A PHASE IIIB, OPEN STUDY TO EVALUATE THE IMMUNOGENICITY, REACTOGENICITY AND SAFETY OF A BOOSTER DOSE OF MENACWY-TT VACCINE ADMINISTERED 10 YEARS AFTER HEALTHY SUBJECTS AGED 11-17 YEARS RECEIVED EITHER MENACWY-TT VACCINE (NIMENRIX(REGISTERED)) OR MENCEVAX ACWY(REGISTERED).
Phase: PHASE3
Conditions: Meningococcal ACWY Disease
Sponsor: Pfizer

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Clinical Study Protocol
Sponsor:
Pfizer, Inc.
235 East 42nd Street
New York, NY 10017, United States
Primary Study vaccines
Meningococcal serogroups A, C, W-135, Y tetanus 
toxoid conjugate (MenACWY-TT) vaccine 
(Nimenrix®, PF-06866681).
Other Study vaccine(s)
NA
Study number and 
Abbreviated Title
C0921005 (MENACWY-TT-101 EXT:036 Y10; 
formerly GSK 116724) 
European Clinical Trials 
Database (EudraCT)
Number
2013-001512-29
Date of protocol
Final Version 2: 03 July 2013 
Date of protocol 
amendment
Amendment 1 Final: 23 October 2013
Amendment 2 Final: 25 February 2016
Amendment 3 Final: 12 July 2017
Title
Immunogenicity, reactogenicity and safety of a booster 
dose of MenACWY-TT vaccine (PF-06866681).
Detailed Title
A phase IIIb, open study to evaluate the 
immunogenicity, reactogenicity and safety of a booster 
dose of MenACWY-TT vaccine administered 10 years 
after healthy subjects aged 11-17 years received either 
MenACWY-TT vaccine (Nimenrix®) or Mencevax 
ACWY®. 
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Protocol Amendment 3 Sponsor Signatory Approval
Study number and 
Abbreviated Title
C0921005 (MENACWY-TT-101 EXT:036 Y10; 
formerly GSK 116724)
EudraCT number
2013-001512-29
Date of protocol
Final Version 2: 03 July 2013 
Date of protocol amendment
Amendment 1 Final: 23 October 2013
Amendment 2 Final: 25 February 2016
Amendment 3 Final: 12 July 2017
Detailed Title 
A phase IIIb, open study to evaluate the 
immunogenicity, reactogenicity and safety of a 
booster dose of MenACWY-TT vaccine administered 
10 years after healthy subjects aged 11-17 years 
received either MenACWY-TT vaccine (Nimenrix®) 
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 3
12 July 2017
Changes were made based on the  
protocol administration 
clarification letter that was 
distributed to sites and included an 
update to Table 4 to indicate that 
pre-vaccination assessment of 
contraception does not require 
documentation in the individual 
case report form (CRF)/electronic 
case report form (eCRF).
A minor editorial change was made 
in Section 6.3 Dosage and 
Administration of Study Vaccine.
Blood draw was increased to up to 
50 mL of whole blood at Visit 2 (1 
month-post booster vaccination) for 
a subset of consenting subjects. 
Several changes were made 
throughout this protocol 
amendment to adjust blood 
volumes collected at Visit 2 for this 
subset. Changes were made to the 
following sections:
Section 1.2
Section 5.5 Table 4
Section 5.6.1
Section 5.6.12.1
Section 5.7.2 Table 6
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Amendment 2
25 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.

Blood sample volume 
increased to 10 mL for pre-
and postbooster samples.

Sections updated / added  in 
line with standard Pfizer 
policy: 
Synopsis – Secondary 
immunogenicity 
objectives
1.1 Background
1.2 Rationale for the study 
and study design
1.3 Benefit : Risk 
assessment
2.2 Secondary objectives
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
5.5 Outline of study 
procedures
5.6.9 Pre-Vaccination 
assessment of 
contraception
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5.6.10 Urine pregnancy test
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
8.1.6.1 Solicited local 
(injection-site) adverse 
events
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 Subject withdrawal
9.2.1 Subject withdrawal 
from the study
9.2.2 Subject withdrawal 
from study vaccine
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10.4 Study cohorts/data sets 
to be analysed
10.6 Statistical analyses
11.3 Record retention
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
Additions to the glossary 
(including the clarification 
of contraception/
abstinence)
List of Abbreviations
Trademarks
Table 4 changes (including 
prevaccination assessment 
of contraception, related 
SAEs, and pregnancy as 
an exclusion criterion)

Taking into consideration the 
timelines for regulatory 
submission and approval in the 
Philippines, the planned study 
start for booster vaccination 
has been delayed. To allow all 
subjects to receive their 
booster vaccination, Visit 1 
will occur at 10 years after the 
primary vaccination in study 
MENACWY-TT-036. The 
study will only have two time 
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points including the booster 
vaccination visit at Month 120 
and the one month post-
booster vaccination visit at 
Month 121. As a result, 
antibody persistence after 
booster vaccination will not be 
assessed in the current study. 

The Document Standard 
template version was promoted 
from v14.0 to v14.1.1. To this 
end, the Section on 
Benefit:Risk Assessment was 
added (Section 1.3) and 
revisions made to biological 
specimens (Section 5.7). 

The total number of subjects 
expected to participate in the 
study and details related to 
sample size have been updated.

In addition, minor editorial 
changes were made.
Amendment 1
23 October 2013
Not applicable (NA)
Original protocol
03-July-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 3 Investigator Agreement
I agree:

To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by Pfizer.

To assume responsibility for the proper conduct of the study at this site.

That I am aware of, and will comply with, ‘Good Clinical Practice’ and all 
applicable regulatory requirements. 

To ensure that all persons assisting me with the study are adequately informed about 
the Pfizer 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
C0921005 (MENACWY-TT-101 EXT:036 Y10; 
formerly GSK 116724) 
EudraCT number
2013-001512-29
Date of protocol
Final Version 2: 03 July 2013 
Date of protocol amendment
Amendment 1 Final: 23 October 2013
Amendment 2 Final: 25 February 2016
Amendment 3 Final: 12 July 2017
Detailed Title
A phase IIIb, open study to evaluate the 
immunogenicity, reactogenicity and safety of a 
booster dose of MenACWY-TT vaccine administered 
10 years after healthy subjects aged 11-17 years 
received either MenACWY-TT vaccine (Nimenrix®) 
or Mencevax ACWY®. 
Investigator name
Signature
Date
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SYNOPSIS
Detailed Title
A phase IIIb, open study to evaluate the immunogenicity, 
reactogenicity and safety of a booster dose of MenACWY-TT 
vaccine administered 10 years after healthy subjects aged 
11-17 years received either MenACWY-TT vaccine 
(Nimenrix®) or Mencevax ACWY®. 
Indication
Active immunization against invasive meningococcal disease 
caused by Neisseria meningitidis serogroups A, C, W-135 and 
Y in healthy subjects aged 11 to 17 years of age.
Rationale for the 
study and study 
design
Subjects aged 11-17 years of age were vaccinated with one 
dose of either MenACWY-TT or Mencevax ACWY in study 
MenACWY-TT-036 (109069). The participants from India 
and the Philippines were further followed for the assessment 
of persistence in study MenACWY-TT-043 (112148). Unless 
they withdrew their consent, subjects were invited for a yearly 
blood sample, regardless of their serostatus at the previous 
persistence time point, up to Year 5 after primary vaccination. 
Five years after vaccination the percentage of subjects with 
rSBA titres ≥ 1:8 for the 4 meningococcal serogroups A, C, 
W-135, and Y ranged between 86.0% - 97.5% in the Nimenrix
vaccinees and between 34.9% - 93.0% in the subjects 
vaccinated with Mencevax ACWY. 
A booster dose 5 years after vaccination has already been 
assessed in individuals primed at the age of 11-25 years. The 
purpose of this study is to evaluate the safety and 
immunogenicity of a booster dose of MenACWY-TT vaccine 
administered 10 years after healthy subjects aged 11-17 years 
received either a single dose of meningococcal serogroup 
ACWY tetanus toxoid conjugate (MenACWY-TT) vaccine or 
Mencevax ACWY. The primary vaccination study 
MenACWY-TT-036 (109069) was conducted in India, the 
Philippines and Taiwan. The MenACWY-TT-043 (112148) 
persistence study up to Year 5 after primary vaccination 
included only India and the Philippines. Due to Good Clinical 
Practice issues in India, this booster study will only be 
conducted in the Philippines.
Objectives
Primary
One month post-booster vaccination with MenACWY-TT 
vaccine in each of the study groups:

To evaluate the immunogenicity of a booster dose of 
MenACWY-TT conjugate vaccine in terms of the 
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percentage of subjects with an rSBA-MenA, rSBA-
MenC, rSBA-MenW-135, rSBA-MenY Booster 
response*. 
*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.
Secondary
Secondary immunogenicity objectives:
One month post-booster vaccination with MenACWY-TT 
vaccine:

To evaluate the immunogenicity of a booster dose of 
MenACWY-TT conjugate vaccine with respect to the 
percentage of subjects with rSBA-MenA, rSBA-MenC, 
rSBA-MenW-135, and rSBA-MenY antibody titers ≥ 1:8, 
≥ 1:128 and Geometric Mean Titres (GMTs).
Pre-booster and one month post-booster vaccination with 
MenACWY-TT vaccine:

To evaluate the percentage of subjects with anti-TT 
concentrations ≥ 0.1 IU/mL, ≥1.0 IU/mL and Geometric 
Mean Concentrations (GMCs). 
Long-term persistence phase ten years after primary 
vaccination with MenACWY-TT or Mencevax ACWY in 
Study MenACWY-TT-036 (109069):

To evaluate the long-term antibody persistence induced by 
MenACWY-TT conjugate vaccine as compared to 
Mencevax ACWY when administered to individuals 11-17 
years of age with respect to the percentage of subjects 
with rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and 
rSBA-MenY antibody titers ≥ 1:8, ≥ 1:128 and GMTs.
Secondary safety objectives:

To evaluate the safety and reactogenicity of a booster 
dose of MenACWY-TT conjugate vaccine. 

