A Phase IIIB, Randomized, Controlled, Observer-blind Study to Evaluate Safety and Immunogenicity of GSK's Meningococcal ABCWY Vaccine When Administered in Healthy Adolescents and Adults, Previously Primed With Meningococcal ACWY Vaccine
Phase: PHASE3
Conditions: Meningitis, Meningococcal
Sponsor: GlaxoSmithKline

Protocol Amendment 3 
Study ID: 213171 
Official Title of the Study: A phase IIIB, randomized, controlled, observer-blind study to evaluate 
safety and immunogenicity of GSK’s meningococcal ABCWY vaccine when administered in healthy 
adolescents and adults, previously primed with meningococcal ACWY vaccine. 
NCT Number: NCT04707391 
Date of Document: 2 November 2021 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
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TITLE PAGE 
Protocol Title: A phase IIIB, randomized, controlled, observer-blind study to evaluate safety 
and immunogenicity of GSK’s meningococcal ABCWY vaccine when administered in healthy 
adolescents and adults, previously primed with meningococcal ACWY vaccine 
Protocol Number: 213171 (MENABCWY-019) 
Amendment Number: 3 
Product: GlaxoSmithKline Biologicals (GSK)’s combined Meningococcal Groups A, B, C, W, 
and Y vaccine (GSK3536819A) 
Short Title: Immunogenicity and safety study of GSK’s MenABCWY vaccine in healthy 
adolescents and adults previously primed with MenACWY vaccine 
Study Phase: IIIB 
Sponsor Name: GlaxoSmithKline Biologicals SA 
Legal Registered Address: Rue de l’Institut, 89, 1330 Rixensart, Belgium  
IND Number: BB-IND-014605 
EudraCT Number: 2019-004982-42 
Date of Protocol Amendment: 1 November 2021 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
2 
Sponsor Signatory: 
 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
Daniela Toneatto, MD 
Clinical and Epidemiology R&D Project Lead 
 
Date 
 
 
 
 
 
Refer to the study reference manual for Medical Monitor name and contact information. 
 
 
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PPD

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
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PROTOCOL AMENDMENT 3 SUMMARY OF CHANGES 
Table 1 
Document History 
Document 
Date 
Substantial 
Region 
Amendment 3 
01 Nov 2021 
Yes 
Global 
Amendment 2 
12 Feb 2021 
Yes 
Global 
Amendment 1 
31 Aug 2020 
No 
Global 
Original Protocol 
04 Jun 2020 
- 
- 
The summary of changes in protocol amendments 1 and 2 is provided in Appendix 7. 
Amendment 3 – 1 November 2021 
This amendment is considered substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for Amendment 3: 
The primary goals of this amendment are: 
1. To extend the window for the priming MenACWY vaccination prior to enrollment from 
4 to 6 years to at least 4 years. This is to increase the pool of potential participants who 
may benefit from the intervention. 
2. To allow for interim analyses of immunological objectives after all participants have 
completed Visit 4, and of safety objectives after at least 50% of participants have 
completed Visit 4. 
3. Other minor changes include the timing for reporting pregnancies and the change of the 
reference N MenB NHBA strain.  
The detailed changes and the rationale for the changes are presented in Table 2. 
 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
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Table 2 
Description of Changes in Amendment 3 
Section # and Name 
Description of Change 
Brief rationale 
Substantial Changes 
1.1 Synopsis 
8.1.2 Laboratory Assays – Table 10 
8.1.3 Immunological Read-outs – 
Table 11, footnotes 
9.4.4.2 Immune Response – 
N. Meningitidis Serogroup B
Indicator Strains (Measured by
hSBA)
9.4.5.1 Immune Response – 
N. Meningitidis Serogroup B
Indicator Strains (Measured by
hSBA)
Appendix 3 Clinical Laboratory Tests 
The NHBA indicator strain M07-0241084 was 
replaced by M13520. All instances in the text 
where the M07-0241084 was used were revised for 
M13520. 
Assay format using M13520 as 
NHBA indicator strain has been 
recently validated for use in 
clinical studies. 
1.3 Schedule of Activities – Table 3 
The double-border line was added after Visit 4 
(Day 211), and the following footnote was added:  
The double-line border following D211 indicates 
the analyses which will be performed on all data 
(i.e., the data that are as clean as possible) obtained 
up to D211. 
To indicate the time point for the 
interim analysis. 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
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Section # and Name 
Description of Change 
Brief rationale 
The visit window for the telephone contacts 2 and 4 
(i.e., T2 and T3) was changed from −5/+14 to 
−3/+3 days.
To correct the error. 
4.2 Scientific Rationale for Study 
Design 
The following change was made (the new text is 
bold and the deleted text is strikethrough): 
Given the aim of the study is to evaluate the 
MenABCWY booster response in healthy 
participants previously primed with MenACWY 
vaccine, eligible participants must have received a 
previous vaccination with a quadrivalent 
meningococcal conjugate vaccine (MenACWY; 
Menveo or Menactra) at least 4 years prior to study 
start. 
To reflect the change in the time 
period for a previous vaccination 
to allow inclusion of a broader 
population. 
5.1 Inclusion Criteria 
The following criterion’s text was revised as 
follows (the new text is bold and the deleted text is 
strikethrough): 
4. Previous vaccination with 1 dose of MenACWY
vaccine at an age of 10 years or older, with an
interval of at least 4 between the previous
MenACWY vaccine and enrollment (informed
consent and assent [as applicable]) into this study.
To allow enrollment of a broader 
population. 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
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Section # and Name 
Description of Change 
Brief rationale 
8.1.2   Laboratory Assays - Table 10, 
footnotes 
8.1.3 Immunological Read-outs – 
Table 11, footnotes 
Appendix 3 Clinical Laboratory Tests 
The following text was removed: 
The NHBA M07-0241084 indicator strain may be 
subject to change to an alternative NHBA indicator 
strain (e.g., strain M13520) during the study. In this 
case, this change will be documented either in a 
protocol amendment or in the CSR. 
Because hSBA using NHBA strain 
M13520 has been recently 
validated. 
8.1.2 Laboratory Assays – Table 10 
footnotes 
The following footnote was removed: 
1    Strain(s) and unit(s) might be subject to change 
during the study (e.g., in case of requalification, 
revalidation or standardization). In this case, this 
will be documented either in a protocol 
amendment or in the clinical report. 
The remaining 2 footnotes shifted accordingly. 
The footnote is no longer 
necessary considering the 
documented change in the strain. 
8.3.6.4 Regulatory Reporting 
Requirements for SAEs – Table 13 
The following footnote was revised as follows (the 
new text is bold and the deleted text is 
strikethrough): 
32 ELISA assay characteristics (e.g., validated assay 
cut-offs and units) for each of the serogroup will be 
determined at the time of the generation of 
validation data. Any change, including the change 
of the format of the assay, will be documented in a 
protocol amendment or in the clinical study 
report.and submitted prior to the submission of 
the clinical study report. 
Because any change on assay 
format will be first submitted and 
endorsed with Health Authorities. 

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Section # and Name 
Description of Change 
Brief rationale 
9.1 
Statistical Hypotheses 
The following introduction was added: 
The following study hypotheses are ordered into 2 
families that will be tested in a fixed sequential 
design with full alpha propagation. Family 1 will be 
tested first and family 2 will only be tested if the 
hypothesis in family one is successfully 
demonstrated.  
For added clarity. 
9.4.1 General Considerations 
The following change was made: 
Fixed sequential testing with full alpha propagation 
in pre-ordered hypotheses families (Family 1 and 
Family 2, as defined in Section 9.1) will be applied. 
The assay cut-off values will be defined by the 
laboratory before analysis and will be documented 
in a protocol amendmentor in the clinical study 
report.  
For accuracy. 
9.4.3.1 Immunological Non-inferiority 
of MenABCWY vs. MenACWY 
The following sentence was added: 
A sensitivity analysis including minimization 
factors as covariates will be performed using a 
logistic model and will be detailed in the SAP. 
To add the details on the 
sensitivity analysis. 

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Section # and Name 
Description of Change 
Brief rationale 
9.4.4.2 Immune Response – 
N. Meningitidis Serogroup B
Indicator Strains (Measured by
hSBA)
9.4.5.1Immune Response – 
N. Meningitidis Serogroup B
Indicator Strains (Measured by
hSBA)
The following phrase was removed: 
*Note: Strains and unit(s) might be subject to
change during the study (e.g., in case of
requalification, revalidation or standardization). In
this case, this will be documented either in a
protocol amendment or in the CSR.
It is no longer necessary because 
the change in the strain has been 
documented in the protocol. 
9.5 Interim Analyses 
The following text was added: 
An interim analysis of safety objectives may be 
conducted after at least 50% of participants have 
completed Visit 4. An interim analysis of 
immunological objectives may also be performed 
after all participants have completed Visit 4. If 
performed, the assessment of the primary 
immunological objectives will follow the order 
described in Section 9.4.3.1 with analysis of family 
1 preceding that of family 2. 
To add details concerning the 
addition of the interim analysis 
after Visit 4. 
9.5.1 Sequence of Analyses 
The phrase “Not applicable” was removed. The 
following text was added: 
The interim analysis for the evaluation of the 
co-primary objectives will respect the hierarchical 
order described in Section 9.4.3.1. 
To reflect the addition of the 
interim analysis. 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
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Section # and Name 
Description of Change 
Brief rationale  
9.5.2 Statistical Consideration for 
Interim Analysis 
The phrase “Not applicable” was removed. The 
following text was added: 
No changes in statistical methodology for the 
immunological and safety objectives are foreseen 
compared to what is planned for the final analysis.  
Data for the interim analysis may be analyzed by an 
independent unblinded group; if so, only group 
unblinded results will be presented. 
For clarity. 
Administrative Changes 
Title Page 
Original text:  
Amendment Number: Amendment 2 
New Text:  
Amendment Number: 3 
Original date: 12 February 2021 
New date: 1 November 2021 
To reflect the change in the 
protocol version. 
Page Headers 
Original text: 
Protocol 213171 (MENABCWY-019) – 
Amendment 2 
New text: 
Protocol 213171 (MENABCWY-019) – 
Amendment 3 
To reflect the change in the 
protocol version. 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
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Section # and Name 
Description of Change 
Brief rationale 
Protocol Amendment Summary of 
Changes 
The summary of changes for Protocol Amendment 
3 was added to this section. The summary of 
changes for Protocol Amendment 2 was transferred 
from this section to a newly added Appendix 7. The 
document history was updated. 
To present the most recent 
summary of changes and the 
protocol history. 
Appendix 7 Protocol Amendment 
History 
The new appendix was added to include the 
summaries of changes for the previous 2 protocol 
amendments (1 and 2) 
To restructure the content for 
better readability. 
Appendix 8 Signature of Investigator 
Originally Appendix 7. Changed to Appendix 8. 
Because the new Appendix 7 was 
added. 
Original text: 
VERSION: Amendment 2 
New text: 
VERSION: Amendment 3 
To reflect the change in the 
protocol version. 
Additional administrative changes 
Page numbers, Table of Contents, Table of Tables 
were updated. Table numbering shifted. Relevant 
editorial changes were also made (e.g., internal 
cross-references, formatting). 
Updates were made according to 
the changes in the content of the 
document. 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
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TABLE OF CONTENTS 
PROTOCOL AMENDMENT 3 SUMMARY OF CHANGES ............................................3 
TABLE OF TABLES .............................................................................................................14 
TABLE OF FIGURES ...........................................................................................................15 
1.0 
PROTOCOL SUMMARY ........................................................................................16 
1.1 
Synopsis ...........................................................................................................16 
1.2 
Schema ............................................................................................................21 
1.3 
Schedule of Activities .....................................................................................22 
2.0 
INTRODUCTION......................................................................................................27 
2.1 
Study Rationale ..............................................................................................27 
2.2 
Background ....................................................................................................28 
2.3 
Benefit/Risk Assessment ................................................................................29 
3.0 
OBJECTIVES AND ENDPOINTS ..........................................................................30 
4.0 
STUDY DESIGN ........................................................................................................34 
4.1 
Overall Design ................................................................................................34 
4.2 
Scientific Rationale for Study Design ...........................................................35 
4.3 
Justification for Dose .....................................................................................36 
4.4 
End of Study Definition .................................................................................37 
5.0 
STUDY POPULATION ............................................................................................38 
5.1 
Inclusion Criteria ...........................................................................................38 
5.2 
Exclusion Criteria ..........................................................................................39 
5.2.1 
Medical Conditions ...........................................................................39 
5.2.2 
Prior/Concomitant Therapy ...............................................................40 
5.2.3 
Prior/Concurrent Clinical Study Experience .....................................40 
5.2.4 
Other Exclusions ...............................................................................40 
5.3 
Lifestyle Considerations ................................................................................41 
5.4 
Screen Failures ...............................................................................................41 
6.0 
STUDY INTERVENTION ........................................................................................42 
6.1 
Study Interventions Administered ...............................................................42 
6.2 
Preparation/Handling/Storage/Accountability ...........................................46 
6.3 
Measures to Minimize Bias: Randomization and Blinding........................46 
6.3.1 
Participant Identification ...................................................................46 
6.3.2 
Randomization to Study Intervention ................................................46 
6.3.3 
Intervention Allocation to the Participant .........................................47 

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6.3.4 
Allocation of Participants to Assay Subsets ......................................47 
6.3.5 
Blinding and Unblinding ...................................................................48 
6.4 
Study Intervention Compliance ....................................................................49 
6.5 
Concomitant Therapy ....................................................................................49 
6.6 
Dose Modification ..........................................................................................50 
6.7 
Criteria for Temporary Delay for Enrollment and/or Vaccination 
and/or Blood Sampling ..................................................................................50 
6.8 
Contraindications to Subsequent Vaccine(s) Administration ...................51 
6.9 
Intervention After the End of the Study ......................................................52 
7.0 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ...................................53 
7.1 
Reasons for Discontinuation/Withdrawal....................................................53 
7.2 
Discontinuation of Study Intervention .........................................................53 
7.3 
Participant Discontinuation/Withdrawal from the Study .........................54 
7.4 
Lost to Follow-up ...........................................................................................54 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ....................................................55 
8.1 
Immunogenicity Assessments .......................................................................55 
8.1.1 
Biological Samples ............................................................................56 
8.1.2 
Laboratory Assays .............................................................................56 
8.1.3 
Immunological Read-outs .................................................................58 
8.1.4 
Clinical Safety Laboratory Assessments ...........................................59 
8.1.5 
Immunological Correlates of Protection ...........................................59 
8.2 
Collection of Demographic Data and Other Baseline 
Characteristics................................................................................................59 
8.3 
Safety Assessments .........................................................................................59 
8.3.1 
Medical History .................................................................................60 
8.3.2 
Physical Examination ........................................................................60 
8.3.3 
Pregnancy Test ..................................................................................61 
8.3.4 
Warnings and Precautions to Vaccination .........................................61 
8.3.5 
Pre-vaccination Body Temperature ...................................................61 
8.3.6 
Adverse Events ..................................................................................61 
8.3.7 
Treatment of Overdose ......................................................................67 
8.3.8 
Medical Device Deficiencies .............................................................67 
8.4 
Pharmacokinetics ...........................................................................................68 
8.5 
Pharmacodynamics ........................................................................................68 
8.6 
Genetics ...........................................................................................................68 
8.7 
Biomarkers .....................................................................................................68 
8.8 
Health Outcomes ............................................................................................68 
8.9 
Study Procedures During Special Circumstances ......................................68 
9.0 
STATISTICAL CONSIDERATIONS .....................................................................70 
9.1 
Statistical Hypotheses ....................................................................................70 
9.2 
Sample Size Determination ...........................................................................71 
9.3 
Populations for Analyses ...............................................................................72 

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9.3.1 
Criteria for Elimination from Analysis ..............................................73 
9.4 
Statistical Analyses.........................................................................................73 
9.4.1 
General Considerations .....................................................................73 
9.4.2 
Participants Disposition .....................................................................74 
9.4.3 
Primary Endpoint(s) ..........................................................................74 
9.4.4 
Secondary Endpoints .........................................................................77 
9.4.6 
Other Analyses ..................................................................................80 
9.5 
Interim Analyses ............................................................................................80 
9.5.1 
Sequence of Analyses ........................................................................80 
9.5.2 
Statistical Consideration for Interim Analysis ..................................80 
9.6 
Data Monitoring Committee .........................................................................80 
10.0 
REFERENCES ...........................................................................................................81 
11.0 
APPENDICES ............................................................................................................82 
Appendix 1 
Abbreviations and Glossary of Terms ...........................................83 
Appendix 2 
Regulatory, Ethical, and Study Oversight Considerations ..........90 
Regulatory and Ethical Considerations ............................................................90 
Financial Disclosure.........................................................................................90 
Informed Consent and Assent Process .............................................................91 
Responsibilities of the Investigator and IRB/EC .............................................91 
Administrative Structure ..................................................................................93 
Medical Monitor ..............................................................................................93 
Dissemination of Clinical Study Data..............................................................93 
Data Quality Assurance ...................................................................................94 
Source Documents ...........................................................................................95 
Study and Study Center Closure ......................................................................95 
Publication Policy ............................................................................................95 
Appendix 3 
Clinical Laboratory Tests ...............................................................96 
Protocol-required Safety Laboratory Assessments ..........................................96 
Laboratory Assays ...........................................................................................96 
Appendix 4 
Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .....................................98 
Appendix 5 
Contraceptive Guidance and Collection of Pregnancy 
Information ...................................................................................................112 
Appendix 6 
Country-specific Requirements ....................................................115 
Appendix 7 
Protocol Amendment History .......................................................116 
Appendix 8 
Signature of Investigator ..............................................................133 
CCI

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TABLE OF TABLES 
Table 1 
Document History ..............................................................................................3 
Table 2 
Description of Changes in Amendment 3 ..........................................................4 
Table 3 
Schedule of Activities ......................................................................................22 
Table 4 
Intervals Between Study Visits ........................................................................25 
Table 5 
Intervals Between Telephone Contacts ............................................................26 
Table 6 
Study Objectives and Endpoints ......................................................................30 
Table 7 
Study Groups, Intervention, and Blinding Foreseen in the Study ...................35 
Table 8 
Study Interventions Administered ...................................................................43 
Table 9 
Biological Samples ..........................................................................................56 
Table 10 
Laboratory Assays ...........................................................................................57 
Table 11 
Immunological Read-outs ................................................................................58 
Table 12 
Timeframes for Collecting and Reporting of Safety Information ...................63 
Table 13 
Timeframes for Submitting SAEs, Pregnancies, and AESIs ...........................66 
Table 14 
Power to Demonstrate Immunological Non-inferiority for Serogroups 
A, C, W, and Y of MenABCWY Compared to MenACWY (Primary) ..........72 
Table 15 
Populations for Analyses .................................................................................73 
Table 16 
Study Administrative Structure........................................................................93 
Table 17 
List of Potential Immune-Mediated Diseases (pIMDs) .................................102 
 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
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TABLE OF FIGURES 
Figure 1 
 Study Design Overview ..................................................................................34 
 
 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
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1.0 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: A phase IIIB, randomized, controlled, observer-blind study to evaluate safety 
and immunogenicity of GSK’s meningococcal ABCWY vaccine when administered in healthy 
adolescents and adults, previously primed with meningococcal ACWY vaccine 
Short Title: Immunogenicity and safety study of GSK’s MenABCWY vaccine in healthy 
adolescents and adults previously primed with MenACWY vaccine 
Rationale: GlaxoSmithKline Biologicals SA (GSK) is developing a combination vaccine 
intended to protect against 5 of the most prevalent serogroups of Neisseria meningitidis 
(N. meningitidis), A, B, C, W, Y, in humans. The availability of a pentavalent meningococcal 
vaccine in a single administration would reduce the number of injections and could increase 
coverage for meningococcal disease caused by N. meningitidis serogroups A, B, C, W, and Y 
worldwide. 
The investigational MenABCWY combination vaccine is based upon 2 established GSK 
vaccines, the quadrivalent meningococcal ACWY (MenACWY) conjugate vaccine (Menveo) 
and the multi-component recombinant meningococcal B (MenB) vaccine (Bexsero). 
The United States (US) Advisory Committee on Immunization Practices (ACIP) recommends 
vaccination with a quadrivalent conjugated meningococcal vaccine for adolescents at 11 to 
12 years of age with a booster dose at 16 years of age, based on the data showing a robust 
immune response to a booster dose of MenACWY vaccines in this age group. The ACIP also 
recommends MenB vaccination in persons aged 10 years and older who are at increased risk for 
MenB disease and in adolescents and young adults aged 16 to 23 years not at increased risk 
based on shared clinical decision making. 
Based on the current ACIP recommendations for a MenACWY booster dose at 16 years of age 
and for MenB vaccination at 16 to 23 years of age, there is a need to evaluate the response to the 
MenABCWY vaccine in MenACWY-vaccine primed individuals. In the context of the 
MenABCWY investigational vaccine development, the MenACWY booster response has been 
evaluated in 2 phase II clinical studies (Sáez-Llorens, 2018; Szenborn, 2018). Although the 
sample size of these studies was small, a robust anamnestic immune response against A, C, W, 
and Y serogroups was demonstrated at 1 month after the administration of the first dose of the 
MenABCWY vaccine in participants previously primed with the GSK MenACWY vaccine. 
The main purpose of this phase IIIB clinical study is to assess the immunogenicity and safety of 
the MenABCWY vaccine when administered as a booster in healthy adolescents and young 
adults, previously primed with a MenACWY vaccine. 

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Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
Immunological non-inferiority: MenABCWY 
vs. MenACWY (Family 1) 
To demonstrate the immunological non-inferiority 
of the MenABCWY vaccine, compared to 
MenACWY vaccine given to healthy participants, 
previously primed with a MenACWY vaccine, as 
measured by the percentages of participants 
achieving a 4-fold rise1 in hSBA titers against 
N. meningitidis serogroups A, C, W, and Y, at 
1 month after the second MenABCWY 
vaccination (0,6-months) and 1 month after the 
MenACWY vaccination (single dose). 
• The percentages of participants with a 4-fold 
rise1 in hSBA titers against N. meningitidis 
serogroups A, C, W, and Y at 1 month after 
the second vaccination for the ABCWY group 
(Day 211, Month 7), and 1 month after the 
single MenACWY vaccination for the ACWY 
group (Day 31, Month 1) relative to baseline 
(Day 1, Month 0). 
Immunological non-inferiority: MenABCWY 
vs. MenACWY (Family 2) 
To demonstrate the immunological non-inferiority 
of the MenABCWY vaccine, compared to 
MenACWY vaccine given to healthy participants, 
previously primed with a MenACWY vaccine, as 
measured by the percentages of participants 
achieving a 4-fold rise1 in hSBA titers against 
N. meningitidis serogroups A, C, W, and Y, at 
1 month after the first MenABCWY vaccination 
(0,6-months) and 1 month after the MenACWY 
vaccination (single dose). 
• The percentages of participants with a 4-fold 
rise1 in hSBA titers against N. meningitidis 
serogroups A, C, W, and Y at 1 month after 
the first vaccination for the ABCWY group 
(Day 31, Month 1), and 1 month after the 
single dose of MenACWY vaccination for the 
ACWY group (Day 31, Month 1), relative to 
baseline (Day 1, Month 0). 
Safety 
To evaluate the safety and reactogenicity of the 
MenABCWY and MenACWY vaccines. 
• The frequencies and percentages of 
participants with solicited administration site 
events (i.e., injection site pain, erythema, 
swelling, induration) and solicited systemic 
events (i.e., fever [body temperature 
≥38.0°C/100.4°F], nausea, fatigue, myalgia, 
arthralgia, headache) during the 7 days 
(including the day of vaccination) following 
vaccination at Day 1, Month 0 (for the 
ABCWY and ACWY groups) and Day 181, 
Month 6 (for the ABCWY group). 
• The frequencies and percentages of 
participants with any unsolicited AEs 
(including all SAEs, AEs leading to 
withdrawal, AESIs and medically attended 
AEs) during the 30 days (including the day of 
vaccination) following vaccination at Day 1, 
Month 0 (for the ABCWY and ACWY 
groups) and Day 181, Month 6 (for the 
ABCWY group). 

