A PHASE III, OPEN, MULTI-CENTRE, CONTROLLED STUDY TO EVALUATE THE LONG-TERM ANTIBODY PERSISTENCE AT 2, 3, 4, 5 AND 6 YEARS AFTER A BOOSTER DOSE OF MENINGOCOCCAL SEROGROUP A, C, W-135, Y- TETANUS TOXOID CONJUGATE VACCINE (MENACWY-TT) OR MENINGITEC (REGISTERED) ADMINISTERED IN HEALTHY 5-YEAR-OLD CHILDREN IN STUDY MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036), WHO WERE PRIMED WITH THE SAME VACCINE IN STUDY MENACWY-TT-039 (109670) AT 12 THROUGH 23 MONTHS OF AGE.
Phase: PHASE3
Conditions: Infections, Meningococcal
Sponsor: Pfizer

C0921001 (MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6, 200088)
Protocol Amendment 1 including non-substantial changes upon sponsorship change
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1
Clinical Study Protocol
Sponsor:
Pfizer, Inc.
235 East 42nd Street
New York, NY 10017, United States
Primary Study vaccine and 
number

Meningococcal serogroups A, C, W-135, Y tetanus 
toxoid conjugate (MenACWY-TT) vaccine 
(PF-06866681)
Other Study vaccine

Meningococcal serogroup C conjugate vaccine 
(Meningitec®)
Study number and 
Abbreviated Title
C0921001 (MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6)
EudraCT number
2012-005816-25
Date of protocol
Final Protocol Amendment 1: 4 January 2016
Title
Persistence of antibodies after meningococcal vaccine PF-
06866681 in healthy children.
Detailed Title
A phase III, open, multi-centre, controlled study to 
evaluate the long-term antibody persistence at 2, 3, 4, 5 
and 6 years after a booster dose of meningococcal
serogroup A, C, W-135, Y- tetanus toxoid conjugate 
vaccine (MenACWY-TT) or Meningitec® administered in 
healthy 5-year-old children in study MENACWY-TT-048 
EXT: 039 Y2, 3, 4, 5 (112036), who were primed with the 
same vaccine in study MENACWY-TT-039 (109670) at 
12 through 23 months of age.
 
 
  

C0921001 (MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6, 200088)
Protocol Amendment 1 including non-substantial changes upon sponsorship change
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Protocol Sponsor Signatory Approval
Study number and 
Abbreviated Title
C0921001 (MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 
6; formerly GSK 200088)
EudraCT number
2012-005816-25
Date of protocol
Protocol Amendment 1: 4 January 2016
Detailed Title 
A phase III, open, multi-centre, controlled study to 
evaluate the long-term antibody persistence at 2, 3, 4, 5 
and 6 years after a booster dose of meningococcal 
serogroup A, C, W-135, Y- tetanus toxoid conjugate 
vaccine (MenACWY-TT) or Meningitec® administered 
in healthy 5-year-old children in study MENACWY-
TT-048 EXT: 039 Y2, 3, 4, 5 (112036), who were 
primed with the same vaccine in study MENACWY-
TT-039 (109670) at 12 through 23 months of age.
Sponsor signatory
, MD
Senior Director Pfizer Vaccines Clinical Research
Signature
Date
PPD

C0921001 (MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6, 200088)
Protocol Amendment 1 including non-substantial changes upon sponsorship change
4-JAN-2016
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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 1
4-January-2016
Protocol amended to reflect sponsorship 
change to Pfizer following the acquisition of 
the GSK meningococcal vaccine Nimenrix by 
Pfizer on 01 October 2015.
Sponsor name updated throughout the protocol 
to Pfizer.
Vaccine trademarks revised to correct 
company names and ® symbols.
Blood sample volume increased to 10 mL for 
visits 4 and 5.
Symbol (≈) added to header of Table 10. 
Sections updated / added  in line with standard 
Pfizer policy: 
- 1.1 Background
- 5.1 Regulatory and ethical considerations, 
including the informed consent process
- 5.3 Method of blinding
- 5.6.2.6 Recording of SAEs
- 5.7 Biological sample handling and analysis
- 8.1.1 Definition of a serious adverse event
- 8.3.1 Time period for detecting and recording 
serious adverse events
- 8.3.2 Post-study adverse events and serious 
adverse events
- 8.3.3.1 Active questioning to detect serious 
adverse events
- 8.4 Reporting of serious adverse events
- 8.6 Subject card
- 9.2.1 Subject withdrawal from the study
- 10.4.2 According-to-protocol (ATP) cohort 
for analysis of persistence at Month X
- 10.7 Interpretation of analyses
-11.5 Posting of information on publicly 
available clinical trial registers and publication 
policy
-11.6 Provision of study results to investigators
-11.7 Reporting of safety issues and serious 
breaches of the protocol or ICH GCP
- Appendix A Laboratory assays
- Appendix B Clinical laboratories
Original protocol
26-March-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.  

C0921001 (MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6, 200088)
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Protocol Investigator Agreement
I agree:

To conduct the study in compliance with this protocol, any future protocol amendments 
or protocol administrative changes, with the terms of the clinical trial agreement and 
with any other study conduct procedures and/or study conduct documents provided by 
Pfizer.

To assume responsibility for the proper conduct of the study at this site.

That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements. 

To ensure that all persons assisting me with the study are adequately informed about the 
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.

C0921001 (MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6, 200088)
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Study number and 
Abbreviated Title
C0921001 (MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 
6; formerly GSK 200088)
EudraCT number
2012-005816-25
Date of protocol
Final Protocol Amendment 1: 4 January 2016
Detailed Title
A phase III, open, multi-centre, controlled study to 
evaluate the long-term antibody persistence at 2, 3, 4, 5 
and 6 years after a booster dose of meningococcal 
serogroup A, C, W-135, Y- tetanus toxoid conjugate 
vaccine (MenACWY-TT) or Meningitec® administered 
in healthy 5-year-old children in study MENACWY-
TT-048 EXT: 039 Y2, 3, 4, 5 (112036), who were 
primed with the same vaccine in study MENACWY-
TT-039 (109670) at 12 through 23 months of age.
Investigator name
Signature
Date

C0921001 (MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6, 200088)
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4-JAN-2016
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SYNOPSIS
Detailed Title
A phase III, open, multi-centre, controlled study to evaluate 
the long-term antibody persistence at 2, 3, 4, 5 and 6 years 
after a booster dose of meningococcal serogroup A, C, 
W-135, Y- tetanus toxoid conjugate vaccine (MenACWY-TT) 
or Meningitec® administered in healthy 5-year-old children in 
study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036), 
who were primed with the same vaccine in study 
MENACWY-TT-039 (109670) at 12 through 23 months of 
age.
Indication
Nimenrix is indicated for active immunisation of individuals 
from the age of 12 months and above against invasive 
meningococcal diseases caused by Neisseria meningitidis
serogroup A, C, W-135 and Y.
Rationale for the 
study and study 
design
There is growing interest in the assessment of long term 
persistence of serological markers of protection following 
meningococcal conjugate vaccination. In study MENACWY-
TT-048 EXT: 039 Y2, 3, 4, 5 (112036), the persistence of the 
immune response of MenACWY-TT vaccine versus 
Meningitec was evaluated up to 4 years after vaccination as 
well as the immune response to a booster dose given 4 years 
after primary vaccination of children aged 12 through 23 
months. In this extended follow-up study C0921001 (formerly 
GSK MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6 
[200088]), the persistence of the immune response as well as
safety of MenACWY-TT vaccine versus Meningitec will be 
evaluated up to 6 years after booster vaccination in children 
who participated in study MENACWY-TT-048 EXT: 039 Y2, 
3, 4, 5 (112036).
Objectives
Primary
Immunogenicity 
Persistence
At 2, 3, 4, 5, 6 years after booster vaccination of children with 
MenACWY-TT or Meningitec

To evaluate the persistence of meningococcal antibodies 
in terms of the percentage of subjects with rSBA antibody 
titres ≥1:8 for each of the four serogroups.

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Secondary
Immunogenicity
Persistence
At 2, 3, 4, 5, 6 years after booster vaccination of children with 
MenACWY-TT or Meningitec

To evaluate the persistence of meningococcal A, C, 
W-135 and Y antibodies in terms of the percentage of 
subjects with rSBA titres ≥1:128 and GMTs and hSBA 
titres ≥1:4 and ≥1:8 and GMTs for each of the four 
serogroups.
Safety

To describe serious adverse events (SAEs) related to 
vaccination and any event related to lack of vaccine 
efficacy (i.e. meningococcal disease) from the subject’s 
last visit in study MENACWY-TT-048 EXT: 039 Y2, 3, 
4, 5 (112036) up to each yearly visit in the current study
in a retrospective manner.
Study design

Experimental design: Phase III, open-label, controlled, 
multi-centric, single-country study with two parallel 
groups.

Duration of the study: Approximately four years per 
subject.

Epoch 001: Persistence Visit 1 (Year 2 [Month 24] 
post-booster vaccination)

Epoch 002: Persistence Visit 2 (Year 3 [Month 36] 
post-booster vaccination)

Epoch 003: Persistence Visit 3 (Year 4 [Month 48] 
post-booster vaccination)

Epoch 004: Persistence Visit 4 (Year 5 [Month 60] 
post-booster vaccination)

Epoch 005: Persistence Visit 5 (Year 6 [Month 72] 
post-booster vaccination).

Study groups:

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Synopsis Table 1
Study groups and epochs foreseen in the study
Study 
groups
Number of 
subjects *
Age at booster 
vaccination in 
years (Min/Max)
Epochs
Epoch 
001
Epoch 
002 
Epoch 
003 
Epoch 
004 
Epoch 
005 
ACWY-TT
185
5 years – 6 years
x
x
x
x
x
MenCCRM 
38
5 years – 6 years
x
x
x
x
x
* The sample size of this study is driven by the number of subjects who received the booster vaccination at Month 48 in 
study MENACWY-TT-048 EXT:039 Y2, 3, 4, 5 (112036) at the participating sites and by assumptions about the annual 
dropout rate.

Control: active control (MenCCRM group).

Vaccination schedule: No vaccine will be administered 
during this long-term persistence study.

Study group allocation: The subjects in this study will be 
allocated to the same groups and will retain the same 
subject number as in study MENACWY-TT-048 EXT: 
039 Y2, 3, 4, 5 (112036):

ACWY-TT group (N 185): Subjects primed and 
boosted with the MenACWY-TT vaccine

MenCCRM group (N 38): Subjects primed and 
boosted with the Meningitec vaccine

Blinding: Study will be conducted in an open manner.
Synopsis Table 2
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
open
Epoch 002 
open
Epoch 003 
open
Epoch 004 
open
Epoch 005 
open

Sampling schedule: Blood samples will be taken at each of 
the study visits, i.e. 2 (Visit 1), 3 (Visit 2), 4 (Visit 3), 5 
(Visit 4) and 6 (Visit 5) years after booster vaccination in 
study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036).

Type of study: self-contained and extension of study
MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036).

Data collection: Electronic Case Report Form (eCRF).