To describe Serious Adverse Events (SAEs) related to 
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study vaccination and any event related to lack of vaccine 
efficacy (i.e. meningococcal disease) from the subject’s 
last visit in study MenACWY-TT-036 (109069) or in 
study MenACWY-TT-043 EXT:036 Y2, 3, 4, 5
(112148).*
*last visit in study MenACWY-TT-036 (109069) will 
only be considered for subjects who did not participate in 
study MenACWY-TT-043 EXT:036 Y2, 3, 4, 5 
(112148).
Study design

Experimental design: Phase IIIb, open study with two 
parallel groups: ACWY-TT group: vaccinated with 
MenACWY-TT in study MenACWY-TT-036 (109069),
MenPS group: vaccinated with Mencevax ACWY in study 
MenACWY-TT-036 (109069). 

Duration of the study: Approximately one month for each 
subject 

Study groups:
Synopsis Table 1
Study groups and epochs foreseen in the study
Study Groups
Number of subjects
Approximate Age (Min -
Max)
(age unit)
Epoch 001
ACWY-TT 
150
20 years –28 years
x 
MenPS
50
20 years –28 years
x
*The sample size of this study with respect to the analysis of immunogenicity, reactogenicity and safety post 
MenACWY-TT booster vaccination is driven by a) the sample size of the primary vaccination study MenACWY-TT-
036 (109069) in the participating site and b) assumptions about the enrolment rate at the present extension study. 
For more information, see Section 10.3.
Synopsis Table 2
Study groups and treatment foreseen in the study
Treatment 
name
Vaccine/Product 
name
Study Groups
ACWY-TT
MenPS 
MenACWY-TT
MenACWY-TT
x
x
NaCl*
x
x
*The lyophilized pellet of MenACWY-TT vaccine is to be reconstituted 
with the supplied saline solution.

Control: uncontrolled.

Vaccination schedule: At Visit 1 (Month 120 post primary 
vaccination), one dose of MenACWY-TT conjugate
vaccine will be administered to all subjects in both study 
groups.

Treatment allocation: The subjects in this study will be 
allocated to the same groups as in the vaccination study 
MenACWY-TT-036 (109069). Subjects will be allocated 
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a new container number, but will retain the same subject 
number as in MenACWY-TT-036.

Blinding: Study will be conducted in an open manner. 
Synopsis Table 3
Blinding of study epoch 
Study Epochs
Blinding
Epoch 001
Open

Sampling schedule: Two blood samples for each subject 
enrolled: 

prior to booster vaccination,

one month after booster vaccination.

Type of study: extension of other protocol(s): 
(MenACWY-TT-036 [109069]; MenACWY-TT-
043EXT:036 Y2, 3, 4 and 5 [112148]).

Data collection: Electronic Case Report Form (eCRF).
Number of subjects
All subjects vaccinated with meningococcal vaccine in study 
MenACWY-TT-036 (109069) from the participating site in the 
Philippines will be considered for invitation to participate in 
this study. It is expected that approximately 200 subjects from 
the participating site in the Philippines will participate in this 
extension study.
Endpoints
Primary
Immunogenicity with respect to the components of the 
investigational vaccine one month after booster vaccination 
with MenACWY-TT vaccine (primary readouts):

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA 
MenY booster response*.
*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.
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Secondary
Immunogenicity with respect to the components of the 
investigational vaccine prior to and one month after booster 
vaccination with MenACWY-TT vaccine (secondary readouts):

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-
MenY titres 1:8, 1:128 and GMTs.

Anti-TT concentrations ≥0.1 IU/mL, ≥1.0 IU/mL and 
GMCs. 
Safety and reactogenicity:

Occurrence of solicited local and general symptoms within 
4 days (Day 0 to Day 3) after MenACWY-TT booster 
vaccination.

Occurrence of unsolicited adverse events, within 31 days 
(Day 0 to Day 30) after MenACWY-TT booster 
vaccination.

Occurrence of all SAEs, Guillain-Barré syndrome and new 
onset of chronic illness(es) [e.g. asthma, autoimmune 
disorders, type I diabetes, allergies] within 31 days (Day 0 
to Day 30) after MenACWY-TT booster vaccination.