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Objectives 
Endpoints 
• The percentages of participants with SAEs, 
AEs leading to withdrawal, AESIs and 
medically attended AEs throughout the study 
period (Month 0 to Month 12). 
Secondary 
To assess the immune response to MenABCWY 
(0,6-month schedule) and MenACWY (single 
dose) vaccines against N. meningitidis serogroups 
A, C, W, and Y, at pre-vaccination and at 1 month 
after the first and last MenABCWY vaccinations 
and 1 month after the MenACWY vaccination. 
• The percentages of participants with hSBA 
titers ≥Lower Limit of Quantitation (LLOQ) 
against serogroups A, C, W, and Y: 
− at baseline (Day 1, Month 0) and at 
1 month after the first (Day 31, 
Month 1) and the last vaccination 
(Day 211, Month 7) for the ABCWY 
group, and 
− at baseline (Day 1, Month 0) and 
1 month after the single MenACWY 
vaccination for the ACWY group 
(Day 31, Month 1). 
• The geometric mean titers (GMTs) against 
serogroups A, C, W, and Y: 
− at baseline (Day 1, Month 0) and at 
1 month after the first (Day 31, 
Month 1) and the last (Day 211, 
Month 7) vaccinations for the 
ABCWY group, and 
− at baseline (Day 1, Month 0) and 
1 month after the single MenACWY 
vaccination for the ACWY group 
(Day 31, Month 1). 
• The geometric mean ratios (GMRs) against 
serogroups A, C, W, and Y: 
− at 1 month after the first (Day 31, 
Month 1) and the last vaccination 
(Day 211, Month 7) for the ABCWY 
group as compared to baseline (Day 
1, Month 0) and 
− at 1 month after the MenACWY 
vaccination (Day 31, Month 1) for the 
ACWY group as compared to 
baseline (Day 1, Month 0). 
To assess the immune response to the 
MenABCWY vaccine (0,6-month schedule) 
against N. meningitidis serogroup B indicator 
strains, at pre-vaccination and at 1 month after the 
last MenABCWY vaccination. 
• The percentages of participants with hSBA 
titers ≥LLOQ for each and all serogroup B 
indicator strains at baseline (Day 1, Month 0) 
and at 1 month after the last vaccination (Day 
211, Month 7) for the ABCWY group. 

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Objectives 
Endpoints 
x The percentages of participants with 4-fold 
rise1 in hSBA titers against each 
N. meningitidis serogroup B indicator strains 
at 1 month after the last vaccination (Day 211, 
Month 7) relative to baseline (Day 1, Month 0) 
for the ABCWY group. 
x GMTs against each serogroup B indicator 
strains at baseline (Day 1, Month 0) and at 
1 month after the last vaccination (Day 211, 
Month 7) for the ABCWY group. 
x GMRs against each serogroup B indicator 
strains at 1 month after the last vaccination 
(Day 211, Month 7) as compared to the 
baseline (Day 1, Month 0) for the ABCWY 
group. 
CCI

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AESI = adverse event of special interest; CI = confidence interval; ELISA = enzyme-linked 
immunosorbent assay; GMC = geometric mean concentration; GMT = geometric mean titer; GMR = 
geometric mean ratio; hSBA = human serum bactericidal assay; LLOQ = lower limit of quantitation; 
N. meningitidis = Neisseria meningitidis; SAE = serious adverse event  
1 Refer to Section 9.0 for the (seroresponse) definition of the 4-fold rise. 
Overall Design: 
This is a phase IIIB, randomized, controlled, observer-blind, multi-centric study with 2 parallel 
study groups of healthy adolescents and young adults aged 15 to 25 years LH\HDUV
364 days). The participants will be randomized at a 1:1 ratio to the ABCWY or ACWY group 
using an Interactive Voice Response System randomization. 
Number of Participants: 
Approximately 1206 participants will be randomly assigned to study intervention or placebo for 
an estimated total of 1084 evaluable participants or 542 evaluable participants per study group. 
For more information, see Section 9.0, Statistical Considerations, and Section 9.2, Sample Size 
Determination.  
Study Groups: 
x ABCWY: 603 participants will receive 2 doses of the MenABCWY vaccine at Visit 1 
(Day 1) and Visit 3 (Day 181) (0,6-month schedule) and 1 dose of placebo at Visit 4 
(Day 211). 
x ACWY: 603 participants will receive 1 dose of MenACWY vaccine at Visit 1 (Day 1) 
(single dose) and 2 doses of MenB vaccine at Visit 3 (Day 181) and Visit 4 (Day 211). 
Duration: The total duration of the study, per participant, will be approximately 12 months (4 
visits), including 6 months of Extended Safety Follow-Up (ESFU) period after the last dose of 
investigational vaccine (Visit 3, Day 181). 
Statistical Methods:  
Immunological non-inferiority: MenABCWY vs. MenACWY 
Non-inferiority will be demonstrated if, the lower limit of 2-sided 95% confidence interval (CI) 
for the percent difference in 4-fold rise in human serum bactericidal assay (hSBA) titers 
(p_MenABCWY í SB0HQ$&:<LVDERYHíIRUHDFKVHURJURXS$&:and Y.  For 
each of the serogroups A, C, W, and Y, the percentages of participants with 4-fold rise and the 
corresponding exact 2-sided 95% CIs based on Clopper-Pearson method (Clopper and Pearson, 
1934) will be calculated for each study group at time point of interest. The standardized 
asymptotic CIs between group differences in percentages will be derived using the method of 
Miettinen and Nurminen method (Miettinen, 1985). 
Immune response to MenABCWY and MenACWY against serogroups A, C, W, and Y 
Immune response of MenABCWY and MenACWY against A, C, W and Y serogroups will be 
HYDOXDWHGIURPWKHSHUFHQWDJHVRISDUWLFLSDQWVZLWKK6%$WLWHUVORZHUOLPLWRITXDQWLWDWLRQ
(LLOQ) for each of the 4 serogroups. The corresponding exact 2-sided 95% CIs based on 
CCI

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
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Clopper-Pearson method will be calculated for each study group, each serogroup and at each 
time point (baseline/pre-vaccination, 1 month after first vaccination and 1 month after last 
vaccination). Geometric mean titers (GMTs) and Geometric mean ratios (GMRs) 
(post-vaccination/baseline titer), and their associated 2-sided 95% CIs will be computed for each 
study group, for each serogroup and at each time point.  
Immune response to MenABCWY against Men B indicator stains 
Immune response of MenABCWY against each and all of the 4 Men B indicator strains 
(M14459, M13520, 96217 and NZ98/254) will be evaluated from the percentages of participants 
with hSBA titers ≥LLOQ and from the percentages of participants with 4-fold rise for each of the 
4 Men B indicator strains. The corresponding exact 2-sided 95% CIs based on Clopper-Pearson 
method will be calculated for each and all Men B indicator strains, at baseline/pre-vaccination 
and 1 month after last vaccination, and separately for 1 month after the first vaccination.  
Geometric mean titers and GMRs (post-vaccination/baseline titer), and their associated 2-sided 
95% CIs will be computed for each Men B indicator strain, at baseline/pre-vaccination and 
1 month after last vaccination, and separately for 1 month after the first vaccination. 
Safety 
The frequencies and percentages of participants will be presented for: 
• solicited administration site and systemic adverse events (AEs) during the 7 days 
(including the day of vaccination) following each vaccination at Day 1 and Day 181 
• unsolicited AEs during the 7 and the 30 days (including the day of vaccination) following 
vaccination at Day 1 and Day 181 
• serious AEs, AEs leading to withdrawal, AEs of special interest and medically attended 
AEs throughout the study period (Day 1 to Day 361) 
Data Monitoring Committee: No. 
See Appendix 1, Glossary of Terms, for the definitions of randomization, Interactive Voice 
Response System, investigator, participants, evaluable participants, solicited and unsolicited 
AEs. 
1.2 
Schema 
This is a phase IIIB, randomized, controlled, observer-blind, multi-centric study with 2 parallel 
groups (see Figure 1). A total of 1206 participants will be randomized in a 1:1 ratio as follows: 
• ABCWY: 603 participants will receive 2 doses of the MenABCWY vaccine at Day 1 and 
Day 181 (0,6-months schedule) and 1 dose of placebo at Day 211. 
• ACWY: 603 participants will receive 1 dose of MenACWY vaccine at Day 1 (single 
dose) and 2 doses of MenB vaccine at Day 181 and Day 211. 

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1.3 
Schedule of Activities 
Table 3 
Schedule of Activities 
Age 
15 to 25 Years (25 Years + 364 Days) at Study Start 
Type of contact 
Visit 
PC 
Visit 
PC 
Visit 
PC 
Visit 
PC 
PC 
Visit/phone contact1 
V1 
T1 
V2 
T2 
V3 
T3 
V4 
T4 
T5 
Time points 
D1 
M0 
D15 
 
D31 
M1 
D91 
M3 
D181 
M6 
D195 
 
D211 
M7 
D271 
M9 
D361 
(ESFU) 
Visit window (days) 
n/a 
(−3/+3) 
(−5/+14) (−3/+3) 
(−5/+14) (−3 /+3) (−5/+14) (−3/+3) 
(−7/+21) 
Days post-vaccination2 
0 
14 
post-vacc 
1 
30 
post-vacc 
1 
90 
post-vacc 
1 
180 
post-vacc 
1 
14 
post-vacc 
2 
30 
post-vacc 
2 
90 
post-vacc 
2 
180 
post-vacc 
2  
Sampling time points 
pre-vacc 
 
 
post-vacc 
1 
 
 
 
post-vacc 
2 
 
 
Informed consent and Informed assent (as applicable) 3 
●4 
 
 
 
 
 
 
 
 
Check inclusion/exclusion criteria5 
●4 
 
 
 
○4 
 
○4 
 
 
Collect demographic data 
●4 
 
 
 
 
 
 
 
 
Vaccine(s)/product 
Study group and treatment number allocation 
○4 
 
 
 
 
 
 
 
 
Treatment number allocation for subsequent doses 
 
 
 
 
○ 
 
○ 
 
 
Recording of administered treatment number 
● 
 
 
 
● 
 
● 
 
 
Vaccine/Product administration 
● 
 
 
 
● 
 
● 
 
 
Post-injection assessment (30 minutes) 6, 11 
● 
 
 
 
● 
 
○ 
 
 
Laboratory assays 
Blood sampling (approximately 20 mL) 7 
●4 
 
●4 
 
 
 
●4 
 
 
Safety assessments 
Medical history 
●4 
 
 
 
 
 
 
 
 

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Age 
15 to 25 Years (25 Years + 364 Days) at Study Start 
Type of contact 
Visit 
PC 
Visit 
PC 
Visit 
PC 
Visit 
PC 
PC 
Visit/phone contact1 
V1 
T1 
V2 
T2 
V3 
T3 
V4 
T4 
T5 
Time points 
D1 
M0 
D15 
 
D31 
M1 
D91 
M3 
D181 
M6 
D195 
 
D211 
M7 
D271 
M9 
D361 
(ESFU) 
Visit window (days) 
n/a 
(−3/+3) 
(−5/+14) (−3/+3) 
(−5/+14) (−3 /+3) (−5/+14) (−3/+3) 
(−7/+21) 
Days post-vaccination2 
0 
14 
post-vacc 
1 
30 
post-vacc 
1 
90 
post-vacc 
1 
180 
post-vacc 
1 
14 
post-vacc 
2 
30 
post-vacc 
2 
90 
post-vacc 
2 
180 
post-vacc 
2  
Sampling time points 
pre-vacc 
 
 
post-vacc 
1 
 
 
 
post-vacc 
2 
 
 
General physical examination9 
○4 
 
 
 
 
 
 
 
 
Symptom-directed physical examination 
 
 
○ 
 
○4 
 
○4 
 
 
Urine pregnancy test for females of childbearing potential10 
●4 
 
 
 
●4 
 
●4 
 
 
Check criteria for temporary delay for enrollment and 
vaccination and/or blood sampling 
○4 
 
○ 
 
○4 
 
○4 
 
 
Check contraindications and warnings and precautions to 
vaccination 
○4 
 
 
 
○4 
 
○4 
 
 
Pre-vaccination body temperature11 
●4 
 
 
 
●4 
 
●4 
 
 
Record any concomitant medication/vaccination 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record any intercurrent medical conditions 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Training and distribution of eDiaries 
○ 
 
 
 
○ 
 
 
 
 
Recording of solicited events (Days 1-7 post-vaccination) in 
eDiary  
× 
 
 
 
× 
 
 
 
 
Recording of unsolicited adverse events (Days 1-30 
post-vaccination)  
● 
● 
● 
 
● 
● 
● 
 
 
Return and review of eDiaries   
 
 
○ 
 
 
 
○ 
 
 
Recording of any AEs leading to vaccine/study withdrawal8 
● 
● 
● 
● 
● 
● 
● 
● 
● 

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Age 
15 to 25 Years (25 Years + 364 Days) at Study Start 
Type of contact 
Visit 
PC 
Visit 
PC 
Visit 
PC 
Visit 
PC 
PC 
Visit/phone contact1 
V1 
T1 
V2 
T2 
V3 
T3 
V4 
T4 
T5 
Time points 
D1 
M0 
D15 
 
D31 
M1 
D91 
M3 
D181 
M6 
D195 
 
D211 
M7 
D271 
M9 
D361 
(ESFU) 
Visit window (days) 
n/a 
(−3/+3) 
(−5/+14) (−3/+3) 
(−5/+14) (−3 /+3) (−5/+14) (−3/+3) 
(−7/+21) 
Days post-vaccination2 
0 
14 
post-vacc 
1 
30 
post-vacc 
1 
90 
post-vacc 
1 
180 
post-vacc 
1 
14 
post-vacc 
2 
30 
post-vacc 
2 
90 
post-vacc 
2 
180 
post-vacc 
2  
Sampling time points 
pre-vacc 
 
 
post-vacc 
1 
 
 
 
post-vacc 
2 
 
 
Recording of medically attended AEs 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of AESIs 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs related to study participation, or to a 
concurrent GSK medication/vaccine12 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of COVID-19 related AEs and SAEs13 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of pregnancies 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Study Conclusion14 
 
 
 
 
 
 
 
 
● 
● study procedure that requires documentation in the individual eCRF.  
○ study procedure that does not require documentation in the individual eCRF. Documentation will be required in the source documents 
× study procedure that requires documentation in the study eDiary 
The double-line border following D211 indicates the analyses which will be performed on all data (i.e., the data that are as clean as possible) obtained up to 
D211. 
AE = adverse event; AESI = adverse events of special interest; COVID-19 = coronavirus disease 2019; D = day; eCRF = electronic case report form; 
eDiary = participant diary (electronic diary); ESFU = extended safety follow-up; GSK = GlaxoSmithKline Biologicals; M = month; PC = phone contact; 
post-vacc = post-vaccination; pre-vacc = pre-vaccination; T = telephone contact; SAE = serious adverse event; V = visit 
1 Home visits are always allowed if deemed suitable and are conducted according to local regulations. 
2 Days post-injection are included to keep track of the intercurrent days between vaccinations, they do not indicate “Study Day” 
3 Confirm consent form and informed assent form (if applicable) signed prior to any procedures. 

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4 Procedure to be performed prior to any vaccination. 
5 Reminder: appropriate written documentation of the identity of the primary MenACWY vaccination and vaccination date to be provided prior to enrollment. 
Individuals for whom written documentation is not available may still be enrolled into the study. 
6 The participants must be observed closely for at least 30 minutes after the administration of the vaccine(s)/product. Appropriate medical treatment must be 
readily available during the observation period in case of anaphylaxis and/or syncope. 
7 Insufficient blood volume may lead to test cancellation and jeopardize the statistical power. Hence, every effort must be done to collect blood volume as per 
protocol requirements. 
8 For information regarding participant discontinuation and withdrawal from the study refer to Section 7.3. 
9 Physical examination must be performed by a qualified health care professional (refer to Appendix 1, Glossary of Terms) in accordance with local regulations 
and licensing requirements designated within the Site Responsibility Delegation Log. 
10 Frequency or urine pregnancy tests can be established at the site according to local regulations. 
11 Fever is defined as body temperature ≥38.0°C/100.4°F. The preferred location for measuring temperature in this study will be oral. In case any other route 
(other than oral) is used for measurement of body temperature/fever, it needs to be recorded in the participant’s eCRF. 
12 Recording of SAEs related to study participation, or to a concurrent GSK medication/vaccine begins from the time a participant/participant’s parent(s)/legally 
acceptable representative(s) signs the consent form and assent form (if applicable) to the end of the study. 
13 Diagnosis of coronavirus disease 2019 (COVID-19) should be made in accordance with the World Health Organization case definitions. Cases should be 
reported as AEs or SAEs (refer to Appendix 4 for the definitions), and routine procedures for recording, evaluation, follow-up, and reporting of AEs, and 
SAEs should be followed in accordance with the protocol-defined time periods (refer to Table 12). In addition, separate COVID-19 specific eCRF form(s) 
should be completed.  
14 Participants who terminate the study early are recommended to complete certain study-related procedures. 
Table 4 
Intervals Between Study Visits 
Interval 
Length of Interval  
Allowed Interval 
Visit 1 to Visit 2 
30 days 
25 to 44 days (−5 to +14 days) 
Visit 1 to Visit 3 
180 days 
175 to 194 days (−5 to +14 days) 
Visit 3 to Visit 4 
30 days 
25 to 44 days (−5 to +14 days) 
Visit 3 to Last Telephone Contact (T5) 
180 days 
173 to 201 days (−7 to +21 days) 
T = telephone contact 

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Table 5 
Intervals Between Telephone Contacts 
Interval 
Length of Interval  
Allowed Interval (Range) 
Visit 1 to Telephone contact T1 
14 days 
11 to 17 days (−3 to +3 days) 
Visit 1 to Telephone contact T2 
90 days 
87 to 93 days (−3 to +3 days) 
Visit 3 to Telephone contact T3 
14 days 
11 to 17 days (−3 to +3 days) 
Visit 3 to Telephone contact T4 
90 days 
87 to 93 days (−3 to +3 days) 
Visit 3 to Last Telephone contact (T5) 
180 days 
173 to 201 days (−7 to +21 days) 
T = telephone contact