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Number of subjects
Parent(s)/ LAR(s) of subjects vaccinated with a booster dose of 
a meningococcal conjugate vaccine in study MENACWY-TT-
048 EXT: 039 Y2, 3, 4, 5 (112036) will be contacted to enrol 
their child/ward in the current study C0921001 (formerly GSK
MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6 [200088]) at 2, 3, 
4, 5 and 6 years after the booster vaccination unless the 
parent(s)/LAR(s) withdrew consent during the study 
MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036) and/or 
sites activities were closed.
The maximum number of subjects to return at Visit 1 (Month 
24) will be 248 subjects in total: 206 in the ACWY-TT group 
and 42 in the MenCCRM group.
If one assumes that approximately 10% of the potential subjects
will not participate to the persistence study at Visit 1 (Month 
24) (based on experience with studies in a similar age group), 
then one expects 223 subjects (185 in the ACWY-TT group and 
38 in the MenCCRM group) to participate at Visit 1 (Month 
24).
Endpoints
Primary

Persistence of antibodies with respect to components of the 
investigational vaccine, 2, 3, 4, 5, 6 years after booster 
vaccination:

rSBA-MenA titres 1:8.

rSBA-MenC titres 1:8.

rSBA-MenW-135 titres 1:8.

rSBA-MenY titres 1:8.
Secondary

Persistence of antibodies with respect to components of the 
investigational vaccine, 2, 3, 4, 5, 6 years after booster 
vaccination:

rSBA-MenA titres 1:128 and GMTs.

rSBA-MenC titres 1:128 and GMTs.

rSBA-MenW-135 titres 1:128 and GMTs.

rSBA-MenY titres 1:128 and GMTs.

hSBA-MenA titres 1:4, 1:8 and GMTs.

hSBA-MenC titres 1:4, 1:8 and GMTs.

hSBA-MenW-135 titres 1:4, 1:8 and GMTs.

hSBA-MenY titres 1:4, 1:8 and GMTs.

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
Serious adverse events:

Occurrence of serious adverse events related to 
vaccination and any event related to lack of vaccine 
efficacy (i.e. meningococcal disease) from the 
subject’s last visit in study MENACWY-TT-048 EXT: 
039 Y2, 3, 4, 5 (112036) up to each yearly visit in the 
current study in a retrospective manner.

C0921001 (MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6, 200088)
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TABLE OF CONTENTS
PAGE
SYNOPSIS ..................................................................................................................... 6
LIST OF ABBREVIATIONS.......................................................................................... 16
GLOSSARY OF TERMS .............................................................................................. 18
TRADEMARKS ............................................................................................................ 21
1.
INTRODUCTION ................................................................................................... 22
1.1.
Background ................................................................................................ 22
1.2.
Rationale for the study and study design.................................................... 23
2.
OBJECTIVES ........................................................................................................ 23
2.1.
Primary objective........................................................................................ 23
2.2.
Secondary objectives ................................................................................. 23
3.
STUDY DESIGN OVERVIEW ................................................................................ 25
4.
STUDY COHORT .................................................................................................. 27
4.1.
Number of subjects/centres ........................................................................ 27
4.2.
Inclusion criteria for enrolment.................................................................... 27
4.3.
Exclusion criteria for enrolment................................................................... 28
5.
CONDUCT OF THE STUDY.................................................................................. 28
5.1.
Regulatory and ethical considerations, including the informed consent 
process....................................................................................................... 28
5.2.
Subject identification................................................................................... 29
5.3.
Method of blinding ...................................................................................... 29
5.4.
General study aspects................................................................................ 30
5.5.
Outline of study procedures........................................................................ 31
5.6.
Detailed description of study procedures.................................................... 32
5.6.1.
Procedures prior to study participation......................................... 32
5.6.1.1.
Reminder phone contact ............................................ 32
5.6.1.2.
Informed consent ....................................................... 32
5.6.1.3.
Check inclusion and exclusion criteria........................ 32
5.6.2.
Procedures during study participation.......................................... 32
5.6.2.1.
Medical history ........................................................... 32
5.6.2.2.
Vaccination history..................................................... 33
5.6.2.3.
Physical examination.................................................. 33
5.6.2.4.
Sampling.................................................................... 33
5.6.2.4.1.
Blood sampling for immune response 
assessments .......................................... 33
5.6.2.5.
Check and record concomitant 
medication/vaccination and intercurrent medical 
conditions................................................................... 33
5.6.2.6.
Recording of SAEs..................................................... 33
5.6.2.7.
Study conclusion........................................................ 34
5.7.
Biological sample handling and analysis..................................................... 34
5.7.1.
Use of specified study materials .................................................. 35

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5.7.2.
Biological samples....................................................................... 35
5.7.3.
Laboratory assays ....................................................................... 35
5.7.4.
Biological samples evaluation...................................................... 36
5.7.4.1.
Immunological read-outs............................................ 37
5.7.5.
Immunological correlates of protection ........................................ 37
5.7.6.
Communication of individual immunology assay results to the 
study investigator......................................................................... 38
6.
STUDY VACCINES AND ADMINISTRATION ....................................................... 38
6.1.
Concomitant medication/product and concomitant vaccination................... 38
6.1.1.
Recording of concomitant medications/products and 
concomitant vaccination .............................................................. 38
6.1.2.
Concomitant medications/products/vaccines that may lead to 
the elimination of a subject from ATP analyses ........................... 39
6.2.
Intercurrent medical conditions that may lead to elimination of a subject 
from ATP analyses ..................................................................................... 39
7.
HEALTH ECONOMICS ......................................................................................... 39
8.
SAFETY................................................................................................................. 40
8.1.
Safety definitions ........................................................................................ 40
8.1.1.
Definition of a serious adverse event........................................... 40
8.1.2.
Clinical laboratory parameters and other abnormal 
assessments qualifying as serious adverse events...................... 41
8.2.
Events or outcomes not qualifying as serious adverse events .................... 41
8.2.1.
Disease/Population-related events or outcomes not qualifying 
as serious adverse events........................................................... 41
8.3.
Detecting and recording serious adverse events ........................................ 41
8.3.1.
Time period for detecting and recording serious adverse 
events.......................................................................................... 41
8.3.2.
Post-Study adverse events and serious adverse events.............. 44
8.3.3.
Evaluation of serious adverse events .......................................... 44
8.3.3.1.
Active questioning to detect serious adverse 
events ........................................................................ 44
8.4.
Reporting of serious adverse events........................................................... 44
8.4.1.
Prompt reporting of serious adverse events................................. 44
8.4.2.
Completion and transmission of SAE reports............................... 45
8.4.3.
Updating of SAE information after freezing of the subject’s 
eCRF........................................................................................... 45
8.4.4.
Regulatory reporting requirements for serious adverse events .... 45
8.5.
Follow-up of serious adverse events........................................................... 45
8.5.1.
Follow-up of serious adverse events............................................ 45
8.5.1.1.
Follow-up during the study ......................................... 45
8.5.1.2.
Follow-up after the subject is discharged from the 
study .......................................................................... 46
8.6.
Subject card ............................................................................................... 46
9.
SUBJECT COMPLETION AND WITHDRAWAL ................................................... 46
9.1.
Subject completion ..................................................................................... 46
9.2.
Subject withdrawal...................................................................................... 46
9.2.1.
Subject withdrawal from the study ............................................... 47
9.2.2.
Subject withdrawal from investigational vaccine .......................... 47
10. STATISTICAL METHODS..................................................................................... 49

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10.1.
Primary endpoints....................................................................................... 49
10.2.
Secondary endpoints.................................................................................. 49
10.3.
Determination of sample size...................................................................... 50
10.4.
Study cohorts/ data sets to be analysed ..................................................... 52
10.4.1.
Total Cohort at Month X............................................................... 52
10.4.2.
According-To-Protocol (ATP) cohort for analysis of 
persistence at Month X................................................................ 52
10.5.
Derived and transformed data .................................................................... 53
10.6.
Statistical analyses..................................................................................... 53
10.6.1.
Persistence analyses................................................................... 53
10.6.1.1.
Analysis of demographics/baseline characteristics..... 53
10.6.1.2.
Analysis of persistence............................................... 54
10.6.1.2.1.
Within group analysis ............................. 54
10.6.1.2.2.
Modeling prediction ................................ 54
10.6.1.2.3.
Between group analysis ......................... 54
10.6.1.3.
Analysis of safety ....................................................... 55
10.7.
Interpretation of analyses ........................................................................... 55
10.8.
Conduct of analyses................................................................................... 55
10.8.1.
Sequence of analyses ................................................................. 55
10.8.2.
Statistical considerations for interim analyses.............................. 55
11. ADMINISTRATIVE MATTERS............................................................................... 56
11.1.
Remote Data Entry instructions .................................................................. 56
11.2.
Study Monitoring......................................................................................... 56
11.3.
Record retention......................................................................................... 57
11.4.
Quality assurance....................................................................................... 57
11.5.
Posting of information on publicly available clinical trial registers and 
publication policy ........................................................................................ 58
11.6.
Provision of study results to investigators ................................................... 58
11.7.
Reporting of safety issues and serious breaches of the protocol or ICH 
GCP ........................................................................................................... 59
12. COUNTRY SPECIFIC REQUIREMENTS .............................................................. 60
13. REFERENCES ...................................................................................................... 61

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LIST OF TABLES
PAGE
Table 1
Study groups and epochs foreseen in the study..................................... 26
Table 2
Blinding of study epochs ........................................................................ 26
Table 3
List of study procedures......................................................................... 31
Table 4
Intervals between study visits ................................................................ 32
Table 5
Biological samples ................................................................................. 35
Table 6
Laboratory assays.................................................................................. 36
Table 7
Immunological read-outs........................................................................ 37
Table 8
Reporting periods for serious adverse events ........................................ 43
Table 9
Timeframes for submitting serious adverse event reports ...................... 44
Table 10
Exact 95% confidence intervals of the percentage of subjects with 
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres 
greater than or equal to 1:8.................................................................... 51
Table 11
Neomed Institute.................................................................................... 64
Table 12
Outsourced laboratory ........................................................................... 64

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LIST OF APPENDICES
PAGE
APPENDIX A LABORATORY ASSAYS ....................................................................... 63
APPENDIX B CLINICAL LABORATORIES.................................................................. 64

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LIST OF ABBREVIATIONS
AE:
Adverse Event
ANOVA:
Analysis of Variance
ATP:
According-To-Protocol
CDC:
Centers for Disease Control
CI:
Confidence Interval
CRM197:
A non-toxic mutant form of Corynebacterium diphtheriae
toxin
CSA:
Clinical Study Agreement
CSR:
Clinical Study Report
DT:
Diphtheria Toxoid
eCRF:
electronic Case Report Form
EU:
European Union
EudraCT:
European Clinical Trials Database
GCP:
Good Clinical Practice
GMT:
Geometric Mean Titre
GSK:
GlaxoSmithKline
hSBA:
Serum bactericidal activity (using human complement)
hSBA-MenA:
Serum bactericidal activity against N. meningitidis
serogroup A (using human complement)
hSBA-MenC:
Serum bactericidal activity against N. meningitidis
serogroup C (using human complement)
hSBA-MenW-135:
Serum bactericidal activity against N. meningitidis 
serogroup W-135 (using human complement)
hSBA-MenY:
Serum bactericidal activity against N. meningitidis
serogroup Y (using human complement)
ICF:
Informed Consent Form
ICH:
International Conference on Harmonisation

