A Sourcing Study to Collect Human Biological (Serum) Samples From Healthy Adults
Phase: PHASE4
Conditions: Meningitis, Meningococcal
Sponsor: GlaxoSmithKline

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CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
3 
Protocol Amendment 4 Sponsor Signatory Approval 
eTrack study number and 
Abbreviated Title 
207911 (MENB REC 2ND GEN-079 HBS) 
EudraCT number 
2017-002919-33  
Date of protocol amendment 
Amendment 4 Final: 28 April 2020 
Detailed Title  
Phase IV, open-label, randomized study to enrol 
healthy adult volunteers, naïve to any previous 
meningococcal vaccination or meningococcal 
disease, aged 18-50 years, to be either vaccinated 
with GSK MenACWY vaccine (Menveo) or GSK 
rMenB+OMV NZ vaccine (Bexsero), and serve as 
donors of human blood for conversion into serum to 
use in the development, qualification, validation and 
maintenance of immunological assays and to support 
preclinical research activities, clinical development 
and life cycle management of GSK Biologicals 
vaccines 
Sponsor signatory 
Michele Pellegrini 
Clinical and Epidemiology Project Lead, Clinical 
RDC Italy 
 
 
Signature 
 
 
 
Date 
 
 
 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
4 
Protocol Amendment 4 Rationale 
Amendment number: 
Amendment 4 
Rationale/background for changes: 
This protocol amendment 4 outlines measures that may be applicable during special 
circumstances (e.g., Coronavirus disease 2019 [COVID-19] pandemic). The purpose of 
the amendment is to protect participant’s welfare, and as far as possible ensure the 
potential benefit to the participant and promote data integrity. 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
5 
Protocol Amendment 4 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 GlaxoSmithKline (GSK) Biologicals. 
• 
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 GSK Biologicals’ study vaccine(s) 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 GSK Biologicals 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 GSK Biologicals in the monitoring process of 
the study and in resolution of queries about the data. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational vaccine(s), and more generally about his/her 
financial ties with the sponsor. GSK Biologicals will use and disclose the 
information solely for the purpose of complying with regulatory requirements. 
Hence I: 
• 
Agree to supply GSK Biologicals 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 GSK Biologicals may disclose any information it has about such 
ownership interests and financial ties to regulatory authorities. 
• 
Agree to provide GSK Biologicals with an updated Curriculum Vitae and other 
documents required by regulatory agencies for this study. 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

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CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
7 
Sponsor Information 
1. Sponsor 
GlaxoSmithKline Biologicals 
Rue de l’Institut 89, 1330 Rixensart, Belgium 
2. Sponsor Medical Expert for the Study 
Refer to the local study contact information document. 
3. Sponsor Study Monitor 
Refer to the local study contact information document. 
4. Sponsor Study Contact for Reporting of a Serious Adverse Event 
GSK Biologicals Central Back-up Study Contact for Reporting SAEs: refer to protocol 
Section 8.4.2. 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
8 
SYNOPSIS 
Detailed Title 
Phase IV, open-label, randomized study to enrol healthy adult 
volunteers, naïve to any previous meningococcal vaccination 
or meningococcal disease, aged 18-50 years, to be either 
vaccinated with GSK MenACWY vaccine (Menveo) or GSK 
rMenB+OMV NZ vaccine (Bexsero), and serve as donors of 
human blood for conversion into serum to use in the 
development, qualification, validation and maintenance of 
immunological assays and to support preclinical research 
activities, clinical development and life cycle management of 
GSK Biologicals vaccines  
Indication 
MenACWY (Menveo) is indicated in Australia for active 
immunization of children (from 2 months of age), adolescents 
and adults to prevent invasive meningococcal disease caused 
by Neisseria meningitidis serogroups A, C, W and Y.  
Menveo is indicated in Europe for active immunization of 
children (from 2 years of age), adolescents and adults at risk 
of exposure to Neisseria meningitidis groups A, C, W and Y, 
to prevent invasive disease. The use of this vaccine should be 
in accordance with official recommendations. 
rMenB+OMV NZ (Bexsero) is indicated for active 
immunization of individuals from 2 months of age and older 
against invasive meningococcal disease caused by Neisseria 
meningitidis group B. 
Rationale for the 
study and study 
design 
• 
Based on an initial assessment of the forthcoming needs 
of human serum in GlaxoSmithKlines’ (GSK) 
Biologicals’ Clinical Laboratory Sciences (CLS) to 
support Neisseria meningitidis human Serum Bactericidal 
Assays (hSBAs) in the 4- to 5-year horizon, one of the 
current main gaps identified is related to the validation 
and maintenance of the hSBAs for each of the serogroups 
A, C, W, Y and B. These activities require large volumes 
of matched pairs of pre- and post-vaccination sera from 
subjects administered GSK meningococcal vaccines. The 
sera must have hSBA titres to cover the full analytical 
range of the respective hSBA’s, including negative and 
positive low, medium and high titres, in order to perform 
all phases of assay development, qualification, validation, 
and maintenance. The sera collected will also support the 
biannual conduct of Quality Control, a Health Authority 
requirement for validated assays. The second main gap to 
support GSK vaccine development is sufficient supply of 
sera from vaccinated subjects to be used as samples in 
preclinical research and clinical development. These gaps 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
9 
are only partially covered by any of the existing sourcing 
activities. Therefore, the purpose of this study is two fold: 
first, to source human serum from baseline and post-
vaccination blood samples collected from healthy adults 
to be used as control samples in the development, 
qualification, validation and maintenance of 
immunological assays supporting the clinical 
development of GSK Biologicals’ vaccines; and second, 
sera generated in this clinical trial will be used as samples 
for preclinical research activities, clinical development 
and life cycle management of other GSK Biologicals’ 
vaccines and to help ensure the quality of the analytical 
methods for those programs.  
• 
Also, it would be preferable to generate large volumes of 
serum from the same donor, rather than obtaining only 
different sera with different titres through a large panel of 
multiple individuals donating small volumes. Current 
clinical trials will not provide sufficient material to meet 
such needs, therefore a sourcing study is necessary.  
• 
The sera generated with this sourcing study are intended 
for laboratory and assay use only and are not intended to 
be used in humans as a product.  
Objective(s) 
Primary 
• 
To collect baseline (Visit 1, Visit 2 or Visit 3, depending 
on the study group) and post vaccination (Visits 5, 8; 
Visits 5, 9; Visits 6, 9 or Visits 7, 9, depending on the 
study group) blood sample donations to serve for the 
development, qualification, validation and maintenance of 
immunological assays and to support the preclinical 
research activities, clinical development and life cycle 
management of GSK Biologicals’ vaccines.  
Secondary 
• 
To descriptively assess the safety of each subject given 
one of the 2 meningococcal vaccines as per the 
recommended dosage and schedule during their 
participation in the study. 
Study design 
• 
Experimental design: Phase IV, open-label, randomised, 
uncontrolled, multi-centric, multi-country study to 
identify healthy adult volunteers to be vaccinated and 
serve as donors of human serum. The subjects, 18-50 
years of age (YoA) at the time of informed consent form 
(ICF) signing, will be randomized into one of the four 
parallel groups, the rMenB+OMV NZ group that will 
receive rMenB+OMV NZ vaccine administered at a 0,2- 
month schedule, and the MenACWY 1, MenACWY 2 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
10 
and MenACWY 3 groups, that will receive one dose 
of MenACWY vaccine. 
• 
Duration of the study is planned over a period of up to 5 
years and the enrolment of the subjects is planned as 
follows: 
− 
Year 1: up to 540 subjects will be enrolled 
− 
Years 2 to 5: up to 120 subjects will be enrolled 
during each study year following year 1 
• 
Duration of the study for individual subjects: for each 
subject enrolled, there will be a study duration of 
approximately 6 to 8 months. 
• 
Epoch 001: Primary starting at Visit 1 (Day -83) and 
ending at Visit 9 (Day 151)  
• 
Primary completion Date (PCD): Visit 9 (Day 151) or last 
visit of Epoch 001 of the last study year  
• 
End of Study (EoS): Last subject last visit at Visit 9 (Day 
151 of the last study year).  
• 
Study groups: 
Synopsis Table 1 Study groups and epochs foreseen in the study 
Study groups 
Number of 
subjects 
Age (Min/Max) 
Epochs 
Epoch 001  
rMenB+OMV NZ 
up to ~510 
18 years – 50 years 
x  
MenACWY 1 
up to ~170 
18 years – 50 years 
x 
MenACWY 2 
up to ~170 
18 years – 50 years 
x 
MenACWY 3 
up to ~170 
18 years – 50 years 
x 
Synopsis Table 2 Study groups and treatment foreseen in the study 
Treatment 
name 
Vaccine/Product name 
Study Groups 
rMenB+OMV NZ  
MenACWY 1 
MenACWY 2 
MenACWY 3 
rMenB+OMV 
NZ (Bexsero) 
rMenB+OMV NZ 
x 
 
 
 
MenACWY 
(Menveo) 
MenA lyo 
 
x 
x 
x 
MenCWY liquid 
 
• 
Control: uncontrolled 
• 
Vaccination schedule(s): 
− 
rMenB+OMV NZ group: at Visit 4 and Visit 7, 
respectively, intramuscular (IM) injection of 
rMenB+OMV NZ vaccine 
− 
MenACWY 1, MenACWY 2 and MenACWY 3 
groups: at Visit 4, IM injection of MenACWY vaccine 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
11 
• 
Treatment allocation: 
− 
rMenB+OMV NZ group: Up to 270 subjects during 
the first study year and up to 60 subjects during each 
of the following study years, 18 through 50 years of 
age at the time of ICF signing, will receive 2 doses of 
rMenB+OMV NZ vaccine 
− 
MenACWY 1, MenACWY 2 and MenACWY 3 
groups: Up to 90 subjects during the first study year 
and up to 20 subjects during each of the following 
study years, in each group, 18 through 50 years of age 
at the time of ICF signing, will receive 1 dose of 
MenACWY vaccine 
• 
Blinding: open 
Synopsis Table 3 
Blinding of study epochs 
Study Epochs 
Blinding 
Epoch 001 
open 
 
• 
Sampling schedule: Blood samples will be collected from 
rMenB+OMV NZ group at Visits 1, 5 and 8; from 
MenACWY 1 group at Visits 1, 5 and 9; from MenACWY 
2 group at Visits 2, 6 and 9 and from MenACWY 3 group 
at Visits 3, 7 and 9  
• 
Type of study: self-contained 
• 
Data collection: Standardised Electronic Case Report Form 
(eCRF)  
• 
Safety monitoring: SAEs will be monitored during the 
entire study. 
Number of subjects • 
Up to 1020 subjects will be enrolled during this study, in 
the rMenB+OMV NZ, MenACWY 1, MenACWY 2 and 
MenACWY 3 study groups, in a 3:1:1:1 ratio, respectively. 
Endpoint(s) 
Primary 
• 
Collection of human blood for conversion into serum to use 
in the development, qualification, validation and 
maintenance of immunological assays and to support the 
preclinical research activities, clinical development and life 
cycle management of GSK Biologicals’ vaccines: at Visit 
1, Visit 5 and Visit 8 for the rMenB+OMV NZ group; and 
at Visit 1, Visit 5 and Visit 9; Visit 2, Visit 6 and Visit 9 
and Visit 3, Visit 7 and Visit 9 for the MenACWY 1, 
MenACWY 2 and MenACWY 3 groups, respectively. 
 