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2.0 INTRODUCTION 
2.1 
Study Rationale 
Neisseria meningitidis (N. meningitidis) bacteria is a leading cause of invasive meningococcal 
disease (IMD) worldwide, capable of causing outbreaks and epidemics. The best option for the 
control of IMD is the use of effective vaccines that would include all 5 of the most common 
serogroups of N. meningitidis. 
GlaxoSmithKline Biologicals SA (GSK) is developing a combination vaccine intended to protect 
against 5 of the most prevalent serogroups of N. meningitidis (A, B, C, W, and Y) in humans. 
The availability of a pentavalent meningococcal vaccine in a single administration would reduce 
the number of injections and could increase coverage for meningococcal disease caused by 
N. meningitidis serogroups A, B, C, W, and Y worldwide. The investigational meningococcal 
ABCWY (MenABCWY) combination vaccine is based upon 2 established GSK vaccines, the 
quadrivalent meningococcal ACWY (MenACWY) conjugate vaccine (Menveo) and the 
multi-component recombinant meningococcal B (MenB) vaccine (Bexsero), for which 
significant nonclinical and clinical data have been generated and used to support marketing 
authorizations in several jurisdictions. 
Guidelines regarding meningococcal vaccination in different countries with overall low disease 
rates vary, but most countries recommend vaccination for defined “at risk” groups based on age, 
underlying host factors, and anticipated occupational and/or travel-related exposures. In 
countries (such as Australia, Canada, the United Kingdom, and the United States), a booster dose 
of conjugate quadrivalent ACWY vaccine is recommended every 5 years for persons at 
continued high risk (Crum-Cianflone and Sullivan, 2016). For example, the US Advisory 
Committee on Immunization Practices (ACIP) recommends routine vaccination with a 
quadrivalent conjugated meningococcal vaccine for adolescents at 11 to 12 years of age with a 
booster dose at 16 years of age, based on a substantial amount of data showing a robust immune 
response to a booster dose of MenACWY vaccines in this age group. The ACIP also 
recommends MenB vaccination in individuals aged 10 years and older who are at increased risk 
for MenB disease and in adolescents and young adults aged 16 to 23 years regardless of an 
increased risk for MenB disease. 
Based on the current ACIP recommendations for a MenACWY booster dose at 16 years of age 
and for MenB vaccination at 16 to 23 years of age, there is a need to evaluate the response to 
MenABCWY vaccine in MenACWY vaccine-primed individuals. In the context of the 
MenABCWY investigational vaccine development, the MenACWY booster response was 
evaluated in 2 phase II clinical studies (Sáez-Llorens, 2018; Szenborn, 2018). Although the 
sample size of these studies was small, a robust anamnestic immune response against MenA, 
MenC, MenW, and MenY serogroups was demonstrated at 1 month after the administration of 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
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the first dose of the MenABCWY vaccine in participants previously primed with the GSK 
MenACWY vaccine. 
The main purpose of this phase IIIB clinical study is to assess the immunogenicity and safety of 
the MenABCWY vaccine when administered as a booster in healthy adolescents and young 
adults, previously primed with a MenACWY vaccine. 
2.2 
Background 
N. meningitidis infections causing IMD are an important public health concern worldwide due to 
the substantial morbidity and mortality they cause, as well as the transmissibility of these 
infections. 
Invasive meningococcal disease occurs when, following an average incubation period of 4 days 
(range 2 to 10 days), the normally asymptomatically carried encapsulated gram-negative 
bacterium N. meningitidis enters the bloodstream and multiplies. If the bacteria cross the 
blood-brain barrier, meningitis occurs. Sepsis and meningitis caused by N. meningitidis are 
serious diseases that can be fatal or leave permanent sequelae. In European Union 
(EU)/European Economic Area countries, despite the availability of advanced medical treatment 
and effective antibiotics, case-fatality rates are high at approximately 7% to 15%, with most 
cases caused by serogroup B (ECDC, 2016). Up to one-fifth of survivors suffer long-term 
sequelae, including mental retardation, hearing loss, and loss of limb use (Rosenstein, 2001). In 
the US, the overall case-fatality ratio remains at 10% to 15%, and 11% to 19% of survivors have 
long-term sequelae (Cohn, 2013). Rates of disease are highest in children younger than 1 year of 
age, followed by a second peak in adolescence (Cohn, 2015). 
Reliable estimates of the global burden of disease are currently not available, as case definitions 
differ and surveillance data from many regions are incomplete (Gossger, 2012). The overall 
incidence of IMD in European countries ranges from approximately 0.1 to 2.4 cases per 
100 000 populations (ECDC, 2016). In the US, incidence is 0.1 cases per 100 000 population 
(CDC, 2018). 
GSK’ MenACWY vaccine is a meningococcal oligosaccharide conjugate vaccine licensed for 
active immunization to prevent IMD caused by N. meningitidis serogroups A, C, W-135, and Y. 
It is approved for adolescents and adults in more than 60 countries; many of these countries have 
also approved its use in children. In the EU, the vaccine is indicated for use in individuals 2 years 
of age and older, and in the US, in individuals 2 months to 55 years of age. 
A single booster dose of GSK’ MenACWY vaccine (Menveo) has recently been approved by the 
US Federal Food and Drug Administration (FDA) for a boosting administration to individuals 
who are at continued risk for IMD if at least 4 years have elapsed since a prior dose of a 
meningococcal (serogroups A, C, W-135, Y) conjugate vaccine. 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
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GSK Biologicals’ MenB vaccine (Bexsero) is approved for use in the EU, US, and several other 
countries for active immunization to prevent IMD caused by N. meningitidis serogroup B. In the 
EU, the vaccine is indicated for use in individuals 2 months of age and older; in the US, in 
individuals 10 to 25 years of age. Worldwide, MenB vaccine is approved for use with different 
schedules depending on the country’s jurisdiction; dosage can vary between 2 to 4 doses per 
participant. 
The investigational MenABCWY combination vaccine is based upon the 2 aforementioned 
well-established GSK’s vaccines, MenACWY and MenB. Both vaccines have been extensively 
tested in clinical trials in order to support marketing authorizations in several jurisdictions. 
Refer to the current Investigator’s Brochure (IB) for information regarding pre-clinical and 
clinical studies and epidemiological information of MenABCWY. 
2.3 
Benefit/Risk Assessment 
Detailed information about the known and expected benefits and risks and reasonably expected 
adverse events (AEs) of MenABCWY can be found in the IB. Refer to the Product Information 
(PI) for information regarding the summary of potential risks and benefits of Bexsero and 
Menveo. 
Benefit considerations include: 
• Medical evaluations/assessments associated with this study (e.g., physical examinations). 
• Contributing to the process of developing new therapies. 
• Potential benefit of receiving the licensed Bexsero and Menveo vaccines to help protect 
against meningococcal IMDs caused by N. meningitidis serogroups A, B, C, W, and Y. 
No significant safety signals have been identified for MenABCWY. Cumulative safety data have 
not identified new important safety risks. The balance of anticipated benefits and apparent risks 
associated with MenABCWY continues to be acceptable following the ongoing systematic 
review of safety data. 
Taking into account the measures taken to minimize risk to participants in this study, the 
potential for risks identified in association with MenABCWY, Bexsero, and Menveo are justified 
by the potential benefits that may be afforded to participants. 

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3.0 OBJECTIVES AND ENDPOINTS 
Objectives and endpoints are presented in Table 6. 
Table 6 
Study Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
Immunological non-inferiority: MenABCWY 
vs. MenACWY (Family 1) 
To demonstrate the immunological non-inferiority 
of the MenABCWY vaccine, compared to 
MenACWY vaccine given to healthy participants, 
previously primed with a MenACWY vaccine, as 
measured by the percentages of participants 
achieving a 4-fold rise1 in hSBA titers against 
N. meningitidis serogroups A, C, W, and Y, at 
1 month after the second MenABCWY 
vaccination (0,6-months) and 1 month after the 
MenACWY vaccination (single dose). 
• The percentages of participants with a 4-fold 
rise1 in hSBA titers against N. meningitidis 
serogroups A, C, W, and Y at 1 month after 
the second vaccination for the ABCWY group 
(Day 211, Month 7), and 1 month after the 
single MenACWY vaccination for the ACWY 
group (Day 31, Month 1) relative to baseline 
(Day 1, Month 0). 
Immunological non-inferiority: MenABCWY 
vs. MenACWY (Family 2) 
To demonstrate the immunological non-inferiority 
of the MenABCWY vaccine, compared to 
MenACWY vaccine given to healthy participants, 
previously primed with a MenACWY vaccine, as 
measured by the percentages of participants 
achieving a 4-fold rise1 in hSBA titers against 
N. meningitidis serogroups A, C, W, and Y, at 
1 month after the first MenABCWY vaccination 
(0,6-months) and 1 month after the MenACWY 
vaccination (single dose). 
• The percentages of participants with a 4-fold 
rise1 in hSBA titers against N. meningitidis 
serogroups A, C, W, and Y at 1 month after 
the first vaccination for the ABCWY group 
(Day 31, Month 1), and 1 month after the 
single dose of MenACWY vaccination for the 
ACWY group (Day 31, Month 1), relative to 
baseline (Day 1, Month 0). 
Safety 
To evaluate the safety and reactogenicity of the 
MenABCWY and MenACWY vaccines. 
• The frequencies and percentages of 
participants with solicited administration site 
events (i.e., injection site pain, erythema, 
swelling, induration) and solicited systemic 
events (i.e., fever [body temperature 
≥38.0°C/100.4°F], nausea, fatigue, myalgia, 
arthralgia, headache) during the 7 days 
(including the day of vaccination) following 
vaccination at Day 1, Month 0 (for the 
ABCWY and ACWY groups) and Day 181, 
Month 6 (for the ABCWY group). 
• The frequencies and percentages of 
participants with any unsolicited AEs 
(including all SAEs, AEs leading to 
withdrawal, AESIs and medically attended 
AEs) during the 30 days (including the day of 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
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Objectives 
Endpoints 
vaccination) following vaccination at Day 1, 
Month 0 (for the ABCWY and ACWY 
groups) and Day 181, Month 6 (for the 
ABCWY group). 
• The percentages of participants with SAEs, 
AEs leading to withdrawal, AESIs and 
medically attended AEs throughout the study 
period (Month 0 to Month 12). 
Secondary 
To assess the immune response to MenABCWY 
(0,6-month schedule) and MenACWY (single 
dose) vaccines against N. meningitidis serogroups 
A, C, W, and Y, at pre-vaccination and 1 month 
after the first and last MenABCWY vaccinations 
and 1 month after the MenACWY vaccination. 
• The percentages of participants with hSBA 
titers ≥Lower Limit of Quantitation (LLOQ) 
against serogroups A, C, W, and Y: 
− at baseline (Day 1, Month 0) and at 
1 month after the first (Day 31, 
Month 1) and the last vaccination 
(Day 211, Month 7) for the ABCWY 
group, and 
− at baseline (Day 1, Month 0) and 
1 month after the single MenACWY 
vaccination for the ACWY group 
(Day 31, Month 1). 
• The geometric mean titers (GMTs) against 
serogroups A, C, W, and Y: 
− at baseline (Day 1, Month 0) and at 
1 month after the first (Day 31, 
Month 1) and the last (Day 211, 
Month 7) vaccinations for the 
ABCWY group, and 
− at baseline (Day 1, Month 0) and 
1 month after the single MenACWY 
vaccination for the ACWY group 
(Day 31, Month 1). 
• The geometric mean ratios (GMRs) against 
serogroups A, C, W, and Y: 
− at 1 month after the first (Day 31, 
Month 1) and the last vaccination 
(Day 211, Month 7) for the ABCWY 
group as compared to baseline (Day 
1, Month 0) and 
− at 1 month after the MenACWY 
vaccination (Day 31, Month 1) for the 
ACWY group as compared to 
baseline (Day 1, Month 0). 

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Objectives 
Endpoints 
To assess the immune response to the 
MenABCWY vaccine (0,6-month schedule) 
against N. meningitidis serogroup B indicator 
strains, at pre-vaccination and at 1 month after the 
last MenABCWY vaccination. 
x The percentages of participants with hSBA 
WLWHUV//24IRUHDFK and all serogroup B 
indicator strains at baseline (Day 1, Month 0) 
and at 1 month after the last vaccination 
(Day 211, Month 7) for the ABCWY group. 
x The percentages of participants with 4-fold 
rise1 in hSBA titers against each 
N. meningitidis serogroup B indicator strains 
at 1 month after the last vaccination (Day 211, 
Month 7) relative to baseline (Day 1, Month 0) 
for the ABCWY group. 
x GMTs against each serogroup B indicator 
strains at baseline (Day 1, Month 0) and at 
1 month after the last vaccination (Day 211, 
Month 7) for the ABCWY group. 
x GMRs against each serogroup B indicator 
strains at 1 month after the last vaccination 
(Day 211, Month 7) as compared to the 
baseline (Day 1, Month 0) for the ABCWY 
group. 
CCI

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Objectives 
Endpoints 
AESI = adverse event of special interest; CI = confidence interval; ELISA = enzyme-linked 
immunosorbent assay; GMC = geometric mean concentration; GMT = geometric mean titer; GMR = 
geometric mean ratio; hSBA = human serum bactericidal assay; LLOQ = lower limit of quantitation; 
N. meningitidis = Neisseria meningitidis; SAE = serious adverse event  
1 Refer to Section 9.0 for the (seroresponse) definition of the 4-fold rise. 
CCI
CCI

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4.0 STUDY DESIGN 
4.1 
Overall Design 
The study design diagram is provided in Figure 1. 
Figure 1 
 Study Design Overview 
 
ACWY = Menveo; BS = blood sample; ESFU = extended safety follow-up; MenB = Bexsero; N = number of 
participants; T = telephone contact; V = visit 
a Insufficient blood volume may lead to test cancellation and jeopardize the statistical power. Hence, every effort 
must be made to collect blood volume as per protocol requirements. 
b Bexsero is given for compliance with standard of care. 
Protocol waivers or exemptions are not allowed except for immediate safety concerns. Therefore, 
adherence to the study design requirements, including those specified in the outline of study 
procedures (Section 1.3), are essential and required for study conduct.  
• Type of study: Self-contained. 
• Experimental design: Phase IIIB, randomized, controlled, observer-blind, multi-centric, 
study with 2 parallel study groups. 
• Duration of the study: The total duration of the study, per participant, will be 
approximately 12 months (4 visits), including the 6 months of Extended Safety 
Follow-Up (ESFU) period after the last dose of investigational vaccine (Visit 3, 
Day 181). 
• Primary completion date (PCD):  Last Participant Last Visit (LSLV) (Day 361). 
• Blinding: Observer-blind. Refer to Section 6.3.5 for details. 
• Data collection: Standardized electronic Case Report Form (eCRF). Solicited events will 
be collected using a Participant Diary (electronic diary [eDiary]). 

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• Safety monitoring: Regular safety follow-up will be done through telephone calls. 
Safety follow-up calls are calls made to the participant by a qualified study center staff 
designated by the investigator on the site log. These calls will follow a script which will 
facilitate the collection of relevant safety information. There will also be ESFU phone 
call 6 months after the last dose of investigational vaccine (Visit 3, Day 181). This ESFU 
phone call will also mark the study conclusion. Refer to the Schedule of Events (SoA) 
(Table 3) and Section 8.3 for details on the safety follow-up. 
• End of study: Refer to Section 4.4. 
• Study groups: 
− ABCWY: 603 participants will receive 2 doses of the MenABCWY vaccine at 
Visit 1 (Day 1) and Visit 3 (Day 181) (0,6-month schedule) and 1 dose of placebo at 
Visit 4 (Day 211). 
− ACWY: 603 participants will receive 1 dose of MenACWY vaccine at Visit 1 
(Day 1) (single dose) and 2 doses of MenB vaccine at Visit 3 (Day 181) and Visit 4 
(Day 211). 
Study groups, intervention and blinding foreseen in the study are presented in Figure 1 and Table 
7.  
See Appendix 1, Glossary of Terms, for definitions of a self-contained study, PCD, solicited 
events, intervention, blinding, and a qualified health care professional. 
Table 7 
Study Groups, Intervention, and Blinding Foreseen in the Study 
Study Group 
Number of 
Participants 
Age 
(Min to Max) 
Intervention 
Blinding 
ABCWY 
603 
15 to 25 years (25 years 
+ 364 days) 
MenABCWY 
V1 to T5: 
Observer-blind 
Placebo 
ACWY 
603 
15 to 25 years 
(25 years + 364 days) 
MenACWY 
V1 to T5: 
Observer-blind 
MenB 
MenACWY = Menveo; MenB = Bexsero; T = telephone contact; V = visit 
4.2 
Scientific Rationale for Study Design 
The study is designed as a randomized, controlled, observer-blind study with 2 parallel groups. 
This study will evaluate the immunogenicity and safety of the MenABCWY vaccine when 
administered as a booster in healthy adolescents and young adults, 15 through 25 years of age, 
previously primed with a MenACWY vaccine. The currently licensed Menveo (MenACWY) 
vaccine will be used as comparator.  

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In order to let the participants in the ACWY group receive 2 doses of MenB vaccine in line with 
ACIP recommendations, the participants in this group will receive vaccinations of MenB on 
Visit 3 (Day 181) and Visit 4 (Day 211). There are no study objectives related to the MenB 
vaccine, as it will be administered only to ensure standard of care. However, to maintain the 
study blinding, solicited events (see Appendix 1, Glossary of Terms, for a definition of solicited 
events) during the 7 days (including the day of vaccination) after the first MenB vaccination will 
be collected and recorded through eDiary, and unsolicited AEs during the 30 days (including the 
day of vaccination) during interview with the participant/participant’s parent(s)/legally 
acceptable representative(s) (LAR[s]) at the next visit (refer to the SoA [Table 3] and 
Section 8.3.6.1 for time and frequency on collection of AEs). Although not part of the study 
objectives, solicited events and unsolicited AEs after the first MenB vaccination will be reported 
in the clinical study report (CSR). 
For this study, a placebo (saline solution) will be administered in the ABCWY group at Visit 4 
(Day 211) (Figure 1). A placebo is the best available option to minimize the potential for 
reporting bias in collecting information about AEs and to ensure the same number of 
vaccinations are administered to participants assigned to either of the 2 study groups.  
Blood will be taken from all participants at specified time points (Visit 1, Visit 2, and Visit 4 
[Figure 1]) (refer to Section 8.1 for details on immunogenicity assessments). Insufficient blood 
volume may lead to test cancellation and jeopardize the statistical power. Hence, every effort 
must be done to collect blood volume as per protocol requirements. 
Blood samples will be taken from all participants irrespective of the testing status in order to 
maintain the study blind. Refer to Section 8.1.1 for further details. 
Given the aim of the study is to evaluate the MenABCWY booster response in healthy 
participants previously primed with MenACWY vaccine, eligible participants must have 
received a previous vaccination with a quadrivalent meningococcal conjugate vaccine 
(MenACWY; Menveo or Menactra) at least 4 years prior to study start. 
4.3 
Justification for Dose 
A number of different vaccine formulations with different amounts of the MenB component of 
the vaccine were evaluated in MenABCWY phase I and II clinical studies. The MenABCWY 
formulation that included the same active ingredient composition for outer membrane vesicles 
(OMV) as Bexsero, induced a higher immune response against serogroup B test strains with a 
comparable reactogenicity profile and no identified safety concerns. Therefore, the formulation 
with the same active ingredient composition as the MenB (Bexsero) and MenACWY (Menveo) 
vaccines was chosen as the final formulation of the MenABCWY investigational vaccine. The 
dosing schedule for MenB and MenACWY is based on approved schedules for those vaccines 
while it is not in major contradiction with vaccination schedules in other countries. The 

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0,6-month schedule for MenABCWY is based on the results of the completed phase II Study 
V102_15. 
4.4 
End of Study Definition 
A participant is considered to have completed the study if he/she returns or is available for the 
last scheduled contact as described in the protocol. 
End of study (EoS): LSLV (Day 361) or last testing results released for the samples collected at 
Visit 4 (Day 211)*.  
*Note: In this case, EoS must be achieved no later than 8 months after LSLV. 

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5.0 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Adherence to the criteria as specified in the protocol is essential. Inclusion criteria deviations are 
not allowed because they can jeopardise the scientific integrity or regulatory acceptability of the 
study or participant safety. 
All participants must satisfy ALL of the following criteria at study entry: 
1. Participants and/or participants’ parents/LARs, who, in the opinion of the investigator, 
can and will comply with the requirements of the protocol (e.g., completion of the 
eDiary, return for follow-up visits). 
2. Written or witnessed/thumb printed informed consent obtained from the 
participant/participant’s parent(s)/LAR(s) of the participant prior to performance of any 
study specific procedure. 
3. Written or witnessed/thumb printed informed assent obtained from participants below the 
legal age of consent prior to performance of any study specific procedure.  
4. Previous vaccination with 1 dose of MenACWY vaccine at an age of 10 years or older, 
with an interval of at least 4 years between the previous MenACWY vaccine and 
enrollment (informed consent and assent [as applicable]) into this study. 
5. A male or female between, and including, 15 and 25 years of age (i.e., 25 years 
+ 364 days) at the time of the first vaccination. 
6. Healthy participants as established by medical history, physical examination, and clinical 
judgment of the investigator before entering into the study. 
7. Female participants 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.  
8. Female participants of childbearing potential may be enrolled in the study, if the 
participant: 
− 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 intervention period 
and for 30 days after completion of the vaccination series. 
*Note: Urine samples for pregnancy testing will be collected from female participants of 
childbearing potential at Visit 1, Visit 3, and Visit 4 prior to the vaccination. Frequency 
or urine pregnancy tests can be established at the site according to local regulations. 

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Refer to Appendix 5 for definitions of woman of childbearing potential and adequate 
contraception.  
Refer to Appendix 1, Glossary of Terms, for definitions of the investigator, eligible participants, 
enrolled participants, and witness. 
5.2 
Exclusion Criteria  
Adherence to criteria specified in the protocol is essential. Exclusion criteria deviations are not 
allowed because they can potentially jeopardize the scientific integrity or regulatory acceptability 
of the study or safety of the participant. 
The following criteria should be checked at the time of study entry. The potential participant 
MUST NOT be included in the study if ANY exclusion criterion applies. 
5.2.1 
Medical Conditions 
1. Current or previous, confirmed or suspected disease caused by N. meningitidis. 
2. Household contact with and/or intimate exposure to an individual with laboratory 
confirmed N. meningitidis infection within 60 days of enrollment. 
3. History of any reaction or hypersensitivity likely to be exacerbated by any component of 
the vaccine(s)/product. 
4. Hypersensitivity, including allergy, to any component of vaccines, including diphtheria 
toxoid (CRM 197) and latex medicinal products or medical equipment whose use is 
foreseen in this study. 
5. Progressive, unstable or uncontrolled clinical conditions 
6. Clinical conditions representing a contraindication to intramuscular vaccination and 
blood draws. 
7. Abnormal function or modification of the immune system resulting from: 
− Autoimmune disorders (including, but not limited to: blood, endocrine, hepatic, 
muscular, nervous system or skin autoimmune disorders; lupus erythematosus and 
associated conditions; rheumatoid arthritis and associated conditions; scleroderma 
and associated disorders) or immunodeficiency syndromes (including, but not limited 
to: acquired immunodeficiency syndromes and primary immunodeficiency 
syndromes). 
− Systemic administration of corticosteroids (oral/intravenous/intramuscular) for more 
than 14 consecutive days within 90 days prior to study vaccination until the following 
post-vaccination blood sample. This will mean prednisone equivalent ≥20 mg/day for 
adult participants / and ≥0.5 mg/kg/day with maximum ≥20 mg/day for pediatric 
participants. Inhaled and topical steroids are allowed. 
− Administration of antineoplastic and immunomodulating agents or radiotherapy 
within 90 days prior to study vaccination. 

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− Administration of long-acting immune-modifying drugs at any time during the study 
period (e.g., infliximab). 
8. Any neuroinflammatory (including but not limited to: demyelinating disorders, 
encephalitis or myelitis of any origin), congenital neurological conditions, 
encephalopathies, seizures (including all subtypes such as: absence seizures, generalized 
tonic-clonic seizures, partial complex seizures, partial simple seizures). History of febrile 
convulsions should not lead to exclusion. 
9. Any other clinical condition that, in the opinion of the investigator, might pose additional 
risk to the participant due to participation in the study. 
5.2.2 
Prior/Concomitant Therapy 
10. Use of any investigational or non-registered product (drug, vaccine, or medical device) 
other than the study vaccine(s)/product during the period beginning 30 days before the 
first dose of study vaccine(s)/product (Day −29 to Day 1), or planned use during the 
study period. 
11. Previous vaccination against any group B meningococcal vaccine at any time prior to 
informed consent and assent as applicable (according to the participant’s age). 
12. Previous vaccination with 2 or more doses of MenACWY vaccine. 
13. Administration/planned administration of immunoglobulins and/or any blood products or 
plasma derivatives during the period starting 3 months before any dose of study 
vaccine(s)/product until the following post-vaccination blood sample. 
14. Chronic administration (defined as more than 14 days in total) of immunosuppressants or 
other immune-modifying drugs during the period starting 3 months prior to any 
vaccine/product dose until the following post-vaccination blood sample. For 
corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants / 
and ≥0.5 mg/kg/day with maximum ≥20 mg/day for pediatric participants. Inhaled and 
topical steroids are allowed. 
Refer to the Appendix 1, Glossary of Terms, for a definition of a study vaccine/product. 
5.2.3 
Prior/Concurrent Clinical Study Experience 
15. Concurrently participating in another clinical study, at any time during the study period, 
in which the participant has been or will be exposed to an investigational or a 
non-investigational vaccine/product (drug or medical device). 
Refer to the Appendix 1, Glossary of Terms, for a definition of an investigational 
vaccine/product. 
5.2.4 
Other Exclusions 
16. Child in care. 

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17. Pregnant or lactating female. 
18. Female planning to become pregnant or planning to discontinue contraceptive 
precautions (see inclusion criterion #8 for the necessary duration of contraception 
practice). 
19. History of/current chronic alcohol and/or drug abuse. 
20. Involvement in the study as a study staff member or being immediate dependents, family, 
or household member of a study staff member. 
Refer to the Appendix 1, Glossary of Terms, for a definition of a child in care. 
5.3 
Lifestyle Considerations 
No dietary, caffeine, alcohol, tobacco use, activity, or other lifestyle restrictions are required. 
5.4 
Screen Failures 
If the individual is determined ineligible for study participation or has not entered into the study 
for other reasons following informed consent but before randomization, he/she is considered a 
screen failure. 