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IEC:
Independent Ethics Committee
IRB:
Institutional Review Board
LAR:
Legally Acceptable Representative
MenACWY-TT:
Meningococcal serogroups A, C, W-135, Y tetanus 
toxoid conjugate vaccine
NA:
Not Applicable
PHE:
Public Health England
PS:
Polysaccharide
RDE:
Remote Data Entry
rSBA:
Serum bactericidal activity (using rabbit complement)
rSBA-MenA:
Serum bactericidal activity against N. meningitidis
serogroup A (using rabbit complement)
rSBA-MenC:
Serum bactericidal activity against N. meningitidis
serogroup C (using rabbit complement)
rSBA-MenW-135:
Serum bactericidal activity against N. meningitidis 
serogroup W-135 (using rabbit complement)
rSBA-MenY:
Serum bactericidal activity against N. meningitidis
serogroup Y (using rabbit complement)
SAE:
Serious Adverse Event
SDV:
Source Document Verification
SPM:
Study Procedures Manual
TT:
Tetanus Toxoid

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GLOSSARY OF TERMS
Adverse event:
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use 
of a medicinal product, whether or not considered related 
to the medicinal product. 
An adverse event (AE) can therefore be any unfavourable 
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal product. 
For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), 
abuse or misuse.
Blinding:
A procedure in which one or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the trial, 
and only when the data are cleaned to an acceptable level 
of quality will appropriate personnel be unblinded or 
when required in case of a serious adverse event. In an 
open-label study, no blind is used. Both the investigator 
and the subject know the identity of the treatment 
assigned.
Child in care:
A child who has been placed under the control or 
protection of an agency, organisation, institution or entity 
by the courts, the government or a government body, 
acting in accordance with powers conferred on them by 
law or regulation. The definition of a child in care can 
include a child cared for by foster parents or living in a 
care home or institution, provided that the arrangement 
falls within the definition above. The definition of a child 
in care does not include a child who is adopted or has an 
appointed legally acceptable representative (LAR).
Core Data Sheet
The Core Data Sheet (CDS) represents the internal 
company medical position for all labeling documents 
worldwide. The CDS is a document containing all 
essential safety information, such as contraindications, 
warnings/precautions, and undesirable effects, which 
Pfizer requires to be included in the proposed labeling of 
all countries where the product is marketed. The Core 
Data Sheet also contains indications and dosing 
information (for all dosage forms) supported worldwide, 
as well as pharmacodynamic, pharmacokinetic and non-
clinical information that has important bearing on the safe 
and effective use of the product. Information contained in 
the Core Data Sheet is based on valid, scientific/medical 

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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 
timepoints or a single timepoint from a single protocol. 
Self-contained means that data collected for all subjects 
at all timepoints 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-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 6.1.2 and 10.4 for details on criteria for 
evaluability).
Immunological correlate 
of protection:
The defined humoral antibody response above which 
there is a high likelihood of protection in the absence of 
any host factors that might increase susceptibility to the 
infectious agent.
Investigational 
vaccine/product:
(Synonym of 
Investigational Medicinal 
Product)
A pharmaceutical form of an active ingredient or placebo 
being tested or used as a reference in a clinical trial, 
including a product with a marketing authorisation when 
used in a way different from the approved form, or when 
used for an unapproved indication, or when used to gain 
further information about an approved use. 
Primary completion 
date:
The date that the final subject was examined or received 
an intervention for the purpose of final collection of data 
for the primary outcome, whether the clinical trial 
concluded according to the pre-specified protocol or was 
terminated.
Randomisation:
Process of random attribution of treatment to subjects in 
order to reduce bias of selection.
Self-contained study:
Study with objectives not linked to the data of another 
study.
Site Monitor:
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at one or 
more investigational sites.

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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.
Treatment number:
A number identifying a treatment to a subject, according 
to the study randomisation or treatment allocation.

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TRADEMARKS
The following trademarks are used in the present protocol.
Note: In the body of the protocol (including the synopsis), the names of the vaccines will 
be written without the superscript symbol ™or ® and will be written in italics.
Trademarks of Pfizer
Generic description
Nimenrix®
Meningococcal serogroups A, C, W-135 and 
Y polysaccharide tetanus toxoid conjugate 
vaccine
Mencevax® ACWY
Meningococcal serogroups A, C, W-135 and 
Y vaccine
Trademarks not owned by Pfizer
Generic description
Meningitec® (Nuron Biotech Inc)
Meningococcal serogroup C
oligosaccharide conjugate vaccine
Menveo® (GSK)
Meningococcal serogroups A, C, W-135 and 
Y oligosaccharide diphtheria CRM197
conjugate vaccine
Menactra® (Sanofi Pasteur Inc)
Meningococcal serogroups A, C, W-135 and 
Y polysaccharide diphtheria toxoid 
conjugate vaccine

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1.
INTRODUCTION
1.1.
Background
Invasive meningococcal disease, including meningitis and meningococcal septicaemia, often 
follows invasive infection by Neisseria meningitidis (meningococcus) and is a major cause of 
death and morbidity throughout the world. The devastating disease caused by the bacteria is 
characterized by rapidly progressive sepsis which can be fatal within a few hours of onset 
leaving antibiotic treatment ineffective. Severe permanent sequelae (e.g. limb necrosis 
requiring amputation, hearing loss, chronic renal failure, neurological damage) can result 
after infection and the mortality rate is 7 – 19 %, even with appropriate therapy [Kirsch, 
1996; Anderson, 1998]. Mortality rates are generally highest in infants and young children 
[Harrison, 2001]. Meningococcal disease continues to be endemic in both industrialized (e.g. 
Europe and the United States of America [USA]) and developing countries. Epidemics occur 
regularly worldwide with the highest attack rates prevailing in the sub-Saharan countries 
[Harrison, 2009].
Neisseria meningitidis serogroups A, B, C, W-135 and Y are the most common causes of 
invasive meningococcal disease worldwide: serogroup A is most common in Africa and Asia, 
while serogroups B and C account for more than 90% of the cases in Europe and Latin 
America [Anderson, 1998; Peltola, 1998; Connolly, 1999; Harrison, 2009]. In recent years, 
an increase in cases due to serogroup C in Europe, and due to both serogroups C and Y in the 
USA have been observed [Lingappa, 2001]. In 2001 and 2002, epidemics of serogroup W-
135 were reported in Muslim pilgrims and in Africa [Anderson, 1998; Jackson, 1995; Peltola, 
1998; CDC, 1999; Decosas, 2002; Wilder-Smith , 2003].
Polysaccharide (PS) vaccines consisting of meningococcal capsular polysaccharides are safe, 
efficacious, and widely used in adults and children over 2 years of age [Morley, 2002]. They 
do not induce a satisfactory response in infants and young children under 2 years of age, the 
age groups most at risk for meningococcal infections [Balmer, 2004]. They also result in 
incomplete maturation of B-cells which leads to a defective B-cell activation [Black, 1991; 
Booy, 1992]. PS vaccines do not reduce mucosal carriage and consequently do not confer 
herd immunity [Hassan-King, 1988]. PS vaccines do not induce immunological memory nor 
the associated affinity/avidity maturation of antibodies [Pollard, 2001]. PS antigens can 
however be made to induce a T-cell response and immunological memory, by their covalent 
coupling to carrier protein (as in conjugate vaccines) [Balmer, 2004].
New meningococcal serogroup C conjugate vaccines using a non-toxic mutant form of 
Corynebacterium diphtheriae toxin (CRM197) or Tetanus Toxoid (TT) carrier proteins have 
been developed and brought to the market in Europe, Canada, Australia and Latin America. 
At this time, 3 quadrivalent meningococcal conjugate vaccines have been licensed. 
MenACWY diphtheria toxoid (DT) conjugate vaccine (Menactra, Sanofi Pasteur Inc.) is 
authorised for active immunization of individuals aged 9 months to 55 years in the USA and 
in Canada [Menactra Product Information, 2009; Menactra Approval Letter, 2011], and for 
individuals aged 2 to 55 years in the Gulf Cooperation States in the Middle East. MenACWY 
CRM197 conjugate vaccine (Menveo, GSK) is authorised for active immunization of 
individuals from 2 years of age in the European Union (EU) [EPAR, 2011], from 2 to 55 
years of age in Canada [Menveo Product Monograph, 2010] and in the United States 
[Menveo Prescribing Information, 2011] and from 11 years of age and above in Australia 

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[Menveo Consumer Medicine Information, 2010]. Recently, a MenACWY-TT conjugate 
vaccine (Nimenrix, Pfizer) has been licensed in the EU for individuals 12 months of age and 
above [European Commission, 2012] and in Canada for individuals from 12 months of age 
up to 55 years of age.
Pfizer completed the acquisition of Nimenrix and Mencevax on 01 October 2015, and will 
therefore assume responsibility of sponsor for this study.
Please refer to the current Core Data Sheet (CDS) for information regarding the pre-clinical 
and clinical studies, and the potential risks and benefits of MenACWY-TT. The CDS is the 
single reference safety document for this study.
1.2.
Rationale for the study and study design
There is growing interest in the assessment of long term persistence of serological markers of 
protection following meningococcal conjugate vaccination. In study MENACWY-TT-048 
EXT: 039 Y2, 3, 4, 5 (112036), the persistence of the immune response of MenACWY-TT 
vaccine versus Meningitec was evaluated up to 4 years after vaccination as well as the 
immune response to a booster dose given 4 years after primary vaccination of children aged 
12 through 23 months. In this extended follow-up study C0921001 (formerly GSK
MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6 [200088]), the persistence of the immune 
response as well as safety of MenACWY-TT vaccine versus Meningitec will be evaluated up 
to 6 years after booster vaccination in children who participated in study MENACWY-TT-
048 EXT: 039 Y2, 3, 4, 5 (112036).
2.
OBJECTIVES
2.1.
Primary objective
Immunogenicity 
Persistence
At 2, 3, 4, 5, 6 years after booster vaccination of children with MenACWY-TT or Meningitec

To evaluate the persistence of meningococcal antibodies in terms of the percentage of 
subjects with rSBA antibody titres ≥1:8 for each of the four serogroups.
Refer to Section 10.1 for the definition of the primary endpoints.
2.2.
Secondary objectives
Immunogenicity
Persistence
At 2, 3, 4, 5, 6 years after booster vaccination of children with MenACWY-TT or Meningitec

To evaluate the persistence of meningococcal A, C, W-135 and Y antibodies in terms of 
the percentage of subjects with rSBA titres ≥1:128 and GMTs and hSBA titres ≥1:4 and
≥1:8 and GMTs for each of the four serogroups.

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Safety

To describe serious adverse events (SAEs) related to vaccination and any event related to 
lack of vaccine efficacy (i.e. meningococcal disease) from the subject’s last visit in study 
MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036) up to each yearly visit in the 
current study in a retrospective manner.
Refer to Section 10.2 for the definition of the secondary endpoints.

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3.
STUDY DESIGN OVERVIEW
ACWY-TT Group: Vaccinated and boosted with MenACWY-TT in studies MENACWY-TT-039 (109670) and MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036)
MenCCRM Group: Vaccinated and boosted with Meningitec in studies MENACWY-TT-039 (109670) and MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036)
BS: Blood sample
Vacc: Vaccination in study MENACWY-TT-039 (109670)
Booster: Booster vaccination at Month 48 in study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036)
Protocol waivers or exemptions are not allowed with the exception of immediate safety concerns. Therefore, adherence to the study design 
requirements, including those specified in the outline of study procedures (Section 5.5), are essential and required for study conduct.

Experimental design: Phase III, open-label, controlled, multi-centric, single-country study with two parallel groups.

Duration of the study: Approximately four years per subject.

