A PHASE IIIB, OPEN, MULTI-CENTER STUDY TO EVALUATE THE LONG-TERM ANTIBODY PERSISTENCE AT 6, 7, 8, 9 AND 10 YEARS AFTER THE ADMINISTRATION OF ONE DOSE OF THE MENINGOCOCCAL CONJUGATE VACCINE MENACWY-TT VERSUS ONE DOSE OF MENINGITEC(REGISTERED) VACCINE OR ONE DOSE OF THE MENINGOCOCCAL POLYSACCHARIDE VACCINE MENCEVAX(REGISTERED) ACWY, AND TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A BOOSTER DOSE OF MENACWY-TT VACCINE ADMINISTERED 10 YEARS AFTER PRIMARY VACCINATION OF 1-10 YEAR OLD SUBJECTS WITH MENACWY-TT, MENINGITEC(REGISTERED) OR MENCEVAX(REGISTERED) ACWY.
Phase: PHASE3
Conditions: Infections, Meningococcal
Sponsor: Pfizer

25-FEB-2016
1
Clinical Study Protocol
Sponsor:
Pfizer, Inc.
235 East 42nd Street
New York, NY 10017, United States
Primary Study vaccine
Meningococcal serogroups A, C, W-135, Y tetanus 
toxoid conjugate (MenACWY-TT) vaccine 
(Nimenrix®, PF-06866681).
Other Study vaccines
NA
Study number and 
Abbreviated Title
C0921004 (MenACWY-TT-100 EXT:027 
Y6,7,8,9,10)
EudraCT number
2013-001549-15
Date of protocol
Final Protocol Amendment 2: 25 February 2016
Title
The long-term antibody persistence of MenACWY-TT 
vaccine (PF-06866681) versus Meningitec® or 
Mencevax® ACWY in healthy adolescents and adults 
and a booster dose of MenACWY-TT administered 10 
years post-primary vaccination.
Detailed Title
A phase IIIb, open, multi-center study to evaluate the 
long-term antibody persistence at 6, 7, 8, 9 and 10 
years after the administration of one dose of the 
meningococcal conjugate vaccine MenACWY-TT 
versus one dose of Meningitec® vaccine or one dose of 
the meningococcal polysaccharide vaccine Mencevax®
ACWY, and to evaluate the safety and immunogenicity 
of a booster dose of MenACWY-TT vaccine 
administered 10 years after primary vaccination of 1-
10 year old subjects with MenACWY-TT, 
Meningitec® or Mencevax® ACWY.
 
 
 
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Protocol Amendment 2 Sponsor Signatory Approval
Study number and 
Abbreviated Title(s)
C0921004 (MenACWY-TT-100 EXT:027 Y6,7,8,9,10;
formerly GSK 200171)
EudraCT number
2013-001549-15
Date of protocol
Protocol Amendment 2: 25 February 2016
Detailed Title 
A phase IIIb, open, multi-center study to evaluate the 
long-term antibody persistence at 6, 7, 8, 9 and 10 years 
after the administration of one dose of the 
meningococcal conjugate vaccine MenACWY-TT 
versus one dose of Meningitec® vaccine or one dose of 
the meningococcal polysaccharide vaccine Mencevax®
ACWY, and to evaluate the safety and immunogenicity 
of a booster dose of MenACWY-TT vaccine 
administered 10 years after primary vaccination of 1-10 
year old subjects with MenACWY-TT, Meningitec® or 
Mencevax® ACWY.
Sponsor signatory
, MD
 Pfizer Vaccines Clinical Research 
Signature
Date
PPD
PPD
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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 2
25-February-2016
Blood sample volume increased to 10 mL for 
visit 4.
Clarification made in section 5.2 (and glossary 
of terms) regarding container number.
Table 16 updated to 24 hours for initial 
pregnancy reporting and follow-up reports and 
updated to indicate that paper SAE and EDP 
reports will be submitted for pregnancies.
Amendment 1
04-February-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.
Additions to the glossary of terms (including a 
clarification for adequate contraception).
Single reference safety document amended to 
Core Data Sheet (CDS).
Outline of study procedures (Table 4) updated 
as per changes made in body of protocol.
Blood sample volume increased to 10 mL for 
pre- and post-booster samples.
Vaccine trademarks revised to correct 
company names and ® symbols.
Sections updated / added in line with standard 
Pfizer policy: 
- 4.1 Number of subjects/centres
- 4.2 Inclusion criteria for enrolment
- 4.3 Exclusion criteria for enrolment 
- 5.1 Regulatory and ethical considerations, 
including the informed consent process
- 5.2 Subject identification and randomisation 
of treatment
- 5.6 Detailed description of study procedures
- 5.7 Biological sample handling and analysis
- 6 Study vaccine and administration
- 8.1.1 Definition of an adverse event
- 8.1.2 Medication errors
- 8.1.3 Occupational exposure
- 8.1.4 Exposure during pregnancy
- 8.1.5 Definition of a serious adverse event
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- 8.1.6 Solicited adverse events
- 8.1.9 Pregnancy
- 8.2.1 Time period for detecting and recording 
adverse events, serious adverse events and 
pregnancies
- 8.2.2 Post-study adverse events and serious 
adverse events
- 8.2.3 Evaluation of adverse events and 
serious adverse events
- 8.3 Reporting of serious adverse events, 
pregnancies, and other events
- 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
- 11.7 Reporting of safety issues and serious 
breaches of the protocol or ICH GCP
- Appendix A Laboratory assays
- Appendix B Clinical laboratories
Original protocol
25-June-2013
Not applicable (NA)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities, institutional review boards/ethics committees 
(IRBs/ECs), etc.  
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Protocol Amendment 2 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(s)
C0921004 (MenACWY-TT-100 EXT:027 
Y6,7,8,9,10; formerly GSK 200171) 
EudraCT number
2013-001549-15
Date of protocol
Final Protocol Amendment 2: 25 February 2016
Detailed Title
A phase IIIb, open, multi-center study to evaluate the 
long-term antibody persistence at 6, 7, 8, 9 and 10 
years after the administration of one dose of the 
meningococcal conjugate vaccine MenACWY-TT 
versus one dose of Meningitec® vaccine or one dose 
of the meningococcal polysaccharide vaccine 
Mencevax® ACWY, and to evaluate the safety and 
immunogenicity of a booster dose of MenACWY-TT 
vaccine administered 10 years after primary 
vaccination of 1-10 year old subjects with 
MenACWY-TT, Meningitec® or Mencevax® ACWY.
Investigator name
Signature
Date
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SYNOPSIS
Detailed Title
A phase IIIb, open, multi-center study to evaluate the long-
term antibody persistence at 6, 7, 8, 9 and 10 years after the 
administration of one dose of the meningococcal conjugate 
vaccine MenACWY-TT versus one dose of Meningitec®
vaccine or one dose of the meningococcal polysaccharide 
vaccine Mencevax® ACWY, and to evaluate the safety and 
immunogenicity of a booster dose of MenACWY-TT vaccine 
administered 10 years after primary vaccination of 1-10 year 
old subjects with MenACWY-TT, Meningitec® or Mencevax®
ACWY.
Indication
Active immunization of individuals from 12 months of age 
against invasive meningococcal diseases caused by Neisseria 
meningitidis serogroups A, C, W-135 and Y.
Rationale for the 
study and study 
design
In study MenACWY-TT-027, 613 healthy subjects between 1 
and 10 years of age were randomized using a (3:1) ratio to 
receive either a single dose of MenACWY-TT vaccine or a 
meningococcal C conjugate vaccine or a meningococcal 
polysaccharide vaccine. The subjects were followed up for 
antibody persistence over five years post-vaccination in 
studies MenACWY-TT-028 through -032. The results showed 
that subjects vaccinated with MenACWY-TT between ages 1 
and 2 years of age had detectable antibodies five years after 
vaccination in 73.5%, 77.6%, 34.7% and 42.9% of subjects 
against serogroups A, C, W-135 and Y, respectively. Subjects 
vaccinated with MenACWY-TT at 2-10 years of age in this 
same study showed that five years after vaccination 90.8%, 
90.8%, 78.6% and 78.6% of subjects had detectable 
antibodies against A, C, W-135 and Y serogroups, 
respectively. The main purpose of this study is to continue to 
evaluate the antibody persistence 6, 7, 8, 9 and 10 years post-
administration of MenACWY-TT conjugate vaccine as 
compared to Meningitec or Mencevax ACWY when given to 
healthy subjects 1 to 10 years of age. In addition, the safety 
and immunogenicity of a booster dose of MenACWY-TT 
vaccine administered to all eligible subjects 10 years after the 
primary vaccination will be evaluated.
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Objectives
Primary
Long-term persistence phase: Six, seven, eight, nine and 
ten years after primary vaccination with MenACWY-TT 
or Meningitec or Mencevax ACWY, in study MenACWY-
TT-027

To evaluate the long-term persistence of the serum 
bactericidal (antibody) titres induced by MenACWY-TT 
vaccine as compared to Meningitec when administered to 
individuals 1-<2 years of age in terms of the percentage 
of subjects with Neisseria meningitidis serogroup A 
(MenA), serogroup C (MenC), serogroup W-135 
(MenW-135), and serogroup Y (MenY) titres 1:8, 
1:128 and GMTs as measured by a serum bactericidal 
assay using rabbit complement (rSBA) in those subjects 
that received MenACWY-TT, and serogroup C (MenC) 
rSBA titres 1:8, 1:128 and GMTs in those subjects that 
received Meningitec.

To evaluate the long-term persistence of the serum 
bactericidal (antibody) titres induced by MenACWY-TT 
vaccine as compared to Mencevax ACWY when 
administered to individuals 2-10 years of age in terms of 
the percentage of subjects with Neisseria meningitidis
serogroup A (MenA), serogroup C (MenC), serogroup 
W-135 (MenW-135), and serogroup Y (MenY) titres 
1:8, 1:128 and GMTs as measured by a serum 
bactericidal assay using rabbit complement (rSBA).
Secondary
Persistence phase:
Long-term persistence phase: six, seven, eight, nine and 
ten years after primary vaccination with MenACWY-TT, 
Meningitec or Mencevax ACWY, in study MenACWY-TT-
027 

To evaluate the long-term persistence induced by 
MenACWY-TT vaccine as compared to Meningitec when 
administered to individuals 1-<2 years of age in terms of 
percentage of subjects with hSBA titres 1:4, 1:8 and 
GMTs for all four serogroups in those subjects that 
received MenACWY-TT and serogroup C (MenC) hSBA 
titres 1:4, 1:8 and GMTs in those subjects that received 
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Meningitec.

To evaluate the long-term persistence induced by 
MenACWY-TT vaccine as compared to Mencevax ACWY
when administered to individuals 2-10 years of age in 
terms of percentage of subjects with hSBA titres 1:4, 
1:8 and GMTs for all four serogroups.
Booster phase:
One month post booster vaccination with MenACWY-TT 
vaccine ten years after primary vaccination:

To evaluate the immunogenicity of a booster dose 
vaccination of MenACWY-TT with respect to the 
percentage of subjects with rSBA-MenA, rSBA-MenC, 
rSBA-MenW-135, and rSBA-MenY antibody titres ≥ 1:8, 
1:128 and GMTs.

To evaluate the immunogenicity of a booster dose 
vaccination of MenACWY-TT with respect to the 
percentage of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW-135, and hSBA-MenY antibody titres ≥ 
1:4, 1:8 and GMTs.

To evaluate the immunogenicity of a booster dose of 
MenACWY-TT conjugate vaccine in terms of the 
percentage of subjects with an rSBA-MenA, rSBA-
MenC, rSBA-MenW-135, rSBA-MenY booster
response*.
*rSBA booster response to meningococcal antigens (A, 
C, W-135 and Y) is defined as:

For initially seronegative subjects (pre-vaccination 
rSBA titer below 1:8): rSBA antibody titer ≥ 1:32 
one month after vaccination, and
- For initially seropositive subjects (pre-vaccination 
rSBA titer 1:8): at least four-fold increase in rSBA 
titers from pre-vaccination to one month after 
vaccination.

To evaluate the immunogenicity of a booster dose of 
MenACWY-TT conjugate vaccine in terms of the 
percentage of subjects with an hSBA-MenA, hSBA-
MenC, hSBA-MenW-135, hSBA-MenY booster 
response*.
*hSBA booster response to meningococcal antigens (A, 
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C, W-135 and Y) is defined as:
-
For initially seronegative subjects (pre-
vaccination hSBA titre below 1:4): hSBA 
antibody titres ≥1:8 one month after vaccination, 
and 
-
For initially seropositive subjects (hSBA titer 
1:4): a 4-fold increase in hSBA titres one month 
after vaccination.
Secondary safety objectives:
Persistence phase:

To describe SAEs related to vaccination and any event 
related to lack of vaccine efficacy (i.e. meningococcal 
disease) from the last persistence time point the subject 
participated in up to each yearly visit in the current study 
in a retrospective manner.
Booster phase:

To evaluate the safety and reactogenicity of a booster 
vaccination dose of MenACWY-TT conjugate vaccine.
Study design

Experimental design: Phase IIIb, open, multi-center study 
with four parallel groups:

ACWY<2 group: vaccinated with MenACWY-TT in 
study MenACWY-TT-027 (108658) and aged <2 
years at the time of primary vaccination,

MenCCRM group: vaccinated with Meningitec in 
study MenACWY-TT-027 (108658),

ACWY2 group: vaccinated with MenACWY-TT in 
study MenACWY-TT-027 (108658) and aged ≥2 
years at the time of primary vaccination,

MenPS group: vaccinated with Mencevax ACWY in 
study MenACWY-TT-027 (108658). 

Duration of the study:
Persistence phase
–
Epoch 001: Persistence Visit 1 [Month 78 (Year 6) 
post primary vaccination]
–
Epoch 002: Persistence Visit 2 [Month 90 (Year 7) 
post primary vaccination]
–
Epoch 003: Persistence Visit 3 [Month 102 (Year 8)
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post primary vaccination]
–
Epoch 004: Persistence Visit 4 [Month 114 (Year 9) 
post primary vaccination]
Booster phase
–
Epoch 005: Booster starting at Visit 5 [Month 126
(Year 10) post primary vaccination] and ending at the
Phone Contact (Month 132 or six months post 
booster)

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, Epoch 005
ACWY<2
183
1-<2 years at primary vaccination
x
MenCCRM
61
1-<2 years at primary vaccination
x
ACWY2 
183
2-10 years at primary vaccination
x
MenPS 
61
2-10 years at primary vaccination
x
*The actual sample size of this study with respect to the analysis of persistence and safety and immunogenicity 
post-booster is determined by a) the sample size of the primary vaccination study MenACWY-TT-027 (108658), b) 
by assumptions about the enrolment rate at the Years 6-10 extension study, and c) by assumptions about the 
annual dropout rate.
Synopsis Table 2
Study groups and treatment foreseen in the study
Treatment name
Vaccine/Product name
Study Groups
ACWY<2
MenCCRM
ACWY2
MenPS
MenACWY-TT 
MenACWY-TT 
● 
● 
● 
● 
NaCl*
● 
● 
● 
● 
*The lyophilized pellet of MenACWY-TT vaccine is to be reconstituted with the 
supplied saline solution.

Control: active control for persistence phase (MenCCRM 
and MenPS groups), uncontrolled for booster phase (all 
subjects receive the same booster vaccination 
[MenACWY-TT vaccine]).

Vaccination schedule: At Visit 5 (Month 126 post 
primary vaccination), one dose of MenACWY-TT will be 
administered to the subjects in all study groups.

Treatment allocation: NA

Blinding: open-label
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Synopsis Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001  
open  
Epoch 002  
open  
Epoch 003
open  
Epoch 004
open  
Epoch 005
open  

Blood sampling: at each study visit a blood sample will be 
collected for each subject enrolled. 

