager and the signs and symptoms will be coded according to the MedDRA Dictionary for 
Adverse Reaction Terminology. 
The percentage of subjects with unsolicited symptoms within 31 days post vaccination (Day 
0 – Day 30) will be tabulated by group and by MedDRA preferred term. Similar tabulation 
will be done for grade 3 unsolicited symptoms, for unsolicited symptoms possibly related to 
vaccination and for grade 3 unsolicited symptoms possibly related to vaccination.
SAEs, withdrawal due to AE(s) and large swelling reactions will be described in detail.
The number and percentage of subjects with SAEs and NOCIs (e.g. autoimmune disorders, 
asthma, type 1 diabetes and allergies) will be tabulated with exact 95% CIs by group.
In addition to the overall analyses, the safety analyses on the Total Vaccinated Cohort will be 
performed by country and by the number of doses of Prevenar 13 received before the study 
(2 or 3 doses).
10.7. Analysis of Persistence
10.7.1. Demography
Demographic characteristics (age [in months] at Year 1, 3 and 5, gender, geographic ancestry 
and months since last dose of vaccination) of each study cohort will be tabulated per group.
The mean age at the persistence timepoint (in months with the range and standard deviation) 
as a whole and per group will be calculated.
The distribution of subjects enrolled at Year 1, 3 and 5 among the study sites will be 
tabulated as a whole and per group and the reason for not attending a visit at Year 1, 3 and 5 
among all vaccinated subjects will be summarised.
The demography analyses will be performed overall, by country and by the number of doses 
of Prevenar 13 received before the study (2 or 3 doses).
10.7.2. Analysis of Persistence
For each Year 1, 3 and 5: The analysis of antibody persistence will be based on the ATP 
cohort for persistence Year 1, 3 and 5. If for any vaccine group, the percentage of subjects 
who come back for the Year 1, 3 and 5 follow-up with serological results excluded from the 
ATP cohort is higher than 5%, a second analysis based on the Total Cohort Year 1, 3 and 5 
will be performed to complement the ATP analysis.
For the ACWY1d, ACWY2d, Co-ad group and PCV-13 group for each antigen assessed at 
each blood sampling timepoint:
Percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY 
titres 1:8 and 1:128 will be calculated.

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Percentage of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY 
titres 1:4 and 1:8 will be calculated.
GMTs with 95% CI will be calculated.
The distribution of antibody titres will also be tabulated and evaluated using reverse 
cumulative curves.
In addition to the overall analyses, the analyses of persistence on the ATP cohort for 
persistence Year 1, 3 and 5 will be performed by country and by the number of doses of 
Prevenar 13 received before the study (2 or 3 doses).
10.7.3. Modelling Prediction
In order to complement the descriptive analyses of observed persistence per timepoint and 
minimize the bias that may have occurred due to the loss to follow-up after the vaccination, a 
longitudinal analysis will be performed after Year 5 for rSBA-MenA, rSBA-MenC, rSBA-
MenW-135 and rSBA-MenY. These analyses will include all results from Month 0 up to 
Year 5 and will be performed on the ATP cohort for immunogenicity adapted per timepoint 
and the ATP cohort for persistence Year 1, 3 and 5, respectively.
10.7.4. Analysis of Safety
At Year 1, all SAEs considered related to vaccination, to study procedures or to a 
concomitant GSK drug or vaccine and any events related to lack of vaccine efficacy will be 
described in detail. At Year 3 and 5, all SAEs considered related to vaccination, to study 
procedures and any events related to lack of vaccine efficacy will be described in detail. 
The analysis will be performed overall and by country and by the number of doses of 
Prevenar 13 received before the study (2 or 3 doses).
10.8. Interpretation of Analyses
Except for analyses on objectives with a pre-defined success criterion and an appropriate 
type I error control (see Section 2.1.2, Section 10.3 and Section 10.6.2.2), comparative 
analyses will be descriptive with the aim to characterise the difference in immunogenicity 
between groups. 
10.9. Conduct of Analyses
Any deviation(s) or change(s) from the original statistical plan outlined in this protocol will 
be described and justified in the final study report.
10.9.1. Sequence of Analyses (Amended 02 July 2014)
Statistical analyses will be done stepwise:
A first analysis will include the data collected up to Month 1 for the ACWY1d and Co-ad 
group and Month 3 for the ACWY2d and PCV-13 groups in order to analyse the 
immunogenicity endpoints, solicited symptoms during the 4-day (Day 0-3) period after each 