Epoch 001: Persistence Visit 1 (Year 2 [Month 24] post-booster vaccination)

Epoch 002: Persistence Visit 2 (Year 3 [Month 36] post-booster vaccination)

Epoch 003: Persistence Visit 3 (Year 4 [Month 48] post-booster vaccination)

Epoch 004: Persistence Visit 4 (Year 5 [Month 60] post-booster vaccination)

Epoch 005: Persistence Visit 5 (Year 6 [Month 72] post-booster vaccination). 

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
Study groups:
Table 1 presents the study groups and epochs foreseen in the study.
Table 1
Study groups and epochs foreseen in the study
Study 
groups
Number of 
subjects *
Age at booster 
vaccination in 
years (Min/Max)
Epochs
Epoch 
001
Epoch 
002 
Epoch 
003 
Epoch 
004 
Epoch 
005 
ACWY-TT
185
5 years – 6 years
x
x
x
x
x
MenCCRM 
38
5 years – 6 years
x
x
x
x
x
* The sample size of this study is driven by the number of subjects who received the booster vaccination at Month 48 in 
study MENACWY-TT-048 EXT:039 Y2, 3, 4, 5 (112036) at the participating sites and by assumptions about the 
annual dropout rate. For more information see Section 10.3.

Control: active control (MenCCRM group).

Vaccination schedule: No vaccine will be administered during this long-term 
persistence study.

Study group allocation: The subjects in this study will be allocated to the same 
groups and will retain the same subject number as in study MENACWY-TT-048 
EXT: 039 Y2, 3, 4, 5 (112036):

ACWY-TT group (N 185): Subjects primed and boosted with the 
MenACWY-TT vaccine

MenCCRM group (N 38): Subjects primed and boosted with the Meningitec
vaccine

Blinding: Study will be conducted in an open manner.
Table 2 presents the blinding of the study epoch.
Table 2
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
open
Epoch 002 
open
Epoch 003 
open
Epoch 004 
open
Epoch 005 
open

Sampling schedule: Blood samples will be taken at each of the study visits, i.e. 2 
(Visit 1), 3 (Visit 2), 4 (Visit 3), 5 (Visit 4) and 6 (Visit 5) years after booster 
vaccination in study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036).

Type of study: self-contained and extension of study MENACWY-TT-048 EXT: 039 
Y2, 3, 4, 5 (112036).

Data collection: Electronic Case Report Form (eCRF).

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4.
STUDY COHORT
4.1.
Number of subjects/centres
The parent(s)/ legally acceptable representative (s) [LARs] of potential subjects will be 
contacted by the site personnel to assess the willingness to have their child/ward 
participate in the current study.
Refer to Section 10.3 for the accuracy expected from the estimated sample size with 
respect to the primary and secondary objectives.
Overview of the recruitment plan:

The study will be conducted at multiple centres in Finland.

Target enrolment: Parent(s)/ LAR(s) of subjects vaccinated with a booster dose of a 
meningococcal conjugate vaccine in study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 
5 (112036) will be contacted to enrol their child/ward in the current study C0921001 
(formerly GSK study MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6 [200088]) at 2, 
3, 4, 5 and 6 years after the booster vaccination unless the parent(s)/LAR(s) 
withdrew consent during the study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 
(112036) and/or sites activities were closed.

The maximum number of subjects to return at Visit 1 (Month 24) will be 248
subjects in total: 206 in the ACWY-TT group and 42 in the MenCCRM group.

If one assumes that approximately 10% of the potential subjects will not participate
to the persistence study at Visit 1 (Month 24) (based on experience with studies in a
similar age group), then one expects 223 subjects (185 in the ACWY-TT group and 
38 in the MenCCRM group) to participate at Visit 1 (Month 24).

Total duration of the study for each subject will be approximately four years.

A subject can join at any visit in the study (for instance a subject can join at Visit 2, 
without Visit 1 being done).
4.2.
Inclusion criteria for enrolment
Deviations from inclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.
All subjects must satisfy ALL the following criteria at study entry:

Subjects’ parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the 
opinion of the investigator, can and will comply with the requirements of the 
protocol (e.g. return for follow-up visits).

A male or female who has received primary and booster vaccination with the 
MenACWY-TT or Meningitec vaccines in studies MENACWY-TT-039 (109670) 
and MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036), respectively.

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
Written informed consent obtained from the parent(s)/LAR(s) of the subject.

Healthy subjects as established by medical history and clinical examination before 
entering into the study.
4.3.
Exclusion criteria for enrolment
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. 
Therefore, adherence to the criteria as specified in the protocol is essential.
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study:

Child in care
Please refer to the glossary of terms for the definition of child in care.

History of meningococcal disease.

Administration of a meningococcal polysaccharide or a meningococcal 
polysaccharide conjugate vaccine outside of studies MENACWY-TT-039 (109670)
and MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036).

Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required).

Bleeding disorders, such as thrombocytopenia, or subjects on anti-coagulant therapy.
5.
CONDUCT OF THE STUDY
5.1.
Regulatory and ethical considerations, including the 
informed consent process
The study will be conducted in accordance with all applicable regulatory requirements.
The study will be conducted in accordance with the ICH Guideline for Good Clinical 
Practice (GCP), all applicable subject privacy requirements and the guiding principles of 
the Declaration of Helsinki (World Medical Association 1996 & 2008), as well as the 
general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002).
The study has been designed and will be conducted in accordance with the ICH 
Harmonised Tripartite Guideline for clinical investigation of medicinal products in the 
paediatric population (ICH E11) and all other applicable ethical guidelines.
Pfizer will obtain favourable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements.
Conduct of the study includes, but is not limited to, the following:

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
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
favourable opinion/approval of study protocol and any subsequent amendments.

Subject’s parent(s)/LAR(s) informed consent.

Investigator reporting requirements as stated in the protocol.
Pfizer will provide full details of the above procedures to the investigator, either verbally, 
in writing, or both.
Freely given and written informed consent must be obtained from each subject’s 
parent(s)/LAR(s), 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.
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
Subjects will keep the same subject number that was attributed in study MENACWY-TT-
048 EXT: 039 Y2, 3, 4, 5 (112036).
The subject number will be used as identification for blood samples and for all data 
collected on the subject throughout the long-term persistence.
5.3.
Method of blinding
The study will be conducted in an open manner.
At each persistence time-point, investigators will be provided with the immunogenicity 
results for all enrolled subjects when the individual listings of the statistical report have 
been released.
The laboratory in charge of the laboratory testing will be blinded to the treatment, and 
codes will be used to link the subject and study (without any link to the treatment 
attributed to the subject) to each sample.

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5.4.
General study aspects
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Procedures Manual (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
Table 3 presents the list of study procedures.
Table 3
List of study procedures
Epochs
001
002
003
004
005
Type of contact §
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Time-points
months 24
months 36
months 48
months 60
months 72
Sampling time-point
Year 2 
Post-
booster 
vaccination 
Year 3 
Post-
booster 
vaccination 
Year 4 
Post-
booster 
vaccination 
Year 5 
Post-
booster 
vaccination 
Year 6 
Post-
booster 
vaccination 
Reminder phone contact #
O
O
O
O
O
Informed consent *
●
●
●
●
●
Check inclusion/exclusion criteria †
●
●
●
●
●
Medical history since the previous visit **
●
●
●
●
●
Meningococcal vaccination history since the 
previous visit **
●
●
●
●
●
Physical examination
O
O
O
O
O
Blood sampling for antibody determination
7 mL
7 mL
7 mL
10 mL
10 mL
Record any relevant medication/vaccination since 
the previous visit **
●
●
●
●
●
Record any intercurrent medical conditions
●
●
●
●
●
Recording of serious adverse events (SAEs) 
related to vaccination and any event related to 
lack of vaccine efficacy since the previous visit ,1 ‡
●
●
●
●
●
Recording of SAEs related to study participation 2
●
●
●
●
●
Study conclusion
●3
●is used to indicate a study procedure that requires documentation in the individual eCRF.
○is used to indicate a study procedure that does not require documentation in the individual eCRF.
Note: Double line border between visits indicates a data base freeze on as clean as possible data in order to proceed 
in the step-wise analysis.
§ A subject can join at any visit in the study (for instance a subject can join at Visit 2, without Visit 1 being done).
# A phone contact will be made approximately 4-8 weeks prior to the persistence visit to ask the subject’s 
parent(s)/LAR(s) if the subject will be participating in the follow-up visit.
* The parent(s)/LAR(s) will sign the informed consent form only once at the subject’s first visit and this first visit could 
be either Visit 1, 2, 3, 4 or 5.
† Check of inclusion and exclusion criteria for the persistence epoch only once at the subject’s first visit and this first 
visit could be either Visit 1, 2, 3, 4 or 5.
1 Occurrence of meningococcal diseases should be documented in the SAE screen in the eCRF during the entire 
study period.
‡At the subject’s first visit in the current study, SAEs experienced since the subject’s last visit in the study MENACWY-
TT-048 EXT: 039 Y2, 3, 4, 5 (112036) should also be recorded.
** At the subject’s first visit in the current study, this reporting should cover the period from the subject’s last visit in the 
study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036).
2 This will also include SAE(s) leading to the withdrawal of the subject from the study.
3To be completed for all subjects who are enrolled in the study

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It is the investigator’s responsibility to ensure that the intervals between visits are strictly 
followed. These intervals determine each subject’s evaluability in the according to 
protocol analyses.
Table 4 presents the intervals between study visits.
Table 4
Intervals between study visits
Interval
Optimal length of interval 1
Allowed interval2
(Vaccination in booster vaccination study [Day 0]
Visit 1 of persistence study [Year 2])
24 months
24 months ± 12 weeks
(Vaccination in booster vaccination study [Day 0] 
Visit 2 of persistence study [Year 3])
36 months
36 months ± 12 weeks
(Vaccination in booster vaccination study [Day 0] 
Visit 3 of persistence study [Year 4])
48 months
48 months ± 12 weeks
(Vaccination in booster vaccination study [Day 0] 
Visit 4 of persistence study [Year 5])
60 months
60 months ± 12 weeks
(Vaccination in booster vaccination study [Day 0] 
Visit 5 of persistence study [Year 6])
72 months
72 months ± 12 weeks
1. Whenever possible the investigator should arrange study visits within this interval.
2. Subjects will not be eligible for inclusion in the According-To-Protocol (ATP) cohort for analysis of persistence if they 
make the study visit outside this interval.
5.6.
Detailed description of study procedures
5.6.1.
Procedures prior to study participation
5.6.1.1.
Reminder phone contact
A phone contact must be made approximately 4-8 weeks prior to the persistence visit to 
ask the subject’s parent(s)/LAR(s) if the subject will be participating in the follow-up 
visit.
5.6.1.2.
Informed consent
The signed informed consent of the subject’s parent(s)/LAR(s) must be obtained before 
study participation. Refer to Section 5.1 for the requirements on how to obtain informed 
consent.
5.6.1.3.
Check inclusion and exclusion criteria
Check all inclusion and exclusion criteria as described in Sections 4.2 and 4.3 before 
enrolment.
5.6.2.
Procedures during study participation
5.6.2.1.
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 

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subject prior to the start of the persistence epochs 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.
5.6.2.2.
Vaccination history
Check the vaccination history for a meningococcal polysaccharide or a meningococcal 
polysaccharide conjugate vaccine of serogroup A, B, C, W-135 and/or Y or any 
investigational vaccine since the previous visit done. Refer to Sections 4.2 and 4.3 for 
more details.
5.6.2.3.
Physical examination
Perform a physical examination of the subject at each persistence visit. 
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
5.6.2.4.
Sampling
Refer to the Module on Biospecimen Management in the SPM for detailed instructions 
for the collection, handling and processing of the samples.
5.6.2.4.1.
Blood sampling for immune response assessments
As specified in the List of Study Procedures in Section 5.5 (Table 3), blood samples are 
taken during each study visit.
A volume of approximately 7 mL (10 mL at visits 4 and 5) of whole blood (to provide 
approximately 2.5 mL [or 5 mL of serum at visits 4 and 5]) should be drawn from all 
subjects. After centrifugation, serum samples should be kept at –20°C or below until 
shipment. Refer to the SPM for more details on sample storage conditions.
5.6.2.5.
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 6.1.
Intercurrent medical conditions must be checked and recorded in the eCRF as described 
in Section 6.2.
5.6.2.6.
Recording of SAEs

Refer to Section 8.3 for procedures for the investigator to record SAEs that are 
related to vaccination and any event related to lack of vaccine efficacy or related to 
study participation. Refer to Section 8.4 for guidelines on how to submit SAE reports 
to Pfizer.

