A PHASE IIIB, OPEN, MULTI-CENTER STUDY TO EVALUATE THE LONG-TERM ANTIBODY PERSISTENCE AT 6, 7, 8, 9 AND 10 YEARS AFTER THE ADMINISTRATION OF ONE DOSE OF MENINGOCOCCAL CONJUGATE VACCINE MENACWY-TT VERSUS ONE DOSE OF MENINGOCOCCAL POLYSACCHARIDE VACCINE MENCEVAX(REGISTERED) ACWY, AND TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A BOOSTER DOSE OF MENACWY-TT VACCINE ADMINISTERED 10 YEARS AFTER PRIMARY VACCINATION OF 11-55 YEAR OLD SUBJECTS WITH MENACWY-TT OR MENCEVAX (REGISTERED) ACWY.
Phase: PHASE3
Conditions: Infections, Meningococcal
Sponsor: Pfizer

C0921002 (MENACWY-TT-099 EXT 015 Y6,7,8,9,10; 116725)
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Clinical Study Protocol
Sponsor:
Pfizer, Inc.
235 East 42nd Street
New York, NY 10017, United States
Primary Study vaccines
Meningococcal serogroups A, C, W-135, Y tetanus 
toxoid conjugate (MenACWY-TT) vaccine
(Nimenrix® PF-06866681).
Study number and
Abbreviated Title
C0921002 (MENACWY-TT-099 EXT 015 
Y6,7,8,9,10; formerly GSK 116725)
European Clinical Trials 
Database (EudraCT) 
Number
2012-005639-10
Date of protocol
Final: 07 November 2012
Date of protocol 
amendment
Protocol Amendment  1: 29 February 2016
Title
The long-term antibody persistence of MenACWY-TT 
vaccine (PF-06866681) versus Mencevax® ACWY in 
healthy adolescents and adults and booster response to 
MenACWY-TT vaccine administered at 10 years post-
primary vaccination.
Detailed Title
A phase IIIb, open, multi-center study to evaluate the 
long-term antibody persistence at 6, 7, 8, 9 and 10 
years after the administration of one dose of 
meningococcal conjugate vaccine MenACWY-TT 
versus one dose of meningococcal polysaccharide 
vaccine Mencevax® ACWY, and to evaluate the safety 
and immunogenicity of a booster dose of MenACWY-
TT vaccine administered 10 years after primary 
vaccination of 11-55 year old subjects with 
MenACWY-TT or Mencevax® ACWY.
 
 
 
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Protocol Amendment 1 Sponsor Signatory Approval
Study number and 
Abbreviated Title
C0921002  (MENACWY-TT-099 EXT 015 
Y6,7,8,9,10; formerly GSK 116725) 
EudraCT number 
2012-005639-10
Date of protocol
Protocol Amendment 1: 29 February 2016
Detailed Title
A phase IIIb, open, multi-center study to evaluate the 
long-term antibody persistence at 6, 7, 8, 9 and 10 
years after the administration of one dose of 
meningococcal conjugate vaccine MenACWY-TT 
versus one dose of meningococcal polysaccharide 
vaccine Mencevax® ACWY, and to evaluate the safety 
and immunogenicity of a booster dose of 
MenACWY-TT vaccine administered 10 years after 
primary vaccination of 11-55 year old subjects with 
MenACWY-TT or Mencevax® ACWY. 
Sponsor signatory
 MD
 Pfizer Vaccines Clinical Research
Signature
Date
PPD
PPD
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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 1
29 February 2016
Protocol amended to reflect sponsorship 
change to Pfizer following the 
acquisition of the GSK meningococcal 
vaccine Nimenrix® by Pfizer on 01 
October 2015.
Sponsor name updated throughout the 
protocol to Pfizer.
Addition of the EudraCT number.
List of abbreviations and glossary of 
terms updated.
GSK contact information removed.
Clarification that the 400 subjects 
eligible for this extension study are those 
who participated in study MENACWY-
TT-015 in the Philippines.
The single reference safety document 
was revised from the investigator’s 
brochure to the core data sheet. 
Information related to electronic SAE 
and pregnancy reports replaced by paper 
SAE and EDP reports throughout the 
protocol.
Information related to GSK 
randomization and treatment allocation 
system removed. 
Secondary objectives updated to clarify 
that the anti-TT analysis is done pre and 
post-booster dose.
Interval between dose 1 in the primary 
vaccination study and Visit 5 booster 
dose increased to 118 to 126 months 
(section 5.5).
Volume of blood sample collected pre-
and post-booster dose increased to 10 
mL (sections 5.6.12.1 and 5.7.2).
Anti-TT assay changed to Direct 
Luminex Immuno Assay (dLIA) 
performed by PPD (sections 5.7.3 and 
5.7.5).
Study cohorts / data sets to be analyzed, 
updated for clarification (section 10.4). 
Table 16 updated to clarify that the
timeframe allowed for pregnancy and 
pregnancy follow-up reporting is 
24 hours after receipt or awareness of the 
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information using paper SAE and EDP 
reports.
Sections updated / added  in line with 
standard Pfizer policy: 
- 4.2 Inclusion criteria for enrolment
- 4.3 Exclusion criteria for enrolment
- 5.1 Regulatory and ethical 
considerations, including the informed 
consent process
- 5.2.2 Study group and treatment 
allocation
- 5.5.5 Outline of study procedures
- 5.6.1 Informed consent
- 5.6.7 Pre-vaccination assessment of 
contraception
- 5.6.8 Urine pregnancy test
- 5.7 Biological sample handling and 
analysis
- 5.7.3 Laboratory assays 
- 6.2 Storage and handling of study 
vaccines
- 6.5.2 Concomitant medications/
products/vaccines that may lead to the 
elimination of a subject from the ATP 
analyses
- 8.1.1 Definition of an adverse event
- 8.1.2 Medication errors
- 8.1.3 Occupational exposure
- 8.1.4 Exposure during pregnancy
- 8.1.5 Definition of a serious adverse 
event
- 8.1.6.1 Solicited local (injection-site) 
adverse events
- 8.2.1 Time period for detecting and 
recording adverse events, serious adverse 
events and pregnancies
- 8.2.3.2.2 Assessment of causality
- 8.3.1 Prompt reporting of serious 
adverse events, pregnancies, and other 
events
- 8.3.3 Completion and transmission of 
pregnancy reports
- 8.6 Subject card
- 9.1 Subject completion
- 9.2.1 Subject withdrawal from the 
study
- 10.3 Determination of sample size
-11.5 Posting of information on publicly 
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available clinical trial registers and 
publication policy
-11.6 Reporting of safety issues and 
serious breaches of the protocol or ICH 
GCP
- Appendix A Laboratory assays
- Appendix B Clinical laboratories
Original protocol
07-November-2012
Not applicable (NA)
This amendment incorporates all revisions to date, including amendments made at the request 
of country health authorities, institutional review boards/ethics committees (IRBs/ECs), etc. 
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Protocol Amendment 1 Investigator Agreement
I agree:

To conduct the study in compliance with this protocol, any future protocol amendments 
or protocol administrative changes, with the terms of the clinical trial agreement and 
with any other study conduct procedures and/or study conduct documents provided by
Pfizer.

To assume responsibility for the proper conduct of the study at this site.

That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements. 

To ensure that all persons assisting me with the study are adequately informed about the  
investigational vaccines 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 vaccines, and more generally about his/her financial ties 
with the sponsor. Pfizer will use and disclose the information solely for the purpose of 
complying with regulatory requirements.
Hence I:

Agree to supply Pfizer with any necessary information regarding ownership interest and 
financial ties (including those of my spouse and dependent children).

Agree to promptly update this information if any relevant changes occur during the 
course of the study and for one year following completion of the study. 

Agree that Pfizer may disclose any information it has about such ownership interests and 
financial ties to regulatory authorities.

Agree to provide Pfizer with an updated Curriculum Vitae and other documents required 
by regulatory agencies for this study.
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Study number and 
Abbreviated Title
C0921002 (MENACWY-TT-099 EXT 015 
Y6,7,8,9,10; formerly GSK 116725) 
Date of protocol
Protocol Amendment 1: 29 February 2016
EudraCT number 
2012-005639-10
Detailed Title
A phase IIIb, open, multi-center study to evaluate the 
long-term antibody persistence at 6, 7, 8, 9 and 10 
years after the administration of one dose of 
meningococcal conjugate vaccine MenACWY-TT 
versus one dose of meningococcal polysaccharide 
vaccine Mencevax® ACWY, and to evaluate the safety 
and immunogenicity of a booster dose of 
MenACWY-TT vaccine administered 10 years after 
primary vaccination of 11-55 year old subjects with 
MenACWY-TT or Mencevax® ACWY. 
Investigator name
Signature
Date
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SYNOPSIS
Detailed Title
A phase IIIb, open, multi-center study to evaluate the long-
term antibody persistence at 6, 7, 8, 9 and 10 years after the 
administration of one dose of meningococcal conjugate 
vaccine MenACWY-TT versus one dose of meningococcal 
polysaccharide vaccine Mencevax ACWY, and to evaluate the 
safety and immunogenicity of a booster dose of MenACWY-
TT vaccine administered 10 years after primary vaccination of 
11-55 year old subjects with MenACWY-TT or Mencevax
ACWY. 
Indication
Active immunization against invasive disease caused by 
Neisseria meningitidis serogroups A, C, W-135, and Y in 
healthy subjects aged 11 to 55 years of age.
Rationale for the 
study and study 
design
In study MENACWY-TT-015, 500 healthy subjects between 
11 and 55 years of age were randomized using a (3:1) ratio to 
receive either a single dose of MenACWY-TT vaccine or 
meningococcal PS vaccine. The subjects were followed up 
over five years post-vaccination. There is interest in the 
assessment of long term persistence of serological markers of 
protection following conjugate vaccination. The main purpose 
of this study is to evaluate the antibody persistence from 6, 7, 
8, 9 to 10 years post-administration of MenACWY-TT 
conjugate vaccine as compared to Mencevax ACWY when 
given to healthy subjects 11 to 55 years of age. In addition, 
the safety and immunogenicity of a booster dose of 
MenACWY-TT vaccine administered to all eligible subjects 
10 years after the primary vaccination will be evaluated.
The primary vaccination study MenACWY-TT-015 was 
conducted in Saudi Arabia and in the Philippines. The 
MenACWY-TT-099 study will only be conducted in the 
Philippines.
Objective(s)
Primary
Long-term persistence phase: Six, seven, eight, nine and 
ten years after primary vaccination with MenACWY-TT 
or Mencevax ACWY, in Study MENACWY-TT-015

To evaluate the long-term persistence of the serum 
bactericidal (antibody) titers induced by MenACWY-TT 
vaccine as compared to Mencevax ACWY when 
administered to individuals 11-55 years of age in terms of
the percentage of subjects with Neisseria meningitidis
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serogroup A (MenA), serogroup C (MenC), serogroup 
W-135 (MenW-135), and serogroup Y (MenY) titers 
1:8, 1:128 and Geometric mean titres (GMTs) as 
measured by a serum bactericidal assay using rabbit 
complement (rSBA).
Secondary
One month post-booster vaccination with MenACWY-TT 
vaccine ten years after primary vaccination:

To evaluate the immunogenicity of a booster vaccination 
of MenACWY-TT with respect to the percentage of 
subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-
135, and rSBA-MenY antibody titers ≥ 1:8, 1:128 and 
GMTs.

To evaluate the immunogenicity of booster vaccination in 
terms of the percentage of subjects with rSBA-MenA, 
rSBA-MenC, rSBA-MenW-135, rSBA-MenY vaccine 
response*.
*rSBA vaccine responses for serogroups A, C, W-135 and Y are 
defined as:

For initially seronegative subjects (pre-vaccination titer below 
the cut-off of 1:8): rSBA antibody titers ≥ 1:32 one month after 
vaccination, and

For initially seropositive subjects (pre-vaccination titer 1:8): 
rSBA antibody titers at least four times the pre-vaccination 
antibody titers, one month after vaccination.
Pre-booster and one month post-booster vaccination with 
MenACWY-TT vaccine ten years after primary 
vaccination

To evaluate the percentage of subjects with anti-TT 
concentrations ≥ 0.1 IU/mL, ≥1.0 IU/mL and GMCs. 
Secondary safety objectives:

To evaluate the safety and reactogenicity of a booster 
vaccination dose of MenACWY-TT in terms of 
solicited symptoms, unsolicited symptoms, Serious 
Adverse Events (SAEs) and New Onset of Chronic 
Illnesses (NOCIs) (e.g., autoimmune disorders, 
asthma, type I diabetes and allergies)
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Study design

Experimental design: Phase IIIb, open, multi-center study 
with two parallel groups.

Duration of the study: 
Persistence phase
–
Epoch 001: Persistence Visit 1 [Month 72 (Year 6) 
post primary vaccination] 
–
Epoch 002: Persistence Visit 2 [Month 84 (Year 7) 
post primary vaccination] 
–
Epoch 003: Persistence Visit 3 [Month 96 (Year 8) 
post primary vaccination] 
–
Epoch 004: Persistence Visit 4 [Month 108 (Year 9) 
post primary vaccination]
Booster phase
–
Epoch 005: Booster starting at Visit 5 [Month 120 
(Year 10) post primary vaccination] and ending at the 
Phone Contact (Month 126 or six months post-
booster)

Study groups:

ACWY-TT group: all subjects vaccinated with
MenACWY-TT in study MENACWY-TT-015 will 
be assigned to this group

MenPS group: all subjects vaccinated with Mencevax 
ACWY in study MENACWY-TT-015 will be 
assigned to this group
Synopsis Table 1
Study groups and epochs foreseen in the study
Study groups
Number of 
subjects*
Age (Min/Max)
Epochs
Epoch 001, Epoch 002, Epoch 
003, Epoch 004, Epoch 005
ACWY-TT group
252
11-55 years at primary vaccination
x
MenPS group
84
11-55 years at primary vaccination
x
*The actual sample size of this study with respect to the analysis of persistence and safety and immunogenicity 
post-booster is determined by a) the sample size of the primary vaccination study MENACWY-TT-015 (107386), b) 
by the actual enrolments rate at the YR6-10 extension study, and c) by the actual annual dropout rate. For more 
information see Section 10.3.
Synopsis Table 2
Study groups and treatment foreseen in the study
Treatment name
Vaccine/Product name
Study Groups
ACWY-TT group 
MenPS group 
MenACWY-TT
MenACWY-TT
● 
● 
Saline diluent *
●
● 
*The lyophilized pellet of MenACWY-TT vaccine is to be reconstituted with the supplied saline solution.

Control: active control for persistence phase (MenPS 
group), uncontrolled for booster phase (all subjects receive 
the same booster vaccination).

Vaccination schedule: At Visit 5 (Month 120 post primary 
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vaccination), one dose of MenACWY-TT will be 
administered to the subjects in both study groups.

Treatment allocation: NA

Blinding: open-label
Synopsis Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001  
open  
Epoch 002  
open  
Epoch 003
open  
Epoch 004
open  
Epoch 005
open  

Blood sampling: at each study visit a blood sample will be 
collected for each subject enrolled. 

Type of study: extension of other protocol [MENACWY-
TT-015 (107386); 016 EXT:015 Y1 (107392); 017 
EXT:015 Y2 (107398); 018 EXT:015 Y3 (107402); 019 
EXT:015 Y4 (107404); 020 EXT:015 Y5 (107406)]

Data collection: Electronic Case Report Form (eCRF)
Number of subjects
Four hundred subjects (299 in the ACWY-TT group and 101 in 
the MenPS group) were enrolled and vaccinated in study 
MENACWY-TT-015 in the Philippines. The subjects who 
completed the vaccination phase of study MenACWY-TT-015 
and received either MenACWY-TT vaccine or Mencevax 
ACWY will be eligible for this study if they meet the inclusion 
criteria and no exclusion criteria.
Endpoints
Primary
Immunogenicity with respect to the components of the 
investigational vaccine six, seven, eight, nine and ten years 
after primary vaccination in Study MENACWY-TT-015:

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-
MenY antibody titres 1:8, 1:128 and GMTs.
Secondary
Immunogenicity with respect to the components of the 
investigational vaccine one month post-booster vaccination 
at ten years after primary vaccination:

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-
MenY antibody titers ≥1:8, 1:128, GMTs and rSBA 
vaccine response.
Immunogenicity with respect to the components of the 
investigational vaccine pre-booster and one month post-
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booster vaccination at ten years after primary vaccination:

Anti-TT concentrations ≥0.1 IU/mL, ≥1.0 IU/mL and 
GMCs.
Safety and reactogenicity

Occurrence of solicited local and general symptoms on 
days 0-3 following the booster vaccination.

Occurrence of unsolicited symptoms up to 31 days 
following booster vaccination.