Secondary 
• Assessment of the occurrence of SAEs related to 
vaccination throughout the study, in all subjects. 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
12 
TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 7 
SYNOPSIS ...................................................................................................................... 8 
LIST OF ABBREVIATIONS ........................................................................................... 19 
GLOSSARY OF TERMS ............................................................................................... 22 
TRADEMARKS ............................................................................................................. 26 
1. 
INTRODUCTION .................................................................................................... 27 
1.1. 
Background ................................................................................................ 27 
1.2. 
Rationale for the study and study design .................................................... 27 
1.3. 
Benefit : Risk Assessment .......................................................................... 28 
1.3.1. 
Risk Assessment ......................................................................... 28 
1.3.2. 
Benefit Assessment ..................................................................... 30 
1.3.3. 
Overall Benefit: Risk Conclusion .................................................. 30 
2. 
OBJECTIVE(S) ...................................................................................................... 31 
2.1. 
Primary objective ........................................................................................ 31 
2.2. 
Secondary objective ................................................................................... 31 
3. 
STUDY DESIGN OVERVIEW ................................................................................ 32 
4. 
STUDY COHORT ................................................................................................... 35 
4.1. 
Number of subjects ..................................................................................... 35 
4.2. 
Inclusion criteria for enrolment .................................................................... 35 
4.3. 
Exclusion criteria for enrolment ................................................................... 36 
5. 
CONDUCT OF THE STUDY .................................................................................. 38 
5.1. 
Regulatory and ethical considerations, including the informed 
consent process.......................................................................................... 38 
5.2. 
Subject identification and randomisation ..................................................... 39 
5.2.1. 
Subject identification .................................................................... 39 
5.2.2. 
Randomisation of treatment ......................................................... 39 
5.2.2.1. 
Randomisation of supplies .......................................... 39 
5.2.2.2. 
Treatment allocation to the subject ............................. 39 
5.2.2.2.1. 
Study group and treatment 
number allocation ................................... 39 
5.2.2.2.2. 
Treatment number allocation for 
subsequent doses .................................. 40 
5.3. 
Method of blinding ...................................................................................... 40 
5.4. 
General study aspects ................................................................................ 40 
5.5. 
Outline of study procedures ........................................................................ 41 
5.6. 
Detailed description of study procedures .................................................... 42 
5.6.1. 
Informed consent ......................................................................... 42 
5.6.2. 
Check inclusion and exclusion criteria ......................................... 42 
5.6.3. 
Collect demographic data ............................................................ 42 
5.6.4. 
Medical history ............................................................................. 42 
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5.6.5. 
Physical examination ................................................................... 43 
5.6.6. 
Pregnancy test ............................................................................. 43 
5.6.7. 
Check contraindications, warnings and precautions to 
vaccination ................................................................................... 43 
5.6.8. 
Study group and treatment number allocation .............................. 43 
5.6.9. 
Sampling...................................................................................... 43 
5.6.9.1. 
Blood sampling for serum collection ........................... 43 
5.6.10. 
Study Vaccine(s) administration ................................................... 44 
5.6.11. 
Check and record concomitant medication/vaccination ................ 44 
5.6.12. 
Recording of SAEs and pregnancies ........................................... 44 
5.6.13. 
Study conclusion .......................................................................... 44 
5.6.14. 
Study procedures during special circumstances 
(Amended, 28 April 2020) ............................................................ 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 
6. 
STUDY VACCINE(S) AND ADMINISTRATION ...................................................... 47 
6.1. 
Description of study vaccine(s) ................................................................... 47 
6.2. 
Storage and handling of study vaccine(s) ................................................... 47 
6.3. 
Dosage and administration of study vaccine(s) ........................................... 48 
6.4. 
Replacement of unusable vaccine .............................................................. 48 
6.5. 
Contraindications to subsequent vaccination .............................................. 48 
6.6. 
Warnings and precautions .......................................................................... 49 
6.7. 
Concomitant medications/products and concomitant vaccinations .............. 49 
6.7.1. 
Recording of concomitant medications/products and 
concomitant vaccinations ............................................................. 49 
6.7.2. 
Concomitant medications/products/vaccines that may lead 
to elimination of the blood sample as a reagent ........................... 50 
6.7.3. 
Reasons for deferring blood collection ......................................... 50 
7. 
HEALTH ECONOMICS .......................................................................................... 51 
8. 
SAFETY ................................................................................................................. 51 
8.1. 
Safety definitions ........................................................................................ 51 
8.1.1. 
Definition of an adverse event ...................................................... 51 
8.1.2. 
Definition of a serious adverse event ........................................... 51 
8.1.3. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as serious adverse events ...................... 52 
8.2. 
Events or outcomes not qualifying as serious adverse events .................... 53 
8.2.1. 
Pregnancy ................................................................................... 53 
8.3. 
Detecting and recording serious adverse events and pregnancies ............. 54 
8.3.1. 
Time period for detecting and recording serious adverse 
events and pregnancies ............................................................... 54 
8.3.2. 
Post-Study serious adverse events .............................................. 54 
8.3.3. 
Evaluation of serious adverse events ........................................... 55 
8.3.3.1. 
Active questioning to detect serious adverse 
events......................................................................... 55 
8.3.3.2. 
Assessment of serious adverse events....................... 55 
8.3.3.2.1. 
Assessment of intensity .......................... 55 
8.3.3.2.2. 
Assessment of causality ......................... 56 
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8.3.3.2.3. 
Assessment of outcomes ........................ 57 
8.4. 
Reporting of serious adverse events and pregnancies ................................ 57 
8.4.1. 
Prompt reporting of serious adverse events and 
pregnancies to GSK Biologicals ................................................... 57 
8.4.2. 
Contact information for reporting serious adverse events 
and pregnancies .......................................................................... 58 
8.4.3. 
Completion and transmission of SAE reports to GSK 
Biologicals ................................................................................... 58 
8.4.3.1. 
Back-up system in case the electronic 
reporting system does not work .................................. 58 
8.4.4. 
Completion and transmission of pregnancy reports to GSK 
Biologicals ................................................................................... 59 
8.4.5. 
Updating of SAE and pregnancy information after removal 
of write access to the subject’s eCRF .......................................... 59 
8.4.6. 
Regulatory reporting requirements for serious adverse 
events .......................................................................................... 59 
8.5. 
Follow-up of serious adverse events and pregnancies ................................ 59 
8.5.1. 
Follow-up of serious adverse events ............................................ 59 
8.5.1.1. 
Follow-up during the study .......................................... 59 
8.5.1.2. 
Follow-up after the subject is discharged from 
the study ..................................................................... 60 
8.5.2. 
Follow-up of pregnancies ............................................................. 60 
8.6. 
Treatment of serious adverse events .......................................................... 60 
8.7. 
Subject card ................................................................................................ 60 
9. 
SUBJECT COMPLETION AND WITHDRAWAL ..................................................... 61 
9.1. 
Subject completion ..................................................................................... 61 
9.2. 
Subject withdrawal ...................................................................................... 61 
9.2.1. 
Subject withdrawal from the study ............................................... 61 
9.2.2. 
Subject withdrawal from study vaccine(s) .................................... 62 
10. STATISTICAL METHODS ...................................................................................... 62 
10.1. 
Primary endpoint ......................................................................................... 62 
10.2. 
Secondary endpoint .................................................................................... 63 
10.3. 
Determination of sample size ...................................................................... 63 
10.4. 
Analysis Sets .............................................................................................. 63 
10.4.1. 
All Enrolled Set ............................................................................ 63 
10.4.2. 
All Exposed Set ........................................................................... 63 
10.5. 
Conduct of analyses ................................................................................... 63 
10.5.1. 
Sequence of analyses.................................................................. 63 
10.5.2. 
Statistical considerations for interim analyses .............................. 64 
11. ADMINISTRATIVE MATTERS ............................................................................... 64 
11.1. 
electronic Case Report Form instructions ................................................... 64 
11.2. 
Study Monitoring by GSK Biologicals .......................................................... 65 
11.3. 
Record retention ......................................................................................... 65 
11.4. 
Quality assurance ....................................................................................... 66 
11.5. 
Posting of information on publicly available clinical trial registers and 
publication policy ........................................................................................ 66 
11.6. 
Provision of study results to investigators ................................................... 67 
11.7. 
Data Sharing ............................................................................................... 67 
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12. COUNTRY SPECIFIC REQUIREMENTS ............................................................... 67 
12.1. 
Requirements for Germany ......................................................................... 67 
13. REFERENCES ....................................................................................................... 68 
14. APPENDICES ........................................................................................................ 69 
 
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LIST OF TABLES 
PAGE 
Table 1 
Study groups and epochs foreseen in the study ..................................... 34 
Table 2 
Study groups and treatment foreseen in the study ................................. 34 
Table 3 
Blinding of study epochs ........................................................................ 34 
Table 4 
Sampling schedule ................................................................................. 34 
Table 5 
List of study procedures for each study year .......................................... 41 
Table 6 
Intervals between study visits (Amended, 28 April 2020) ........................ 42 
Table 7 
Biological samples ................................................................................. 46 
Table 8 
Study vaccine(s)..................................................................................... 47 
Table 9 
Dosage and administration ..................................................................... 48 
Table 10 
Reporting periods for collecting safety information ................................. 54 
Table 11 
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK Biologicals ................................................. 57 
Table 12 
GSK Biologicals’ laboratories ................................................................. 69 
 
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LIST OF FIGURES 
PAGE 
Figure 1. 
Study Design .......................................................................................... 32 
 
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LIST OF APPENDICES 
PAGE 
APPENDIX A CLINICAL LABORATORIES .................................................................. 69 
APPENDIX B AMENDMENTS AND ADMINISTRATIVE CHANGES TO THE 
PROTOCOL ........................................................................................... 70 
 
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LIST OF ABBREVIATIONS 
ADEM 
Acute disseminated encephalomyelitis 
AE 
Adverse Event 
ATEAM 
Advanced Temperature Excursion Analysis and Management 
BMI 
Body Mass Index 
°C 
Celsius, degrees 
CFS 
Chronic fatigue syndrome 
CLS 
Clinical Laboratory Sciences 
COVID-19 
Coronavirus Disease 2019 
dL 
Deciliters 
eCRF 
electronic Case Report Form 
EoS 
End of Study 
EoY 
End of Study Year 
°F 
Fahrenheit, degrees 
fHbp 
Factor H binding protein 
g 
Grams 
GBS 
Guillain-Barre Syndrome 
GCP 
Good Clinical Practice 
GDS 
Global Data Sheet 
GSK 
GlaxoSmithKline 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IM 
Intramuscular 
IND 
Investigational New Drug 
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IRB 
Institutional Review Board 
ITP 
Immune thrombocytopenic purpura 
IV 
Intravenous 
kg 
kilogram 
LSLV 
Last Subject Last Visit 
m2 
Square meter 
Max 
Maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
MenACWY 
Meningococcal serogroups A, C, W and Y 
mg 
Milligram 
Min 
Minimum 
mL 
Milliliters 
NadA 
Neisserial adhesin Antigen 
NHBA 
Neisseria Heparin Binding Antigen 
NZ PorA 
New Zealand serogroup B strain, PorA P1.4 
OMV NZ 
Outer Membrane Vesicle New Zealand 
PCD 
Primary Completion Date 
PI 
Prescribing Information 
PO 
Per os, i.e., orally 
QC 
Quality check 
rMenB 
Meningococcal group B recombinant 
SAE 
Serious Adverse Event 
SAS 
Statistical Analysis System 
SBA 
Serum Bactericidal Assay 
SBIR 
Source Data Base for Internet Randomization 
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SDV 
Source Document Verification 
SmPC 
Summary of Product Characteristics 
SPM 
Study Procedures Manual 
Vacc 
Vaccination 
YoA 
Years of Age 
(Amended, 28 April 2020) 
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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, 
• 
Combined oestrogen and progesterone oral 
contraceptives, 
• 
injectable progestogen, 
• 
implants of etenogestrel or levonorgestrel, 
• 
Contraceptive 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), and/or 
progesterone alone oral contraceptive. 
• 
male condom plus partner use of contraceptive 
vaginal ring. 
Adequate contraception does not apply to subjects of 
child bearing potential with same sex partners, or for 
subjects who are and will continue to be abstinent from 
penile-vaginal intercourse on a long term and persistent 
basis, 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. 
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For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), 
abuse or misuse. 
Blinding: 
A procedure in which one or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the trial, 
and only when the data are cleaned to an acceptable level 
of quality will appropriate personnel be unblinded or 
when required in case of a serious adverse event. In an 
open-label study, no blind is used. Both the investigator 
and the subject know the identity of the treatment 
assigned.  
Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
End of Study  
(Synonym of End of 
Trial) 
For studies without collection of human biologicals 
samples or imaging data EoS is the Last Subject Last 
Visit (LSLV).  
For studies with collection of Human Biologicals 
Samples or imaging data, EoS is defined as the date of the 
last testing/reading released of the Human Biological 
Samples or imaging data, related to primary and 
secondary endpoints. EoS must be achieved no later than 
8 months after LSLV 
Epoch: 
An epoch is a set of consecutive timepoints or a single 
timepoint from a single protocol. Epochs are defined to 
support a main purpose which is either to draw 
conclusions on subject participation or to draw a 
complete conclusion to define or precise the targeted 
label of the product. Supporting means that data collected 
at the timepoints included in an epoch must be sufficient 
to fulfil the purpose of the epoch. 
Typical examples of epochs are screening, primary 
vaccinations, boosters, yearly immunogenicity follow-
ups, and surveillance periods for efficacy or safety. 
eTrack: 
GSK’s tracking tool for clinical trials. 
Immunological correlate 
of protection: 
The defined immune 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. 
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Investigational vaccine: 
(Synonym of 
Investigational 
Medicinal Product) 
A pharmaceutical form of an active ingredient being 
tested 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). 
Menopause: 
Menopause is the age associated with complete cessation 
of menstrual cycles, menses, and implies the loss of 
reproductive potential by ovarian failure. A practical 
definition accepts menopause after 1 year without menses 
with an appropriate clinical profile at the appropriate age 
e.g. > 45 years. 
Primary completion 
date: 
The date that the final subject was examined or received 
an intervention for the purpose of final collection of data 
for all primary outcomes, whether the clinical trial was 
concluded according to the pre-specified protocol or was 
terminated. 
Protocol amendment: 
The International Conference on Harmonisation (ICH) 
defines a protocol amendment as: ‘A written description 
of a change(s) to or formal clarification of a protocol.’ 
GSK Biologicals further details this to include a change 
to an approved protocol that affects the safety of 
subjects, scope of the investigation, study design, or 
scientific integrity of the study. 
Randomisation: 
Process of random attribution of treatment/schedule to 
subjects in order to reduce bias of selection. 
Self-contained study: 
Study with objectives not linked to the data of another 
study. 
Site Monitor: 
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at one or 
more investigational sites. 
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Study vaccine/product: 
Any investigational vaccine/product being tested and/or 
any authorized use of a vaccine/ product /placebo as a 
reference or administered concomitantly, in a clinical trial 
that evaluates the use of an investigational 
vaccine/product. 
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) 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. 
Treatment number: 
A unique number identifying a treatment to a subject, 
according to treatment allocation. 
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TRADEMARKS 
The following trademarks are used in the present protocol. 
Note: In the body of the protocol (including the synopsis), the names of the vaccines will 
be written without the superscript symbol ™ or ® and in italics. 
Trademarks of the GSK group of 
companies 
 
Generic description 
Menveo 
 
Meningococcal (Groups A, C, W and Y) 
Oligosaccharide Diphtheria CRM197 
Conjugate Vaccine 
Bexsero 
 