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
The subjects’ parent(s)/LAR(s) will be instructed to contact the investigator 
immediately should the subjects manifest any signs or symptoms they perceive as 
serious.
5.6.2.7.
Study conclusion
The investigator will:

review data collected to ensure accuracy and completeness

complete the Study Conclusion screen in the eCRF.
5.7.
Biological sample handling and analysis
Please refer to the SPM for details on biospecimen management (handling, storage and 
shipment). See section 5.6.2.4.1 for a brief description of the procedure for collection, 
preparation and storage of serum samples.
Samples will not be labelled with information that directly identifies the subject but will 
be coded with the identification number for the subject (subject number).
Under the following circumstances, additional testing on the samples may be performed 
outside the scope of this protocol:

Collected samples may be used in other assays, for test improvement or development 
of analytical methods related to the study vaccine and its constituents or the disease 
under study.

Collected samples may be used for purposes related to the quality assurance of data 
generated linked to the study vaccine or the disease under study, such as for 
maintenance of assays described in this protocol and comparison between analytical 
methods and/or laboratories.
Information on further investigations and their rationale can be obtained from Pfizer.
Any sample testing will be done in line with the consent of the individual subject’s 
parent(s)/LAR(s).
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s). 
If additional testing is performed, the marker priority ranking given in Section 5.7.4 may 
be changed.
Collected samples will be stored for a maximum of 15 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with Pfizer.

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5.7.1.
Use of specified study materials
When materials are provided by Pfizer or designee, it is MANDATORY that all clinical 
samples (including serum samples) be collected and stored exclusively using those 
materials in the appropriate manner. The use of other materials could result in the 
exclusion of the subject from the ATP analysis (See Section 10.4 for the definition of 
study cohorts/ data sets to be analysed). The investigator must ensure that his/her 
personnel and the laboratory(ies) under his/her supervision comply with this requirement. 
Refer to the Module on Clinical Trial Supplies in the SPM.
5.7.2.
Biological samples
Table 5 presents the biological samples used in the study.
Table 5
Biological samples
Sample type
Quantity
Unit
Time-point
Blood
Approximately 7
mL
Month 24 (Visit 1)
Blood
Approximately 7
mL
Month 36 (Visit 2)
Blood
Approximately 7
mL
Month 48 (Visit 3)
Blood
Approximately 10
mL
Month 60 (Visit 4)
Blood
Approximately 10
mL
Month 72 (Visit 5)
5.7.3.
Laboratory assays
Please refer to APPENDIX A for a detailed description of the assays performed in the 
study. Please refer to APPENDIX B for the address of the clinical laboratories used for 
sample analysis.
Approximately 7 mL (10 mL at visits 4 and 5) of whole venous blood will be collected 
using Vacutainer tubes with serum separator. After blood centrifugation and serum 
separation, samples will be stored at -20°C until collection by the sponsor. The serum 
samples (approximately 2.5 mL [or 5 mL for visits 4 and 5]) will be sent to the Neomed 
Institute (Table 11) or to a laboratory designated by Pfizer (Table 12), to be analysed 
using standardised and validated procedures (refer to Table 6).
Table 6 presents the laboratory assays to be used in the study.

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Table 6
Laboratory assays
System
Component
Method
Kit/ 
Manufacturer
Unit
Cut-off
Laboratory
#
Humoral
Neisseria meningitidis 
Serogroup A L10 3125 
Ab
Serum Bactericidal 
Assay, using rabbit 
complement
NA
1/dilution
8
PHE*
Humoral
Neisseria meningitidis 
Serogroup C L3v C11 
Ab
Serum Bactericidal 
Assay, using rabbit 
complement
NA
1/dilution
8
PHE*
Humoral
Neisseria meningitidis 
Serogroup W L3v 
MP01240070 Ab
Serum Bactericidal 
Assay, using rabbit 
complement
NA
1/dilution
8
PHE*
Humoral
Neisseria meningitidis 
Serogroup Y L3v 
S1975 Ab
Serum Bactericidal 
Assay, using rabbit 
complement
NA
1/dilution
8
PHE*
Humoral
Neisseria meningitidis 
Serogroup A L10 3125 
Ab
Serum Bactericidal 
Assay, using human 
complement
NA
1/dilution
4
Neomed**
Humoral
Neisseria meningitidis 
Serogroup C L3v C11 
Ab
Serum Bactericidal 
Assay, using human 
complement
NA
1/dilution
4
Neomed**
Humoral
Neisseria meningitidis 
Serogroup W L3v 
MP01240070 Ab
Serum Bactericidal 
Assay, using human 
complement
NA
1/dilution
4
Neomed**
Humoral
Neisseria meningitidis 
Serogroup Y L3v 
S1975 Ab
Serum Bactericidal 
Assay, using human 
complement
NA
1/dilution
4
Neomed**
# Refer to APPENDIX B for the laboratory addresses.
* PHE = Public Health England
** Neomed Institute, Laval, Quebec, Canada.
5.7.4.
Biological samples evaluation
Table 7 presents the immunological read-outs.

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5.7.4.1.
Immunological read-outs
Table 7
Immunological read-outs
Blood sampling time-point
Marker
No. of 
subjects*
Marker priority rank
Timing
Month Visit no.
Post-booster 
vaccination 
Study Month 24
24
1
rSBA-MenA, rSBA-MenC, rSBA-
MenW-135, rSBA-MenY
223
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-
MenY > hSBA-MenC > hSBA-
MenW-135 > hSBA-MenA > 
hSBA-MenY
hSBA-MenA, hSBA-MenC, 
hSBA-MenW-135, hSBA-MenY
223
Post-booster 
vaccination 
Study Month 36
36
2
rSBA-MenA, rSBA-MenC, rSBA-
MenW-135, rSBA-MenY
201
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-
MenY > hSBA-MenC > hSBA-
MenW-135 > hSBA-MenA > 
hSBA-MenY
hSBA-MenA, hSBA-MenC, 
hSBA-MenW-135, hSBA-MenY
201
Post-booster 
vaccination 
Study Month 48
48
3
rSBA-MenA, rSBA-MenC, rSBA-
MenW-135, rSBA-MenY
181
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-
MenY > hSBA-MenC > hSBA-
MenW-135 > hSBA-MenA > 
hSBA-MenY
hSBA-MenA, hSBA-MenC, 
hSBA-MenW-135, hSBA-MenY
181
Post-booster 
vaccination 
Study Month 60
60
4
rSBA-MenA, rSBA-MenC, rSBA-
MenW-135, rSBA-MenY
163
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-
MenY > hSBA-MenC > hSBA-
MenW-135 > hSBA-MenA > 
hSBA-MenY
hSBA-MenA, hSBA-MenC, 
hSBA-MenW-135, hSBA-MenY
163
Post-booster 
vaccination 
Study Month 72
72
5
rSBA-MenA, rSBA-MenC, rSBA-
MenW-135, rSBA-MenY
146
rSBA-MenC > rSBA-MenA > 
rSBA-MenW-135 > rSBA-
MenY > hSBA-MenC > hSBA-
MenW-135 > hSBA-MenA > 
hSBA-MenY
hSBA-MenA, hSBA-MenC, 
hSBA-MenW-135, hSBA-MenY
146
* No. of subjects is based on the assumption described in Section 10.3.
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 7.
The assays will be performed as follows:

rSBA testing will be done on all enrolled subjects at each time-point.

hSBA testing will be done on all enrolled subjects at each time-point.
5.7.5.
Immunological correlates of protection
For the following antigens in the MenACWY-TT vaccine, an immunological correlate of 
protection has been established.
Antibodies against N. meningitidis serogroups A, C, W-135 and Y
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 rSBA 1:8 

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cut-off has shown to be the most consistent with observed efficacy at 4 weeks post-
vaccination with the meningococcal serogroup C conjugate vaccine in post-licensure 
efficacy estimates in the United Kingdom [Andrews, 2003]. The threshold for protection 
for other serogroups is still to be defined, although it is common practice to extend the 
1:8 cut-off to rSBA-MenA, rSBA-MenW-135 and rSBA-MenY [CDC, 2006].
Bactericidal assay using human complement (hSBA-MenA, hSBA-MenC, hSBA-MenW-
135 and hSBA-MenY)
For hSBA-MenC testing, a titre 1:4 has been shown to be a correlate of protection 
[Goldschneider, 1969]. It is common practice to extend this cut-off as a correlate of 
protection for serogroups A, W-135 and Y.
5.7.6.
Communication of individual immunology assay results to the 
study investigator
At each persistence time-point, investigators will be provided with the immunogenicity 
results for all enrolled subjects when the individual listings of the statistical report have 
been released.
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 VACCINES AND ADMINISTRATION
No vaccines will be administered in this persistence study. The MenACWY-TT and 
Meningitec vaccines under study were administered in the primary vaccination study 
MENACWY-TT-039 (109670) and study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 
(112036).
6.1.
Concomitant medication/product and concomitant 
vaccination
At each study visit, the investigator should question the subject’s parent(s)/LAR(s) about 
any medication/product taken and vaccination received by the subject.
6.1.1.
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 6.1.2.

Any concomitant medication/product/vaccine relevant to an SAE* or administered at 
any time during the study period for the treatment of an SAE*.

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* SAEs that are required to be reported per protocol.
6.1.2.
Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from ATP analyses
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the subject from the study but may determine a subject’s evaluability in the 
ATP analysis. See Section 10.4 for study cohorts/ data sets to be analysed.

Any investigational or non-registered product (drug or vaccine) other than the study 
vaccine(s) used 30 days prior to each study visit.

Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. consecutive use for more than 14 days) during the study period. For 
corticosteroids, this will mean prednisone 0.5 mg/kg/day, or equivalent. Inhaled 
and topical steroids are allowed.

Administration of immunoglobulins and/or any blood products within the three 
months prior to each study visit.

Administration of a meningococcal vaccine not foreseen by the study protocol at any 
time during the study period. 

A vaccine not foreseen by the study protocol administered during the 30-day period 
before each blood sampling, with the exception of inactivated influenza vaccine 
which can be administered at any time during the study according to the local 
recommendations.
6.2.
Intercurrent medical conditions that may lead to elimination 
of a subject from ATP analyses
At each study visit subsequent to the booster vaccination visit, it must be verified if the 
subject has experienced or is experiencing any intercurrent medical condition. If it is the 
case, the condition(s) must be recorded in the eCRF. Occurrence of these intercurrent 
medical conditions will not require withdrawal of the subject from the study but may 
determine a subject’s evaluability in the ATP analysis.