Occurrence of serious AEs, and new onset chronic 
illness(es) (e.g. autoimmune disorders, asthma, type 1 
diabetes and allergies), GBS and meningococcal disease 
from administration of the vaccine dose until study end.
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TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT 1 SPONSOR SIGNATORY APPROVAL................ 2
DOCUMENT HISTORY........................................................................................ 3
PROTOCOL AMENDMENT 1 INVESTIGATOR AGREEMENT .......................... 6
SYNOPSIS........................................................................................................... 8
LIST OF ABBREVIATIONS................................................................................20
GLOSSARY OF TERMS.....................................................................................23
TRADEMARKS...................................................................................................27
1.
INTRODUCTION ..........................................................................................28
1.1.
Background........................................................................................28
1.2.
Rationale for the study and study design ...........................................28
2.
OBJECTIVES...............................................................................................29
2.1.
Primary objective................................................................................29
2.2.
Secondary objectives.........................................................................29
3.
STUDY DESIGN OVERVIEW.......................................................................30
4.
STUDY COHORT .........................................................................................31
4.1.
Number of subjects/centres ...............................................................31
4.2.
Inclusion criteria for enrolment ...........................................................32
4.3.
Exclusion criteria for enrolment..........................................................33
5.
CONDUCT OF THE STUDY.........................................................................35
5.1.
Regulatory and ethical considerations, including the informed 
consent process.................................................................................35
5.2.
Subject identification and randomisation of treatment........................36
5.2.1.
Subject identification ............................................................36
5.2.2.
Study group and treatment allocation...................................36
5.3.
Method of blinding..............................................................................37
5.4.
General study aspects .......................................................................37
5.5.
Outline of study procedures ...............................................................37
5.6.
Detailed description of study procedures ...........................................41
5.6.1.
Informed consent .................................................................41
5.6.2.
Check inclusion and exclusion criteria .................................41
5.6.3.
Collect demographic data.....................................................41
5.6.4.
Medical history since last visit done .....................................42
5.6.5.
Vaccination history...............................................................42
5.6.6.
History directed physical examination..................................42
5.6.7.
Pre-vaccination assessment of contraception......................42
5.6.8.
Urine pregnancy test............................................................42
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5.6.9.
Check contraindications, warnings and precautions to 
vaccination ...........................................................................43
5.6.10.
Assess pre-vaccination body temperature ...........................43
5.6.11.
Study group and treatment allocation...................................43
5.6.12.
Sampling ..............................................................................43
5.6.12.1. Blood sampling for immune response 
assessments ........................................................43
5.6.13.
Study Vaccine administration...............................................43
5.6.14.
Check and record concomitant medication/vaccination 
and intercurrent medical conditions......................................44
5.6.15.
Recording of AEs, SAEs and pregnancies...........................44
5.6.15.1. Recording of GBS and NOCIs .............................44
5.6.15.2. Recording of data during the phone contact at 
Month 126............................................................45
5.6.16.
Study conclusion..................................................................45
5.7.
Biological sample handling and analysis............................................45
5.7.1.
Use of specified study materials...........................................46
5.7.2.
Biological samples ...............................................................46
5.7.3.
Laboratory assays................................................................46
5.7.4.
Biological samples evaluation ..............................................48
5.7.4.1.
Immunological read-outs......................................48
5.7.5.
Immunological correlates of protection.................................48
5.7.5.1.
Communication of individual immunological 
assay results to study investigator .......................49
6.
STUDY VACCINE AND ADMINISTRATION................................................50
6.1.
Description of study vaccine ..............................................................50
6.2.
Storage and handling of study vaccines.............................................50
6.3.
Dosage and administration of study vaccines ....................................51
6.4.
Warnings and precautions .................................................................51
6.5.
Concomitant medication/product and concomitant vaccination..........52
6.5.1.
Recording of concomitant medications/products and 
concomitant vaccination.......................................................52
6.5.2.
Concomitant medications/products/vaccines that may 
lead to the elimination of a subject from ATP analyses........52
6.6.
Intercurrent medical conditions that may lead to elimination of a 
subject from ATP analyses ................................................................53
7.
HEALTH ECONOMICS ................................................................................54
8.
SAFETY........................................................................................................54
8.1.
Safety definitions................................................................................54
8.1.1.
Definition of an adverse event..............................................54
8.1.2.
Medication Errors.................................................................55
8.1.3.
Occupational Exposure ........................................................56
8.1.4.
Exposure During Pregnancy ................................................56
8.1.5.
Definition of a serious adverse event ...................................57
8.1.6.
Solicited adverse events ......................................................58
8.1.6.1.
Solicited local (injection-site) adverse events.......58
8.1.6.2.
Solicited general adverse events .........................59
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8.1.7.
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events.....................................................................59
8.1.8.
Adverse events of specific interest.......................................60
8.1.8.1.
List of New Onset of Chronic Illnesses.................60
8.1.9.
Pregnancy............................................................................63
8.2.
Detecting and recording adverse events, serious adverse events 
and pregnancies.................................................................................64
8.2.1.
Time period for detecting and recording adverse events, 
serious adverse events and pregnancies.............................64
8.2.2.
Post-Study adverse events and serious adverse events......67
8.2.3.
Evaluation of adverse events and serious adverse events ..67
8.2.3.1.
Active questioning to detect adverse events 
and serious adverse events .................................67
8.2.3.2.
Assessment of adverse events ............................67
8.2.3.2.1.
Assessment of intensity.....................67
8.2.3.2.2.
Assessment of causality ....................69
8.2.3.3.
Assessment of outcomes.....................................70
8.2.3.4.
Medically attended visits ......................................71
8.2.3.5.
Adverse events of specific interest.......................71
8.3.
Reporting of serious adverse events, pregnancies, and other 
events ................................................................................................71
8.3.1.
Prompt reporting of serious adverse events, 
pregnancies, and other events.............................................71
8.3.2.
Completion and transmission of SAE reports.......................72
8.3.3.
Completion and transmission of pregnancy reports .............72
8.3.4.
Updating of SAE and pregnancy information after 
freezing of the subject’s eCRF .............................................72
8.3.5.
Regulatory reporting requirements for serious adverse 
events ..................................................................................73
8.4.
Follow-up of adverse events, serious adverse events, and 
pregnancies .......................................................................................73
8.4.1.
Follow-up of adverse events and serious adverse events....73
8.4.1.1.
Follow-up during the study...................................73
8.4.1.2.
Follow-up after the subject is discharged from 
the study ..............................................................73
8.4.2.
Follow-up of pregnancies .....................................................74
8.5.
Treatment of adverse events .............................................................74
8.6.
Subject card .......................................................................................74
9.
SUBJECT COMPLETION AND WITHDRAWAL .........................................75
9.1.
Subject completion.............................................................................75
9.2.
Subject withdrawal .............................................................................75
9.2.1.
Subject withdrawal from the study........................................75
9.2.2.
Subject withdrawal from investigational vaccine ..................76
10. STATISTICAL METHODS............................................................................77
10.1. Primary endpoint................................................................................77
10.2. Secondary endpoints .........................................................................77
10.3. Determination of sample size.............................................................77
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10.4. Study cohorts/ data sets to be analysed ............................................80
10.4.1.
Total cohort at Year X ..........................................................80
10.4.2.
According-To-Protocol (ATP) cohort for persistence at 
Year X ..................................................................................80
10.4.3.
Total Vaccinated Cohort at Visit 6 (Month 121)....................80
10.4.4.
According-To-Protocol (ATP) cohort for safety at Visit 6 
(Month 121)..........................................................................81
10.4.5.
According To Protocol (ATP) cohort for immunogenicity 
at Visit 6 (Month 121)...........................................................81
10.5. Derived and transformed data............................................................81
10.5.1.
Immunogenicity....................................................................81
10.5.2.
Reactogenicity and Safety....................................................82
10.6. Persistence analyses .........................................................................82
10.6.1.
Analysis of demographics/baseline characteristics ..............82
10.6.2.
Analysis of persistence ........................................................83
10.6.3.
Analysis of safety (Persistence epoch) ................................83
10.7. Post-booster analyses........................................................................83
10.7.1.
Analysis of demographics/baseline characteristics ..............83
10.7.2.
Analysis of post-booster immunogenicity .............................84
10.7.3.
Analysis of post-booster safety ............................................84
10.8. Interpretation of analyses...................................................................85
10.9. Conduct of analyses...........................................................................85
10.9.1.
Sequence of analyses..........................................................85
10.9.2.
Statistical considerations for interim analyses......................85
11. ADMINISTRATIVE MATTERS .....................................................................85
11.1. Case Report Form/Remote Data Entry instructions ...........................86
11.2. Study Monitoring ................................................................................86
11.3. Record retention.................................................................................87
11.4. Quality assurance ..............................................................................87
11.5. Posting of information on publicly available clinical trial registers 
and publication policy.........................................................................88
11.6. Reporting of Safety Issues and Serious Breaches of the Protocol 
or ICH GCP........................................................................................89
11.7. Provision of study results to investigators ..........................................90
12. COUNTRY SPECIFIC REQUIREMENTS.....................................................90
13. REFERENCES .............................................................................................90
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LIST OF TABLES
PAGE
Table 1
Study groups and epochs foreseen in the study............................31
Table 2
Study groups and treatment foreseen in the study ........................31
Table 3
Blinding of study epochs................................................................31
Table 4
List of study procedures.................................................................38
Table 5
Intervals between study visits ........................................................41
Table 6
Biological samples .........................................................................46
Table 7
Humoral Immunity (Antibody determination)..................................47
Table 8
Immunological read-outs................................................................48
Table 9
Study vaccine ................................................................................50
Table 10
Dosage and administration ............................................................51
Table 11
Solicited local adverse events........................................................58
Table 12
Solicited general adverse events...................................................59
Table 13
List of NOCIs .................................................................................61
Table 14
Reporting periods for adverse events, serious adverse events 
and pregnancies ............................................................................66
Table 15
Intensity scales for solicited symptoms in adults............................68
Table 16
Timeframes for submitting serious adverse event, pregnancy 
and other events reports................................................................72
Table 17
Exact 95% confidence intervals of the percentage of subjects 
with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-
MenY titers ≥ 1:8............................................................................79
Table 18
Outsourced laboratories.................................................................94
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LIST OF FIGURES
PAGE
Figure 1
Study design figure ........................................................................30
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LIST OF APPENDICES
PAGE
APPENDIX A .................................................................................LABORATORY ASSAYS
93
APPENDIX B ...........................................................................CLINICAL LABORATORIES
94
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LIST OF ABBREVIATIONS
AE
Adverse event
ATP
According-to-protocol
CDC
Centers for Disease Control and Prevention (United States of 
America)
CDS
Core Data Sheet 
CI
Confidence interval
CRF
Case report form
CSA
Clinical Study Agreement
D
Deltoid
dLIA
Direct Luminex  Immuno Assay
DU
Dispensable unit
eCRF
Electronic case report form
EDD
Estimated date of delivery
EDP
Exposure during pregnancy 
EGA
Estimated gestational age
ESFU
Extended Safety Follow-Up
EU
European Union
EudraCT
European Clinical Trials Database
GBS
Guillain-Barré Syndrome
GCP
Good Clinical Practice
GMC
Geometric mean concentration 
GMT
Geometric mean titre
GSK
GlaxoSmithKline 
HIV
Human immunodeficiency virus
IAF 
Informed Assent Form 
ICF
Informed Consent Form 
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
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IM
Intramuscular(ly)
IRB
Institutional Review Board
IRT 
Interactive Response Technology 
LAR
Legally acceptable representative
LLOQ
Lower limit of quantitation
LMP
Last menstrual period
MACDP
Metropolitan Atlanta Congenital Defects Program
MedDRA
Medical Dictionary for Regulatory Activities
MenA
Neisseria meningitidis serogroup A
MenC
Neisseria meningitidis serogroup C
MenW-135
Neisseria meningitidis serogroup W-135
MenY
Neisseria meningitidis serogroup Y
MenACWY-TT
Meningococcal serogroups A, C, W-135, Y tetanus toxoid 
conjugate vaccine
mL
milliliter
NA
Not Applicable
ND
Non dominant
NOCI
New Onset of Chronic Illness
PHE
Public Health England
PI
Prescribing Information
pIMD
Potential immune mediated disorder
PPD
Pharmaceutical Product Development
PS
Polysaccharide
PSA
Polysaccharide Neisseria meningitidis serogroup A
PSC
Polysaccharide Neisseria meningitidis serogroup C
PSW-135
Polysaccharide Neisseria meningitidis serogroup W-135
PSY
Polysaccharide Neisseria meningitidis serogroup Y
RDE
Remote Data Entry
rSBA-MenA
Serum bactericidal assay/activity against Neisseria 
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meningitidis serogroup A (using rabbit complement)
rSBA-MenC
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup C (using rabbit complement)
rSBA-MenW-135
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup W-135 (using rabbit complement)
rSBA-MenY
Serum bactericidal assay/activity against Neisseria 
meningitidis serogroup Y (using rabbit complement)
SAE
Serious adverse event
SBA
Serum bactericidal assay
SDV
Source Document Verification
SPC
Summary of Product Characteristics
SPM
Study Procedures Manual 
SRSD
Single reference safety document
TT
Tetanus toxoid
US; USA
United States; United States of America
WHO
World Health Organisation
g
Microgram
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GLOSSARY OF TERMS
Adequate contraception:
Adequate contraception is defined as a contraceptive 
method with failure rate of less than 1% per year when 
used consistently and correctly and when applicable, in 
accordance with the product label for example: 

abstinence from penile-vaginal intercourse, when this 
is their preferred and usual lifestyle (any version of 
temporary or episodic abstinence is not considered 
adequate contraception),

oral contraceptives, either combined or progestogen 
alone,

injectable progestogen,

implants of etenogestrel or levonorgestrel,

estrogenic vaginal ring,

percutaneous contraceptive patches,

intrauterine device or intrauterine system,

male partner sterilisation prior to the female subject’s 
entry into the study, and this male is the sole partner 
for that subject,
The information on the male sterility can come from 
the site personnel’s review of the subject’s medical 
records; or interview with the subject on her medical 
history.

male condom combined with a vaginal spermicide 
(foam, gel, film, cream or suppository),

male condom combined with a female diaphragm, 
either with or without a vaginal spermicide (foam, 
gel, film, cream, or suppository). 
Adequate contraception does not apply to subjects of 
child bearing potential with same sex partners, when this 
is their preferred and usual lifestyle.
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 
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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 representatives (LAR).
Container number:
A number identifying a treatment to a subject, according 
to the study randomisation or treatment allocation.
Core Data Sheet:
The Core Data Sheet (CDS) represents the internal 
company medical position for all labeling documents 
worldwide. The CDS is a document containing all 
essential safety information, such as contraindications, 
warnings/precautions, and undesirable effects, which 
Pfizer requires to be included in the proposed labeling of 
all countries where the product is marketed. The Core 
Data Sheet also contains indications and dosing 
information (for all dosage forms) supported worldwide, 
as well as pharmacodynamic, pharmacokinetic and non-
clinical information that has important bearing on the safe 
and effective use of the product. Information contained in 
the Core Data Sheet is based on valid, scientific/medical 
data. The Core Data Sheet is a vehicle by which 
information on a marketed product is communicated to 
the appropriate stakeholders worldwide.
Eligible:
Qualified for enrolment into the study based upon strict 
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adherence to inclusion/exclusion criteria.
Epoch:
An epoch is a self-contained set of consecutive time 
points or a single time point from a single protocol. Self-
contained means that data collected for all subjects at all 
time points within that epoch permits drawing a complete 
conclusion to define or refine the targeted label of the 
product. Typical examples of epochs are primary 
vaccinations, boosters, yearly immunogenicity follow-
ups, and surveillance periods for efficacy or safety.
Evaluable:
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the according-to-protocol (ATP) analysis (see 
Sections 6.5.2 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. 
Menarche:
Menarche is the onset of menses for the first time in a 
young female and is preceded by several changes 
associated with puberty including breast development and 
pubic hair growth. Menarche usually occurs within 1-2 
years of breast development, thelarche. However, a young 
female can become pregnant before her first menses. 
Thus, a conservative definition of non-childbearing 
potential in a pre-menarcheal female is a young female 
who has not yet entered puberty as evidenced by lack of 
breast development (palpable glandular breast tissue).
Post-menopause
Achieved post-menopausal status, defined as follows: 
cessation of regular menses for at least 12 consecutive 
months with no alternative pathological or physiological 
cause; status may be confirmed by a serum follicle-
stimulating hormone (FSH) level confirming the 
post-menopausal state.
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Potential Immune-
Mediated Disease:
Potential immune-mediated diseases (pIMDs) are a subset 
of AEs that include autoimmune diseases and other 
inflammatory and/or neurologic disorders of interest 
which may or may not have an autoimmune aetiology.
Primary completion 
date:
The date that the final subject was examined or received 
an intervention for the purpose of final collection of data 
for the primary outcome, whether the clinical trial 
concluded according to the pre-specified protocol or was 
terminated.
Randomisation:
Process of random attribution of treatment to subjects in 
order to reduce bias of selection.
Site Monitor:
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at one or 
more investigational sites.
Solicited adverse event:
The presence/occurrence/intensity of these events is 
actively solicited from the subject or an observer during a 
specified post-vaccination follow-up period.
Subject:
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, either as a recipient of 
the vaccine(s)/product(s) or as a control.
Subject number:
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study.
Treatment:
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject, 
identified by a unique number, according to the study 
randomisation or treatment allocation.
Unsolicited adverse 
event:
Any AE reported in addition to those solicited during the 
clinical study. Also any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse 
event.
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TRADEMARKS
The following trademarks are used in the present concept protocol.
Note: In the body of the protocol (including the synopsis), the names of the vaccines will be 
written without the superscript symbol ™ or ® and will be written in italics.
Trademarks of Pfizer
Generic description
Nimenrix®
Meningococcal serogroups A, C, W-135 and 
Y tetanus toxoid conjugate vaccine
Mencevax® ACWY
Meningococcal serogroups A, C, W-135 and 
Y plain polysaccharide vaccine
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1.
INTRODUCTION
1.1.
Background
Invasive diseases caused by Neisseria meningitidis are serious threats to global health. The 
infection rates are highly age dependent. The risk of meningococcal disease is highest in 
infancy, with a secondary, slightly smaller peak in late adolescence [Rosenstein, 2001]. Case-
fatality rates of invasive disease are around 10% and up to 20% of patients who recover 
develop significant long-term sequelae [Healy, 2002]. Meningococcal disease continues to be 
endemic in both industrialized (e.g. Europe and United States of America) and developing 
countries. Epidemics occur regularly worldwide with the highest attack rates prevailing in the 
sub-Saharan countries [Harrison, 2009]. The most common serogroups causing invasive 
disease are A, B, C, W-135 and Y [Harrison, 2010]. Prevention of meningococcal disease 
relies on effective immunization programs.
GSK Biologicals has developed a tetravalent meningococcal ACWY conjugate vaccine using 
tetanus toxoid (TT) as carrier (MenACWY-TT); the vaccine has been shown to be 
immunogenic and well tolerated in individuals as of 12 months of age [Baxter, 2011; Bermal, 
2011; Knuf, 2010; Knuf, 2011; Memish, 2011; Ostergaard, 2009; Vesikari, 2011]. The 
European Commission granted a marketing authorisation for the vaccine, registered under the 
tradename of Nimenrix, on 20 April 2012 [European Commission, 2012].
Pfizer completed the acquisition of Nimenrix and Mencevax on 01 October 2015, and will 
therefore assume responsibility of sponsor for this study.
Please refer to the current Core Data Sheet (CDS) for information regarding the pre-clinical 
and clinical studies and the potential risks and benefits of MenACWY-TT conjugate vaccine.
The CDS is the single reference safety document (SRSD) for this study.
1.2.
Rationale for the study and study design
In study MENACWY-TT-015, 500 healthy subjects between 11 and 55 years of age were 
randomized using a (3:1) ratio to receive either a single dose of MenACWY-TT vaccine or 
meningococcal PS vaccine. The subjects were followed up over five years post-vaccination. 
There is interest in the assessment of long term persistence of serological markers of 
protection following conjugate vaccination. The main purpose of this study is to evaluate the 
antibody persistence from 6, 7, 8, 9 to 10 years post-administration of MenACWY-TT 
conjugate vaccine as compared to Mencevax ACWY when given to healthy subjects 11 to 55 
years of age. In addition, the safety and immunogenicity of a booster dose of MenACWY-TT 
vaccine administered to all eligible subjects 10 years after the primary vaccination will be 
evaluated.
The primary vaccination study MenACWY-TT-015 was conducted in Saudi Arabia and in 
the Philippines. The MenACWY-TT-099 study will only be conducted in the Philippines.
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2.
OBJECTIVES
2.1.
Primary objective
Long-term persistence phase: Six, seven, eight, nine and ten years after primary 
vaccination with MenACWY-TT or Mencevax ACWY, in Study MENACWY-TT-015

To evaluate the long-term persistence of the serum bactericidal (antibody) titers induced 
by MenACWY-TT vaccine as compared to Mencevax ACWY when administered to 
individuals 11-55 years of age in terms of the percentage of subjects with Neisseria 
meningitidis serogroup A (MenA), serogroup C (MenC), serogroup W-135 (MenW-135), 
and serogroup Y (MenY) titers 1:8, 1:128 and Geometric mean titres (GMTs) as 
measured by a serum bactericidal assay using rabbit complement (rSBA).
Refer to Section 10.1 for the definition of the primary endpoint(s).
2.2.
Secondary objectives
One month post-booster vaccination with MenACWY-TT vaccine ten years after 
primary vaccination:

To evaluate the immunogenicity of a booster vaccination of MenACWY-TT with respect 
to the percentage of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and 
rSBA-MenY antibody titers ≥ 1:8, 1:128 and GMTs.