Occurrence of SAEs related to primary vaccination and any 
event related to lack of vaccine efficacy (i.e. 
meningococcal disease) from the subject’s last visit in the 
primary study MenACWY-TT-036 (109069) or in the 
persistence study MenACWY-TT-043EXT:036 Y2, 3, 4, 5 
(112148) until entry in study C0921005 (MenACWY-TT-
101 EXT:036 Y10) (116724).
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TABLE OF CONTENTS
PAGE
SYNOPSIS....................................................................................................................10
LIST OF ABBREVIATIONS...........................................................................................21
GLOSSARY OF TERMS ...............................................................................................24
TRADEMARKS .............................................................................................................28
1.
INTRODUCTION....................................................................................................29
1.1.
Background ................................................................................................29
1.2.
Rationale for the study and study design ....................................................30
1.3.
Benefit : Risk Assessment ..........................................................................30
1.3.1.
Risk Assessment .........................................................................30
1.3.2.
Benefit Assessment.....................................................................32
1.3.3.
Overall Benefit:Risk Conclusion...................................................32
2.
OBJECTIVES.........................................................................................................33
2.1.
Primary objective ........................................................................................33
2.2.
Secondary objectives..................................................................................33
3.
STUDY DESIGN OVERVIEW ................................................................................34
4.
STUDY COHORT...................................................................................................36
4.1.
Number of subjects/centres ........................................................................36
4.2.
Inclusion criteria for enrolment....................................................................36
4.3.
Exclusion criteria for enrolment...................................................................37
5.
CONDUCT OF THE STUDY ..................................................................................38
5.1.
Regulatory and ethical considerations, including the informed 
consent process..........................................................................................38
5.2.
Subject identification and randomisation of treatment .................................39
5.2.1.
Subject identification....................................................................39
5.2.1.1.
Treatment allocation to the subject.............................39
5.2.1.1.1.
Study group and container 
number allocation ...................................39
5.3.
Method of blinding ......................................................................................40
5.4.
General study aspects ................................................................................40
5.5.
Outline of study procedures ........................................................................41
5.6.
Detailed description of study procedures ....................................................42
5.6.1.
Informed consent.........................................................................42
5.6.2.
Check inclusion and exclusion criteria .........................................43
5.6.3.
Collect demographic data ............................................................43
5.6.4.
Check contraindications, warnings and precautions to 
vaccination...................................................................................43
5.6.5.
Medical history.............................................................................43
5.6.6.
Recording of meningococcal and TT vaccination history..............43
5.6.7.
History directed physical examination..........................................43
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5.6.8.
Assess pre-vaccination body temperature ...................................43
5.6.9.
Pre-Vaccination assessment of contraception .............................44
5.6.10.
Urine pregnancy test....................................................................44
5.6.11.
Container number allocation ........................................................44
5.6.12.
Sampling......................................................................................44
5.6.12.1.
Blood sampling for safety or immune response 
assessments ..............................................................44
5.6.13.
Study Vaccine administration.......................................................45
5.6.14.
Check and record concomitant medication/vaccination and 
intercurrent medical conditions ....................................................45
5.6.15.
Recording of AEs, SAEs and pregnancies...................................45
5.6.15.1.
Recording of GBS and New Onset of Chronic 
Illnesses (NOCIs) .......................................................46
5.6.16.
Study conclusion..........................................................................46
5.7.
Biological sample handling and analysis.....................................................46
5.7.1.
Use of specified study materials ..................................................47
5.7.2.
Biological samples.......................................................................47
5.7.3.
Laboratory assays .......................................................................47
5.7.4.
Biological samples evaluation......................................................48
5.7.4.1.
Immunological read-outs ............................................48
5.7.5.
Immunological correlates of protection.........................................48
6.
STUDY VACCINE AND ADMINISTRATION...........................................................49
6.1.
Description of study vaccine .......................................................................49
6.2.
Storage and handling of study vaccine .......................................................50
6.3.
Dosage and administration of study vaccine...............................................51
6.4.
Warnings and precautions ..........................................................................51
6.5.
Concomitant medication/product and concomitant vaccination ...................52
6.5.1.
Recording of concomitant medications/products and 
concomitant vaccination...............................................................52
6.5.2.
Concomitant medications/products/vaccines that may lead 
to the elimination of a subject from ATP analyses........................52
6.6.
Intercurrent medical conditions that may lead to elimination of a 
subject from ATP analyses .........................................................................53
7.
HEALTH ECONOMICS ..........................................................................................53
8.
SAFETY.................................................................................................................53
8.1.
Safety definitions ........................................................................................54
8.1.1.
Definition of an adverse event......................................................54
8.1.2.
Medication Errors.........................................................................55
8.1.3.
Occupational Exposure................................................................55
8.1.4.
Exposure During Pregnancy ........................................................56
8.1.5.
Definition of a serious adverse event ...........................................57
8.1.6.
Solicited adverse events..............................................................58
8.1.6.1.
Solicited local (injection-site) adverse events..............58
8.1.6.2.
Solicited general adverse events................................58
8.1.7.
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events ............................................................................59
8.1.8.
Adverse events of specific interest...............................................59
8.1.8.1.
List of New Onset of Chronic Illnesses .......................59
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8.1.9.
Pregnancy ...................................................................................62
8.2.
Detecting and recording adverse events, serious adverse events 
and pregnancies .........................................................................................63
8.2.1.
Time period for detecting and recording adverse events, 
serious adverse events and pregnancies.....................................63
8.2.2.
Post-Study adverse events and serious adverse events..............66
8.2.3.
Evaluation of adverse events and serious adverse events...........66
8.2.3.1.
Active questioning to detect adverse events 
and serious adverse events........................................66
8.2.3.2.
Assessment of adverse events...................................67
8.2.3.2.1.
Assessment of intensity..........................67
8.2.3.2.2.
Assessment of causality .........................68
8.2.3.3.
Assessment of outcomes............................................69
8.2.3.4.
Medically attended visits.............................................70
8.2.3.5.
Adverse events of specific interest .............................70
8.3.
Reporting of serious adverse events, pregnancies, and other events .........70
8.3.1.
Prompt reporting of serious adverse events, pregnancies, 
and other events..........................................................................70
8.3.2.
Completion and transmission of SAE reports...............................71
8.3.3.
Completion and transmission of pregnancy reports .....................71
8.3.4.
Updating of SAE and pregnancy information after removal 
of write access to the subject’s eCRF ..........................................71
8.3.5.
Regulatory reporting requirements for serious adverse 
events..........................................................................................72
8.4.
Follow-up of adverse events, serious adverse events, and 
pregnancies................................................................................................72
8.4.1.
Follow-up of adverse events and serious adverse events............72
8.4.1.1.
Follow-up during the study..........................................72
8.4.1.2.
Follow-up after the subject is discharged from 
the study.....................................................................72
8.4.2.
Follow-up of pregnancies.............................................................73
8.5.
Treatment of adverse events ......................................................................73
8.6.
Subject card................................................................................................73
9.
SUBJECT COMPLETION AND WITHDRAWAL.....................................................74
9.1.
Subject completion .....................................................................................74
9.2.
Subject withdrawal......................................................................................74
9.2.1.
Subject withdrawal from the study ...............................................74
9.2.2.
Subject withdrawal from study vaccine ........................................75
10. STATISTICAL METHODS......................................................................................75
10.1.
Primary endpoint.........................................................................................75
10.2.
Secondary endpoints ..................................................................................76
10.3.
Determination of sample size......................................................................76
10.4.
Study cohorts/ data sets to be analysed .....................................................77
10.4.1.
Booster Total Vaccinated cohort..................................................77
10.4.2.
Booster According-to-protocol cohort for safety ...........................77
10.4.3.
Booster According-to-protocol cohort for immunogenicity ............78
10.4.4.
Total cohort at Month 120............................................................78
10.4.5.
According-to-protocol cohort for persistence at Month 120 ..........78
10.5.
Derived and transformed data.....................................................................79
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10.5.1.
Immunogenicity............................................................................79
10.6.
Statistical analyses .....................................................................................79
10.6.1.
Analysis of demographics/baseline characteristics ......................79
10.6.2.
Analysis of post-booster immunogenicity .....................................80
10.6.2.1.
Within group analysis .................................................80
10.6.3.
Analysis of antibody persistence..................................................80
10.6.3.1.
Within group analysis .................................................81
10.6.4.
Analysis of reactogenicity and safety ...........................................81
10.7.
Interpretation of analyses............................................................................82
10.8.
Conduct of analyses ...................................................................................82
10.8.1.
Sequence of analyses..................................................................82
11. ADMINISTRATIVE MATTERS ...............................................................................83
11.1.
electronic Case Report Form instructions ...................................................83
11.2.
Study Monitoring.........................................................................................83
11.3.
Record retention .........................................................................................84
11.4.
Quality assurance.......................................................................................84
11.5.
Posting of information on publicly available clinical trial registers and 
publication policy ........................................................................................85
11.6.
Provision of study results to investigators ...................................................85
11.7.
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP.....................................................................................................87
12. COUNTRY SPECIFIC REQUIREMENTS...............................................................87
13. REFERENCES.......................................................................................................87
CCI
CCI
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LIST OF TABLES
PAGE
Table 1
Study groups and epochs foreseen in the study.....................................35
Table 2
Study groups and treatment foreseen in the study .................................35
Table 3
Blinding of study epochs ........................................................................35
Table 4
List of study procedures .........................................................................41
Table 5
Intervals between study visits.................................................................42
Table 6
Biological samples for the ACWY-TT and MenPS groups ......................47
Table 7
Humoral Immunity (Antibody determination)...........................................48
Table 8
Immunological read-outs........................................................................48
Table 9
Study vaccine.........................................................................................50
Table 10
Dosage and administration.....................................................................51
Table 11
Solicited local adverse events ................................................................58
Table 12
Solicited general adverse events............................................................59
Table 13
List of NOCIs..........................................................................................60
Table 14
Reporting periods for adverse events, serious adverse events 
and pregnancies.....................................................................................65
Table 15
Intensity scales for solicited symptoms...................................................67
Table 16
Timeframes for submitting serious adverse event, exposure 
during pregnancy and other events reports ............................................71
Table 17
Exact 95% confidence intervals of the percentage of subjects 
with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY 
booster response ...................................................................................77
Table 18
Outsourced laboratories.........................................................................92
LIST OF FIGURES
PAGE
Figure 1
Study design diagram ............................................................................34
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LIST OF APPENDICES
PAGE
APPENDIX A LABORATORY ASSAYS .......................................................................91
APPENDIX B CLINICAL LABORATORIES ..................................................................92
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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, US
CDS
Core Data Sheet
CI
Confidence Interval
CRF
Case Report Form
CRM197
Non-toxic mutant form of the diphtheria toxin
CSA
Clinical Study Agreement
dLIA
Direct Luminex Immunoassay
DU
Dispensible Unit
EC
Ethics Committee
eCRF
Electronic Case Report Form
EDP
Exposure During Pregnancy
EGA
Estimated Gestational Age
ELISA
Enzyme-Linked Immunosorbent Assay
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration, US
GBS
Guillain-Barré Syndrome
GCP
Good Clinical Practice
GMC
Geometric Mean Concentration
GMT
Geometric Mean Titre
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GSK
GlaxoSmithKline
HPA
Health Protection Agency
IAF
Informed Assent Form
ICD
International Classification of Diseases
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IM
Intramuscular(ly)
IMP
Investigational Medicinal Product
IRB
Institutional Review Board
IRT
Interactive Response Technology
LAR
Legally Acceptable Representative
LL
Lower Limit
LLOQ
Lower Limit of Quantitation
LMP
Last Menstrual Period
MedDRA
Medical Dictionary for Regulatory Activities
MenA
N. meningitidis serogroup A
MenC
N. meningitidis serogroup C
MenW-135
N. meningitidis serogroup W
MenY
N. meningitidis serogroup Y
mL
milliliter(s)
NA
Not Applicable
NOCI
New Onset of Chronic Illness(es)
PHE
Public Health England (previously the Health Protection 
Agency [HPA])
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pIMD
Potential Immune-Mediated Disorder
rSBA
Serum Bactericidal Assay (using baby rabbit complement)
rSBA-MenA
Serum Bactericidal Assay/activity against N. meningitidis
serogroup A (using baby rabbit complement)
rSBA-MenC
Serum Bactericidal Assay/activity against N. meningitidis
serogroup C (using baby rabbit complement)
rSBA-MenW-135
Serum Bactericidal Assay/activity against N. meningitidis
serogroup W-135 (using baby rabbit complement)
rSBA-MenY
Serum Bactericidal Assay/activity against N. meningitidis
serogroup Y (using baby rabbit complement)
SAE
Serious Adverse Event
SBA
Serum Bactericidal Assay
SDV
Source Data Verification
SPM
Study Procedures Manual
SRSD
Single Safety Reference Document
TT
Tetanus Toxoid
g
Microgram(s)
UL
Upper Limit
US; United States
United States; United States of America
WHO
World Health Organization
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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 and when applicable, in 
accordance with the product label for example: 

abstinence from penile-vaginal intercourse, when this 
is the subject’s preferred and usual lifestyle (any 
version of temporary or episodic abstinence is not 
considered adequate contraception),

oral contraceptives, either combined or progestogen 
alone,

injectable progestogen,

implants of etenogestrel or levonorgestrel,

estrogenic vaginal ring,

percutaneous contraceptive patches,

intrauterine device or intrauterine system,

male partner sterilisation prior to the female subject’s 
entry into the study, and this male is the sole partner 
for that subject,
The information on the male sterility can come from 
the site personnel’s review of the subject’s medical 
records; or interview with the subject on her medical 
history.

male condom combined with a vaginal spermicide 
(foam, gel, film, cream or suppository),