Occurrence of meningococcal disease.

Occurrence of a condition that has the capability of altering the immune response of 
the subject.

Occurrence of confirmed or suspected immunodeficiency or any medical condition 
which potentially impacts the safety of the subject (based on medical history and 
physical examination [no laboratory testing is required]).
7.
HEALTH ECONOMICS
Not applicable.

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8.
SAFETY
The investigator or site staff is/are responsible for the detection, documentation and 
reporting of events meeting the criteria and definition of an adverse event (AE) or serious 
adverse event (SAE) as provided in this protocol.
Each subject’s parent(s)/LAR(s) will be instructed to contact the investigator immediately 
should the subject manifest any signs or symptoms they perceive as serious.
8.1.
Safety definitions
8.1.1.
Definition of 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
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 

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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.
8.1.2.
Clinical laboratory parameters and other abnormal assessments 
qualifying as 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 an SAE if they 
meet the definition of an SAE (refer to Section 8.1.1). 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 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 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.
8.2.
Events or outcomes not qualifying as serious adverse 
events
8.2.1.
Disease/Population-related events or outcomes not qualifying as 
serious adverse events
Not applicable.
8.3.
Detecting and recording serious adverse events
8.3.1.
Time period for detecting and recording serious adverse events
See Section 8.4 for instructions on reporting of SAEs.
All SAEs leading to withdrawal from the study will be collected and recorded from the 
subject’s last visit in study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036).
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 study 
MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036) 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 

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collected and recorded from the time the subject consents to participate in the study until 
he/she is discharged from the study.

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An overview of the protocol-required reporting periods for serious adverse events (SAEs) is given in the table below (Table 8).
Table 8
Reporting periods for serious adverse events
Study activity
Since the subject’s last visit 
in study MENACWY-TT-048 
EXT: 039 Y2, 3, 4, 5 (112036)
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Month 24
Month 36
Month 48
Month 60
Month 72
SAEs related to the 
investigational vaccine and any 
event related to lack of vaccine 
efficacy , 
SAEs related to study 
participation*
Occurrence of meningococcal disease should be documented in the SAE screens in the eCRF during the entire study period
SAEs occurring from the subject’s last visit in study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036) to study entry in study MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6 (200088) 
will be recorded. Subject’s parent(s)/LAR(s) will be questioned at study entry of study C0921001 (formerly GSK MENACWY-TT-102 EXT: 048 Y2, 3, 4, 5, 6 [200088]) whether any 
SAEs occurred during that time frame.
* To be collected and recorded from the time the subject consents to participate in the study until he/she is discharged from the study. This will also include SAE(s) leading to the 
withdrawal of the subject from the study.
Type
Serious adverse events
Period of SAEs
From the subject’s last visit in study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036)
until study end (Year 6 [Month 72]) in study C0921001 (formerly GSK MENACWY-TT-
102 EXT: 048 Y2, 3, 4, 5, 6 [200088]).
Method for reporting SAEs
Paper forms

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8.3.2.
Post-Study adverse events and serious adverse events
A post-study SAE is defined as any event that occurs outside of the SAE reporting period 
defined in Table 8. Investigators are not obligated to actively seek SAEs in former study 
participants. However, if the investigator learns of any SAE at any time after a subject 
has been discharged from the study, and he/she considers the event reasonably related to 
the investigational vaccine/product, the investigator will report the event to Pfizer.
8.3.3.
Evaluation of serious adverse events
8.3.3.1.
Active questioning to detect serious adverse events
When an 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 SAE 
on the SAE report. The investigator is not allowed to send photocopies of the subject’s 
medical records to Pfizer. 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 SAE and not the individual signs/symptoms.
8.4.
Reporting of serious adverse events
8.4.1.
Prompt reporting of serious adverse events 
SAEs that occur in the time period defined in Section 8.3 will be reported promptly 
within the timeframes described in Table 9, once the investigator determines that the 
event meets the protocol definition of a SAE.
Table 9
Timeframes for submitting serious adverse event reports 
Type of Event
Initial Reports
Follow-up of Relevant Information on a Previous 
Report
Timeframe
Documents
Timeframe
Documents
All SAEs
24 hours*
paper SAE report
24 hours*
paper SAE report
* Timeframe allowed after receipt or awareness of the information.

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8.4.2.
Completion and transmission of SAE reports
Once an investigator becomes aware that an SAE has occurred in a study subject, the 
investigator (or designate) must complete the information on 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.
8.4.3.
Updating of SAE information after freezing of the subject’s eCRF
When additional SAE information is received after freezing of the subject’s eCRF, new 
or updated information should be recorded on a paper report, with all changes signed and 
dated by the investigator. The updated report should be faxed to Pfizer within the 
designated reporting time frames specified in Table 9.
8.4.4.
Regulatory reporting requirements for serious adverse events
The investigator will promptly report all SAEs to Pfizer in accordance with the 
procedures detailed in Section 8.4.1. Pfizer has a legal responsibility to promptly notify, 
as appropriate, both the local regulatory authority and other regulatory agencies about the 
safety of a product under clinical investigation. Prompt notification of SAEs by the 
investigator to the Study Contact for Reporting SAEs is essential so that legal obligations 
and ethical responsibilities towards the safety of other subjects are met.
Investigator safety reports are prepared according to the current Pfizer policy and are 
forwarded to investigators as necessary. An investigator safety report is prepared for a 
SAE(s) that is both attributable to the investigational vaccine/product and unexpected. 
The purpose of the report is to fulfil specific regulatory and GCP requirements, regarding 
the product under investigation.
8.5.
Follow-up of serious adverse events
8.5.1.
Follow-up of serious adverse events
8.5.1.1.
Follow-up during the study
After the initial SAE report, the investigator is required to proactively follow-up on each 
subject and provide additional relevant information on the subject’s condition to Pfizer 
(within 24 hours for SAEs; refer to Table 9).
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.

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8.5.1.2.
Follow-up after the subject is discharged from the study
The investigator will follow-up on subjects:

with SAEs or subjects withdrawn from the study as a result of an SAE, until the 
event has resolved, subsided, stabilised, disappeared, or until the event is otherwise 
explained, or the subject is lost to follow-up.
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to Pfizer using an SAE 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 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.
8.6.
Subject card
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational compound identifiers, subject study 
numbers, contact information for the investigational site, and contact details for a contact 
center in the event that the investigational site staff cannot be reached to provide advice 
on a medical question or problem originating from another healthcare professional not 
involved in the subject’s participation in the study.  The contact number can also be used 
by investigational staff if they are seeking advice on medical questions or problems; 
however, it should be used only in the event that the established communication 
pathways between the investigational site and the study team are not available.  It is 
therefore intended to augment, but not replace, the established communication pathways 
between the investigational site and the study team for advice on medical questions or 
problems that may arise during the study.  The contact number is not intended for use by 
the subject directly, and if a subject calls that number, he or she will be directed back to 
the investigational site.
9.
SUBJECT COMPLETION AND WITHDRAWAL
9.1.
Subject completion
A subject who returns for the concluding visit/is available for the concluding contact 
foreseen in the protocol is considered to have completed the study.
9.2.
Subject withdrawal
Withdrawals will not be replaced.

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9.2.1.
Subject withdrawal from the study
From an analysis perspective, a ‘withdrawal’ from the study refers to any subject who did 
not come back for the concluding visit/was not available for the concluding contact 
foreseen in the protocol. 
All data collected until the date of withdrawal/last contact of the subject will be used for 
the analysis.
A subject is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this subject from the date of withdrawal/last contact.
Investigators will make an attempt to contact those subjects who do not return for 
scheduled visits or follow-up. Lost to follow-up is defined by the inability to reach the 
subject after a minimum of 2 documented phone calls, faxes, or e-mails as well as lack of 
response by the subject to 1 registered mail letter.  All attempts should be documented in 
the subject’s medical records.
Information relative to the withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject’s parent(s) or LAR(s), or by the investigator, as well as which of the 
following possible reasons was responsible for withdrawal:

Serious adverse event.

Non-serious adverse event.

Protocol violation (specify).

Consent withdrawal, not due to an adverse event*.

Moved from the study area.

Lost to follow-up.

Other (specify).
* In case a subject is withdrawn from the study because the subject’s parent(s) or LAR(s) 
has withdrawn consent, the investigator will document the reason for withdrawal of 
consent, if specified subject’s parent(s) or LAR(s), in the eCRF.
Subjects who are withdrawn from the study because of SAEs 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 an SAE until resolution of 
the event (see Section 8.5.1.2).
9.2.2.
Subject withdrawal from investigational vaccine
A ‘withdrawal’ from the investigational vaccine refers to any subject who does not 
receive the complete treatment, i.e. when no further planned dose is administered from 

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the date of withdrawal. A subject withdrawn from the investigational vaccine may not 
necessarily be withdrawn from the study as further study procedures or follow-up may be 
performed (safety or immunogenicity) if planned in the study protocol.
Information relative to premature discontinuation of the investigational vaccine will be 
documented on the Vaccine Administration screen of the eCRF. The investigator will 
document whether the decision to discontinue further vaccination/treatment was made by 
the subject’s parent(s) or LAR(s), or by the investigator, as well as which of the 
following possible reasons was responsible for withdrawal:

Serious adverse event.

Non-serious adverse event.

Other (specify).

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10.
STATISTICAL METHODS
10.1.
Primary endpoints

Persistence of antibodies with respect to components of the investigational vaccine, 
2, 3, 4, 5, 6 years after booster vaccination:

rSBA-MenA titres ≥1:8.

rSBA-MenC titres ≥1:8.

rSBA-MenW-135 titres ≥1:8.

rSBA-MenY titres ≥1:8.
10.2.
Secondary endpoints

Persistence of antibodies with respect to components of the investigational vaccine, 
2, 3, 4, 5, 6 years after booster vaccination:

rSBA-MenA titres ≥1:128 and GMTs.

rSBA-MenC titres ≥1:128 and GMTs.

rSBA-MenW-135 titres ≥1:128 and GMTs.

rSBA-MenY titres ≥1:128 and GMTs.

hSBA-MenA titres ≥1:4, ≥1:8 and GMTs.

hSBA-MenC titres ≥1:4, ≥1:8 and GMTs.

hSBA-MenW-135 titres ≥1:4, ≥1:8 and GMTs.

hSBA-MenY titres ≥1:4, ≥1:8 and GMTs.

Serious adverse events:

Occurrence of serious adverse events related to vaccination and any event 
related to lack of vaccine efficacy (i.e. meningococcal disease) from the 
subject’s last visit in study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036)
up to each yearly visit in the current study in a retrospective manner.

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10.3.
Determination of sample size
The sample size of this study is driven by the sample size of study MENACWY-TT-048 
EXT: 039 Y2, 3, 4, 5 (112036).
Subjects vaccinated with a booster meningococcal vaccine in study MENACWY-TT-048 
EXT: 039 Y2, 3, 4, 5 (112036) except those for whom consent was withdrawn and/or 
sites activities were closed will be contacted for follow-up studies. Parent(s)/LAR(s) will 
be contacted to ask if they accept to enrol their child/ward in this persistence study.
The maximum number of subjects to return at Visit 1 (Month 24) will be 248 subjects in 
total: 206 in the ACWY-TT group and 42 in the MenCCRM group).
If one assumes that approximately 10% of non-evaluable subjects, will not 
participate/will drop out of the persistence study every next visit (based on experience 
with studies in a similar age group), then one expects the following numbers of subjects 
to participate at each persistence time-point:

For the analysis of Month 24, it is estimated that approximately 223 subjects will be
enrolled (185 in the ACWY-TT group and 38 in the MenCCRM group).