Type of study: extension of other protocol [MenACWY-
TT-027 (108658); 028 EXT:027 Y1 (108660); 029 
EXT:027 Y2 (108661); 030 EXT:027 Y3 (108663) 031 
EXT:027 Y4 (108665); 032 EXT:027 Y5 (108668)]

Data collection: electronic Case Report Form (eCRF)
Number of subjects
The subjects who were vaccinated in the vaccination phase of 
study MenACWY-TT-027 and received either MenACWY-TT 
vaccine, Meningitec or Mencevax ACWY will be eligible for this 
study if they meet the inclusion criteria and no exclusion 
criteria. Approximately 488 subjects will participate in this 
extension study.
Endpoints
Primary
Immunogenicity with respect to the components of the 
investigational vaccine six, seven, eight, nine and ten years 
after primary vaccination in study MenACWY-TT-027:

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-
MenY antibody titres 1:8, 1:128 and GMTs.
Secondary
Persistence phase:
Immunogenicity with respect to the components of the 
investigational vaccine six, seven, eight, nine and ten years 
after primary vaccination in study MenACWY-TT-027:

hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-
MenY antibody titres 1:4, 1:8 and GMTs.
Booster phase:
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Immunogenicity with respect to the components of the 
investigational vaccine one month post booster vaccination 
at ten years after primary vaccination:

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-
MenY antibody titres 1:8, 1:128 and GMTs and rSBA 
booster response.

hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-
MenY antibody titres 1:4, 1:8 and GMTs and hSBA 
booster response.
Safety and reactogenicity
Persistence phase:

Occurrence of serious adverse events related to vaccination 
and any event related to lack of vaccine efficacy (i.e. 
meningococcal disease) since the last persistent time point 
the subject participated in up to each yearly visit in the 
current study in a retrospective manner.
Booster phase

Occurrence of solicited local and general symptoms on 
days 0-3 following the booster vaccination.

Occurrence of unsolicited symptoms up to 31 days 
following booster vaccination.

Occurrence of all serious AEs, and new onset chronic 
illness(es) (e.g. autoimmune disorders, asthma, type 1 
diabetes and allergies) from administration of the vaccine 
dose until study end.
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TABLE OF CONTENTS
   PAGE
SYNOPSIS........................................................................................................... 7
LIST OF ABBREVIATIONS.................................................................................20
GLOSSARY OF TERMS.....................................................................................23
TRADEMARKS ...................................................................................................27
1.
INTRODUCTION ..........................................................................................28
1.1.
Background........................................................................................28
1.2.
Rationale for the study and study design ...........................................29
2.
OBJECTIVE(S).............................................................................................29
2.1.
Primary objectives..............................................................................29
2.2.
Secondary objectives.........................................................................29
3.
STUDY DESIGN OVERVIEW.......................................................................32
4.
STUDY COHORT .........................................................................................34
4.1.
Number of subjects/centres ...............................................................34
4.2.
Inclusion criteria for enrolment ...........................................................35
4.3.
Exclusion criteria for enrolment..........................................................36
5.
CONDUCT OF THE STUDY.........................................................................37
5.1.
Regulatory and ethical considerations, including the informed 
consent process.................................................................................37
5.2.
Subject identification and randomisation of treatment........................39
5.2.1.
Subject identification ............................................................39
5.2.2.
Study group and treatment allocation...................................39
5.3.
Method of blinding..............................................................................40
5.4.
General study aspects .......................................................................40
5.5.
Outline of study procedures ...............................................................40
5.6.
Detailed description of study procedures ...........................................45
5.6.1.
Informed consent .................................................................45
5.6.2.
Check inclusion and exclusion criteria .................................45
5.6.3.
Collect demographic data.....................................................46
5.6.4.
Medical history .....................................................................46
5.6.5.
Recording of meningococcal and TT vaccination history .....46
5.6.6.
History directed physical examination..................................46
5.6.7.
Pre-vaccination assessment of contraception......................46
5.6.8.
Urine pregnancy test............................................................46
5.6.9.
Check contraindications, warnings and precautions to 
vaccination ...........................................................................47
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5.6.10.
Assess pre-vaccination body temperature ...........................47
5.6.11.
Container number allocation ................................................47
5.6.12.
Sampling ..............................................................................47
5.6.12.1. Blood sampling for immune response 
assessments ........................................................47
5.6.13.
Study Vaccine administration...............................................47
5.6.14.
Check and record concomitant medication/vaccination and 
intercurrent medical conditions.............................................48
5.6.15.
Recording of AEs, SAEs and pregnancies...........................48
5.6.15.1. Recording of GBS and NOCIs .............................48
5.6.16.
Study conclusion..................................................................49
5.7.
Biological sample handling and analysis............................................49
5.7.1.
Use of specified study materials...........................................50
5.7.2.
Biological samples ...............................................................50
5.7.3.
Laboratory assays................................................................50
5.7.4.
Biological samples evaluation ..............................................52
5.7.4.1.
Immunological read-outs......................................52
5.7.5.
Immunological correlates of protection.................................53
6.
STUDY VACCINE AND ADMINISTRATION.................................................54
6.1.
Description of the study vaccine.........................................................54
6.2.
Storage and handling of the study vaccine ........................................54
6.3.
Dosage and administration of study vaccine......................................55
6.4.
Warnings and precautions .................................................................56
6.5.
Concomitant medication/product and concomitant vaccination..........56
6.5.1.
Recording of concomitant medications/products and 
concomitant vaccination.......................................................56
6.5.2.
Concomitant medications/products/vaccines that may lead 
to the elimination of a subject from ATP analyses................57
6.6.
Intercurrent medical conditions that may lead to elimination of a 
subject from ATP analyses ................................................................57
7.
HEALTH ECONOMICS.................................................................................58
8.
SAFETY........................................................................................................58
8.1.
Safety definitions................................................................................58
8.1.1.
Definition of an adverse event..............................................58
8.1.2.
Medication Errors.................................................................59
8.1.3.
Occupational Exposure ........................................................60
8.1.4.
Exposure During Pregnancy ................................................60
8.1.5.
Definition of a serious adverse event ...................................61
8.1.6.
Solicited adverse events ......................................................62
8.1.6.1.
Solicited local (injection-site) adverse events.......62
8.1.6.2.
Solicited general adverse events .........................63
8.1.7.
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events.....................................................................63
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8.1.8.
Adverse events of specific interest.......................................64
8.1.8.1.
List of New Onset of Chronic Illnesses.................64
8.1.9.
Pregnancy............................................................................67
8.2.
Detecting and recording adverse events, serious adverse events and 
pregnancies .......................................................................................68
8.2.1.
Time period for detecting and recording adverse events, 
serious adverse events and pregnancies.............................68
8.2.2.
Post-Study adverse events and serious adverse events......71
8.2.3.
Evaluation of adverse events and serious adverse events ..71
8.2.3.1.
Active questioning to detect adverse events and 
serious adverse events ........................................71
8.2.3.2.
Assessment of adverse events ............................71
8.2.3.2.1.
Assessment of intensity.....................71
8.2.3.2.2.
Assessment of causality ....................73
8.2.3.3.
Assessment of outcomes.....................................74
8.2.3.4.
Medically attended visits ......................................75
8.3.
Reporting of serious adverse events, pregnancies, and other events75
8.3.1.
Prompt reporting of serious adverse events, pregnancies, 
and other events ..................................................................75
8.3.2.
Completion and transmission of SAE reports.......................75
8.3.3.
Completion and transmission of pregnancy reports .............76
8.3.4.
Updating of SAE and pregnancy information after freezing of 
the subject’s eCRF...............................................................76
8.3.5.
Regulatory reporting requirements for serious adverse 
events ..................................................................................76
8.4.
Follow-up of adverse events, serious adverse events, and 
pregnancies .......................................................................................76
8.4.1.
Follow-up of adverse events and serious adverse events....76
8.4.1.1.
Follow-up during the study...................................76
8.4.1.2.
Follow-up after the subject is discharged from the 
study ....................................................................77
8.4.2.
Follow-up of pregnancies .....................................................77
8.5.
Treatment of adverse events .............................................................78
8.6.
Subject card .......................................................................................78
9.
SUBJECT COMPLETION AND WITHDRAWAL...........................................78
9.1.
Subject completion.............................................................................78
9.2.
Subject withdrawal .............................................................................78
9.2.1.
Subject withdrawal from the study........................................79
9.2.2.
Subject withdrawal from investigational vaccine ..................80
10. STATISTICAL METHODS ............................................................................80
10.1. Primary endpoint................................................................................80
10.2. Secondary endpoint(s).......................................................................80
10.3. Determination of sample size.............................................................81
10.4. Study cohorts/ data sets to be analysed ............................................84
10.4.1.
Persistence cohorts..............................................................84
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10.4.1.1. Total cohort at Month X........................................84
10.4.1.2. According-To-Protocol (ATP) cohort for 
persistence – MenC at Month X...........................84
10.4.1.3. According-To-Protocol (ATP) cohort for 
persistence – MenAWY at Month X .....................84
10.4.2.
Booster cohort......................................................................85
10.4.2.1. Booster Total Vaccinated Cohort .........................85
10.4.2.2. Booster According-To-Protocol (ATP) cohort for 
safety ...................................................................85
10.4.2.3. Booster According To Protocol (ATP) cohort for 
immunogenicity - MenC .......................................86
10.4.2.4. Booster According To Protocol (ATP) cohort for 
immunogenicity – MenAWY.................................86
10.5. Derived and transformed data............................................................87
10.5.1.
Persistence analyses ...........................................................87
10.5.1.1. Analysis of demographics/baseline characteristics87
10.5.1.2. Analysis of persistence ........................................88
10.5.1.2.1. Within group analysis.........................88
10.5.1.2.2. Between group analysis.....................88
10.5.1.3. Analysis of safety (Persistence epoch) ................89
10.5.2.
Post-booster analyses..........................................................89
10.5.2.1. Analysis of demographics/baseline characteristics89
10.5.2.2. Analysis of post-booster immunogenicity.............89
10.5.2.2.1. Within group analysis.........................89
10.5.2.3. Analysis of post-booster safety ............................90
10.6. Interpretation of analyses...................................................................91
10.7. Conduct of analyses...........................................................................91
10.7.1.
Sequence of analyses..........................................................91
10.7.2.
Statistical considerations for interim analyses......................91
11. ADMINISTRATIVE MATTERS......................................................................91
11.1. Remote Data Entry instructions..........................................................92
11.2. Study Monitoring ................................................................................92
11.3. Record retention.................................................................................93
11.4. Quality assurance ..............................................................................93
11.5. Posting of information on publicly available clinical trial registers and 
publication policy................................................................................94
11.6. Provision of study results to investigators ..........................................94
11.7. Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP ............................................................................................95
12. COUNTRY SPECIFIC REQUIREMENTS.....................................................96
13. REFERENCES .............................................................................................97
CCI
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LIST OF TABLES
PAGE
Table 1
Study groups and epochs foreseen in the study............................33
Table 2
Study groups and treatment foreseen in the study ........................34
Table 3
Blinding of study epochs................................................................34
Table 4
List of study procedures.................................................................41
Table 5
Intervals between study visits ........................................................45
Table 6
Biological samples .........................................................................50
Table 7
Humoral Immunity (Antibody determination)..................................51
Table 8
Immunological read-outs................................................................52
Table 9
Study vaccine ................................................................................54
Table 10
Dosage and administration ............................................................55
Table 11
Solicited local adverse events........................................................62
Table 12
Solicited general adverse events...................................................63
Table 13
List of NOCIs .................................................................................64
Table 14
Reporting periods for adverse events, serious adverse events and 
pregnancies ...................................................................................69
Table 15
Intensity scales for solicited symptoms..........................................72
Table 16
Timeframes for submitting serious adverse event, pregnancy and 
other events reports.......................................................................75
Table 17
Exact 95% confidence intervals of the percentage of subjects with 
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres 
≥ 1:8...............................................................................................83
Table 18
Neomed Institute..........................................................................100
Table 19
Outsourced laboratories...............................................................100
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LIST OF FIGURES
PAGE
Figure 1
Study design figure ........................................................................32
LIST OF APPENDICES
PAGE
APPENDIX A .................................................................................LABORATORY ASSAYS
99
APPENDIX B ...........................................................................CLINICAL LABORATORIES
100
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LIST OF ABBREVIATIONS
AE
Adverse event
ANOVA
Analysis of variance
ATP
According-to-protocol
CDC
Centers for Disease Control and Prevention, United States of 
America
CDS
Core Data Sheet
CFU
Colony-forming unit
CI
Confidence interval
CRM197
a non-toxic mutant of Corynebacterium dipththeriae toxin
CSA
Clinical Study Agreement
D
Deltoid
DT
Diphtheria Toxoid
DU
Dispensable Unit
eCRF
electronic Case Report Form
EDD
Estimated Date of Delivery
EDP
Exposure during pregnancy
EGA
Estimated Gestational Age
ESFU
Extended Safety Follow-Up
EU
European Union
EudraCT
European Clinical Trials Database
GBS
Guillain-Barré Syndrome
GCP
Good Clinical Practice
GMT
Geometric Mean Titre
GSK
GlaxoSmithKline 
HIV
Human Immunodeficiency Virus
hSBA-MenA
Serum bactericidal assay/activity against Neisseria 
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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)
IAF
Informed Assent Form
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IM
Intramuscular
IMP
Investigational Medicinal Product
IRB
Institutional Review Board
IRT
Interactive Response Technology
LAR
Legally Acceptable Representative
LMP
Last Menstrual Period
MedDRA
Medical Dictionary for Regulatory Activities
MenA
Neisseria meningitidis serogroup A
MenC
Neisseria meningitidis serogroup C
MenW-135
Neisseria meningitidis serogroup W-135
MenY
Neisseria meningitidis serogroup Y
MenACWY-TT
Meningococcal serogroups A, C, W-135, Y tetanus toxoid 
conjugate vaccine
mL
milliliter
NA
Not Applicable
NOCI
PHE
New Onset of Chronic Illness
Public Health England
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pIMD
Potential Immune Mediated Disorder
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
SAP
Serious Adverse Event
Statistical Analysis Plan
SBA
Serum Bactericidal Assay/Activity
SDV
Source Data Verification
SPM
Study Procedures Manual
TT
Tetanus Toxoid
US
United States
WHO
World Health Organisation
g
Microgram
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GLOSSARY OF TERMS
Adequate contraception:
Adequate contraception is defined as a contraceptive 
method with failure rate of less than 1% per year when 
used consistently and correctly (when applicable, as 
mentioned in the product label) for example abstinence
(any version of temporary or episodic abstinence is not 
considered adequate contraception), combined or 
progestogen oral contraceptives, injectable progestogen, 
implants of levonorgestrel, oestrogenic vaginal ring, 
percutaneous contraceptive patches or intrauterine device 
or intrauterine system, vasectomy with documented 
azoospermia of the sole male partner or male condom 
combined with a vaginal spermicide (foam, gel, film, 
cream or suppository) or male condom combined with a 
female diaphragm, either with or without a vaginal 
spermicide (foam, gel, film, cream, or suppository).
For azoospermia, ‘documented’ refers to the outcome of 
the investigator’s/designee’s medical examination of the 
subject or review of the subject’s medical history for 
study eligibility, as obtained via a verbal interview with 
the subject or from the subject’s medical records.
Adverse event (AE):
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 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.
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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. 
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.
Container number
A number identifying a treatment to a subject, according 
to the study randomisation or treatment allocation.
Core Data Sheet
The Core Data Sheet (CDS) represents the internal 
company medical position for all labeling documents 
worldwide. The CDS is a document containing all 
essential safety information, such as contraindications, 
warnings/precautions, and undesirable effects, which 
Pfizer requires to be included in the proposed labeling of 
all countries where the product is marketed. The Core 
Data Sheet also contains indications and dosing 
information (for all dosage forms) supported worldwide, 
as well as pharmacodynamic, pharmacokinetic and non-
clinical information that has important bearing on the safe 
and effective use of the product. Information contained in 
the Core Data Sheet is based on valid, scientific/medical 
data. The Core Data Sheet is a vehicle by which 
information on a marketed product is communicated to 
the appropriate stakeholders worldwide.
Eligible:
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria.
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Epoch:
An epoch is a well defined part of a protocol that covers a 
set of consecutive time points. Generally, an epoch is 
self-contained and allows to perform a data analysis to 
address some of the trial objectives (e.g. primary, booster, 
yearly follow-ups,…).
Evaluable:
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the according-to-protocol (ATP) analysis.
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.
Menarche:
Menarche is the onset of menses for the first time in a 
young female and is preceded by several changes 
associated with puberty including breast development and 
pubic hair growth. Menarche usually occurs within 1-2 
years of breast development, thelarche. However, a young 
female can become pregnant before her first menses. 
Thus, a conservative definition of non-childbearing 
potential in a pre-menarcheal female is a young female 
who has not yet entered puberty as evidenced by lack of 
breast development (palpable glandular breast tissue).
Potential Immune-
Mediated Disease
Potential immune-mediated diseases (pIMDs) are a subset 
of AEs that include autoimmune diseases and other 
inflammatory and/or neurologic disorders of interest 
which may or may not have an autoimmune aetiology.
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 
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terminated.
Randomization:
Process of random attribution of treatment to subjects in 
order to reduce bias of selection.
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 investigational product(s) or as a control.
Subject number:
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study.
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.
Unsolicited adverse 
event:
Any adverse event (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 and 
Y tetanus toxoid conjugate vaccine
Mencevax® ACWY
Meningococcal serogroups A, C, W-135 and 
Y plain polysaccharide vaccine
Trademarks not owned by Pfizer 
Generic description
Meningitec® (Nuron Biotech Inc.)
Meningococcal Serogroup C conjugate 
vaccine
Menveo® (GSK)
Meningococcal (Groups A, C, Y and W-135) 
Oligosaccharide Diphtheria CRM197 
Conjugate Vaccine
Menactra® (Sanofi Pasteur Inc)
Meningococcal Polysaccharide (Serogroups 
A, C, Y and W-135) Diphtheria Toxoid 
Conjugate Vaccine
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1.
INTRODUCTION
1.1.
Background
Invasive diseases caused by Neisseria meningitidis are serious threats to global health. The 
infection rates are highly age dependent. The risk of meningococcal disease is highest in infancy, 
with a secondary, slightly smaller peak in late adolescence [Rosenstein, 2001]. Case-fatality rates 
of invasive disease are around 10% and up to 20% of patients who recover develop significant 
long-term sequelae [Healy, 2002]. Prevention of meningococcal disease relies on effective 
immunization programs. The most common serogroups are A, B, C, W-135 and Y [Harrison, 
2010].
Meningococcal disease affects mostly young children with a second peak in adolescents (15-19 
year age group). For those vaccinated during early childhood a booster might be needed before 
adolescence and for those vaccinated as young adolescent’s long-term antibody persistence is 
needed to ensure protection throughout this peak in disease incidence [Cohn, 2010]. Hence there 
is a need to understand how long immunity persists in case of re-exposure through frequent 
travels.
Currently, there are three quadrivalent meningococcal conjugate vaccines available in various 
countries worldwide for vaccination of children and adolescents/adults; MenACWY diphtheria 
toxoid (DT) conjugate vaccine (Menactra, Sanofi Pasteur Inc.) is authorised for active 
immunization of subjects aged 9 months to 55 years in the US [Menactra Product Information, 
2009; Menactra Approval Letter, 2011], Canada and Gulf Cooperation States in the Middle East. 
MenACWY CRM-197 conjugate vaccine (Menveo, GSK) is authorised for active immunization 
of subjects from 2 years of age in the European Union [EPAR, 2012] and Australia [Menveo 
Consumer Medicine Information, 2010], and from 2 through 55 years of age in Canada and the 
United States [Menveo Product Monograph, 2010; Menveo Prescribing Information, 2011]. A
quadrivalent vaccine (Nimenrix) was developed for the prevention of invasive infections with 
Neisseria meningitidis serogroups A, C, Y, and W-135, using tetanus toxoid as the carrier. This 
vaccine, which was granted a marketing authorisation on 20 April 2012 by the European 
Commission and licensed in Canada for individuals 12 months to 55 years as of March, 2013,
has been shown to be immunogenic and well tolerated in individuals as of 12 months of age
[European Commission, 2012].
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 Core Data Sheet (CDS) for information regarding the pre-clinical and 
clinical studies and the potential risks and benefits of the MenACWY-TT vaccine. The CDS is 
the single reference safety document for this study.
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1.2.
Rationale for the study and study design
In study MenACWY-TT-027, 613 healthy subjects between 1 and 10 years of age were 
randomized using a (3:1) ratio to receive either a single dose of MenACWY-TT vaccine or a 
meningococcal C conjugate vaccine or a meningococcal polysaccharide vaccine. The subjects 
were followed up for antibody persistence over five years post-vaccination in studies 
MenACWY-TT-028 through -032. The results showed that subjects vaccinated with 
MenACWY-TT between ages 1 and 2 years of age had detectable antibodies five years after 
vaccination in 73.5%, 77.6%, 34.7% and 42.9% of subjects against serogroups A, C, W-135 and 
Y, respectively. Subjects vaccinated with MenACWY-TT at 2-10 years of age in this same study 
showed that five years after vaccination 90.8%, 90.8%, 78.6% and 78.6% of subjects had 
detectable antibodies against A, C, W-135 and Y serogroups, respectively. The main purpose of 
this study is to continue to evaluate the antibody persistence 6, 7, 8, 9 and 10 years post-
administration of MenACWY-TT conjugate vaccine as compared to Meningitec or Mencevax 
ACWY when given to healthy subjects 1 to 10 years of age. In addition, the safety and 
immunogenicity of a booster dose of MenACWY-TT vaccine administered to all eligible 
subjects 10 years after the primary vaccination will be evaluated.
2.
OBJECTIVE(S)
2.1.
Primary objectives
Long-term persistence phase: Six, seven, eight, nine and ten years after primary 
vaccination with MenACWY-TT or Meningitec or Mencevax ACWY, in study MenACWY-
TT-027