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vaccine dose, unsolicited symptoms during the 31-day (Day 0-30) period after each vaccine 
dose and SAEs. The analyses will be performed on data as clean as possible. 
A second analysis will be done on the SAEs and NOCIs reported from administration of the 
first study vaccine dose until Month 9. If unsolicited symptoms that occurred during the 
31-day (Day 0-30) period are encoded after the first analysis was performed, unsolicited 
symptoms will be analysed again in the second analysis. These analyses will be performed on 
data as clean as possible. 
Further analyses will be done at the end of epochs 002, 003 and 004 and these will include 
data on immunogenicity endpoints. In addition, the SAEs of epoch 001 and SAEs considered 
related to vaccination of epochs 002, 003 and 004 will be analyzed. The analyses of epochs 
002 and 003 will be done on data as clean as possible and the analyses of epoch 004 will be 
done on clean data.
10.9.2. Statistical Considerations for Interim Analyses
No interim analysis will be performed.
11. ADMINISTRATIVE MATTERS
To comply with ICH GCP administrative obligations relating to data collection, monitoring, 
archiving data, audits, confidentiality and publications must be fulfilled. 
11.1. Remote Data Entry Instructions
Remote Data Entry (RDE), a validated computer application, will be used as the method for 
data collection. 
In all cases, subject initials will not be collected nor transmitted to Pfizer. Subject data 
necessary for analysis and reporting will be entered/transmitted into a validated database or 
data system.  Clinical data management will be performed in accordance with applicable 
Pfizer standards and data cleaning procedures.
While completed eCRFs are reviewed by a Pfizer or designee Site Monitor at the study site, 
omissions or inconsistencies detected by subsequent eCRF review may necessitate 
clarification or correction of omissions or inconsistencies with documentation and approval 
by the investigator or appropriately qualified designee. In all cases, the investigator remains 
accountable for the study data. 
The investigator will be provided with a CD-ROM of the final version of the data generated 
at the investigational site once the database is archived and the study report is complete and 
approved by all parties.
11.2. Study Monitoring
Pfizer or designee will monitor the study to verify that, amongst others, the: 
Data are authentic, accurate, and complete.

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Safety and rights of subjects are being protected.
Study is conducted in accordance with the currently approved protocol, any other study 
agreements, GCP and all applicable regulatory requirements. 
The investigator and the head of the medical institution (where applicable) agrees to allow 
the monitor direct access to all relevant documents.
The investigator must ensure provision of reasonable time, space and qualified personnel for 
monitoring visits.
Direct access to all study-site related and source data is mandatory for the purpose of 
monitoring review. The monitor will perform a RDE review and a Source Data Verification 
(SDV). By SDV we understand verifying RDE entries by comparing them with the source 
data that will be made available by the investigator for this purpose. 
The Source Documentation Agreement Form describes the source data for the different data 
in the RDE. This document should be completed and signed by the site monitor and 
investigator and should be filed in the monitor’s and investigator’s study file. Any data item 
for which the RDE will serve as the source must be identified, agreed and documented in the 
source documentation agreement form. 
For RDE, the monitor will mark completed and approved screens at each visit.
Upon completion or premature discontinuation of the study, the monitor will conduct site 
closure activities with the investigator or site staff, as appropriate, in accordance with 
applicable regulations, GCP, and Pfizer procedures.
11.3. Record Retention
Following closure of the study, the investigator must maintain all site study records (except 
for those required by local regulations to be maintained elsewhere) in a safe and secure 
location. The records must be easily accessible, when needed (e.g. audit or inspection), and 
must be available for review in conjunction with assessment of the facility, supporting 
systems, and staff. Where permitted by applicable laws/regulations or institutional policy, 
some or all of these records can be maintained in a validated format other than hard copy 
(e.g. microfiche, scanned, electronic); however, caution needs to be exercised before such 
action is taken. The investigator must ensure that all reproductions are legible and are a true 
and accurate copy of the original and meet accessibility and retrieval standards, including re-
generating a hard copy, if required. Furthermore, the investigator must ensure that an 
acceptable back-up of the reproductions exists and that there is an acceptable quality control 
procedure in place for making these reproductions.
Pfizer will inform the investigator/institution of the time period for retaining these records to 
comply with all applicable regulatory requirements. However, the investigator/institution 
should seek the written approval of the sponsor before proceeding with the disposal of these 
records. The minimum retention time will meet the strictest standard applicable to a 