For the analysis of Month 36, it is estimated that approximately 201 subjects will be
enrolled (167 in the ACWY-TT group and 34 in the MenCCRM group).

For the analysis of Month 48, it is estimated that approximately 181 subjects will be
enrolled (150 in the ACWY-TT group and 31 in the MenCCRM group).

For the analysis of Month 60, it is estimated that approximately 163 subjects will be
enrolled (135 in the ACWY-TT group and 28 in the MenCCRM group).

For the analysis of Month 72, it is estimated that approximately 146 subjects will be
enrolled (121 in the ACWY-TT group and 25 in the MenCCRM group).
The primary objective of this study is to evaluate the persistence of meningococcal
antibodies in terms of percentage of subjects with rSBA titres ≥1:8 for each of the four
serogroups.
Table 10 illustrates the accuracy that can be expected from sample sizes of 223 evaluable 
subjects at Month 24, 201 evaluable subjects at Month 36, 181 evaluable subjects at 
Month 48, 163 evaluable subjects at Month 60 and 146 evaluable subjects at Month 72
for evaluating the percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-
135 and rSBA-MenY titres greater than or equal to 1:8 for each serogroup.

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Table 10
Exact 95% confidence intervals of the percentage of subjects with 
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titres 
greater than or equal to 1:8
Month 24
≈%
ACWY-TT (N = 185)
MenCCRM (N = 38)
20
[14.5; 26.5]
[9.6; 37.3]
30
[23.7; 37.4]
[15.4; 45.9]
40
[32.9; 47.4]
[24.0; 56.6]
50
[42.8; 57.7]
[33.4; 66.6]
60
[52.6; 67.1]
[43.4; 76.0]
70
[63.1; 76.8]
[54.1; 84.6]
80
[73.5; 85.5]
[62.7; 90.4]
90
[85.1; 94.1]
[75.2; 97.1]
100
[98.0; 100.00]
[90.7; 100.0]
Month 36
≈ %
ACWY-TT (N = 167)
MenCCRM (N = 34)
20
[14.0; 26.6]
[8.7; 37.9]
30
[23.1; 37.5]
[15.1; 47.5]
40
[32.6; 48.0]
[24.6; 59.3]
50
[42.5; 58.1]
[32.4; 67.6]
60
[52.0; 67.4]
[40.7; 75.4]
70
[62.5; 76.9]
[52.5; 84.9]
80
[73.4; 86.0]
[62.1; 91.3]
90
[84.2; 94.0]
[76.3; 98.1]
100
[97.8; 100.0]
[89.7; 100.0]
Month 48
≈ %
ACWY-TT (N = 150)
MenCCRM (N = 31)
20
[13.9; 27.3]
[7.5; 37.5]
30
[22.8; 38.0]
[14.2; 48.0]
40
[32.1; 48.3]
[21.8; 57.8]
50
[41.7; 58.3]
[33.1; 69.8]
60
[51.7; 67.9]
[42.2; 78.2]
70
[62.0; 77.2]
[52.0; 85.8]
80
[72.7; 86.1]
[62.5; 92.5]
90
[84.0; 94.3]
[74.2; 98.0]
100
[97.6; 100.0]
[88.8; 100.0]
Month 60
≈ %
ACWY-TT (N = 135)
MenCCRM (N = 28)
20
[13.6; 27.7]
[8.3; 41.0]
30
[22.8; 38.9]
[13.2; 48.7]
40
[31.7; 48.8]
[21.5; 59.4]
50
[41.6; 59.1]
[30.6; 69.4]
60
[51.2; 68.3]
[40.6; 78.5]
70
[61.9; 77.9]
[51.3; 86.8]
80
[72.3; 86.4]
[59.0; 91.7]
90
[84.1; 94.8]
[71.8; 97.7]
100
[97.3; 100.0]
[87.7; 100.0]

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Month 72
≈ %
ACWY-TT (N = 121)
MenCCRM (N = 25)
20
[13.1; 28.1]
[6.8; 40.7]
30
[21.8; 38.7]
[14.9; 53.5]
40
[30.9; 49.0]
[21.1; 61.3]
50
[41.2; 59.6]
[31.3; 72.2]
60
[51.0; 69.1]
[38.7; 78.9]
70
[61.3; 78.2]
[50.6; 87.9]
80
[71.9; 86.9]
[59.3; 93.2]
90
[83.3; 94.8]
[74.0; 99.0]
100
[97.0; 100.0]
[86.3; 100.0]
10.4.
Study cohorts/ data sets to be analysed
10.4.1.
Total Cohort at Month X
The Total Cohort at Month X will include all subjects who received primary vaccination 
in study MENACWY-TT-039 (109670) and booster vaccination in study MENACWY-
TT-048 EXT: 039 Y2, 3, 4, 5 (112036). The analysis of persistence at Month X will 
include all vaccinated subjects for whom data concerning persistence endpoint measures 
are available at Month X.
10.4.2.
According-To-Protocol (ATP) cohort for analysis of persistence
at Month X
The ATP cohort for persistence at Month X will include all subjects:

who have received the primary and booster vaccination with MenACWY-TT or 
Meningitec vaccine in studies MENACWY-TT-039 (109670) and MENACWY-TT-
048 EXT: 039 Y2, 3, 4, 5 (112036), respectively.

who have available assay results for at least one tested antigen at Month X.

who have not received a meningococcal polysaccharide or a meningococcal
polysaccharide conjugate vaccine not planned in protocol MENACWY-TT-048 
EXT: 039 Y2, 3, 4, 5 (112036) before Month X.

who do not have a history of meningococcal serogroup A, C, W-135, and Y disease
prior to Month X.

who comply with the blood sampling intervals defined in the protocol for Month X 
(see Section 5.5).

who do not have an immune compromising 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.

who were not excluded from the Booster ATP for immunogenicity or ATP cohort for 
persistence at Month 60 in the MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036)
study, unless the reason for exclusion was either non-compliance with the protocol-

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defined serum sampling windows or a lack of availability of immunogenicity results 
at a previous time-point.
10.5.
Derived and transformed data
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 for the considered parameter.

The cut-off value is defined by the laboratory before the analysis and is described in 
Section 5.7.3.

A seronegative subject is a subject whose titre is below the cut-off value.

A seropositive subject is a subject whose titre is greater than or equal to the cut-off 
value.

The Geometric Mean Titres (GMTs) calculations are performed by taking the anti-
log10 of the mean of the log10 titre transformations. Antibody titres below the cut-off 
of the assay will be given an arbitrary value of half the cut-off for the purpose of 
GMT calculation.
Safety
For a given subject to describe SAEs related to vaccination and any event related to the 
lack of vaccine efficacy (i.e. meningococcal disease) from the subject’s last visit in study 
MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036) up to each persistence visit in the 
current study in a retrospective manner.
10.6.
Statistical analyses
10.6.1.
Persistence analyses
10.6.1.1.
Analysis of demographics/baseline characteristics

Demographic characteristics of each study cohort will be tabulated: age at each study 
visit and months since the booster vaccination at the corresponding persistence time-
point, gender, and geographic ancestry.

The mean age (at the persistence time-point [with the range and standard deviation]) 
as well as the proportion of males and females will be calculated and presented by 
group.

The distribution of subjects enrolled at each study visit among the study sites will be 
tabulated as a whole and per group and reason for not attending a visit at each study 
visit among all subjects who participated in study MENACWY-TT-048 EXT: 039 
Y2, 3, 4, 5 (112036) will be summarized.

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10.6.1.2.
Analysis of persistence
Persistence data will be analyzed at Month 24, Month 36, Month 48, Month 60 and 
Month 72 as soon as results for all individual subjects at each time-point are available.
For Month X: The analysis of antibody persistence will be based on the ATP cohort for 
persistence at Month X. If, for any vaccine group, the percentage of subjects who come 
back for the Month X follow-up with serological results excluded from the ATP cohort is 
higher than 5%, a second analysis based on the Total Cohort at Month X will be 
performed to complement the ATP analysis.
10.6.1.2.1. Within group analysis
For each vaccine group, at each blood sampling time point, for each antigen assessed:

Geometric mean titres (GMT) with 95% CIs will be tabulated.

Percentages of subjects with titres above the proposed cut-offs with exact 95% CIs 
will be calculated.

The distribution of antibody titres will be tabulated and also presented using reverse 
cumulative curves.
10.6.1.2.2. Modeling prediction
In order to complement the descriptive analyses of observed persistence per time-point 
and evaluate the bias that may have occurred due to the loss to follow-up after the 
vaccination, a longitudinal analysis will be performed at the last persistence time-point at 
Month 72 for rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY as well as 
hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY. These analyses will 
include all results from pre- and post-booster, Month 12 (Month 60 in study 
MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036)), Month 24 up to Month 72 for 
subjects that belong to the Booster ATP cohort for immunogenicity at Month 0 and 
Month 1, ATP cohort for persistence at Month 60 in study MENACWY-TT-048 EXT: 
039 Y2, 3, 4, 5 (112036) or ATP cohort for persistence Month 24 up to Month 72,
respectively.
10.6.1.2.3. Between group analysis
An exploratory evaluation of the differences in the immune response at approximately 
24, 36, 48, 60 and 72 months after the booster vaccination will be performed in terms of:

Differences in the percentage of subjects with rSBA-MenC titres ≥1:8 and ≥1:128
between the ACWY-TT group and the MenCCRM group, with their standardized 
asymptotic 95% CIs.

Differences in the percentage of subjects with hSBA-MenC titres ≥1:4 and ≥1:8 
between the ACWY-TT group and the MenCCRM group, with their standardized 
asymptotic 95% CIs.

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
Ratio of GMTs between the ACWY-TT group and the MenCCRM group, with their 
standardized asymptotic 95% CIs for rSBA-MenC antibody titres and hSBA-MenC 
antibody titres. This will be performed using an Analysis of Variance (ANOVA)
model on the logarithm10 transformation of the titres using the vaccine group as 
covariate.
10.6.1.3.
Analysis of safety
At each persistence time-point, all reported SAEs related to vaccination and any event 
related to lack of vaccine efficacy (i.e. meningococcal disease) from the subject’s last 
visit in study MENACWY-TT-048 EXT: 039 Y2, 3, 4, 5 (112036) up to each persistence 
visit in the current study will be described in detail in a retrospective manner.
10.7.
Interpretation of analyses
All the analyses will be descriptive with the aim to characterise the immunogenicity and 
the safety within each group.
10.8.
Conduct of analyses
Any deviation(s) or change(s) from the original statistical plan outlined in this protocol 
will be described and justified in the final study report.
10.8.1.
Sequence of analyses
The analysis will be done by epoch and in a stepwise fashion:

Analysis of persistence data at Months 24, 36, 48, 60 and 72 will be conducted as 
soon as the results for all individual subjects are available at each time-point.
These analyses will be done on a validated and frozen database. The data at Months 24, 
36, 48, 60 will be as clean as possible. All analyses described in Section 10.6.1 will be 
performed but limited to the time period that is covered by the analysis. The analyzed 
data at Month 24 will be reported in a full clinical study report (CSR). The analysed data 
at Months 36, 48 and 60 will be reported yearly in separate annex CSRs in a cumulative 
manner. Therefore, the Month 72 full CSR will include all the persistence data.
10.8.2.
Statistical considerations for interim analyses
All immunogenicity analyses will be conducted on final data and therefore no statistical 
adjustment for interim analyses is required.