male condom combined with a female diaphragm, 
either with or without a vaginal spermicide (foam, 
gel, film, cream, or suppository). 
Adequate contraception does not apply to subjects of 
child bearing potential with same sex partners, when this 
is their preferred and usual lifestyle.
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Adverse event:
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use 
of a medicinal product, whether or not considered related 
to the medicinal product. 
An adverse event (AE) can therefore be any unfavourable 
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal product. 
For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), 
abuse or misuse.
Blinding:
In an open-label study, no blind is used. Both the 
investigator and the subject know the identity of the 
treatment assigned. 
Container Number
A number identifying a treatment to a subject, according 
to the study randomisation or treatment allocation.
Core Data Sheet (CDS):
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.
Epoch:
An epoch is a self-contained set of consecutive time 
points or a single time point from a single protocol. Self-
contained means that data collected for all subjects at all 
time points within that epoch allows to draw a complete 
conclusion to define or precise the targeted label of the 
product. Typical examples of epochs are primary 
vaccinations, boosters, yearly immunogenicity follow-
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ups, and surveillance periods for efficacy or safety.
Evaluable:
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the according-to-protocol (ATP) analysis (see 
Sections 6.5.2 and 10.4 for details on criteria for 
evaluability).
Menarche:
Menarche is the onset of menses for the first time in a 
young female and is preceded by 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).
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. 
Potential Immune-
Mediated Disorder:
Potential immune-mediated disorders 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.
Post-menopause
Achieved post-menopausal status, defined as follows: 
cessation of regular menses for at least 12 consecutive 
months with no alternative pathological or physiological 
cause; status may be confirmed by a serum follicle-
stimulating hormone (FSH) level confirming the 
post-menopausal state.
Randomisation:
Process of random attribution of treatment to subjects in 
order to reduce bias of selection.
Self-contained study:
Study with objectives not linked to the data of another 
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study.
Site Monitor:
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at one or 
more investigational sites.
Solicited adverse event:
The presence/occurrence/intensity of these events is 
actively solicited from the subject or an observer during a 
specified post-vaccination follow-up period.
Subject:
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, either as a recipient of 
the vaccine(s)/product(s) or as a control.
Subject number:
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study.
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 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 ® and will be written in italics.
Trademarks of Pfizer
Generic description
Nimenrix®
Meningococcal group 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
Menveo® (GSK Biologicals)
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 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]. Meningococcal vaccines are also given to travellers, including Muslim 
pilgrims [Mimouni, 1998; Tawfiq, 2012]. Hence there is a need to understand how long 
immunity persists in case of re-exposure.
It has been observed that previous meningococcal polysaccharide vaccination may 
influence the immune response of a meningococcal conjugate vaccine administered three 
years later [Keyserling, 2005; Dbaibo, 2012a]. It is of interest to evaluate whether this 
phenomenon is also observed after a longer interval between the administration of the 
polysaccharide and the conjugate vaccine and the potential benefit of priming with a 
conjugate vaccine on the booster response.
Currently, there are three quadrivalent meningococcal conjugate vaccines available in 
various countries worldwide for vaccination of children and adolescents/adults; 
MenACWY diphtheria toxoid conjugate vaccine (Menactra, Sanofi Pasteur Inc.) is 
authorised for active immunization of subjects aged 9 months to 55 years in the United 
States (US) [Menactra Product Information, 2009; Menactra Approval Letter 2011], 
Canada [Menactra Product Mongraph, 2012] and in the Gulf Cooperation States in the 
Middle East. MenACWY CRM-197 conjugate vaccine (Menveo, GlaxoSmithKline 
(GSK) Biologicals) is authorised for active immunization of subjects from 2 years of age 
in the European Union [Menveo Summary of Product Characteristics, 2014], from 11 
years of age in Australia [Menveo Consumer Medicine Information, 2015] and from 2 
months to 55 years of age in Canada and the US [Menveo Product Monograph, 2014; 
Menveo Highlights on Prescribing Information, 2013]. GlaxoSmithKline (GSK)
Biologicals has developed a quadrivalent candidate vaccine (MenACWY-TT) for the 
prevention of invasive infections with Neisseria meningitidis serogroups A, C, Y, and 
W-135, using Tetanus Toxoid (TT) as the carrier. This vaccine, which was granted a 
marketing authorisation on 20 April 2012 by the European Commission for the active 
immunisation of individuals from the age of 12 months and above against invasive 
meningococcal disease caused by Neisseria meningitidis serogroups A, C, W and Y
[European Commission, 2012] and is currently licensed in more than 63 countries 
including all European Union (EU) Member States, Iceland, Norway, Canada and 
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Australia. Cumulative post-marketing exposure to Nimenrix since launch up to April 
2015 is estimated to be 1,711,167 subjects.
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 for information regarding the pre-clinical and 
clinical studies and the potential risks and benefits of Nimenrix. The Core Data Sheet is 
the single reference safety document (SRSD) for this study.
1.2.
Rationale for the study and study design
Subjects aged 11-17 years of age were vaccinated with one dose of either 
MenACWY-TT or Mencevax ACWY in study MenACWY-TT-036 (109069). The 
participants from India and the Philippines were further followed for the assessment of 
persistence in study MenACWY-TT-043 (112148). Unless they withdrew their consent, 
subjects were invited for a yearly blood sample, regardless of their serostatus at the 
previous persistence time point, up to Year 5 after primary vaccination. Five years after 
vaccination, the percentage of subjects with rSBA titres ≥ 1:8 for the 4 meningococcal 
serogroups A, C, W-135, and Y ranged between 86.0% - 97.5% in the Nimenrix
vaccinees and between 34.9% - 93.0% in the subjects vaccinated with Mencevax ACWY.
A booster dose 5 years after vaccination has already been assessed in individuals primed 
at the age of 11-25 years. The purpose of this study is to evaluate the safety and
immunogenicity of a booster dose of MenACWY-TT vaccine administered 10 years after 
healthy subjects aged 11-17 years received either a single dose of meningococcal 
serogroup ACWY tetanus toxoid conjugate (MenACWY-TT) vaccine or Mencevax 
ACWY. The primary vaccination study MenACWY-TT-036 (109069) was conducted in 
India, the Philippines and Taiwan. The MenACWY-TT-043 (112148) persistence study 
up to Year 5 after primary vaccination included only India and the Philippines. Due to 
Good Clinical Practice (GCP) issues in India, this booster study will only be conducted in 
the Philippines.
In order to support assay development, subjects who have voluntarily signed the 
informed consent document (ICD) addendum will have up to 50 mL, rather than 10 mL,
of blood drawn at Visit 2.
1.3.
Benefit : Risk Assessment
Summaries of data from pre-clinical and clinical studies conducted with MenACWY-TT, 
epidemiological information and the summary of potential risks and benefits can be 
found in the Core Data Sheet or prescribing information/product label.
1.3.1.
Risk Assessment
The MenACWY-TT conjugate vaccine (Nimenrix) has demonstrated a favourable safety 
profile in the clinical studies performed till now.
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The current section outlines the risk assessment and mitigation strategy for this study 
protocol. Based on the non-clinical and clinical development experience with the 
MenACWY-TT vaccine and post-marketing reports available at this time, there are no 
important identified risks associated with the MenACWY-TT vaccine. The vaccine was 
well tolerated without key safety findings.
The following events were assessed as potential risks associated with the MenACWY-TT 
vaccine based on clinical trial data or post-marketing experience:

Cases of Guillain-Barré syndrome (GBS) have been reported in the US following 
administration of Menactra. Although no cases of GBS have been reported after 
vaccination with MenACWY-TT up to now, occurrence of GBS will be closely 
monitored in all studies (see Section 8.4.1). Subjects with a history of any 
neurological disorders or seizures, including GBS, will be excluded from 
participation into the study (see Section 4.3).

Anaphylaxis may occur following exposure to allergens via immunization. Subjects 
who experience or have ever experienced anaphylaxis following the administration 
of (a) vaccine(s) will be excluded from participation into the study (see Section 4.3). 
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 (see Section 5.6.13).

No vaccine completely protects every vaccinated individual and a protective immune 
response may not be elicited in all vaccinees. Therefore, lack of efficacy will be 
recorded as Adverse Event (AE) as part of the safety monitoring (see Section 8.1.1).

In the MenACWY-TT clinical development program, the MenACWY-TT vaccine 
was administered intramuscularly (IM). Therefore, Section 6.4 ‘Warnings and 
Precautions’ of this protocol highlights that the vaccine should under no 
circumstances be administered intravascularly, intradermally or subcutaneously. 
Additionally, Section 6.4 highlights that the vaccine should be administered with 
caution to subjects with thrombocytopenia or a bleeding disorder as bleeding may 
occur following an IM administration to these subjects.

Since tetanus toxoid has been associated with arthus type reactions and although 
there was limited evidence of a higher incidence of grade 3 local reactions following 
MenACWY-TT administration compared to Mencevax, extensive limb swelling and 
severe injection site reactions were identified as a potential risk following 
vaccination with MenACWY-TT. Injection site reactions will be actively solicited in 
this study (see Section 8.1.6).

Due to the limited experience with the use of MenACWY-TT in pregnant women, 
pregnant or lactating females will be excluded from the study (see Section 4.3). 
Female subjects of childbearing potential are to have a urine pregnancy test prior to 
the study vaccine administration and will not be vaccinated if the test is positive (see 
Section 5.6.10).

In addition, specific events (i.e., purpura, vasculitis, acute disseminated 
encephalomyelitis and brachial neuritis) have been reported following administration 
of meningococcal or other childhood vaccines. These events are monitored as part of 
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the routine pharmacovigilance plan and no specific risk minimisation is needed as 
part of this study.
Related to the study procedures, Section 6.4 ‘Warnings and Precautions’ of this protocol 
highlights that syncope (fainting) can occur following, or even before, any vaccination as 
a psychogenic response to needle injection and that procedures should be in place to 
avoid injury from faints.
In non-clinical studies, the current formulation of the MenACWY-TT vaccine (third 
generation) was examined for its local reactogenicity after a single IM injection and for 
local and general toxicity and reactogenicity after five repeated IM injections in rabbits. 
A reproductive toxicology study was performed to evaluate the effect of the vaccine on 
embryo-fetal, pre- and post-natal development in the rat. The results of these studies 
indicated that the vaccine was well tolerated in animal models and no key safety findings 
were observed.
1.3.2.
Benefit Assessment
In clinical studies, a single dose of MenACWY-TT was shown to have a good 
immunogenicity profile in toddlers [Knuf, 2010; Knuf, 2011], children aged 2-10 years 
[Memish, 2011; Knuf, 2010; Vesikari, 2011], adolescents [Bermal, 2011; Baxter, 2011; 
Østergaard, 2012] and adults [Østergaard, 2009; Dbaibo, 2012b; Aplasca-De Los Reyes, 
2012; Dbaibo, 2013]. The vaccine conferred protection against invasive meningococcal 
diseases caused by Neisseria meningitidis serogroups A, C, W-135 and Y to unprimed 
study participants . Since the introduction of monovalent meningococcal serogroup C 
conjugate vaccines and the implementation of national vaccination programmes for 
infants and toddlers, a waning of protection following primary vaccination with MenC 
conjugate vaccines was observed and a booster dose in teenagers might be needed to 
maintain protection into adolescents [Borrow, 2013]. Several countries have already 
introduced booster vaccination in teenagers [Pollard, 2010]. It is also known that titres 
are waning over time for all serogroups [Baxter, 2011;Baxter, 2014; Baxter, 2015]. 
Therefore, the-primed participants of this study might also benefit from a booster dose of 
the study vaccine.
In addition, study participants may benefit from the medical procedures performed during 
the study.
1.3.3.
Overall Benefit:Risk Conclusion
The potential risks identified in association with MenACWY-TT are justified by the 
anticipated benefits that may be afforded by a booster dose administered to adults primed 
at 11 to 17 years for protection against Neisseria meningitidis serogroups A, C, W-135 
and Y.
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2.
OBJECTIVES
2.1.
Primary objective
One month post-booster vaccination with MenACWY-TT vaccine in each of the study 
groups:

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*.
*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.
Refer to Section 10.1 for the definition of the primary endpoint.
2.2.
Secondary objectives
Secondary immunogenicity objectives:
One month post-booster vaccination with MenACWY-TT vaccine:

To evaluate the immunogenicity of a booster dose of MenACWY-TT conjugate 
vaccine with respect to the percentage of subjects with rSBA-MenA, rSBA-MenC, 
rSBA-MenW-135, and rSBA-MenY antibody titers ≥ 1:8, ≥ 1:128 and Geometric 
Mean Titres (GMTs). 
Pre-booster and one month post-booster vaccination with MenACWY-TT vaccine:

To evaluate the percentage of subjects with anti-TT concentrations ≥ 0.1 IU/mL, 
≥1.0 IU/mL and Geometric Mean Concentrations (GMCs). 
Long-term persistence phase ten years after primary vaccination with MenACWY-TT or 
Mencevax ACWY in Study MenACWY-TT-036 (109069):

To evaluate the long-term antibody persistence induced by MenACWY-TT conjugate
vaccine as compared to Mencevax ACWY when administered to individuals 11-17 
years of age with respect to the percentage of subjects with rSBA-MenA, rSBA-
MenC, rSBA-MenW-135, and rSBA-MenY antibody titers ≥ 1:8, ≥ 1:128 and GMTs.
Secondary safety objectives:

To evaluate the safety and reactogenicity of a booster dose of MenACWY-TT 
conjugate vaccine.