To evaluate the long-term persistence of the serum bactericidal (antibody) titres induced by 
MenACWY-TT vaccine as compared to Meningitec when administered to individuals 1-<2 
years of age in terms of the percentage of subjects with Neisseria meningitidis serogroup A 
(MenA), serogroup C (MenC), serogroup W-135 (MenW-135), and serogroup Y (MenY) 
titres 1:8, 1:128 and GMTs as measured by a serum bactericidal assay using rabbit 
complement (rSBA) in those subjects that received MenACWY-TT, and serogroup C 
(MenC) rSBA titres 1:8, 1:128 and GMTs in those subjects that received Meningitec.

To evaluate the long-term persistence of the serum bactericidal (antibody) titres induced by 
MenACWY-TT vaccine as compared to Mencevax ACWY when administered to individuals 
2-10 years of age in terms of the percentage of subjects with Neisseria meningitidis
serogroup A (MenA), serogroup C (MenC), serogroup W-135 (MenW-135), and serogroup 
Y (MenY) titres 1:8, 1:128 and GMTs as measured by a serum bactericidal assay using 
rabbit complement (rSBA).
Refer to Section 10.1 for the definition of the primary endpoints.
2.2.
Secondary objectives
Persistence phase:
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Long–term persistence phase: six, seven, eight, nine and ten years after primary 
vaccination with MenACWY-TT, Meningitec or Mencevax ACWY, in study MenACWY-
TT-027

To evaluate the long-term persistence induced by MenACWY-TT vaccine as compared to 
Meningitec when administered to individuals 1-<2 years of age in terms of percentage of 
subjects with hSBA titres 1:4, 1:8 and GMTs for all four serogroups in those subjects that 
received MenACWY-TT and serogroup C (MenC) hSBA titres 1:4, 1:8 and GMTs in 
those subjects that received Meningitec.

To evaluate the long-term persistence induced by MenACWY-TT vaccine as compared to 
Mencevax ACWY when administered to individuals 2-10 years of age in terms of percentage 
of subjects with hSBA titres 1:4, 1:8 and GMTs for all four serogroups.
Booster phase:
One month post booster vaccination with MenACWY-TT vaccine ten years after primary 
vaccination:

To evaluate the immunogenicity of a booster dose vaccination of MenACWY-TT with 
respect to the percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and 
rSBA-MenY antibody titres ≥ 1:8, 1:128 and GMTs.

To evaluate the immunogenicity of a booster dose vaccination of MenACWY-TT with 
respect to the percentage of subjects with hSBA-MenA, hSBA-MenC, hSBA-MenW-135, 
and hSBA-MenY antibody titres ≥ 1:4, 1:8 and GMTs.

To evaluate the immunogenicity of a booster dose of MenACWY-TT conjugate vaccine in 
terms of the percentage of subjects with an rSBA-MenA, rSBA-MenC, rSBA-MenW-135, 
rSBA-MenY booster response*.
*rSBA booster response to meningococcal antigens (A, C, W-135 and Y) is defined as:

For initially seronegative subjects (pre-vaccination rSBA titer below 1:8): rSBA 
antibody titer ≥ 1:32 one month after vaccination, and
- For initially seropositive subjects (pre-vaccination rSBA titer 1:8): at least four-fold 
increase in rSBA titers from pre-vaccination to one month after vaccination.

To evaluate the immunogenicity of a booster dose of MenACWY-TT conjugate vaccine in 
terms of the percentage of subjects with an hSBA-MenA, hSBA-MenC, hSBA-MenW-135,
hSBA-MenY booster response*.
*hSBA booster response to meningococcal antigens (A, C, W-135 and Y) is defined as:
-
For initially seronegative subjects (pre-vaccination hSBA titre below 1:4): hSBA 
antibody titres ≥1:8 one month after vaccination, and 
-
For initially seropositive subjects (hSBA titer 1:4): a 4-fold increase in hSBA titres 
one month after vaccination.
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Secondary safety objectives:
Persistence phase:

To describe SAEs related to vaccination and any event related to lack of vaccine efficacy 
(i.e. meningococcal disease) from the last persistence time point the subject participated in
up to each yearly visit in the current study in a retrospective manner.
Booster phase:

To evaluate the safety and reactogenicity of a booster vaccination dose of MenACWY-TT 
conjugate vaccine.
Refer to Section 10.2 for the definition of the secondary endpoints.
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3.
STUDY DESIGN OVERVIEW
Figure 1
Study design figure
BS= blood sample
TC = Telephone Contact
Vacc = vaccination
ESFU = Extended safety follow-up
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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 IIIB, open-label, multi-centric, study with four parallel groups:

ACWY<2 group: vaccinated with MenACWY-TT in study MenACWY-TT-027
(108658) and aged <2 years at the time of primary vaccination,

MenCCRM group: vaccinated with Meningitec in study MenACWY-TT-027 (108658),

ACWY2 group: vaccinated with MenACWY-TT in study MenACWY-TT-027
(108658) and aged ≥2 years at the time of primary vaccination,

MenPS group: vaccinated with Mencevax ACWY in study MenACWY-TT-027
(108658). 

Duration of the study:
Persistence phase
–
Epoch 001: Persistence Visit 1 [Month 78 (Year 6) post primary vaccination]
–
Epoch 002: Persistence Visit 2 [Month 90 (Year 7) post primary vaccination]
–
Epoch 003: Persistence Visit 3 [Month 102 (Year 8) post primary vaccination]
–
Epoch 004: Persistence Visit 4 [Month 114 (Year 9) post primary vaccination]
Booster phase
–
Epoch 005: Booster starting at Visit 5 [Month 126 (Year 10) post primary vaccination]
and ending at the Phone Contact (Month 132 or six months post booster)

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, Epoch 005
ACWY<2
183
1-<2 years at primary vaccination
x
MenCCRM
61
1-<2 years at primary vaccination
x
ACWY2 
183
2-10 years at primary vaccination
x
MenPS 
61
2-10 years at primary vaccination
x
*The actual sample size of this study with respect to the analysis of persistence and safety and immunogenicity 
post-booster is determined by a) the sample size of the primary vaccination study MenACWY-TT-027 (108658), b) 
by assumptions about the enrolment rate at the Years 6-10 extension study, and c) by assumptions about the 
annual dropout rate.
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Table 2
Study groups and treatment foreseen in the study
Treatment name
Vaccine/Product name
Study Groups
ACWY<2
MenCCRM
ACWY2
MenPS
MenACWY-TT 
MenACWY-TT 
● 
● 
● 
● 
NaCl*
● 
● 
● 
● 
*The lyophilized pellet of MenACWY-TT vaccine is to be reconstituted with the 
supplied saline solution (see Section 6).

Control: active control for persistence phase (MenCCRM and MenPS groups), uncontrolled 
for booster phase (all subjects receive the same booster vaccination [MenACWY-TT 
vaccine]).

Vaccination schedule: At Visit 5 (Month 126 post primary vaccination), one dose of 
MenACWY-TT will be administered to the subjects in all study groups.

Treatment allocation: NA

Blinding: open-label
Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001  
open  
Epoch 002  
open  
Epoch 003
open  
Epoch 004
open  
Epoch 005
open  

Blood sampling: at each study visit a blood sample will be collected for each subject 
enrolled. 

Type of study: extension of other protocol [MenACWY-TT-027 (108658); 028 EXT:027 Y1 
(108660); 029 EXT:027 Y2 (108661); 030 EXT:027 Y3 (108663) 031 EXT:027 Y4 
(108665); 032 EXT:027 Y5 (108668)]

Data collection: electronic Case Report Form (eCRF)
4.
STUDY COHORT
4.1.
Number of subjects/centres
Six hundred and thirteen subjects (460 in the ACWY-TT group, 75 in the MenCCRM group and 
78 in the MenPS group) were enrolled and vaccinated in study MenACWY-TT-027 (108658). 
The subjects who were vaccinated in the vaccination phase of study MenACWY-TT-027 and 
received either MenACWY-TT vaccine, Meningitec or Mencevax ACWY will be eligible for this 
study if they meet the inclusion criteria and no exclusion criteria.
At the time of the study and prior to every visit, the investigator will contact all of the 
subjects/parents/legally acceptable representative(s) (LAR[s]) who agreed to participate in a 
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follow-up study. If at any contact of the long term study, any subject or parent(s)/LAR(s) of a 
subject declines participation, refusal will be documented in the source documents. Subjects will 
be able to enter the study at any visit up to Visit 5. An informed consent form for this protocol 
must be signed prior to any study-related procedure. Any subject who turns of legal age during 
the study and had previously given assent will need to sign an informed consent form.  Subjects 
will be able to participate in any study visit 1, 2, 3, 4, or 5 independent of other study visits, at 
their own or at their parent/LAR’s discretion as applicable (e.g., it is possible that a subject 
comes to Visit 1 and Visit 3 but not Visit 2).
Refer to Section 10.3 for the accuracy expected from the estimated sample size with respect to 
the primary objective.
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 the following criteria at study entry to the persistence phase:

Subjects and/or subjects’ parent(s)/LAR(s) who, in the opinion of the investigator, can and 
will comply with the requirements of the protocol (e.g. completion of the diary cards, return 
for follow-up visits).

A male or female who has received a primary vaccination with the MenACWY-TT, 
Meningitec or Mencevax ACWY vaccines in study MenACWY-TT-027 (108658).

In alignment with local laws and regulations, written informed consent obtained from 
parent(s)/LAR(s) of the subject and written informed assent obtained from the subject if the 
subject is less than 15 years of age, or written informed consent obtained from the subject if 
the subject has achieved the 15th birthday. The subjects 15 years of age at the time of 
enrolment will sign the informed consent form, even if the parent/ LAR previously signed 
the ICF before the subject reached the legal age of consent.

Healthy subjects as established by medical history and history-directed physical examination 
before entering into the study.
All subjects must satisfy the following additional criteria prior to entry of the booster 
phase:

Female subjects of non-childbearing potential may be enrolled in the study. 

Non-childbearing potential is defined as pre-menarche, hysterectomy or bilateral
ovariectomy.
Please refer to the glossary of terms for the definition of menarche.
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
Male subjects able to father children and female subjects of childbearing potential (including 
females who have had tubal ligation) and at risk for pregnancy may be enrolled in the study, 
if the subject:

has practiced adequate contraception for 30 days prior to vaccination, and

has a negative pregnancy test on the day of vaccination (for females only), and

has agreed to continue adequate contraception during the entire treatment period and for 
2 months after completion of the vaccination.
Please refer to the glossary of terms for the definition of adequate contraception.
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:
Exclusion criteria for study entry

Child in care
Please refer to the glossary of terms for the definition of child in care.