To evaluate the immunogenicity of booster vaccination in terms of the percentage of 
subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY vaccine 
response*.
*rSBA vaccine responses for serogroups A, C, W-135 and Y are defined as:

For initially seronegative subjects (pre-vaccination titer below the cut-off of 1:8): rSBA antibody 
titers ≥ 1:32 one month after vaccination, and

For initially seropositive subjects (pre-vaccination titer 1:8): rSBA antibody titers at least four 
times the pre-vaccination antibody titers, one month after vaccination.
Pre-booster and one month post-booster vaccination with MenACWY-TT vaccine ten 
years after primary vaccination

To evaluate the percentage of subjects with anti-TT concentrations ≥ 0.1 IU/mL, ≥1.0 
IU/mL and GMCs. 
Secondary safety objectives:

To evaluate the safety and reactogenicity of a booster vaccination dose of MenACWY-
TT in terms of solicited symptoms, unsolicited symptoms, Serious Adverse Events 
(SAEs) and New Onset of Chronic Illnesses (NOCIs) (e.g., autoimmune disorders, 
asthma, type I diabetes and allergies)
Refer to Section 10.2 for the definition of the secondary endpoint(s).
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Table 1
Study groups and epochs foreseen in the study
Study groups
Number of 
subjects*
Age (Min/Max)
Epochs
Epoch 001, Epoch 002, Epoch 
003, Epoch 004, Epoch 005
ACWY-TT group
252 
11-55 years at primary vaccination
x
MenPS group
84
11-55 years at primary vaccination
x
*The actual sample size of this study with respect to the analysis of persistence and safety and immunogenicity 
post-booster is determined by a) the sample size of the primary vaccination study MENACWY-TT-015 (107386), b) 
by the actual enrolment rates at the YR6-10 extension study, and c) by the actual annual dropout rate. For more 
information see Section 10.3.
Table 2
Study groups and treatment foreseen in the study
Treatment name
Vaccine/Product name
Study Groups
ACWY-TT group 
MenPS group 
MenACWY-TT
MenACWY-TT
● 
● 
Saline diluent *
● 
● 
*The lyophilized pellet of MenACWY-TT vaccine is to be reconstituted with the supplied saline solution.

Control: active control for persistence phase (MenPS group), uncontrolled for booster 
phase (all subjects receive the same booster vaccination).

Vaccination schedule: At Visit 5 (Month 120 post primary vaccination), one dose of 
MenACWY-TT will be administered to the subjects in both study groups.

Treatment allocation: NA

Blinding: open-label
Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001  
open  
Epoch 002  
open  
Epoch 003
open  
Epoch 004
open  
Epoch 005
open  

Blood sampling: at each study visit a blood sample will be collected for each subject 
enrolled. 

Type of study: extension of other protocol [MENACWY-TT-015 (107386); 016 
EXT:015 Y1 (107392); 017 EXT:015 Y2 (107398); 018 EXT:015 Y3 (107402); 019 
EXT:015 Y4 (107404); 020 EXT:015 Y5 (107406)]

Data collection: Electronic Case Report Form (eCRF)
4.
STUDY COHORT
4.1.
Number of subjects/centres
Four hundred subjects (299 in the ACWY-TT group and 101 in the MenPS group) were 
enrolled and vaccinated in study MENACWY-TT-015 in the Philippines. The subjects who 
completed the vaccination phase of study MenACWY-TT-015 and received either 
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MenACWY-TT vaccine or Mencevax ACWY will be eligible for this study if they meet the 
inclusion criteria and no exclusion criteria.
Subjects will be able to enter the study at any visit up to Visit 5. An informed consent form 
for this protocol must be signed prior to any study-related procedure. Subjects will be able to 
participate in any study visit 1, 2, 3, 4, or 5 independent of other study visits, at their own or 
at their parent/LAR’s discretion as applicable (e.g., it is possible that a subject comes to Visit 
1 and Visit 3 but not Visit 2).
If one assumes approximately 10% of subjects dropout of the persistence study at every visit, 
then one expects the following numbers of subjects to participate at each persistence time
point.

For the analysis of Month 72, it is estimated that approximately 336 subjects will be 
enrolled (252 in the ACWY-TT group and 84 in the MenPS group)

For the analysis of Month 84, it is estimated that approximately 304 subjects will be 
enrolled (228 in the ACWY-TT group and 76 in the MenPS group)

For the analysis of Month 96, it is estimated that approximately 274 subjects will be 
enrolled (205 in the ACWY-TT group and 69 in the MenPS group)

For the analysis of Month 108, it is estimated that approximately 248 subjects will be 
enrolled (186 in the ACWY-TT group and 62 in the MenPS group)

For the analysis of Month 120, it is estimated that approximately 224 subjects will be 
enrolled (168 in the ACWY-TT group and 56 in the MenPS group)
Refer to Section 10.3 for the accuracy expected from the estimated sample size with respect 
to the primary objective.
At the time of initiation of the extension study, the investigator will contact ALL subjects 
who completed the primary study, unless the parent(s)/LAR(s) withdrew consent during the 
primary vaccination study MENACWY-TT-015 (107386). The reason for non-participation 
in the extension study will be recorded in the eCRF for ALL subjects (regardless if they 
completed the primary study or not).
4.2.
Inclusion criteria for enrolment
Deviations from inclusion criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.
All subjects must satisfy the following criteria at study entry to the persistence phase:

Subjects who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of the diary cards, return for follow-up 
visits). Or /and 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. completion of the diary cards, return for follow-up visits).

A male or female between and including 17 and 66 years of age at the time of entry into 
the present study. 
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
Has completed the vaccination phase of the vaccination study MENACWY-TT-015 (i.e., 
not withdrawn, had received one dose of study vaccine).

In alignment with local laws and regulations, written informed consent obtained from 
parent(s)/LAR(s) of the subject and written informed assent obtained from the subject if 
the subject is less than 18 years of age, or written informed consent obtained from the 
subject if the subject has achieved the 18th birthday. The subjects 18 years of age at the 
time of enrolment will sign the informed consent form, even if the parent/ LAR 
previously signed the ICF before the subject reached the legal age of consent.

Healthy subjects as established by medical history and history-directed physical 
examination before entering into the study.
All subjects must satisfy the following additional criteria prior to entry of the booster 
phase:

Female subjects of non-childbearing potential may be enrolled in the study. 

Non-childbearing potential is defined as pre-menarche, hysterectomy, bilateral 
ovariectomy or post-menopause. 
Please refer to the glossary of terms for the definitions of menarche and post-menopause.

Male subjects able to father children and female subjects of childbearing potential
(including female subjects who have had tubal ligation) and at risk for pregnancy may be 
enrolled in the study, if the subject:

has practiced adequate contraception for 30 days prior to vaccination, and

has a negative pregnancy test on the day of vaccination (for females only), and

has agreed to continue adequate contraception during the entire treatment period and 
for 2 months after completion of the vaccination.
Please refer to the glossary of terms for the definition of adequate contraception.
4.3.
Exclusion criteria for enrolment
Deviations from exclusion criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study:
Exclusion criteria for study entry

Child in care
Please refer to the glossary of terms for the definition of child in care.

Previous vaccination with meningococcal polysaccharide or conjugate vaccine outside of 
study MENACWY-TT-015.

History of meningococcal disease due to serogroup A, C, W-135 or Y.
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
Any confirmed or suspected immunosuppressive or immunodeficient condition 
(congenital or secondary), including Human Immunodeficiency Virus (HIV) infection, 
based on medical history and physical examination (no laboratory testing required). 

Major congenital defects or serious chronic illness.

Family history of congenital or hereditary immunodeficiency.

History of chronic alcohol consumption and/or drug abuse.
Additional exclusion criteria for booster phase at Month 120 study entry (to be checked 
at Month 120) for all subjects

Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccine within 30 days preceding the booster dose of study vaccine, or planned use 
during the follow-up period.

Chronic administration (defined as more than 14 days in total) of immunosuppressants or 
other immune-modifying drugs within six months prior to the booster vaccine dose (for 
corticosteroids, this will mean prednisone 10 mg/day, or equivalent). Inhaled, topical
and intra-articular steroids are allowed.

Administration of a vaccine not foreseen by the study protocol in the period starting 30 
days before the booster dose of study vaccine or planned administration within 30 days 
after vaccination (with the day of vaccination considered Day 0), with the exception of a 
licensed inactivated influenza vaccine.

Administration of immunoglobulins and/or any blood products within the three months 
preceding the booster vaccination or planned administration during the follow-up period.

Concurrently participating in another clinical study, at any time during the study period, 
in which the subject has been or will be exposed to an investigational or a non-
investigational vaccine/product (pharmaceutical product or device).

Previous vaccination with tetanus toxoids within the last month (i.e., TT-containing
vaccine within the last month).

History of any reaction or hypersensitivity likely to be exacerbated by any component of 
the vaccines.

History of any neurological disorders or seizures, including Guillain-Barré syndrome 
(GBS). History of a simple, single febrile seizure is permitted.

Acute disease and/or fever at the time of vaccination. 

Fever is defined as temperature 37.5°C for oral, axillary or tympanic route, or 
38.0°C for rectal route. The preferred route for recording temperature in this study 
will be oral.

Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory 
infection) without fever may be vaccinated at the discretion of the investigator. 

Pregnant or lactating female.

Female planning to become pregnant or planning to discontinue contraceptive 
precautions.

Male subjects able to father children who are planning to discontinue contraceptive 
precautions.
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
Subjects who are investigational site staff members directly involved in the conduct of 
the study and their family members, site staff members otherwise supervised by the 
investigator, or subjects who are Pfizer employees directly involved in the conduct of the 
study.
5.
CONDUCT OF THE STUDY
5.1.
Regulatory and ethical considerations, including the informed 
consent process
The study will be conducted in accordance with all applicable regulatory requirements.
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:

Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
favourable opinion/approval of study protocol and any subsequent amendments.

Subject/ subject’s parent(s)/LAR(s) informed consent and subject informed assent, as 
appropriate. 