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6.0 STUDY INTERVENTION 
A “study intervention” is defined as a set of investigational or marketed product or placebo 
intended to be administered to a participant during the study. 
Refer to the study reference manual for additional details. 
6.1 
Study Interventions Administered 
The study interventions that will be administered in the study are provided in Table 8. 
The participants must be observed closely for at least 30 minutes after the administration of the 
vaccine(s)/product. Appropriate medical treatment must be readily available during the 
observation period in case of anaphylaxis and/or syncope.

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Table 8 
Study Interventions Administered 
Study 
Intervention 
Name 
MenABCWY1,2 
Menveo3,2,4 
Bexsero5 
Placebo5,6 
Vaccine(s)/ 
Product 
MenACWY lyo 
rMenB+OMV NZ 
MenA  
MenCWY  
rMenB+OMV NZ 
NaCl 
Presentation 
Vial 
Syringe 
Vial 
Vial 
Syringe 
Syringe 
Dose form 
Powder for suspension 
for injection 
Suspension for 
injection 
Powder for solution 
for injection 
Solution for 
solution for 
injection 
Suspension for 
injection 
Solution for 
injection 
Vaccines(s)/ 
Product 
Formulation7 
MenA(10 µg)-CRM₁₉₇; 
MenC(5 µg)-CRM₁₉₇; 
MenW135(5 µg)-CRM₁₉₇; 
MenY(5 µg)-CRM₁₉₇ 
Recombinant 
N. meningitidis 
serogroup B NHBA 
fusion protein 
(50 µg) adsorbed on 
aluminum 
hydroxide; 
Recombinant 
N. meningitidis 
serogroup B NadA 
protein (50 µg) 
adsorbed on 
aluminum 
hydroxide; 
Recombinant 
N. meningitidis 
serogroup B fHbp 
fusion protein 
(50 µg) adsorbed on 
aluminum 
hydroxide; Outer 
membrane vesicles 
from 
N. meningitidis, 
serogroup B Strain 
NZ98/254 (25 µg 
PorA P1.4) adsorbed 
Meningococcal 
group A 
oligosaccharides 
(10 µg) conjugated 
to Corynebacterium 
diphtheriae C7 
(β197) M8 
(CRM197) protein 
(16.7-33.3 µg); 
Potassium 
dihydrogen 
phosphate; Sucrose 
Meningococcal 
group C 
oligosaccharides 
(5 µg) conjugated 
to Corynebacterium 
diphtheriae C7 
(β197) M8 
(CRM197) protein 
(7.1-12.5 µg); 
Meningococcal 
group W-135 
oligosaccharides 
(5 µg) conjugated 
to Corynebacterium 
diphtheriae C7 
(β197) M8 
(CRM197) protein 
(3.3-8.3 µg); 
Meningococcal 
group W-135 
oligosaccharides 
(5 µg) conjugated 
to Corynebacterium 
diphtheriae C7 
(β197) M8 
(CRM197) protein 
(5.6-10 µg); NaCl; 
Recombinant 
N. meningitidis 
serogroup B 
NHBA fusion 
protein (50 µg) 
adsorbed on 
aluminum 
hydroxide; 
Recombinant 
N. meningitidis 
serogroup B NadA 
protein (50 µg) 
adsorbed on 
aluminum 
hydroxide; 
Recombinant 
N. meningitidis 
serogroup B fHbp 
fusion protein 
(50 µg) adsorbed 
on aluminum 
hydroxide; Outer 
membrane vesicles 
from 
N. meningitidis, 
serogroup B Strain 
NZ98/254 (25 µg 
Sodium chloride 
(NaCl) (0.9%); 
Water for 
injections 

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Study 
Intervention 
Name 
MenABCWY1,2 
Menveo3,2,4 
Bexsero5 
Placebo5,6 
on aluminum 
hydroxide; 
Aluminum 
hydroxide (0.5 mg 
Al³⁺); Sucrose; 
Histidine; NaCl; 
Water for injections 
q.s. 0.5 mL10 
Sodium dihydrogen 
phosphate 
monohydrate; 
Disodium 
phosphate 
dihydrate; Water 
for injections q.s. 
0.5 mL 
PorA P1.4) 
adsorbed on 
aluminum 
hydroxide; 
Aluminum 
hydroxide (0.5 mg 
Al³⁺); Sucrose; 
Histidine; NaCl; 
Water for 
injections q.s. 
0.5 mL  
Product type 
Combination 
Biological 
Combination 
Combination 
Type 
Study 
Control 
Additional 
Additional 
Route of 
Administration 
Intramuscular use 
Intramuscular use  
Intramuscular use 
Intramuscular use 
Administration 
site: 
 
  
Location8 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
  
Laterality8 
Non-dominant 
Non-dominant 
Non-dominant 
Non-dominant 
Number of 
doses to be 
administered 
2 
1 
2 
1 
Volume to be 
administered9 
0.5 mL 
0.5 mL 
0.5 mL 
0.65 mL11 
Packaging, 
labelling 
Refer to study reference manual for details 
Refer to study reference manual for 
details 
Refer to study 
reference manual 
for details 
Refer to study 
reference manual 
for details 
Manufacturer 
GSK Biologicals SA 
GSK Biologicals SA 
GSK Biologicals 
SA 
GSK Biologicals 
SA 

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CRM = cross reacting material; fHbp = factor H binding protein; GSK = GlaxoSmithKline; NaCl = sodium chloride; NHBA = Neisseria heparin binding antigen; 
NZ = New Zealand 
1 
MenABCWY formulation consisting of a MenACWY lyo (lyophilized component) and of a rMenB+OMV liquid component, to be reconstituted together 
before administration (0.5 mL) by qualified health care practitioner (refer to Appendix 1, Glossary of Terms). 
2 Investigational vaccine. 
3 Menveo commercial formulation consisting of a MenA lyophilized component and of a MenCWY liquid component, to be reconstituted together before 
administration (0.5 mL) by qualified health care practitioner (refer to Appendix 1, Glossary of Terms). 
4 In the US, the approved specifications for Menveo are described as MenA lyo: MenA=10µg, CRM197=12.5 µg-33 µg; Potassium dihydrogen phosphate; 
sucrose and MenCWY liquid: MenC=5µg; CRM197=6.25 µg-12.5 µg; MenW=5 µg,CRM197=3.3 µg-10 µg; MenY=5µg,CRM197=3.3 µg-10 µg; Sodium 
chloride; Sodium dihydrogen phosphate monohydrate; Disodium phosphate dihydrate; water for injections q.s. 0.5 mL.  
5 Non-investigational vaccine or placebo. 
6 Administered in the ABCWY group at Visit 4 to maintain the study observer-blind. 
7 The composition per dose is presented here. 
8 The 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.  
9 Refer to the study reference manual for details. 
10 Both the manufacture and the final composition of the MenB component of the MenABCWY are identical to that of the commercial Bexsero. However, to 
ensure a consistent reconstitution procedure and to reduce the risk of under-dosing the MenB component, the filling weight has been increased from a 
nominal 0.609 g present in commercial Bexsero to 0.640 g in the MenB component, used to reconstitute MenABCWY. Refer to the study reference manual 
for details. 
11 The volume of the saline PFS may be between 0.6 mL and 0.8 mL. The full volume is to be injected. 
 

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6.2 
Preparation/Handling/Storage/Accountability 
The study vaccine(s)/product must be stored in a safe, locked place at the temperature 
specified on the vaccine/product label. The storage temperature should be continuously 
monitored with calibrated (if not validated) temperature monitoring device(s) and 
recorded.  
Only authorized study personnel should be allowed access to the study 
vaccine(s)/product. Storage conditions will be assessed by the sponsor’s designee 
(IQVIA, see the study administrative structure in Table 16) during pre-study activities. 
Refer to the study reference manual for more details on storage and handling of the study 
vaccine(s)/product. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for the study vaccine(s)/product accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
The investigator, a member of the study center staff, or a hospital pharmacist must 
maintain an adequate record of the receipt and distribution of all study vaccine(s)/product 
using the Product Accountability Form. These forms must be available for inspection at 
any time. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Participant Identification 
Participant identification numbers (IDs) will be assigned sequentially to the participants 
who have consented or provided assent with consent from each participant’s 
parent(s)/LAR(s) to participate in the study, according to the range of Participant IDs 
allocated to each study center. The Participant IDs will be documented in the Screening 
and Enrollment log. 
The eligibility of the participant will be determined based on the inclusion and exclusion 
criteria listed in Section 5.0. The Participant ID will be the participant’s unique 
identification number for all eCRFs and associated study documentation that will be used 
for duration of the study. If the participant is terminated from the study, his/her 
Participant ID cannot be re-assigned. 
6.3.2 
Randomization to Study Intervention 
All eligible participants will be centrally randomized using Interactive Voice Response 
System (IVRS) randomization (refer to Appendix 1, Glossary of Terms, for a definition 
of IVRS). Before the study is initiated, login information and directions for the IVRS will 
be provided to each study center. 

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The participants will receive a unique treatment number (refer to Appendix 1, Glossary of 
Terms, for a definition of a treatment number). Once a treatment number has been 
assigned, it cannot be re-assigned. To allow the sponsor to take advantage of greater rates 
of recruitment in this multicenter study and to thus reduce the overall study recruitment 
period, an over-randomization of supplies will be prepared. 
6.3.3 
Intervention Allocation to the Participant 
The target sample size to be enrolled in this study is 1206 participants to be assigned to 
the 2 study groups in a 1:1 ratio: 
• ABCWY: 603 participants will receive 2 doses of the MenABCWY vaccine at 
Visit 1 (Day 1) and Visit 3 (Day 181) (0,6-month schedule) and 1 dose of placebo 
at Visit 4 (Day 211). 
• ACWY: 603 participants will receive 1 dose of MenACWY vaccine at Visit 1 
(Day 1) (single dose) and 2 doses of MenB vaccine at Visit 3 (Day 181) and 
Visit 4 (Day 211). 
Refer to Section 9.2 for a detailed description of the criteria used in the estimation of 
sample size. 
The system’s randomization algorithm will use a minimization procedure accounting for 
country. Upon providing the Participant ID, the randomization system will determine the 
study group and will provide the treatment number to be used for the first vaccination. 
The treatment number(s) to be used for subsequent dose administration(s) will be 
provided by the same randomization system. 
See Appendix 1, Glossary of Terms, for a definition of a treatment number. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration form/screen. 
When the specified randomization system is not available, refer to the randomization 
system user guide or the study reference manual for specific instructions. 
Refer to the study reference manual for additional information relative to the treatment 
number allocation. 
6.3.4 
Allocation of Participants to Assay Subsets  
Immunogenicity assessments are planned as outlined in Section 8.1.  
Refer to Section 9.3 for descriptions of analysis populations. 

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6.3.5 
Blinding and Unblinding 
6.3.5.1 
Blinding 
Data will be collected in an observer-blind manner, i.e., participants, investigators, and 
teams responsible for assessment of any study endpoints will be blinded to the 
administered vaccine(s)/product. Study vaccine(s)/product will be prepared and 
administered by qualified study personnel who will not participate in data collection, 
evaluation, review, or the entry of any study endpoint (i.e., reactogenicity, safety, 
immunogenicity). 
The laboratory in charge of the laboratory testing will be blinded to the treatment, subject 
and visit number, and codes will be used to link the subject, visit and study (without any 
link to the treatment attributed to the subject) to each sample.  
6.3.5.2 
Emergency Unblinding 
Unblinding a participant’s individual intervention number should occur ONLY in case of 
a medical emergency when knowledge of the intervention is essential for the clinical 
management or welfare of the participant. 
The emergency unblinding process enables the investigator to have unrestricted, 
immediate and direct access to the participant’s individual study intervention through 
IVRS. At study activation, the study centers will be provided instructions and/or other 
applicable information for emergency unblinding. 
The Interactive Response Technology used by the IVRS provider will be programmed 
with blind-breaking instructions. In case of an emergency, the investigator has the sole 
responsibility for determining if unblinding of a participant’s treatment is warranted. 
Participant safety must always be the first consideration in making such a determination. 
If the investigator decides that unblinding is warranted, the investigator should make 
every effort to contact the Medical Monitor (see the definition in Appendix 1, Glossary of 
Terms) prior to unblinding unless this could delay emergency intervention of the 
participant. If a participant’s intervention assignment is unblinded, the IQVIA’s Medical 
Monitor must be notified within 24 hours after breaking the blind. The date and reason 
that the blind was broken must be recorded in the source documentation and eCRF, as 
applicable. A participant may continue in the study if that participant’s intervention 
assignment is unblinded. 
In the event of a Quality Assurance audit, the auditor(s) may be allowed access to 
unblinded study treatment information records to verify that randomization/study 
vaccine(s)/products dispensing has been done accurately. 
A non-investigator physician (e.g., physician from emergency room) or 
participant/caregiver (see Appendix 1, Glossary of Terms, for a definition of a 

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caregiver)/family member may also request emergency unblinding. Instructions for this 
will be provided to the participant/participant’s parent(s)/LAR(s) at enrollment. 
6.4 
Study Intervention Compliance 
When participants are dosed at the study center, they will receive study intervention from 
the authorized qualified study center staff listed on the site log. This study center staff 
member will prepare and administer the vaccine(s)/product and will be unblinded to the 
intervention but will not participate in any post-injection participant assessments. A 
blinded observer will participate in the participant’s post-injection assessments, perform 
clinical evaluations and record the clinical data. A delegated second-shift or back-up 
study staff member can be assigned to perform any of these activities. Only blinded staff 
can participate in any clinical evaluations and recording of clinical data. The date of each 
dose administered at the study center will be recorded in the source documents and in the 
eCRF. The dose of study intervention and Participant ID will be confirmed at the time of 
dosing by a study staff member other than the person administering the study 
intervention.  
Refer to the SoA (Table 3) for the study intervals. 
6.5 
Concomitant Therapy 
At each study visit/contact, the investigator or authorized study center staff member 
should question the participant and/or the participant’s parent(s)/LAR(s) about any 
medications/products taken and vaccinations received by the participant. 
The following concomitant medications/products/vaccines must be recorded in the eCRF: 
• Any concomitant medications/products/vaccines administered for the prevention 
or treatment of a solicited event or AE to be recorded as per the protocol-specified 
reporting period (see Section 8.3.6.1). 
• Any concomitant medications/products/vaccines leading to the withdrawal or 
non-eligibility of the participant from the study (refer to the Section 5.2.2 for 
further details). 
• Any concomitant medications/products/vaccines relevant to a serious adverse 
event (SAE) or an AE of special interest (AESI) (see definitions in Appendix 4) to 
be reported as per protocol or administered at any time during the study period for 
the treatment of an SAE/AESI. Concomitant medications relevant to SAEs and 
AESI must be recorded on the Expedited AE Report. 
• Any concomitant vaccination administered in the period starting 14 days before 
the first dose of study vaccine(s) and ending at the last study contact (Day −14 to 
Day 361). 
• The use of antipyretic and/or other medications to prevent (prophylactic use) 
and/or treat fever during the first 7 days after vaccination to be recorded in the 

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eCRF as well. Medications taken for prophylaxis are those intended to prevent the 
onset of symptoms. Medications taken for treatment are intended to reduce or 
eliminate the presence of symptoms that are present. An antipyretic is considered 
to be prophylactic when it is given in the absence of fever and any other 
symptom, to prevent fever from occurring (fever is defined as temperature 
≥38.0°C/100.4°F regardless the location of measurement). The preferred location 
for measuring temperature in this study is oral. 
• The use of antipyretics and/or analgesic medications within 24 hours prior to 
vaccination must be identified and the reason for their use (prophylaxis versus 
treatment) must be described in the source document and Concomitant 
Medications eCRF. 
• The use of systemic antibiotics within 3 days prior to blood sampling visit is a 
reason to delay blood sample withdrawal (see Section 6.7 for criteria for 
temporary delay of vaccination).  
Any concomitant medications or products taken during the study 14 days before the first 
dose of study vaccine(s) and ending at the last study contact that don’t fall under the 
listed conditions, should also be recorded if deemed important per investigator’s 
judgment. 
The reason for use, dates of administration (start and end dates) and dosage information 
(dose and frequency) for medications/products/vaccines will be recorded in the eCRF. 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.6 
Dose Modification 
Not applicable. 
6.7 
Criteria for Temporary Delay for Enrollment and/or Vaccination 
and/or Blood Sampling 
Enrollment and/or vaccination and/or blood sampling may be postponed within the 
permitted time interval until transient circumstances cited below are resolved:  
• Acute disease and/or fever at the time of vaccination. Refer to the SoA (Table 3) 
for fever definition and preferred location for measuring temperature in this study. 
• Significant acute illness within the previous 7 days. 
• Receipt of systemic antibiotics within 3 days prior to blood sampling visit 
(Visit 1, Visit 2, and Visit 4) (this will defer the blood draw). 
• Receipt of a vaccine not foreseen by the study protocol administered during the 
period starting 7 days (for inactivated vaccine) or 14 days (for live vaccines) days 

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before each dose and ending 7 days (for inactivated vaccine) or 14 days (for live 
vaccines) after each dose of vaccine(s)/product administration*. 
*Note: In case an emergency mass vaccination for an unforeseen public health threat 
(e.g., a pandemic) is organized by the public health authorities, outside the routine 
immunization program, the time period described above can be reduced if necessary for 
that vaccine provided it is licensed and used according to its Prescribing Information and 
according to the local governmental recommendations and provided a written approval 
of GSK is obtained. 
Under such circumstances, a participant may be considered eligible for study enrollment 
and/or vaccination after the appropriate window for delay described above, or as defined 
by local health authorities, has passed and inclusion/exclusion criteria have been 
re-checked, and if the participant is confirmed to be eligible. 
6.8 
Contraindications to Subsequent Vaccine(s) Administration 
Participants must be evaluated to confirm they are eligible for subsequent vaccination 
before administering each additional study vaccine dose.  
Participants who meet any of the criteria listed below or criteria listed in Section 5.2 
should not receive additional vaccinations. However, these participants should be 
encouraged to continue other study procedures at the discretion of the investigator (refer 
to Appendix 4 for instructions on follow-up of AEs). The relevant criteria for 
discontinuing vaccination must be recorded in the eCRF.  
• Participants who experience any SAE judged to be possibly or probably related to 
study vaccine or non-study vaccines, including hypersensitivity reactions. 
• Participants who develop any new condition which, in the opinion of the 
investigator, may pose additional risk to the participant if he/she continues to 
participate in the study. 
• Occurrence of a new AESI or the exacerbation of an existing AESI that, in the 
opinion of the investigator, exposes the participant to unacceptable risk from 
subsequent vaccination. Refer to Appendix 1, Glossary of Terms, for the 
definition of AESIs. 
• Occurrence of a new potential immune-mediated diseases (pIMD) or the 
exacerbation of an existing pIMD that, in the opinion of the investigator, expose 
the participant to unacceptable risk from subsequent vaccination. In such cases, 
the investigator should use his/her clinical judgment prior to administering the 
next dose of the vaccine(s)/product. Refer to Appendix 1, Glossary of Terms, for 
the definition of pIMDs.  
• Any condition that in the judgment of the investigator would make intramuscular 
injection unsafe. 
• Anaphylaxis following the administration of vaccines. 

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• Pregnancy. 
• Any occurrence of an event listed in the exclusion criteria which must be always 
re-assessed by the investigator before administration of the next dose of study 
vaccine. 
6.9 
Intervention After the End of the Study 
During the study conclusion contact, the investigator will ask each 
participant/participant’s parent(s)/LAR(s) if they are interested in participating/allowing 
the participant to join a booster study/long-term study. If a participant/participant’s 
parent(s)/LAR(s) is/are not interested in joining the long-term study the reason for refusal 
will be documented, when available, in the participant’s eCRF. 
The investigator is encouraged to share immunological assay results for non-responders 
with the study participants/participants’ parent(s)/LAR(s). 
For participants identified as non-responders, it is the responsibility of the investigator in 
charge of the participant’s clinical management to determine the medical care needed as 
per local/regional practices (such as re-vaccination of the participant[s]). 
Refer to Section 8.1.5 for information regarding the immunological correlates of 
protection. 

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7.0 DISCONTINUATION OF STUDY INTERVENTION 
AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL  
7.1 
Reasons for Discontinuation/Withdrawal 
• The participant may withdraw or participant’s parent(s)/LAR(s) may withdraw a 
participant from the study at any time on request, or a participant may be withdrawn 
at any time at the discretion of the investigator for safety, behavioural, compliance, or 
administrative reasons. 
• If the participant/participant’s parent(s)/LAR(s) withdraw consent for disclosure of 
future information, the sponsor may retain and continue to use any data collected 
before such a withdrawal of consent. 
• If a participant is withdrawn from the study, the participant/participant’s 
parent(s)/LAR(s) may request destruction of any samples taken and not tested, and 
the investigator must document this in the study center study records. 
Participants who discontinue study intervention or are withdrawn from the study will not 
be replaced. The eCRF should be completed as much as possible. 
If a participant is withdrawn from the study because he/she/the participant’s 
parent(s)/LAR(s) have withdrawn consent and provided the reason for its withdrawal, the 
investigator must document this reason in the eCRF. 
7.2 
Discontinuation of Study Intervention 
“Discontinuation” of study intervention (study vaccine(s)/product) means any participant 
who has not received all planned doses of vaccine(s)/product. A participant who 
discontinued study vaccine(s)/product may, if deemed appropriate by the investigator, 
continue other study procedures (e.g., safety or immunogenicity) if planned in the study 
protocol.  
The primary reason for premature discontinuation of the study vaccine(s)/product will be 
documented on the eCRF based on the following: 
• AE requiring expedited reporting to IQVIA 
• Unsolicited non-serious AE  
• Solicited AE 
• Protocol deviation 
• Not willing to be vaccinated 
• Other (specify) 

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7.3 
Participant Discontinuation/Withdrawal from the Study 
A participant 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 participant from the date of withdrawal/last contact.  
From an analysis perspective, a “withdrawal” from the study refers to any participant 
who was not available for the concluding contact foreseen in the protocol.  
Investigators or designated study center personnel will attempt to contact those 
participants who do not return for scheduled visits or follow-up. 
All data and samples collected until the date of withdrawal/last contact of the participant 
will be used for the analysis. 
The primary reason for study withdrawal will be documented in the eCRF based on the 
list below: 
• AEs requiring expedited reporting to IQVIA 
• Unsolicited non-serious AE 
• Solicited AE 
• Protocol deviation  
• Withdrawal by participant, not due to an AE (see Section 7.1) 
• Migrated/Moved from the study area 
• Lost to follow-up 
• Sponsor study termination 
• Other (specify) 
Participants who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigators will 
follow participants who are withdrawn from the study as result of an SAE/AE until the 
event is resolved (refer to Appendix 4 for instructions on follow-up of AEs). 
7.4 
Lost to Follow-up 
A participant will be considered “lost to follow-up” if he/she fails to return for scheduled 
visits and is unable to be contacted by the study center.  
Refer to the study reference manual for a description of the actions to be taken before 
considering the participant as lost to follow-up. 