Meningococcal Group B Vaccine 
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1. 
INTRODUCTION 
1.1. 
Background 
The Serum Bactericidal Assay (SBA) using human serum as the source of complement, is 
routinely used as immunological assay to measure the induction of functional bactericidal 
antibodies directed against Neisseria meningitidis, as a primary efficacy outcome. 
The development and maintenance of human Serum Bactericidal Assays (hSBA) requires 
the use of high volumes of a large panel of control sera obtained by selecting pre- and 
post-vaccination serum samples of vaccinated subjects. Control sera are selected as to 
have a strain-dependent range of titres covering the analytical range of the assays, and 
preferably no change in controls should take place during a study. A panel of control sera 
can act as a reference serum panel to test large numbers of strains, in order to further 
guarantee the maintenance of the quality of the assays in addition to samples required 
throughout the development and life cycle of the vaccines. 
A lack of quality in the assays can lead to improper study conclusions, increased patient 
risk and protracted regulatory review of potentially lifesaving vaccines. 
MenACWY (Menveo) is indicated in Australia for active immunization of children (from 
2 months of age), adolescents and adults to prevent invasive meningococcal disease 
caused by Neisseria meningitidis serogroups A, C, W and Y.  
Menveo is indicated in Europe for active immunization of children (from 2 years of age), 
adolescents and adults at risk of exposure to Neisseria meningitides groups A, C, W and 
Y, to prevent invasive disease. The use of this vaccine should be in accordance with 
official recommendations.  
rMenB+OMV NZ (Bexsero) is indicated for active immunization of individuals from 2 
months of age and older against invasive meningococcal invasive disease caused by 
Neisseria meningitidis serogroup B. 
1.2. 
Rationale for the study and study design 
Based on an initial assessment of the forthcoming needs of human serum in 
GlaxoSmithKlines’ (GSK) Biologicals’ Clinical Laboratory Sciences (CLS) to support 
Neisseria meningitidis hSBAs in the 4- to 5-year horizon, one of the current main gaps 
identified is related to the validation and maintenance of the hSBA for each of the 
serogroups A, C, W, Y and B. These activities require large volumes of matched pairs of 
pre- and post-vaccination sera from subjects administered GSK meningococcal vaccines. 
The sera must have hSBA titres to cover the full analytical range of the respective 
hSBA’s, including negative, and positive low, medium and high titres, in order to 
perform all phases of assay development, qualification, validation, and maintenance. The 
sera collected will also support the biannual conduct of Quality Control, a Health 
Authority requirement for validated assays. The second main gap to support GSK vaccine 
development is sufficient supply of sera from vaccinated subjects to be used as samples 
in preclinical research and clinical development. These gaps are only partially covered by 
any of the existing sourcing activities. 
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Therefore, the purpose of this study is two-fold: first, to source human serum from 
baseline and post-vaccination blood samples collected from healthy adults to be used as 
control samples in the development, qualification, validation and maintenance of 
immunological assays supporting the clinical development of GSK Biologicals’ vaccines; 
and second, sera generated in this clinical trial will be used as samples for preclinical 
research activities, clinical development and life cycle management of other GSK 
Biologicals’ vaccines and to help ensure the quality of the analytical methods for those 
programs.  
Also, it would be preferable to generate large volumes of serum from the same donor, 
rather than obtaining only different sera with different titres through a large panel of 
multiple individuals donating small volumes. Current clinical trials will not provide 
sufficient material to meet such needs, therefore a sourcing study is necessary.  
The sera generated with this sourcing study are intended for laboratory and assay use 
only, and will not be used in humans as a product. 
1.3. 
Benefit : Risk Assessment 
Please refer to the Prescribing Information (PI) for information regarding the summary 
potential risks and benefits of Bexsero and Menveo. 
The following section outlines the risk assessment and mitigation strategy for this study 
protocol:   
1.3.1. 
Risk Assessment 
Important Potential/Identified 
Risk 
Data/Rationale for Risk  
Mitigation Strategy 
Bexsero 
Important identified risk: Fever 
As with other vaccines, fever may occur 
following vaccination. Fever is listed in 
the Bexsero (see PI). 
Acute severe febrile illness 
constitutes a contraindication (see 
Section 6.5).  
Important potential risk: 
Guillain-Barre Syndrome 
(GBS) 
GBS has been observed with other 
vaccines. No cases have been reported 
during the Bexsero clinical development 
program.  
The potential risk of events of 
possible autoimmune aetiology might 
occur (see Informed Consent Form 
[ICF]). GBS will be monitored through 
the SAE collection. 
Important potential risk:  
Acute disseminated 
encephalomyelitis (ADEM) 
ADEM has been observed with other 
vaccines. No cases have been reported 
during the Bexsero clinical development 
program. 
The potential risk of events of 
possible autoimmune aetiology might 
occur (see ICF). ADEM will be 
monitored through the SAE 
collection. 
Important potential risk: 
Anaphylaxis and 
anaphylactic shock 
No cases of anaphylaxis to be related to 
Bexsero have been reported in the 
Bexsero clinical development program. 
However, one related case of 
anaphylaxis within 30 minutes was 
reported in a third party expanded 
access program (V72_70TP). Allergic 
reaction (including anaphylactic 
reaction) is listed (see PI). 
Anaphylaxis following the 
administration of Bexsero constitutes 
a contraindication (see Section 6.5). 
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Important Potential/Identified 
Risk 
Data/Rationale for Risk  
Mitigation Strategy 
Important potential risk:  
Chronic fatigue syndrome 
(CFS) 
No cases of CFS have been reported 
from clinical trials nor from post-
marketing experience for Bexsero. A 
potential concern was raised with CFS 
following the vaccination with MenBvac 
(another Outer Membrane Vesicles 
[OMV] vaccine) in Norway. The results 
of a case-control study showed no 
increased risk [Magnus, 2009]. 
No specific mitigation: serious 
adverse event (SAE) collection is part 
of the study protocol. 
Important potential risk: 
Decrease of immunogenicity 
secondary to prophylactic 
use of paracetamol 
Prophylactic use of paracetamol 
reduces the incidence and severity of 
fever without affecting the 
immunogenicity of either Bexsero or 
routine vaccines. The effect of 
antipyretics other than paracetamol on 
the immune response has not been 
studied.  
No specific risk mitigation in place for 
this study. 
Menveo 
Important potential risk: 
Reconstitution errors 
Reports describing medication errors 
occurred due to administration of the 
serogroup CWY vaccine component 
only, without addition of the lyophilized 
serogroup. 
See Section 6.1. 
Important potential risk: 
Guillain-Barré syndrome 
GBS has been observed with other 
vaccines. No cases have been reported 
during the Menveo clinical development 
program.  
The potential risk of events of 
possible autoimmune aetiology might 
occur (see ICF). GBS will be 
monitored through the SAE 
collection. 
Important potential risk: Acute 
disseminated 
encephalomyelitis (ADEM) 
ADEM has been observed with other 
vaccines. Two cases from clinical trials 
and 5 cases from spontaneous 
reporting were retrieved from the GSK’s 
global safety database. None has 
provided sufficient evidence of a causal 
association between ADEM and 
Menveo. 
The potential risk of events of 
possible autoimmune aetiology might 
occur (see ICF). ADEM will be 
monitored through the SAE 
collection. 
Important Potential risk: 
Thrombocytopenia 
Immune thrombocytopenic purpura 
(ITP) has been reported in associations 
with several licensed vaccines. Two 
cases related to Menveo were reported 
during the clinical development 
program, but none has provided a clear 
association between thrombocytopenia 
and the vaccine. 
ITP will be monitored through the 
SAE collection. 
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Important Potential/Identified 
Risk 
Data/Rationale for Risk  
Mitigation Strategy 
Important Potential risk: Facial 
Paresis 
Facial paresis was recognised as an 
important potential risk following the 
results of a sponsored observational 
study (V59_34OB) which found an 
imbalance of cases of facial paresis 
following vaccination with Menveo. No 
cases of facial paresis were reported 
from interventional clinical trials. 
The potential risk of events of 
possible autoimmune aetiology that 
might occur (see ICF). No specific 
risk mitigation in place in this study. 
Important Potential risk: 
Vaccination failure (lack of 
efficacy) 
It is known that a protective immune 
response may not be generated in 
every recipient. The number of reports 
suggestive for vaccination failure 
reported cumulatively do not suggest a 
significantly or unexpectedly high rate of 
vaccine failure.  
Proper administration, storage and 
handling. 
Study Procedures  
Risk for large volumes of blood 
samples 
Blood sampling associated risk of 
discomfort, syncope, dizziness, infection 
at the site after or during venipuncture. 
Blood samples will be obtained by a 
trained professional and medical 
assistance will be available (see 
Section 5.6.9.1). The reasons for 
deferring the blood draw, including 
the ones to mitigate potential adverse 
events linked to the blood draw, are 
listed in Section 6.7.3.  
Risk from lesion sampling. 
Needle sampling associated risk of 
infection, and discomfort related to the 
procedure. 
The potential risk of some temporary 
discomfort during the sampling 
procedure and the precautionary use 
of an anti-bacterial ointment to 
reduce the risk of infection will be 
mentioned in the ICF. 
1.3.2. 
Benefit Assessment 
Benefits assessments include: 
• 
Potential benefit of receiving the study vaccines, to protect against meningococcal 
diseases caused by Neisseria meningitidis serogroups A, C, W and Y, or serogroup 
B. 
• 
Contributing to the process of developing new therapies. 
1.3.3. 
Overall Benefit: Risk Conclusion 
The potential or identified risks in association with MenACWY and rMenB+OMV NZ 
vaccines are justified by the potential benefits (prevention) that may be afforded to 
subject(s) receiving immunization to prevent invasive meningococcal disease caused by 
Neisseria meningitidis. 
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2. 
OBJECTIVE(S) 
2.1. 
Primary objective 
• 
To collect baseline (Visit 1, Visit 2 or Visit 3, depending on the study group) and 
post vaccination (Visits 5, 8; Visits 5, 9; Visits 6, 9 or Visits 7, 9, depending on the 
study group) blood sample donations to serve for the development, qualification, 
validation and maintenance of immunological assays and to support the preclinical 
research activities, clinical development and life cycle management of GSK 
Biologicals’ vaccines. 
Refer to Section 10.1 for the definition of the primary endpoint(s). 
2.2. 
Secondary objective 
• 
To descriptively assess the safety of each subject given one of the 2 meningococcal 
vaccines as per the recommended dosage and schedule during their participation in 
the study. 
Refer to Section 10.2 for the definition of the secondary endpoint(s).  
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3. 
STUDY DESIGN OVERVIEW  
Figure 1. 
Study Design 
 
rMenB+OMV NZ group: subjects receiving 2 doses of rMenB+OMV NZ vaccine 
MenACWY 1, MenACWY 2 and MenACWY 3 groups: subjects receiving 1 dose of MenACWY vaccine 
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Based on data from completed rMenB+OMV NZ clinical trials, the Day 8 and Day 98 
timepoints are sufficient for the rMenB+OMV NZ vaccine arm to provide the target 
panel of hSBA titres covering the anticipated analytical range. Due to the necessity to 
have representative hSBA titers that would cover the full targeted analytical range 
(negative, and positive low, medium and high titers), the MenACWY vaccine arm will be 
split in 3 groups, with different post-vaccination blood sampling timepoints. To obtain 
the range of titres for A, C, W and W hSBA assays, Day 31, Day 61 and Day 151 
timepoints are needed based on a previous GSK study (Men-ABCWY-Epi-002).  
The three MenACWY groups are also necessary due to large volumes of blood required 
at each blood draw, because the timing between consecutive blood samplings must 
comply with the minimum interval, required by local health authorities and guidelines 
[Australian Red Cross, 2016]. The only way to ensure a blood draw at Day 31, Day 61 
and Day 151 timepoints is to have 3 MenACWY groups. The rMenB+OMV NZ vaccine 
arm will not be split, due to the sufficient interval between the post-vaccinations blood 
sampling timepoints (Day 8 and Day 98).  
Duration of the study is planned over a period of up to 5 years and the enrolment of the 
subjects is planned as follows: 
• 
Year 1: up to 540 subjects will be enrolled 
• 
Years 2 to 5: up to 120 subjects will be enrolled each study year following year 1 
Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns. Therefore, adherence to the study design requirements, 
including those specified in the outline of study procedures (Section 5.5), are essential 
and required for study conduct.  
• 
Experimental design: Phase IV, open-label, randomised, uncontrolled, multi-centric, 
multi-country study to identify healthy adult volunteers to be vaccinated and serve as 
donors of human serum. The subjects, 18-50 years of age (YoA) at the time of ICF 
signing, will be randomized in four parallel groups, the rMenB+OMV NZ group that 
will receive rMenB+OMV NZ vaccine administered at a 0,2- month schedule and the 
MenACWY 1, MenACWY 2 and MenACWY 3 groups, that will receive one dose 
of MenACWY vaccine. 
• 
Duration of the study for individual subjects: For each subject enrolled, there will be 
a study duration of approximately 6 to 8 months. 
− 
Epoch 001: Primary starting at Visit 1 (Day -83) and ending at Visit 9 (Day 151)  
− 
Primary completion Date (PCD): Visit 9 (Day 151) or last visit of Epoch 001 of 
the last study year  
Refer to glossary of terms for the definition of PCD. 
• 
End of Study (EoS): Last subject last visit at Visit 9 (Day 151) of the last study year  
Refer to glossary of terms for the definition of EoS. 
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• 
Study groups: 
Table 1 
Study groups and epochs foreseen in the study 
Study groups 
Number of 
subjects 
Age (Min/Max) 
Epochs 
Epoch 001  
rMenB+OMV NZ  
up to ~510 
18 years – 50 years 
x 
MenACWY 1 
up to ~170 
18 years – 50 years 
x 
MenACWY 2 
up to ~170 
18 years – 50 years 
x 
MenACWY 3 
up to ~170  
18 years – 50 years 
x 
Table 2 
Study groups and treatment foreseen in the study 
Treatment 
name 
Vaccine/Product 
name 
Study Groups 
rMenB+OMV NZ  
MenACWY 1   
MenACWY 2   
MenACWY 3  
rMenB+OMV 
NZ (Bexsero) 
rMenB+OMV NZ    
x 
 
 
 