Previous vaccination with meningococcal polysaccharide or conjugate vaccine outside of 
study MenACWY-TT-027.
Note: Subjects who were revaccinated with a monovalent MenC conjugate vaccine because 
of suboptimal response during the persistence phase of the MenACWY-TT-027 study (i.e. 
MenACWY-TT-028, -029, -030, -031 and -032) are allowed to participate as they will be 
followed for the persistence of MenA, MenW-135 and MenY.

History of meningococcal disease due to serogroup A, C, W-135 or Y.

Previous vaccination with meningococcal B vaccine.

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). 

Family history of congenital or hereditary immunodeficiency.

Major congenital defects or serious chronic illness.

History of chronic alcohol consumption and/or drug abuse.

Subjects who withdrew consent to be contacted for follow-up studies 
Additional exclusion criteria for booster phase at Month 126 study entry (to be checked at 
Month 126) for all subjects
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
Use of any investigational or non-registered product (drug or vaccine) other than the study 
vaccine within 30 days preceding the booster dose of study vaccine, or planned use during 
the follow-up period.

Administration of a vaccine not foreseen by the study protocol in the period starting 30 days 
before the booster dose of study vaccine or planned administration within 30 days after 
vaccination, with the exception of a licensed inactivated influenza vaccine.

Chronic administration (defined as more than 14 days in total) of immunosuppressants or 
other immune-modifying drugs within six months prior to the booster vaccine dose (for 
corticosteroids, this will mean prednisone 10 mg/day, or equivalent). Inhaled and topical 
steroids are allowed.

Administration of immunoglobulins and/or any blood products within the three months 
preceding the booster vaccination or planned administration during the follow-up period.

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).

History of any reaction or hypersensitivity likely to be exacerbated by any component of the 
vaccines.

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 vaccination. 

Fever is defined as temperature 37.5°C for oral, axillary, tympanic, or 38.0C for 
rectal route. The preferred route for recording temperature in this study will be oral.

Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) 
without fever may be vaccinated at the discretion of the investigator. 

Pregnant or lactating female.

Female planning to become pregnant or planning to discontinue contraceptive precautions.

Male subjects able to father children who are planning to discontinue contraceptive 
precautions.

Subjects who are investigational site staff members directly involved in the conduct of the 
study and their family members, site staff members otherwise supervised by the investigator, 
or subjects who are Pfizer employees directly involved in the conduct of the study.
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.
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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/ subject’s parent(s)/LAR(s) informed consent and subject informed assent, as 
appropriate. 

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.
Freely given and written informed consent must be obtained from each subject and/or each 
subject’s parent(s)/LAR(s) and subject informed assent, as appropriate, prior to participation in 
the study. 
Pfizer will prepare a model Informed Consent Form (ICF) which will embody the ICH GCP and 
Pfizer required elements. While it is strongly recommended that this model ICF is to be followed 
as closely as possible, the informed consent 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. 
In accordance with the ICH Harmonised Tripartite Guidelines for Good Clinical Practice, those 
subjects who can only be enrolled in the study with the consent of the subject’s legally 
acceptable representative (e.g. minors), should be informed about the study to the extent 
compatible with the subject’s understanding and, if capable, the subject should sign and 
personally date a written informed assent form (IAF). It is required that the assent be signed by 
each subject, if capable, in addition to the informed consent that is to be signed by his/her legal 
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representative. It should be assessed whether an assent is required depending of the age of the 
study population and the local requirements.
If the subject reaches the age of consent during the study they will be asked to provide consent at 
the next study visit (if applicable). This procedure should be applied according to local laws and 
regulations.
The investigator has the final responsibility for the final presentation of the ICF, 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.
5.2.
Subject identification and randomisation of treatment
5.2.1.
Subject identification
Approximately 488 subjects are expected to participate in this study (183 subjects from the 
ACWY<2 and ACWY2 groups each, and 61 subjects from the MenCCRM and MenPS groups 
each).
Subjects will retain the same subject number as in MenACWY-TT-027 (108658).
5.2.2.
Study group and treatment allocation
All subjects who received either MenACWY-TT, Mencevax ACWY or Meningitec in study 
MenACWY-TT-027 (108658) will be eligible for this study if they meet the inclusion/exclusion 
criteria. All subjects that were vaccinated in MenACWY-TT-027 will be invited to participate in 
this study. Approximately, 488 subjects are expected to participate in the study.
There will be no randomization for allocation to study groups in this study. The subjects in this 
study will be allocated to the same groups as in the vaccination study MenACWY-TT-027 
(108658). Subjects will be allocated a new container number.
Allocation of subjects to vaccine groups will proceed through the use of an interactive response 
technology (IRT) system. The site personnel (study coordinator or specified designee) will be 
required to enter or select information including but not limited to the user’s identification (ID) 
and password, the protocol number, the subject number and the date of birth of the subject. The 
site personnel will then be provided with a vaccine assignment and dispensable unit (DU) or 
container number. The IRT system will provide a confirmation report containing the subject 
number and DU or container number assigned.
After obtaining the signed and dated ICF/IAF from the subject/subjects’ parent(s)/LAR(s) and 
having checked the eligibility of the subject at the subject’s first persistence visit in the study, the 
site staff in charge of the vaccine administration will access IRT. Upon providing the subject 
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identification number, the randomisation system will provide the container number to be used for 
the dose. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen.
When IRT is not available, please refer to the IRT user guide or the Study Procedures Manual 
(SPM) for specific instructions.
5.3.
Method of blinding 
This study will be conducted in an open manner.
Any person involved in the clinical conduct of the study (including data cleaning) will stay as 
blind as possible during the study.
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
See Table 4 for the list of study procedures.
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Table 4
List of study procedures
Visit
VISIT 1*
VISIT 2*
VISIT 3*
VISIT 4*
VISIT 5*
VISIT 6 *
Phone Contact 
Timing
Month 78 (Year 6)
Month 90 (Year 7)
Month 102 (Year 8)
Month 114 (Year 9)
Month 126 (Year 10)
Month 127  
Month 132
Epoch
Epoch 001 
Epoch 002 
Epoch 003 
EPOCH 004
Epoch 005 
Sampling time point
Year 6 post-primary 
vaccination 
Year 7 post-primary 
vaccination 
Year 8 post-primary 
vaccination 
Year 9 post-primary 
vaccination 
Year 10 post-primary 
vaccination and Pre-
booster vaccination 
One month 
post-booster 
vaccination 
ESFU 
Informed consent1
●
●
●
●
●
informed assent1
O
O
O
O
O
Check inclusion/exclusion
criteria2
●
●
●
●
●
Check additional
inclusion/exclusion criteria for 
booster phase
●3
Check contraindications 
O
Check warnings and precautions 
O
Check medical history since last 
visit done4
●
●
●
●
●
Meningococcal vaccination 
history since last visit done4
●
●
●
●
●
Vaccination history of TT 
containing vaccines since last 
visit done4
●
●
●
●
●
History-directed physical 
examination
●
Pre-vaccination assessment of 
contraception
●
Collect urine for pregnancy test 
for females of childbearing 
potential
●
Pre-vaccination assessment of 
body temperature
●
Record container number
●
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Visit
VISIT 1*
VISIT 2*
VISIT 3*
VISIT 4*
VISIT 5*
VISIT 6 *
Phone Contact 
Timing
Month 78 (Year 6)
Month 90 (Year 7)
Month 102 (Year 8)
Month 114 (Year 9)
Month 126 (Year 10)
Month 127  
Month 132
Epoch
Epoch 001 
Epoch 002 
Epoch 003 
EPOCH 004
Epoch 005 
Blood sampling for antibody 
determination (approximate 
volume)
7 mL
7 mL
7 mL
10 mL
10 mL
10 mL
Record timing related to 
reconstitution and vaccination
●
Vaccination (MenACWY-TT)
●
Observation of subjects for 30 
minutes post vaccination
O
Distribution of diary cards
O
Daily post-vaccination recording 
of solicited adverse events within 
4 days (Days 0-3) after 
administration of the booster 
dose
●
Recording of non-serious 
adverse event 30 days post-
vaccination by investigator
●
●
Return of diary cards5
O
Diary card transcription 
O
Record any concomitant 
medication/vaccination6
●
●
●
●
●
●
●
Record any intercurrent medical 
conditions 7,8
●
●
●
●
●
●
●
Recording of all SAEs8,12
●
●
●
Recording of serious adverse 
events (SAEs) related to study 
vaccination and any event 
related to lack of vaccine efficacy 
since the previous visit.8,9
●
●
●
●
●
●
●
Recording of SAEs related to 
study participation10  
●
●
●
●
●
●
●
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Visit
VISIT 1*
VISIT 2*
VISIT 3*
VISIT 4*
VISIT 5*
VISIT 6 *
Phone Contact 
Timing
Month 78 (Year 6)
Month 90 (Year 7)
Month 102 (Year 8)
Month 114 (Year 9)
Month 126 (Year 10)
Month 127  
Month 132
Epoch
Epoch 001 
Epoch 002 
Epoch 003 
EPOCH 004
Epoch 005 
Recording of new onset of 
chronic illness (NOCI)11,13
●
●
●
Recording of Guillain Barré 
Syndrome (GBS)12,13
●
●
●
Recording of pregnancies14
●
●
Study Conclusion 
●15
Note: the double-line border following Months 78, 90, 102, 114, 127 and 132 indicates the analysis which will be performed on as clean as possible data obtained up to those time 
points. 
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 to be captured in site source records that does not require documentation in the individual eCRF.
*Subjects/subject’s parent(s)/LAR(s) will be contacted by phone 4-8 weeks beforehand to come in for the persistence visit. The subject may return at any visit during the persistence 
epochs.
1 Informed consent is only required at Visit 2, Visit 3, Visit 4 or Visit 5 if the informed consent form was not signed at previous study visits, i.e. if either Visit 2, Visit 3, Visit 4 or Visit 5 is 
the first persistence visit for a given subject. Subjects will be able to participate in any study visit 1, 2, 3, 4, or 5 independent of other study visits, at their own or at their parent/LAR’s 
discretion as applicable (e.g., it is possible that a subject comes to Visit 1 and Visit 3 but not Visit 2).
2 Check of inclusion and exclusion criteria for the persistence epochs at Visit 2, Visit 3, Visit 4 and Visit 5 is only required if these checks were not performed at a previous study visit, 
i.e. if Visit 2, Visit 3, Visit 4 or Visit 5 is the first persistence visit for a given subject. 
3Note that Visit 5 is part of the persistence epoch (Month 126: Visit 5) as well as the pre-booster vaccination visit. Thus if a subject first enters the study at Visit 5, eligibility criteria for 
both the persistence epoch and for the booster epoch will be checked. 
4 Including since the last visit from the last persistence study the subject attended until the enrollment visit in this extension study.
5 If the subject returns for the Visit 6 blood draw prior to the end of the 31-day safety follow-up period (Day 30), the subject will continue to record safety information on the diary card 
until 31 days post-vaccination (Day 30), and will mail the diary card into the site.
6 See section 6.5.2 for medications and timeframe for recording. 
7 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 disease, any confirmed or suspected immunosuppressive or immunodeficient condition and diagnosis of serious chronic illness) collected throughout the study along 
with other AEs. 
8 This will also include SAE(s) leading to withdrawal of the subject from the study. Occurrence of meningococcal diseases should be reported as SAEs and documented in the AE 
screen in the eCRF during the entire study period.
9When the subject comes in for the first visit in the current study, SAEs related to study vaccination and any event related to lack of vaccine efficacy experienced since the last 
persistent time point the subject participated in should also be recorded.
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10 This will also include SAE(s) leading to the withdrawal of the subject from the study.
11 New onset of chronic illnesses (NOCIs) (e.g. autoimmune disorders, allergies, type 1 diabetes, asthma) will be recorded from Visit 5 until the end of the study and will be recorded as 
unsolicited AEs or SAEs as appropriate.. A non-exhaustive list of NOCIs is shown in Table 13.
12 In the event of GBS, subjects/subjects' parent(s)/LAR(s) should be contacted to obtain clinical details as outlined in the 'Potential immune mediated disorders (pIMDs): standard 
questionnaires and list of preferred terms'. All occurrences of GBS have to be recorded as an SAE.
13 Recording will start after administration of the vaccine dose.
14Pregnancies occurring between vaccination (Day 0) and 31 days after vaccination (Day 30) will be recorded. Subjects will be questioned at Month 132, 6 months after the booster 
vaccination, whether any unreported pregnancies occurred between Day 0 and Day 30 and these pregnancies will be recorded retrospectively. If, after having been vaccinated, a 
subject is found to have been pregnant at vaccination, the pregnancy will be recorded as an exclusion criterion. 
15 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/contacts are 
strictly followed. These intervals determine each subject’s evaluability in the according-to-
protocol (ATP) analyses. Subjects are able to participate in any study visit 1, 2, 3, 4, or 5 
independent of other study visits, at their own or at their parent/LAR’s discretion as applicable 
(e.g., it is possible that a subject comes to Visit 1 and Visit 3 but not Visit 2).
Table 5 presents the intervals between study visits.
Table 5
Intervals between study visits
Interval
Optimal length of interval 1
Allowed interval2
Dose 1 in primary vaccination study
MenACWY-TT-027 (108658)Visit 1
78 months
78 months ± 12 weeks
Dose 1 in primary vaccination study
MenACWY-TT-027 (108658)Visit 2 
90 months
90 months ± 12 weeks
Dose 1 in primary vaccination study
MenACWY-TT-027 (108658)Visit 3 
102 months
102 months ± 12 weeks
Dose 1 in primary vaccination study
MenACWY-TT-027 (108658) Visit 4 
114 months
114 months ± 12 weeks
Dose 1 in primary vaccination study
MenACWY-TT-027 (108658)Visit 5 
126 months
126 months ± 12 weeks
Visit 5 Visit 6
30 days
21-48 days3
Visit 5 Phone Contact
6 months
180-210 days
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 immunogenicity if they make the study visit outside this interval.
3 For the safety evaluation an interval of 30 days is needed. If the subject returns for Visit 6 prior to Day 30, they should take 
home the diary card, continue to record unsolicited safety information until Day 30 and then provide the card to the study site.
5.6.
Detailed description of study procedures
5.6.1.
Informed consent
The signed informed consent of the subject/subject’s parent(s)/LAR(s) must be obtained before 
study participation. The signed 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 and assent, as appropriate.
If the subject becomes of legal age during the course of the study the subject will be asked to 
sign the ICF per local regulation. Only the informed consent date at study entry will be collected 
in the eCRF.
5.6.2.
Check inclusion and exclusion criteria
Check all inclusion and exclusion criteria as described in Sections 4.2 and 4.3 before 
enrolment. 
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5.6.3.
Collect demographic data
Record demographic data such as date of birth and gender 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 
start of the persistence epochs in the eCRF.
5.6.5.
Recording of meningococcal and TT vaccination history
Record the history of meningococcal vaccination and the last tetanus toxoid (TT) vaccination 
date prior to the start of each epoch in the eCRF.
5.6.6.
History directed physical examination
Perform a history directed physical examination. If the investigator determines that the subject’s 
health on the day of vaccination temporarily precludes vaccination, the visit will be rescheduled.
Collected information needs to be recorded in the eCRF.
Treatment of any abnormality observed during this 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.
Pre-vaccination assessment of contraception
The investigator or his/her designee will discuss with the subject the need to use adequate 
contraception consistently and correctly according to the glossary of terms (and outline of study 
procedures) and document such conversation in the subject’s medical records. In addition, the 
investigator or his/her designee will instruct the subject to call immediately if the selected 
contraception method is discontinued or if pregnancy is known or suspected in the subject or the 
subject’s partner.
5.6.8.
Urine pregnancy test
For female subjects of childbearing potential, a urine pregnancy test, with sensitivity of at least 
25 mIU/mL, will be performed immediately before administration of each vaccine dose.  A 
negative pregnancy test result is required before the subject may receive the study vaccine.  In 
the case of a positive confirmed pregnancy, the subject will be withdrawn from administration of 
study vaccine but may remain in the study. Pregnancy tests may also be repeated as per request 
of institutional review boards (IRBs)/ethics committees (ECs) or if required by local regulations. 
Note: The urine pregnancy test must be performed even if the subject is menstruating at the time 
of the study visit.
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5.6.9.
Check contraindications, warnings and precautions to vaccination
Contraindications, warnings and precautions to vaccination must be checked at the beginning of 
the vaccination visit. Refer to Section 6.4 for more details. 
5.6.10.
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/ product administration. The preferred route for recording temperature in 
this study will be oral. If the subject has fever [fever is defined as temperature 37.5°C for oral, 
axillary or tympanic route, or 38.0°C for rectal route] on the day of vaccination, the 
vaccination visit will be rescheduled within the allowed interval for this visit (see Table 5).
5.6.11.
Container number allocation
Container number allocation will be performed as described in Section 5.2. The number of each 
administered treatment must be recorded in the eCRF.
5.6.12.
Sampling
Refer to the Module on Biospecimen Management in the SPM for detailed instructions for the 
collection, handling and processing of the samples.
5.6.12.1.
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 7 mL (10 mL at visits 4, 5 and 6) of whole blood (to provide 
approximately 2.5 mL of serum [or 5 mL of serum at visits 4, 5 and 6]) should be drawn 
from all subjects included in the immunogenicity sub-cohort for each analysis of humoral 
immune response at each pre-defined time point. After centrifugation, serum samples should 
be kept at –20°C or below until shipment. Refer to the SPM for more details on sample 
storage conditions.
5.6.13.
Study Vaccine administration

The study vaccine will be administered at Visit 5. After completing all prerequisite 
procedures prior to vaccination, one dose of study vaccine will be administered 
intramuscularly (IM) in the deltoid of preferably the non-dominant arm (refer to Section 6.3
for detailed description of the vaccine administration procedure). If the investigator or 
delegate determines that the subject’s health on the day of administration temporarily 
precludes vaccine administration, the visit will be rescheduled within the allowed interval 
for this visit (refer to Table 5).