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8.0 STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Table 3). 
• Adherence to the protocol is required for study conduct. 
• Protocol waivers or exemptions are not allowed unless necessary for the 
management of an immediate safety concerns.  
• The investigator is not allowed to do testing on samples outside of what has been 
agreed upon by the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB). 
• Immediate safety concerns should be discussed with IQVIA as soon as they occur 
or when the study team is aware of them. The purpose of this communication is to 
determine if the participant(s) should discontinue the study intervention. 
• All screening evaluations (i.e., eligibility criteria check) must be completed and 
the results reviewed before confirming that potential participants meet all 
eligibility criteria.  
• The investigator will maintain a screening log of all participants screened. All 
relevant information, such as confirmation of eligibility and reasons for screening 
failure will be mentioned in this screening log.  
• The study reference manual provides the investigator and study center personnel 
with administrative and detailed technical information that does not impact 
participant safety. 
8.1 
Immunogenicity Assessments 
Collected biological 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. 
Future findings may make it desirable to use the samples acquired in this study for future 
research not described in this protocol. Therefore, all participants in countries where this 
is allowed will be asked to give a specific consent to allow the sponsor or a contracted 
partner to use the samples for future research. Future research will be participant to 
IEC/IRB approval if required per local legislation. 
Additional serological assays may be performed in the future to further characterize the 
disease and/or the antibody response to the antigens included in the study vaccines or 
hSBA against an additional panel of strains of Neisseria species. These assays may not be 
represented in the objectives/endpoints of the study protocol. 
Information on further investigations and their rationale can be obtained from GSK.  
Sample testing will be done in accordance with the recorded consent of the individual 
participant/participant’s parent(s)/LAR(s). 

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If additional testing is performed, the marker priority ranking given in the Section 8.1.3 
may be changed. 
Collected samples will be stored for a maximum of 20 years. This storage period begins 
when the last participant performed the last study visit, unless local rules, regulations or 
guidelines require different timeframes or procedures, which would then be in line with 
participant consent. These extra requirements need to be communicated formally to and 
discussed and agreed with GSK. 
8.1.1 
Biological Samples 
An overall volume of approximately 60 mL of blood per participant will be collected 
during the entire study period.  
Refer to Table 9 and the SoA (Table 3) for details of blood volumes collected for 
different assessments. 
Table 9 
Biological Samples 
Sample Type 
Quantity 
Time Point 
Subset Name1 
Blood 
Approximately 20 mL2 
Visit 1 (Day 1) 
Not applicable 
Blood 
Approximately 20 mL2 
Visit 2 (Day 31) 
Not applicable 
Blood 
Approximately 20 mL2 
Visit 4 (Day 211) 
Not applicable 
1 Refer to Section 6.3.4 and Section 8.1 for information regarding assay subsets. 
2 Insufficient blood volume may lead to test cancellation and jeopardize the statistical power. Hence, 
every effort must be done to collect blood volume as per protocol requirements. 
8.1.2 
Laboratory Assays 
All laboratory testing will be performed at GSK’s laboratory or in a laboratory designated 
by GSK. 
Serum bactericidal activity which is a functional measure of the ability of antibodies, in 
conjunction with human complement, to kill meningococci, is widely accepted and 
generally recognized as the serological surrogate marker for protection.  
Immunogenicity of the vaccine against serogroups A, B, C, W, and Y will be evaluated 
with the serum bactericidal assay using exogenous source of human complement (hSBA). 
The 4 indicator strains representing serogroups Men A, C, W, and Y will be tested in the 
hSBA using the agar-overlay technology, while the 4 indicator strains representing 
serogroup MenB will be tested in the hSBA using the manual (tilt) technology. 
The induction of anti-polysaccharide antibodies directed against serogroup A, C, W, and 
Y meningococci following MenACWY vaccination may be measured by Enzyme-Linked 
Immunosorbent Assay (ELISA). The ELISA procedure is used to detect the amount of 

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serum immunoglobulin G (IgG) antibodies in response to specific N. meningitidis 
polysaccharide antigens. See Table 10 for details. 
Table 10 
Laboratory Assays  
System 
Component 
Method 
Laboratory 
Serum 
N men A (3125) Ab 
hSBA 
GSK1 or 
laboratory 
designated by 
GSK 
Biologicals 
N men C (C11) Ab 
N men W (240070) Ab 
N men Y (860800) Ab 
Serum 
N men B fHbp (M14459) Ab 
hSBA 
N men B NadA (96217) Ab   
N men B PorA (NZ98/254) Ab  
N men B NHBA (M13520) Ab 
Serum 
N men A Ab IgG 
ELISA2 
N. men C Ab IgG 
N men W Ab IgG 
N men Y Ab IgG 
Ab = Antibody; ELISA = enzyme-linked immunosorbent assay; fHbp = factor H binding protein; 
hSBA = serum bactericidal assay using human complement; IgG = Immunoglobin G; 
N men = Neisseria meningitidis; NadA = Neisserial adhesin A; NHBA = Neisseria Heparin Binding 
Antigen; PorA = Porin A 
1 GSK Biologicals laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart or Wavre, 
Belgium. CLS may delegate testing to GSK Research laboratories in Siena, Italy, or to Nexelis in 
Marburg, Germany, or other external laboratories.  
2 ELISA assay characteristics (e.g., validated assay cut-offs and units) for each of the serogroup will be 
determined at the time of the generation of validation data. Any change, including the change of the 
format of the assay, will be documented and submitted prior to the submission of the clinical study 
report. 
Refer to Appendix 3 for a detailed description of the assays performed in the study. The 
addresses of clinical laboratories used for sample analysis will be provided in a separate 
document. 
GSK clinical laboratories and designated laboratories have established a Quality System 
supported by procedures. The activities of GSK clinical and designated laboratories are 
audited regularly for quality assessment by an internal (sponsor-dependent) but 
laboratory-independent Quality Department. 
Laboratory/analyte results that could unblind the study will not be reported to study 
centers or other blinded personnel until the study has been unblinded. 

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8.1.3 
Immunological Read-outs 
In case of insufficient blood sample volume to perform assays for all antibodies, the 
samples will be analyzed according to priority ranking provided in Table 11. The subsets 
for immunological read-outs will be randomly selected from the pool of blood draws and 
will be described in separate randomization list(s) and handed over to the laboratory. The 
trigger for the randomization list(s) will be completion of blood draws for a given visit. 
Table 11 
Immunological Read-outs 
Blood Sampling Time Point No. 
Planned 
Participa
nts1  
Method2 Component 
Components 
Priority 
Rank3 
Type of 
Contact and 
Time Point 
Sampling 
Time Point 
Visit 1 (Day 1) Pre-Vacc 1  
12064 
hSBA 
N men A (3125) Ab  
1 
hSBA 
N men C (C11) Ab 
1 
hSBA 
N men W (240070) Ab  
1 
hSBA 
N men Y (860800) Ab 
1 
2094 
hSBA 
N men B (M14459) Ab 
2 
hSBA 
N men B (M13520) Ab 
2 
hSBA 
N men B (96217) Ab 
2 
hSBA 
N men B (NZ98/254) Ab 
2 
Visit 2 
(Day 31) 
Post-Vacc 1  12064 
hSBA 
N men A (3125) Ab  
1 
hSBA 
N men C (C11) Ab 
1 
hSBA 
N men W (240070) Ab  
1 
hSBA 
N men Y (860800) Ab 
1 
2094 
hSBA 
N men B (M14459) Ab 
2 
hSBA 
N men B (M13520) Ab 
2 
hSBA 
N men B (96217) Ab 
2 
hSBA 
N men B (NZ98/254) Ab 
2 
Visit 4 
(Day 211) 
Post-Vacc 2 2704 
hSBA 
N men A (3125) Ab  
1 
hSBA 
N men C (C11) Ab 
1 
hSBA 
N men W (240070) Ab  
1 
hSBA 
N men Y (860800) Ab 
1 
2094 
hSBA 
N men B (M14459) Ab 
2 
hSBA 
N men B (M13520) Ab 
2 
hSBA 
N men B (96217) Ab 
2 
hSBA 
N men B (NZ98/254) Ab 
2 
Ab = antibody; hSBA = serum bactericidal assay using human complement; IgG = Immunoglobin G; 
N men = Neisseria meningitidis; Pre-Vacc = pre-vaccination; Post-Vacc = post-vaccination 

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1 Approximate number of participant samples tested. 
2 For details regarding the method refer to Table 10. 
3 Priority ranking for the serum bactericidal assay using human complement (hSBA) testing using the 
8 indicator strains may be participant to change during the study (e.g., in case of requalification, 
revalidation or standardization). This will be documented in a protocol amendment  
4 For the N Men B test strains: samples from 189 participants in the ABCWY group and 20 participants in 
the control group to maintain the study blinding at all time points (Day 1, Day 31, and Day 211). For 
the N Men A, C, W, Y serogroups: samples from all study participants will be tested at Day 1 and 
Day 31, and samples from 250 participants in the ABCWY group and 20 participants in the control 
group to maintain the study blinding will be tested at Day 211. Evaluation of the tertiary objective is 
participant to the availability of samples and may or not be performed. 
8.1.4 
Clinical Safety Laboratory Assessments 
A urine pregnancy test will be conducted as needed for women of childbearing potential 
(refer to Section 8.3.3). The test will be conducted locally according to the clinical 
laboratory manual and the SoA (Table 3). 
8.1.5 
Immunological Correlates of Protection 
No generally accepted immunological correlate (see Appendix 1, Glossary of Terms, for 
a definition of immunological correlate) of protection has been demonstrated so far 
against N. meningitidis serogroups A, B, W-135, and Y. 
An hSBA titer ≥4 is a generally accepted correlate of protection against invasive 
meningococcal disease caused by N. meningitidis serogroup C. The immunological assay 
results will be communicated to the investigator.  
Refer to Section 6.9 for details regarding treatment for non-responders. 
8.2 
Collection of Demographic Data and Other Baseline 
Characteristics 
At Visit 1, demographic data such as date of birth (month and year), gender, race, and 
ethnic origin will be recorded in the participant’s eCRF. Height and weight will be 
measured using calibrated equipment, and the body mass index will be derived. 
8.3 
Safety Assessments 
The investigator and investigator’s designee(s) are responsible for detecting, 
documenting, and reporting events that meet the definition of an AE or SAE. The 
investigator and investigator’s designee(s) remain responsible for following up AEs that 
are serious, considered related to the study intervention or the study, or that caused the 
participant to discontinue the study treatment or study. 
Data will be collected in an observer-blind manner, i.e., participants, investigators, and 
teams responsible for assessment of any study endpoints will be blinded to the 
administered vaccine(s)/product. 

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Safety follow-up calls are calls made to the participant by a qualified health care 
professional designated on the Study Site Responsibility Delegation Log. These calls will 
follow a script which will facilitate the collection of relevant safety information. 
8.3.1 
Medical History 
Participant’s vaccination history will be obtained by interviewing the 
participant/participant’s parent(s)/LAR(s) and/or review of the participant’s medical 
records. The appropriate written documentation of the identity of the primary 
MenACWY vaccination and vaccination date should to be provided prior to enrollment. 
Individuals for whom written documentation is not available may still be enrolled into the 
study. Any pre-existing participant conditions, signs and/or symptoms present prior to the 
first vaccination will be recorded in the eCRF. 
Medical history will be collected at Visit 1, including but not limited to any medical 
history that may be relevant to participant eligibility for study participation such as prior 
vaccinations, concomitant medications (refer to Section 5.2.2), and previous and ongoing 
illnesses or injuries. Relevant medical history can also include any medical history that 
contributes to the understanding of an AE that occurs during study participation, if it 
represents an exacerbation of an underlying disease/pre-existing problem. 
8.3.2 
Physical Examination  
At Visit 1, a general physical examination will be performed by a qualified health care 
professional. “Qualified health care professional” refers to any licensed or certified health 
care practitioner who is permitted by institutional policy to perform protocol-required 
procedures and who is identified within the Study Staff Signature Log.  
The physical examination may include examination of organ systems that are relevant to 
the investigation based on medical history and review of systems (e.g., measurement of 
heart rate, blood pressure, height and weight, body temperature).  
Review of systems is a structured interview that queries the participant and/or 
parent(s)/LAR(s) as to any complaints the participant has experienced across each organ 
system. 
At Visits 2 through 4, a brief symptom-directed physical examination is to be performed 
if necessary according to symptoms the participant/participant’s parent(s)/LAR(s) has 
either recorded in the eDiary or reported. This is a physical examination that will include 
an examination of organ systems that are relevant to the investigator based only on 
review of the participant’s reported AEs and concomitant medication use. This 
assessment may include measurement of heart rate and temperature. It should be 
performed prior to the administration of study vaccine(s)/product and should be 
documented in source documents.  

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Should the physical assessment reveal any abnormal values or events, these must be 
documented in the eCRF AE Form. 
If the investigator determines that the participant’s health on the day of vaccination 
temporarily precludes vaccination, the visit will be rescheduled within the allowed 
interval between study visits (Table 4) (refer to Section 6.7). 
Treatment of any abnormality observed during this examination should be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider. Concomitant medications should be documented in the eCRF. 
8.3.3 
Pregnancy Test 
Female participants of childbearing potential must perform a urine pregnancy test prior to 
any study vaccine administration. Pregnancy testing must be performed even if the 
participant is menstruating at the time of the study visit. The study vaccine(s)/product 
may only be administered if the pregnancy test is negative.  
Refer to the Appendix 5 for the contraceptive guidance and information on study 
continuation for a participant who becomes pregnant during the study. 
8.3.4 
Warnings and Precautions to Vaccination 
Warnings and precautions to vaccination must be checked at the beginning of each 
vaccination visit prior to any study vaccine(s)/product administration.  
Please refer to the IB for MenABCWY and to the approved product label/package insert 
for the commercial Bexsero and Menveo vaccines. 
8.3.5 
Pre-vaccination Body Temperature 
The body temperature (preferably oral*) of each participant needs to be measured prior to 
any study vaccines administration. If the participant has fever, defined as body 
temperature ≥38.0°C/100.4°F regardless the location of measurement, on the day of 
vaccination, the vaccination visit will be rescheduled within the allowed interval for this 
visit (refer to Section 6.7). 
*Note: If the body temperature is measured by any other route (other than oral), this 
needs to be recorded in the participant’s eCRF. 
8.3.6 
Adverse Events 
8.3.6.1 
Time Period and Frequency for Collecting AE and SAE Information  
Solicited administration site and systemic events occurring during the 7 days (including 
the day of vaccination) following vaccination at Day 1 and Day 181, will be collected 
using a pre-defined participant eDiary (refer to the SoA [Table 3]). See Appendix 1, 

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Glossary of Terms, for definitions of various types of AEs and to Appendix 4 for further 
details on solicited AEs. Solicited administration site and systemic events that are 
ongoing after the 7-day reporting period will continue to be recorded in the eDiary until 
resolution or up to 30 days post-vaccination (i.e., recording period for unsolicited AEs) 
whichever occurs first and do not need to be entered as an AE in the AE eCRF or the 
participant’s source document. 
Any solicited AE that has not resolved within 30 days post-vaccination and is reported 
during clinic visits or safety follow-up calls will be entered into the subject’s eCRF as an 
unsolicited AE. It will also be included in the subject’s source documents at the site by 
the investigator/site staff as a verbally reported event. It will not be included in the 
Subject eDiary. These AEs will be analyzed as unsolicited AEs (i.e., in the Unsolicited 
Safety Set). 
Unsolicited AEs are AEs that are not solicited using a participant eDiary occurring during 
the 30 days (including the day of vaccination) following vaccination at Day 1 and 
Day 181 (refer to the SoA [Table 3]), and must be recorded in the appropriate section of 
the eCRF, irrespective of intensity or whether or not they are considered vaccination-
related. 
The time period for collecting and recording AEs leading to vaccine/study withdrawal, 
medically attended AEs, SAEs, pregnancies, and AESIs will begin at Day 1 (i.e., the first 
receipt of study vaccines) and will end 6 months following administration of the last dose 
of investigational vaccine for each participant (i.e., study end). Refer to Section 8.3.6.4 
for instructions on reporting of SAEs, pregnancies, and AESIs. 
In addition to the above-mentioned reporting requirements and in order to fulfill 
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 
consent until the participant is discharged from the study. Details regarding follow-up of 
AEs, SAEs, and AESIs are provided in Appendix 4. 
An overview of the protocol-required reporting periods for solicited administration site 
and systemic events, unsolicited AEs, medically attended AEs, AEs leading to 
vaccine/study withdrawal, SAEs, AESIs, SAEs related to study participation or 
concurrent GSK medication/vaccine and pregnancy is provided in Table 12. 

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Table 12 
Timeframes for Collecting and Reporting of Safety Information 
Time Points 
Pre- 
Vacc1 
Vacc 1 
Post- 
Vacc 1 
PC 
Post- 
Vacc 1 
PC 
 
Vacc 2 
Post- 
Vacc 2 
PC 
Post- 
Vacc 2 
PC 
PC 
Visit 
- 
V1 
 
T1 
V2 
T2 
 
V3 
 
T3 
V4 
T4 
T5 
ESFU 
Day 
- 
D1 
D72 
D15 
D313 
D91 
 
D181 
D1872 
D195 
D2113 
D271 
D361 
Month 
- 
M0 
M0 
 
M1 
M3 
- 
M6 
M6 
 
M7 
M9 
M12 
Solicited 
administration site 
and systemic 
events4,5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All unsolicited 
AEs4,6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to 
intervention/study 
withdrawal4,6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medically 
attended AEs4,6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs4,6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AESIs4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Time Points 
Pre- 
Vacc1 
Vacc 1 
Post- 
Vacc 1 
PC 
Post- 
Vacc 1 
PC 
 
Vacc 2 
Post- 
Vacc 2 
PC 
Post- 
Vacc 2 
PC 
PC 
Visit 
- 
V1 
 
T1 
V2 
T2 
 
V3 
 
T3 
V4 
T4 
T5 
ESFU 
Day 
- 
D1 
D72 
D15 
D313 
D91 
 
D181 
D1872 
D195 
D2113 
D271 
D361 
Month 
- 
M0 
M0 
 
M1 
M3 
- 
M6 
M6 
 
M7 
M9 
M12 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to 
study participation 
or concurrent GSK 
medication/vaccin
e4,6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs = adverse events; AESIs = adverse events of special interest; D = day; ESFU = extended safety follow-up; M = month; PC = phone contact; SAE = serious 
adverse event; T = telephone call; V = visit; Vacc = vaccination. 
1 Consent obtained. 
2 Seven consecutive days post-vaccination (including the day of vaccination). 
3 Thirty consecutive days post-vaccination (including the day of vaccination). 
4 All concomitant medications/products, except vitamins and dietary supplements, administered to treat an AE/SAE, occurred during the entire study period (Day 1 
to Day 361), should be recorded in the eCRF and participant’s medical records. 
5 All solicited administration site and systemic events that occur during the 7 days following administration of study vaccine at Visit 1 (Day 1) and Visit 3 
(Day 181). 
6 For coronavirus disease 2019 (COVID-19) related AEs/SAEs, follow routine AE/SAE collection and reporting processes as outlined in the protocol. 

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The investigator or investigator’s designee will record and immediately report all SAEs 
to IQVIA via the Expedited AE Reporting Form. This reporting should, under no 
circumstances, occur later than 24 hours after the investigator becomes aware of an SAE, 
as indicated in Appendix 4. The investigator will submit any updated SAE data to IQVIA 
within 24 hours of it being available. 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting periods defined in Table 12. Investigators are not obligated to actively seek AEs 
or SAEs in former study participants. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, and 
he/she considers the event to be reasonably related to the study vaccine(s)/product, the 
investigator will promptly notify IQVIA. 
The method of recording, evaluating, and assessing causality of AE and SAE and the 
procedures for completing and transmitting SAE reports are provided in Appendix 4. 
8.3.6.2 
Method of Detecting AEs and SAEs 
Methods of detecting and recording AE/SAE/AESI/pregnancies, and the assessment of 
AE/SAE intensity, causality and outcome are provided in Appendix 4. 
Open-ended and non-leading verbal questioning of the participants/participants’ 
parents/LARs is the preferred method of acquiring information related to an 
AE/SAE/AESI/pregnancy. 
8.3.6.3 
Follow-up of AEs and SAEs 
Instructions on follow-up of AEs and SAEs are provided in Appendix 4. 
8.3.6.4 
Regulatory Reporting Requirements for SAEs 
Once an investigator becomes aware that a study participant has experienced an 
SAE/AESI/pregnancy, he/she must report it to IQVIA within the timeframes provided in 
Table 13. This is essential for meeting legal obligations and ethical responsibilities for 
participant safety and the safety of a study intervention under clinical investigation. 
For SAEs/AESIs, the investigator will always provide an assessment of causality at the 
time of the initial report, as defined in the Appendix 4. 
Local regulatory requirements and sponsor’s policy for the preparation of an investigator 
safety report for suspected unexpected serious adverse reactions (SUSARs) must be 
followed. These reports will be forwarded to investigators as necessary. 
The sponsor has a legal responsibility to notify local authorities and other regulatory 
agencies about the safety of a study intervention under clinical investigation. The sponsor 

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will comply with country-specific regulatory requirements related to safety reporting to 
the regulatory authority, IRB/IEC, and investigators. 
Refer to Appendix 4 for further details regarding the reporting of 
SAEs/AESIs/pregnancies. 
Table 13 
Timeframes for Submitting SAEs, Pregnancies, and AESIs 
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAE 
24 hours1,2,3 
electronic Expedited 
AE Report 
24 hours1 
electronic Expedited AE 
Report 
Pregnancy 
24 hours1 
electronic Pregnancy 
Report 
24 hours 
electronic Pregnancy 
Report  
AESI 
24 hours2,4 
electronic Expedited 
AE Report 
24 hours1 
electronic Expedited AE 
Report 
AE = adverse event; AESI = adverse event of special interest; SAE = serious adverse event 
1 Timeframe allowed after receipt or awareness of the information by the investigator/study center staff. 
2 The investigator will be required to confirm review of the SAE/AESI causality by ticking the 
“reviewed” box in the electronic Expedited AE Report within 72 hours of submission of the 
SAE/AESI. 
3 For coronavirus disease 2019 (COVID-19) related SAEs, reports should be submitted following routine 
procedures for SAEs. 
4 Timeframe allowed once the investigator determines that the event meets the protocol definition of an 
AESI. 
8.3.6.5 
Treatment of Adverse Events 
Any medication administered for the treatment of an SAE/AESI should be recorded in the 
Expedited AE Report of the participant’s eCRF screen (refer to Appendix 4). 
8.3.6.6 
Participant Card 
The investigator or investigator’s designee must provide the participant/participant’s 
parent(s)/LAR(s) with a “participant card” containing information about the clinical 
study. The participant/participant’s parent(s)/LAR(s) must be instructed to keep the 
participant card in his/her/their possession at all times throughout the study. In an 
emergency, this card serves to inform the responsible attending 
physician/LAR/caregiver/family member that the participant is in a clinical study and that 
relevant information may be obtained by contacting the investigator. 