MenACWY 
(Menveo) 
MenA lyo   
 
x 
x 
x 
MenCWY liquid    
• 
Control: uncontrolled 
• 
Vaccination schedule(s): 
− 
rMenB+OMV NZ group: at Visit 4 and Visit 7, respectively, intramuscular (IM) 
injection of rMenB+OMV NZ vaccine 
− 
MenACWY 1, MenACWY 2 and MenACWY 3 groups: at Visit 4, IM injection 
of MenACWY vaccine 
• 
Treatment allocation:  
− 
rMenB+OMV NZ group: Up to 270 subjects during the first study year and up 
to 60 subjects during each of the following study years, 18 through 50 years of 
age at the time of ICF signing, will receive 2 doses of rMenB+OMV NZ vaccine 
− 
MenACWY 1, MenACWY 2 and MenACWY 3 groups: Up to 90 subjects, 
during the first study year and up to 20 subjects during each of the following 
study years, in each group, 18 through 50 years of age at the time of ICF 
signing, will receive 1 dose of MenACWY vaccine  
Please refer to Section 5.2 for a detailed description of the randomisation method. 
• 
Blinding: Open 
Table 3 
Blinding of study epochs 
Study Epochs 
Blinding 
Epoch 001  
open 
• 
Sampling schedule: 
Table 4 
Sampling schedule 
Study groups 
Blood donation schedule 
Blood sample volume [mL] at each visit 
rMenB+OMV NZ  
Visit 1; Visit 5 and Visit 8 
300 
MenACWY 1  
Visit 1, Visit 5 and Visit 9 
300 
MenACWY 2  
Visit 2, Visit 6 and Visit 9 
300 
MenACWY 3  
Visit 3, Visit 7 and Visit 9 
300 
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• 
Type of study: self-contained 
• 
Data collection: Standardised Electronic Case Report Form (eCRF). 
• 
Safety monitoring: SAEs will be monitored during the entire study 
4. 
STUDY COHORT 
4.1. 
Number of subjects 
During the first study year, the target will be to enrol up to 540 healthy adults, naïve to 
any previous meningococcal vaccination or meningococcal and gonorrhoea diseases, 
aged 18-50 years at the time of ICF signing, into 4 study groups, in a 3:1:1:1 ratio. 
During each of the following four years, the target will be to enrol up to 120 healthy 
adults, naïve to any previous meningococcal vaccination or meningococcal and 
gonorrhoea diseases, aged 18-50 years at the time of ICF signing, into 4 study groups, in 
a 3:1:1:1 ratio. 
The subjects enrolled during the first study year will be randomized to the rMenB+OMV 
NZ group (up to 270 subjects) to receive 2 doses of rMenB+OMV NZ vaccine, and the 
MenACWY groups (MenACWY 1, MenACWY 2 and MenACWY 3; up to 270 subjects 
in a 1:1:1 ratio), to receive 1 dose of MenACWY vaccine.  
The subjects enrolled during each of the following four study years will be randomized to 
the rMenB+OMV NZ group (up to 60 subjects) to receive 2 doses of rMenB+OMV NZ 
vaccine, and the MenACWY groups (MenACWY 1, MenACWY 2 and MenACWY 3; 
up to 60 subjects in a 1:1:1 ratio), to receive 1 dose of MenACWY vaccine. 
4.2. 
Inclusion criteria for enrolment 
Deviations from inclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity, regulatory acceptability of the study or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential. 
All subjects must satisfy ALL the following criteria at study entry: 
1. Subjects who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol. 
2. Written informed consent obtained from the subject prior to performing any study 
specific procedure. 
3. A male or female between, and including, 18 and 50 years of age at the time of the 
first study visit. 
4. Healthy subjects as established by medical history and clinical examination before 
entering into the study.* 
5. Subjects must weigh at least 110 pounds (50 kg), but not to present obesity (BMI < 
32kg/m2). 
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6. Female subjects of non-childbearing potential may be enrolled in the study.  
− 
Non-childbearing potential is defined as pre-menarche, current bilateral tubal 
ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. 
− 
Please refer to the glossary of terms for the definition of menarche and 
menopause. 
7. Female subjects of childbearing potential 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 and 
− 
has agreed to continue adequate contraception during the entire treatment period 
and for 1 month, after completion of the vaccination series. 
Please refer to the glossary of terms for the definition of adequate contraception. 
* Healthy subjects with no medical conditions that, in the opinion of the investigator, 
prevents the subject from participating in the study. 
4.3. 
Exclusion criteria for enrolment 
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity, regulatory acceptability of the study 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: 
Each subject must not have: 
1. Progressive, unstable or uncontrolled clinical conditions. 
2. Hypersensitivity, including allergy, to any component of vaccines, medicinal 
products or medical equipment whose use is foreseen in this study. 
3. Clinical conditions representing a contraindication to intramuscular vaccination and 
blood draws. 
4. Abnormal function of the immune system resulting from: 
− 
Clinical conditions. 
− 
Systemic administration of corticosteroids  (PO/IV/IM) within 90 days prior to 
informed consent. 
− 
Administration of antineoplastic and immunomodulating agents or radiotherapy 
within 90 days prior to informed consent. 
5. Received immunoglobulins or any blood products within 180 days prior to informed 
consent. 
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6. Received an investigational or non-registered medicinal product within 30 days prior 
to informed consent. 
7. Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the subject due to participation in the study. 
8. Any history of meningococcal vaccination or meningococcal and gonorrhoea 
diseases. 
9. Enrolment in any activity requiring a blood donation greater than 50 mL during the 
period starting 30 days before the first study visit (Day -83, Day -60 or Day -30) or 
for the duration of the study period. 
10. Administration of long-acting immune-modifying drugs at any time during the study 
period (e.g. infliximab). 
11. Subjects with blood disorders (e.g., congenital or haemolytic anaemias, 
haemochromatosis). 
12. Subjects with a history of difficulty in providing blood samples (bad veins). 
13. Any antibiotic intake 7 days prior to blood collection (please refer to Section 6.7.3: it 
is possible to delay blood draw 7 days after the last dose of antibiotics). 
14. Subjects who donated >450 mL of blood within 60 days prior to any blood collection 
visits. 
15. Subjects who lost >200 mL during a single apheresis or who lost red blood cells on 
more than one occasion during apheresis within the previous 60 days (please refer to 
Section 6.7.3). 
16. 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). 
17. Ongoing anaemia as indicated by haemoglobin values below the lower limit of the 
laboratory-specified reference range (females:  haemoglobin < 12.5 g/dl; males:   
haemoglobin < 13.0 g/dl or as per country specific recommendations/regulations).  If 
the finger prick method demonstrates an anaemia, no further protocol procedures 
will be performed, and the subject will be referred for appropriate medical 
management. The subject may participate in this study following therapy and 
evidence that the anaemia has been resolved. 
18. History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccines. 
19. Pregnant or lactating female. 
20. Female planning to become pregnant or planning to discontinue contraceptive 
precautions. 
21. Any confirmed or suspected immunosuppressive or immunodeficiency condition 
based on medical history and physical examination (no laboratory testing required). 
22. Family history of congenital or hereditary immunodeficiency. 
23. Serious chronic illness. 
24. History of chronic alcohol consumption and/or drug abuse. 
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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 GCP, all 
applicable subject privacy requirements and the guiding principles of the Declaration of 
Helsinki.  
GSK will obtain favourable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study in that country. 
Conduct of the study includes, but is not limited to, the following: 
• 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
favourable opinion/approval of study protocol and any subsequent amendments. 
• 
Subject informed consent.  
• 
Investigator reporting requirements as stated in the protocol. 
GSK will provide full details of the above procedures to the investigator, either verbally, 
in writing, or both. 
Freely given and written or witnessed/ thumb printed informed consent must be obtained 
from each subject, as appropriate, prior to participation in the study.  
GSK Biologicals will prepare a model Informed Consent Form (ICF) which will embody 
the ICH GCP and GSK Biologicals required elements. While it is strongly recommended 
that this model ICF is to be followed as closely as possible, the informed consent 
requirements given in this document are not intended to pre-empt any local regulations 
which require additional information to be disclosed for informed consent to be legally 
effective. Clinical judgement, local regulations and requirements should guide the final 
structure and content of the local version of the ICF.  
The investigator has the final responsibility for the final presentation of the ICF, 
respecting the mandatory requirements of local regulations. The ICF generated by the 
investigator with the assistance of the sponsor’s representative must be acceptable to 
GSK Biologicals and be approved (along with the protocol, and any other necessary 
documentation) by the IRB/IEC. 
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5.2. 
Subject identification and randomisation 
5.2.1. 
Subject identification 
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study, according to the range of subject identification 
numbers allocated to each study centre. 
5.2.2. 
Randomisation of treatment 
An internet randomisation system (Source Data Base for Internet Randomization system, 
SBIR) will be used for treatment number allocation and for enrolment tracking purposes. 
5.2.2.1. 
Randomisation of supplies 
The randomisation of supplies within blocks will be performed at GSK Biologicals, using 
MATerial EXcellence (MATEX), a program developed for use in Statistical Analysis 
System (SAS®) (Cary, NC, USA) by GSK Biologicals. Entire blocks will be shipped to 
the study centres /warehouse(s). 
To allow GSK Biologicals to take advantage of greater rates of recruitment than 
anticipated at individual centres in this multi-centre study and to thus reduce the overall 
study recruitment period, an over-randomisation of supplies will be prepared.  
5.2.2.2. 
Treatment allocation to the subject 
The treatment numbers will be allocated by dose. 
5.2.2.2.1. Study group and treatment number allocation 
The target will be to enrol up to 1020 eligible subjects who will be randomly assigned to 
four study groups in a (3: 1: 1: 1) ratio (up to 510: 170: 170: 170 subjects in each group). 
Allocation of the subject to a study group at the investigator site will be performed using 
the SBIR system. The randomisation algorithm will use a minimisation procedure 
accounting for centre and study. Minimisation factors will have equal weight in the 
minimisation algorithm. 
After obtaining the signed and dated ICF from the subject and having checked the 
eligibility of the subject, the site staff in charge of the vaccine administration will access 
SBIR. Upon providing the subject identification number, the randomisation system will 
determine the study group. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen. 
When SBIR is not available, please refer to the SBIR user guide or the Study Procedures 
Manual (SPM) for specific instructions. 
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5.2.2.2.2. Treatment number allocation for subsequent doses 
For each dose subsequent to the first dose, the study staff in charge of the vaccine 
administration will access SBIR, provide the subject identification number, and the 
system will provide a treatment number consistent with the allocated study group. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen. 
5.3. 
Method of blinding  
This is an open-label study with four treatment groups. 
5.4. 
General study aspects 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects. 
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5.5. 
Outline of study procedures 
Table 5 
List of study procedures for each study year 
Epoch  
Epoch 001 
Type of contact 
Visit 1 Visit  
2 
Visit 
3 
Visit 4 Visit 
5 
Visit 
6 
Visit 
7* 
Visit  
8 
Visit  
9 
Timepoint (s) 
Day  
-83 
Day 
-60 
Day  
-30 
Day 
 1 
Day 
8  
Day 
31  
Day 
 61  
Day  
98  
Day 
151 
Sampling timepoint(s) 
 Pre-
Vacc 
Pre-
Vacc 
Pre-
Vacc 
Vacc  
I 
 
 
Vacc II EoY/EoS EoY/EoS 
Informed consent 
● 
● 
● 
 
 
 
 
 
 
Check inclusion/exclusion criteria 
● 
● 
● 
 
 
 
 
 
 
Collect demographic data 
● 
● 
● 
 
 
 
 
 
 
Medical history 
● 
● 
● 
 
 
 
 
 
 
Physical examination 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Urine pregnancy test (locally) 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Check contraindications and warnings and 
precautions to vaccination 
 
 
 
O 
 
 
O 
 
 
Measure/ record height 
● 
● 
● 
 
 
 
 
 
 
Measure/ record weight 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Check reasons for deferring blood 
collection 
● 
● 
● 
 
● 
● 
● 
● 
● 
Study group and treatment number 
allocation 
O 
O 
O 
 
 
 
 
 
 
Recording of administered treatment 
number 
 
 
 
●  
 
 
●  
 
 
MenACWY vaccine administration 
 
 
 
● 
 
 
 
 
 
rMenB+OMV NZ vaccines administration 
 
 
 
● 
 
 
● 
 
 
Blood sampling for haemoglobin (~ one 
drop of blood) 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Collection of 300 mL blood samples 
● 
● 
● 
 
● 
● 
● 
● 
● 
Record any concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of all SAEs and pregnancies 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Study Conclusion 
 
 
 
 
 
 
 