Investigator reporting requirements as stated in the protocol.
Pfizer will provide full details of the above procedures to the investigator, either verbally, in 
writing, or both.
Freely given and written informed consent must be obtained from each subject and/or each 
subject’s parent(s)/LAR(s) and subject informed assent, as appropriate, prior to participation 
in the study. 
Pfizer will prepare a model Informed Consent Form (ICF) which will embody the ICH GCP 
and Pfizer required elements. While it is strongly recommended that this model ICF is to be 
followed as closely as possible, the informed consent requirements given in this document are 
not intended to pre-empt any local regulations which require additional information to be 
disclosed for informed consent to be legally effective. Clinical judgement, local regulations 
and requirements should guide the final structure and content of the local version of the ICF. 
In accordance with the ICH Harmonised Tripartite Guidelines for Good Clinical Practice, 
those subjects who can only be enrolled in the study with the consent of the subject’s legally 
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acceptable representative (e.g. minors), should be informed about the study to the extent 
compatible with the subject’s understanding and, if capable, the subject should sign and 
personally date a written informed assent form (IAF). It is required that the assent be signed 
by each subject, if capable, in addition to the informed consent that is to be signed by his/her 
legal representative. It should be assessed whether an assent is required depending of the age 
of the study population and the local requirements.
If the subject reaches the age of consent during the study they will be asked to provide 
consent at the next study visit (if applicable). This procedure should be applied according to 
local laws and regulations.
The investigator has the final responsibility for the final presentation of the ICF, respecting 
the mandatory requirements of local regulations. The ICF generated by the investigator with 
the assistance of the sponsor’s representative must be acceptable to Pfizer and be approved 
(along with the protocol, and any other necessary documentation) by the IRB/IEC.
5.2.
Subject identification and randomisation of treatment
5.2.1.
Subject identification
Subjects will retain the same subject number as in MENACWY-TT-015 (107386).
5.2.2.
Study group and treatment allocation
All subjects who completed study MENACWY-TT-015 (107386) and received either 
MenACWY-TT vaccine or Mencevax ACWY will be eligible for this study if they meet the 
inclusion/exclusion criteria. 400 subjects (299 in the ACWY-TT group and 101 in the MenPS 
group) were enrolled and vaccinated in study MENACWY-TT-015 (107386).
There will be no randomization in this study. The subjects in this study will be allocated to 
the same groups as in the vaccination study MENACWY-TT-015 (107386). Subjects will be 
allocated a new container number, but will retain the same subject number as in 
MENACWY-TT-015 (107386).
Allocation of subjects to vaccine groups will proceed through the use of an interactive 
response technology (IRT) system. The site personnel (study coordinator or specified 
designee) will be required to enter or select information including but not limited to the user’s 
identification (ID) and password, the protocol number, the subject number and the date of 
birth of the subject. The site personnel will then be provided with a vaccine assignment and 
dispensable unit (DU) or container number. The IRT system will provide a confirmation 
report containing the subject number and DU or container number assigned.
After obtaining the signed and dated ICF/IAF from the subject and having checked the 
eligibility of the subject, the site staff in charge of the vaccine administration will access IRT. 
Upon providing the subject identification number, the randomisation system will provide the 
container number to be used for the dose. 
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The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen.
When IRT is not available, please refer to the IRT user guide or the Study Procedures Manual 
(SPM) for specific instructions.
5.3.
Method of blinding 
This study will be conducted in an open manner.
Any person involved in the clinical conduct of the study (including data cleaning) will stay as 
blind as possible during the study. Investigators will be provided with the immunogenicity 
results for subjects identified as non-responders after each persistence timepoint.
The laboratory in charge of the laboratory testing will be blinded to the treatment, and codes 
will be used to link the subject and study (without any link to the treatment attributed to the 
subject) to each sample.
5.4.
General study aspects
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects.
5.5.
Outline of study procedures
Table 4 presents the list of study procedures.
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Table 4
List of study procedures
Visit
VISIT 1*
VISIT 2 *
VISIT 3*
VISIT 4*
VISIT 5*
VISIT 6*
phone contact
Timing
Month 72 
(Year 6)
Month 84 
(Year 7)
Month 96 
(Year 8)
Month 108 
(Year 9)
Month 120 
(Year 10)
Month 121
Month 126
Epoch
Epoch 001
Epoch 002
Epoch 003
Epoch 004
Epoch 005
Sampling time point
Year 6 post 
vaccination
Year 7 post 
vaccination
Year 8 post 
vaccination
Year 9 post 
vaccination
Pre-booster 
vaccination
One month post-
booster
ESFU
Informed consent1
●
●
●
●
●
Informed assent1
O
O
Check inclusion/exclusion criteria2
●
●
●
●
●
Check additional inclusion/exclusion criteria for 
booster phase
●3
Check contraindications 
O
Check warnings and precautions 
O
Check medical history since last visit done4
●
●
●
●
●
Meningococcal vaccination history since last visit 
done
●
●
●
●
●
Vaccination history of TT containing vaccines 
since last visit done
●
●
●
●
●
History-directed physical examination
●
Collect urine for pregnancy test for females of 
childbearing potential
●
Pre-vaccination assessment of contraception
(see section 4.2)
●
Pre-vaccination assessment of body 
temperature
●
Record container number
●
Blood sampling for antibody determination 
(approximate volume)
7 mL
7 mL
7 mL
7 mL
10 mL
10 mL
Record timing related to reconstitution and 
vaccination
●
Vaccination (MenACWY-TT)
●
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Visit
VISIT 1*
VISIT 2 *
VISIT 3*
VISIT 4*
VISIT 5*
VISIT 6*
phone contact
Timing
Month 72 
(Year 6)
Month 84 
(Year 7)
Month 96 
(Year 8)
Month 108 
(Year 9)
Month 120 
(Year 10)
Month 121
Month 126
Epoch
Epoch 001
Epoch 002
Epoch 003
Epoch 004
Epoch 005
Observation of subjects for 30 minutes post 
vaccination
O
Distribution of diary cards
O
Daily post-vaccination recording of solicited 
adverse events within 4 days (Days 0-3) after 
administration of the booster dose
●
Return of diary cards5
O
Diary card transcription
O
Recording of non-serious adverse event days 0-
30 post-vaccination by investigator
●
●
Record any concomitant medication/vaccination6
●
●
●
●
●
●
●
Record any intercurrent medical conditions 7,8
●
●
●
●
●
●
●
Reporting of all SAEs8
●
●
●
Reporting of SAEs related to study participation 
or any fatal SAE8
●
●
●
●
●
●
Reporting of new onset of chronic illness 
(NOCI)9,11
●
●
●
Reporting of Guillain Barré Syndrome (GBS)10,11
●
●
●
Reporting of pregnancies12
●
●
Study Conclusion 
●13
Note: the double-line border following Months 72, 84, 96, 108, 121 and 126 indicates the analysis which will be performed on as clean as possible data obtained up to those time 
points. 
ESFU: Extended Safety Follow-Up
is used to indicate a study procedure that requires documentation in the individual eCRF.
O is used to indicate a study procedure to be captured in site source records that does not require documentation in the individual eCRF.
*Subjects will be contacted by phone 4-8 weeks beforehand to come in for the persistence visit. The subject may return at any visit during the persistence epochs.
1 Informed consent is only required at Visit 2, Visit 3, Visit 4 or Visit 5 if the informed consent form was not signed at previous study visits, i.e. if either Visit 2, Visit 3, Visit 4 or Visit 5 is 
the first persistence visit for a given subject unless the ICF has been amended wherein a signed amended ICF would be necessary. Subjects will be able to participate in any study visit 
1, 2, 3 4, or 5 independent of other study visits, at their own or at their parent/LAR’s discretion as applicable (e.g., it is possible that a subject comes to Visit 1 and Visit 3 but not Visit 
2). The subjects 18 years of age at the time of enrolment will sign the informed consent form, even if the parent/ LAR previously signed the ICF before the subject reached the legal 
age of consent. The subjects’ parent(s)/LAR(s) will sign the informed consent form if the subject is a minor. All minors will give assent to decisions about his/her participation in the 
study in addition to the consent provided by the parent(s)/LAR(s). Only the informed consent date will be collected in the eCRF.
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2Check of inclusion and exclusion criteria for the persistence epochs at Visit 2, Visit 3 and Visit 4 is only required if these checks were not performed at a previous study visit, i.e. if Visit 
2, Visit 3 or Visit 4 Visit 5 is the first persistence visit for a given subject. Additional criteria prior to entry of the booster phase need to be checked for all subjects. Subjects will be able 
to participate in any study visit 1, 2, 3 4, or 5 independent of other study visits, at their own or at their parent/LAR’s discretion as applicable (e.g., it is possible that a subject comes to 
Visit 1 and Visit 3 but not Visit 2). 
3Note that Visit 5 is part of the persistence epoch (Month 120: Visit 5) as well as the pre-booster vaccination visit. Thus if a subject first enters the study at Visit 5, eligibility criteria for 
both the persistence epoch and for the booster epoch will be checked. If the subject will continue into the booster epoch, a history-directed physical exam will be required at Month 120 
(Visit 5), to be documented in the subject’s eCRF.
4 Including since the last visit of the primary vaccination study MENACWY-TT-015.
5 For the safety evaluation an interval of 30 days is needed. If the subject returns for the Visit 6 blood draw prior to the end of the 31-day safety follow-up period, the subject will 
continue to record safety information on the diary card until 31 days post-vaccination, and will mail the diary card in to the site.
6 From Visit 5 and up to Visit 6, all non-study vaccines administered within 30 days preceding the booster dose, and any medications/non-study vaccinations taken on Days 0-30 
following booster vaccination (day of booster vaccination is considered Day 0) will be recorded. Throughout the whole study, any investigational or non-registered medication or 
vaccine, any meningococcal vaccine and any medications used to treat SAEs will be recorded. Subjects will be questioned at MENACWY-TT-099 study entry whether any 
investigational or non-registered medication or vaccine, any meningococcal vaccine and any medications used to treat SAEs were used from Month 60 (last visit of study MENACWY-
TT-020 EXT:015 Y5) to study entry in MENACWY-TT-099.
7 These conditions include: Any confirmed or suspected condition that has the capability of altering the subject's immune response (e.g. intercurrent lymphopenia, the occurrence of 
meningococcal disease, any confirmed or suspected immunosuppressive or immunodeficient condition and diagnosis of serious chronic illness) throughout the study. 
8 This will also include SAE(s) leading to withdrawal of the subject from the study. Occurrence of meningococcal diseases should be reported as SAE and documented in the AE 
screen in the eCRF during the entire study period.
9 New onset of chronic illnesses (NOCIs) (e.g. auto-immune disorders, allergies, type 1 diabetes, asthma) will be recorded until the end of the study (up to the phone contact at Month 
126) and will be reported as unsolicited AEs or SAEs as appropriate. A non-exhaustive list of NOCIs is provided in Section 8.1.8.1.
10 In the event of GBS, subjects/subjects' parent(s)/LAR(s) should be contacted to obtain clinical details as outlined in the 'Potential immune mediated disorders (pIMDs): standard 
questionnaires and list of preferred terms'. All occurrences of GBS have to be reported as an SAE.
11 Recording will start after administration of the first vaccine dose.
12 Pregnancies occurring between booster vaccination (Month 120) and 31 days after vaccination (Day 30) will be recorded. Subjects will be questioned at Month 126, 6 months after 
the booster vaccination, whether any unreported pregnancies occurred between Day 0 (booster vaccination) and Day 30 and these pregnancies will be recorded retrospectively.
If, after having been vaccinated, a subject is found to have been pregnant at vaccination, the pregnancy will be recorded as an exclusion criterion.
13 To be completed for all subjects who are enrolled in the study.
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It is the investigator’s responsibility to ensure that the intervals between visits/contacts 
are strictly followed. These intervals determine each subject’s evaluability in the 
according-to-protocol (ATP) analyses.
Table 5 presents the intervals between study visits.
Table 5
Intervals between study visits
Interval
Optimal length of interval 1
Allowed interval2
Dose 1 in primary vaccination study 
MENACWY-TT-015 (107386)Visit 1
6 years
72 months ± 12 weeks
Dose 1 in primary vaccination study 
MENACWY-TT-015 (107386)Visit 2 
7 years
84 months ± 9 weeks
Dose 1 in primary vaccination study 
MENACWY-TT-015 (107386)Visit 3 
8 years
96 months ± 9 weeks
Dose 1 in primary vaccination study 
MENACWY-TT-015 (107386) Visit 4 
9 years
108 months ± 9 weeks
Dose 1 in primary vaccination study 
MENACWY-TT-015 (107386)Visit 5
10 years
(120 months)
118 months to 126 months
Visit 5 Visit 6 
30 days
21-48 days3
Visit 5 Phone Contact
6 months
180-210 days
1 Whenever possible the investigator should arrange study visits within this interval.
2 Subjects will not be eligible for inclusion in the ATP cohort for immunogenicity if they make the study visit outside this 
interval.
3 For the safety evaluation an interval of 30 days is needed. If the subject returns for visit 6 prior to Day 30, they should 
take home the diary card, continue to record unsolicited safety information until Day 30 and then provide the card to 
the study site.
5.6.
Detailed description of study procedures
5.6.1.
Informed consent
The signed informed consent of the subject/subject’s parent(s)/LAR(s) must be obtained 
before study participation. The signed informed assent of the subject below the age of 
consent (i.e. minor) should be obtained in addition to the signed informed consent by 
his/her parent(s)/LAR(s) according to local rules and regulations. Refer to Section 5.1 for 
the requirements on how to obtain informed consent and assent, as appropriate.
If the subject become of legal age during the course of the study, the subject will be asked 
to sign the ICF per local regulation. Only the informed consent date at study entry will be 
collected in the eCRF.
5.6.2.
Check inclusion and exclusion criteria
Check all inclusion and exclusion criteria as described in Sections 4.2 and 4.3 before 
enrolment. 
5.6.3.
Collect demographic data
Record demographic data such as date of birth, gender, geographic ancestry and ethnicity 
in the subject’s eCRF.
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5.6.4.
Medical history since last visit done
Obtain the subject’s medical history by interview and/or review of the subject’s medical 
records and record any pre-existing conditions or signs and/or symptoms present in a 
subject prior to the study visit in the eCRF.
5.6.5.
Vaccination history
Vaccination history of any meningococcal and TT containing vaccines received since last 
visit has to be recorded. If no record is available, information has to be provided as to the 
best of the subject’s parent(s)/LAR(s)’ knowledge.
5.6.6.
History directed physical examination
Perform a history directed physical examination. If the investigator determines that the 
subject’s health on the day of vaccination temporarily precludes vaccination, the visit will 
be rescheduled.
Treatment of any abnormality observed during this examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider.
5.6.7.
Pre-vaccination assessment of contraception
The investigator or his/her designee will discuss with the subject the need to use adequate 
contraception consistently and correctly according to the glossary of terms (and outline of 
study procedures) and document such conversation in the subject’s medical records. In 
addition, the investigator or his/her designee will instruct the subject to call immediately 
if the selected contraception method is discontinued or if pregnancy is known or 
suspected in the subject or the subject’s partner.
5.6.8.
Urine pregnancy test
For female subjects of childbearing potential, a urine pregnancy test, with sensitivity of at 
least 25 mIU/mL, will be performed immediately before administration of the vaccine 
dose.  A negative pregnancy test result is required before the subject may receive the 
study vaccine.  In the case of a positive confirmed pregnancy, the subject will be 
withdrawn from administration of study vaccine but may remain in the study. Pregnancy 
tests may also be repeated as per request of institutional review boards (IRBs)/ethics 
committees (ECs) or if required by local regulations.
Note: The urine pregnancy test must be performed even if the subject is menstruating at 
the time of the study visit.
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5.6.9.
Check contraindications, warnings and precautions to 
vaccination
Contraindications, warnings and precautions to vaccination must be checked at the 
beginning of the vaccination visit. Refer to Section 6.4 for more details. 
5.6.10.
Assess pre-vaccination body temperature
The axillary, rectal, oral or tympanic body temperature of all subjects needs to be 
measured prior to any study vaccine administration. The preferred route for recording 
temperature in this study will be oral. If the subject has fever [Fever is defined as 
temperature 37.5°C for oral, axillary or tympanic route, or 38.0°C for rectal route.] on 
the day of vaccination, the vaccination visit will be rescheduled within the allowed 
interval for this visit (see Table 5).
5.6.11.
Study group and treatment allocation
Container number allocation will be performed as described in Section 5.2.2. The number 
of each administered treatment must be recorded in the eCRF.
5.6.12.
Sampling
Refer to the Module on Biospecimen Management in the SPM for detailed instructions 
for the collection, handling and processing of the samples.
5.6.12.1.
Blood sampling for immune response assessments
Blood samples will be taken during certain study visits as specified in Section 5.5 List of 
Study Procedures.

A volume of approximately 7 mL (10 mL at visits 5 and 6) of whole blood (to 
provide approximately 2.5 mL of serum [5 mL of serum at visits 5 and 6]) should be 
drawn from all subjects for each analysis of humoral immune response at each pre-
defined time point. After centrifugation, serum samples should be kept at –20°C or 
below until shipment. Refer to the SPM for more details on sample storage 
conditions.
5.6.13.
Study Vaccine administration
Study vaccine will be administered at Visit 5 (Month 120).

After completing all prerequisite procedures prior to vaccination, one dose of study 
vaccine will be administered intramuscularly (IM) in the deltoid of the non-dominant 
arm (refer to Section 6.3 for detailed description of the vaccine administration 
procedure). If the investigator or delegate determines that the subject’s health on the 
day of administration temporarily precludes vaccine administration, the visit will be 
rescheduled within the allowed interval for this visit (refer to Table 5).

The time of reconstitution and administration of the vaccine will be recorded.
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
The subjects will be observed closely for at least 30 minutes following the 
administration of the vaccine, with appropriate medical treatment readily available in 
case of anaphylaxis.
5.6.14.
Check and record concomitant medication/vaccination and 
intercurrent medical conditions
Concomitant medication/vaccination must be checked and recorded in the eCRF as 
described in Section 6.5.
Intercurrent medical conditions must be checked and recorded in the eCRF as described 
in Section 6.6.
5.6.15.
Recording of AEs, SAEs and pregnancies

Refer to Section 8.2 for procedures for the investigator to record AEs, SAEs and 
pregnancies. Refer to Section 8.3 for guidelines on how to submit SAE and Exposure 
During Pregnancy (EDP) reports to Pfizer.

The subjects/subjects’ parent(s)/LAR(s) will be instructed to contact the investigator 
immediately should they/the subjects manifest any signs or symptoms they perceive 
as serious. 

At the vaccination visit, diary cards will be provided to the subject/subjects’ 
parent(s)/LAR(s). The subject/subjects’ parent(s)/LAR(s) will record body 
temperature (preferred route: oral) and any solicited local/general AEs (i.e. on the 
day of vaccination and during the next 3 days) or any unsolicited AEs (i.e. on the day 
of vaccination and during the next 30 days occurring after vaccination. The subject 
will be instructed to return the completed diary card to the investigator at the next 
study visit.

Collect and verify completed diary cards during discussion with the subject at Visit 6 
(30 days after the vaccine dose). If the subject returns for Visit 6 prior to 30 days 
after the vaccine dose, they should take home the diary card, continue to record 
unsolicited safety information until 30 days after the vaccine dose and then provide 
the card to the study site.

Any unreturned diary cards will be sought from the subject through telephone call(s) 
or any other convenient procedure. The investigator will transcribe the collected 
information into the eCRF in English.
5.6.15.1.
Recording of GBS and NOCIs

Please refer to Section 8.2 for procedures for the investigator to record GBS and 
NOCIs. Refer to Section 8.3 for guidelines on how to report GBS and NOCIs.

In the event of GBS, subjects should be contacted to obtain clinical details as 
outlined in the ‘Potential immune mediated disorders: standard questionnaires and 
list of preferred term’. All occurrences of GBS have to be reported as SAE(s).

NOCIs (e.g. auto-immune disorders, asthma, type 1 diabetes, allergies) will be 
reported as unsolicited AEs or SAE as appropriate.
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5.6.15.2.
Recording of data during the phone contact at Month 126
At the end of the ESFU period, data collection will be handled by a phone contact with 
the subjects. A script will be used in order to assure standardization and completeness of 
data collection.
SAEs, NOCIs and GBSs will be collected and should be entered in the eCRF.
5.6.16.
Study conclusion
The investigator or delegate will:

review data collected to ensure accuracy and completeness

complete the Study Conclusion screen in the eCRF.
5.7.
Biological sample handling and analysis
Refer to the SPM for details on biospecimen management (handling, storage and 
shipment). See section 5.6.12.1 for a brief description of the procedure for collection, 
preparation and storage of serum samples.
Samples will not be labelled with information that directly identifies the subject but will 
be coded with the identification number for the subject (subject number). 
Under the following circumstances, additional testing on the samples may be performed 
by Pfizer outside the scope of this protocol:

Collected samples may be used in other assays, for test improvement or development 
of analytical methods related to the study vaccine and its constituents or the disease 
under study. 