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8.3.7 
Treatment of Overdose 
8.3.7.1 
Vaccine Administration Error 
Vaccine administration error is defined as receiving a dose of study vaccine that was not 
reconstituted as instructed or administered by a different route from the intended route of 
administration. 
Any vaccine administration error detailed in this protocol must be reported as an AE, and 
if overdose is associated with an SAE, it must be reported as such within 24 hours to 
IQVIA. 
8.3.7.2 
Overdose of Study Vaccine 
An overdose of study vaccine (whether accidental or intentional) is defined when a 
dosage higher than the recommended dosage is administered in 1 dose of study vaccine 
MenABCWY and/or MenB and/or MenACWY. 
An overdose would also occur if 2 doses of the study vaccine are administered within 
2 weeks of the recommended interval between doses. 
Any overdose of study vaccine detailed in this protocol must be reported as an AE, and if 
overdose is associated with an SAE, it must be reported as such within 24 hours to the 
sponsor’s designee. 
8.3.8 
Medical Device Deficiencies 
The study interventions (MenABCWY and Bexsero) are combination products 
constituted of a device and biologic product (e.g., pre-filled syringes). Refer to 
Appendix 1 for the definition of a combination product and a medical device deficiency. 
8.3.8.1 
Detection, Follow-up and Prompt Reporting of Medical Device Deficiency 
The investigator is responsible for the detection, documentation and prompt reporting of 
any medical device deficiency occurring during the study to the sponsor’s designee. This 
applies to any medical device provided for the conduct of the study.  
Device deficiencies will be reported to the sponsor’s designee within 24 hours after the 
investigator determines that the event meets the protocol definition of a device 
deficiency. Refer to Appendix 4 for definitions and details on recording and reporting of 
these events.  
The investigator will ensure that follow-up includes any additional investigations to 
elucidate the nature and/or causality of the deficiency. Follow-up applies to all 
participants, including those who discontinue study intervention or the study. 

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New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator and reported to the sponsor’s designee 
within 24 hours. 
8.3.8.2 
Regulatory Reporting of Medical Device Deficiency When Used as 
Combination Product  
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal 
responsibility to notify appropriate regulatory authorities and other entities about certain 
safety information relating to medical devices being used in clinical studies. Refer to 
Appendix 4 for details of reporting. 
The investigator, or responsible person according to local requirements (e.g., the head of 
the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of device deficiencies to the IRB/IEC. 
8.4 
Pharmacokinetics 
Pharmacokinetic parameters will not be evaluated in this study. 
8.5 
Pharmacodynamics 
Pharmacodynamic parameters will not be evaluated in this study. 
8.6 
Genetics 
No samples will be collected during this study for genetic or pharmacogenetic research. 
8.7 
Biomarkers 
No biomarkers will be collected for pharmacogenetic research in this study. 
8.8 
Health Outcomes 
No economic health outcome measures will be collected in this study. 
8.9 
Study Procedures During Special Circumstances 
During special circumstances (e.g., coronavirus disease 2019 [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:  
• Safety follow-up may be made by a telephone call, other means of virtual contact 
or home visit, if appropriate. 

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• If an eDiary device was provided to the participant, it may be returned to the 
study center by conventional mail after the end of the relevant data collection 
period. 
• Visits for suspected AEs may take place in a different location* other than the 
study center or at participant’s home. If this is not feasible, then the medical 
evaluation of AEs may take place virtually with documentation of symptoms by 
other means of communication (e.g., phone call or videoconference), if possible. 
• Biological samples may be collected at a different location* other than the study 
center or at participant’s home. Biological samples should not be collected if they 
cannot be processed in a timely manner or appropriately stored until the intended 
use. 
*Note: It is the investigator’s responsibility to identify an alternate location. The 
investigator should ensure that this alternate location meets ICH Good Clinical Practice 
(GCP) requirements, such as adequate facilities to perform study procedures, 
appropriate training of the staff and documented delegation of responsibilities in this 
location. This alternate location should be covered by proper insurance for the conduct 
of study on participants by investigator and study center staff other than the designated 
study center. Refer to EMA Guidance on the Management of Clinical Trials during the 
COVID-19 pandemic (version 2, 27 March, 2020) for more details. 
Impact on the per protocol set (PPS) for immunogenicity will be determined on a case by 
case basis. 

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9.0 STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
The following study hypotheses are ordered into 2 families that will be tested in a fixed 
sequential design with full alpha propagation. Family 1 will be tested first and family 2 
will only be tested if the hypothesis in family one is successfully demonstrated.  
First Co-Primary Immunogenicity Objective (Family 1) 
The first co-primary immunogenicity objective is to demonstrate the immunological 
non-inferiority (NI) of the antibody response to MenABCWY vaccine, compared to 
MenACWY vaccine given to healthy participants, previously primed with MenACWY, 
as measured by percentage of participants with 4-fold rise in hSBA titer against each of 
the N. meningitidis serogroups A, C, W, and Y, at 1 month after the second MenABCWY 
vaccination and 1 month after the MenACWY vaccination (single dose). This translates 
to the following hypotheses: 
H0: 
(p1_MenABCWY(i) – p1_MenACWY(i) ≤−10% 
vs. 
H1: 
(p1_MenABCWY(i) – p1_MenACWY(i) >−10% 
Where  p1_MenABCWY(i) denotes the percentages of participants with 4-fold rise in 
hSBA titers for serogroups i=A, C, W, and Y, 1 month after the second vaccination of 
MenABCWY group and p1_MenACWY(i) denotes the percentages of participants with 
4-fold rise in hSBA titers for serogroups i=A, C, W, and Y, 1 month after the single 
vaccination of MenACWY group. 
NI criterion: Non-inferiority will be demonstrated if the lower limit of the two-sided 95% 
CI for the percent difference in the 4-fold rise in hSBA titers (p_MenABCWY– 
p_MenACWY) is above −10% for each serogroup A, C, W, and Y. 
Second Co-Primary Immunogenicity Objective (Family 2) 
The second co-primary immunogenicity objective is to demonstrate the immunological 
NI of the antibody response to MenABCWY vaccine, compared to MenACWY vaccine 
given to healthy participants, previously primed with MenACWY, as measured by 
percentage of participants with 4-fold rise in hSBA titer against each of the N. 
meningitidis serogroups A, C, W, and Y, at 1 month after the first MenABCWY 
vaccination and 1 month after the MenACWY vaccination (single dose). This translates 
to the following hypotheses: 
H0: 
(p2_MenABCWY(i) – p2_MenACWY(i) ≤−10% 
vs. 

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H1: 
(p2_MenABCWY(i) – p2_MenACWY(i) >−10% 
Where  p2_MenABCWY(i) denotes the percentages of participants with 4-fold rise in 
hSBA titers for serogroups i=A, C, W, and Y, 1 month after the first vaccination of 
MenABCWY group and p2_MenACWY(i) denotes the percentages of participants with 
4-fold rise in hSBA titers for serogroups i=A, C, W, and Y, 1 month after the single 
vaccination of MenACWY group. 
NI criterion: Non-inferiority will be demonstrated if the lower limit of the two-sided 95% 
CI for the percent difference in the 4-fold rise in hSBA titers (p_MenABCWY– 
p_MenACWY) is above −10% for each serogroup A, C, W, and Y. 
9.2 
Sample Size Determination  
The sample size calculation was based on data from the MenABCWY, V102_03E1 study 
after adjusting for the variabilities due to different settings of the study (e.g., differences 
in population, differences in antibody assays, and different strain for serogroup A) (Table 
14).  
Assuming that MenACWY group will induce a 4-fold rise in about 95% of the 
participants for each of the 4 serogroups; MenABCWY will induce a 4-fold rise in about 
91% of the participants for A and W serogroups, and 93% of the participants for C and Y 
serogroups; and using a 1-sided score test (Miettinen, 1985), non-inferiority margin of 
−10% and actual margins as given in Table 14, an estimated number of evaluable 
participants (n=542) and individual powers of 96.00%, 99.95%, 96.00%, and 99.95% for 
each A, C, W, and Y serogroup test, will give a global power of 90% to demonstrate NI 
of MenABCWY vs MenACWY. 
Family 1:  Assuming that MenABCWY and MenACWY groups will induce a 4-fold rise 
in about 95% of the participants for each of the 4 serogroups (Table 14), and using a 
1-sided score test (Miettinen, 1985), non-inferiority margin of −10% and actual margin of 
0%, an estimated number of evaluable participants (n = 225) and individual powers of 
99.87% for each A, C, W, and Y serogroup test, will give a global power of 99.48% to 
demonstrate non-inferiority of MenABCWY versus MenACWY. 
Family 2: Assuming that MenACWY group will induce a 4-fold rise in about 95% of the 
participants for each of the 4 serogroups; MenABCWY will induce a 4-fold rise in about 
91% of the participants for A and W serogroups, and 93% of the participants for C and Y 
serogroups; and, using a 1-sided score test (Miettinen, 1985), non-inferiority margin of 
−10% and actual margins as given in Table 14, an estimated evaluable participants 
(n=542) and individual powers of 96.00%, 99.95%, 96.00%, and 99.95% for each A, C, 
W, and Y serogroup test, will give a global power of 91% to demonstrate NI of 
MenABCWY versus MenACWY. 

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For the multiplicity adjustment, all hypotheses will be ranked into two families according 
to the following power of test: 
Table 14 
Power to Demonstrate Immunological Non-inferiority for Serogroups 
A, C, W, and Y of MenABCWY Compared to MenACWY (Primary) 
Serogroup 
4-fold rate  
4-fold rate 
MenABCWY 
NI 
margin 
Actual 
margin 
Power 
N  
MenACWY 
ABCWY/ 
  
ACWY 
Family 1: NI, 2-sided score test (Miettinen and Nurminen, 1985) 
A 
95% 
95% 
−10% 
0% 
99.87% 
225  
C 
95% 
95% 
−10% 
0% 
99.87% 
225  
W 
95% 
95% 
−10% 
0% 
99.87% 
225  
Y 
95% 
95% 
−10% 
0% 
99.87% 
225  
Global Power 
99.48% 
 
Family 2: NI, 2-sided score test (Miettinen and Nurminen, 1985) 
A 
95% 
91% 
−10% 
−4% 
96.00% 
542 
C 
95% 
93% 
−10% 
−2% 
99.95% 
542 
W 
95% 
91% 
−10% 
−4% 
96.00% 
542 
Y 
95% 
93% 
−10% 
−2% 
99.95% 
542 
Global Power 
91.00%   
n = number of participants; NI = non-inferiority 
Considering that approximately 10% of the selected participants might withdraw or not 
be evaluable for the immunogenicity objectives, the target sample size to be analyzed will 
be 270 participants per group and 603 participants per group for the first co-primary and 
the second co-primary objectives, respectively. 
Evaluable means all participants included in the set for the statistical analysis defined in 
Section 9.3. The sample size calculation was performed in PASS 12 (Hintze, 2013). The 
global power for all 4 strains across Family 1 and Family 2 is the product of individual 
powers. 
Approximately 1206 participants will be randomized in a 1:1 ratio to achieve 
1084 evaluable participants (542 per group).  
Withdrawals will not be replaced. 
9.3 
Populations for Analyses 
Populations for analyses in this study are defined in Table 15. 

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Table 15 
Populations for Analyses 
Analysis set 
Description 
Enrolled Set (Enr) 
Participant who agreed/participant for whom parent(s)/LAR(s) agreed 
to participate in a clinical study after completion of the informed 
consent process and randomized or received study intervention or 
undergone an invasive procedure. 
Exposed Set (ES)  
All participants who received at least 1 dose of the study intervention. 
The allocation in a group is done in function of all administered 
interventions. 
Full Analysis Set (FAS) 
All participant who received at least 1 dose of the study intervention 
and have post-vaccination immunogenicity data  
Per Protocol Set (PPS) 
All participants who received at least 1 dose of the study intervention 
to which they are randomized and have post-vaccination data (FAS) 
minus participants with protocol deviations that lead to exclusion 
from the PPS. 
Unsolicited Safety Set (USS) 
All participants who received at least 1 dose of the study intervention 
(ES) that report unsolicited AEs/report not having unsolicited AEs 
Solicited Safety Set (SSS) 
All participants who received at least 1 dose of the study intervention 
(ES) that report solicited safety data 
AE = adverse event; LAR = legally acceptable representative 
9.3.1 
Criteria for Elimination from Analysis  
If the participant meets 1 of the criteria mentioned in the Section 6.8, he/she may be 
eliminated from per protocol analysis. 
9.4 
Statistical Analyses 
The statistical analysis plan (SAP) will be finalized prior to First Participant First Visit; 
the SAP will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses of 
endpoints. 
9.4.1 
General Considerations 
Immunogenicity: 
• Non-inferiority criterion: NI will be demonstrated if, the lower limit of 2-sided 
95% confidence interval (CI) for the percent difference in 4-fold rise in hSBA 
titers (p_MenABCWY − p_MenACWY) is above −10%, for each N. meningitidis 
A, C, W, and Y serogroup. 
•  Fixed sequential testing with full alpha propagation in pre-ordered hypotheses 
families (Family 1 and Family 2, as defined in Section 9.1) will be applied. The 
assay cut-off values will be defined by the laboratory before analysis and will be 
documented in a protocol amendment.  

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• For the primary and secondary endpoints, the percentages of participants with 
hSBA titers ≥Lower Limit of Quantitation (LLOQ) and with a 4-fold rise in hSBA 
titers against each of the N. meningitidis serogroup B test strains and against 
N. meningitidis serogroups A, C, W, and Y will be determined. 
• For the serogroups A, C, W, Y and for each of the serogroup B indicator strains 
evaluation the 4-fold rise is defined as: 
− a post-vaccination hSBA titer ≥16 for participants with a pre-vaccination 
hSBA titer <4;  
− a post-vaccination hSBA titer ≥4 times the LLOQ for participants with a 
pre-vaccination hSBA titer ≥limit of detection (LOD) but <LLOQ; and,  
− a post-vaccination hSBA titer ≥4 times the pre-vaccination titer for 
participants with a pre-vaccination hSBA titer ≥LLOQ. 
• The geometric mean titers (GMTs)/geometric mean concentrations (GMCs) 
calculations are performed by taking the anti-log of the mean of the log titer 
transformations. Values to be used for the antibody concentrations/titers below the 
assay cut-off will be described in the SAP. 
• Handling of missing data will be discussed in the SAP. 
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 will be applied.  For the duration of such special circumstances, 
some measures may impact the data and analysis (e.g., missing visits, early study 
discontinuation, see Section 8.9). The impact will be determined on a case by case basis 
and the analysis methodology described in the SAP will account for such cases, if any. 
9.4.2 
Participants Disposition 
The number of enrolled, vaccinated (at least 1 vaccination, full vaccination course), 
completed participants, screening failures, reason for withdrawal, and reason for 
elimination from analysis sets, as well as number of participants in FAS and PPS will be 
reported by group for the enrolled analysis population. 
9.4.3 
Primary Endpoint(s) 
9.4.3.1 
Immunological Non-inferiority of MenABCWY vs. MenACWY 
Analysis set: The analysis of NI will be based on the PPS. 
Statistical method (Family 1): For each of the serogroups A, C, W, and Y, the 
percentages of participants with 4-fold rise (refer to Section 9.4.1), and the corresponding 
exact 2-sided 95% CIs based on Clopper-Pearson method (Clopper and Pearson, 1934) 
will be calculated for each study group at 1 month after the second vaccination. The 

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standardized asymptotic CIs between group differences in percentages will be derived 
using the method of Miettinen and Nurminen (Miettinen, 1985). 
NI criterion: Non-inferiority will be demonstrated if, the lower limit of 2-sided 95% CI 
for the percent difference in 4-fold rise in hSBA titers 
(p1_MenABCWY − p1_MenACWY) is above −10%, for each serogroup A, C, W, 
and Y. 
Statistical method (Family 2): For each of the serogroups A, C, W, and Y, the 
percentages of participants with 4-fold rise (refer to Section 9.4.1), and the corresponding 
exact 2-sided 95% CIs based on Clopper-Pearson method (Clopper and Pearson, 1934) 
will be calculated for each study group at 1 month after the first vaccination. The 
standardized asymptotic CIs between group differences in percentages will be derived 
using the method of Miettinen and Nurminen (Miettinen, 1985). 
NI criterion: Non-inferiority will be demonstrated if, the lower limit of 2-sided 95% CI 
for the percent difference in 4-fold rise in hSBA titers 
(p1_MenABCWY − p1_MenACWY) is above −10%, for each serogroup A, C, W, 
and Y. 
A sensitivity analysis including minimization factors as covariates will be performed 
using a logistic model and will be detailed in the SAP. 
9.4.3.2 
Safety Analysis 
Distribution of participants by vaccinations will be summarized by vaccine group for the 
exposed set. In case of vaccination error, participants will be analyzed “as treated” 
(according to the vaccine the participant actually received). 
The standard coding for medical history, AE, SAE, and concomitant medications data 
will be done by GSK Clinical Dictionary. The coded terms received from the sponsor will 
be merged into the appropriate datasets before the transfer to IQVIA for statistical 
analyses. 
9.4.3.2.1 
Solicited Events 
These analyses will be performed on the solicited safety set. 
The frequencies and percentages of participants with solicited administration site (i.e., 
injection site pain, erythema, swelling, induration) and systemic (i.e., fever [temperature 
≥38.0°C/100.4°F], nausea, fatigue, myalgia, arthralgia, headache) events during the 
7 days (including the day of vaccination) following each vaccination at Day 1 and 
Day 181 will be presented. 
All solicited administration site and systemic events will be summarized according to 
defined severity grading scales (Appendix 4). Frequencies and percentages of participants 

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experiencing each solicited administration site and systemic events will be presented for 
each symptom severity. Summary tables showing the occurrence of any solicited 
administration site or systemic event overall and at each time point will also be presented. 
Post-vaccination solicited AEs reported from Day 1 to Day 7 will be summarized for the 
intervals Day 1-3, Day 4-7, and Day 1-7 by maximal severity and by vaccine group, 
excluding the 30-minute measurement, which will be summarized separately. The 
severity of solicited administration events, including redness at injection site, swelling of 
skin at injection site, and hardness of skin at injection site will be summarized according 
to categories described in Appendix 4. 
Injection site and systemic reactions (except fever) occurring up to 7 days after each 
study vaccination (Day 1 and Day 181), will be summarized according to “mild”, 
“moderate” or “severe” as described in Appendix 4. 
Each solicited administration site and systemic event will also be further summarized as 
“none” versus “any” (for fever the latter will be ≥38.0°C/100.4°F). 
Use of antipyretics and analgesics will be summarized by frequency by type of use 
(prophylactic versus treatment) and percentage of participants reporting use. 
Body temperature will be summarized by 0.5°C/32.9°F increments from 36.0°C/96.8°F 
up to ≥40°C/104°F and will be broken down according by route of measurement, if 
applicable. Frequencies and percentages of participants with temperatures 
≥38.0°C/100.4°F and temperatures ≥40.0°C/104°F will also be presented. 
9.4.3.2.2 
Unsolicited AEs 
These analyses will be performed on the unsolicited safety set. 
The frequencies and percentages of participants with any unsolicited AEs (including all 
SAEs, AEs leading to withdrawal, AESIs and medically attended AEs [see all relevant 
AE definitions in Appendix 1, Glossary of Terms]) during the 7 and the 30 days 
(including the day of vaccination) following vaccination at Day 1 and Day 181 will be 
presented. 
The frequencies and percentages of participants with SAEs, AEs leading to withdrawal, 
AESIs and medically attended AEs throughout the study period will be presented. 
This analysis applies to all AEs occurring during the study, judged either as probably 
related, possibly related or not related to vaccination by the investigator, recorded in AE 
eCRF, with a start date on or after the date of first vaccination (Table 12). AE starting 
prior to the first vaccination will only be listed. The original verbatim terms used by 
investigators to identify AEs in the eCRFs will be mapped to preferred terms (PTs) using 
the Medical Dictionary for Regulatory Activities (MedDRA) dictionary. The AEs will 

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then be grouped by MedDRA PTs into frequency tables according to system organ class 
(SOC). 
All reported AEs, as well as AEs judged by the investigator as related to study vaccine, 
will be summarized according to SOC and PT within SOC. These summaries will be 
presented by vaccine group and by interval of study observation. When an AE occurs 
more than once for a participant, the maximal severity and strongest relationship to the 
vaccine group will be counted. 
Separate summaries will be produced for the following categories: 
• SAE 
• AE related to vaccine 
• AESI 
• AE leading to withdrawal 
• AE leading to a medically attended visit 
Data listings of all AEs will be provided by participant. In addition, AEs in the categories 
above will be provided as listed data. 
9.4.4 
Secondary Endpoints 
9.4.4.1 
Immune Response N. Meningitidis Serogroups A, C, W, and Y (Measured 
by hSBA)  
Analysis set: The analysis will be based on the FAS. 
Statistical method: For each of the 4 N. meningitidis serogroups A, C, W, and Y the 
percentages of participants with hSBA titers ≥LLOQ and the corresponding exact 2-sided 
95% CIs based on Clopper-Pearson method (Clopper and Pearson, 1934) will be 
calculated for ABCWY and ACWY study groups. Refer to Section 9.4.3.1 for the 
definition of 4-fold rise for the Men A, C, W, and Y evaluation. 
Geometric mean titers and associated 2-sided 95% CIs will be computed for each group 
and for each strain at each visit. The titers at baseline (Day 1, Month 0), at 1 month after 
the first (Day 31, Month 1) and the last vaccination (Day 211, Month 7) for the ABCWY 
group, and at 1 month after the single MenACWY vaccination (Day 31, Month 1) in the 
ACWY group, will be logarithmically transformed (base10) to fulfill the normal 
distribution assumption. 
Geometric mean titers and 95% CIs will be calculated by exponentiating (base 10) the 
least squares means and the lower and upper limits of the 95% CIs of the log-transformed 
titers (base10) obtained from a 2-way Analysis of covariance (ANCOVA) with factors 
for vaccine group and country. The ANCOVA will include baseline titers as covariate, 
and it will be performed to take into consideration the possible effect of these on the 
post-vaccination titers. 