● 
● 
Pre-Vacc: prior to vaccination. 
EoY: End of study year. 
EoS: end of study. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
Notes: The list of study procedures will be repeated for each study year. Please refer to Section 10.3. 
*At Visit 7, the rMenB+OMV NZ group will be scheduled for the second vaccination and should follow the same 
procedures as those listed at Visit 4, while the MenACWY 3 group will be scheduled for blood sampling and should 
follow the same procedures as those listed at Visit 6. Please refer to Section 3 for further details on the groups for 
whom Visits 1, 2, 3 and Visits 5, 6, 7, 8, 9 are applicable. 
Whenever possible, the investigator should arrange study visits within the interval 
described in Table 6, and should keep an interval of at least 90 days between: 
• 
Visit 1 and Visit 5 for group rMenB+OMV NZ and group MenACWY1;  
• 
Visit 2 and Visit 6 for group MenACWY2;  
• 
Visit 3 and Visit 7, and Visit 7 and Visit 9  for group MenACWY3. 
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Table 6 
Intervals between study visits (Amended, 28 April 2020) 
Groups 
Interval 
Optimal length of interval 
rMenB+OMV NZ  Visit 1 → Visit 4  
83 ± 7 days  
Visit 1 → Visit 5 
90 + 14 days  
Visit 4 → Visit 5  
At least 7 days 
Visit 5 → Visit 7  
53 + 14 days  
Visit 7 → Visit 8  
37 + 14 days  
MenACWY 1  
Visit 1 → Visit 4  
83 ± 7 days  
Visit 1 → Visit 5  
90 + 14 days  
Visit 4 → Visit 5  
At least 7 days 
Visit 5 → Visit 9  
143 + 14 days  
MenACWY 2  
Visit 2 → Visit 4  
60  ± 3 days  
Visit 2 → Visit 6  
90 + 14 days  
Visit 4 → Visit 6  
At least 30 days 
Visit 6 → Visit 9  
120 + 14 days  
MenACWY 3  
Visit 3 → Visit 4  
30 ± 2 days  
Visit 3 → Visit 7  
90 + 14 days  
Visit 4 → Visit 7  
At least 60 days 
Visit 7 → Visit 9  
90 + 14 days  
Note: Under special circumstances, like during COVID-19 pandemic, the length of interval between visits for 
the collection of biological samples or for the vaccine administration may be extended, please refer to Section 
5.6.14 
5.6. 
Detailed description of study procedures 
5.6.1. 
Informed consent 
The signed/witnessed/thumb printed informed consent of the subject must be obtained 
before study participation. Refer to Section 5.1 for the requirements on how to obtain 
informed consent. 
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, sex and race in the subject’s eCRF. 
5.6.4. 
Medical history 
Obtain the subject’s medical history by interview and/or review of the subject’s medical 
records and record any pre-existing conditions or signs and/or symptoms present in a 
subject prior to the first/the study vaccination in the eCRF. 
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5.6.5. 
Physical examination 
Perform a physical examination of the subject, including assessment of oral body 
temperature and resting vital signs: systolic/diastolic blood pressure, heart rate and 
respiratory rate after at least 10 minutes of rest. Weight, height and haemoglobin values 
will be assessed. Collected information needs to be recorded in the eCRF.  
Physical examination will be performed at each study visit. 
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 physical examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider.  
5.6.6. 
Pregnancy test 
Female subjects of childbearing potential are to have a urine pregnancy test at each study 
visit. The blood sampling can be collected and the study vaccine(s) may be administered 
only if the pregnancy test is negative. 
Note: Pregnancy test must be performed even if the subject is menstruating at the time of 
the study visit. 
5.6.7. 
Check contraindications, warnings and precautions to 
vaccination 
Contraindications, warnings and precautions to vaccination must be checked at the 
beginning of each vaccination visit. Refer to Sections 6.5 and 6.6 for more details. 
5.6.8. 
Study group and treatment number allocation 
Study group and treatment number allocation will be performed as described in Section 
5.2.2. The number of each administered treatment must be recorded in the eCRF. 
5.6.9. 
Sampling 
Refer to the Module on Biospecimen Management in the SPM for detailed instructions 
for the collection, handling and processing of the samples. 
5.6.9.1. 
Blood sampling for serum collection  
Blood samples will be taken from the rMenB+OMV NZ group at Visit 1, Visit 5 and 
Visit 8,  from the MenACWY 1 group at Visit 1, Visit 5 and Visit 9, from the 
MenACWY 2 group at Visit 2, Visit 6 and Visit 9, and from the MenACWY 3 group at 
Visit 3, Visit 7 and Visit 9 (see Section 5.5). 
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• 
A volume of 300 mL of whole blood (to provide on average 120 mL of serum) 
should be drawn from all subjects at each pre-defined timepoint. After processing, 
serum samples should be kept at preferably -80°C/ –112°F, but –70°C/ –94°F is also 
acceptable, until shipment. Refer to the SPM for more details on sample storage 
conditions.  
• 
An overall volume of 900 mL of whole blood will be collected during the entire 
study period, from each subject. 
• 
The subjects will be observed closely for at least 15 minutes following the blood 
sampling, with appropriate medical treatment readily available or per local country 
recommendations and regulations. 
5.6.10. 
Study Vaccine(s) administration 
• 
After completing all prerequisite procedures prior to vaccination, one dose of study 
vaccine(s) will be administered intramuscularly (IM) in the deltoid of the non-
dominant arm (refer to Section 6.3 for detailed description of the vaccine(s) 
administration procedure). If the investigator or delegate determines that the 
subject’s health on the day of administration temporarily precludes vaccine(s) 
administration, the visit will be rescheduled within the allowed interval for this visit 
(refer to Table 6). 
The country-specific Prescribing Information for each vaccine will be followed regarding 
treatment of subjects post vaccination, with appropriate medical treatment readily 
available in case of anaphylaxis.  
5.6.11. 
Check and record concomitant medication/vaccination 
Concomitant medication/vaccination must be checked and recorded in the eCRF as 
described in Section 6.7. 
5.6.12. 
Recording of SAEs and pregnancies 
• 
Refer to Section 8.3 for procedures for the investigator to record SAEs and 
pregnancies. Refer to Section 8.4 for guidelines and how to report SAE and 
pregnancy to GSK Biologicals. 
• 
The subjects will be instructed to contact the investigator immediately should the 
subjects manifest any signs or symptoms they perceive as serious.  
5.6.13. 
Study conclusion 
The investigator will: 
• 
review data collected to ensure accuracy and completeness 
• 
complete the Study Conclusion screen in the eCRF. 
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5.6.14. 
Study procedures during special circumstances (Amended, 28 
April 2020) 
During special circumstances (e.g., COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be applied. For the duration of such special circumstances, 
the following measures may be implemented for enrolled participants: 
• 
If despite best efforts it is not possible to collect the biological samples within the 
interval predefined in the protocol (refer to Table 6), then the interval may be 
extended. 
• 
If despite best efforts it is not possible to administer the dose of study intervention 
as defined in the protocol (refer to Table 6), then the interval may be extended. 
5.7. 
Biological sample handling and analysis 
Please refer to the SPM  and Central Laboratory Manual for details on Biospecimen 
Management (handling, storage and shipment). 
Samples will not be labelled with information that directly identifies the subject but will 
be coded with a unique sample identifier, subject and visit numbers. 
• 
Collected samples will be used for protocol mandated research and purposes related 
to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. This may include the management of the quality of these 
tests, the maintenance or improvement of these tests, the development of new test 
methods, as well as making sure that new tests are comparable to previous methods 
and work reliably. 
• 
It is also possible that future findings may make it desirable to use the samples 
acquired in this study for future research, not described in this protocol. Therefore, 
all subjects in countries where this is allowed will be asked to give a specific consent 
to allow GSK or a contracted partner to use the samples for future research. Future 
research will be subject to the laws and regulations in the respective countries and 
will only be performed once an independent Ethics Committee or Review Board has 
approved this research. 
Information on further investigations and their rationale can be obtained from GSK 
Biologicals.  
Any sample testing will be done in line with the consent of the individual subject. 
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s).  
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Collected samples will be stored for a maximum of 20 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 GSK Biologicals. 
5.7.1. 
Use of specified study materials 
When materials are provided by GSK Biologicals, 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 per-protocol analysis (See Section 10.4 for the 
definition of analysis sets to be analysed). The investigator must ensure that his/her 
personnel and the laboratory(ies) under his/her supervision comply with this requirement. 
However, when GSK Biologicals does not provide material for collecting and storing 
clinical samples, appropriate materials from the investigator’s site must be used. Refer to 
the Module on Clinical Trial Supplies in the SPM. 
5.7.2. 
Biological samples 
Table 7 
Biological samples 
Sample type 
Quantity 
Unit 
Timepoint 
Study group  
Blood donation 
for hSBA assay  
development 
300  
ml  
Visit 1, Visit 5 and Visit 8  
rMenB+OMV NZ  
300  
ml  
Visit 1, Visit 5 and Visit 9  
MenACWY 1  
300  
ml  
Visit 2, Visit 6 and Visit 9  
MenACWY 2  
300  
ml  
Visit 3, Visit 7 and Visit 9  
MenACWY 3  
5.7.3. 
Laboratory assays 
The primary objective of this study is the collection of baseline and post vaccination 
blood samples from healthy adults to be used in the development, qualification, 
validation and maintenance of immunological assays and to support the preclinical 
research activities, clinical development and life cycle management of GSK Biologicals 
for other studies or for development activities. The samples will be measured for 
concentration of antibodies induced by the administered vaccine, but not as an endpoint. 
Further serological tests may be performed to characterise the response to the vaccine, or 
to support further clinical development and life cycle management of GSK Biologicals 
vaccines, in case of availability of a sufficient amount of sera.  
Additional exploratory testing on the vaccine and/or on the disease under study may be 
performed within the framework of the study if deemed necessary for accurate 
interpretation of the data or should such assay(s) become available at GSK. These assays 
may not be represented in the objectives/endpoints of the study protocol. 
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6. 
STUDY VACCINE(S) AND ADMINISTRATION 
6.1. 
Description of study vaccine(s) 
The Quality Control Standards and Requirements for each candidate vaccine are 
described in separate Quality Assurance documents (e.g. release protocols, certificate of 
analysis) and the required approvals have been obtained.  
The vaccine(s) are labelled and packed according to applicable regulatory requirements. 
Commercial vaccine(s) are assumed to comply with the specifications given in the 
manufacturer’s Summary of Product Characteristics. 
Table 8 
Study vaccine(s) 
Treatment 
name 
Vaccine name 
Formulation 
Presentation 
Volume to be 
administered 
Number 
of doses 
MenACWY 
MenA lyo 
MenA=10µg CRM197; 
CRM197=16.7-33.3µg  
Lyophilized pellet in 
a mono dose vial  
0.5 ml 
1 
MenCWY liquid  
MenC=5µg CRM197; 
MenW=5µg CRM197; 
MenY=5µg CRM197; 
CRM197=16-30.8µg   
Liquid in a prefilled 
vial  
rMenB+OMV 
NZ  
rMenB+OMV NZ  rp936-741=50µg; 
rp287-953=50µg; 
rp961c=50µg; OMV 
NZ98/254=25µg; 
Al(OH)₃=1.5mg; 
Histidine=776µg; 
NaCl=3.125mg; 
Sucrose=10mg    
Suspension in a 
glass pre-filled 
syringe 
0.5 ml  
2 
Note: Menveo commercial formulation consisting of a MenA lyophilized component and a MenCWY liquid component 
to be reconstituted together before administration (0.5mL). 
6.2. 
Storage and handling of study vaccine(s) 
The study vaccine(s) must be stored at the respective label storage temperature conditions 
in a safe and locked place. Access to the storage space should be limited to authorized 
study personnel. The storage conditions will be assessed during pre-study activities under 
the responsibility of the sponsor study contact. The storage temperature should be 
continuously monitored with calibrated (if not validated) temperature monitoring 
device(s) and recorded. Refer to the Module on Clinical Trial Supplies in the SPM for 
more details on storage of the study vaccine(s). 
Temperature excursions must be reported in degree Celsius. 
Non-IMPs that are impacted by a temperature excursion may not be used and must be 
quarantined at label storage conditions until usage approval has been obtained from/via 
the local study contact (e.g. Site Monitor). There is no need for reporting via the 
Advanced Temperature Excursion Analysis and Management (ATEAM). 
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Refer to the Module on Clinical Trial Supplies in the SPM for details and instructions on 
the temperature excursion reporting and usage decision process, packaging and 
accountability of the study vaccine(s). 
6.3. 
Dosage and administration of study vaccine(s)  
Table 9 
Dosage and administration  
Type of 
contact and 
timepoint 
Study group Treatment 
name 
Volume to be 
administered Route1 
Site 
Location 
Directionality2 Laterality3 
Visit 4  
 (Day 1) 
rMenB+OMV 
NZ  
rMenB+OMV 
NZ 
0.5 ml 
IM 
Deltoid 
Upper 
Non-
dominant 
Visit 4  
(Day 1) 
MenACWY 1  MenACWY 
0.5 ml 
IM 
Deltoid 
Upper 
Non-
dominant 
MenACWY 2  
MenACWY 3  
Visit 7  
(Day 61 ) 
rMenB+OMV 
NZ  
rMenB+OMV 
NZ  
0.5 ml  
IM  
Deltoid  
Upper 
Non-
dominant  
1Intramuscular (IM)  
2Directionality is a qualifier for further detailing the location of the vaccine administration (e.g. Upper, Lower) 
3The non-dominant arm is the preferred arm of injection. In case it is not possible to administer the vaccine in the non-
dominant arm, an injection in the dominant arm may be performed. 
6.4. 
Replacement of unusable vaccine 
In addition to the vaccine doses provided for the planned number of subjects (including 
over-randomisation when applicable), at least 20% additional vaccine doses will be 
supplied to replace those that are unusable.  
6.5. 
Contraindications to subsequent vaccination 
The following events constitute absolute contraindications to further administration of 
rMenB+OMV NZ. If any of these events occur during the study, the subject must not 
receive additional doses of vaccine but may continue other study procedures at the 
discretion of the investigator (see Section 8.5).  
• 
Anaphylaxis following the administration of vaccine(s). 
• 
Pregnancy (see Section 8.2.1) 
• 
Any condition that in the judgment of the investigator would make intramuscular 
injection unsafe. 
The following events constitute contraindications to administration of rMenB+OMV NZ 
or MenACWY at that point in time; if any of these events occur at the time scheduled for 
vaccination, the subject may be vaccinated at a later date, within the time window 
specified in the protocol (see Section 5.5), or the subject may be withdrawn at the 
discretion of the investigator (see Section 8.5).  
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• 
Acute disease and/or fever at the time of vaccination.  
− 
Fever is defined as temperature  37.5°C / 99.5°F. The preferred location for 
digitally measuring temperature in this study will be the oral cavity.* 
− 
Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory 
infection) without fever can be administered all vaccines. 
• 
* There will be a minimum of 5 consecutive days without fever, before the subject 
becomes eligible for vaccination. 
6.6. 
Warnings and precautions 
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic 
response to the needle injection. This can be accompanied by several neurological signs 
such as transient visual disturbance, paresthesias and tonic-clonic limb movements during 
recovery. It is important that procedures are in place to avoid injury from faints. 
Syncope (fainting) can occur following, or even before blood sampling, as a psychogenic 
response to the needle injection. This can be accompanied by bruising and prolonged 
bleeding. It is important that procedures are in place to avoid injury from faints and that 
subjects have fluids and some sustenance after the blood draw.  
Additional warnings and precautions are listed as exclusion criteria. 
Refer to the approved product label/package insert for information on the vaccines in this 
study. 
6.7. 
Concomitant medications/products and concomitant 
vaccinations 
At each study visit, the investigator or delegate should question the subject about any 
medications/products taken and vaccinations received by the subject. 
6.7.1. 
Recording of concomitant medications/products and 
concomitant vaccinations  
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF. 
The investigator will only ask about the concomitant medications/products/vaccines 
listed below (Section 6.7.2) that were taken/given prior to the vaccination or blood 
collection visits. For blood products, the investigator should ask if any have been 
received within 3 months of any vaccination or blood collection and for 
immunosuppressants or other immune-modifying drugs he/she should ask if any have 
been received from 6 months prior to vaccination or blood collection. For antibiotics, the 
investigator should ask if any have been given within 14 days of the vaccination/ blood 
collection visit and for investigational products, the investigator should ask if any have 
been received throughout the study. 
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• 
Any concomitant vaccination administered in the period starting 14 days before the 
first dose of study vaccine(s) and ending at the last study visit (Day 98 to Day 151)  
• 
Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination). 
• 
Any concomitant medications/products/vaccines listed in Section 6.7.2. 
• 
Any concomitant medications/products/vaccines relevant to a SAE to be reported as 
per protocol or administered at any time during the study period, for the treatment of 
a SAE. In addition, concomitant medications relevant to SAEs need to be recorded 
on the expedited Adverse Event report. 
6.7.2. 
Concomitant medications/products/vaccines that may lead to 
elimination of the blood sample as a reagent 
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the subject from the study but may lead to elimination of the blood sample 
as a reagent. 
• 
Any investigational or non-registered product (drug or vaccine) other than the study 
vaccines used during the study period.  
• 
Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. more than 14 days in total) during the study period. For corticosteroids, this will 
mean prednisone  20 mg/day (for adult subjects), or equivalent. Inhaled and topical 
steroids are allowed.  
• 
Any antibiotic intake 7 days prior to blood collection. The subject will have a 7-day 
delay for blood draw. 
• 
Immunoglobulins and/or any blood products administered within 3 months preceding 
the dose of study vaccine or blood collection. 
6.7.3. 
Reasons for deferring blood collection 
Blood collection will be deferred for the following reasons and will be recorded in the 
eCRF. After resolution of the condition, or once the protocol-forbidden interval for 
repeating blood collection is exceeded, the subject may undergo blood collection, as long 
as it is in within the protocol-specified window. 
• 
Low haemoglobin levels prior to each blood collection. The subjects can donate 
blood once the levels have returned to normal.   
• 
Current presence of a bleeding disorder. 
• 
Subjects who donated >450 mL of blood within 60 days prior to any blood collection 
visits.  
• 
Subjects who lost >200 mL during a single apheresis or who lost red blood cells on 
more than one occasion during apheresis within the previous 60 days.  
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• 
Subjects who received any antibiotic within the 7 days before the planned collection 
of blood. The subjects can donate blood with a 7-days delay after the last dose of 
antibiotics. 
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 serious adverse event (SAE) 
as provided in this protocol.  
Each subject 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.  
8.1.2. 
Definition of a serious adverse event  
A SAE 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, 
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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, OR 
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. 
Medical or scientific judgement should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalisation but may jeopardise the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious. 
Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalisation. 
8.1.3. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as serious adverse events  
In absence of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, 
haematology, urinalysis) or other abnormal assessments (e.g. imaging analysis) that are 
judged by the investigator to be clinically significant will be recorded as SAE if they 
meet the definition of an SAE (refer to Section 8.1.2). Clinically significant abnormal 
laboratory findings or other abnormal assessments that are present at baseline and 
significantly worsen following the start of the study will also be reported as 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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8.2. 
Events or outcomes not qualifying as serious adverse 
events  
8.2.1. 
Pregnancy 
Female subjects who are pregnant or lactating at the time of vaccination must not receive 
additional doses of study vaccine(s) and may not continue other study procedures.  
While pregnancy itself is not considered an SAE, any adverse pregnancy outcome or 
complication or elective termination of a pregnancy for medical reasons will be recorded 
and reported as an SAE. 
Note: The pregnancy itself should always be recorded on an electronic pregnancy report. 
The following should always be considered as SAE and will be reported as described in 
Sections 8.4.1 and 8.4.3: 
• 
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 study vaccine(s) will be reported to 
GSK Biologicals as described in Section 8.4.3. While the investigator is not obligated to 
actively seek this information from former study participants, he/she may learn of a 
pregnancy through spontaneous reporting. 
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8.3. 
Detecting and recording serious adverse events and 
pregnancies 
8.3.1. 
Time period for detecting and recording serious adverse events 
and pregnancies 
The time period for collecting and recording SAEs will begin at the first receipt of study 
vaccine(s) and will continue throughout the study for each subject. See Section 8.4 for 
instructions on reporting of SAEs. 
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) or are 
related to a concurrent GSK medication/vaccine 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 study visit 
and will continue throughout the study for each subject. See section 8.4 for instructions 
on reporting of pregnancies. 
An overview of the protocol-required reporting periods for SAEs and pregnancies is 
given in Table 10. 
Table 10 
Reporting periods for collecting safety information  
Event 
Epoch 001 
Visit 1 
(Day 
 -83) 
Visit 2  
(Day   
-60) 
Visit 3  
(Day  
-30) 
Visit 4  
(Day 
1) 
Visit 5  
(Day 
8) 
Visit 6  
(Day 
31) 
Visit 7  
(Day 
61) 
Visit 8 
(Day 
98) 
Visit 9 
(Day 
151) 
SAEs  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation or 
concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.3.2. 
Post-Study serious adverse events 
A post-study SAE is defined as any event that occurs outside of the SAE reporting period 
defined in Table 10. Investigators are not obligated to actively seek SAEs in former study 
participants. However, if the investigator learns of any SAE at any time after a subject 
has been discharged from the study, and he/she considers the event reasonably related to 
the study vaccine(s), the investigator will promptly notify the Study Contact for 
Reporting SAEs. 
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8.3.3. 
Evaluation of serious adverse events 
8.3.3.1. 
Active questioning to detect serious adverse events 
As a consistent method of collecting SAEs, 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 a 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 a SAE in 
the eCRF. The investigator is not allowed to send photocopies of the subject’s medical 
records to GSK Biologicals instead of appropriately completing the eCRF. However, 
there may be instances when copies of medical records for certain cases are requested by 
GSK Biologicals. In this instance, all subject identifiers will be blinded on the copies of 
the medical records prior to submission to GSK Biologicals. 
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the SAE and not the individual signs/symptoms. 
8.3.3.2. 
Assessment of serious adverse events 
8.3.3.2.1. Assessment of intensity 
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. 
Every effort should be made by the investigator to evaluate safety information reported 
by a subject for an underlying diagnosis and to capture this diagnosis as the event in the 
AE page. In other words, the practice of reporting only symptoms (e.g., “cough” or “ear 
pain”) are better reported according to the underlying cause (e.g., “asthma exacerbation” 
or “otitis media”). 
The severity of events reported on the Adverse Events eCRF will be determined by the 
investigator as: 
Mild: 
transient with no limitation in normal daily activity. 
Moderate: 
some limitation in normal daily activity. 
Severe: 
unable to perform normal daily activity. 
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8.3.3.2.2. Assessment of causality 
The investigator is obligated to assess the relationship between study vaccine(s) and the 