Collected samples may be used for purposes related to the quality assurance of data 
generated linked to the study vaccine or the disease under study, such as for 
maintenance of assays described in this protocol and comparison between analytical 
methods and/or laboratories.
Information on further investigations and their rationale can be obtained from Pfizer. Any 
sample testing will be done in line with the consent of the individual subject/subject’s 
parent(s)/LAR(s).
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s). 
If additional testing is performed, the marker priority ranking given in Section 5.7.4.1
may be changed.
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Collected samples will be stored for a maximum of 15 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with Pfizer.
5.7.1.
Use of specified study materials
When materials are provided by Pfizer or designee, it is MANDATORY that all clinical 
samples (including serum samples) be collected and stored exclusively using those 
materials in the appropriate manner. The use of other materials could result in the 
exclusion of the subject from the ATP analysis (See Section 10.4 for the definition of 
study cohorts/ data sets to be analysed). The investigator must ensure that his/her 
personnel and the laboratory(ies) under his/her supervision comply with this requirement. 
Refer to the Module on Clinical Trial Supplies in the SPM.
5.7.2.
Biological samples
Table 6 presents the biological samples at which biological samples will be taken.
Table 6
Biological samples
Sample type
Quantity
Unit
Time point
Subset
Blood Sample
Approximately 7
ml
Visit 1 (months 72)
All subjects
Blood Sample
Approximately 7
ml
Visit 2 (months 84)
All subjects
Blood Sample
Approximately 7
ml
Visit 3 (months 96)
All subjects
Blood Sample
Approximately 7
ml
Visit 4 (months 108)
All subjects
Blood Sample
Approximately 10
ml
Visit 5 (months 120)
All subjects
Blood Sample
Approximately 10
ml
Visit 6 (months 121)
All subjects
5.7.3.
Laboratory assays
Please refer to APPENDIX A for a detailed description of the assays performed in the 
study. Please refer to APPENDIX B for the address of the clinical laboratories used for 
sample analysis.
Serological assays will be performed at Public Health England (PHE; Manchester, UK)
and at Pharmaceutical Product Development (PPD) Inc. Bioanalytical Laboratories
(Richmond, VA, USA) using standardized and validated procedures.
See Table 7 for details of the laboratory assays.
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Table 7
Humoral Immunity (Antibody determination)
Component
Method
Test kit/ 
Manufacturer
Unit
Cut-off
Laboratory*
Neisseria 
meningitidis 
Serogroup A 
L10 3125 Ab 
Bactericidal assay using rabbit 
complement
NA
Last dilution with at 
least 50% killing
1:8
PHE
Neisseria 
meningitidis 
Serogroup C 
L3v C11 Ab 
Bactericidal assay using rabbit 
complement
NA
Last dilution with at 
least 50% killing
1:8
PHE
Neisseria 
meningitidis 
Serogroup W 
L3v 
MP01240070 
Ab 
Bactericidal assay using rabbit 
complement
NA
Last dilution with at 
least 50% killing
1:8
PHE
Neisseria 
meningitidis 
Serogroup Y 
L3v S1975 Ab 
Bactericidal assay using rabbit 
complement
NA
Last dilution with at 
least 50% killing
1:8
PHE
Clostridium 
tetani.Tetanus 
Toxoid Ab.IgG 
Direct Luminex Immuno Assay
NA
IU/mL
0.1
PPD
*PHE = Public Health England (formerly HPA: Health Protection Agency)
PPD = Pharmaceutical Product Development (PPD), Inc. Bioanalytical Laboratories
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5.7.4.
Biological samples evaluation
5.7.4.1.
Immunological read-outs
Table 8
Immunological read-outs
Blood sampling time -point
No. 
subjects
Component
Components
priority rank
Type of contact 
and time -point
Sampling 
time -point
visit 1 (month 72)
Post-Vacc 
400
rSBA-MenA, rSBA-MenW-135, 
rSBA-MenY, rSBA-MenC
rSBA-MenC > rSBA-MenA 
> rSBA-MenW-135 > rSBA-MenY
visit 2 (month 84)
Post-Vacc 
360
rSBA-MenA, rSBA-MenW-135, 
rSBA-MenY, rSBA-MenC
rSBA-MenC > rSBA-MenA 
> rSBA-MenW-135 > rSBA-MenY
visit 3 (month 96)
Post-Vacc 
324
rSBA-MenA, rSBA-MenW-135, 
rSBA-MenY, rSBA-MenC
rSBA-MenC > rSBA-MenA 
> rSBA-MenW-135 > rSBA-MenY
visit 4 (month 108)
Post-Vacc
292
rSBA-MenA, rSBA-MenW-135, 
rSBA-MenY, rSBA-MenC
rSBA-MenC > rSBA-MenA 
> rSBA-MenW-135 > rSBA-MenY
visit 5 (month 120)
Pre-Booster
263
rSBA-MenA, rSBA-MenW-135, 
rSBA-MenY, rSBA-MenC, 
anti-TT
rSBA-MenC > rSBA-MenA 
> rSBA-MenW-135 
> rSBA-MenY> anti-TT
visit 6 (month 121)
Post-Booster
263
rSBA-MenA, rSBA-MenW-135, 
rSBA-MenY, rSBA-MenC, 
anti-TT
rSBA-MenC > rSBA-MenA 
> rSBA-MenW-135 
> rSBA-MenY> anti-TT
Vacc: Vaccination
In case of insufficient blood sample volume to perform assays for all antibodies, the 
samples will be analysed according to priority ranking provided in Table 8. 
5.7.5.
Immunological correlates of protection
Bactericidal assay using rabbit complement (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 
and rSBA-MenY):
Bactericidal antibodies are recognized as surrogate markers of protection. The 1:8 cut-off
was shown to be the most consistent with observed efficacy at 4 weeks after vaccination 
with the meningococcal C conjugate vaccine in post-licensure efficacy estimates in the 
United Kingdom [Andrews, 2003]. The threshold for protection for other serogroups is 
still to be defined, although it is common practice to extend the 1:8 cut-off to rSBA-
MenA, rSBA-MenW-135 and rSBA-MenY [Centers for Disease Control and Prevention, 
2006; WHO, 2011]. 
Antibodies against tetanus toxoid (Anti-TT):
Tetanus toxoid antibody concentrations greater than or equal to 0.1 IU/mL are considered 
as protective [McComb, 1964; Newell, 1971]. The dLIA lower limit of quantitation 
(LLOQ) for tetanus toxoid based on Pfizer’s validation is 0.05 IU/mL at 1:1000 dilution.
Based on this value, a dLIA result of <0.1 IU/mL is considered a negative clinical 
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response and a dLIA result ≥0.1 IU/mL (protective threshold) is considered a positive 
clinical response.
5.7.5.1.
Communication of individual immunological assay results to study 
investigator
Persistence phase
At each immunogenicity time point investigators will be provided with the 
immunogenicity results and group allocation for all subjects when the individual listings 
of the statistical report have been released.  
Booster phase
Immunogenicity results and group allocation of all subjects will be provided when the 
individual listings of the statistical report have been released.
When a generally accepted correlate of protection exists, individual immunological assay 
results for the subjects identified as non-responders (i.e., antibody level below the 
established correlate of protection measured one month after vaccination) could be 
defined using the following thresholds:

rSBA-MenC antibody titer < 1:8

tetanus toxoid antibody titers < 0.1 IU/mL
Although no correlate of protection is established for Neisseria meningitidis serogroups 
A, W-135 and Y, individual immunology assay results for these 3 antigens will also be 
provided to the study investigator.
For the study subjects identified as non-responders, it remains the responsibility of the 
study investigator in charge of the subject’s clinical management to determine the 
medical need for re-vaccination and to re-vaccinate the subjects as per local/regional 
practices.
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6.
STUDY VACCINE AND ADMINISTRATION
6.1.
Description of study vaccine
The conjugate vaccine (MenACWY-TT) to be used in this study has been developed and 
manufactured by GSK Biologicals. MenACWY-TT was acquired by Pfizer on 
01 October 2015.
The vaccines are labelled and packed according to applicable regulatory requirements.
Table 9 presents the description of the study vaccine.
Table 9
Study vaccine
Treatment name
Vaccine/
product name
Formulation
Presentation
Volume to be 
administered*
Number of 
doses
MenACWY-
TT 
MenACWY-
TT 
5 µg of PSA, 5 µg of 
PSC, 5 µg of PSW-135, 5 
µg of PSY conjugated to 
Tetanus toxoid conjugate 
~ 44 µg Tris-HCL, pH 6.8 
± 0.3 1.6 mM; Sucrose 28 
mg 
Lyophilized pellet to 
be reconstituted 
with saline diluent 
0.5 mL
1
Saline 
diluent**
saline solution 
liquid 
*Refer to the Study Procedures Manual (SPM) for the volume after reconstitution
**The lyophilized pellet of MenACWY-TT vaccine is to be reconstituted with the supplied saline solution.
6.2.
Storage and handling of study vaccines
The study vaccine will be shipped at +2°C to +8°C to each study site upon request. Upon 
receipt at the study site, the vaccines should be immediately transferred to a +2°C to 
+8°C temperature-monitored refrigerator for storage. Storage conditions stated in the 
SRSD (ie, CDS) may be superseded by the storage conditions described in the product 
labeling. 
The study vaccines must be stored in a safe and locked place. Access to the storage space 
should be limited to authorized study personnel. The storage conditions will be assessed 
during pre-study activities under the responsibility of the sponsor study contact. The 
storage temperature should be continuously monitored with calibrated (if not validated) 
temperature monitoring device(s) and recorded. Refer to the Module on Clinical Trial 
Supplies in the SPM for more details on storage of the study vaccines.
Temperature excursions must be reported in degree Celsius. 
Any excursions from the product label storage conditions should be reported upon 
discovery. The site should actively pursue options for returning the product to the storage 
conditions as described in the labeling, as soon as possible.  Deviations from the storage 
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requirements, including any actions taken, must be documented and reported to the 
sponsor.  Once an excursion is identified, the study vaccine must be quarantined and not 
used until the sponsor provides documentation of permission to use the study vaccine.  It 
will not be considered a protocol deviation if the sponsor approves the use of the study 
vaccine after the temperature excursion. Use of the study vaccine prior to sponsor 
approval will be considered a protocol deviation.
Specific details regarding information the site should report for each excursion will be 
provided to the site. Refer to the Module on Clinical Trial Supplies in the SPM for details 
and instructions on the temperature excursion reporting and usage decision process, 
packaging and accountability of the study vaccines.
6.3.
Dosage and administration of study vaccines
Table 10
Dosage and administration
Type of contact and 
time point
Volume to 
be 
administered
Study Group
Treatment name
Route 1
Site 2
Side 3
visit 5 (months 120 )
0.5 mL
ACWY-TT group 
MenACWY-TT 
IM 
D 
N-D 
0.5 mL
MenPS group 
MenACWY-TT  
IM 
D 
N-D 
1Intramuscular (IM) ; 2Deltoid (D) ; 3Non-dominant (N-D)
Reconstitution of the MenACWY-TT vaccine
The lyophilized white pellet of MenACWY-TT is to be reconstituted with the supplied 
saline solution to obtain 0.5 mL for administration. Please refer to the CDS for more 
details.
6.4.
Warnings and precautions
Any specific warnings and precautions associated with the administration of MenACWY-
TT have been mentioned in the exclusion criteria.
Administration of study vaccines through routes not specified in the protocol should be 
avoided under any circumstances.
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Syncope (fainting) can occur following, or even before, any vaccination especially in 
adolescents as a psychogenic response to the needle injection. This can be accompanied 
by several neurological signs such as transient visual disturbance, paraesthesia and tonic-
clonic limb movements during recovery. It is important that procedures are in place to 
avoid injury from faints.
6.5.
Concomitant medication/product and concomitant 
vaccination
At each study visit/contact, the investigator should question the subject and/or the 
subject’s parent(s)/LAR(s) about any medication/product taken and vaccination received 
by the subject.
6.5.1.
Recording of concomitant medications/products and 
concomitant vaccination
The following concomitant medications/products/vaccines must be recorded in the 
eCRF if administered during the indicated recording period:

All concomitant medications/products, except vitamins and dietary supplements, 
administered 30 days following the dose of study vaccine.

Any concomitant vaccination administered in the period 30 days before each blood 
sampling during the persistence phase, as well as the in the period starting 30 days 
before the booster dose of study vaccine and ending at visit 6.

Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination).
E.g. an anti-pyretic is considered to be prophylactic when it is given in the absence 
of fever and any other symptom, to prevent fever from occurring [Fever is defined as 
temperature 37.5°C for oral, axillary or tympanic route, or 38.0°C for rectal
route].

Any concomitant medications/products/vaccines listed in Section 6.5.2.

Any concomitant medication/product/vaccine relevant to a SAE* or administered at 
any time during the study period for the treatment of a SAE*.
* SAEs that are required to be reported per protocol.
6.5.2.
Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from ATP analyses
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the subject from the study but may determine a subject’s evaluability in the 
ATP analysis. See Section 10.4 for study cohorts/ data sets to be analysed.

Any investigational or non-registered product (drug or vaccine) other than the study 
vaccine(s) used during the study period. 
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
Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. more than 14 days) during the study period. (For corticosteroids, this will mean 
prednisone 10 mg/day or equivalent. Inhaled, topical and intra-articular steroids are 
allowed)

A vaccine not foreseen by the study protocol administered during the period starting 
from 30 days before the study vaccine dose and ending 30 days after*, with the 
exception of inactivated influenza vaccine
*In case an emergency mass vaccination for an unforeseen public health threat (e.g.: 
a pandemic) is organised by the public health authorities, outside the routine 
immunisation program, the time period described above can be reduced if necessary 
for that vaccine provided it is licensed and used according to its SPC (Summary of 
Product Characteristics) or PI (Prescribing Information) and according to the local 
governmental recommendations.

Administration of a meningococcal PS, meningococcal conjugate PS or TT 
containing vaccine not foreseen by the study protocol at any time during the study 
period. 

Immunoglobulins and/or any blood products administered during the study period.

Drug and/or alcohol abuse.
A detailed, comprehensive list of reasons for elimination from ATP analyses will be 
established at the time of data cleaning.
6.6.
Intercurrent medical conditions that may lead to elimination 
of a subject from ATP analyses
At each study visit subsequent to the vaccination visit, it must be verified if the subject 
has experienced or is experiencing any intercurrent medical condition. If it is the case, the 
condition(s) must be recorded in the eCRF.
The following may result in the elimination of subjects from the ATP cohort for 
immunogenicity, but not necessarily from the study

Occurrence of meningococcal disease*.

Any confirmed or suspected Human immunodeficiency virus (HIV) infection based 
on medical history and physical examination (no laboratory testing required)

Any confirmed or suspected condition that has the capability of altering the subject’s 
immune response (e.g. intercurrent lymphopenia)

Any confirmed or suspected immunosuppressive or immunodeficient condition 
based on medical history and physical examination (no laboratory testing required)

Diagnosis of any serious chronic illness
* Occurrence of meningococcal disease should be reported as an SAE.
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7.
HEALTH ECONOMICS
Not applicable.
8.
SAFETY
The investigator or site staff is/are responsible for the detection, documentation and 
reporting of events meeting the criteria and definition of an adverse event (AE) or serious 
adverse event (SAE) as provided in this protocol. 
Each subject/subject’s parent(s)/LAR(s) will be instructed to contact the investigator 
immediately should they/the subject manifest any signs or symptoms they perceive as 
serious.
8.1.
Safety definitions
8.1.1.
Definition of an adverse event
An AE is any untoward medical occurrence in a clinical investigation subject, temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product.
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with 
the use of a medicinal product. For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. 
Examples of an AE include:

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after investigational vaccine(s)/product(s) 
administration even though they may have been present prior to the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
investigational vaccine(s)/product(s) or a concurrent medication (overdose per se 
should not be reported as an AE/SAE).

Signs, symptoms temporally associated with vaccine administration.

Pre- or post-treatment events that occur as a result of protocol-mandated procedures 
(i.e. invasive procedures, modification of subject’s previous therapeutic regimen).

Medication error.

Occupational exposure.
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AEs to be recorded as solicited AEs are described in Section 8.1.6. All other AEs will be 
recorded as UNSOLICITED AEs.
Examples of an AE DO NOT include:

Medical or surgical procedures (e.g. endoscopy, appendectomy); the condition that 
leads to the procedure is an AE/SAE.

Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 

Pre-existing conditions or signs and/or symptoms present in a subject prior to the 
first study vaccination. These events will be recorded in the medical history section 
of the eCRF.
8.1.2.
Medication Errors
Medication errors may result, in this study, from the administration or consumption of the 
wrong product, by the wrong subject, at the wrong time, or at the wrong dosage strength.  
Such medication errors occurring to a study participant are to be captured on the 
medication error CRF, which is a specific version of the AE page, and on the SAE form 
when appropriate.  In the event of medication dosing error, the sponsor should be notified 
immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving subject exposure to the study vaccine;

Potential medication errors or uses outside of what is foreseen in the protocol that 
do or do not involve the participating subject.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is captured on the medication error version of the AE 
page and, if applicable, any associated AE(s) are captured on an AE CRF page.
Other examples include, but are not limited to:

The administration of expired study vaccine;

The administration of an incorrect study vaccine;

The administration of an incorrect dosage;

The administration of study vaccine that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
study vaccine under question is acceptable for use.
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8.1.3.
Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to the drug safety unit within 24 hours of the 
investigator’s awareness, using the SAE report form, regardless of whether there is an 
associated AE/SAE.  Since the information does not pertain to a subject enrolled in the 
study, the information is not reported on a CRF; however, a copy of the completed SAE 
report form is maintained in the investigator site file.
8.1.4.
Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or having 
been exposed (eg, because of treatment or environmental exposure) to the study 
vaccine; or the female becomes or is found to be pregnant after discontinuing 
and/or being exposed to the study vaccine; 
2. An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).
3. A male has been exposed (eg, because of treatment or environmental exposure) to 
the study vaccine prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy. 
If a study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the study vaccine, the investigator must submit this 
information to the Pfizer drug safety unit on an SAE report form and an EDP 
supplemental form, regardless of whether an SAE has occurred.  In addition, the 
investigator must submit information regarding environmental exposure to a Pfizer 
product in a pregnant woman (eg, a subject reports that she is pregnant and has been 
exposed to a cytotoxic product by inhalation or spillage) using the EDP supplemental 
form.  This must be done irrespective of whether an AE has occurred and within 24 hours 
of awareness of the exposure.  The information submitted should include the anticipated 
date of delivery (see below for information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome 
for all EDP reports with an unknown outcome.  The investigator will follow the 
pregnancy until completion (or until pregnancy termination) and notify Pfizer of the 
outcome as a follow-up to the initial EDP supplemental form.  In the case of a live birth, 
the structural integrity of the neonate can be assessed at the time of birth.  In the event of 
a termination, the reason(s) for termination should be specified and, if clinically possible, 
the structural integrity of the terminated fetus should be assessed by gross visual 
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inspection (unless preprocedure test findings are conclusive for a congenital anomaly and 
the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in 
a live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), 
the investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without 
regard to causality, as SAEs.  In addition, infant deaths after 1 month should be 
reported as SAEs when the investigator assesses the infant death as related or 
possibly related to exposure to the study vaccine. 
Additional information regarding the EDP may be requested by the investigator.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the study subject with the Pregnant Partner Release of 
Information Form to deliver to his partner.  The investigator must document in the source 
documents that the subject was given the Pregnant Partner Release of Information Form 
to provide to his partner.
8.1.5.
Definition of a serious adverse event 
A serious adverse event is any untoward medical occurrence that:
a.
Results in death,
b.
Is life-threatening,
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the subject was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, had it been more severe.
c.
Requires hospitalisation or prolongation of existing hospitalisation,
Note: In general, hospitalisation signifies that the subject has been admitted at the 
hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or in an out-patient setting. Complications 
that occur during 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,
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Note: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhoea, influenza like illness, and accidental trauma (e.g. sprained 
ankle) which may interfere or prevent everyday life functions but do not constitute a 
substantial disruption.
e.
Is a congenital anomaly/birth defect in the offspring of a study subject, OR
f.
Lack of efficacy.
Medical or scientific judgement should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalisation but may jeopardise the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious. 
Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalisation.
8.1.6.
Solicited adverse events
A 4-day follow-up (Day 0 - Day 3) of solicited local and general symptoms will be 
performed after the study vaccine administration.
8.1.6.1.
Solicited local (injection-site) adverse events
The following local (injection-site) AEs will be solicited:
Table 11
Solicited local adverse events
Pain at injection site
Redness at injection site
Swelling at injection site
If subjects/subject’s parent(s)/LAR(s) observe any large injection site reaction, they 
should contact the study personnel as soon as possible to determine if a visit to the 
investigator’s office for evaluation is necessary.
A large injection site reaction is:
a swelling that measures more than 100 mm across where the vaccine was given, 
or
a noticeable irregular/uneven swelling where the vaccine was given, or
a noticeable increase in size of the arm that interferes with or prevents everyday 
activities (e.g., writing, use of computer, school attendance, sleeping, etc.).
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In case of questions or uncertainties, the subject/subject’s parent(s)/LAR(s) should 
contact the investigator by phone and the investigator will determine whether or not a 
visit should be arranged.
The investigator will record detailed information describing the AE on a specific large 
injection site reaction screen in the eCRF. An SAE report should also be completed if the 
large injection site reaction meets the definition of an SAE.
8.1.6.2.
Solicited general adverse events
The following general AEs will be solicited:
Table 12
Solicited general adverse events
Fatigue
Fever*
Gastrointestinal symptoms †
Headache
* Fever is defined as temperature 37.5°C for oral, axillary or tympanic route, or 38.0°C for rectal route.
†Gastrointestinal symptoms include nausea, vomiting, diarrhoea and/or abdominal pain.
Note: Temperature will be recorded in the evening. Should additional temperature 
measurements be performed at other times of day, the highest temperature will be 
recorded in the eCRF.
8.1.7.
Clinical laboratory parameters and other abnormal assessments 
qualifying as adverse events or serious adverse events 
In absence of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, 
haematology, urinalysis) or other abnormal assessments (e.g. medical imaging) that are 
judged by the investigator to be clinically significant will be recorded as AE or SAE if 
they meet the definition of an AE or SAE (refer to Sections 8.1.1 and 8.1.5). Clinically 
significant abnormal laboratory findings or other abnormal assessments that are present at 
baseline and significantly worsen following the start of the study will also be reported as 
AEs or SAEs. However, clinically significant abnormal laboratory findings or other 
abnormal assessments that are associated with the disease being studied, unless judged by 
the investigator as more severe than expected for the subject’s condition, or that are 
present or detected at the start of the study and do not worsen, will not be reported as AEs 
or SAEs.
The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant.
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8.1.8.
Adverse events of specific interest
AEs of specific interest for safety monitoring include the occurrence of 

NOCIs such as autoimmune disorders, asthma, type 1 diabetes and allergies. Refer to 
Section 8.1.8.1 for a non-exhaustive list of illnesses that can be recorded as NOCIs.