The time of reconstitution and administration of the vaccine will be recorded.
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
The subjects will be observed closely for at least 30 minutes following the administration of 
the vaccine, with appropriate medical treatment readily available in case of anaphylaxis.
5.6.14.
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 6.5.
Intercurrent medical conditions must be checked and recorded in the eCRF as described in 
Section 6.6.
5.6.15.
Recording of AEs, SAEs and pregnancies

Refer to Section 8.2 for procedures for the investigator to record AEs, SAEs and 
pregnancies. Refer to Section 8.3 for guidelines on how to submit SAE and pregnancy 
reports to Pfizer.

The subjects/subjects’ parent(s)/LAR(s) will be instructed to contact the investigator 
immediately should they/the subjects manifest any signs or symptoms they perceive as 
serious. 

At the vaccination visit a diary card will be provided to the subject/subject’s 
parent(s)/LAR(s). The subject/subject’s parent(s)/LAR(s) will record body (oral) 
temperature and any solicited local/general AEs (i.e. on the day of vaccination and during 
the next 3 days) or any unsolicited AEs (i.e. on the day of vaccination and during the next 30 
days occurring after vaccination). The subject/subject’s parent(s)/LAR(s) will be instructed 
to return the completed diary card to the investigator at the next study visit.
Note: Diary cards can be filled in by a minor subject under the supervision of the subject’s 
parent(s)/LAR(s) provided that the minor has the competency to assess and report the 
information to be provided in the diary card. The ultimate accountability for the completion 
of the diary cards remains with the subject’s parent(s)/LAR(s). The investigator should 
discuss this accountability with the subject’s parent(s)/LAR(s).  

Collect and verify the completed diary card during discussion with the subject/subject’s 
parent(s)/LAR(s) on Visit 6.
Note: If the diary card has been filled in by a minor subject, the investigator or delegate 
should verify the reported information during a discussion with the minor subject preferably 
in the presence of his/her parent(s)/LAR(s).

Any unreturned diary cards will be sought from the subject/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.
5.6.15.1.
Recording of GBS and NOCIs

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.
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
In the event of GBS, subjects should be contacted to obtain clinical details as outlined in the 
‘Potential immune mediated disorders: standard questionnaires and list of preferred term’. 
All occurrences of GBS have to be reported as SAE(s).

NOCIs (e.g. autoimmune disorders, asthma, type 1 diabetes, allergies) will be reported as 
unsolicited AEs 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
Please refer to the SPM for details on biospecimen management (handling, storage and 
shipment).  See section 5.6.12 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 outside 
the scope of this protocol:

Collected samples may be used in other assays, for test improvement or development of analytical 
methods related to the study vaccine 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 vaccine 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/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.
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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 6 presents the volume and time each biological sample will be taken.
Table 6
Biological samples
Sample type
Quantity
Unit
Time point
Subset
Blood Sample
Approximately 7
ml
Visit 1 (months 78)
All subjects
Blood Sample
Approximately 7
ml
Visit 2 (months 90)
All subjects
Blood Sample
Approximately 7
ml
Visit 3 (months 102)
All subjects
Blood Sample
Approximately 10
ml
Visit 4 (months 114)
All subjects
Blood Sample
Approximately 10
ml
Visit 5 (months 126)
All subjects
Blood Sample
Approximately 10
ml
Visit 6 (months 127)
All subjects
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.
Serological assays will be performed at Public Health England (PHE; Manchester, UK) and 
Neomed Institute (Laval, Quebec, Canada) using standardised and validated procedures (refer to 
Table 7).
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Table 7
Humoral Immunity (Antibody determination)
Component
Method
Test kit/ 
Manufacturer
Unit
Cut-off
Laboratory
Neisseria 
meningitidis
Serogroup A 
L10 3125 Ab  
Bactericidal assay using rabbit 
complement
NA
Dilution for at least 
50% killing
1:8
PHE*
Neisseria 
meningitidis
Serogroup C 
L3v C11 Ab  
Bactericidal assay using rabbit 
complement
NA
Dilution for at least 
50% killing
1:8
PHE*
Neisseria 
meningitidis
Serogroup W 
L3v 
MP01240070 
Ab  
Bactericidal assay using rabbit 
complement
NA
Dilution for at least 
50% killing
1:8
PHE*
Neisseria 
meningitidis
Serogroup Y 
L3v S1975 Ab
Bactericidal assay using rabbit 
complement
NA
Dilution for at least 
50% killing
1:8
PHE*
Neisseria 
meningitidis
Serogroup A 
L10 3125 Ab  
Bactericidal assay using human
complement
NA
Dilution for 50% 
killing
1:4
Neomed**
Neisseria 
meningitidis
Serogroup C 
L3v C11 Ab  
Bactericidal assay using human 
complement
NA
Dilution for 50% 
killing
1:4
Neomed**
Neisseria 
meningitidis
Serogroup W 
L3v 
MP01240070 
Ab  
Bactericidal assay using human
complement
NA
Dilution for 50% 
killing
1:4
Neomed**
Neisseria 
meningitidis
Serogroup Y 
L3v S1975 Ab  
Bactericidal assay using human
complement
NA
Dilution for 50% 
killing
1:4
Neomed**
*PHE = Public Health England (formerly HPA = Health Protection Agency)
**Neomed Institute Laval, Quebec, Canada.
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5.7.4.
Biological samples evaluation
5.7.4.1.
Immunological read-outs
Table 8 provides the immunological read-outs.
Table 8
Immunological read-outs
Blood sampling time point
No. subjects
Component
Components
priority rank
Type of contact 
and time point
Sampling 
time point
visit 1 (month 78)
Post-Vacc 
488
rSBA-MenA, rSBA-
MenW-135, rSBA-
MenY, rSBA-MenC
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-MenY
visit 1 (month 78)
Post-Vacc
488
hSBA-MenA, hSBA-
MenW-135, hSBA-
MenY, hSBA-MenC
hSBA-MenC > hSBA-MenA > 
hSBA-MenW-135 > hSBA-
MenY
visit 2 (month 90)
Post-Vacc 
440
rSBA-MenA, rSBA-
MenW-135, rSBA-
MenY, rSBA-MenC
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-MenY
visit 2 (month 90)
Post-Vacc 
440
hSBA-MenA, hSBA-
MenW-135, hSBA-
MenY, hSBA-MenC
hSBA-MenC > hSBA-MenA > 
hSBA-MenW-135 > hSBA-
MenY
visit 3 (month 102)
Post-Vacc 
400
rSBA-MenA, rSBA-
MenW-135, rSBA-
MenY, rSBA-MenC
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-MenY
visit 3 (month 102)
Post-Vacc 
400
hSBA-MenA, hSBA-
MenW-135, hSBA-
MenY, hSBA-MenC
hSBA-MenC > hSBA-MenA > 
hSBA-MenW-135 > hSBA-
MenY
visit 4 (month 114)
Post-Vacc
360
rSBA-MenA, rSBA-
MenW-135, rSBA-
MenY, rSBA-MenC
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-MenY
visit 4 (month 114)
Post-Vacc
360
hSBA-MenA, hSBA-
MenW-135, hSBA-
MenY, hSBA-MenC
hSBA-MenC > hSBA-MenA > 
hSBA-MenW-135 > hSBA-
MenY
visit 5 (month 126)
Pre-
Booster
326
rSBA-MenA, rSBA-
MenW-135, rSBA-
MenY, rSBA-MenC 
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-MenY
visit 5 (month 126)
Pre-
Booster
326
hSBA-MenA, hSBA-
MenW-135, hSBA-
MenY, hSBA-MenC
hSBA-MenC > hSBA-MenA > 
hSBA-MenW-135 > hSBA-
MenY
visit 6 (month 127)
Post-
Booster
326
rSBA-MenA, rSBA-
MenW-135, rSBA-
MenY, rSBA-MenC, 
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-MenY
visit 6 (month 127)
Post-
Booster
326
hSBA-MenA, hSBA-
MenW-135, hSBA-
MenY, hSBA-MenC
hSBA-MenC > hSBA-MenA > 
hSBA-MenW-135 > hSBA-
MenY
Vacc: Vaccination
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In case of insufficient blood sample volume to perform assays for all antibodies, the samples will 
be analysed according to priority ranking provided in Table 8. Note that the rSBA assays will 
take priority over the hSBA assays.
5.7.5.
Immunological correlates of protection
Bactericidal assay using rabbit complement (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and 
rSBA-MenY):
Bactericidal antibodies are recognized as surrogate markers of protection. The 1:8 cut-off was 
shown to be the most consistent with observed efficacy at 4 weeks after vaccination with the 
meningococcal C conjugate vaccine in post-licensure efficacy estimates in the United Kingdom 
[Andrews, 2003]. The threshold for protection for other serogroups is still to be defined, 
although it is common practice to extend the 1:8 cut-off to rSBA-MenA, rSBA-MenW-135 and 
rSBA-MenY [Centres for Disease Control, 2006; WHO, 2011]. 
Bactericidal assay using human complement (hSBA-MenA, hSBA-MenC, hSBA-MenW-135 
and hSBA-MenY):
For MenC, a baseline serum bactericidal titre of 1:4 was a strong predictor of protection 
[Goldschneider, 1969]. To date, no MenA, MenW-135 and MenY baseline serum bactericidal 
titre predictive of protection has been published. However, in the absence of a demonstrated 
correlate of protection for MenA, MenW-135 and MenY, it has been common practice to extend 
the 1:4 cut-off to hSBA-MenA, hSBA-MenW-135 and hSBA-MenY as well.
Persistence phase
At each immunogenicity time point investigators will be provided with the immunogenicity 
results and group allocation for all subjects participating at their centre when the individual 
listings of the statistical report have been released.
Booster phase
Immunogenicity results and group allocation for subjects at the investigators centre will be 
provided when the individual listings of the statistical report have been released.
When a generally accepted correlate of protection exists, individual immunological assay results 
for the subjects identified as non-responders (i.e., antibody level below the established correlate 
of protection measured one month after vaccination.) could be defined using the following 
thresholds:

rSBA-MenC antibody titre < 1:8 and hSBA-MenC antibody titre <1:4
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Although no correlate of protection is established for Neisseria meningitidis serogroups A, W-
135 and Y, individual immunology assay results for these 3 antigens will also be provided to the 
study investigator.
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.
6.
STUDY VACCINE AND ADMINISTRATION
6.1.
Description of the study vaccine
The vaccine (MenACWY-TT) to be used in this study was acquired by Pfizer on 01 October 
2015.
The vaccine is labelled and packed according to applicable regulatory requirements.
Table 9 presents the description of the study vaccine.
Table 9
Study vaccine
Treatment name
Vaccine/
product name
Formulation
Presentation
Volume to be 
administered
Number of 
doses
MenACWY-TT 
MenACWY-TT 
5 µg of PSA, 5 µg of PSC, 5 
µg of PSW-135, 5 µg of 
PSY conjugated to Tetanus 
toxoid conjugate ~ 44 µg 
Tris-HCL, pH 6.8 ± 0.3 1.6 
mM; Sucrose 28 mg 
Lyophilized pellet to 
be reconstituted with 
saline diluent
0.5 mL
1
NaCl 
NaCl=150mM*
liquid
*The lyophilized pellet of MenACWY-TT vaccine is to be reconstituted with the supplied saline solution.
6.2.
Storage and handling of the study vaccine
The study vaccine 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. Refer to the Module on 
Clinical Trial Supplies in the SPM for more details on storage of the study vaccine.
Temperature excursions must be reported in degree Celsius.  
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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 vaccine.
Any excursions from the product label storage conditions should be reported upon discovery. 
The site should actively pursue options for returning the product to the storage conditions as 
described in the labeling, as soon as possible.  Deviations from the storage requirements, 
including any actions taken, must be documented and reported to the sponsor.  Once an 
excursion is identified, the study vaccine must be quarantined and not used until the sponsor 
provides documentation of permission to use the study vaccine.  It will not be considered a 
protocol deviation if the sponsor approves the use of the study vaccine after the temperature 
excursion.  Use of the study vaccine prior to sponsor approval will be considered a protocol 
deviation.  
Specific details regarding information the site should report for each excursion will be provided 
to the site.
6.3.
Dosage and administration of study vaccine
Table 10
Dosage and administration
Type of contact and 
time point
Volume to 
be 
administered 
Study Group
Treatment 
name
Route 1
Site 2
Side 3
visit 5 (months 126 )
0.5 mL
ACWY<2 
MenACWY-TT  
IM 
D 
Left or 
Right 
0.5 mL
MenCCRM 
MenACWY-TT  
IM 
D 
Left or 
Right
0.5 mL
ACWY2 
MenACWY-TT  
IM 
D 
Left or 
Right
0.5 mL
MenPS 
MenACWY-TT  
IM 
D 
Left or 
Right 
1Intramuscular (IM) ; 2Deltoid (D) ; 3Non-Dominant is preferred
Reconstitution of vaccine
The lyophilized white pellet of MenACWY-TT vaccine is to be reconstituted with the supplied 
saline solution to obtain 0.5 mL for administration. Refer to the CDS for full reconstitution 
instructions.
Injection technique
A needle of at least 25 mm (1 inch), 22-25 gauge should be used for injection in the deltoid.
The following injection technique is recommended:

Use of aseptic technique with reconstitution and delivery of injection.
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
To avoid injection into subcutaneous tissue, spread the skin of the selected vaccine 
administration site taut between the thumb and forefinger, isolating the muscle. 

Insert the needle fully into the muscle at a 90°C angle and inject the vaccine into the tissue.

Withdraw the needle and apply light pressure to the injection site for several seconds with a 
dry cotton ball or gauze.
6.4.
Warnings and precautions
Any specific warnings and precautions associated with the administration of MenACWY-TT 
have been mentioned in the exclusion criteria.
The study vaccine should under no circumstances be administered intravascularly, intradermally 
or subcutaneously.
Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents 
as a psychogenic response to the needle injection. This can be accompanied by several 
neurological signs such as transient visual disturbance, paraesthesis and tonic-clonic limb 
movements during recovery. It is important that procedures are in place to avoid injury from 
faints.
6.5.
Concomitant medication/product and concomitant vaccination
At each study visit/contact, the investigator should question the subject and/or the subject’s 
parent(s)/LAR(s) about any medication/product taken and vaccination received by the subject.
6.5.1.
Recording of concomitant medications/products and concomitant 
vaccination
The following concomitant medications/products/vaccines must be recorded in the eCRF if 
administered during the indicated recording period:

All concomitant medications/products, except vitamins and dietary supplements, 
administered for 30 days following the booster dose of study vaccine.