occurrence of each SAE using clinical judgement. In case of concomitant administration 
of multiple vaccines/products, if possible, the investigator should specify if the SAE 
could be causally related to a specific vaccine/product administered (i.e investigational, 
control/placebo or co-administered vaccine). When causal relationship to a specific 
vaccine(s)/product(s) cannot be determined the investigator should indicate the SAE to be 
related to all products. 
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 
study vaccine(s) will be considered and investigated. The investigator will also consult 
the Prescribing Information for marketed products to determine his/her assessment. 
There may be situations when a SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK Biologicals. However, it is very 
important that the investigator always makes an assessment of causality for every event 
prior to submission of the Expedited Adverse Events Report to GSK Biologicals. The 
investigator may change his/her opinion of causality in light of follow-up information and 
update the SAE information accordingly. The causality assessment is one of the criteria 
used when determining regulatory reporting requirements. 
Is there a reasonable possibility that the SAE may have been caused by the study 
vaccine? 
YES 
: 
There is a reasonable possibility that the study vaccine(s) contributed to 
the SAE.  
NO 
: 
There is no reasonable possibility that the SAE 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 SAE. 
If an event meets the criteria to be determined as ‘serious’ (see Section 8.1.2), additional 
examinations/tests will be performed by the investigator in order to determine ALL 
possible contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the vaccine(s), if applicable. 
• 
Erroneous administration. 
• 
Other cause (specify). 
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8.3.3.2.3. Assessment of outcomes 
The investigator will assess the outcome of all SAEs recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 
8.4. 
Reporting of serious adverse events and pregnancies 
8.4.1. 
Prompt reporting of serious adverse events and pregnancies to 
GSK Biologicals 
SAEs that occur in the time period defined in Section 8.3 will be reported promptly to 
GSK within the timeframes described in Table 11, once the investigator determines that 
the event meets the protocol definition of a SAE. 
Pregnancies that occur in the time period defined in Section 8.3 will be reported promptly 
to GSK within the timeframes described in Table 11, once the investigator becomes 
aware of the pregnancy.  
Table 11 
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK Biologicals 
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡ 
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
Pregnancies  
2 weeks* 
electronic pregnancy report  
2 weeks* 
electronic pregnancy report  
*Timeframe allowed after receipt or awareness of the information. 
‡ The investigator will be required to confirm review of the SAE causality by ticking the ‘reviewed’ box in the electronic 
Expedited Adverse Events Report within 72 hours of submission of the SAE. 
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8.4.2. 
Contact information for reporting serious adverse events and 
pregnancies  
Study Contact for Reporting SAEs and pregnancies  
Refer to the local study contact information document. 
Back-up Study Contact for Reporting SAEs and pregnancies  
24/24 hour and 7/7 day availability: 
GSK Biologicals Clinical Safety & Pharmacovigilance 
Outside US & Canada sites: 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: Rix.CT-safety-vac@gsk.com 
8.4.3. 
Completion and transmission of SAE reports to GSK Biologicals 
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator (or designate) must complete the information in the electronic Expedited 
Adverse Events Report WITHIN 24 HOURS. The 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. The investigator will be required to confirm the review of the SAE causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the SAE. 
8.4.3.1. 
Back-up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designate) must 
complete, then date and sign a paper Expedited Adverse Events Report and fax it to the 
Study Contact for Reporting SAEs (refer to the Sponsor Information) or to GSK 
Biologicals Clinical Safety and Pharmacovigilance department within 24 hours.  
This back-up system should only be used if the electronic reporting system is not working 
and NOT if the system is slow. As soon as the electronic reporting system is working 
again, the investigator (or designate) must complete the electronic Expedited Adverse 
Events Report within 24 hours. The final valid information for regulatory reporting will 
be the information reported through the electronic SAE reporting system.  
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8.4.4. 
Completion and transmission of pregnancy reports to GSK 
Biologicals 
Once the investigator becomes aware that a subject is pregnant, the investigator (or 
designate) must complete the required information onto the electronic pregnancy report 
WITHIN 2 WEEKS. 
Note: Conventionally, the estimated gestational age (EGA) of a pregnancy is dated from 
the first day of the last menstrual period (LMP) of the cycle in which a woman conceives. 
If the LMP is uncertain or unknown, dating of EGA and the estimated date of delivery 
(EDD) should be estimated by ultrasound examination and recorded in the pregnancy 
report. 
8.4.5. 
Updating of SAE and pregnancy information after removal of 
write access to the subject’s eCRF 
When additional SAE and pregnancy information is received after removal of the write 
access to the subject’s eCRF, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study Contact for Reporting SAEs (refer to the 
Sponsor Information) or to GSK Biologicals Clinical Safety and Pharmacovigilance 
department within the designated reporting time frames specified in Table 11. 
8.4.6. 
Regulatory reporting requirements for serious adverse events 
The investigator will promptly report all SAEs to GSK in accordance with the procedures 
detailed in Section 8.4.1. GSK Biologicals has a legal responsibility to promptly notify, 
as appropriate, both the local regulatory authority and other regulatory agencies about the 
safety of a product under clinical investigation. Prompt notification of SAEs by the 
investigator to the Study Contact for Reporting SAEs is essential so that legal obligations 
and ethical responsibilities towards the safety of other subjects are met. 
Investigator safety reports are prepared according to the current GSK policy and are 
forwarded to investigators as necessary. An investigator safety report is prepared for a 
SAE(s) that is both attributable to the study vaccine(s) and unexpected. The purpose of 
the report is to fulfil specific regulatory and GCP requirements, regarding the product 
under investigation. 
8.5. 
Follow-up of serious adverse events and pregnancies 
8.5.1. 
Follow-up of serious adverse events  
8.5.1.1. 
Follow-up during the study 
After the initial SAE report, the investigator is required to proactively follow each subject 
and provide additional relevant information on the subject’s condition to GSK 
Biologicals (within 24 hours for SAEs; refer to Table 11). 
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All SAEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until the 
last visit of the subject. 
8.5.1.2. 
Follow-up after the subject is discharged from the study 
The investigator will follow subjects: 
• 
with SAEs until the event has resolved, subsided, stabilised, disappeared, or until the 
event is otherwise explained, or the subject is lost to follow-up.  
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to GSK Biologicals using a paper/ electronic 
Expedited Adverse Events Report and/or pregnancy report as applicable. 
GSK Biologicals may request that the investigator performs or arranges the conduct of 
additional clinical examinations/tests and/or evaluations to elucidate as fully as possible 
the nature and/or causality of the SAE. The investigator is obliged to assist. If a subject 
dies during participation in the study or during a recognised follow-up period, GSK 
Biologicals will be provided with any available post-mortem findings, including 
histopathology. 
8.5.2. 
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 GSK Biologicals using the electronic pregnancy report and 
the Expedited Adverse Events Report if applicable. Generally, the follow-up period 
doesn’t need to be longer than six to eight weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is a 
SAE, it should always be reported as SAE. 
8.6. 
Treatment of serious adverse events 
Treatment of any SAE is at the sole discretion of the investigator and according to current 
good medical practice. Any medication administered for the treatment of a SAE should 
be recorded in Expedited Adverse Event Report of the subject’s eCRF (refer to Section 
6.7). 
8.7. 
Subject card 
Study subjects must be provided with the address and telephone number of the main 
contact for information about the clinical study. 
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The investigator (or designate) must therefore provide a “subject card” to each subject. In 
an emergency situation this card serves to inform the responsible attending physician that 
the subject is in a clinical study and that relevant information may be obtained by 
contacting the investigator. 
Subjects must be instructed to keep subject cards in their possession at all times during 
the study duration. 
9. 
SUBJECT COMPLETION AND WITHDRAWAL 
9.1. 
Subject completion 
A subject who returns for the concluding visit foreseen in the protocol is considered to 
have completed the study. 
9.2. 
Subject withdrawal 
Withdrawals will not be replaced. 
9.2.1. 
Subject withdrawal from the study 
From an analysis perspective, a ‘withdrawal’ from the study refers to any subject who did 
not come back for the concluding visit foreseen in the protocol.  
All data collected until the date of withdrawal/last contact of the subject will be used for 
the analysis. 
A subject is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this subject from the date of withdrawal/last contact. 
Investigators will make an attempt (3 telephone calls and a certified letter) to contact 
those subjects who do not return for scheduled visits or follow-up. 
Information relative to the withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject himself/herself or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal: 
• 
Serious adverse event. 
• 
Unsolicited non-serious adverse event. 
• 
Solicited adverse event. 
• 
Protocol violation (specify). 
• 
Consent withdrawal, not due to an adverse event*. 
• 
Moved from the study area. 
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• 
Lost to follow-up. 
• 
Other (specify). 
*In case a subject is withdrawn from the study because he/she/the subject’s 
parent(s)/LAR(s) has withdrawn consent, the investigator will document the reason for 
withdrawal of consent, if specified by the subject/subject’s parent(s)/LAR(s), in the 
eCRF. 
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 8.5.1.2). 
9.2.2. 
Subject withdrawal from study vaccine(s) 
A ‘withdrawal’ from the study vaccine(s) refers to any subject who does not receive the 
complete treatment, i.e. when no further planned dose is administered from the date of 
withdrawal. A subject withdrawn from the study vaccine(s) may not necessarily be 
withdrawn from the study as further study procedures or follow-up may be performed 
(safety or immunogenicity) if planned in the study protocol.  
Information relative to premature discontinuation of the study vaccine(s) 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 or by the investigator, as well as which of the 
following possible reasons was responsible for withdrawal: 
• 
Serious adverse event. 
• 
Unsolicited non-serious adverse event. 
• 
Solicited adverse event. 
• 
Not willing to be vaccinated. 
• 
Other (specify). 
10. 
STATISTICAL METHODS 
10.1. 
Primary endpoint 
• 
Collection of human blood for conversion into serum to use in the development, 
qualification, validation and maintenance of immunological assays and to support the 
preclinical research activities, clinical development and life cycle management of 
GSK Biologicals’ vaccines:  
− 
at Visit 1, Visit 5 and Visit 8 for the rMenB+OMV NZ group;  
− 
at Visit 1, Visit 5 and Visit 9; Visit 2, Visit 6 and Visit 9 and Visit 3, Visit 7 and 
Visit 9 for the MenACWY 1, MenACWY 2 and MenACWY 3 groups, 
respectively. 
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10.2. 
Secondary endpoint 
• 
Assessment of the occurrence of SAEs related to vaccination throughout the study, in 
all subjects.   
10.3. 
Determination of sample size 
No formal statistical sample size and power calculations will be performed.   
The purpose of the study is to support the laboratory with sufficient serum from 
vaccinated subjects. The two meningococcal vaccines are licensed, and there is no 
immunogenicity endpoint. Therefore, no formal statistical sample size and power 
calculations are required to meet the endpoints. The objectives are the collection of serum 
and descriptive assessment of the safety. Sample size is determined by CLS based on the 
volumes of sera and the number of individual subjects pre/post vaccination sera that CLS 
requires (including expected loss due to drop-outs). 
Up to 540 subjects, in the first study year, and up to 120 subjects, in each of the following 
four study years, will be enrolled to identify healthy adult individuals to donate human 
blood for use in the QC panels for GSK Biologicals’ assays. 
10.4. 
Analysis Sets 
10.4.1. 
All Enrolled Set 
All screened subjects who provide informed consent and provide demographic and/or 
baseline screening assessments, regardless of the subject’s randomization and treatment 
status in the study and received a Subject ID. 
10.4.2. 
All Exposed Set 
All subjects in the enrolled set who receive a study vaccination. 
10.5. 
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 report. 
10.5.1. 
Sequence of analyses 
All analyses (including interim analysis) will be conducted on data as clean as possible. 
An interim report will be prepared annually and, at the end of the study, a clinical study 
report will be prepared, and both will include the following: 
• 
The number of subjects enrolled. 
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• 
The number of subjects that attended each visit. 
• 
The volume of blood collected per subject. 
• 
A listing of all SAEs and pregnancies, that occurred during the entire study 
participation. 
An integrated clinical study report containing all data will be written and made available 
to the investigators. 
10.5.2. 
Statistical considerations for interim analyses 
In order to obtain early data regarding the study objectives and to comply with internal 
reporting obligations, an interim analysis will be performed yearly on the cumulative data 
from subjects enrolled up to the respective year. This analysis will present a summary of 
the number of subjects enrolled, subjects who are compliant with the study visits, the 
volume of blood collected per subject and also listings of all SAEs with no statistical 
analysis. Individual listings will also be provided. As the study is not blinded, the interim 
analysis will be performed by the Sponsor. This analysis will not be used to alter the 
study conduct nor to conclude on the study objective, there will be no statistical 
adjustment.  
11. 
ADMINISTRATIVE MATTERS 
To comply with ICH GCP administrative obligations relating to data collection, 
monitoring, archiving data, audits, confidentiality, public disclosure requirements and 
publications must be fulfilled.  
11.1. 
electronic Case Report Form instructions 
A validated GSK defined electronic data collection tool will be used as the method for 
data collection.  
In all cases, subject initials will not be collected nor transmitted to GSK. 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 GSK standards and data cleaning procedures. 
While completed eCRFs are reviewed by a GSK Biologicals’ Site Monitor at the study 
site, omissions or inconsistencies detected by subsequent eCRF review may necessitate 
clarification or correction by the investigator or appropriately qualified designee. In all 
cases, the investigator remains accountable for the study data.  
The investigator will be provided with an electronic format in read only mode 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. 
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11.2. 
Study Monitoring by GSK Biologicals 
GSK will monitor the study to verify that, amongst other items, the:  
• 
Data are authentic, accurate, and complete. 
• 
Safety and rights of subjects are being protected. 
• 
Study is conducted in accordance with the currently approved protocol, any other 
study agreements, GCP and all applicable regulatory requirements.  
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents. 
The investigator must ensure provision of reasonable time, space and qualified personnel 
for monitoring visits. 
Direct access to all study-site related and source data is mandatory for the purpose of 
monitoring review. The monitor will perform a eCRF review and a Source Document 
Verification (SDV). By SDV we understand verifying eCRF entries by comparing them 
with the source data that will be made available by the investigator for this purpose.  
The Source Documentation Agreement Form describes the source data for the different 
data in the eCRF. This document should be completed and signed by the site monitor and 
investigator and should be filed in the investigator’s study file. Any data item for which 
the eCRF will serve as the source must be identified, agreed and documented in the 
source documentation agreement form.  
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 GSK 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. 
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GSK will inform the investigator/institution of the time period for retaining these records 
to comply with all applicable regulatory requirements. 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 GSK standards/procedures, 
otherwise, the minimum retention period will default to 25 years after completion of the 
study report. 
The investigator/institution must notify GSK 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, GSK may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory 
inspection of this study. Such audits/inspections can occur at any time during or after 
completion of the study. If an audit or inspection occurs, the investigator and institution 
agree to allow the auditor/inspector direct access to all relevant documents and to allocate 
his/her time and the time of his/her staff to the auditor/inspector to discuss findings and 
any relevant issues. 
11.5. 
Posting of information on publicly available clinical trial 
registers and publication policy  
GSK assures that the key design elements of this protocol will be posted on the GSK 
website and in publicly accessible database(s) such as clinicaltrials.gov, in compliance 
with the current regulations. 
GSK also assures that results of this study will be posted on the GSK website and in 
publicly accessible regulatory registry(ies) within the required time-frame, in compliance 
with the current regulations. The minimal requirement is to have primary endpoint 
summary results disclosed at latest 12 months post primary completion date (PCD) and to 
have secondary endpoint disclosed at latest 12 months after the last subject last visit 
(LSLV) as described in the protocol. 
As per EU regulation, summaries of the results of GSK interventional studies (phase I-
IV) in adult population conducted in at least one EU member state will be posted on 
publicly available EMA registers within 12 months of EoS (as defined in the protocol) in 
the concerned EU member state. However, where, for scientific reasons detailed in the 
protocol, it is not possible to submit a summary of the results within one year in the 
concerned EU member state, the summary of results shall be submitted as soon as it is 
available. In this case, the protocol shall specify when the results are going to be 
submitted, together with a justification.  
Interventional studies that do not evaluate vaccines/products are progressed for 
publication in the scientific literature when the results provide important scientific or 
medical knowledge or are relevant for patient care, and will be considered for disclosure 
on the GSK website and in publicly accessible regulatory registry(ies). 
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11.6. 
Provision of study results to investigators 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location. 
GSK Biologicals 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. 
11.7. 
Data Sharing 
Under the framework of the SHARE initiative, results of GSK studies may be combined 
with non- GSK studies, to investigate further about the study product(s) and other 
product(s), and /or the disease/condition under investigation and related diseases and 
conditions. 
12. 
COUNTRY SPECIFIC REQUIREMENTS 
All countries will comply with SAE reporting as described in Section 8.4 of the protocol. 
Additionally, countries and sites will follow all applicable local regulations and 
guidelines for AE and SAE reporting as required by their respective healthcare authorities 
and ethics committees. 
12.1. 
Requirements for Germany 
EXPLANATORY STATEMENT CONCERNING GENDER DISTRIBUTION 
(ARTICLE 7, PARAGRAPH 2 (12) OF THE GERMAN GCP ORDER) 
For this MENB REC 2ND GEN-079 HBS study, there is no intention to conduct specific 
analyses investigating the relationship between gender and the safety and efficacy of the 
Menveo and Bexsero vaccines. Serum will not be assessed for immunogenicity or 
efficacy as an endpoint of this trial. Recruitment will include males and females. Females 
enrolled in this trial will either be of non-childbearing potential, or if they are of 
childbearing potential, they must practice adequate contraception for 30 days prior to the 
beginning of the administration of study treatment, have a negative pregnancy test and 
continue such precautions during the entire study treatment period and for 2 months after 
completion of the injection series (Refer to the study protocol, Section 4.2 “Inclusion 
criteria” and Section 4.3 “Exclusion criteria”). The recruitment will be closed to females 
who are pregnant or lactating. Similarly, patients becoming or deciding to become 
pregnant during the study must stop the study treatment administrations.  
The two vaccines used in this study are licensed and intended for use in both genders, 
therefore the clinical immunological assays are developed, qualified, validated and 
maintained using both male and female sera. 
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13. 
REFERENCES 
Australian Red Cross Blood Service - Eligibility, 2016 
http://www.donateblood.com.au/eligibility. Accessed 27 July 2017  
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 
EMA Guideline on the exposure to medicinal products during pregnancy: need for post-
authorization data (Doc. Ref. EMEA/CHMP/313666/2005 ) ‘adopted at Community level 
in May 2006); 
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_g
uideline/2009/11/WC500011303.pdf 
Magnus P, Brubakk O, Nyland H, Wold BH, Gjessing HK, Brandt I, Eidem T, Nøkleby 
H, Stene-Larsen G. Vaccination as teenagers against meningococcal disease and the risk 
of the chronic fatigue syndrome. Vaccine. 2009; 27(1): 23-27.  
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14. 
APPENDICES 
APPENDIX A 
CLINICAL LABORATORIES 
Table 12 
GSK Biologicals’ laboratories 
Laboratory 
Address 
GSK Biological’s Clinical Laboratory 
Sciences, Rixensart  
Biospecimen Reception - B7/44 
Rue de l'Institut, 89 - B-1330 Rixensart – Belgium  
GSK Biological’s Clinical Laboratory 
Sciences, Wavre-Nord Noir Epine 
Avenue Fleming, 20 - B-1300 Wavre - Belgium 
GSK Vaccines GmbH 
Clinical Laboratory Sciences, 
Marburg, Germany 
Emil-von-Behring-Str. 76 
35041 Marburg 
Germany 
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Rationale/background for changes:  
• 
The detailed title was reworded, to assure consistency with the text of the Protocol, 
where “rMenB+OMV NZ” is used as vaccine name instead of “Meningococcal B 
recombinant” 
• 
The name of a contributing author has been updated 
• 
The primary objective was reworded, in order to clarify the timepoints specific for 
each study group 
• 
The duration of the study for individual subjects has been updated to 
“approximately 6 to 8 months”, as the duration will vary depending on the study 
group the subject will be assigned to 
• 
In the Synopsis, the sampling schedule was reworded, for clarification purposes 
• 
The List of abbreviations and Glossary of terms were updated 
• 
To avoid misinterpretation, the volume of blood to be collected was changed, from 
“maximum 300mL” to “300mL” 
• 
The exclusion criteria no. 17 was amended to remove haematocrit values, as 
haemoglobin values will suffice for detecting anaemia 
• 
The list of study procedures was updated (Table 5), to collect demographic data, 
have physical examination at each study visit and have different timepoints for 
recording height and weight of the subjects. As a consequence, Section 5.6. 
Detailed description of study procedures was updated to reflect the changes in 
Table 5 
• 
Mandatory wording in Section 5.6.6. Pregnancy test was altered, for consistency 
with the contraindications for vaccine administration  
• 
The rMenB+OMV NZ vaccine formulation presented in the Vaccine name and 
Formulation columns in Table 8 was updated, as requested by the German 
Regulatory team, to ensure consistency with all other Bexsero related documents, 
clinical and regulatory 
• 
Following comments received from PI, Section 6.6. Warnings and precautions was 
updated with blood draw warnings and precautions  
• 
Wording containing adverse events (AEs) was deleted, to avoid confusion, as this 
study will not collect AEs 
• 
Mandatory wording regarding the time period for collecting and recording 
pregnancies was altered, for consistency with exclusion criteria and study 
procedures 
• 
Minor edits have been made in alignment with the GSK protocol template. 
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections: 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