GBS (to be reported as an SAE).

Meningococcal disease (to be reported as an SAE).
See Section 8.2 and 8.3 for information on recording and reporting of these events.
8.1.8.1.
List of New Onset of Chronic Illnesses
Table 13 presents a non-exhaustive list of illnesses that can be recorded as NOCIs.
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Table 13
List of NOCIs
Disease/Disorder
Blood autoimmune disorders
Anaemia haemolytic autoimmune
Antiphospholipid syndrome
Cold type haemolytic anaemia
Coombs positive haemolytic anaemia
Idiopathic thrombocytopenic purpura
Pernicious anaemia
Warm type haemolytic anaemia
Autoimmune thrombocytopenia
Evan’s syndrome
Autoimmune neutropenia
Thrombocytopenias
Endocrine autoimmune disorder
Basedow’s disease
Insulin autoimmune syndrome
Polyglandular autoimmune syndrome type I
Polyglandular autoimmune syndrome type II
Autoimmune thyroiditis
Diabetic mastopathy
Lymphocytic hypophysitis
Polyglandular autoimmune syndrome type III
Endocrine symptoms
Hyperthyroidism
Hypothyroidism
Goiter
Hepatic autoimmune disorder
Autoimmune hepatitis
Biliary cirrhosis primary
Muscular autoimmune disorder
Myasthenia gravis
Myasthenia gravis neonatal
Polymyalgia
Polypyalgia rheumatica
Polymyositis
Ocular myasthenia
Myasthenia gravis crisis
Lupus erythematosus and associated 
conditions
Lupoid hepatic cirrhosis
Lupus encephalitis
Lupus nephritis
SLE arthritis
Systemic lupus erythematosus
Systemic lupus erythematosus rash
Lupus-like syndrome
Cutaneous lupus erythematosus
Lupus pneumonitis
Neonatal lupus erythematosus
Lupus vasculitis
Pericarditis lupus
Lupus endocarditis
Peritonitis lupus
Neuropsychiatric lupus
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Disease/Disorder
Autoimmune disorders NEC
Ankylosis spondylitis
Cryoglobulinaemia
Gastritis atrophic
Goodpasture’s syndrome
Keratoconjunctivitis sicca
Keratoderma blenorrhagica
Mixed connective tissue disease
Reiter’s syndrome
Sicca syndrome
Sjogren’s syndrome
Sympathetic ophtalmia
Leukoencephalomyelitis
Toxic oil syndrome
Cryofibrinogenaemia
Encephalitis allergic
Nephritis autoimmune
Acute haemorrhagic leukoencephalitis
Autoimmune disorder
Rheumatoid arthritis and associated conditions
Felty’s syndrome
Rheumatoid arthritis
Rheumatoid lung
Rheumatoid vasculitis
Rheumatoid nodule
Juvenile arthritis
Laryngeal rheumatoid arthritis
Scleroderma and associated disorders
CREST syndrome
Morphoea
Scleroderma
Systemic sclerosis
Systemic sclerosis pulmonary
Scleroderma renal crisis
Skin autommune disorders NEC
Benign familial pemphigus
Dermatitis herpetiformis
Dermatomyosistis
Eosinophilic fasciitis
Herpes gestationis
Linear IgA disease
Pemphigoid
Pemphigus
Vitiligo
Acute and chronic thyroiditis
Thyroiditis
Thyroiditis acute
Thyroiditis chronic
Thyroiditis subacute
Autoimmune thyroiditis
Optic neuritis
Optic neuritis
Optic neuritis retrobulbar
Vision blurred
Blindness
Visual acuity reduced
Visual evoked potential abnormaly
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Disease/Disorder
Multiple sclerosis
Multiple sclerosis
Demyelineting disorder
Gait disturbances
Muscle weakness
Paraesthesias
(Cognitive impairment)
(Nuclear magnetic resonance imaging brain abnormal)
Transverse myelitis
Myelitis Transverse
Muscle weakness
Low back pain
Paraesthesias and dysaesthesias
Paralysis
(Urinary retention)
(Neurogenic bladder)
Guillain-Barre syndrome
Guillain-Barre syndrome
Muscle weakness
Paraesthesias and dysaesthesias
Diabetes mellitus insulin-dependent
Diabetes mellitus
Diabetes mellitus (incl. subtypes)
Glucose metabolism disorders (incl. diabetes mellitus)
Uveitis
Uveitis
Eye pain
Eye redness
Photophobia
Glomerulonephritis
Lupus nephritis
Proteinuria
Haematuria
Glomerular filtration rate decreased
(Hypoproteinemia)
(Oedema)
Blood urea increased
Blood creatinine increase
Inflammatory bowel disease
Inflammatory bowel disease
Crohn’s disease
Crohn’s disease
Ulcerative colitis
Ulcerative colitis
Rectal bleeding
Coeliac disease
Coeliac disease
Sarcoidosis
Sarcoidosis
Angiotensin converting enzyme increased
Asthma
Asthma
Allergies
Immune system disorders
Allergic conditions
Auto immunity analyses
Asthmatic crisis
Asthmatic crisis
8.1.9.
Pregnancy
Female subjects who become pregnant after the vaccination may continue the study at the 
discretion of the investigator.
While pregnancy itself is not considered an AE or SAE, any adverse pregnancy outcome 
or complication or elective termination of a pregnancy for medical reasons will be 
recorded and reported as an AE or a SAE.
Note: The pregnancy itself should always be recorded on an EDP form.
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The following should always be considered as SAE and will be reported as described in 
Sections 8.3.1 and 8.3.2:

Spontaneous pregnancy loss, including:

spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of 
gestation)

ectopic and molar pregnancy

stillbirth (intrauterine death of foetus after 22 weeks of gestation).
Note: the 22 weeks cut-off in gestational age is based on WHO-ICD 10 noted in the 
EMA Guideline on pregnancy exposure [EMA, 2006]. It is recognized that national 
regulations might be different.

Any early neonatal death (i.e. death of a live born infant occurring within the first 7 
days of life). 

Any congenital anomaly or birth defect (as per [CDC MACDP] guidelines) 
identified in the offspring of a study subject (either during pregnancy, at birth or 
later) regardless of whether the foetus is delivered dead or alive. This includes 
anomalies identified by prenatal ultrasound, amniocentesis or examination of the 
products of conception after elective or spontaneous abortion.
Furthermore, any SAE occurring as a result of a post-study pregnancy AND considered 
by the investigator to be reasonably related to the investigational vaccine(s)/product(s) 
will be reported to Pfizer as described in Section 5.6.15. While the investigator is not 
obligated to actively seek this information from former study participants, he/she may 
learn of a pregnancy through spontaneous reporting.
8.2.
Detecting and recording adverse events, serious adverse 
events and pregnancies
8.2.1.
Time period for detecting and recording adverse events, serious 
adverse events and pregnancies
All AEs and SAEs starting within 30 days following administration of the dose of study 
vaccine must be recorded into the appropriate section of the eCRF, irrespective of 
intensity or whether or not they are considered vaccination-related.
The time period for collecting and recording SAEs will begin at the receipt of study 
vaccine and will end 6 months following administration of the dose of study vaccine for 
each subject. See Section 8.3 for instructions on reporting of SAEs.
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the time of the receipt of study vaccine.
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SAEs that are related to the investigational vaccine/product will be collected and 
recorded from the time of the receipt of study vaccine/placebo/comparator until the 
subject is discharged from the study.
In addition to the above-mentioned reporting requirements and in order to fulfil 
international reporting obligations, SAEs that are related to study participation (i.e. 
protocol-mandated procedures, invasive tests, a change from existing therapy) will be 
collected and recorded from the time the subject consents to participate in the study until 
she/he is discharged from the study.
The time period for collecting and recording pregnancies will begin at the first receipt of 
study vaccine and will end 30 days following administration of the dose of study vaccine. 
See section 8.3 for instructions on reporting of pregnancies.
Occurrences of NOCIs (e.g. auto-immune disorders, asthma, type 1 diabetes, allergies) 
will be recorded from administration of the vaccine dose until 6 months after 
administration of the vaccine dose, whether or not they are considered to be possibly 
related to vaccine administration. Medical documentation of the events will be reported 
either as an unsolicited AE or as an SAE as appropriate in the eCRF.
Occurrences of GBS will be recorded from administration of the vaccine dose until 6
months after administration of the vaccine dose. Clinical details should be obtained as 
outlined in the ‘Potential immune mediated disorders: standard questionnaires and list of 
preferred terms’. All occurrences of GBS have to be reported as SAEs.
An overview of the protocol-required reporting periods for AEs, SAEs, and pregnancies 
is given in Table 14.
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8.2.2.
Post-Study adverse events and serious adverse events
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Table 14. Investigators are not obligated to actively seek AEs 
or SAEs in former study participants. However, if the investigator learns of any SAE at 
any time after a subject has been discharged from the study, and he/she considers the 
event reasonably related to the investigational vaccine/product, the investigator will 
promptly report the SAEs to Pfizer.
8.2.3.
Evaluation of adverse events and serious adverse events
8.2.3.1.
Active questioning to detect adverse events and serious adverse 
events
As a consistent method of collecting AEs, the subject should be asked a non-leading 
question such as:
‘Have you felt different in any way since receiving the vaccine or since the previous 
visit?’
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
subject’s medical records to Pfizer instead of appropriately completing the SAE form and 
AE CRF. However, there may be instances when copies of medical records for certain 
cases are requested by Pfizer. In this instance, all subject identifiers will be blinded on the 
copies of the medical records prior to submission to Pfizer.
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms.
8.2.3.2.
Assessment of adverse events
8.2.3.2.1.
Assessment of intensity
The intensity of the following solicited AEs will be assessed as described:
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Table 15
Intensity scales for solicited symptoms in adults
Adults
Adverse Event
Intensity grade
Parameter
Pain at injection site
0
None
1
Mild: Any pain neither interfering with nor preventing 
normal every day activities.
2
Moderate: Painful when limb is moved and interferes with 
every day activities.
3
Severe: Significant pain at rest. Prevents normal every 
day activities.
Redness at injection site
Record greatest surface diameter in mm
Swelling at injection site
Record greatest surface diameter in mm
Fever*
Record temperature in °C/°F
Headache
0
Normal
1
Mild: Headache that is easily tolerated
2
Moderate: Headache that interferes with normal activity
3
Severe: Headache that prevents normal activity
Fatigue
0
Normal
1
Mild: Fatigue that is easily tolerated
2
Moderate: Fatigue that interferes with normal activity
3
Severe: Fatigue that prevents normal activity
Gastrointestinal symptoms
0
Gastrointestinal symptoms normal
(nausea, vomiting, diarrhoea and/or 
abdominal pain)
1
Mild: Gastrointestinal symptoms that are easily tolerated
2
Moderate: Gastrointestinal symptoms that interfere with 
normal activity
3
Severe: Gastrointestinal symptoms that prevent normal 
activity
* Fever is defined as temperature 37.5°C for oral, axillary or tympanic route, or 38.0°C for rectal route. The 
preferred route for recording temperature in this study will be oral.
The maximum intensity of local injection site redness/swelling will be scored as follows:
0
:
None
1
:
> 0 - 20 mm
2
:
> 20 - 50 mm
3
:
> 50 mm
The maximum intensity of fever will be scored as follows for oral/axillary or tympanic 
route:
0
:
< 37.5°C 
1
:
37.5°C to 38.0°C 
2
:
38.1°C to 39.0°C
3
:
> 39.0°
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The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgement.
The intensity should be assigned to one of the following categories:
1 (mild)
=
An AE which is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities.
2 (moderate)
=
An AE which is sufficiently discomforting to interfere with 
normal everyday activities.
3 (severe)
=
An AE which prevents normal, everyday activities 
Such an AE would, for example, prevent attendance at 
work/school and would necessitate the administration of corrective 
therapy.
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. Grade 
3 is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets one of the pre-
defined outcomes as described in Section 8.1.5.
8.2.3.2.2.
Assessment of causality
The definitions for ‘NO’ and ‘YES’ have been written in such a way that all events that 
have been attributed a ‘NO’ can be pooled with events which in the primary vaccination 
study were determined to be ‘not related’ or ‘unlikely to be related’ to vaccination. Those 
events that are attributed a ‘YES’ can be pooled with those events that in the past were 
determined to have a ‘suspected’ or ‘probable’ relationship to vaccination in the primary 
vaccination study.
The investigator is obligated to assess the relationship between investigational 
vaccine/product and the occurrence of each unsolicited AEs (including SAEs) and for 
general solicited AEs. The investigator will use clinical judgement to determine the 
relationship. Alternative plausible causes, such as natural history of the underlying 
diseases, concomitant therapy, other risk factors, and the temporal relationship of the 
event to the investigational vaccine/product will be considered and investigated. The 
investigator will also consult the SRSD to determine his/her assessment.
There may be situations when a SAE has occurred and the investigator has minimal 
information to include in the initial report to Pfizer. However, it is very important that the 
investigator always makes an assessment of causality for every event prior to submission 
of the SAE report to Pfizer. The investigator may change his/her opinion of causality in 
light of follow-up information and update the SAE information accordingly. The 
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causality assessment is one of the criteria used when determining regulatory reporting 
requirements.
In case of concomitant administration of multiple vaccines, it may not be possible to 
determine the causal relationship of general AEs to the individual vaccines administered. 
The investigator should, therefore, assess whether the AE could be causally related to 
vaccination rather than to the individual vaccines.
All solicited local (injection site) reactions will be considered causally related to 
vaccination. Causality of all other AEs should be assessed by the investigator using the 
following question:
Is there a reasonable possibility that the AE may have been caused by the investigational 
vaccine/product?
YES
:
There is a reasonable possibility that the vaccine(s) contributed to
the AE. 
NO
:
There is no reasonable possibility that the AE is causally related to 
the administration of the study vaccine(s). There are other, more 
likely causes and administration of the study vaccine(s) is not 
suspected to have contributed to the AE.
If an event meets the criteria to be determined as ‘serious’ (see Section 8.1.5), additional 
examinations/tests will be performed by the investigator in order to determine ALL 
possible contributing factors for each SAE.
Possible contributing factors include:

Medical history.

Other medication.

Protocol required procedure.

Other procedure not required by the protocol.

Lack of efficacy of the vaccine, if applicable.

Erroneous administration.

Other cause (specify).
8.2.3.3.
Assessment of outcomes
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as:

Recovered/resolved.

Recovering/resolving.
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
Not recovered/not resolved.

Recovered with sequelae/resolved with sequelae.

Fatal (SAEs only).
8.2.3.4.
Medically attended visits
For each solicited and unsolicited symptom the subject experiences, the subject will be 
asked if he/she /the subject received medical attention defined as hospitalisation, or an 
otherwise unscheduled visit to or from medical personnel for any reason, including 
emergency room visits. This information will be recorded in the eCRF. 
8.2.3.5.
Adverse events of specific interest
AEs of specific interest for safety monitoring include:

NOCIs such as autoimmune diseases, asthma, type I diabetes and allergies. Refer to 
Section 8.1.8.1 for a non-exhaustive list of illnesses that can be recorded as NOCI.

GBS.