To describe Serious Adverse Events (SAEs) related to study vaccination and any 
event related to lack of vaccine efficacy (i.e. meningococcal disease) from the 
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subject’s last visit in study MenACWY-TT-036 (109069) or in study MenACWY-
TT-043 EXT:036 Y2, 3, 4, 5 (112148).*

*last visit in study MenACWY-TT-036 (109069) will only be considered for 
subjects who did not participate in study MenACWY-TT-043 EXT:036 Y2, 3, 4, 5 
(112148).
Refer to Section 10.2 for the definition of the secondary endpoints.
3.
STUDY DESIGN OVERVIEW
Figure 1
Study design diagram
Randomization (3:1)
Visit 1(M0)
Vacc
BS1
Visit 2 (M1)
BS2
TC 
or Visit 3 (M6)
ESFU
M120
Visit 1
MenACWY-TT
Booster
BS1
M121
Visit 2
BS2
Epoch 001
MenACWY-TT-036
* MenACWY-TT-43 EXT: 036 Y2,  Y3, Y4, Y5
MenACWY-TT-101 EXT 036 Y10
Group ACWY-TT, 
(N = 768)
MenACWY-TT
Group MenPS, 
(N = 257)
Mencevax ACWY
M24, 36, 48 and 
60*
Follow-up visits 
Persistence phase
M = Month
BS = Blood Sample
Vacc = Vaccination
TC = Telephone contact
ESFU = Extended Safety Follow-Up
N = number of subjects in the primary total vaccinated cohort.
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), is essential and required for 
study conduct. 

Experimental design: Phase IIIb, open study with two parallel groups: ACWY-TT 
group: vaccinated with MenACWY-TT in study MenACWY-TT-036 (109069), 
MenPS group: vaccinated with Mencevax ACWY in study MenACWY-TT-036 
(109069).
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
Duration of the study: Approximately one month for each subject.

Epoch 001: Booster starting at Visit 1 (at Booster vaccination[Day 0]) and 
ending at Visit 2 (one month post-booster vaccination [Day 30])

Study groups:
Table 1
Study groups and epochs foreseen in the study
Study Groups
Number of subjects
Age (Min - Max)
(age unit)
Epoch 001
ACWY-TT 
150
20 years –28 years
x
MenPS
50
20 years –28 years
x
*The sample size of this study with respect to the analysis of immunogenicity, reactogenicity and safety post 
MenACWY-TT booster vaccination is driven by a) the sample size of the primary vaccination study MenACWY-TT-
036 (109069) in the participating site and b) assumptions about the enrolment rate at the present extension study. 
For more information see Section 10.3.
Table 2
Study groups and treatment foreseen in the study
Treatment name
Vaccine/Product name
Study Groups
ACWY-TT
MenPS 
MenACWY-TT
MenACWY-TT
x
x
NaCl *
x
x
*The lyophilized pellet of MenACWY-TT vaccine is to be reconstituted with the supplied saline solution.

Control: uncontrolled.

Vaccination schedule: At Visit 1 (Month 120 post primary vaccination), one dose of 
MenACWY-TT conjugate vaccine will be administered to all subjects in both study 
groups.

Treatment allocation: The subjects in this study will be allocated to the same groups 
as in the vaccination study MenACWY-TT-036 (109069). Subjects will be allocated 
a new container number, but will retain the same subject number as in MenACWY-
TT-036.

Blinding: Study will be conducted in an open manner. 
Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
Open

Sampling schedule: Two blood samples for each subject enrolled: 

prior to booster vaccination,

one month after booster vaccination.

Type of study: extension of other protocol(s): [MenACWY-TT-036 (109069); 
MenACWY-TT-043EXT:036 Y2, 3, 4 and 5 (112148)].

Data collection: Electronic Case Report Form (eCRF).
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4.
STUDY COHORT
4.1.
Number of subjects/centres
All subjects vaccinated with meningococcal vaccine in study MenACWY-TT-036 
(109069) from the participating site in the Philippines will be considered for invitation to 
participate in this study. It is expected that approximately 200 subjects from the 
participating site in the Philippines will participate in this extension study.
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 ALL the following criteria at study entry:

Subjects 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).

Written informed consent obtained from the subject prior to performing any study 
specific procedure.

Healthy male or female subjects as established by medical history and history-
directed physical examination before entering into the study.

Having completed the vaccination in study MenACWY-TT-036 (109069) as per 
protocol.

Female subjects of non-childbearing potential may be enrolled in the study.

Non-childbearing potential is defined as pre-menarche, hysterectomy, bilateral 
ovariectomy or post-menopause.
Please refer to the GLOSSARY OF TERMS for the definitions of menarche and 
post-menopause.

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.
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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:

Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccine within 30 days preceding the dose of study vaccine, or planned use 
during the study period.

Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs within six months prior to 
the vaccine dose. For corticosteroids, this will be 10 mg/day prednisone, or 
equivalent. Inhaled,  topical, and intra-articular steroids are allowed.

Administration of a vaccine not foreseen by the study protocol within the period 
starting 30 days before and ending 30 days after the study vaccine dose, with the 
exception of a licensed inactivated influenza vaccine which can be administered at 
any time during the study according to the local recommendations.

Administration of immunoglobulins and/or any blood products within the 3 months 
preceding the study vaccination or planned administration during the booster 
vaccination phase of the study (i.e. between Visit 1 and Visit 2).

Concurrently participating in another clinical study, at any time during the study 
period, in which the subject has been or will be exposed to an investigational or a 
non-investigational vaccine/product (pharmaceutical product or device).

Previous vaccination with meningococcal vaccine except the meningococcal 
vaccination received in the MenACWY-TT-036 study.

Any confirmed or suspected immunosuppressive or immunodeficient condition 
(congenital or secondary), including human immunodeficiency virus infection, based 
on medical history and physical examination (no laboratory testing required).

Family history of congenital or hereditary immunodeficiency.

History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccine, and history of serious allergic reaction (anaphylaxis) 
following the administration of vaccine(s).

Major congenital defects or serious chronic illness.

History of any neurological disorders or seizures, including GBS. History of a 
simple, single febrile seizure is permitted.

Acute disease and/or fever at the time of vaccination. 
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
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.

Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory 
infection) without fever may be vaccinated at the discretion of the investigator.

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.

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.
5.
CONDUCT OF THE STUDY
5.1.
Regulatory and ethical considerations, including the 
informed consent process
The study will be conducted in accordance with all applicable regulatory requirements.
The study will be conducted in accordance with the International Conference on 
Harmonisation (ICH) Guideline for 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 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.
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 informed consent. 