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particular site, as dictated by ICH GCP, any institutional requirements, applicable laws or 
regulations, or Pfizer standards/procedures; otherwise, the minimum retention period will 
default to 15 years. 
The investigator/institution must notify Pfizer of any changes in the archival arrangements, 
including, but not limited to archival at an off-site facility, transfer of ownership of the 
records in the event the investigator leaves the site. 
11.4. Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, Pfizer may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory 
inspection of this study. Such audits/inspections can occur at any time during or after 
completion of the study. If an audit or inspection occurs, the investigator and institution 
agree to allow the auditor/inspector direct access to all relevant documents and to allocate 
his/her time and the time of his/her staff to the auditor/inspector to discuss findings and any 
relevant issues.
11.5. Posting of Information on Publicly Available Clinical Trial Registers and 
Publication Policy
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 for studies in 
adult populations or within 6 months of the primary completion date for studies in pediatric 
populations.
Primary completion date 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.

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EudraCT
Pfizer posts 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 primary completion date for studies in adult populations or within 6 months of the 
primary completion date for studies in pediatric populations.
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.
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrolment of subjects begins.
Publication Policy: 
Pfizer supports the exercise of academic freedom and has no objection to publication by 
principal investigator of the results of the study based on information collected or generated 
by principal investigator, 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 they are 
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 study sites, and that any subsequent publications by the 
principal investigator 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.

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Publication of study results is also provided for in the clinical study agreement (CSA)
between Pfizer and the institution.  In this section on 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.
11.6. Provision of Study Results to Investigators
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report. The investigator will be provided reasonable 
access to statistical tables, figures, and relevant reports and will have the opportunity to 
review the complete study results at a Pfizer site or other mutually-agreeable location.
Pfizer will also provide the investigator with the full summary of the study results. 
11.7. 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 
competent 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 study vaccine, 
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.
12. COUNTRY SPECIFIC REQUIREMENTS
Not applicable.
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Knuf M, Kieninger-Baum D, Habermehl P, et al. A dose-range study accessing 
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meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine 
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Maslanka SE, Gheesling LL, Libutti DE et al. Standardization and a multilaboratory 
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Memish ZA, Dbaibo G, Montellano M, et al. Immunogenicity of a single dose of tetravalent 
meningococcal serogroups A, C, W-135 and Y conjugate vaccine administered to 2- to 
10- year olds is non-inferior to a licensed-ACWY polysaccharide vaccine with an acceptable 
safety profile. Pediatr Infec Dis J. 2011;30:e56-62. 
Menactra Prescribing Information. US. November 2011.
Menveo Consumer Medicine Information. Australia. July 2010.
Menveo Package Leaflet. Europe. June 2012.
Menveo Prescribing Information. US. March 2011.
Menveo Product Monograph. Canada. June 2011.
Ostergaard L, Lebacq E, Poolman J, Maechler G, Boutriau D. Immunogenicity, 
reactogenicity and persistence of meningococcal A, C, W-135 and Y tetanus toxoid candidate 
conjugate (MenACWY-TT) vaccine formulation in adolescents aged 15-25 years. Vaccine. 
2009;27:161-168. 
Pollard AJ, Frasch C. Development of natural immunity to Neisseria meningitidis. Vaccine. 
2001;19:1327-1346.
Quataert SA, Rittenhouse-Olson K, Kirch SA, et al. Assignment of weight-based antibody 
units for 13 serotypes to a human antipneumococcal standard reference serum, lot 89-S. Clin 
Diagn Lab Immunol. 2004;1064-1069.
Ramsay ME, Andrews NJ, Trotter CL, et al. Herd immunity from meningococcal serogroup 
C conjugate vaccination in England: database analysis. BMJ. 2003;326:365-366.