Meningococcal disease.
Occurrences of NOCIs will be reported up to six months after the vaccine dose regardless 
of seriousness and whether or not they are considered to be possibly related to the 
treatment administration. Medical documentation of the events will be reported either as 
an unsolicited AE or as an SAE as appropriate in the eCRF.
Occurrences of GBS will be reported up to six months after the vaccine dose regardless 
of seriousness. Clinical details should be obtained as outlined in the ‘Potential immune 
mediated disorders: standard questionnaires and list of preferred terms’. All occurrences 
of GBS have to be reported as an SAE.
Occurrences of meningococcal disease will be reported during the entire course of the 
study up the study end regardless of seriousness and have to be reported as an SAE.
8.3.
Reporting of serious adverse events, pregnancies, and 
other events
8.3.1.
Prompt reporting of serious adverse events, pregnancies, and 
other events
SAEs that occur in the time period defined in Section 8.2 will be reported promptly 
within the timeframes described in Table 16, once the investigator determines that the 
event meets the protocol definition of a SAE.
Pregnancies that occur in the time period defined in Section 8.2 will be reported promptly 
within the timeframes described in Table 16, once the investigator becomes aware of the 
pregnancy. 
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Table 16
Timeframes for submitting serious adverse event, pregnancy 
and other events reports
Type of Event
Initial Reports
Follow-up of Relevant Information on a 
Previous Report
Timeframe
Documents
Timeframe
Documents
All SAEs
24 hours*
Paper SAE report
24 hours*
Paper SAE report
Pregnancies
24 hours*
Paper SAE and EDP reports
24 hours*
Paper SAE and EDP reports
GBS
24 hours*
Paper  SAE report
24 hours*
Paper SAE report
Meningococcal 
disease
24 hours*
Paper SAE report
24 hours*
Paper SAE report
* Timeframe allowed after receipt or awareness of the information.
8.3.2.
Completion and transmission of SAE reports
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator (or designate) must complete the information in the paper SAE report 
WITHIN 24 HOURS. The SAE report will always be completed as thoroughly as 
possible with all available details of the event. Even if the investigator does not have all 
information regarding a SAE, the report should still be completed within 24 hours. Once 
additional relevant information is received, the report should be updated WITHIN 24 
HOURS.
The investigator will always provide an assessment of causality at the time of the initial 
report.
8.3.3.
Completion and transmission of pregnancy reports
Once the investigator becomes aware that a subject is pregnant, the investigator (or 
designate) must complete the required information onto the EDP report WITHIN 24 hours
of awareness of the exposure.
Note: Conventionally, the estimated gestational age (EGA) of a pregnancy is dated from 
the first day of the last menstrual period (LMP) of the cycle in which a woman conceives. 
If the LMP is uncertain or unknown, dating of EGA and the estimated date of delivery 
(EDD) should be estimated by ultrasound examination and recorded in the EDP report.
8.3.4.
Updating of SAE and pregnancy information after freezing of the 
subject’s eCRF
When additional SAE or pregnancy information is received after freezing of the subject’s 
eCRF, new or updated information should be recorded on a paper report, with all changes 
signed and dated by the investigator. The updated report should be faxed to Pfizer within 
the designated reporting time frames specified in Table 16.
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8.3.5.
Regulatory reporting requirements for serious adverse events
The investigator will promptly report all SAEs to Pfizer in accordance with the 
procedures detailed in Section 8.3.1. Pfizer has a legal responsibility to promptly notify, 
as appropriate, both the local regulatory authority and other regulatory agencies about the 
safety of a product under clinical investigation. Prompt notification of SAEs by the 
investigator to Pfizer is essential so that legal obligations and ethical responsibilities 
towards the safety of other subjects are met.
Investigator safety reports are prepared according to the current Pfizer policy and are 
forwarded to investigators as necessary. An investigator safety report is prepared for a 
SAE(s) that is both attributable to the investigational vaccine/product and unexpected. 
The purpose of the report is to fulfil specific regulatory and GCP requirements, regarding 
the product under investigation.
8.4.
Follow-up of adverse events, serious adverse events, and 
pregnancies
8.4.1.
Follow-up of adverse events and serious adverse events 
8.4.1.1.
Follow-up during the study
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject and provide additional relevant information on the subject’s condition to Pfizer
(within 24 hours for SAEs; refer to Table 16).
All SAEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until the 
end of the study.
All AEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until   
study end.
NOCIs and GBS documented at a previous visit/contact and designated as not 
recovered/not resolved or recovering/resolving will be reviewed at subsequent 
visits/contacts until six months after the vaccine dose.
8.4.1.2.
Follow-up after the subject is discharged from the study
The investigator will follow subjects:

with SAEs, or subjects withdrawn from the study as a result of an AE, until the event 
has resolved, subsided, stabilised, disappeared, or until the event is otherwise 
explained, or the subject is lost to follow-up. 
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
with other AEs of specific interest (i.e. NOCIs), until six months after the vaccine 
dose or they are lost to follow-up. 
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to Pfizer using a paper SAE and/or EDP report as 
applicable.
Pfizer may request that the investigator performs or arranges the conduct of additional 
clinical examinations/tests and/or evaluations to elucidate as fully as possible the nature 
and/or causality of the AE or SAE. The investigator is obliged to assist. If a subject dies 
during participation in the study or during a recognised follow-up period, Pfizer will be 
provided with any available post-mortem findings, including histopathology.
8.4.2.
Follow-up of pregnancies
Pregnant subjects will be followed to determine the outcome of the pregnancy. At the end 
of the pregnancy, whether full-term or premature, information on the status of the mother 
and child will be forwarded to Pfizer using the EDP report and the SAE report if 
applicable. Generally, the follow-up period doesn’t need to be longer than six to eight 
weeks after the estimated date of delivery.
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is a 
SAE, it should always be reported as an SAE.
8.5.
Treatment of adverse events
Treatment of any AE is at the sole discretion of the investigator and according to current 
good medical practice. Any medication administered for the treatment of an AE should 
be recorded in the subject’s eCRF (refer to Section 6.5).
8.6.
Subject card
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational compound identifiers, subject study 
numbers, contact information for the investigational site, and contact details for a contact 
center in the event that the investigational site staff cannot be reached to provide advice 
on a medical question or problem originating from another healthcare professional not 
involved in the subject’s participation in the study.  The contact number can also be used 
by investigational staff if they are seeking advice on medical questions or problems; 
however, it should be used only in the event that the established communication 
pathways between the investigational site and the study team are not available.  It is 
therefore intended to augment, but not replace, the established communication pathways 
between the investigational site and the study team for advice on medical questions or 
problems that may arise during the study.  The contact number is not intended for use by 
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the subject directly, and if a subject calls that number, he or she will be directed back to 
the investigational site.
Subjects must be instructed to keep subject cards in their possession at all times.
9.
SUBJECT COMPLETION AND WITHDRAWAL
9.1.
Subject completion
A subject who returns for the concluding visit/is available for the concluding contact 
foreseen in the protocol is considered to have completed the study.
A subject who completes a given epoch is considered to have completed the 
corresponding persistence time point.  
At each persistence time point, the number of subjects completing the indicated 
persistence visit and the number of subjects withdrawn at the indicated persistence visit 
will be calculated.
9.2.
Subject withdrawal
Subjects who are withdrawn because of SAEs/AEs must be clearly distinguished from 
subjects who are withdrawn for other reasons. Investigators will follow subjects who are 
withdrawn as result of an SAE/AE until resolution of the event (see Section 8.4.1.2).
Withdrawals will not be replaced.
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.  
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Information relative to the withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject himself/herself, by the subject’s parent(s) or LAR(s), or by the investigator, as 
well as which of the following possible reasons was responsible for withdrawal:

Serious adverse event.

Non-serious adverse event.

Protocol violation (specify).

Consent withdrawal, not due to an adverse event*.

Moved from the study area.

Lost to follow-up.

Other (specify).
*In case a subject is withdrawn from the study because he/she/the subject’s parent(s) has 
withdrawn consent, the investigator will document the reason for withdrawal of consent, 
if specified by the subject, in the CRF.
Subjects who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from subjects who are withdrawn for other reasons. Investigators will 
follow subjects who are withdrawn from the study as result of a SAE/AE until resolution 
of the event (see Section 8.4.1.2).
9.2.2.
Subject withdrawal from investigational vaccine
A ‘withdrawal’ from the investigational vaccine refers to any subject who does not 
receive the complete treatment, i.e. when no further planned dose is administered from 
the date of withdrawal. A subject withdrawn from the investigational vaccine may not 
necessarily be withdrawn from the study as further study procedures or follow-up may be 
performed (safety or immunogenicity) if planned in the study protocol. 
Information relative to premature discontinuation of the investigational vaccine will be 
documented on the Vaccine Administration page/screen of the eCRF. The investigator 
will document whether the decision to discontinue further vaccination/treatment was 
made by the subject himself/herself, by the subject’s parent(s) or LAR(s), or by the 
investigator, as well as which of the following possible reasons was responsible for 
withdrawal:

Serious adverse event.

Non-serious adverse event.

Other (specify).
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10.
STATISTICAL METHODS
10.1.
Primary endpoint
Immunogenicity with respect to the components of the investigational vaccine six, 
seven, eight, nine and ten years after primary vaccination in Study MENACWY-
TT-015:

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY antibody titres 1:8, 
1:128 and GMTs.
10.2.
Secondary endpoints
Immunogenicity with respect to the components of the investigational vaccine one 
month post-booster vaccination at ten years after primary vaccination:

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY antibody titers ≥1:8,
1:128, GMTs and rSBA vaccine response.
Immunogenicity with respect to the components of the investigational vaccine pre-
booster and one month post-booster vaccination at ten years after primary 
vaccination:

Anti-TT concentrations ≥0.1 IU/mL, ≥1.0 IU/mL and GMCs. 
Safety and reactogenicity

Occurrence of solicited local and general symptoms on days 0-3 following the 
booster vaccination.

Occurrence of unsolicited symptoms up to 31 days following booster vaccination.

Occurrence of serious AEs, and new onset chronic illness(es) (e.g. autoimmune 
disorders, asthma, type 1 diabetes and allergies), GBS and meningococcal disease 
from administration of the vaccine dose until study end.
10.3.
Determination of sample size
The actual sample size of this study with respect to the analysis of persistence and safety 
and immunogenicity post-booster is determined by a) the sample size of the primary 
vaccination study MENACWY-TT-015 (107386), b) the actual enrolment rates at the 
YR6-10 extension study, and c) the actual annual drop out rate. All subjects who 
completed study MENACWY-TT-015 (107386) and received either MenACWY-TT 
vaccine or Mencevax ACWY will be eligible for this study if they meet the 
inclusion/exclusion criteria. 400 subjects (299 in the ACWY-TT group and 101 in the 
MenPS group) were enrolled and vaccinated in study MENACWY-TT-015 (107386) in 
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the Philippines. An enrollment rate equivalent to approximately 80% of the vaccinated 
population in study MENACWY-TT-015 (107386) is assumed, and an annual drop out 
rate of 10% is assumed.
If one assumes approximately 10% of subjects drop out of the persistence study at every 
visit, then one expects the following numbers of subjects to participate at each persistence 
time point.

For the analysis of Month 72, it is estimated that approximately 336 subjects will be 
enrolled (252 in the ACWY-TT group and 84 in the MenPS group)

For the analysis of Month 84, it is estimated that approximately 304 subjects will be 
enrolled (228 in the ACWY-TT group and 76 in the MenPS group)

For the analysis of Month 96, it is estimated that approximately 274 subjects will be 
enrolled (205 in the ACWY-TT group and 69 in the MenPS group)

For the analysis of Month 108, it is estimated that approximately 248 subjects will be 
enrolled (186 in the ACWY-TT group and 62 in the MenPS group)

For the analysis of Month 120, it is estimated that approximately 224 subjects will be 
enrolled (168 in the ACWY-TT group and 56 in the MenPS group)
The primary objective of this study is to evaluate at 6, 7, 8, 9 and 10 years after primary 
vaccination of MenACWY-TT and Mencevax ACWY, the long term persistence of 
antibodies induced by MenACWY-TT vaccine as compared to Mencevax ACWY when 
administered at 11-55 years of age in terms of the percentage of subjects with rSBA-
MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titers ≥ 1:8, ≥ 1:128 and GMTs.
Table 17 illustrates the accuracy one can expect from a sample size of evaluable subjects 
at year 6, at year 7, at year 8, at year 9 and at year 10 for evaluation the percentage of 
subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titers ≥ 1:8 
in each group.
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Table 17
Exact 95% confidence intervals of the percentage of subjects 
with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-
MenY titers ≥ 1:8
Year 6
Approx %
ACWY-TT (N = 252 )
Men-PS (N = 84)
20
[
15.1
;
25.3
]
[
12.3
;
30.4
]
30
[
24.6
;
36.2
]
[
20.3
;
40.7
]
40
[
34.0
;
46.4
]
[
29.9
;
51.7
]
50
[
43.7
;
56.3
]
[
38.9
;
61.1
]
60
[
53.6
;
66.0
]
[
48.3
;
70.1
]
70
[
63.8
;
75.4
]
[
59.3
;
79.7
]
80
[
74.7
;
84.9
]
[
69.6
;
87.7
]
90
[
85.7
;
93.5
]
[
82.1
;
95.8
]
100
[
98.5
;
100
]
[
95.7
;
100
]
Year 7
%
ACWY-TT (N = 228)
Men-PS (N = 76)
20
[
15.2
;
26.0
]
[
11.5
;
30.5
]
30
[
24.0
;
36.2
]
[
20.2
;
41.9
]
40
[
33.5
;
46.6
]
[
28.4
;
51.4
]
50
[
43.3
;
56.7
]
[
38.3
;
61.7
]
60
[
53.4
;
66.5
]
[
48.6
;
71.6
]
70
[
63.8
;
76.0
]
[
58.1
;
79.8
]
80
[
74.0
;
84.8
]
[
69.5
;
88.5
]
90
[
85.2
;
93.5
]
[
80.3
;
95.3
]
100
[
98.4
;
100
]
[
95.3
;
100
]
Year 8
%
ACWY-TT (N = 205)
Men-PS (N = 69)
20
[
14.8
;
26.1
]
[
11.6
;
31.7
]
30
[
24.0
;
37.0
]
[
19.9
;
42.7
]
40
[
33.2
;
47.1
]
[
28.9
;
53.1
]
50
[
43.2
;
57.3
]
[
38.4
;
63.0
]
60
[
52.9
;
66.8
]
[
46.9
;
71.1
]
70
[
63.5
;
76.4
]
[
57.3
;
80.1
]
80
[
73.9
;
85.2
]
[
68.3
;
88.4
]
90
[
85.3
;
93.9
]
[
80.2
;
95.8
]
100
[
98.2
;
100
]
[
94.8
;
100
]
Year 9
%
ACWY-TT (N = 186)
Men-PS (N = 62)
20
[
14.4
;
26.4
]
[
10.4
;
31.4
]
30
[
23.6
;
37.2
]
[
19.6
;
43.7
]
40
[
32.7
;
47.2
]
[
28.1
;
53.6
]
50
[
42.6
;
57.4
]
[
37.0
;
63.0
]
60
[
52.8
;
67.3
]
[
46.4
;
71.9
]
70
[
62.8
;
76.4
]
[
56.3
;
80.4
]
80
[
73.6
;
85.6
]
[
68.6
;
89.6
]
90
[
84.5
;
93.7
]
[
80.1
;
96.4
]
100
[
98.0
;
100
]
[
94.2
;
100
]
Year 10
%
ACWY-TT (N = 168)
Men-PS (N = 56)
20
[
14.4
;
27.1
]
[
10.2
;
32.4
]
30
[
23.0
;
37.3
]
[
18.8
;
44.1
]
40
[
32.4
;
47.7
]
[
26.5
;
53.2
]
50
[
42.2
;
57.8
]
[
36.3
;
63.7
]
60
[
52.3
;
67.6
]
[
46.8
;
73.5
]
70
[
62.7
;
77.0
]
[
55.9
;
81.2
]
80
[
72.9
;
85.6
]
[
67.6
;
89.8
]
90
[
84.3
;
94.0
]
[
78.1
;
96.0
]
100
[
97.8
;
100
]
[
93.6
;
100
]
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10.4.
Study cohorts/ data sets to be analysed
Five cohorts are defined for the purpose of analysis:

Total cohort at Year X.

ATP cohort for persistence at Year X.

Total vaccinated cohort at Visit 6 (Month 121)

ATP cohort for safety at Visit 6 (Month 121)

ATP cohort for immunogenicity Visit 6 (Month 121)
10.4.1.
Total cohort at Year X
The Total Cohort will include all vaccinated subjects in study MENACWY-TT-015 
(107386). For the analysis of persistence at year x, this will include all vaccinated 
subjects for whom data concerning persistence endpoint measures are available at year x.
10.4.2.
According-To-Protocol (ATP) cohort for persistence at Year X
The ATP cohort for antibody persistence for year x will include all  subjects: 

who were eligible in study MENACWY-TT-015 (107386).

who have received the primary vaccination with MenACWY-TT or Mencevax 
ACWY during study MENACWY-TT-015 (107386).

who have available assay results for at least one tested antigen at year x.

who have not received a meningococcal polysaccharide or a meningococcal 
polysaccharide conjugate vaccine not planned in protocol MENACWY-TT-015 
(107386) before year x.

who do not have a history of meningococcal serogroup A, C, W-135, and Y disease 
prior to year x.

who comply with the blood sampling intervals defined in Table 5 of the protocol for 
year x.

who do not have an immunocompromising medical condition.

who have not received any immunosuppressant(s) or other immune-modifying 
drug(s), immunoglobulins, any blood products, investigational drugs, and/or 
investigational vaccines during the timeframe specified in the protocol. 

who were not excluded from the ATP cohort in the primary study MENACWY-TT-
015 PRI (107386) and from the previous ATP persistence cohorts, unless the reason 
for exclusion was either non-compliance with the protocol-defined serum sampling 
windows or a lack of availability of immunogenicity results at previous time point
10.4.3.
Total Vaccinated Cohort at Visit 6 (Month 121)
Except for the related SAE listings that may be generated at Persistence Year 6, 7, 8, 9 
and 10 on the Total cohort at Year X, safety analyses will be done post-booster 
vaccination only. The Total Vaccinated Cohort for safety following the booster 
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vaccination will include all vaccinated subjects in the primary vaccination study 
MENACWY-TT-015 with a booster vaccine administration documented.
For the analysis of immunogenicity post-vaccination the Total Vaccinated Cohort will 
include all subjects for whom data concerning post-booster immunogenicity endpoint 
measures are available.
10.4.4.
According-To-Protocol (ATP) cohort for safety at Visit 6 (Month
121)
The ATP cohort for safety following booster vaccination will include all subjects:

who met all inclusion criteria and no exclusion criteria for the study

who have received a dose of study vaccine MenACWY-TT or Mencevax ACWY in 
the primary study MENACWY-TT-015.

who have not received a vaccine not specified or forbidden in the protocol (subjects 
who received a vaccine not foreseen by the study protocol from 30 days before until 
30 days after the study vaccine dose will be eliminated from the ATP cohort for 
safety if the vaccine not foreseen by the protocol was administered before the post-
vaccination blood sample).

who have received a booster dose of study vaccine.

for whom the administration site of the vaccine/control is known.
10.4.5.
According To Protocol (ATP) cohort for immunogenicity at Visit 6 
(Month 121)
The ATP cohort for immunogenicity will include all evaluable subjects (i.e. those 
meeting all eligibility criteria, complying with the procedures defined in the protocol and 
with no elimination criteria during the study) from the ATP cohort for safety for whom 
assay results are available for antibodies against at least one study vaccine antigen 
component for the blood sample taken one month post-vaccination, and who were not 
administered a vaccine not foreseen by the study protocol before the post-vaccination 
blood sample. The interval between Visit 5 and Visit 6 for inclusion in the Booster ATP 
cohort for immunogenicity will be defined as 21 to 48 days.
10.5.
Derived and transformed data
10.5.1.
Immunogenicity

For a given subject and a given immunogenicity measurement, missing or non-
evaluable measurements will not be replaced. Therefore, an analysis will exclude 
subjects with missing or non-evaluable measurements.