Investigator reporting requirements as stated in the protocol.
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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 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 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, he/she 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 200 subjects are expected to participate in this study (150 from the 
ACWY-TT group and 50 from the MenPS group). Subjects will retain the same subject 
number as in MenACWY-TT-036 (109069). 
5.2.1.1.
Treatment allocation to the subject
The container numbers will be allocated by booster dose administered.
5.2.1.1.1.
Study group and container number allocation
Subjects who received either MenACWY-TT or Mencevax ACWY vaccine in study 
MenACWY-TT-036 will be invited to participate in this study and will be eligible for this 
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study if they meet the inclusion/exclusion criteria. Approximately 200 subjects are 
expected to participate in the study. 
There will be no randomisation 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-036 (109069). 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 from the subject and having checked the 
eligibility of the subject, the site staff in charge of the vaccine administration will access 
IRT. Upon providing the subject identification number, the randomisation system will 
determine the study group and 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.
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.
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5.5.
Outline of study procedures
See Table 4 for the list of study procedures.
Table 4
List of study procedures
Epoch
Epoch 001 
Visit
VISIT 1*
VISIT 2
Timing
Month 120
(10 years post-
primary vaccination)
Month 121
Sampling time point
Pre-booster vaccination
One month-post 
booster vaccination
Informed consent
●
●1
Demography
●
Check inclusion/exclusion criteria
●
Check contraindications
O
Check warnings and precautions
O
Check general medical history
●†
Meningococcal vaccination history 
●‡
Recording of last TT vaccination date 
●
History-directed physical examination
●
Pre-vaccination assessment of body temperature
●
Pre-vaccination assessment of contraception (see section 4.2)
O
Urine pregnancy test for females
●
Blood sampling: for antibody determination (approximately 10 mL)
●
●2
Record timing related to reconstitution and vaccination
●
Vaccination (MenACWY-TT)
●
Record container number
●
Observation of subjects for 30 minutes post vaccination
O
Daily post-vaccination recording by subjects, of solicited adverse 
events within 4 days (Days 0-3) after administration of the booster dose
●
Recording by subjects, of non-Serious Adverse Events (SAE) Days 0-
30 post-vaccination
●
●
Return of diary cards 3
O
Diary card transcription 
O
Record any concomitant medication/vaccination 4
●
●
Record any intercurrent medical conditions 5
●
●
Reporting of all SAEs 6
●
●
Recording of SAEs related to study vaccination and any event related 
to lack of vaccine efficacy since the previous visit 6,7
●
●
Recording of SAEs related to study participation 
●
●
Reporting of New Onset of Chronic Illness (NOCI) 8,10
●
●
Reporting of Guillain Barré Syndrome (GBS) 9,10
●
●
Reporting of Pregnancies 11
●
●
Study Conclusion 
● 12
●is used to indicate a study procedure that requires documentation in the individual eCRF.
O is used to indicate a study procedure that does not require documentation in the individual CRF/eCRF.
*The subject will be contacted by phone approximately 4-8 weeks beforehand to come in for the first visit 
†It is important to collect and document in the eCRF a complete assessment of the medical history for all subjects at 
Visit 1. Record all medical conditions/signs/symptoms current or past at the time of visit 1.
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‡ At the subject’s first visit in the current study, medical and meningococcal vaccination history since the subject’s last 
visit done in the study MenACWY-TT-036 (109069) or in the study MENACWY-TT-043 EXT:036 Y2, 3, 4, 5 (112148).
1 If the subject agrees to have up to 50 mL of blood drawn at Visit 2, he or she must sign the addendum to the consent 
form before the sample is taken. This consent can be signed at Visit 1.
2 Subjects who have consented will have up to 50 mL of blood drawn at Visit 2.
3If the subject returns for Visit 2 prior to Day 30, the subject should take home the diary card, continue to record 
unsolicited safety information until Day 30 and then provide the card to the study site.
4See Section 6.5.2 for medications and timeframe for reporting.
5 These conditions include: 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 and diagnosis of serious chronic illness) throughout the study.
6Occurrence of meningococcal diseases should be documented on the SAE report and in the eCRF.
7 At the subject’s first visit in the current study, SAEs experienced since the subject’s last visit in the persistence study 
MENACWY- TT-043 EXT:036 Y2, 3, 4, 5 (112148) should also be recorded. For subjects not enrolled in the 
MENACWY- TT-043 EXT:036 Y2, 3, 4, 5 (112148) study, the recording will be done since the subject’s last visit in the 
MenACWY-TT-036 (109069) study.
8 NOCIs (e.g. auto-immune disorders, allergies, type 1 diabetes, asthma) will be recorded within 31 days from booster
vaccination (Day 30) with day of booster vaccination considered Day 0. NOCIs will be reported as unsolicited AEs or 
SAEs as appropriate. A non-exhaustive list of NOCIs is provided in Table 13. 
9In 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 an SAE. 
10Recording will start after administration of the booster vaccination (Day 0) and ending 31 days from booster
vaccination (Day 30).
11Pregnancies occurring between vaccination (Day 0) and 31 days from 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.
12 To be completed for all subjects who are enrolled in the study.
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.
Table 5 presents the intervals between study visits.
Table 5
Intervals between study visits
Interval
Optimal length of interval1
Allowed interval2
Primary vaccinationVisit 1
520 weeks
520 26 weeks
Visit 1Visit 2 
30 days
21-48 days 3
1Whenever possible the investigator should arrange study visits within this interval.
2Subjects will not be eligible for inclusion in the ATP cohort for immunogenicity if they make the study visit outside this 
interval (see Section 10.4 for the definition of the study cohorts).
3 For the safety evaluation an interval of 30 days is needed. If the subject returns for Visit 2 prior to Day 30, the subject 
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 must be obtained before study participation. 
Refer to Section 5.1 for the requirements on how to obtain informed consent. If the 
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subject agrees to have up to 50 mL of blood drawn at Visit 2, he or she must sign the ICD 
addendum before the sample is taken.
Signing of ICF will be recorded 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. 
5.6.3.
Collect demographic data
Record demographic data such as partial date of birth (month and year) and gender in the 
subject’s eCRF.
5.6.4.
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.
5.6.5.
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  study vaccination in the eCRF.
5.6.6.
Recording of meningococcal and TT vaccination history
Record the history of meningococcal vaccination and the last TT vaccination date in the 
eCRF.
5.6.7.
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.
5.6.8.
Assess pre-vaccination body temperature
The axillary, rectal, oral or tympanic body temperature of all subjects needs to be 
measured prior to any study vaccine administration. The preferred route for recording 
temperature in this study will be 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 
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the day of vaccination, the vaccination visit will be rescheduled within the allowed 
interval for this visit (see Table 5).
5.6.9.
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.
5.6.10.
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 the 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.
5.6.11.
Container number allocation
Container number allocation will be performed as described in Section 5.2.1.1.1. The 
number of each administered container 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 safety or immune response assessments
Blood samples will be taken during the two study visits as specified in Section 5.5 List of 
Study Procedures.

A volume of approximately 10 mL of whole blood (to provide approximately 5 mL 
of serum) should be drawn by venipuncture from all subjects at each visit.
Alternatively, subjects who signed the ICD addendum will have up to 50 mL of 
whole blood drawn at Visit 2. 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.
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5.6.13.
Study Vaccine administration

Study vaccine will be administered at Visit 1. After completing all prerequisite 
procedures prior to vaccination, one dose of study vaccine will be administered IM 
preferably in the deltoid of the non-dominant arm (refer to Section 6.3 for a 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.

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 and how to report SAEs and 
Exposure During Pregnancy (EDP) reports to Pfizer.

The subjects will be instructed to contact the investigator immediately should they
manifest any signs or symptoms they perceive as serious. 

After the vaccination visit, diary cards will be provided to the subject. The subject 
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 one month [the next 30 days]) after vaccination. The 
subject will be instructed to return the completed diary card to the investigator at the 
next study visit.

Collect and verify completed diary cards during discussion with the subject at Visit 2 
(scheduled one month [30 days] after the vaccine dose). If the subject returns for 
Visit 2 prior to one month [Day 30], the subject should take home the diary card, 
continue to record unsolicited safety information until one month [Day 30] and then 
provide the card to the study site.

Any unreturned diary cards will be sought from the subject through telephone call(s) 
or any other convenient procedure. The investigator will transcribe the collected 
information into the eCRF in English.
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5.6.15.1.
Recording of GBS and New Onset of Chronic Illnesses (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.

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. auto-immune 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
Refer to the SPM for details on biospecimen management (handling, storage and 
shipment). See section 5.6.12.1 for a brief description of the procedure for collection, 
preparation, and storage of serum samples.
Samples will not be labelled with information that directly identifies the subject but will 
be coded with the identification number for the subject (subject number). 

Collected samples will be used for protocol mandated research and purposes related 
to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. This may include the management of the quality of these 
tests, the maintenance or improvement of these tests, the development of new test 
methods, as well as making sure that new tests are comparable to previous methods 
and work reliably.

It is also possible that future findings may make it desirable to use the samples 
acquired in this study for future research, not described in this protocol. Therefore, 
all subjects in countries where this is allowed, will be asked to give a specific 
consent to allow Pfizer or a contracted partner to use the samples for future research. 
Future research will be subject to the laws and regulations in the respective countries 
and will only be performed once an IEC or Review Board has approved this 
research.
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.
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). 
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If additional testing is performed, the marker priority ranking given in Section 5.7.4 may 
be changed.
Collected samples will be stored for a maximum of 15 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with Pfizer.
5.7.1.
Use of specified study materials
When materials are provided by Pfizer or designee, it is MANDATORY that all clinical 
samples (including serum samples) be collected and stored exclusively using those 
materials in the appropriate manner. The use of other materials could result in the 
exclusion of the subject from the ATP analysis (See Section 11.5 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
The sample type, quantity and time point for blood draws for the ACWY-TT and MenPS 
groups is shown in Table 6.
Table 6
Biological samples for the ACWY-TT and MenPS groups
Sample type
Quantity
Unit
Time points
Blood
Approximately 10
mL
Visit 1 (pre-booster), Visit 2 (post-
booster)
Blood
Up to 50 (voluntary subjects)
mL
Visit 2 (post-booster)*
*In order to support assay development, subjects who signed the ICD addendum will have up to 50 mL, rather than 10 
mL, of blood drawn at Visit 2.
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) 
using standardised and validated procedures (refer to Table 7).
See Table 7 for details of the laboratory assays.
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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
rSBA 
NA
1/DIL
8
PHE*
Neisseria meningitidis Serogroup 
C L3v C11 Ab
rSBA 
NA
1/DIL
8
PHE*
Neisseria meningitidis Serogroup 
W L3v MP01240070 Ab
rSBA
NA
1/DIL
8
PHE*
Neisseria meningitidis Serogroup 
Y L3v S1975 Ab
rSBA
NA
1/DIL
8
PHE*
Clostridium tetani.Tetanus Toxoid 
Ab.IgG
dLIA**
NA
IU/mL
0.1
***PPD
rSBA = Serum Bactericidal Assay (using baby rabbit complement)
1/DIL = Dilution for at least 50% killing
*PHE = Public Health England (previously the Health Protection Agency [HPA])
**dLIA – Direct Luminex Immunoassay
***PPD – Pharamceutical Product Development, Inc. Bioanalytical Laboratories
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 (Month120)
Pre-booster 
vaccination 
200
rSBA-MenA, rSBA-MenW-135, 
rSBA-MenY, rSBA-MenC, anti-TT
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-MenY 
> anti-TT
Visit 2 (Month121)
One month-
post booster 
vaccination 
180
rSBA-MenA, rSBA-MenW-135, 
rSBA-MenY, rSBA-MenC, anti-TT
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-MenY 
> anti-TT
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. 
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 use of 1:8 
and 1:128 as rSBA endpoints when using rabbit complement for rSBA-MenC has been 
discussed at a recent World Health Organisation (WHO) conference [WHO, 2011].
Effectiveness data in the United Kingdom have further validated rSBA-MenC 1:8 as 
protective [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 [WHO, 2011]. For meningococcal (unconjugated) 
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PSs, a 4-fold increase in SBA titres from pre-vaccination to post-vaccination is 
commonly accepted as a marker of immunogenicity [Anonymous, 1999; WHO, 1981].
Antibodies against tetanus toxoid (Anti-TT):
Tetanus toxoid antibody concentrations greater than or equal to 0.1 IU/mL are considered 
as protective [McComb, 1964; Newell, 1971]. The direct Luminex immunoassay (dLIA)
lower limit of quantitation (LLOQ) for tetanus toxoid based on Pfizer’s validation is 
0.05 IU/mL at 1:1000 dilution. Based on this value, a dLIA result of <0.1 IU/mL is 
considered a negative clinical response and a dLIA result ≥0.1 IU/mL is considered a 
positive clinical response.
Communication of individual immunological assay results to study investigator
Where 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 one month after vaccination) could be defined using 
the following threshold.