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11.
ADMINISTRATIVE MATTERS
To comply with ICH GCP administrative obligations relating to data collection, 
monitoring, archiving data, audits, confidentiality and publications must be fulfilled.
11.1.
Remote Data Entry instructions
Remote Data Entry (RDE), a validated computer application, will be used as the method 
for data collection. 
In all cases, subject initials will not be collected nor transmitted to Pfizer. Subject data 
necessary for analysis and reporting will be entered/transmitted into a validated database 
or data system. Clinical data management will be performed in accordance with 
applicable Pfizer standards and data cleaning procedures.
While completed eCRFs are reviewed by Pfizer or its designee at the study site, 
omissions or inconsistencies detected by subsequent eCRF review may necessitate 
clarification or correction of omissions or inconsistencies with documentation and 
approval by the investigator or appropriately qualified designee. In all cases, the 
investigator remains accountable for the study data. 
The investigator will be provided with a CD-ROM of the final version of the data 
generated at the investigational site once the database is archived and the study report is 
complete and approved by all parties.
11.2.
Study Monitoring
Pfizer, or its designee, will monitor the study to verify that, amongst others, the: 

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol, any other 
study agreements, GCP and all applicable regulatory requirements. 
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents.
The investigator must ensure provision of reasonable time, space and qualified personnel 
for monitoring visits.
Direct access to all study-site related and source data is mandatory for the purpose of 
monitoring review. The monitor will perform a RDE review and a Source Document 
Verification (SDV). By SDV we understand verifying RDE entries by comparing them 
with the source data that will be made available by the investigator for this purpose. 
The Source Documentation Agreement Form describes the source data for the different 
data in the RDE. This document should be completed and signed by the site monitor and 

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investigator and should be filed in the monitor’s and investigator’s study file. Any data 
item for which the RDE will serve as the source must be identified, agreed and 
documented in the source documentation agreement form. 
For RDE, the monitor will mark completed and approved screens at each visit.
Upon completion or premature discontinuation of the study, the monitor will conduct site 
closure activities with the investigator or site staff, as appropriate, in accordance with 
applicable regulations, GCP, and Pfizer procedures.
11.3.
Record retention
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere) in a safe and 
secure location. The records must be easily accessible, when needed (e.g. audit or 
inspection), and must be available for review in conjunction with assessment of the 
facility, supporting systems, and staff. Where permitted by applicable laws/regulations or 
institutional policy, some or all of these records can be maintained in a validated format 
other than hard copy (e.g. microfiche, scanned, electronic); however, caution needs to be 
exercised before such action is taken. The investigator must ensure that all reproductions 
are legible and are a true and accurate copy of the original and meet accessibility and 
retrieval standards, including re-generating a hard copy, if required. Furthermore, the 
investigator must ensure that an acceptable back-up of the reproductions exists and that 
there is an acceptable quality control procedure in place for making these reproductions.
Pfizer will inform the investigator/institution of the time period for retaining these 
records to comply with all applicable regulatory requirements. However, the 
investigator/institution should seek the written approval of the sponsor before proceeding 
with the disposal of these records. The minimum retention time will meet the strictest 
standard applicable to a particular site, as dictated by ICH GCP, any institutional 
requirements, applicable laws or regulations, or Pfizer standards/procedures; otherwise, 
the minimum retention period will default to 15 years.
The investigator/institution must notify Pfizer of any changes in the archival 
arrangements, including, but not limited to archival at an off-site facility, transfer of 
ownership of the records in the event the investigator leaves the site.
11.4.
Quality assurance
To ensure compliance with GCP and all applicable regulatory requirements, Pfizer may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory 
inspection of this study. Such audits/inspections can occur at any time during or after 
completion of the study. If an audit or inspection occurs, the investigator and institution 
agree to allow the auditor/inspector direct access to all relevant documents and to allocate 
his/her time and the time of his/her staff to the auditor/inspector to discuss findings and 
any relevant issues.

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11.5.
Posting of information on publicly available clinical trial 
registers and publication policy
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical 
Trials Database (EudraCT), and/or www.pfizer.com, and other public registries in 
accordance with applicable local laws/regulations. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country 
in which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies conducted in patients that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  
US Basic Results are submitted for posting within 1 year of the primary completion date 
for studies in adult populations or within 6 months of the primary completion date for 
studies in pediatric populations.
Primary completion date is defined as the date that the final subject was examined or 
received an intervention for the purposes of final collection of data for the primary 
outcome, whether the clinical study concluded according to the prespecified protocol or 
was terminated.
EudraCT
Pfizer posts EU Basic Results on EudraCT for all Pfizer-sponsored interventional studies 
that are in scope of EU requirements.  EU Basic Results are submitted for posting within 
1 year of the primary completion date for studies in adult populations or within 6 months 
of the primary completion date for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com 
for Pfizer-sponsored interventional studies at the same time the US Basic Results 
document is posted to www.clinicaltrials.gov.
11.6.
Provision of study results to investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by 
principal investigator of the results of the study based on information collected or 
generated by principal investigator, whether or not the results are favorable to the Pfizer 
product.  However, to ensure against inadvertent disclosure of confidential information or 
unprotected inventions, the investigator will provide Pfizer an opportunity to review any 

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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 entitled Publications by Investigators, 
the defined terms shall have the meanings given to them in the CSA.
If there is any conflict between the CSA and any Attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will 
control as to any issue regarding treatment of study subjects, and the CSA will control as 
to all other issues.
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 
investigational product, Pfizer should be informed immediately.  
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes 
aware of.

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12.
COUNTRY SPECIFIC REQUIREMENTS
Not applicable.

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13.
REFERENCES
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editor. Textbook of Pediatric Infectious Diseases. Philadelphia:WB Saunders, 1998:1143-
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Andrews N, Borrow R, Miller E. Validation of serological correlate of protection for 
meningococcal C conjugate vaccine by using efficacy estimates from postlicensure 
surveillance in England. Clin Diagn Lab immunol. 2003;10 (5):780-786.
Balmer P, Borrow R. Serologic correlates of protection for evaluating the response to 
meningococcal vaccines. Expert Rev Vaccines. 2004;3(1):77-87.
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Haemophilus influenzae type b (HbOC) vaccine in a United States population of 61080 
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Booy R, Moxon ER, MacFarlane JA et al. Efficacy of Haemophilus influenzae type b 
conjugate vaccines in the Oxford region. Lancet. 1992;340:847.
CDC. Inadvertent Misadministration of Meningococcal Conjugate Vaccine - United 
States, June-August 2005. MMWR. 2006;55(37):1016-1017.
CDC. Meningococcal Disease - New England, 1993-1998. MMWR. 1999;48(29):629-
633.
Connolly M, Noah N. Is group C meningococcal disease increasing in Europe? A report 
of surveillance of meningococcal infection in Europe 1993-6. Epidemiol Infect. 
1999;122(1):41-49.
Decosas J, Koama JB. Chronicle of an outbreak foretold: meningococcal meningitis 
W135 in Burkina Faso. Lancet Infect Dis. 2002;2(12):763-765.
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marketing authorisation under Regulation (EC) No 726/2004 of the European Parliament 
and of the Council for “Nimenrix – Meningococcal Group A, C, W-135 and Y conjugate 
vaccine” a medicinal product for human use. C(2012)2813 
http://ec.europa.eu/health/documents/community-
register/2012/20120420120470/dec_120470_en.pdf Accessed 07 February 2013
European Public Assessment Report (EPAR). May 2011. 
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uman/001095/WC500090147.pdf. Accessed on 07 February 2013
Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus. 
I. The role of humoral antibodies. J Exp Med. 1969;129:1307-1326.

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Harrison LH, Pass MA, Mendelsohn AB, et al. Invasive meningococcal disease in 
adolescents and young adults. JAMA. 2001;286(6):694–699.
Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal disease. 
Vaccine. 2009;27S:B51-B63.
Hassan-King MK, Wall RA, Greenwood BM. Meningococcal carriage, meningococcal 
disease and vaccination. J Infect 1988 Jan;16 (1):55-59.
Jackson LA, Schuchat A, Reeves MW et al. Serogroup C meningococcal outbreaks in the 
United States: an emerging threat. JAMA. 1995;273:383-389.
Kirsch EA, Barton RP, Kitchen L et al. Pathophysiology, treatment and outcome of 
meningococcemia: a review and recent experience. Pediatr Infect Dis J. 1996;11:967-
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Lingappa J, Rosenstein N, Zell E et al. CDC - Surveillance for meningococcal disease 
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2001;19(1):4566-4575.
Maslanka SE, Gheesling LL, Libutti DE et al. Standardization and a multilaboratory 
comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. Clin. 
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Menactra Approval Letter. April 2011. 
http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm252511.ht
m. Accessed 22 June 2011
Menactra Product Information. US. May 2009.
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Menveo Product Monograph. Canada. May 2010.
Morley SL, Pollard AJ. Vaccine prevention of meningococcal disease coming soon?. 
Vaccine. 2002;20:666-687.
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1998;55(5):347-366.
Pollard AJ, Frasch C. Development of natural immunity to Neisseria meningitidis. 
Vaccine. 2001;19:1327-1346.
Wilder-Smith A, Goh KT, Barkham T et al. Hajj-associated outbreak strain of Neisseria 
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APPENDIX A
LABORATORY ASSAYS
The following tests will be performed:

Functional anti-meningococcal serogroup activity using rabbit complement as 
exogenous complement source (rSBA-MenA, rSBA-MenC, rSBA-MenW-135, 
rSBA-MenY) will be determined by a serum bactericidal test according to the 
Centers for Disease Control and Prevention (CDC) protocol [Maslanka, 1997]. The 
testing will be performed at the laboratory of Public Health England (PHE) in the 
United Kingdom. Titres will be expressed as the reciprocal of the last dilution 
resulting in at least 50% inhibition.

Functional anti-meningococcal serogroup activity using human complement as 
exogenous complement source (hSBA-MenA, hSBA-MenC, hSBA-MenW-135, 
hSBA-MenY) will be determined by a serum bactericidal assay based on the CDC 
protocol [Maslanka, 1997]. The testing will be performed at the Neomed Institute.
The cut-off of the test is a dilution of 1:4. Titres will be expressed as the reciprocal 
of the dilution resulting in 50% inhibition.

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APPENDIX B
CLINICAL LABORATORIES
Table 11 presents the Neomed Institute.
Table 11
Neomed Institute
Laboratory
Address
Testing
Neomed Institute –
Laval, Quebec, 
Canada
Biospecimen Reception - Clinical Serology
525 Cartier blvd West - Laval - Quebec - Canada -
H7V 3S8
hSBA testing at all time-points
Table 12 presents the outsourced laboratory.
Table 12
Outsourced laboratory
Laboratory
Address
Testing
PHE laboratory
Vaccine Evaluation Unit
Manchester Medical Microbiology Partnership
2nd Floor, Clinical Sciences Building II
Manchester Royal Infirmary
Oxford Road
Manchester, England
M13 9WZ
rSBA testing at all time-points