Any concomitant vaccination administered from study start and ending at visit 6.

Prophylactic medication (i.e. medication administered in the absence of ANY symptom and 
in anticipation of a reaction to the vaccination).
E.g. 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 temperature 
37.5°C for oral, axillary or tympanic route, or 38.0°C for rectal route].

Any concomitant medications/products/vaccines listed in Section 6.5.2

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.
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6.5.2.
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.

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 10 
mg/day or equivalent. Inhaled and topical steroids are allowed.)

A vaccine not foreseen by the study protocol administered during the period starting from 30 
days before the study vaccine dose and ending 30 days after *, with the exception of 
inactivated influenza vaccine.
*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 CDS or PI (Prescribing Information) and 
according to the local governmental recommendations.

Administration of a meningococcal vaccine of any serogroup not foreseen by the study 
protocol at any time during the study period. 

Immunoglobulins and/or any blood products administered during the study period.

Drug and/or alcohol abuse.
A detailed, comprehensive list of reasons for elimination from ATP analyses will be established 
at the time of data cleaning.
6.6.
Intercurrent medical conditions that may lead to elimination of a 
subject from ATP analyses
At each study visit subsequent to the vaccination visit, it must be verified if the subject has 
experienced or is experiencing any intercurrent medical condition. If it is the case, the 
condition(s) must be recorded in the eCRF.
The following may result in the elimination of subjects from the ATP cohort for 
immunogenicity, but not necessarily from the study:

Occurrence of meningococcal disease*.

Any confirmed or suspected condition that has the capability of altering the subject’s 
immune response (e.g. intercurrent lymphopenia).

Any confirmed or suspected immunosuppressive or immunodeficient condition, including 
Human immunodeficiency virus (HIV) infection based on medical history and physical 
examination (no laboratory testing required).
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
Diagnosis of any serious chronic illness.
* Occurrence of meningococcal disease should be recorded 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/subject’s parent(s)/LAR(s) will be instructed to contact the investigator 
immediately should they/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.
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:

Significant or unexpected worsening or exacerbation of the condition/indication under study.

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).
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
Medication error.

Occupational exposure.
AEs to be recorded as solicited AEs are described in Section 8.1.6. 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.
Medication Errors
Medication errors may result, in this study, from the administration or consumption of the wrong 
product, by the wrong subject, at the wrong time, or at the wrong dosage strength.  Such 
medication errors occurring to a study participant are to be captured on the medication error 
CRF, which is a specific version of the AE page, and on the SAE form when appropriate.  In the 
event of medication dosing error, the sponsor should be notified immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving subject exposure to the study vaccine;

Potential medication errors or uses outside of what is foreseen in the protocol that do or do 
not involve the participating subject.
Whether or not the medication error is accompanied by an AE, as determined by the investigator, 
the medication error is captured on the medication error version of the AE page and, if 
applicable, any associated AE(s) are captured on an AE CRF page.  
Other examples include, but are not limited to:

The administration of expired study vaccine;

The administration of an incorrect study vaccine;

The administration of an incorrect dosage;
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
The administration of study vaccine that has undergone temperature excursion from the 
specified storage range, unless it is determined by the sponsor that the study vaccine under 
question is acceptable for use.
8.1.3.
Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person (whether 
a healthcare professional or otherwise) gets in unplanned direct contact with the product, which 
may or may not lead to the occurrence of an AE.
An occupational exposure is reported to the drug safety unit within 24 hours of the investigator’s 
awareness, using the SAE report form, regardless of whether there is an associated AE/SAE.  
Since the information does not pertain to a subject enrolled in the study, the information is not 
reported on a CRF; however, a copy of the completed SAE report form is maintained in the 
investigator site file.
8.1.4.
Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy occurs if:
1.
A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the study vaccine; or the 
female becomes or is found to be pregnant after discontinuing and/or being exposed to 
the study vaccine; 
2.
An example of environmental exposure would be a case involving direct contact with a 
Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has been 
exposed to chemotherapeutic products).
3.
A male has been exposed (eg, because of treatment or environmental exposure) to the 
study vaccine prior to or around the time of conception and/or is exposed during his 
partner’s pregnancy. 
If a study subject or study subject’s partner becomes or is found to be pregnant during the study 
subject’s treatment with the study vaccine, the investigator must submit this information to the 
Pfizer drug safety unit on an SAE report form and an EDP supplemental form, regardless of 
whether an SAE has occurred.  In addition, the investigator must submit information regarding 
environmental exposure to a Pfizer product in a pregnant woman (eg, a subject reports that she is 
pregnant and has been exposed to a cytotoxic product by inhalation or spillage) using the EDP 
supplemental form.  This must be done irrespective of whether an AE has occurred and within 24 
hours of awareness of the exposure.  The information submitted should include the anticipated 
date of delivery (see below for information related to termination of pregnancy).
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Follow-up is conducted to obtain general information on the pregnancy and its outcome for all 
EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer of the outcome as a follow-up to 
the initial EDP supplemental form.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless preprocedure test findings 
are conclusive for a congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a live-
born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the investigator 
should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported as SAEs follows: 
•
Spontaneous abortion includes miscarriage and missed abortion;
•
Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the study vaccine. 
Additional information regarding the EDP may be requested by the investigator.  Further follow-
up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on preterm infants to 
identify developmental delays).  In the case of paternal exposure, the investigator will provide 
the study subject with the Pregnant Partner Release of Information Form to deliver to his partner.  
The investigator must document in the source documents that the subject was given the Pregnant 
Partner Release of Information Form to provide to his partner.
8.1.5.
Definition of a serious adverse event 
A serious adverse event is any untoward medical occurrence that:
a.
Results in death,
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 
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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.
Is a congenital anomaly/birth defect in the offspring of a study subject, OR
f.
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.
8.1.6.
Solicited adverse events
8.1.6.1.
Solicited local (injection-site) adverse events
The following local (injection-site) AEs will be solicited:
Table 11
Solicited local adverse events
Pain at injection site
Redness at injection site
Swelling at injection site
If subjects/subject’s parent(s)/LAR(s) observe any large injection site reaction, they should 
contact the study personnel to determine if a visit to the investigator’s office for evaluation is 
necessary.
A large injection site reaction is:

a swelling that measures more than 100 mm across where the vaccine was given, or

a noticeable irregular/uneven swelling where the vaccine was given, or
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
a noticeable increase in size of the arm that interferes with or prevents everyday 
activities (e.g., writing, use of computer, school attendance, sleeping, etc.).
In case of questions or uncertainties, the subject/subject’s parent(s)/LAR(s) should contact the 
investigator by phone and the investigator will determine whether or not a visit should be 
arranged.
The investigator will record detailed information describing the AE on a specific large injection 
site reaction screen in the eCRF. An SAE report should also be completed if the large injection 
site reaction meets the definition of SAE.
8.1.6.2.
Solicited general adverse events
The following general AEs will be solicited:
Table 12
Solicited general adverse events
Fatigue
Fever*
Gastrointestinal symptoms †
Headache
* The preferred route for temperature measurement is oral. Fever is defined as: 37.5°C for oral, axillary or tympanic route, or 
38.0°C for the rectal route.
†Gastrointestinal symptoms include nausea, vomiting, diarrhoea and/or abdominal pain.
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.
8.1.7.
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 Sections 8.1.1 and 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.
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.
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8.1.8.
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 8.1.8.1 for a non-exhaustive list of illnesses that can be recorded as NOCIs.

GBS (to be reported as an SAE).

Meningococcal disease (to be reported as an SAE).
See Section 8.2 and 8.3 for information on recording and reporting of these events.
8.1.8.1.
List of New Onset of Chronic Illnesses
Table 13 presents a non-exhaustive list of illnesses that can be recorded as NOCIs.
Table 13
List of NOCIs
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
Muscular autoimmune disorder
Myasthenia gravis
Myasthenia gravis neonatal
Polymyalgia
Polypyalgia rheumatica
Polymyositis
Ocular myasthenia
Myasthenia gravis crisis
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Disease/Disorder
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
Scleroderma and associated disorders
CREST syndrome
Morphoea
Scleroderma
Systemic sclerosis
Systemic sclerosis pulmonary
Scleroderma renal crisis
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Disease/Disorder
Skin autoimmune 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 abnormality
Multiple sclerosis
Multiple sclerosis
Demyelinating 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
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
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Disease/Disorder
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
8.1.9.
Pregnancy
Female subjects who become pregnant after the vaccination may continue the study at the 
discretion of the investigator.
While pregnancy itself is not considered an AE or SAE, any adverse pregnancy outcome or 
complication or elective termination of a pregnancy for medical reasons will be recorded and 
reported as an AE or a SAE.
Note: The pregnancy itself should always be recorded on an Exposure During Pregnancy (EDP) 
form.
The following should always be considered as SAE and will be reported as described in Sections 
8.3.1 and 8.3.2:

Spontaneous pregnancy loss, including:

spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of gestation)

ectopic and molar pregnancy

stillbirth (intrauterine death of foetus after 22 weeks of gestation).
Note: the 22 weeks cut-off in gestational age is based on WHO-ICD 10 noted in the EMA Guideline 
on pregnancy exposure [EMA, 2006]. It is recognized that national regulations might be different.

Any early neonatal death (i.e. death of a live born infant occurring within the first 7 days of life). 

Any congenital anomaly or birth defect (as per [CDC MACDP] guidelines) identified in the offspring 
of a study subject (either during pregnancy, at birth or later) regardless of whether the foetus is 
delivered dead or alive. This includes anomalies identified by prenatal ultrasound, amniocentesis or 
examination of the products of conception after elective or spontaneous abortion.
Furthermore, any SAE occurring as a result of a post-study pregnancy AND considered by the 
investigator to be reasonably related to the investigational vaccine(s)/product(s) will be reported 
to Pfizer as described in Section 8.3.2. While the investigator is not obligated to actively seek 
this information from former study participants, he/she may learn of a pregnancy through 
spontaneous reporting.
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8.2.
Detecting and recording adverse events, serious adverse events 
and pregnancies
8.2.1.
Time period for detecting and recording adverse events, serious 
adverse events and pregnancies
All AEs starting within 30 days following administration of the 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 study start and will end 6 
months following administration of the study vaccine dose for each subject. See Section 8.3 for 
instructions on reporting of SAEs.
All SAEs should be collected and recorded following administration of the study vaccine dose up 
to 6 months after. 
SAEs that are related to the investigational vaccine and any event related to lack of vaccine 
efficacy will be collected and recorded from the time of the 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.
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from study 
start.
The time period for collecting and recording pregnancies will begin from administration of the 
study vaccine dose and will end 30 days following administration of the study vaccine. See 
section 8.3 for instructions on reporting of pregnancies.
Occurrences of NOCIs (e.g. auto-immune disorders, asthma, type 1 diabetes, allergies) will be 
recorded from administration of the study vaccine dose until 6 months after administration of the 
study vaccine, whether or not they are considered to be possibly related to vaccine 
administration. Medical documentation of the events will be reported either as an unsolicited AE 
or as an SAE as appropriate in the eCRF.
Occurrences of GBS will be recorded from administration of the study vaccine dose until 6
months after administration of the study vaccine. 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 SAEs.
An overview of the protocol-required reporting periods for AEs, SAEs, and pregnancies is given 
in Table 14.
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Table 14
Reporting periods for adverse events, serious adverse events and pregnancies
Study activity
Persistence visits
Booster Vacc.1
4 days 
Post-vacc.1
31 days
Post-vacc.1
ESFU
ICF signed
Visit 1
Month 78
Visit 2
Month 90
Visit 3
Month 102
Visit 4
Month 114
Visit 5 Month 
126
Month 
126+3days
Visit 6 Month 
126+30 Days
Phone 
Contact
Month 132
Recording of solicited local 
and general AEs
Recording of unsolicited AEs
Recording of NOCI2
Recording of All SAEs
Recording of serious 
adverse events (SAEs) 
related to study vaccination 
and any event related to lack 
of vaccine efficacy since the 
previous visit.3, 4
Recording of SAEs related to 
study participation5  
Recording of GBS6
Recording of pregnancies7
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1 Vacc.: vaccination; Post-vacc.: post-vaccination.
2 NOCI = new onset of chronic illness(es) (e.g. autoimmune disorders, asthma type I diabetes and allergies [a non-exhaustive list of NOCIs is provided in Table 13). These AEs are 
collected from Month 126 through Month 132.
3 Occurrence of meningococcal disease should be documented in the SAE report in the eCRF during the entire study period.
4 Including SAEs related to study vaccination and any event related to lack of vaccine efficacy occurring from the subject’s last persistence visit to study entry in study MENACWY-TT-
100 EXT: 027 Y6, 7, 8, 9, 10 will be recorded. Subject’s parent(s)/LAR(s) will be questioned at study entry of study MENACWY-TT-100 whether any SAEs occurred during that time 
frame.
5This will also include SAE(s) leading to the withdrawal of the subject from the study.
6 In the event of GBS, subjects 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 Pregnancies occurring between vaccination (Day 0) and 31 days after vaccination (Day 30) will be recorded. If, after having been vaccinated, a subject is found to have been pregnant 
at vaccination, the pregnancy will be recorded as an exclusion criterion. Subjects will be questioned at Month 132, 6 months after the booster vaccination, whether any unreported 
pregnancies occurred between Day 0 and Day 30 and these pregnancies will be recorded retrospectively.
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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 14. 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 report the event 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 or the subject’s parent(s)/LAR(s) should be 
asked a non-leading question such as:
‘Have you felt different in any way since receiving the vaccine or since the previous visit?’
‘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 CRF/paper SAE report as applicable the eCRF. 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:
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Table 15
Intensity scales for solicited symptoms
Adverse Event
Intensity grade
Parameter
Pain at injection site
0
None
1
Mild: Any pain neither interfering with nor preventing 
normal every day activities.
2
Moderate: Painful when limb is moved and interferes 
with every day activities.
3
Severe: Significant pain at rest. Prevents normal 
every day activities.
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
Headache
0
Normal
1
Mild: Headache that is easily tolerated
2
Moderate: Headache that interferes with normal 
activity
3
Severe: Headache that prevents normal activity
Fatigue
0
Normal
1
Mild: Fatigue that is easily tolerated
2
Moderate: Fatigue that interferes with normal activity
3
Severe: Fatigue that prevents normal activity
Gastrointestinal symptoms
0
Gastrointestinal symptoms normal
(nausea, vomiting, diarrhoea 
and/or abdominal pain)
1
Mild: Gastrointestinal symptoms that are easily 
tolerated
2
Moderate: Gastrointestinal symptoms that interfere 
with normal activity
3
Severe: Gastrointestinal symptoms that prevent 
normal activity
*Fever is defined as temperature 37.5°C for oral, axillary or tympanic route, or 38.0°C for rectal route. The preferred 
route for recording temperature in this study will be oral.
The maximum intensity of local injection site redness/swelling will be scored as follows:
0
:
None
1
:
> 0 - 20 mm
2
:
> 20 - 50 mm
3
:
> 50 mm
The maximum intensity of fever will be scored as follows for oral/axillary or tympanic route:
0
:
< 37.5 °C
1
:
37.5 °C - 38.5 °C
2
:
> 38.5 °C - 39.5 °C
3
:
> 39.5 °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 
Such an AE would, for example, prevent attendance at 
work/school and would necessitate the administration of corrective 
therapy.
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 definitions for ‘NO’ and ‘YES’ have been written in such a way that all events that have 
been attributed a ‘NO’ can be pooled with events which in the primary vaccination study were 
determined to be ‘not related’ or ‘unlikely to be related’ to vaccination. Those events that are 
attributed a ‘YES’ can be pooled with those events that in the past were determined to have a 
‘suspected’ or ‘probable’ relationship to vaccination in the primary vaccination study.
The investigator is obligated to assess the relationship between investigational vaccine/product 
and the occurrence of unsolicited AEs (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 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, it may not be possible to determine 
the causal relationship of general AEs to the individual vaccines administered. The investigator 
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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?
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, 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/subject’s 
parent(s)/LAR(s) will be asked if he/she /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 CRF/paper SAE 
report as applicable in the eCRF. 
8.3.
Reporting of serious adverse events, pregnancies, and other 
events
8.3.1.
Prompt reporting of serious adverse events, pregnancies, and other 
events 
SAEs, including those due to GBS and invasive meningococcal disease, that occur in the time 
period defined in Section 8.2 will be reported promptly within the timeframes described in Table
16, once the investigator determines that the event meets the protocol definition of a SAE.
Pregnancies that occur in the time period defined in Section 8.2 will be reported promptly within 
the timeframes described in Table 16, once the investigator becomes aware of the pregnancy. 
Table 16
Timeframes for submitting serious adverse event, pregnancy and 
other events reports
Type of Event
Initial Reports
Follow-up of Relevant Information on a 
Previous Report
Timeframe
Documents
Timeframe
Documents
All SAEs
24 hours*
paper SAE report
24 hours*
paper SAE report
Pregnancies
24 hours*
paper SAE and EDP reports
24 hours*
paper SAE and EDP reports
GBS
24 hours*
paper SAE report
24 hours*
paper SAE report
Invasive 
meningococcal 
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.
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8.3.3.
Completion and transmission of pregnancy reports 
Once the investigator becomes aware that a subject is pregnant, the investigator (or designate) 
must complete the required information onto the EDP report WITHIN 24 HOURS.
Note: Conventionally, the estimated gestational age (EGA) of a pregnancy is dated from the first 
day of the last menstrual period (LMP) of the cycle in which a woman conceives. If the LMP is 
uncertain or unknown, dating of EGA and the estimated date of delivery (EDD) should be 
estimated by ultrasound examination and recorded in the pregnancy report.
8.3.4.
Updating of SAE and pregnancy information after freezing of the 
subject’s eCRF
When additional SAE and pregnancy 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 16. 
8.3.5.
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 the Study Contact for 
Reporting SAEs 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, serious adverse events, and 
pregnancies
8.4.1.
Follow-up of adverse events and serious adverse events 
8.4.1.1.
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 16).
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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 six months 
after the vaccine dose.
8.4.1.2.
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 AEs (i.e NOCIs), until 6 months after the study vaccine (M132) 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 an  SAE and/or EDP report as applicable.
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.
8.4.2.
Follow-up of pregnancies
Pregnant subjects will be followed to determine the outcome of the pregnancy. At the end of the 
pregnancy, whether full-term or premature, information on the status of the mother and child will 
be forwarded to Pfizer using the EDP report and the SAE report if applicable. Generally, the 
follow-up period doesn’t need to be longer than six to eight weeks after the estimated date of 
delivery.
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is a SAE, it 
should always be reported as SAE.
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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 6.5).
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.
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.
A subject who completes a given epoch is considered to have completed the corresponding 
persistence time point.  
At each persistence time point the number of subjects completing each persistence visit and the 
number of subjects withdrawn at each persistence visit will be calculated.
9.2.
Subject withdrawal
Subjects who are withdrawn because of SAEs/AEs must be clearly distinguished from subjects 
who are withdrawn for other reasons. Investigators will follow subjects who are withdrawn as 
result of an SAE/AE until resolution of the event (see Section 8.4.1.2).
Withdrawals will not be replaced.
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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. 
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 
himself/herself, 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 
8.4.1.2).
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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. 
Information relative to premature discontinuation of the investigational vaccine will be 
documented on the Vaccine Administration page/screen of the eCRF. The investigator will 
document whether the decision to discontinue further vaccination/treatment was made by the 
subject himself/herself, 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 endpoint
Immunogenicity with respect to the components of the investigational vaccine six, seven, 
eight, nine and ten years after primary vaccination in study MenACWY-TT-027:

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY antibody titres 1:8, 1:128 
and GMTs.
10.2.
Secondary endpoint(s)
Persistence phase:
Immunogenicity with respect to the components of the investigational vaccine six, seven, 
eight, nine and ten years after primary vaccination in study MenACWY-TT-027:

hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY antibody titres 1:4, 1:8 
and GMTs.
Booster phase:
Immunogenicity with respect to the components of the investigational vaccine one month 
post booster vaccination at ten years after primary vaccination:

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY antibody titres 1:8, 1:128 
and GMTs and rSBA booster response.
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
hSBA-MenA, hSBA-MenC, rhSBA-MenW-135 and hSBA-MenY antibody titres 1:4, 1:8 
and GMTs and hSBA booster response.
Safety and reactogenicity
Persistence phase:

Occurrence of serious adverse events related to vaccination and any event related to lack of 
vaccine efficacy (i.e. meningococcal disease) since the last persistent time point the subject 
participated in up to each yearly visit in the current study in a retrospective manner.
Booster phase

Occurrence of solicited local and general symptoms on days 0-3 following the booster 
vaccination.

Occurrence of unsolicited symptoms up to 31 days following booster vaccination.

Occurrence of all serious AEs, and new onset chronic illness(es) (e.g. autoimmune 
disorders, asthma, type 1 diabetes and allergies) from administration of the vaccine dose 
until study end.
10.3.
Determination of sample size
The actual sample size of this study with respect to the analysis of persistence and safety and 
immunogenicity post-booster is determined by a) the sample size of the primary vaccination 
study MenACWY-TT-027 (108658), b) by assumptions about the enrolment rate at the Year 6-
10 extension study, and c) by assumptions about the annual dropout rate. All subjects who were 
vaccinated in study MenACWY-TT-027 (108658) and received either MenACWY-TT vaccine, 
Meningitec or Mencevax ACWY in study MenACWY-TT-027 (108658) will be eligible for this 
study if they meet the inclusion/exclusion criteria. Six hundred and thirteen subjects (460 in the 
ACWY-TT group and 75 in the MenCCRM group and 78 in the MenPS group) were enrolled 
and vaccinated in study MenACWY-TT-027 (108658). An enrollment rate equivalent to 
approximately 80% of the vaccinated population in study MenACWY-TT-027 (108658) is 
assumed, and an annual dropout rate of 10%. 
If one assumes approximately 10% of subjects dropping out of the persistence study at every 
visit, then one expects the following numbers of subjects to participate at each persistence time 
point.

For the analysis at Year 6, it is estimated that approximately 488 subjects will be enrolled 
(183 in the ACWY<2, 183 in the ACWY2 group, 61 in the MenCCRM group and 61 in the 
MenPS group)

For the analysis at Year 7, it is estimated that approximately 440 subjects will be enrolled 
(165 in the ACWY<2, 165 in the ACWY2 group, 55 in the MenCCRM group and 55 in the 
MenPS group)
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
For the analysis at Year 8, it is estimated that approximately 400 subjects will be enrolled 
(150 in the ACWY<2, 150 in the ACWY2 group, 50 in the MenCCRM group and 50 in the 
MenPS group)

For the analysis at Year 9, it is estimated that approximately 360 subjects will be enrolled 
(135 in the ACWY<2, 135 in the ACWY2 group, 45 in the MenCCRM group and 45 in the 
MenPS group)

For the analysis at Year 10, it is estimated that approximately 326 subjects will be enrolled 
(122 in the ACWY<2, 122 in the ACWY2 group, 41 in the MenCCRM group and 41 in the 
MenPS group)
The primary objective of this study is to evaluate at 6, 7, 8, 9 and 10 years after primary 
vaccination of MenACWY-TT or Meningitec or Mencevax ACWY, the long term persistence of 
antibodies induced by MenACWY-TT vaccine as compared to Meningitec or Mencevax ACWY
when administered at 1-10 years of age in terms of the percentage of subjects with rSBA-MenA, 
rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres ≥ 1:8, ≥ 1:128 and GMTs.
Table 17 illustrates the accuracy one can expect from a sample size of evaluable subjects at year 
6, at year 7, at year 8, at year 9 and at year 10 for evaluation the percentage of subjects with 
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres ≥ 1:8 in each group.
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Table 17
Exact 95% confidence intervals of the percentage of subjects with 
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres ≥ 
1:8
Year 6
%
ACWY<2 or ACWY≥2 (N = 183)
MenCCRM or Men-PS (N = 61)
20
[
14.7
;
26.8
]
[
10.6
;
31.8
]
30
[
23.5
;
37.3
]
[
18.5
;
42.6
]
40
[
32.7
;
47.4
]
[
27.1
;
52.7
]
50
[
42.8
;
57.7
]
[
37.7
;
63.9
]
60
[
52.6
;
67.3
]
[
47.3
;
72.9
]
70
[
62.7
;
76.5
]
[
57.4
;
81.5
]
80
[
73.2
;
85.3
]
[
68.2
;
89.4
]
90
[
84.9
;
94.1
]
[
79.8
;
96.3
]
100
[
98.0
;
100
]
[
94.1
;
100
]
Year 7
%
ACWY<2 or ACWY≥2 (N = 165)
MenCCRM or Men-PS (N = 55)
20
[
14.2
;
26.9
]
[
10.4
;
33.0
]
30
[
23.4
;
37.9
]
[
19.1
;
44.8
]
40
[
32.5
;
47.9
]
[
27.0
;
54.1
]
50
[
42.4
;
58.2
]
[
37.1
;
64.6
]
60
[
52.1
;
67.5
]
[
45.9
;
73.0
]
70
[
62.7
;
77.2
]
[
57.1
;
82.4
]
80
[
73.1
;
85.8
]
[
67.0
;
89.6
]
90
[
84.7
;
94.4
]
[
80.0
;
97.0
]
100
[
97.8
;
100
]
[
93.5
;
100
]
Year 8
%
ACWY<2 or ACWY≥2 (N = 150)
MenCCRM or Men-PS (N = 50)
20
[
13.9
;
27.3
]
[
10.0
;
33.7
]
30
[
22.8
;
38.0
]
[
17.9
;
44.6
]
40
[
32.1
;
48.3
]
[
26.4
;
54.8
]
50
[
41.7
;
58.3
]
[
35.5
;
64.5
]
60
[
51.7
;
67.9
]
[
45.2
;
73.6
]
70
[
62.0
;
77.2
]
[
55.4
;
82.1
]
80
[
72.7
;
86.1
]
[
66.3
;
90.0
]
90
[
84.0
;
94.3
]
[
78.2
;
96.7
]
100
[
97.6
;
100
]
[
92.9
;
100
]
Year 9
%
ACWY<2 or ACWY≥2 (N = 135)
MenCCRM or Men-PS (N = 45)
20
[
13.6
;
27.7
]
[
9.6
;
34.6
]
30
[
22.8
;
38.9
]
[
18.2
;
46.6
]
40
[
31.7
;
48.8
]
[
25.7
;
55.7
]
50
[
41.6
;
59.1
]
[
35.8
;
66.3
]
60
[
51.2
;
68.3
]
[
44.3
;
74.3
]
70
[
61.9
;
77.9
]
[
55.7
;
83.6
]
80
[
72.3
;
86.4
]
[
65.4
;
90.4
]
90
[
84.1
;
94.8
]
[
78.8
;
97.5
]
100
[
97.3
;
100
]
[
92.1
;
100
]
Year 10
%
ACWY<2 or ACWY≥2 (N = 122)
MenCCRM or Men-PS (N = 41)
20
[
13.0
;
27.8
]
[
8.8
;
34.9
]
30
[
22.3
;
39.3
]
[
16.1
;
45.5
]
40
[
31.4
;
49.4
]
[
24.2
;
55.5
]
50
[
40.8
;
59.2
]
[
35.1
;
67.1
]
60
[
50.6
;
68.6
]
[
44.5
;
75.8
]
70
[
60.7
;
77.7
]
[
54.5
;
83.9
]
80
[
72.2
;
87.0
]
[
65.1
;
91.2
]
90
[
83.4
;
94.8
]
[
76.9
;
97.3
]
100
[
97.0
;
100
]
[
91.4
;
100
]
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10.4.
Study cohorts/ data sets to be analysed
A total of 7 cohorts are defined for the purpose of analysis.
10.4.1.
Persistence cohorts
10.4.1.1.
Total cohort at Month X
The Total cohort at Month X will include all vaccinated subjects in the vaccination stage of study 
MenACWY-TT-027 (108658) who return for the Month X follow-up. For the analysis of
persistence, this will include all vaccinated subjects for whom data concerning persistence 
endpoint measures are available.
10.4.1.2.
According-To-Protocol (ATP) cohort for persistence – MenC at Month X
Analysis of persistence of MenC antibody titres for Month X will be done on ATP cohort for 
persistence – MenC at Month X. The ATP cohort for antibody persistence – MenC at Month X 
will include all evaluable subjects: 

who were eligible in study MenACWY-TT-027 (108658).

who have received the primary vaccination with MenACWY-TT or Meningitec or Mencevax 
ACWY during study MenACWY-TT-027 (108658) according to their treatment group.

who have available assay results for MenC antigen at Month X.

who have not received a meningococcal vaccine not planned in protocol MenACWY-TT-
027 (108658) before Month X.

who do not have a history of meningococcal disease prior to Month X.

who comply with the blood sampling intervals defined in Table 5 for Month X.

who do not have an immunocompromising medical condition.

who have not received any immunosuppressant(s) or other immune-modifying drug(s), 
immunoglobulins, any blood products, investigational drugs, and/or investigational vaccines 
within 30 days of persistence blood sample.

who were not excluded from the ATP cohort in the primary study MenACWY-TT-027
(108658) and from the previous ATP persistence cohorts, unless the reason for exclusion 
was either non-compliance with the protocol-defined serum sampling windows or a lack of 
availability of immunogenicity results at previous time point
10.4.1.3.
According-To-Protocol (ATP) cohort for persistence – MenAWY at Month X
Analysis of persistence of MenA, W-135 and Y antibody titres at Month X will be done on the 
ATP cohort for persistence – MenAWY at Month X. The ATP cohort for persistence Month X –
MenAWY will include all evaluable subjects: 

who were eligible in study MenACWY-TT-027 (108658).
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
who have received the primary vaccination with MenACWY-TT or Meningitec or Mencevax 
ACWY during study MenACWY-TT-027 (108658) according to their treatment group.

who have available assay results for at least one of three antigens (MenA or W-135 or 
MenY) at Month X.

who have not received a meningococcal vaccine not planned in protocol MenACWY-TT-
027 (108658) before Month X with the exception of a monovalent MenC conjugate vaccine 
because of suboptimal response to N. meningitidis serogroup C after vaccination in the 
primary study MenACWY-TT-027 (108568).

who do not have a history of meningococcal disease prior to Month X.

who comply with the blood sampling intervals defined in Table 5 for Month X.

who do not have an immunocompromising medical condition.

who have not received any immunosuppressant(s) or other immune-modifying drug(s), 
immunoglobulins, any blood products, investigational drugs, and/or investigational vaccines 
within 30 days of persistence blood sample. 

who were not excluded from the ATP cohort in the primary study MenACWY-TT-027
(108658) and from the previous ATP persistence cohorts, unless the reason for exclusion was 
either non-compliance with the protocol-defined serum sampling windows or a lack of 
availability of immunogenicity results at previous time point or  re-vaccination with a 
monovalent meningococcal polysaccharide conjugate vaccine of serogroup C due to 
suboptimal response to N. meningitidis serogroup C after vaccination in the primary study 
MenACWY-TT-027 (108658).
10.4.2.
Booster cohort 
10.4.2.1.
Booster Total Vaccinated Cohort
The Booster Total Vaccinated Cohort for safety following the booster vaccination will include 
all vaccinated subjects in the primary vaccination study MenACWY-TT-027 (108658) with a 
booster vaccine administration documented.
For the analysis of immunogenicity post-booster vaccination the Booster Total Vaccinated 
Cohort will include all subjects for whom data concerning post-booster immunogenicity 
endpoint measures are available.
10.4.2.2.
Booster According-To-Protocol (ATP) cohort for safety
The Booster ATP cohort for safety following booster vaccination will include all subjects:

who met all inclusion criteria and no exclusion criteria for the study

who have received a dose of study vaccine MenACWY-TT or Meningitec or Mencevax
ACWY in the primary study MenACWY-TT-027 according to their treatment group.
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
who have not received a vaccine not specified or forbidden in the protocol (subjects who 
received a vaccine not foreseen by the study protocol from 30 days before until 30 days after 
administration of the study vaccine dose will be eliminated from the ATP cohort for safety if 
the vaccine not foreseen by the protocol was administered before the post-vaccination blood 
sample).