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Geometric mean ratios (GMRs) (post-vaccination/baseline titer) and associated 2-sided 
95% CIs will be computed for each group and for each strain at each visit. Geometric 
mean ratios will be calculated by exponentiating (base10) the least squares means and the 
lower and upper limits of the 95% CIs of the log-transformed titers (base10) obtained 
from a 2-way ANOVA with factors for vaccine group and country. 
Additionally, GMTs and GMRs group ratios between the 2 intervention groups and their 
respective 95% CIs will be computed by exponentiating the difference of the least square 
means of the log-transformed titers and the lower and upper limits of the 95% CIs on the 
difference obtained from the ANCOVA/ANOVA model above. 
9.4.4.2 
Immune Response – N. Meningitidis Serogroup B Indicator Strains 
(Measured by hSBA) 
Analysis set: The analysis will be based on the FAS. 
Statistical method: For each of N. meningitidis B indicator strain (M14459 for factor H 
binding protein [fHbp] antigen, M13520 for Neisseria Heparin Binding Antigen (NHBA) 
antigen, 96217 for Neisseria adhesin A (NadA) antigen and NZ98/254 for PorA P1.4 
antigen) the percentages of participantVZLWKK6%$WLWHUV//24DQGRIparticipants with 
4-fold rise (refer to Section 9.4.1), and the corresponding exact 2-sided 95% CIs based on 
Clopper-Pearson method will be calculated for MenABCWY study group at 1 month 
after the last MenABCWY vaccination . 
A composite endpoint defined as the percentage of participantVZLWKK6%$WLWHUV//24
for all (4) N. meningitidis B indicator strains will be derived.  For this composite 
endpoint, the percentage of participants ZLWKK6%$WLWHUV//24for all (4) B indicator 
strains and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method 
will be calculated for MenABCWY study group at 1 month after the last MenABCWY 
vaccination. 
Geometric mean titers and GMRs, and associated 2-sided 95% CIs will be computed for 
each strain at each visit. The hSBA titers at baseline (Day 1, Month 0), and the hSBA 
titers at 1 month after the last vaccination (Day 211, Month 7) for the ABCWY group, 
will be logarithmically transformed (base10) to fulfill the normal distribution assumption.  
CCI

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CCI

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9.4.6 
Other Analyses 
No other analyses are planned. 
9.4.6.1 
Demography and Baseline Characteristics Analyses 
Descriptive statistics (mean, standard deviation [SD], median, minimum and maximum) 
for age, height, weight, and body mass index will be calculated overall and by vaccine 
group. 
Distributions of participants by sex, race, and ethnic origin will be summarized overall 
and by vaccine group. 
Demography will be done for the FAS and PPS. 
9.5 
Interim Analyses  
An interim analysis of safety objectives may be conducted after at least 50% of 
participants have completed Visit 4. An interim analysis of immunological objectives 
may also be performed after all participants have completed Visit 4. If performed, the 
assessment of the primary immunological objectives will follow the order described in 
Section 9.4.3.1 with analysis of family 1 preceding that of family 2. The final study report 
will contain the final analyses of all primary and secondary endpoints and made available 
to the investigators. 
9.5.1 
Sequence of Analyses 
The interim analysis for the evaluation of the co-primary objectives will respect the 
hierarchical order described in Section 9.4.3.1. 
9.5.2 
Statistical Consideration for Interim Analysis 
No changes in statistical methodology for the immunological and safety objectives are 
foreseen compared to what is planned for the final analysis.  
Data for the interim analysis may be analyzed by an independent unblinded group; if so, 
only group unblinded results will be presented. 
9.6 
Data Monitoring Committee 
Not applicable. 

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10.0 REFERENCES 
• Center for Disease Control (CDC). Enhanced meningococcal disease surveillance 
report, 2018. CDC; 2018 [cited 20-DEC-2019]. Available from 
https://www.cdc.gov/meningococcal/downloads/NCIRD-EMS-Report-2018.pdf  
• Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the 
case of binomial. Biometrika. 1934; 26:404-413. 
• Cohn AC, Macneil JR, Clark TA, et al. Prevention and control of meningococcal 
disease: recommendations of the Advisory Committee on Immunization Practices 
(ACIP). MMWR Recomm Rep. 2013;62, 1-28. 
• Cohn A and Macneil J. The Changing Epidemiology of Meningococcal Disease. 
Infectious Disease Clinics of North America. 2015; 29, 667-677. 
• Crum-Cianflone N, Sullivan E. Meningococcal Vaccinations. Infect Dis 
Ther.2016;5(2):89‐112. 
• European Centre for Disease Prevention and Control (ECDC). Annual 
Epidemiological Report 2016 – Invasive meningococcal disease. [Internet]. 
Stockholm: ECDC; 2016 [cited 09-DEC-2019]. Available from 
https://ecdc.europa.eu/sites/portal/files/documents/Invasive%20meningococcal%2
0disease%20AER.pdf 
• Gossger N, Snape MD, Yu L-M et al. Immunogenicity and tolerability of 
recombinant serogroup B meningococcal vaccine administered with or without 
routine infant vaccinations according to different immunization schedules. JAMA: 
The Journal of the American Medical Association 2012;307(6):573–82. 
• Hintze, J. (2013). PASS 12. NCSS, LLC. Kaysville, Utah, USA. www.ncss.com.  
• ICH Harmonised Tripartite ICH Guideline for Good Clinical Practices E6 (R1). 
1997 Federal Register, 62 (90):25691-25709 
• Miettinen O., Nurminen M. Comparative analysis of 2 rates. Statistics in Medicine 
1985; 4(2):213-26. 
• Rosenstein NE, Perkins BA, Stephens DS, et al. Meningococcal disease. N Engl J 
Med. 2001; 344: 1378-88. 
• Sáez-Llorens X et al. Four-year antibody persistence and response to a booster 
dose of a pentavalent MenABCWY vaccine administered to healthy adolescents 
and young adults. Hum Vaccin Immunother. 2018;14(5):1161-74. 
• Szenborn L, Block SL, Jackowska T et al. Immune responses to booster 
vaccination with meningococcal ABCWY vaccine after primary vaccination with 
either investigational or licensed vaccines. Pediatr Infect Dis J 2018;37:475–82. 

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11.0 APPENDICES 

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Appendix 1 
Abbreviations and Glossary of Terms 
Abbreviations 
Abbreviation 
Definition 
ACIP 
Advisory Committee on Immunization Practices 
AE 
Adverse event 
ADE 
Adverse device effect 
AESI 
Adverse event of special interest 
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CLS 
Clinical Laboratory Sciences 
COVID-19 
Coronavirus disease 2019 
CRM 
Cross-reacting Material 
CSR 
Clinical Study Report 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture System 
eDiary 
Participant Diary (Electronic Diary) 
ES 
Exposed Set 
ELISA 
Enzyme-linked immunosorbent assay 
Enr 
Enrolled Set 
EoS 
End of Study 
EU 
European Union 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
fHbp 
Factor H binding protein 
GCP 
Good Clinical Practice 
GMC 
Geometric mean concentration 
GMR 
Geometric mean ratio 
GMT 
Geometric mean titer 
GSK 
GlaxoSmithKline 
HRT 
Hormone replacement therapy 
hSBA 
Human Serum Bactericidal Assay 
IB 
Investigator’s Brochure 

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Abbreviation 
Definition 
IAF 
Informed Assent Form 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation 
IEC 
Independent Ethics Committee 
IMD 
Invasive meningococcal disease 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IVRS 
Interactive Voice Response System 
LAR 
Legally acceptable representative 
LLOQ 
Lower limit of quantitation 
LOD 
Limit of detection 
LSLV 
Last Participant Last Visit 
M 
Month 
MedDRA 
Medical Dictionary for Regulatory Activities 
MenABCWY 
Meningococcal serogroups A, B, C, W, and Y investigational 
vaccine 
MenACWY 
Meningococcal serogroups A, C, W, and Y conjugate vaccine 
MenB 
Meningitis B 
NadA 
Neisseria adhesin A 
NHBA 
Neisseria Heparin Binding Antigen 
NI 
Non-inferiority 
NZ 
New Zealand 
OMV 
Outer membrane vesicles 
PCD 
Primary completion date 
pIMD 
Potential immune-mediated disease 
PT 
Preferred term 
PorA 
Porin A 
PPS 
Per Protocol Set 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SoA 
Schedule of Activities 
SOC 
System organ class 
SSS 
Solicited Safety Set 
SUSAR 
Suspected unexpected serious adverse reaction 

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Abbreviation 
Definition 
T 
Telephone contact 
USADE 
Unexpected serious adverse device effect 
US 
United States (of America) 
USS 
Unsolicited Safety Set 
V 
Visit 
Glossary of Terms 
Term 
Definition 
Blinding 
A procedure in which 1 or more parties to the study are 
kept unaware of the intervention assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
study, 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 
observer-blind study, the participant, the study center and 
sponsor or sponsor’s designee’s personnel involved in the 
clinical evaluation of the participants are blinded while 
other study personnel may be aware of the treatment 
assignment.  
Caregiver 
A “caregiver” is someone who lives in the close 
surroundings of a participant and has a continuous caring 
role or has substantial periods of contact with a participant 
and is engaged in his/her daily health care (e.g., a relative 
of the participant, a nurse who helps with daily activities 
in case of residence in a nursing home). 
In the context of a clinical study, a caregiver could include 
an individual appointed to oversee and support the 
participant's compliance with protocol specified 
procedures. 
Child in care 
A child who has been placed under the control or 
protection of an agency, organization, institution or entity 
by the courts, the government or a government body, 
acting in accordance with powers conferred on them by 
law or regulation. The definition of a child in care can 
include a child cared for by foster parents or living in a 
care home or institution, provided that the arrangement 

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falls within the definition above. The definition of a child 
in care does not include a child who is adopted. 
Combination product 
Combination product comprises any combination of  
• drug  
• device  
• biological product  
Each drug, device, and biological product included in a 
combination product is a constituent part. 
Eligible (participant) 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrolled (participant) 
“Enrolled” means a participant’s/participant’s 
parent(s)’/LAR(s)’ agreement to participate in a clinical 
study following completion of the informed consent 
process. Potential participants who are screened for the 
purpose of determining eligibility for the study, but do not 
participate in the study, are not considered enrolled, 
unless otherwise specified by the protocol. Refer to the 
Section 9.3 for the definition of “enrolled” applicable to 
the study. 
Essential documents 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of the 
data produced. 
Evaluable (participant) 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis. Refer to Section 9.3 
for details on criteria for evaluability. 
Immunological correlate 
of protection 
A correlate of risk that has been validated to predict a 
certain level of protection from the targeted endpoint. 
Intervention 
Term used throughout the clinical study to denote a set of 
investigational product or marketed product or placebo 
intended to be administered to a participant. 
Investigational 
vaccine/product 
 
A pharmaceutical form of an active ingredient being 
tested in a clinical study, including a product with a 
marketing authorization 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. 
Investigator 
A person responsible for the conduct of the clinical study 
at a study center. If a study is conducted by a team of 

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individuals at a study center, the investigator is the 
responsible leader of the team and may be called the 
principal investigator.  
The investigator can delegate study-related duties and 
functions conducted at the study center to qualified 
individual or party to perform those study-related duties 
and functions. 
Interactive voice response 
system (IVRS) 
The software that enables the randomizing of participants 
into clinical trials and allocation of the study product to 
them in a blinded fashion. This technology allows study 
centers to interact with a database by pressing keypad 
buttons on a phone and following voice prompts in order 
to enter in information. 
Legally acceptable 
representative 
An individual or juridical or other body authorized under 
applicable law to consent, on behalf of a prospective 
participant, to the participant's participation in the clinical 
study. 
The terms legal representative, legally authorized 
representative are used in some settings. 
Medical device 
deficiency: 
A device deficiency is an inadequacy of a medical device 
with respect to its identity, quality, durability, reliability, 
safety, or performance. Device deficiencies include 
malfunctions, use errors and information supplied by the 
manufacturer. 
Medically attended AEs 
Symptoms or illnesses requiring hospitalization, or 
emergency room visit, or visit to/by a health care 
provider.  
Study/Site Monitor 
An individual assigned by the sponsor or sponsor’s 
designee and responsible for assuring proper conduct of 
clinical studies at 1 or more study centers. The terms 
Clinical Research Monitor and Clinical Research 
Associate are used in some settings. 
Participant 
Term used throughout the protocol to denote an individual 
who has been contacted to participate or participates in the 
clinical study, either as a recipient of the 
vaccine(s)/product or as a control. 
Synonym: participant 
Participant number 
A unique identification number assigned to each 
participant who consents to participate in the study. 

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Primary completion date 
(PCD) 
The date that the final participant was examined or 
received an intervention for the purpose of final collection 
of data for all primary outcomes, whether the clinical 
study was concluded according to the pre-specified 
protocol or was terminated. 
Protocol amendment 
The International Council on Harmonisation (ICH) 
defines a protocol amendment as “A written description of 
a change(s) to or formal clarification of a protocol.” GSK 
further details this to include a change to an approved 
protocol that affects the safety of participants, scope of the 
investigation, study design, or scientific integrity of the 
study. 
Qualified health care 
professional 
Term used to refer to any licensed or certified health care 
professional who is permitted by institutional policy to 
perform protocol required procedures, and who is 
identified within the Study Staff Signature Log.  
Randomization 
Process of random attribution of intervention to 
participants to reduce selection bias. 
Self-contained study 
Study with objectives not linked to the data of another 
study. 
Solicited event 
Events to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the participant or an observer 
during a specified post-vaccination follow-up period. 
Source data 
All information in original records and certified copies of 
original records of clinical findings, observations, or other 
activities in a clinical study necessary for the 
reconstruction and evaluation of the study. Source data are 
contained in source documents (original records or 
certified copies). A certified copy is a copy (irrespective 
of the type of media used) of the original record that has 
been verified (i.e., by a dated signature or by generation 
through a validated process) to have the same information, 
including data that describe the context, content, and 
structure, as the original. 
Source documents 
Original legible documents, data, and records (e.g., 
hospital records, clinical and office charts, laboratory 
notes, memoranda, participants' diaries or evaluation 
checklists, pharmacy dispensing records, recorded data 
from automated instruments, copies or transcriptions 

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certified after verification as being accurate copies, 
microfiches, photographic negatives, microfilm or 
magnetic media, X-rays, participant files, and records kept 
at the pharmacy, at the laboratories and at medico-
technical departments involved in the clinical study). 
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 
study that evaluates the use of an investigational 
vaccine/product. 
Treatment 
Term used throughout the clinical study to denote a set of 
investigational product or marketed product or placebo 
intended to be administered to a participant. 
Treatment number 
A number identifying intervention given to a participant, 
according to intervention allocation. 
Unsolicited adverse event 
Any AE reported in addition to those solicited during the 
clinical study. Also, any “solicited” symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited AE. 
Witness (impartial 
witness) 
The witness is an individual independent of the study, 
whose role is to attend the informed consent process if the 
participant/participant’s parent(s)/LAR(s) cannot read. 
The witness reads the documents supplied to the 
participant/participant’s parent(s)/LAR(s) and signs them 
after the participant/participant’s parent(s)/LAR(s) 
sign/thumb print the applicable documents. The witness 
cannot in any way influence participant’s/participant’s 
parent(s)’/LAR(s)’ decision to participate in the study. 
 

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Appendix 2 
Regulatory, Ethical, and Study Oversight 
Considerations 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with: 
− Consensus ethical principles derived from international guidelines including 
the Declaration of Helsinki and Council for International Organisations of 
Medical Sciences (CIOMS) International Ethical Guidelines 
− Applicable ICH GCP Guidelines 
− Applicable laws and regulations 
• The protocol, protocol amendments, ICF and Informed Assent Form (IAF) if 
applicable, IB, and other relevant documents (e.g., advertisements) must be 
submitted to an IRB/IEC by the investigator for review and approval. These 
documents will be signed and dated by the investigator before the study is 
initiated. 
• Any protocol amendments will require IEC/IRB approval before implementation 
of changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants.  
• IQVIA will provide full details of the above procedures to the investigator, either 
verbally, in writing, or both. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/IEC. 
− Notifying the IRB/IEC of SAE(s) or other significant safety findings as 
required by IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the study center and 
adherence to requirements of Code of Federal Regulations Title 21 (21 CFR), 
ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical 
studies (if applicable), and all other applicable local regulations. 
• After reading the protocol, each investigator will sign the protocol signature page 
(Appendix 8) and send a copy of the signed page to IQVIA. The study will not 
start at any study center at which the investigator has not signed the protocol. 
Financial Disclosure 
Investigators and sub-investigators will provide IQVIA with sufficient, accurate financial 
information as requested to allow the sponsor or IQVIA to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing financial interest information prior to initiation 

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of the study center. Investigators are responsible for providing the financial information 
update if their financial interests change at any point during their participation in a study 
and for 1 year after completion of the study. 
Insurance 
Sponsor will provide insurance in accordance with local guidelines and requirements as a 
minimum for the participants in this study. The terms of the insurance will be kept in the 
study files. 
Informed Consent and Assent Process 
• The investigator or his/her representative will explain the nature of the study to 
the participant/participant’s parent(s)/LAR(s) and answer all questions regarding 
the study. 
• Participant/participant/s parent(s)/LAR(s) must be informed that their 
participation is voluntary. Participants/participants’ parents/LARs will be required 
to sign a statement of informed consent or assent (if applicable) that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, and 
the IRB/IEC. 
• The medical record must include a statement that informed consent and assent (if 
applicable) was obtained before the participant was enrolled in the study and the 
date the written consent and assent (if applicable) was obtained. The authorized 
person obtaining the informed consent and assent (if applicable) must also sign 
the ICF. 
• Participants must be re-consented to the most current version of the ICF(s) and 
assent form(s) during their participation in the study. 
• A copy of the ICF(s) and assent form(s) (if applicable) must be provided to the 
participant participants’ parent(s)/LAR(s). 
• Re-consent must be obtained in accordance with local laws and regulations for 
participants who become legally emancipated during the study, i.e. reach the legal 
age of consent. The participant can provide consent by signing/witnessing/thumb 
printing an ICF, similar to that provided to the parent(s)/LAR(s) at study start, 
which summarizes the study and includes a consent statement and documents that 
the participant agrees to continue participating in the study. 
Responsibilities of the Investigator and IRB/EC 
The protocol and the proposed informed consent form must be reviewed and approved by 
a properly constituted IRB/EC before study start. Properly constituted IRB/EC is defined 
in ICH Guideline for GCP E6 (R1), Section 3 (ICH, 1997). A signed and dated statement 
that the protocol and informed consent have been approved by the IEC/IRB must be 
given to IQVIA before study initiation. Prior to study start and at any time the protocol is 

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amended during study conduct, the investigator is required to sign a protocol signature 
page confirming his/her agreement to conduct the study in accordance with these 
documents and all of the instructions and procedures found in this protocol and to give 
access to all relevant data and records to the Medical Monitor, auditors, GSK Clinical 
Quality Assurance representatives, designated agents of GSK, IEC/IRB, and regulatory 
authorities as required. If an inspection of the study center is requested by a regulatory 
authority, the investigator must inform IQVIA immediately that this request has been 
made. 
The investigator also responsible for the following: 
• Maintaining a list of appropriately qualified persons to whom the investigator has 
delegated significant study-related duties. 
• Demonstrating the capability of recruiting the required number of suitable 
participants within the recruitment period. 
• Demonstrating sufficient time and staffing to properly conduct and complete the 
study within the agreed study period. 
• Ensuring that all persons assisting with the study are adequately informed about 
the protocol, the investigational product, and their study-related duties and 
functions 
• Ensuring that appropriately trained health care professionals are responsible for 
all study-related medical decisions and for ensuring appropriate medical care of 
participants experiencing any adverse event related to the study. 
• If permission to do so is given by the participant and/or participant’s 
parent(s)/LAR(s), ensuring that the participant’s primary health care provider is 
informed of the participant’s participation in the study. 
The investigator should not implement any deviation from, or changes of the protocol 
without agreement by the sponsor and prior review and documented approval/favorable 
opinion from the IEC/IRB of an amendment, except where necessary to eliminate an 
immediate hazard to study participants, or when the change involves only logistical or 
administrative aspects. In addition, the investigator, or person designated by the 
investigator, should document and explain any deviation from the approved protocol. 
The investigator may implement a deviation from, or a change of, the protocol to 
eliminate an immediate hazard(s) to study participants without prior IEC/IRB 
approval/favorable opinion. As soon as possible, the implemented deviation or change, 
the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be 
submitted: 
• to the IEC/IRB for review and approval/favorable opinion,  
• to the sponsor for agreement and, if required, 
• to the regulatory authority(ies). 

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Administrative Structure 
Table 16 
Study Administrative Structure 
Function 
Responsible Organization 
Study Operations Management 
Medical Monitoring, Study Master File 
IQVIA 
Randomization, Blinding, Unblinding 
Cenduit 
Clinical Supply Management, Quality Assurance 
Auditing 
GSK 
Biostatistics, Medical Writing 
IQVIA 
Laboratory Assessments 
GSK 
Medical Monitor 
Refer to the study reference manual. 
Dissemination of Clinical Study Data 
• The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study register in compliance with 
the applicable regulations/GSK policy. GSK will aim to register protocols 
summaries prior to study start and target results summaries submission within 
12 months of primary completion date. Where external regulations require earlier 
disclosure, GSK will follow those timelines.  
• Where required by regulation, summaries will also be posted on applicable 
national or regional clinical study registers. 
• Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the study report, and provided reasonable 
access to statistical tables, figures, and relevant reports. IQVIA 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 participants, as 
appropriate. 
• IQVIA will provide the investigator with the randomization codes for their study 
center only after completion of the full statistical analysis. 
• GSK intends to make anonymized patient-level data from this study available to 
external researchers for scientific analyses or to conduct further research that can 
help advance medical science or improve patient care. This helps ensure the data 
provided by study participants are used to maximum effect in the creation of 
knowledge and understanding. 

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Data Quality Assurance 
• The investigator should maintain a record of the location(s) of their respective 
essential documents including source documents (see Appendix 1, Glossary of 
Terms, for definitions of essential documents and source documents). The storage 
system used during the study and for archiving (irrespective of the type of media 
used) should provide for document identification, version history, search, and 
retrieval.  
• Essential study documents may be added or removed where justified (in advance 
of study initiation) based on their importance and relevance to the study. When a 
copy is used to replace an original document (e.g., source documents, eCRF), the 
copy should fulfill the requirements for certified copies.  
• All participant data relating to the study will be recorded on eCRF (or printed 
CRF in case of an electronic data capture system [EDC] failure) unless 
transmitted to the sponsor or IQVIA electronically (e.g., laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct 
by physically or electronically signing the eCRF.  
• The investigator must maintain adequate and accurate source documents and 
study records that include all pertinent observations on each of the study center’s 
participants that supports information entered in the eCRF.  
• The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source documents 
or certified copies.  
• IQVIA is responsible for the data management of this study including quality 
checking of the source data.  
• Study/Site Monitors (see a definition in Appendix 1, Glossary of Terms) will 
perform ongoing source data verification to confirm that data entered into the 
eCRF by authorized study center personnel are attributable, legible, 
contemporaneous, original, accurate, and complete. Changes to source data should 
be traceable, should not obscure the original entry, and should be explained if 
necessary (e.g., via an audit trail). The safety and rights of participants must be 
protected and study be conducted in accordance with the currently approved 
protocol and any other study agreements, ICH GCP, and all applicable regulatory 
requirements.  
• Study records and source documents, including signed ICF/IAF (as applicable), 
pertaining to the conduct of this study must be retained by the investigator for 
25 years from the issue of the final CSR/equivalent summary unless local 
regulations or institutional policies require a longer retention period. No records 
may be destroyed during the retention period without the written approval from 
the sponsor. No records may be transferred to another location or party without 
written notification to the sponsor or IQVIA. 