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Treatment 
name 
Vaccine/Product 
name 
Study Groups 
rMenB+OMV NZ  MenACWY 1 
MenACWY 2 
MenACWY 3 
rMenB+OMV 
NZ (Bexsero) 
Men B 
recombinant 
rMenB+OMV NZ 
x 
 
 
 
MenACWY 
(Menveo) 
MenA lyo 
 
x 
x 
x 
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PPD
PPD

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
73 
 
• 
Sampling schedule: Blood samples will be collected 
from all four groups rMenB+OMV NZ group at Visits 
1, 5 and 8; from MenACWY 1 group at Visits 1, 5 and 
9; from MenACWY 2 group at Visits 2, 6 and 9 and 
from MenACWY 3 group at Visits 3, 5, Visit 6, Visit7, 
Visit 8 and Visit and 9. 
LIST OF ABBREVIATIONS 
pIMD 
Potential Immune-Mediated Disease 
GLOSSARY OF TERMS 
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. 
Protocol amendment: 
The International Conference on Harmonisation (ICH) 
defines a protocol amendment as: ‘A written description 
of a change(s) to or formal clarification of a protocol.’ 
GSK Biologicals further details this to include a change 
to an approved protocol that affects the safety of 
subjects, scope of the investigation, study design, or 
scientific integrity of the study. 
2.1. 
Primary objective 
To collect baseline (Visit 1, Visit 2 and or Visit 3, depending on the study group) and 
post vaccination (Visit 5, Visit 6, Visit 7, Visit 8 and Visit 9 Visits 5, 8; Visits 5, 9; Visits 
6, 9 or Visits 7, 9, depending on the study group) blood sample donations to serve for the 
development, qualification, validation and maintenance of immunological assays and to 
support the preclinical research activities, clinical development and life cycle 
management of GSK Biologicals’ vaccines. 
3. 
STUDY DESIGN OVERVIEW 
• 
Duration of the study for individual subjects: For each subject enrolled, there will be 
a study duration of approximately 6 to 8 months. 
• 
End of Study (EoS): Last subject last visit at Visit 8 or 9 (Day 97 or Day 150, ending 
date dependent on the vaccine received by the subject, single dose of MenACWY or 
0,2-month schedule of rMenB+OMV NZ) of the last study year 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
74 
Table 2 
Study groups and treatment foreseen in the study 
Treatment 
name 
Vaccine/Product 
name 
Study Groups 
rMenB+OMV NZ  MenACWY 1 
MenACWY 2 
MenACWY 3 
rMenB+OMV 
NZ (Bexsero) 
Men B 
recombinant 
rMenB+OMV NZ 
x 
 
 
 
MenACWY 
(Menveo) 
MenA lyo 
 
x 
x 
x 
MenCWY liquid 
Table 4 
Sampling schedule  
Study groups 
Blood donation schedule 
Blood sample volume [mL] at 
each visit 
rMenB+OMV NZ  
Visit 1; Visit 5 and Visit 8 
max. 300 
MenACWY 1  
Visit 1, Visit 5 and Visit 9 
max. 300 
MenACWY 2  
Visit 2, Visit 6 and Visit 9 
max. 300 
MenACWY 3  
Visit 3, Visit 7 and Visit 9 
max. 300 
max., maximum. 
4.1. 
Number of subjects 
During the first study year, the target will be to enrol up to 540 healthy adults, naïve to 
any previous meningococcal vaccination or meningococcal and gonorrhoea diseases, 
aged 18-50 years at the time of ICF signing, into 4 study groups, in a 3:1:1:1 ratio.  
During each of the following four years, the target will be to enrol up to 120 healthy 
adults, naïve to any previous meningococcal vaccination or meningococcal and 
gonorrhoea diseases, aged 18-50 years at the time of ICF signing, into 4 study groups, in 
a 3:1:1:1 ratio. 
4.3. 
Exclusion criteria for enrolment 
• 
17. Ongoing anaemia as indicated by haemoglobin values below the lower limit of 
the laboratory-specified reference range (females:  haematocrit < 38%, haemoglobin 
< 12.5 g/dl; males:   haematocrit < 39%, haemoglobin < 13.0 g/dl or as per country 
specific recommendations/regulations).  If the finger prick method demonstrates an 
anaemia, no further protocol procedures will be performed, and the subject will be 
referred for appropriate medical management. The subject may participate in this 
study following therapy and evidence that the anaemia has been resolved. 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
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28-APR-2020 
75 
5.5. 
Outline of study procedures 
Table 5 
List of study procedures for each study year 
Epoch  
Epoch 001 
Type of contact 
Visit 1 Visit  
2 
Visit 
3 
Visit 4 Visit 
5 
Visit 
6 
Visit 
7* 
Visit  
8 
Visit  
9 
Timepoint (s) 
Day  
-83 
Day 
-60 
Day  
-30 
Day 
 1 
Day 
 7 
Day 
30  
Day 
 60  
Day  
97  
Day 
150 
Sampling timepoint(s) 
 Pre-
Vacc 
Pre-
Vacc 
Pre-
Vacc 
Vacc  
I 
 