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Richmond P, Kaczmarski E, Borrow R, et al. Meningococcal C polysaccharide vaccine 
induces immunologic hyporesponsiveness in adults that is overcome by meningococcal C 
conjugate vaccine. J Infect Dis. 2000;181:761-764.
Romero-Steiner S, Libutti D, Pais LB et al. Standardization of an Opsonophagocytic Assay 
for the Measurement of Functional Antibody Activity against Streptococcus pneumoniae 
Using Differentiated HL-60 Cells. Clin Diagn Lab Immunol.1997;4(4):415-422.
Rosenstein N, Levine O, Taylor J, et al. Efficacy of meningococcal vaccine and barriers to 
vaccination. JAMA. 1998; 279:435-439.
Trotter CL, Andrews NJ, Kaczmarski EB, et al. Effectiveness of meningococcal serogroup C 
conjugate vaccine 4 years after introduction. Lancet. 2004;364:365-367.
Vesikari T, Karvonen A, Bianco V, et al. Tetravalent meningococcal serogroups A, C, 
W-135 and Y conjugate vaccine is well tolerated and immunogenic when co-administered 
with measles-mumps-rubella-varicella vaccine during the second year of life: An open, 
randomized controlled trial. Vaccine. 2011;29:4274-4284.
Whalen CM, Hockin JC, Ryan A, et al. The changing epidemiology of invasive 
meningococcal disease in Canada, 1985 through 1992: emergence of a virulent clone of 
Neisseria meningitidis. JAMA. 1995;273:390-394.

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APPENDIX A
LABORATORY ASSAYS
The following HIV test will be performed prior to enrolment for subjects in South Africa 
only (HIV-negative subjects with documentation of previous HIV test will be eligible to 
participate to the study without additional testing):
HIV testing will be performed using the HIV 1/2 Rapid Test, a rapid 
immunochromatography assay for the qualitative detection of antibodies to HIV 1/2 virus in 
human serum, plasma and whole blood (Amended 02 July 2014).
The following tests will be performed:

Functional anti-meningococcal serogroup activity (SBA-MenA, SBA-MenC, SBA 
MenW-135, SBA-MenY) will be determined by:
i.
serum bactericidal assay using rabbit complement (rSBA) at Public Health 
England (PHE) according to the Centers for Disease Control and Prevention 
(CDC) protocol [Maslanka, 1997]; and 
ii.
serum bactericidal assays using human complement (hSBA) at the Neomed 
Institute.
rSBA titres will be expressed as the reciprocal of the highest serum dilution resulting 
in at least 50% reduction of meningococcoal colony-forming units (CFUs).
hSBA titres will be expressed as the reciprocal of the interpolated serum dilution 
resulting in 50% reduction of meningococcal CFUs. The clinical cut-offs (ie, positive 
titre) for the rSBA is titre 1:8 and for hSBA is titre 1:4.

Pneumococcal serotype specific total Immunoglobulin G (IgG) antibodies (antibodies 
to 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) will each be measured by 
22F-inhibition enzyme-linked immunosorbent assay (ELISA) [Concepcion, 2001] at 
the Institute of Child Health. The antibody concentration will be determined by 
logistic log comparison of the ELISA curves with a standard reference serum 89-SF 
or SP007 available from the US Food and Drug Administration (FDA) for which 
concentration of IgG to the 13 serotypes are known in g/mL [Quataert, 2004; 
Goldblatt, 2011]. The cut-off of the assay is 0.15 g/mL.

Streptococcus pneumoniae opsonophagocytic activity (OPA) will be measured by a 
killing-assay using a HL60 cell line [Romero-Steiner, 1997]. The results will be 
presented as the dilution of serum (opsonophagocytic titre) able to sustain 50% killing 
of live pneumococci under the assay conditions. The cut-off of the assay is a dilution 
of 1:8.

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APPENDIX B
CLINICAL LABORATORIES
Table 24 presents the Clinical laboratories.
Table 24.
Laboratories
Laboratory
Address
Testing
Neomed Institute, Laval, Quebec, 
Canada
Biospecimen Reception - Clinical 
Serology
525 Cartier blvd West 
Laval, Quebec, H7V 3S8
Canada
MenA, MenC, MenW-135. and 
MenY  hSBA assay
Public Health England (PHE)
Public Health England
Public Health Laboratory –
Manchester
Manchester Medical Microbiology 
Partnership
2nd Floor, Clinical Sciences Building 
II
Manchester Royal Infirmary
Oxford Road
Manchester, M13 9WZ
United Kingdom
rSBA-MenA, rSBA-MenC,
rSBA-MenW-135, rSBA-MenY
Institute of Child Health (UCL)
University College of London
Institute of Child Health
30 Guilford Street
London, WC1N 1EH
United Kingdom
ELISA and OPA for 
pneumococcal serotypes 1, 3, 4, 
5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 
19F and 23F

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