The cut-off value is defined by the laboratory before the analysis and is described in 
Section 5.7.3.

A seronegative subject is a subject whose titre is below the cut-off value.
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
A seropositive subject is a subject whose titre is greater than or equal to the cut-off 
value.

The Geometric Mean Titres/Concentrations (GMTs/GMCs) calculations are 
performed by taking the anti-log of the mean of the log titre transformations. 
Antibody titres below the cut-off value of the assay will be given an arbitrary value 
of half the cut-off value for the purpose of GMT/GMC calculation.

rSBA vaccine response for serogroups A, C, W-135 and Y after the vaccine dose is 
defined as:

For initially seronegative subjects (pre-vaccination titer below the cut-off of 
1:8): rSBA antibody titers post-vaccination titer 1:32 one month after 
vaccination, and

For initially seropositive subjects (pre-vaccination titer 1:8): rSBA antibody 
titers at least four times the pre-vaccination antibody titers, one month after 
vaccination.

Seroconversion is defined as the appearance of antibodies (i.e. titre greater than or 
equal to the cut-off value) in the serum of subjects seronegative before vaccination.

Handling of missing data: for a given subject and a given immunogenicity 
measurement, missing or non-evaluable measurements will not be replaced. 
10.5.2.
Reactogenicity and Safety

For a given subject and the analysis of solicited AEs within four days post-
vaccination, missing or non-evaluable measurements will not be replaced. Therefore 
the analysis of the solicited AEs based on the Total Vaccinated cohort will include 
only vaccinated subjects and doses with documented safety data (i.e. symptom 
screen completed).

For analysis of unsolicited AEs, such as SAEs or AEs by primary MedDRA 
(Medical Dictionary for Regulatory Activities) term, and for the analysis of 
concomitant medications, all vaccinated subjects will be considered. Subjects who 
did not report an event or a concomitant medication will be considered as subjects 
without an event or a concomitant medication respectively.

For summaries reporting both solicited and unsolicited AEs, all vaccinated subjects 
will be considered. Subjects who did not report an event or a concomitant medication 
will be considered as subjects without an event or a concomitant medication.
10.6.
Persistence analyses
10.6.1.
Analysis of demographics/baseline characteristics
Demographic characteristics of each study cohort will be tabulated: age at Year X and 
months since the primary vaccination at 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.
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The distribution of subjects enrolled at Year X among the study sites will be tabulated as 
a whole and per group and reason for not attending a visit at Year X among all subjects 
who participated in the primary vaccination study MENACWY-TT-015 (107386) will be 
summarized.
10.6.2.
Analysis of persistence
For each Year X: The analysis of antibody persistence will be based on the ATP cohort 
for antibody persistence at Year X. If, for any vaccine group, the percentage of subjects 
who come back for the Year X follow-up with serological results excluded from the ATP 
cohort is higher than 5%, a second analysis based on the Total Vaccinated Cohort Year X 
will be performed to complement the ATP analysis.
For each treatment group, at each blood sampling time-point, for each antigen assessed:

Geometric mean antibody titres or concentration (GMTs) with 95% CIs will be 
tabulated.

Percentages of subjects with titres above the proposed cut-offs with exact 95% CIs 
will be calculated.

The distribution of antibody titres will be tabulated and also presented using reverse 
cumulative curves.
Modelling prediction
In order to complement the descriptive analyses of observed persistence per timepoint 
and minimize the bias that may have occurred due to the loss to follow-up after the 
vaccination, a longitudinal analysis will be performed at the last timepoint for rSBA-
MenA, C, W-135 and Y.
10.6.3.
Analysis of safety (Persistence epoch)
At each persistence time-point, all reported SAEs considered related to study procedures 
will be described in detail.
10.7.
Post-booster analyses
10.7.1.
Analysis of demographics/baseline characteristics
Demographic characteristics of each study cohort will be tabulated: age at booster 
vaccination, gender and geographic ancestry.
The mean age (at the booster time-point [with the range and standard deviation]) as well 
as the proportion of males and females and of each geographic ancestry will be calculated 
and presented by group.
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10.7.2.
Analysis of post-booster immunogenicity
The analysis of post-booster immunogenicity will be based on the ATP cohort for 
immunogenicity at Visit 6 (Month 121). If, for any vaccine group, the percentage of 
subjects who come back with serological results excluded from the ATP cohort is higher 
than 5%, a second analysis based on the Total Vaccinated Cohort at Visit 6 (Month 121)
will be performed to complement the ATP analysis.
For each treatment group, at each blood sampling time-point (Visit 5 [Month 120] and
Visit 6 [Month 121]), for each antigen assessed:

GMTs with 95% CIs will be tabulated.

Percentages of subjects with titres above proposed cut-offs and vaccine response 
with 95% CIs will be calculated.

The antibody titres will be tabulated and also presented using reverse cumulative 
curves.
10.7.3.
Analysis of post-booster safety
The primary analysis will be performed on the Total Vaccinated Cohort at Visit 6 (Month 
121) and, if more than 5% of the enrolled subjects are eliminated from the ATP cohort 
for safety at Visit 6 (Month 121) a second analysis will be performed on the ATP cohort 
for safety at Visit 6 (Month 121) to support the analyses of the Total Vaccinated Cohort 
at Visit 6 (Month 121).
For each treatment group, after the booster vaccination at Visit 5:
The percentage of subjects with at least one local adverse event (solicited and 
unsolicited), with at least one general adverse event (solicited and unsolicited) and with 
any adverse event during the 4-day (Days 0-3) solicited follow-up period will be 
tabulated with exact 95% CI. The same calculations will be performed for symptoms 
rated as grade 3 and for symptoms related to vaccination.
The percentage of subjects reporting each individual solicited local (any grade, grade 3, 
medical advice) and general (any grade, grade 3, related, grade 3 and related, medical 
advice) adverse event during the 4-day follow-up period (Days 0-3) after vaccination and 
its exact 95% CI will be tabulated. Occurrence of fever will also be reported per 0.5°C 
cumulative increment as well as the percentage of subjects with oral temperature 
>39.5°C. 
The verbatim reports of unsolicited symptoms will be reviewed by a Clinical 
Development Manager and the signs and symptoms will be coded according to the 
MedDRA Dictionary for Adverse Reaction Terminology. The percentage of subjects with 
unsolicited symptoms within 31 days post vaccination (Days 0-30) and its exact 95% CI 
will be tabulated by group and by MedDRA preferred term. Similar tabulation will be 
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done for grade 3 unsolicited symptoms, for unsolicited symptoms possibly related to 
vaccination and for grade 3 unsolicited symptoms possibly related to vaccination.
The number and percentage of subjects who experienced serious adverse events and new 
onset of chronic illness within six months following vaccination will be tabulated with 
exact 95% CI.
The percentage of subjects using concomitant medication (any medication, any 
antipyretic/analgesic, any antipyretic/analgesic taken prophylactically, respectively) 
during the 4-day and 31-day follow-up periods (Days 0-3 and Days 0-30, respectively) 
after vaccination will be summarized.
10.8.
Interpretation of analyses
All the analyses will be descriptive with the aim to characterise the immunogenicity 
within each group. 
10.9.
Conduct of analyses
Any deviation(s) or change(s) from the original statistical plan outlined in this protocol 
will be described and justified in the final study report.
10.9.1.
Sequence of analyses
The persistence analysis will be done in stepwise fashion after the persistence time-points 
for year 6, 7, 8, 9 and 10 as soon as results are available.
The analysis of immunogenicity, safety and reactogenicity will be done after the booster 
time point as soon as results are available for visit 5 and visit 6.
The persistence analyses will be done on as clean as possible data. The analysis at the end 
of the study (Month 126) will be done on clean data.
The analysis for each time-point will be reported separately in a clinical study report in a 
cumulative manner until the final year’s report which will include all the persistence as 
well as booster data.
10.9.2.
Statistical considerations for interim analyses
No statistical adjustment for interim analyses is required.
11.
ADMINISTRATIVE MATTERS
To comply with ICH GCP administrative obligations relating to data collection, 
monitoring, archiving data, audits, confidentiality and publications must be fulfilled. 
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11.1.
Case Report Form/Remote Data Entry instructions
Remote Data Entry (RDE), a validated computer application, will be used as the method 
for data collection. 
In all cases, subject initials will not be collected nor transmitted to Pfizer Subject data 
necessary for analysis and reporting will be entered/transmitted into a validated database 
or data system. Clinical data management will be performed in accordance with 
applicable Pfizer standards and data cleaning procedures.
While completed eCRFs are reviewed by a Pfizer or designee site monitor at the study 
site, omissions or inconsistencies detected by subsequent eCRF review may necessitate 
clarification or correction of omissions or inconsistencies with documentation and 
approval by the investigator or appropriately qualified designee. In all cases, the 
investigator remains accountable for the study data. 
The investigator will be provided with a CD-ROM of the final version of the data 
generated at the investigational site once the database is archived and the study report is 
complete and approved by all parties.
11.2.
Study Monitoring
Pfizer or a designee will monitor the study to verify that, amongst others, the: 

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol, any other 
study agreements, GCP and all applicable regulatory requirements. 
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents.
The investigator must ensure provision of reasonable time, space and qualified personnel 
for monitoring visits.
Direct access to all study-site related and source data is mandatory for the purpose of 
monitoring review. The monitor will perform a RDE review and a Source Document 
Verification (SDV). By SDV we understand verifying RDE entries by comparing them 
with the source data that will be made available by the investigator for this purpose. 
The Source Documentation Agreement Form describes the source data for the different 
data in the RDE. This document should be completed and signed by the site monitor and 
investigator and should be filed in the monitor’s and investigator’s study file. Any data 
item for which the RDE will serve as the source must be identified, agreed and 
documented in the source documentation agreement form. 
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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.
Publication Policy 
Pfizer supports the exercise of academic freedom and has no objection to publication by 
principal investigator of the results of the study based on information collected or 
generated by principal investigator, whether or not the results are favorable to the Pfizer 
product.  However, to ensure against inadvertent disclosure of confidential information or 
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unprotected inventions, the investigator will provide Pfizer an opportunity to review any 
proposed publication or other type of disclosure of the results of the study (collectively, 
“Publication”) before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before they are 
submitted for publication or otherwise disclosed.  If any patent action is required to 
protect intellectual property rights, the investigator agrees to delay the disclosure for a 
period not to exceed an additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication 
is to be a joint publication covering all study sites, and that any subsequent publications 
by the principal investigator will reference that primary publication.  However, if a joint 
manuscript has not been submitted for publication within 12 months of completion or 
termination of the study at all participating sites, the investigator is free to publish 
separately, subject to the other requirements of this section.
For all publications relating to the study, the institution will comply with recognized
ethical standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements 
for Manuscripts Submitted to Biomedical Journals, 
http://www.icmje.org/index.html#authorship, established by the International Committee 
of Medical Journal Editors.
Publication of study results is also provided for in the clinical study agreement (CSA)
between Pfizer and the institution.  In this section on publications by investigators, the 
defined terms shall have the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will 
control as to any issue regarding treatment of study subjects, and the CSA will control as 
to all other issues.
11.6. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
vaccine, Pfizer should be informed immediately.  
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and 
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of any serious breaches of this protocol or of ICH GCP that the investigator becomes 
aware of.
11.7.
Provision of study results to investigators
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a Pfizer site or other mutually-
agreeable location.
Pfizer will also provide the investigator with the full summary of the study results. The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
12.
COUNTRY SPECIFIC REQUIREMENTS
Not applicable.
13.
REFERENCES
Andrews N, Borrow R, Miller E. Validation of serological correlate of protection for 
meningococcal C conjugate vaccine by using efficacy estimates from postlicensure 
surveillance in England. Clin Diagn Lab Immunol. 2003;10(5):780-786. 
Baxter R, Baine Y, Ensor K, et al. Immunogenicity and safety of an investigational 
quadrivalent meningococcal ACWY tetanus toxoid conjugate vaccine in healthy 
adolescents and young adults 10 to 25 years of age. Pediatr. Infect. Dis. J. 2011;30:e41-
48.
Bermal N, Huang LM, Dubey A, et al. Safety and immunogenicity of a tetravalent 
meningococcal serogroups A, C, W-135 and Y conjugate vaccine in adolescents and 
adults. Human Vacc. 2011;7(2):239-247.
Centers for Disease Control and Prevention Metropolitan Atlanta Congenital Defects 
Program (CDC MACDP) guidelines. Birth defects and genetic diseases branch 6-digit 
code for reportable congenital anomalies; 
http://www.cdc.gov/ncbddd/birthdefects/documents/MACDPcode0807.pdf Accessed 05
Nov 2015.
Centers for Disease Control and Prevention. Inadvertent Misadministration of 
Meningococcal Conjugate Vaccine – United States, June-August 2005. MMWR. 
2006;55(37):1016-1017.
EMA. Guideline on the exposure to medicinal products during pregnancy: need for post-
authorization data (Doc. Ref. EMEA/CHMP/313666/2005 ) ‘adopted at Community level 
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in May 
2006);http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_proced
ural_guideline/2009/11/WC500011303.pdf Accessed 05 Nov 2015.
European Commission. Commission implementing decision of 20.04.2012. granting 
marketing authorisation under Regulation (EC) No 726/2004 of the European Parliament 
and of the Council for “Nimenrix – Meningococcal Group A, C, W-135 and Y conjugate 
vaccine” a medicinal product for human use. C(2012)2813 
http://ec.europa.eu/health/documents/community-
register/2012/20120420120470/dec_120470_en.pdf Accessed 05 Nov 201516 May 2012.
Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal disease. 
Vaccine. 2009;27S:B51-B63.
Harrison LH. Epidemiological profile of meningococcal disease in the United States. Clin 
Infect Dis. 2010;50 Suppl 2:S37-44
Healy CM, Butler KM, Smith EO et-al. Influence of serogroup on the presentation, 
course, and outcome of invasive meningococcal disease in children in the Republic of 
Ireland, 1995-2000. Clin. Infect. Dis. 2002;34 (10): 1323-30.
Knuf M, Kleninger-Baum D, Habermehl P, Muttonen P, et al. A dose-range study 
accessing immunogenicity and safety of one dose of a new candidate meningococcal 
serogroups A, C, W-135 and Y tetanus toxoid conjugate (MenACWY-TT) vaccine 
administered in the second year of life and in young children. Vaccine. 2010;28:744-753. 
Knuf M, Pantazi-Chatzikonstantinou A, Pfletschinger U, et al. An investigational 
tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate 
vaccine co-administered with Infanrix hexa is immunogenic with an acceptable safety 
profile in 12-23 month-old children. Vaccine. 2011;29:4264-4273.
Maslanka SE, Gheesling LL, Libutti DE et al. Standardization and a multilaboratory 
comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. Clin. 
Diagn. Lab. Immunol. 1997;4(2):156-167. 
Memish ZA, Dbaibo G, Montellano M, et al. Immunogenicity of a single dose of 
tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine 
administered to 2- to 10- year olds is non-inferior to a licensed-ACWY polysaccharide 
vaccine with an acceptable safety profile. Pediatr. Infec. Dis J. 2011;30:e56-62. 
McComb J. The prophylactic dose of homologous tetanus antitoxin. N. Engl. J. Med. 
1964; 270:175-178
Newell KW, Leblanc DR, Edsall G et al. The serological assessment of a tetanus toxoid 
field trial. Bull World Health Organ. 1971;45(6):773-85.
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Ostergaard L, Lebacq E, Poolman J, Maechler G, Boutriau. Immunogenicity, 
reactogenicity and persistence of meningococcal A, C, W-135 and Y tetanus toxoid 
candidate conjugate (MenACWY-TT) vaccine formulation in adolescents aged 15-25 
years. Vaccine. 2009;27:161-168.
Rosenstein NE, Perkins BA, Stephens DS et-al. Meningococcal disease. N. Engl. J. Med. 
2001;344 (18): 1378-88.
Vesikari T, Karvonen A, Bianco V, et al. Tetravalent meningococcal serogroups A, C, 
W-135 and Y conjugate vaccine is well tolerated and immunogenic when co-
administered with measles-mumps-rubella-varicella vaccine during the second year of 
life: An open, randomized controlled trial. Vaccine. 2011;29:4274-4284.
WHO position paper on Meningococcal vaccines. Weekly epidemiological record No. 
47, 2011; 8.
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APPENDIX A
LABORATORY ASSAYS
The following tests will be performed using the aliquots of serum:

Functional anti-meningococcal serogroup bactericidal activity (ie, rSBA-MenA, 
rSBA-MenC, rSBA-MenW-135, rSBA-MenY) will be determined by a serum 
bactericidal assay using rabbit complement (rSBA) at the Public Health England
(PHE; formerly known as Health Protection Agency) according to the Centers for 
Disease Control and Prevention (CDC) Protocol [Maslanka, 1997]. rSBA titres will 
be expressed as the reciprocal of the highest serum last dilution resulting in at least 
50% reduction of meningococcal colony-forming units.

Specific antibody against tetanus toxoid will be measured by dLIA. The cut-off of 
the assay is 0.1 IU/mL [McComb, 1964; Newell, 1971].
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APPENDIX B
CLINICAL LABORATORIES
Table 18
Outsourced laboratories
Laboratory
Address
Public Health England (PHE)
Vaccine Evaluation Unit
Health Protection Agency North West
Manchester Medical Microbiology Partnership
2nd Floor, Clinical Sciences Building II
Manchester Royal Infirmary
Oxford Road
Manchester, England
M13 9WZ
Pharmaceutical Product 
Development (PPD), Inc. 
Bioanalytical Laboratories
Bioanalytical Laboratories
2244 Dabney Road
Richmond, VA 23230 USA
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