rSBA-MenC antibody titer < 1:8

tetanus toxoid antibody titers < 0.1 IU/mL
Although no correlate of protection is established for N. meningitidis serogroups A, 
W-135 and Y, individual immunology assay results for these 3 antigens will also be 
provided to the study investigator.
The immunological assay results will be communicated to the investigators.
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 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.
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Table 9
Study vaccine
Treatment name
Vaccine/
product name
Formulation
Presentation
Volume to be 
administered 
Number of 
doses
MenACWY-TT 
MenACWY-TT *
PSA=5µg TT; 
PSC=5µg TT; 
PSW₁₃₅=5µg TT; 
PsY=5µg TT; 
TT~=44µg 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 study vaccine
The study vaccine will be shipped at +2°C to +8°C to each study site upon request. Upon 
receipt at the study site, the vaccine should be immediately transferred to a +2°C to +8°C 
temperature-monitored refrigerator for storage. Storage conditions stated in the SRSD (ie, 
CDS) may be superseded by the storage conditions stated in the labeling.
The study vaccine must be stored 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.  
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.
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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
Route1
Site 
Side2
Visit 1 (Month120)
0.5 mL
ACWY-TT 
MenACWY-TT 
IM 
Deltoid 
Left or Right
0.5 mL
MenPS 
MenACWY-TT 
IM 
Deltoid 
Left or Right
1Intramuscular (IM)
2Preferably the non-dominant side
Reconstitution of the MenACWY-TT 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. The vaccine reconstitution 
will be described in detail in the Core Data Sheet.
Injection technique
A needle of at least 25 mm (1 inch), 22-25 gauge should be used for injection in the 
deltoid muscle.
The following injection technique is recommended:

Use of aseptic technique with reconstitution and delivery of injection

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° 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
MenACWY-TT should under no circumstances be administered intravascularly, 
intradermally or subcutaneously.
MenACWY-TT should be given with caution to individuals with thrombocytopenia or 
any coagulation disorder since bleeding may occur following an IM administration to 
these subjects.
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.
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6.5.
Concomitant medication/product and concomitant 
vaccination
At each study visit/contact, the investigator should question the subject about any 
medications/products taken and vaccinations 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:

Any concomitant medications/products/vaccines listed in Section 6.5.2.

All concomitant medications/products, except vitamins and dietary supplements, 
administered 30 days following the booster dose of study vaccine.

Any concomitant vaccination administered in the period starting 30 days before the 
booster dose of study vaccine and ending at the last study visit.

Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination) from just prior to 
vaccination up to Visit 2.
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 relevant to a SAE* or administered 
at any time during the study period for the treatment of a SAE*. In addition, 
concomitant medications relevant to SAEs need to be recorded on the Serious 
Adverse Event Report Form.
* SAEs that are required to be reported per protocol.
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. See Section 10.4 for cohorts to be analysed.

Any investigational or non-registered product (drug or vaccine) other than the study 
vaccine used during the study period.

Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. more than 14 days in total) during the study period. For corticosteroids, this will 
mean prednisone 0.5 mg/kg/day with an upper limit of 10 mg/day or equivalent. 
Inhaled, topical, and intra-articular steroids are allowed.
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
A vaccine not foreseen by the study protocol administered during the period starting 
30 days before the booster dose of vaccine and ending 30 days after*, with the 
exception of inactivated influenza vaccine which can be administered at any time 
during the study according to the local recommendations.
*In case an emergency mass vaccination for an unforeseen public health threat (e.g.: 
a pandemic) is organised by the public health authorities, outside the routine 
immunisation program, the time period described above can be reduced if necessary 
for that vaccine provided it is licensed and used according to its summary of product 
characteristics or product information and according to the local governmental 
recommendations.

Administration of a meningococcal vaccine not foreseen by the study protocol at any 
time during the study period.

Immunoglobulins and/or any blood products administered within the 3 months 
preceding the study vaccination or planned administration during the study (i.e. 
between Visit 1 and Visit 2).
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 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 
based on medical history and physical examination (no laboratory testing required)
* Occurrence of meningococcal disease should be reported as an SAE.
7.
HEALTH ECONOMICS
Not applicable
8.
SAFETY
The investigator or site staff is/are responsible for the detection, documentation and 
reporting of events meeting the criteria and definition of an AE or SAE as provided in 
this protocol. 
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Each subject will be instructed to contact the investigator immediately should they 
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 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 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).

Medication errors.

Occupational exposure.
AEs to be recorded as endpoints (solicited AEs) are described in Section 10.2. 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).
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
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;

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 
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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 (EDP) 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).
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: 
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
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 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
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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 listed in Table 11 will be solicited:
Table 11
Solicited local adverse events
Pain at injection site
Redness at injection site
Swelling at injection site
If the subjects observe any large injection site reaction, they should contact the study 
personnel and 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

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 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 listed in Table 12 will be solicited:
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Table 12
Solicited general adverse events
Fatigue
Fever*
Gastrointestinal symptoms †
Headache
*Fever is defined as temperature 37.5°C for oral, axillary or tympanic route, or 38.0°C for 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.
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 a SAE).

Meningococcal disease (to be reported as an SAE).
See Section 8.2.3.5 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.
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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
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
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Disease/Disorder
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
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
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Disease/Disorder
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
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.
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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 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.
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 one month (i.e. 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 the receipt of study 
vaccine and will end one month (i.e. study end) following administration of the dose of 
study vaccine for each subject. See Section 8.3 for instructions on reporting of SAEs.
SAEs that are related to the investigational vaccine and any event related to lack of 
vaccine efficacy will be collected and recorded from the subject’s last visit in the 
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persistence study MENACWY-TT-043 EXT:036 Y2, 3, 4, 5 (112148) 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 
the time of the receipt of study vaccine.
The time period for collecting and recording pregnancies will begin from administration 
of the study vaccine and will end one month (i.e. study end) 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 one month (i.e. study 
end) post 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 
one month (i.e. study end) post 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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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 
promptly report the SAEs to Pfizer.
8.2.3.
Evaluation of adverse events and serious adverse events
8.2.3.1.
Active questioning to detect adverse events and serious adverse events
As a consistent method of collecting AEs, the subject 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?’
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
subject’s medical records to Pfizer instead of appropriately completing the SAE form and 
CRF. However, there may be instances when copies of medical records for certain cases 
are requested by Pfizer. In this instance, all subject identifiers will be blinded on the 
copies of the medical records prior to submission to Pfizer.
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms.
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8.2.3.2.
Assessment of adverse events
8.2.3.2.1.
Assessment of intensity
The intensity of the following solicited AEs will be assessed as described:
Table 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 greatest 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
(nausea, vomiting, diarrhoea 
and/or abdominal pain)
0
Gastrointestinal symptoms normal
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
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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.
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 each unsolicited AE (including SAEs) and for 
general solicited AEs. The investigator will use clinical judgement to determine the 
relationship. Alternative plausible causes, such as natural history of the underlying 
diseases, concomitant therapy, other risk factors, and the temporal relationship of the 
event to the investigational vaccine/product will be considered and investigated. The 
investigator will also consult the CDS 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.
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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 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 will be 
asked if he/she received medical attention defined as hospitalisation, or an otherwise 
unscheduled visit to or from medical personnel for any reason, including emergency 
room visits. This information will be recorded in the eCRF. 
8.2.3.5.
Adverse events of specific interest
AEs of specific interest for safety monitoring include:

NOCIs such as autoimmune diseases, asthma, type I diabetes and allergies. Refer to 
Section 8.1.8.1 for a non-exhaustive list of illnesses that can be recorded as NOCI.

GBS.

Meningococcal disease.
Occurrences of NOCIs will be reported up to one month after the vaccine dose regardless 
of seriousness and whether or not they are considered to be possibly related to the 
treatment 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 reported up to one month after the vaccine dose. 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 an SAE.
Occurrences of meningococcal disease will be reported during the entire course of the 
study up the study end and have to be reported as an SAE.
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. 
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Table 16
Timeframes for submitting serious adverse event, exposure during 
pregnancy and other events reports
Type of Event
Initial Reports
Follow-up of Relevant Information on a Previous 
Report
Timeframe
Documents
Timeframe
Documents
All serious 
adverse events 
(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
Guillain Barré 
Syndrome
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 designee) must complete the information in the paper SAE report
WITHIN 24 HOURS. The SAE report will always be completed as thoroughly as 
possible with all available details of the event. Even if the investigator does not have all 
information regarding a SAE, the report should still be completed within 24 hours. Once 
additional relevant information is received, the report should be updated WITHIN 24 
HOURS.
The investigator will always provide an assessment of causality at the time of the initial 
report.
8.3.3.
Completion and transmission of pregnancy reports 
Once the investigator becomes aware that a subject is pregnant, the investigator (or 
designee) must complete the required information onto the EDP report WITHIN 24 hours 
of awareness of the exposure.
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 should be estimated by ultrasound examination and recorded in the pregnancy 
report.
8.3.4.
Updating of SAE and pregnancy information after removal of 
write access to the subject’s eCRF
When additional SAE or pregnancy information is received after removal of the write 
access to 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. 
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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 Pfizer is essential so that legal obligations and ethical responsibilities 
towards the safety of other subjects are met.
Investigator safety reports are prepared according to the current Pfizer policy and are 
forwarded to investigators as necessary. An investigator safety report is prepared for a 
SAE(s) that is both attributable to the investigational vaccine/product and unexpected. 
The purpose of the report is to fulfil specific regulatory and GCP requirements, regarding 
the product under investigation.
8.4.
Follow-up of adverse events, 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).
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 study 
end.
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 study end.
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 of specific interest (i.e. NOCIs, GBS, meningococcal disease) until 
one month after the vaccine dose or until the subject is lost to follow-up. 
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If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to Pfizer using a paper 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.
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.
Subjects must be instructed to keep subject cards in their possession at all times.
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9.
SUBJECT COMPLETION AND WITHDRAWAL
9.1.
Subject completion
A subject who returns for the concluding visit foreseen in the protocol is considered to 
have completed the study.
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.
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 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 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).
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*In case a subject is withdrawn from the study because he/she 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).
9.2.2.
Subject withdrawal from study vaccine
A ‘withdrawal’ from the study 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 study 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 study 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 one month 
after booster vaccination with MenACWY-TT vaccine (primary readouts):

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA MenY booster response*.
*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.
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10.2.
Secondary endpoints
Immunogenicity with respect to the components of the investigational vaccine prior to 
and one month after booster vaccination with MenACWY-TT vaccine (secondary 
readouts):

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres ≥1:8, ≥1:128 
and GMTs.

Anti-TT concentrations ≥0.1 IU/mL, ≥1.0 IU/mL and GMCs.
Safety and reactogenicity

Occurrence of solicited local and general symptoms within 4 days (Day 0 to Day 3) 
after MenACWY-TT booster vaccination.

Occurrence of unsolicited AEs, within 31 days (Day 0 to Day 30) after MenACWY-
TT booster vaccination.