who have received a booster dose of study vaccine MenACWY-TT in the booster epoch.

for whom the administration site of the vaccine is known.

who were not excluded from the ATP cohort for persistence Year 10, unless the reason for 
exclusion was either non-compliance with the protocol-defined serum sampling windows or 
a lack of availability of immunogenicity results at Year 10 (pre Booster vaccination).
10.4.2.3.
Booster According To Protocol (ATP) cohort for immunogenicity - MenC
At post booster time point, the analysis of immunogenicity for MenC antibody titres will be done 
on Booster ATP cohort for immunogenicity – MenC cohort.  The Booster ATP cohort for 
immunogenicity – MenC 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 Booster ATP cohort for safety for whom assay results are available 
for antibodies against MenC antigen for the blood sample taken one month post-vaccination, and 
who were not administered a vaccine not foreseen by the study protocol from 30 days before the 
booster administration until the post-vaccination blood sample, and who have not received a 
monovalent MenC conjugate vaccine or MenACWY conjugate vaccine because of suboptimal 
response to N. meningitidis serogroup C between the vaccination in the primary study 
MenACWY-TT-027 (108568) and the booster vaccine in this study. The interval between Visit 5 
and Visit 6 for inclusion in the Booster ATP cohort for immunogenicity will be defined as 21 to 
48 days.
10.4.2.4.
Booster According To Protocol (ATP) cohort for immunogenicity – MenAWY
At post booster time point, the analysis of immunogenicity for MenA, W-135 and Y antibody 
titres will be done on Booster ATP cohort for immunogenicity – MenAWY. The Booster ATP 
cohort for immunogenicity – MenAWY cohort 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 Booster ATP cohort for safety for whom assay 
results are available for antibodies against at least one of the three antigens (MenA or MenW-
135 or MenY) for the blood sample taken one month post-vaccination, and who were not 
administered a vaccine not foreseen by the study protocol from 30 days before the booster 
administration until the post-vaccination blood sample and who have not received a MenACWY 
conjugate vaccine because of sub-optimal response between the vaccination in the primary study 
MenACWY-TT-027 (108568) and the booster vaccine in this study. If a subject previously 
received monovalent MenC conjugate vaccine because of suboptimal response to N. meningitidis
serogroup C after vaccination in the primary study MenACWY-TT-027 (108568), the subject 
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can still be included in the Booster ATP cohort for MenAWY. The interval between Visit 5 and 
Visit 6 for inclusion in the Booster ATP cohort for immunogenicity – MenAWY will be defined 
as 21 to 48 days.
10.5.
Derived and transformed data

For a given subject and a given immunogenicity measurement, missing or non-evaluable 
measurements will not be replaced. Therefore, an analysis will exclude subjects with 
missing or non-evaluable measurements.

The cut-off value is defined by the laboratory before the analysis and is described in Section
5.7.3.

A seronegative subject is a subject whose titre is below the cut-off value.

A seropositive subject is a subject whose titre is greater than or equal to the cut-off value.

The Geometric Mean Titres (GMTs) calculations are performed by taking the anti-log of the 
mean of the log titre transformations. Antibody titres below the cut-off value of the assay 
will be given an arbitrary value of half the cut-off value for the purpose of GMT calculation.

rSBA booster response for serogroups A, C, W-135 and Y after the vaccine dose is defined 
as:

For initially seronegative subjects (pre-vaccination titer below the cut-off of 1:8): rSBA 
antibody titers 1:32 one month after vaccination, and

For initially seropositive subjects (pre-vaccination titer 1:8): rSBA antibody titers at 
least four times the pre-vaccination antibody titers, one month after vaccination.

hSBA booster response for serogroups A, C, W-135 and Y after the vaccine dose is defined 
as:

For initially seronegative subjects (pre-vaccination hSBA titre below 1:4): hSBA 
antibody titres ≥1:8 one month after vaccination, and 

For initially seropositive subjects (hSBA titer 1:4): a 4-fold increase in hSBA titres 
one month after vaccination.
10.5.1.
Persistence analyses
10.5.1.1.
Analysis of demographics/baseline characteristics
Demographic characteristics of each study cohort will be tabulated: age (in years) at Month X 
and months since the primary vaccination at persistence time point, gender, and geographic 
ancestry.
The mean age [in years] (at the persistence time point [with the range and standard deviation]) as 
well as the proportion of males and females will be calculated and presented by group.
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The distribution of subjects enrolled at Month X among the study sites will be tabulated as a 
whole and per group and reason for not attending a visit at Month X among all subjects who 
participated in the primary vaccination study MenACWY-TT-027 (108658) will be summarized.
10.5.1.2.
Analysis of persistence
For each Month X: The analysis of antibody persistence for MenC will be based on the ATP 
cohort for persistence – MenC – adapted for each time point. The analysis of antibody 
persistence for MenA, MenW-135 and MenY will be based on the ATP cohort for persistence –
MenAWY – adapted for each time point. If, for any vaccine group, the percentage of subjects 
who come back for the Month X follow-up with serological results excluded from the ATP 
cohort is higher than 10%, a second analysis based on the Total Vaccinated Cohort Month X will 
be performed to complement the ATP analysis.
10.5.1.2.1. Within group analysis
For each treatment group, at each blood sampling time point, for each antigen assessed:

Geometric mean antibody titres (GMTs) with 95% CIs will be tabulated.

Percentages of subjects with titres above the proposed cut-offs with exact 95% CIs will be 
calculated.

The distribution of antibody titres will be tabulated and also presented using reverse 
cumulative curves.
10.5.1.2.2. Between group analysis
An exploratory evaluation of the differences in the immune response at approximately 78, 90, 
102, 114 and 126 months after the primary vaccination will be performed in terms of:

Differences in the percentage of subjects with rSBA titres ≥1:8 and ≥1:128 and hSBA titres 
≥1:4 and ≥1:8 between the ACWY2 and MenPS (primed) groups, with their standardized 
asymptotic 95% CIs for the four serogroups and the differences in the percentage of subjects 
with rSBA-MenC titres ≥1:8 and ≥1:128 and hSBA-MenC titres ≥1:4 and ≥1:8 between the 
ACWY2 and MenCCRM (primed) groups with their standardized asymptotic 95% CIs.

Ratio of GMTs between the ACWY2 and MenPS groups for the four serogroups and the 
ratio of MenC GMTs between the ACWY2 and MenCCRM (primed) groups, with their 
standardized asymptotic 95% CIs. This will be performed using an Analysis of Variance 
(ANOVA) model on the logarithm10 transformation of the titres using the vaccine group and 
age stratum as covariates. 
Modelling prediction
In order to complement the descriptive analyses of observed persistence per time point and 
minimize the bias that may have occurred due to the loss to follow-up after the vaccination, a
longitudinal analysis will be performed at the last persistence time point before booster 
vaccination for rSBA-MenA, C, W-135 and Y and/or hSBA-MenA, C, W-135 and Y.
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More details on the modeling predication that will be done will be further described in the 
Statistical Analysis Plan (SAP).
10.5.1.3.
Analysis of safety (Persistence epoch)
At each persistence time point, all reported SAEs related to vaccination and any event related to 
lack of vaccine efficacy since the last persistent time point the subject participated in up to each 
persistence visit in the current study will be described in detail in a retrospective manner.
10.5.2.
Post-booster analyses
10.5.2.1.
Analysis of demographics/baseline characteristics
Demographic characteristics of each study cohort will be tabulated: age (in years) at booster 
vaccination, gender and geographic ancestry.
The mean age [in years] (at the booster time point [with the range and standard deviation]) as 
well as the proportion of males and females and of each geographic ancestry will be calculated 
and presented by group.
The distribution of subjects among the study sites will be tabulated as a whole and per group.
10.5.2.2.
Analysis of post-booster immunogenicity
The analysis of post-booster immunogenicity for MenC will be based on the Booster ATP cohort 
for immunogenicity - MenC. The analysis of post-booster immunogenicity for MenA, MenW-
135 and MenY will be based on the Booster ATP cohort for immunogenicity - MenAWY. If, for 
any vaccine group, the percentage of subjects who come back with serological results excluded 
from the Booster ATP cohort is higher than 10%, a second analysis based on the Booster Total 
Vaccinated Cohort will be performed to complement the Booster ATP analysis.
10.5.2.2.1. Within group analysis
For each treatment group, at each blood sampling time point (Month 126 and Month 127), for 
each antigen assessed:

GMTs with 95% CIs will be tabulated.

Percentages of subjects with titres above proposed cut-offs and booster response (M127) 
with 95% CIs will be calculated.

The antibody titres will be tabulated and also presented using reverse cumulative curves.
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10.5.2.3.
Analysis of post-booster safety
The primary analysis will be performed on the Booster Total Vaccinated Cohort and, if more 
than 10% of the enrolled subjects are eliminated from the Booster ATP cohort for safety a 
second analysis will be performed on the Booster ATP cohort for safety to support the analyses 
of the Booster Total Vaccinated Cohort.
For each treatment group, after the booster vaccination administered at Visit 5:
The percentage of subjects with at least one local adverse event (solicited and unsolicited), with 
at least one general adverse event (solicited and unsolicited) and with any adverse event during 
the 4-day (Days 0-3) solicited follow-up period will be tabulated with exact 95% CI. 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, medical 
advice) and general (any grade, grade 3, related, grade 3 and related, medical advice) adverse 
event during the 4-day follow-up period (Days 0-3) after vaccination and its exact 95% CI will 
be tabulated. Occurrence of fever will also be reported per 0.5°C cumulative increment as well as 
the percentage of subjects with oral temperature
>39.5°C. Additionally, large injection site reactions will be described in detail.
The verbatim reports of unsolicited symptoms will be reviewed 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 (Days 0-30) 
and its exact 95% CI 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.
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The number and percentage of subjects who experienced serious adverse events and new onset of 
chronic illness within one month following vaccination will be tabulated with exact 95% CI.
The percentage of subjects using concomitant medication (any medication, any 
antipyretic/analgesic, any antipyretic/analgesic taken prophylactically, respectively) during the 4-
day and 31-day follow-up periods (Days 0-3 and Days 0-30, respectively) after vaccination will 
be summarized.
10.6.
Interpretation of analyses
All the analyses will be descriptive with the aim to characterise the immunogenicity within and 
between study groups. 
 
 
10.7.
Conduct of analyses
Any deviations or changes from the original statistical plan outlined in this protocol will be 
described and justified in the final study report.
10.7.1.
Sequence of analyses
The persistence analysis will be done in stepwise fashion after the persistence time points for 
Months 78, 90, 102, 114 and 126 as soon as results are available.
The analysis of immunogenicity, safety and reactogenicity will be done after the booster time 
point as soon as results are available for Visit 5 and Visit 6.
The analysis will be done on a validated and frozen database. The persistence analyses will be 
done on as clean as possible data. 
The analysis for each time point will be reported in separate annex clinical study reports in a 
cumulative manner. The final report containing all persistence, post-booster, and ESFU 
endpoints will be done on fully cleaned data.
10.7.2.
Statistical considerations for interim analyses
No statistical adjustment for interim analyses is required.
11.
ADMINISTRATIVE MATTERS
To comply with ICH GCP administrative obligations relating to data collection, monitoring, 
archiving data, audits, confidentiality and publications must be fulfilled. 
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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 a 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.

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 Document 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 
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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 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.
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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.
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
11.6.
Provision of study results to investigators
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 
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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.
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.
11.7.
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.  
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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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13.
REFERENCES
Andrews N, Borrow R, Miller E. Validation of serological correlate of protection for 
meningococcal C conjugate vaccine by using efficacy estimates from postlicensure surveillance 
in England. Clin Diagn Lab Immunol. 2003;10(5):780-786. 
Centers for Disease Control and  Prevention Metropolitan Atlanta Congenital Defects Program 
(CDC MACDP) guidelines. Birth defects and genetic diseases branch 6-digit code for reportable 
congenital anomalies; 
http://www.cdc.gov/ncbddd/birthdefects/documents/MACDPcode0807.pdf
Centres for Disease Control. Inadvertent Misadministration of Meningococcal Conjugate 
Vaccine – United States, June-August 2005. MMWR. 2006;55(37):1016-1017.
Cohn AC, NacNeil JR, Harrison LH, Hatcher C, et al. Changes in Neisseria meningitidis disease 
epidemiology in the United States, 1998-2007: implications for prevention of meningococcal 
disease. Clin Infect Dis. 2010: 50(2):184-191.
EMA Guideline on the exposure to medicinal products during pregnancy: need for post-
authorization data (Doc. Ref. EMEA/CHMP/313666/2005 ) ‘adopted at Community level in 
May 2006);
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guidelin
e/2009/11/WC500011303.pdf
European Commission. Commission implementing decision of 20.04.2012. granting marketing 
authorisation under Regulation (EC) No 726/2004 of the European Parliament and of the Council 
for “Nimenrix – Meningococcal Group A, C, W-135 and Y conjugate vaccine” a medicinal 
product for human use. C(2012)2813 http://ec.europa.eu/health/documents/community-
register/2012/20120420120470/dec_120470_en.pdf Accessed 05 Nov 2015.
European Public Assessment Report (EPAR). May 2012. 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Public_assessment_report/human/001095/WC500090150.pdf
Goldschneider I, Goltschlich EC, Artenstein MS. Human immunity to meningococcus II. 
Development of natural immunity. J Exp Med. 1969;129:1327-1348. 
Harrison LH. Epidemiological profile of meningococcal disease in the United States. Clin Infect 
Dis. 2010;50 Suppl 2:S37-44
Healy CM, Butler KM, Smith EO et-al. Influence of serogroup on the presentation, course, and 
outcome of invasive meningococcal disease in children in the Republic of Ireland, 1995-2000. 
Clin. Infect. Dis. 2002;34 (10): 1323-30.
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Maslanka SE, Gheesling LL, Libutti DE et al. Standardization and a multilaboratory comparison 
of Neisseria meningitidis serogroup A and C serum bactericidal assays. Clin. Diagn. Lab. 
Immunol. 1997;4(2):156-167. 
Menactra Approval Letter. April 2011. 
http://www.fda.gov/BiologicsBloodVaccine/Vaccines/ApprovedProducts/ucm252511.htm. 
Accessed 23 September 2011.
Menactra Product Information. US. May 2009.
Menveo Consumer Medicine Information. Australia. July 2010.
Menveo Prescribing Information. US. March 2011.
Menveo Product Monograph. Canada. May 2010.
Rosenstein NE, Perkins BA, Stephens DS et-al. Meningococcal disease. N. Engl. J. Med. 
2001;344 (18): 1378-88
WHO position paper on Meningococcal vaccines. Weekly epidemiological record No. 47, 2011; 
86:521-540.
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APPENDIX A
LABORATORY ASSAYS

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 the 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 meningococcal colony-forming units (CFU). 

hSBA titres will be expressed as the reciprocal of the interpolated serum dilution resulting in 
50% reduction of meningococcal CFU. The clinical cut-offs (ie, positive titre) for the rSBA 
is titre 1:8 and for hSBA is titre 1:4.
Note: Any additional serology may be performed if deemed necessary if any findings in the 
present study or in other studies necessitate investigation of the immunogenicity of the 
vaccine.
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APPENDIX B
CLINICAL LABORATORIES
Table 18
Neomed Institute
Laboratory
Address
Component
Neomed Institute Laval, 
Quebec, Canada
Biospecimen Reception - Clinical Serology
525 Cartier blvd West - Laval - Quebec -
Canada - H7V 3S8
MenA, MenC, MenW-135. and MenY hSBA 
assay,
Table 19
Outsourced laboratories
Laboratory
Address
Component
PHE laboratory*
Vaccine Evaluation Unit,
Public Health England North West,
Manchester Medical Microbiology 
Partnership,
2nd Floor, Clinical Sciences Building H,
Manchester Royal Infirmary,
Oxford Road, Manchester,
England, M13 9WZ
MenA, MenC, MenW-135 and MenY rSBA 
assay
*PHE was formally called HPA (Health Protection Agency)
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