 
Vacc II EoY/EoS EoY/EoS 
Informed consent 
● 
● 
● 
 
 
 
 
 
 
Check inclusion/exclusion criteria 
● 
● 
● 
 
 
 
 
 
 
Collect demographic data 
● 
● 
● 
 
 
 
 
 
 
Medical history 
● 
● 
● 
 
 
 
 
 
 
Physical examination 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Urine pregnancy test (locally) 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Check contraindications and warnings and 
precautions to vaccination 
 
 
 
O 
 
 
O 
 
 
Pre-vaccination body temperature 
 
 
 
● 
 
 
● 
 
 
Measure/record height 
● 
● 
● 
 
 
 
 
 
 
Measure/record height and weight 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Check reasons for deferring blood 
collection 
● 
● 
● 
 
● 
● 
● 
● 
● 
Study group and treatment number 
allocation 
O 
O 
O 
 
 
 
 
 
 
Recording of administered treatment 
number 
 
 
 
●  
 
 
●  
 
 
MenACWY vaccine administration 
 
 
 
● 
 
 
 
 
 
rMenB+OMV NZ vaccines administration 
 
 
 
● 
 
 
● 
 
 
Blood sampling for haemoglobin (~ one 
drop of blood) 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Collection of maximum 300 mL blood 
samples 
● 
● 
● 
 
● 
● 
● 
● 
● 
Record any concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of all SAEs and pregnancies 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Study Conclusion 
 
 
 
 
 
 
 
● 
● 
*At Visit 7, the rMenB+OMV NZ group will be scheduled for the second vaccination and should follow the same 
procedures as those listed at Visit 4, while the MenACWY 3 group will be scheduled for blood sampling and should 
follow the same procedures as those listed at Visit 6. Please refer to Section 3 for further details on the groups for 
whom Visits 1, 2, 3 and Visits 5, 6, 7, 8, 9 are applicable. 
5.6.3. 
Collect demographic data 
Record demographic data such as date of birth, sex and race in the subject’s eCRF. 
5.6.5. 
Physical examination 
Physical examination will be performed at each study visit subsequent to the first 
vaccination visit, will be performed only if the subject indicates during questioning that 
there might be some underlying pathology(ies) or if deemed necessary by the Investigator 
or delegate. 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
76 
5.6.6. 
Pregnancy test 
Female subjects of childbearing potential are to have a urine pregnancy test prior to any 
at each study vaccine administration visit. The blood sampling can be collected and the 
study vaccine(s) may only be administered only if the pregnancy test is negative. 
 5.6.8. 
Assess pre-vaccination body temperature 
The oral body temperature of each subject needs to be measured prior to any study 
vaccine(s) administration. If the subject has fever [fever is defined as temperature 
37.5°C/99.5°F regardless the location of measurement]on the day of vaccination, the 
vaccination visit will be rescheduled within the allowed interval for this visit (see Table 
6). 
5.6.9.1. 
Blood sampling for serum collection 
• 
A volume of maximum 300 mL of whole blood (to provide on average 120 mL of 
serum) should be drawn from all subjects at each pre-defined timepoint. After 
processing, serum samples should be kept at preferably -80°C/ –112°F, but –70°C/ –
94°F is also acceptable, until shipment. Refer to the SPM for more details on sample 
storage conditions. 
• 
An overall volume of maximum 900 mL of whole blood will be collected during the 
entire study period, from each subject. 
• 
The subjects will be observed closely for at least 3015 minutes following the blood 
sampling, with appropriate medical treatment readily available or per local country 
recommendations and regulations. 
5.7.2. 
Biological samples 
Table 7 
Biological samples 
Sample type 
Quantity 
Unit 
Timepoint 
Study group  
Blood donation 
for hSBA assay  
development 
max.300  
ml  
Visit 1, Visit 5 and Visit 8  rMenB+OMV NZ 
max.300  
ml  
Visit 1, Visit 5 and Visit 9  MenACWY 1 
max.300  
ml  
Visit 2, Visit 6 and Visit 9  MenACWY 2 
max.300  
ml  
Visit 3, Visit 7 and Visit 9  MenACWY 3 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
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28-APR-2020 
77 
6.1. 
Description of study vaccine(s) 
Table 8 
Study vaccine(s) 
Treatment 
name 
Vaccine name 
Formulation 
Presentation 
Volume to be 
administered 
Number 
of doses 
MenACWY 
MenA lyo   
MenA=10µg CRM197; 
CRM197=16.7-33.3µg  
Lyophilized pellet in 
a mono dose vial 
0.5ml  
1 
MenCWY liquid  
MenC=5µg CRM197; 
MenW=5µg CRM197; 
MenY=5µg CRM197; 
CRM197=16-30.8µg   
Liquid in a prefilled 
vial 
rMenB+OMV 
NZ  
Men B 
Recombinant 
rMenB+OMV NZ  
Men B 961c=50µg; 
Men B 936-
741=50µg; Men B 
287-953=50µg; 
Al(OH)₃  
rp936-741=50ug; 
rp961 c=50ug; 
OMV 
NZ98/254=25ug;  
Al(OH)₃=1.5ug; 
Histidine=776ug; 
NaCl=3.125mg 
Sucrose=10mg    
Suspension in a 
glass pre-filled 
syringe 
0.5ml 
2 
6.6. 
Warnings and precautions 
Syncope (fainting) can occur following, or even before blood sampling, as a 
psychogenic response to the needle injection. This can be accompanied by bruising and 
prolonged bleeding. It is important that procedures are in place to avoid injury from 
faints and that subjects have fluids and some sustenance after the blood draw. 
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.  
8.1.3. 
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. imaging analysis) that are 
judged by the investigator to be clinically significant will be recorded as AE or SAE if 
they meet the definition of an SAE (refer to Sections 8.1.1 and 8.1.2). Clinically 
significant abnormal laboratory findings or other abnormal assessments that are present at 
baseline and significantly worsen following the start of the study will also be reported as 
AEs or SAEs. 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
78 
8.2. 
Events or outcomes not qualifying as adverse events or serious adverse 
events 
8.2.1. 
Pregnancy 
Female subjects who are pregnant or lactating at the time of vaccination must not receive 
additional doses of study vaccine(s) but and may not continue other study procedures 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. 
8.3.1. 
Time period for detecting and recording serious adverse events and 
pregnancies 
The time period for collecting and recording pregnancies will begin at the first receipt of 
study vaccine(s) visit and will continue throughout the study for each subject. See section 
8.4 for instructions on reporting of pregnancies. 
8.3.3.2.3. 
Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

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CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
80 
3. 
STUDY DESIGN OVERVIEW 
 
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207911 (MENB REC 2ND GEN-079 HBS) 
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81 
Based on data from completed rMenB+OMV NZ clinical trials, the Day 7 8 and Day 97 
98 timepoints are sufficient for the rMenB+OMV NZ vaccine arm to provide the target 
panel of hSBA titres covering the anticipated analytical range. Due to the necessity to 
have representative hSBA titers that would cover the full targeted analytical range 
(negative, and positive low, medium and high titers), the MenACWY vaccine arm will be 
split in 3 groups, with different post-vaccination blood sampling timepoints. To obtain 
the range of titres for A, C, W and W hSBA assays, Day 3031, Day 60 61 and Day 150 
151 timepoints are needed based on a previous GSK study (Men-ABCWY-Epi-002).  
The three MenACWY groups are also necessary due to large volumes of blood required 
at each blood draw, because the timing between consecutive blood samplings must 
comply with the minimum interval, required by local health authorities and guidelines 
[Australian Red Cross, 2016]. The only way to ensure a blood draw at Day 3031, Day 
6061 and Day 150 151 timepoints is to have 3 MenACWY groups. The rMenB+OMV 
NZ vaccine arm will not be split, due to the sufficient interval between the post-
vaccinations blood sampling timepoints (Day 7 8 and Day 9798). 
• 
Duration of the study for individual subjects: For each subject enrolled, there will be 
a study duration of approximately 6 to 8 months. 
− 
Epoch 001: Primary starting at Visit 1 (Day -83) and ending at Visit 9 (Day 
150151) 
− 
Primary completion Date (PCD): Visit 9 (Day 150151) or last visit of Epoch 001 
of the last study year 
Refer to glossary of terms for the definition of PCD. 
End of Study (EoS): Last subject last visit at Visit 9 (Day 150151) of the last study year 
5.5 
Outline of study procedures 
Table 5 
List of study procedures for each study year 
Epoch  
Epoch 001 
Type of contact 
Visit 1 Visit  
2 
Visit 
3 
Visit 4 Visit 
5 
Visit 
6 
Visit 
7* 
Visit  
8 
Visit  
9 
Timepoint (s) 
Day  
-83 
Day 
-60 
Day  
-30 
Day 
 1 
Day 
 78 
Day 
3031  
Day 
 6061  
Day  
9798  
Day 
150151 
Sampling timepoint(s) 
 Pre-
Vacc 
Pre-
Vacc 
Pre-
Vacc 
Vacc  
I 
 
 
Vacc II EoY/EoS EoY/EoS 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
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28-APR-2020 
82 
Table 6 
Intervals between study visits 
Groups 
Interval 
Optimal length of interval 
rMenB+OMV NZ  
Visit 1 → Visit 4  
83 ± 7 days  
Visit 1 → Visit 5 
90 + 14 days  
Visit 4 → Visit 5  
7 + 7 days  
Visit 5 → Visit 7  
6053 + 14 days  
Visit 7 → Visit 8  
3037 + 14 days  
MenACWY 1  
Visit 1 → Visit 4  
83 ± 7 days  
Visit 1 → Visit 5  
90 + 14 days  
Visit 4 → Visit 5  
7 + 7 days  
Visit 5 → Visit 9  
140143 + 14 days  
MenACWY 2  
Visit 2 → Visit 4  
60  ± 3 days  
Visit 2 → Visit 6  
90 + 14 days  
Visit 4 → Visit 6  
30 + 14 days  
Visit 6 → Visit 9  
120 + 14 days  
MenACWY 3  
Visit 3 → Visit 4  
30 ± 2 days  
Visit 3 → Visit 7  
90 + 14 days  
Visit 4 → Visit 7  
60 + 14 days  
Visit 7 → Visit 9  
90 + 14 days  
6.3 
Dosage and administration of study vaccine(s)  
Table 9 
Dosage and administration 
Type of 
contact and 
timepoint 
Study group 
Treatment 
name 
Volume to 
be 
administered 
Route1 
Site 
Location 
Directionality2 Laterality3 
Visit 4  
 (Day 1) 
rMenB+OMV 
NZ  
rMenB+OMV 
NZ 
0.5 ml 
IM 
Deltoid 
Upper 
Non-
dominant 
Visit 4  
(Day 1) 
MenACWY 1  
MenACWY 
0.5 ml 
IM 
Deltoid 
Upper 
Non-
dominant 
MenACWY 2  
MenACWY 3  
Visit 7  
(Day 6061 ) 
rMenB+OMV 
NZ  
rMenB+OMV 
NZ  
0.5 ml  
IM  
Deltoid  
Upper 
Non-
dominant  
1Intramuscular (IM)  
2Directionality is a qualifier for further detailing the location of the vaccine administration (e.g. Upper, Lower) 
3The non-dominant arm is the preferred arm of injection. In case it is not possible to administer the vaccine in the non-
dominant arm, an injection in the dominant arm may be performed. 
6.7.1. 
Recording of concomitant medications/products and concomitant 
vaccinations 
• 
Any concomitant vaccination administered in the period starting 14 days before the 
first dose of study vaccine(s) and ending at the last study visit (Day 9798 to Day 
150151) 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
83 
8.3.1. 
Time period for detecting and recording serious adverse events and 
pregnancies 
Table 10 
Reporting periods for collecting safety information 
Event 
Epoch 001 
Visit 1 
(Day 
 -83) 
Visit 2  
(Day   
-60) 
Visit 3  
(Day  
-30) 
Visit 4  
(Day 
1) 
Visit 5  
(Day 
78) 
Visit 6  
(Day 
3031) 
Visit 7  
(Day 
6061) 
Visit 8 
(Day 
9798) 
Visit 9 
(Day 
150151) 
SAEs  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to 
study participation or 
concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0

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37 + 14 days  
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Visit 1 o Visit 5  
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Visit 5 o Visit 9  
143 + 14 days  
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Visit 2 o Visit 6  
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Visit 4 o Visit 6  
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Visit 6 o Visit 9  
120 + 14 days  
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Visit 3 o Visit 4  
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CONFIDENTIAL 
207911 (MENB REC 2ND GEN-079 HBS) 
Protocol Amendment 4 Final 
28-APR-2020 
87 
LIST OF ABBREVIATIONS 
COVID-19 
Coronavirus Disease 2019 
5.5 
Outline of study procedures 
Table 6 
Intervals between study visits (Amended, 28 April 2020) 
Note: Under special circumstances, like during COVID-19 pandemic, the length of interval between visits for 
the collection of biological samples or for the vaccine administration may be extended, please refer to Section 
5.6.14 
5.6.14 Study procedures during special circumstances (Amended, 28 April 2020) 
During special circumstances (e.g., COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be applied. For the duration of such special circumstances, 
the following measures may be implemented for enrolled participants: 
• 
If despite best efforts it is not possible to collect the biological samples within the 
interval predefined in the protocol (refer to Table 6), then the interval may be 
extended. 
• 
If despite best efforts it is not possible to administer the dose of study intervention 
as defined in the protocol (refer to Table 6), then the interval may be extended. 
207911 | Protocol Amendment 4 05 May 2020 | TMF-1762210 | 2.0