Occurrence of all SAEs, GBS and NOCIs [e.g. asthma, autoimmune disorders, type I 
diabetes, allergies] within 31 days (Day 0 to Day 30) after MenACWY-TT booster 
vaccination.

Occurrence of SAEs related to primary vaccination and any event related to lack of 
vaccine efficacy (i.e. meningococcal disease) from the subject’s last visit in the 
primary study MenACWY-TT-036 (109069) or in the persistence study MenACWY-
TT-043EXT:036 Y2, 3, 4, 5 (112148) until entry in study C0921005 (MenACWY-
TT-101EXT:036 Y10) (116724). 
10.3.
Determination of sample size
The sample size of this study with respect to the analysis of safety and immunogenicity 
post-booster is driven by the sample size of the primary vaccination study MenACWY-
TT-036 (109069), the enrolment rate in the persistence extension study of MenACWY-
TT-036 [MenACWY-TT-043EXT036 Y2, 3, 4 and 5 (112148)] and the estimated 
number of potential participating subjects based on the feedback from the site 
participating in this extension study. Subjects from the Philippines who received either 
MenACWY-TT or Mencevax ACWY vaccine will be eligible for this study if they meet 
the inclusion/exclusion criteria. 
Subjects from the Philippines that were vaccinated in the MenACWY-TT-036 at the 
participating site will be invited to participate to this study with approximately 200
subjects expected to participate.
For the analysis at Month 121, one month after the booster vaccination, it is estimated 
that approximately 10% of the subjects will not be evaluable. Around 180 subjects will 
be included in the Booster ATP cohort of immunogenicity (135 in the ACWY-TT group 
and 45 in the MenPS group).
The primary objective of this study is to evaluate the immunogenicity of the booster dose 
in terms of the percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 
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and rSBA-MenY booster response.
Table 17 illustrates the precision one can expect for percentage of subjects with rSBA-
MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY booster response from a group 
of 180 subjects.
Table 17
Exact 95% confidence intervals of the percentage of subjects with 
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY booster 
response
Approx. 
%
ACWY-TT group Exact 2-sided 95% CI (N =135)
MenPS group Exact 2-sided 95% CI (N =45)
Lower Limit (LL)
Upper Limit (LL)
Lower Limit (UL)
Upper Limit (UL)
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
100.0
92.1
100.0
10.4.
Study cohorts/ data sets to be analysed
A total of 5 cohorts are defined for the purpose of analysis.
10.4.1.
Booster Total Vaccinated cohort
The Booster Total Vaccinated cohort for safety will include all vaccinated subjects in the 
study MenACWY-TT-036 (109069) with a MenACWY-TT 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.
Booster According-to-protocol cohort for safety
The Booster ATP cohort for safety 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 Mencevax ACWY in 
the primary study MenACWY-TT-036 (109069).

who have received a MenACWY-TT booster dose.

for whom the administration site of the booster vaccine is known.

who have not received a vaccine not specified or forbidden in the protocol (subjects 
who received a vaccine not foreseen by the study protocol 30 days after the study 
vaccine dose will be eliminated from the Booster ATP cohort for safety if the 
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vaccine not foreseen by the protocol was administered before the post-vaccination 
blood sample).

who were not excluded from the ATP cohort for persistence at Month 120, 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 Month 120
(pre-booster vaccination).
10.4.3.
Booster According-to-protocol cohort for immunogenicity 
The Booster ATP cohort for immunogenicity 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 study 
vaccine antigen component for the blood sample taken one month post-vaccination, and 
who were not administered a vaccine not foreseen by the study protocol before the post-
vaccination blood sample.
The interval between Visit 1 and Visit 2 for inclusion in the Booster ATP cohort for 
immunogenicity will be defined as 21 to 48 days.
10.4.4.
Total cohort at Month 120
The Total cohort at Month 120 will include all vaccinated subjects in the vaccination 
stage of study MenACWY-TT-036 (109069) who return for the Month 120 follow-up.
For the analysis of persistence, this will include all vaccinated subjects for whom data 
concerning persistence endpoint measures are available.
10.4.5.
According-to-protocol cohort for persistence at Month 120
The ATP cohort for antibody persistence at Month 120 will include all evaluable 
subjects: 

who were eligible in study MenACWY-TT-036 (109069).

who have received the primary vaccination with MenACWY-TT or Mencevax 
ACWY during study MenACWY-TT-036 (109069).

who have available assay results for at least one tested antigen at Month 120.

who have not received a meningococcal vaccine not planned in protocol 
MenACWY-TT-036 (109069) before Month 120.

who do not have a history of meningococcal serogroup A, C, W-135, or Y disease 
prior to Month 120.

who comply with the blood sampling intervals defined in Section 5.5 of the protocol.

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 during the timeframe specified in the protocol.
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
who were not excluded from the ATP cohort for immunogenicity in the primary 
study MenACWY-TT-036 (109069), 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 a 
previous time point.
10.5.
Derived and transformed data
10.5.1.
Immunogenicity

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 GMTs/GMCs calculations are performed by taking the anti-log of the mean of 
the log titre/concentration transformations. Antibody titres/concentrations 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/GMC 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 post-vaccination titer 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.

Handling of missing data: for a given subject and a given immunogenicity 
measurement, missing or non-evaluable measurements will not be replaced. 
10.6.
Statistical analyses
10.6.1.
Analysis of demographics/baseline characteristics
Demographic characteristics of each study cohort will be tabulated: age at booster 
vaccination (in years), gender and geographic ancestry.
The reason for not attending the post-booster visit among all subjects who received the 
booster vaccination will be summarized.
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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. 
11.1.
electronic Case Report Form instructions
A validated Pfizer defined electronic data collection tool will be used as the method for 
data collection.
In all cases, subject initials will not be collected nor transmitted to Pfizer. Subject data 
necessary for analysis and reporting will be entered/transmitted into a validated database 
or data system. Clinical data management will be performed in accordance with 
applicable Pfizer standards and data cleaning procedures.
While completed eCRFs are reviewed by a Pfizer or designee Site Monitor at the study 
site, omissions or inconsistencies detected by subsequent eCRF review may necessitate 
clarification or correction of omissions or inconsistencies with documentation and 
approval by the investigator or appropriately qualified designee. In all cases, the 
investigator remains accountable for the study data. 
The investigator will be provided with 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 eCRF review and a Source Data
Verification (SDV). By SDV we understand verifying eCRF entries by comparing them 
with the source data that will be made available by the investigator for this purpose.
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The Source Documentation Agreement Form describes the source data for the different 
data in the eCRF. 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 eCRF will serve as the source must be identified, agreed and 
documented in the source documentation agreement form. 
For eCRF, 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
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a Pfizer site or other mutually-
agreeable location.
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Pfizer will also provide the investigator with the full summary of the study results. The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
Pfizer supports the exercise of academic freedom and has no objection to publication by 
principal investigator of the results of the study based on information collected or 
generated by principal investigator, whether or not the results are favorable to the Pfizer 
product.  However, to ensure against inadvertent disclosure of confidential information or 
unprotected inventions, the investigator will provide Pfizer an opportunity to review any 
proposed publication or other type of disclosure of the results of the study (collectively, 
“Publication”) before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before they are 
submitted for publication or otherwise disclosed.  If any patent action is required to 
protect intellectual property rights, the investigator agrees to delay the disclosure for a 
period not to exceed an additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication 
is to be a joint publication covering all study sites, and that any subsequent publications 
by the principal investigator will reference that primary publication.  However, if a joint 
manuscript has not been submitted for publication within 12 months of completion or 
termination of the study at all participating sites, the investigator is free to publish 
separately, subject to the other requirements of this section.
For all publications relating to the study, the institution will comply with recognized 
ethical standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements 
for Manuscripts Submitted to Biomedical Journals, 
http://www.icmje.org/index.html#authorship, established by the International Committee 
of Medical Journal Editors.
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.
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11.7. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
vaccine, Pfizer should be informed immediately.  
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes 
aware of.
12.
COUNTRY SPECIFIC REQUIREMENTS
Not applicable.
13.
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Borrow R., Abad R., Trotter C. et al, Effectiveness of meningococcal serogroup C
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Keyserling H, Papa T, Koranyi K, Ryall R, Bassily E, et al. Safety, immunogenicity, and 
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Knuf M, Kieninger-Baum D, Habermehl P, et al. A dose-range study assessing 
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second year of life and in young children. Vaccine. 2010;28(3):744-53.
Knuf M, Pantazi-Chatzikonstantinou A, Pfletschinger U, et al. An investigational 
tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate 
vaccine co-administered with Infanrix™ hexa is immunogenic, with an acceptable safety 
profile in 12-23-month-old children. Vaccine. 2011;29(25):4264-73.
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Memish Z, Dbaibo G, Montellano M, et al. Immunogenicity of a single dose of 
tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine 
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Mimouni D, Gdalevich M, Mandel Y et al. Meningococcal polysaccharide vaccination of 
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APPENDIX A
LABORATORY ASSAYS
The following tests will be performed using the aliquots of serum:
Functional anti-meningococcal serogroup bactericidal activity (ie, rSBA-MenA, rSBA-
MenC, rSBA-MenW-135, rSBA-MenY) will be determined by a serum bactericidal assay 
using rabbit complement (rSBA) at Public Health England (PHE) according to the 
Centers for Disease Control and Prevention (CDC) protocol [Maslanka, 1997] .  rSBA 
titres will be expressed as the reciprocal of the highest serum dilution resulting in at least 
50% reduction of meningococcal colony-forming units.

Specific antibody against tetanus toxoid will be measured by dLIA. The cut-off of 
the assay is 0.1 IU/mL [McComb, 1964; Newell, 1971].
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APPENDIX B
CLINICAL LABORATORIES
Table 18
Outsourced laboratories
Laboratory
Address
Public Health England (PHE)
Vaccine Evaluation Unit
Public Health England North West
Manchester Medical Microbiology Partnership
2nd Floor, Clinical Sciences Building II
Manchester Royal Infirmary
Oxford Road, Manchester
England, M13 9WZ
Pharmaceutical Product 
Development (PPD), Inc. 
Bioanalytical Laboratories
Bioanalytical Laboratories
2244 Dabney Road
Richmond, VA 23230 USA
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