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Source Documents 
• Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Investigator should maintain a 
record of the location(s) of their source documents.  
• Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, 
depending on the study. Also, current medical records must be available. 
• Definition of what constitutes source data and source documents can be found in 
the Appendix 1, Glossary of Terms. 
Study and Study Center Closure 
IQVIA reserves the right to close the study center or terminate the study at any time for 
any reason at the sole discretion of the sponsor, provided there is sufficient notice given 
to account for participant’s safe exit from study participation. Study center regular 
closure will occur upon study completion. A study center is considered closed when all 
required data/documents and study supplies have been collected and a study center 
closure visit has been performed.  
The investigator may initiate study center closure at any time, provided there is 
reasonable cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study center by IQVIA/GSK or investigator may 
include but are not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the investigator 
• Discontinuation of further study intervention development 
• Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, IQVIA shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, for the reason for termination or 
suspension, as specified by the applicable regulatory requirements. The investigator shall 
promptly inform the participants and should assure appropriate participant therapy and/or 
follow-up. 
Publication Policy 
The sponsor aims to submit for publication the results of the study in searchable, peer 
reviewed scientific literature within 18 months from LSLV for interventional studies and 
follows authorship and other guidance from the International Committee of Medical 
Journal Editors. 

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Appendix 3 
Clinical Laboratory Tests  
Protocol-required Safety Laboratory Assessments 
A urine pregnancy test will be conducted as needed for women of childbearing potential. 
Laboratory Assays 
MenACWY Serum Bactericidal Assays Using Human Complement (hSBA)  
The induction of functional anti-meningococcal activity by bactericidal antibodies 
directed against N. meningitidis serogroups A, C, W, and Y will be also determined by 
hSBA using a new format, so-called agar overlay hSBA, using a higher throughput 
colony counting method compared to the manual hSBA based on the Tilt method. 
This new hSBA is also based on the measurement of human complement-dependent 
bactericidal killing of meningococci. As with all functional hSBAs, the assay includes a 
first step of heat inactivation of the human serum samples to inactivate the endogenous 
complement, followed by serial dilution of the serum samples in which a fixed amount of 
bacteria and of human exogenous complement are added. The reactions are incubated to 
allow the association of meningococcal specific antibodies and their target antigen. The 
antibody-antigen complex activates the classical pathway of complement which 
ultimately results in bacterial lysis. 
As a measure of the meningococcal specific antibody titer of each serum sample, the 
MenACWY agar-overlay hSBA follows the principle of detecting and counting the 
surviving meningococcal bacteria after bacterial growth within solid agar media, using an 
automatic colony counter (AxioLab Image Analysis System – detection of 
colony-forming units). 
MenACWY IgG ELISA 
• The anti-MenACWY total IgG antibody concentrations will be measured by using 
an Enzyme-Linked Immunosorbent Assay (ELISA) or equivalent to evaluate the 
immunogenicity of the capsular polysaccharides of serogroups A, C, W, and Y in 
MenACWY vaccine. 
• The assay characteristics (e.g., validated assay cut-offs and units) for each of the 
serogroup will be determined at the time of the generation of validation data. Any 
change, including the change of the format of the assay, will be documented in a 
protocol amendment. 
MenB Serum Bactericidal Assays Using Human Complement (hSBA) 
Serum bactericidal activity against MenB will be determined by using a validated manual 
(Tilt-based) hSBA against a standard panel consisting of 4 meningococcal B indicator 

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strains M14459, 96217, NZ98/254 and M13520. Each of these strains measures 
bactericidal activity primarily directed against one of the major bactericidal antigens 
included in the vaccine: strain M14459 measures hSBA against the 741 part of the 
936-741 antigen, also known as fHbp variant 1.1; strain 96217 measures hSBA against 
antigen 961c, also known as NadA; strain NZ98/254 measures hSBA against PorA P1.4, 
the immunodominant antigen in the OMV NZ vaccine component; strain M13520 
measures hSBA against the 287 part of the 287-953 antigen, also known as NHBA. 
CCI

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Appendix 4 
Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
Definitions of AEs 
Adverse Events 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally 
associated with the use of study intervention, whether or not considered related to the study 
intervention. 
Note: 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 study 
intervention. 
 
Events Meeting the AE Definition 
• 
Significant or unexpected worsening or exacerbation of the condition/indication under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study vaccine(s)/product administration even though 
they may have been present prior to the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study vaccine(s)/product 
or a concurrent medication (overdose per se should not be reported as an AE/SAE). 
• 
Signs or symptoms temporally associated with study vaccine(s)/product administration. 
• 
Signs, symptoms that require medical attention (e.g., hospital stays, physician visits and emergency 
room visits). 
• 
Significant failure of an expected pharmacologic or biological action.  
• 
Pre- or post-intervention events that occur as a result of protocol-mandated procedures (i.e., invasive 
procedures, modification of participant’s previous therapeutic regimen). 
• 
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. 
• 
AEs will be recorded as solicited AEs if they do not meet the definition of unsolicited AEs. 
• 
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE 
or SAE if they fulfill the definition of an AE or SAE. 
 
Events NOT Meeting the AE Definition 
• 
Situations where an untoward medical occurrence did not occur (e.g., social and/or convenience 
admission to a hospital, admission for routine examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen.  
• 
Pre-existing conditions or signs and/or symptoms present in a participant prior to the first study 
vaccination. These events will be recorded in the medical history section of the eCRF. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or diagnosed prior to 

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informed consent signature) that did not worsen from baseline. 
• 
Clinically significant abnormal laboratory findings or other abnormal assessments that are present or 
detected at the start of the study and do not worsen. 
Serious Adverse Events 
An 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 participant 
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 inpatient hospitalization or prolongation of existing hospitalization 
Note: In general, hospitalization signifies that the participant 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 outpatient setting. Complications that occur during hospitalization are also 
considered as AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event will also be considered serious. When in doubt as to whether “hospitalization” occurred, or was 
necessary, the AE should be considered serious. 
d) Results in disability/incapacity  
Note: The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, 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 participant  
f) 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy). 
g) Other situations 
Medical or scientific judgment 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 hospitalization but may jeopardize the participant or may require medical or surgical 
intervention to prevent 1 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 hospitalization. 
Solicited Events 
Solicited Events will include the following: 
a) Solicited administration site events 
The following administration site events will be solicited for all age groups: 
• 
Pain  
• 
Redness  
• 
Swelling  
• 
Induration 

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Solicited Events will include the following: 
Note: participants/participants’ parents/LARs will be instructed to measure “Solicited administration site 
events” using the ruler provided by the site. Should multiple measurements be performed during the day, 
participants/participants’ parent(s)/LAR(s) will be instructed to record the highest grading in the eDiary. 
b) Solicited systemic events 
The following systemic events will be solicited for adults 15 to 25 years: 
• 
Fever 
• 
Fatigue 
• 
Nausea 
• 
Headache 
• 
Arthralgia 
• 
Myalgia 
Note: participants/participants’ parents/LARs will be instructed to measure and record the preferably 
oral body temperature in the evening using the thermometer provided by the site. Should additional 
temperature measurements be performed at other times of day, participants/participants’ parents/LARs 
will be instructed to record the highest temperature in the eDiary. 
Note: Any solicited event that meets any of the following criteria must be entered into the participant’s 
source documents and eCRF: 
• 
Solicited administration site or systemic event that leads to a visit to a health care provider 
(medically attended AE). 
• 
Solicited administration site or systemic event leading to the participant withdrawing from the 
study or the participant being withdrawn from the study by the investigator (AE leading to 
withdrawal). 
• 
Solicited administration site or systemic event that otherwise meets the definition of an SAE. 
Unsolicited AEs 
Definition of an Unsolicited AE:  
An unsolicited AE is an AE that was not solicited using an eDiary and that was spontaneously 
communicated by a participant/participant’s parent(s)/LAR(s) who has signed the informed consent. 
Unsolicited AEs include serious and non-serious AEs. 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses requiring a 
hospitalization, or emergency room visit, or visit to/by a health care provider). The 
participants/participants’ parents/LARs will be instructed to contact the study center as soon as possible 
to report medically attended events, as well as any events that, though not medically attended, are of 
participant/parental/LAR’s concern. Detailed information about reported unsolicited AEs will be 
collected by qualified study center personnel and documented in the participant’s records. 
Unsolicited AEs that are not medically attended nor perceived as a concern by participant/participant’s 
parent(s)/LAR(s) will be collected during interview with the participants/participant’s parent(s)/LAR(s) 
and by review of available medical records at the next visit. 
COVID-19 Cases 
Diagnosis of COVID-19 should be made in accordance with the WHO case definition. 
Cases should be categorized as AEs or SAEs, and routine procedures for recording, 

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evaluation, follow-up, and reporting of AEs, and SAEs should be followed in accordance 
with the time period set out in the protocol (Table 12, Table 13). 
Adverse Events of Special Interest (AESIs) 
Definition of an AESI 
Adverse events of special interest (AESIs) are predefined (serious or non-serious) AEs of scientific and 
medical concern specific to the product or program, for which ongoing monitoring and rapid 
communication by the investigator to the sponsor can be appropriate, because such an event might 
warrant further investigation in order to characterize and understand it. 
Potential Immune-Mediated Diseases (pIMDs) 
Potential immune-mediated diseases are a subset of AESIs that include autoimmune 
diseases and other inflammatory and/or neurologic disorders of interest which may or 
may not have an autoimmune etiology. Adverse events that need to be recorded and 
reported as pIMDs include those listed in the Table 17. 
However, the investigator will exercise his/her medical and scientific judgment to 
determine whether other diseases have an autoimmune origin (i.e., pathophysiology 
involving systemic or organ-specific pathogenic autoantibodies) and should also be 
recorded as a pIMD. 
In order to facilitate the documentation of pIMDs in the eCRF, a pIMD standard 
questionnaire and a list of MedDRA PTs and PT codes corresponding to the above 
diagnoses will be available to investigators at study start. 

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Table 17 
List of Potential Immune-Mediated Diseases (pIMDs) 
Neuroinflammatory Disorders 
Musculoskeletal Disorders 
Skin Disorders 
• 
Cranial nerve neuropathy, including paralysis and 
paresis (e.g., Bell’s palsy). 
• 
Optic neuritis. 
• 
Multiple sclerosis. 
• 
Transverse myelitis. 
• 
Guillain-Barré syndrome, including Miller Fisher 
syndrome and other variants. 
• 
Acute disseminated encephalomyelitis, including 
site specific variants such as non-infectious 
encephalitis, encephalomyelitis, myelitis, 
myeloradiculoneuritis. 
• 
Myasthenia gravis, including Lambert-Eaton 
myasthenic syndrome. 
• 
Demyelinating peripheral neuropathies including: 
− Chronic inflammatory demyelinating 
polyneuropathy,  
− Multifocal motor neuropathy, 
− Polyneuropathies associated with 
monoclonal gammopathy. 
• 
Narcolepsy. 
• 
Systemic lupus erythematosus and associated 
conditions. 
• 
Systemic scleroderma (Systemic sclerosis), 
including: 
− Diffuse scleroderma, 
− CREST syndrome. 
• 
Idiopathic inflammatory myopathies, including: 
− Dermatomyositis,  
− Polymyositis, 
− Anti-synthetase syndrome. 
• 
Rheumatoid arthritis and associated conditions 
including:  
− Juvenile idiopathic arthritis, 
− Still’s disease, 
− Polymyalgia rheumatica. 
• 
Spondyloarthropathies, including:  
− Ankylosing spondylitis,  
− Reactive arthritis (Reiter's Syndrome), 
− Undifferentiated spondyloarthritis, 
− Psoriatic arthritis, 
− Enteropathic arthritis. 
• 
Relapsing Polychondritis. 
• 
Mixed connective tissue disorder. 
• 
Gout. 
• 
Psoriasis. 
• 
Vitiligo. 
• 
Erythema nodosum. 
• 
Autoimmune bullous skin diseases 
including:  
− Pemphigus, 
− Pemphigoid, 
− Dermatitis herpetiformis. 
• 
Lichen planus. 
• 
Sweet’s syndrome. 
• 
Localised scleroderma (morphoea). 
Vasculitis 
Blood Disorders 
Others 
• 
Large vessels vasculitis including:  
− Giant cell arteritis (temporal arteritis), 
• 
Autoimmune haemolytic anemia. 
• 
Autoimmune thrombocytopenia. 
• 
Autoimmune glomerulonephritis including: 
− IgA nephropathy,  

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− Takayasu's arteritis.  
• 
Medium sized and/or small vessels vasculitis 
including:  
− Polyarteritis nodosa, 
− Kawasaki's disease,  
− Microscopic polyangiitis,  
− Wegener's granulomatosis (granulomatosis 
with polyangiitis), 
− Churg–Strauss syndrome (allergic 
granulomatous angiitis or eosinophilic 
granulomatosis with polyangiitis),  
− Buerger’s disease (thromboangiitis 
obliterans),  
− Necrotising vasculitis (cutaneous or 
systemic),  
− Anti-neutrophil cytoplasmic antibody 
(ANCA) positive vasculitis (type 
unspecified), 
− Henoch-Schonlein purpura (IgA vasculitis),  
− Behcet's syndrome, 
− Leukocytoclastic vasculitis. 
• 
Antiphospholipid syndrome. 
• 
Pernicious anemia. 
• 
Autoimmune aplastic anemia. 
• 
Autoimmune neutropenia. 
• 
Autoimmune pancytopenia. 
− Glomerulonephritis rapidly 
progressive,  
− Membranous glomerulonephritis,  
− Membranoproliferative 
glomerulonephritis,  
− Mesangioproliferative 
glomerulonephritis.  
• 
Tubulointerstitial nephritis and uveitis 
syndrome. 
• 
Ocular autoimmune diseases including: 
− Autoimmune uveitis, 
− Autoimmune retinitis. 
• 
Autoimmune myocarditis. 
• 
Sarcoidosis. 
• 
Stevens-Johnson syndrome. 
• 
Sjögren’s syndrome. 
• 
Alopecia areata. 
• 
Idiopathic pulmonary fibrosis. 
• 
Goodpasture syndrome. 
• 
Raynaud’s phenomenon. 
Liver Disorders 
Gastrointestinal Disorders 
Endocrine Disorders 
• 
Autoimmune hepatitis. 
• 
Primary biliary cirrhosis. 
• 
Primary sclerosing cholangitis. 
• 
Autoimmune cholangitis. 
• 
Inflammatory bowel disease, including: 
− Crohn’s disease,  
− Ulcerative colitis,  
− Microscopic colitis,  
− Ulcerative proctitis. 
• 
Celiac disease. 
• 
Autoimmune pancreatitis. 
• 
Autoimmune thyroiditis (Hashimoto 
thyroiditis). 
• 
Grave's or Basedow’s disease. 
• 
Diabetes mellitus type I. 
• 
Addison’s disease. 
• 
Polyglandular autoimmune syndrome. 
• 
Autoimmune hypophysitis. 
 

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Other AEs of Special Interest 
When there is enough evidence to make any of the above diagnoses, the AE must be reported as 
AESI. Symptoms, signs or conditions which might (or might not) represent the above diagnoses, 
should be recorded and reported as AEs but not as AESI until the final or definitive diagnosis has 
been determined, and alternative diagnoses have been eliminated or shown to be less likely.  
 Arthritis 
Cases of arthritis are defined according to the following ad-hoc definition:  
• Presence of physical examination findings of swelling, redness, heat, or limitation in 
range of motion 
and/or 
• Presence of diagnostic imaging studies interpreted by a health care provider as 
demonstrating evidence of joint inflammation and/or arthrocentesis results evidencing 
inflammation 
Due to the heterogeneity of the presentation of arthritis, which can be either acute or chronic, the 
threshold of duration of 6 weeks is to be considered. 
The list of PTs corresponding to the diagnosis of arthritis are those included in the Standardized 
MedDRA Queries (SMQ) Narrow “Arthritis”. For any new diagnosis of arthritis (serious or 
non-serious) in a study participant, the investigator (or designate) must complete an electronic 
Expedited Adverse Events Report and an ad-hoc eCRF page on arthritis to further characterize 
this AESI. 
Clinical Laboratory Parameters and Other Abnormal Assessments Qualifying as AEs or 
SAEs  
In the absence of a diagnosis, abnormal laboratory findings (e.g., clinical chemistry, hematology, 
urinalysis) or other abnormal assessments the investigator considers clinically significant will be 
recorded as an AE or SAE if they meet the definition of an AE or SAE.  
The investigator will exercise his or her medical and scientific judgment in deciding whether an 
abnormal laboratory finding or other abnormal assessment is clinically significant. 
 

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Events or Outcomes Not Qualifying as AEs or SAEs  
Pregnancy 
Female participants who become pregnant after the first vaccination must not receive subsequent 
doses of the study vaccine(s)/product, but may continue other study procedures at the discretion 
of the investigator. 
While pregnancy itself is not considered an AE or SAE, any abnormal pregnancy outcome or 
complication or elective termination of a pregnancy for medical reasons will be recorded and 
reported as an SAE. 
Recording and Follow-up of AEs, SAEs, AESIs, and Pregnancies 
AE and SAE Recording 
• 
The participants/participants’ parents/LARs will be instructed to contact the investigator immediately should 
the participants manifest any signs or symptoms they perceive as serious.  
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation (e.g., 
hospital progress notes, laboratory and diagnostics reports) relative to the event. The investigator will then 
record all relevant information regarding an AE/SAE in the eCRF. The investigator is not allowed to send 
photocopies of the participant’s medical records to neither the sponsor nor IQVIA instead of appropriately 
completing the eCRF. However, there may be instances when copies of medical records for certain cases are 
requested by the sponsor or IQVIA. In this instance, all participant identifiers will be blinded on the copies of 
the medical records prior to submission to the sponsor or IQVIA. 
• 
The investigator will attempt to establish a diagnosis pertaining to the event based on signs, symptoms, 
and/or other clinical information. In such cases, the diagnosis should be documented as the AE/SAE and not 
the individual signs/symptoms. 
• 
An eDiary will be used in this study to capture solicited administration site or systemic events. The 
participant should be trained on how and when to complete each field of the eDiary. 
• 
Any individual(s) who perform the measurements of administration site or systemic events and who will 
enter the information into the eDiary should be trained on the use of the eDiary. This training must be 
documented in the participant’s source record. If any other individual other than the participant/participant’s 
parent(s)/LAR(s) is making entries in the eDiary, their identity should be documented in the participant’s 
source record. 
• 
Refer to the study reference manual for more information regarding the use of eDiary. 
 
Time Period for Collecting and Recording AEs, SAEs, AESIs, and Pregnancies  
All solicited events that occur during 7 days following administration of each dose of study vaccine(s)/product 
(including the day of vaccination) (Day 1 and Day 181) must be recorded into the eDiary, irrespective of 
intensity. All other AEs occurring within the time frame described in Table 12 should be recorded into the 
appropriate section of the eCRF, irrespective of intensity or whether or not they are considered 
vaccination-related. 
Refer to Section 8.3.6.1 for collecting and reporting of safety information. 
 

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Follow-up of AEs, SAEs, AESIs, Pregnancies, or any Other Events of Interest  
After the initial AE/SAE/AESI/pregnancy or any other event of interest for the study, the investigator is required 
to proactively follow each participant at subsequent visits/contacts. All SAEs, and non-serious AEs of special 
interest, will be followed until the event is resolved, stabilized, otherwise explained, or the participant is lost to 
follow-up. 
Other non-serious AEs must be followed until the last contact or until the participant is lost to follow-up. 
Follow-up During the Study 
AEs/AESIs documented at a previous visit/contact and defined as not recovered/not resolved or 
recovering/resolving will be reviewed at subsequent visits/contacts until the last visit/contact of the participant. 
If the participant dies during participation in the study or during a recognized follow-up period, IQVIA will be 
provided with any available post-mortem findings, including histopathology. 
Follow-up After the Participant is Discharged From the Study 
The investigator will provide any new or updated relevant information on previously reported SAE/AESI to 
IQVIA using electronic Expedited Adverse Events Report and/or pregnancy report as applicable. The investigator 
is obliged to perform or arrange for the conduct of supplemental clinical examinations/tests and/or evaluations to 
elucidate the nature and/or causality of the AE or SAE as fully as possible.   
Follow-up of Pregnancies 
Pregnant participants 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 IQVIA 
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 6 to 8 weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is an SAE, it should always 
be reported as SAE. 
Furthermore, in case if the investigator becomes aware of 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)/product, he/she 
has to report this information to IQVIA as described in Section 8.3.6.4. 
Updating of SAE, AESI, and Pregnancy Information After Removal of Write Access to the Participant’s 
eCRF 
When additional SAE, AESI, or pregnancy information is received after removal of write access to the 
participant’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 IQVIA as described in the 
relevant section within the timeframes specified in Table 13). 
Assessment of Intensity 
Maximum Intensity for Solicited Events 
The intensity of the following solicited AEs will be assessed as described in the table below. 
Intensity Scales for Solicited Events in Adults and Children of 6 Years of Age or Older 
Adults/Child (≥10 years) 
Event 
Intensity Grade Parameter 
Pain at administration site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing normal 
everyday activities. 
 
2 
Moderate: Painful when limb is moved and interferes with 
everyday activities. 
 
3 
Severe: Significant pain at rest. Prevents normal everyday 

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activities. 
Redness at administration site 
Record greatest surface diameter in mm 
Swelling at administration site 
Record greatest surface diameter in mm 
Induration at administration site 
Record greatest surface diameter in mm 
Temperature* 
 
Record temperature in °C/°F (with 1 decimal) 
Nausea 
0 
Normal 
1 
Mild: Nausea that is easily tolerated 
2 
Moderate: Nausea that interferes with normal activity 
3 
Severe: Nausea that prevents normal activity 
Headache 
0 
Normal 
1 
Mild: Headache that is easily tolerated 
2 
Moderate: Headache that interferes with normal activity 
3 
Severe: Headache that prevents normal activity 
Fatigue 
0 
Normal 
1 
Mild: Fatigue that is easily tolerated 
2 
Moderate: Fatigue that interferes with normal activity 
3 
Severe: Fatigue that prevents normal activity 
Myalgia  
0 
None 
1 
Mild: Myalgia present but does not interfere with activity 
2 
Moderate: Myalgia that interferes with normal activity 
3 
Severe: Myalgia that prevents normal activity 
Arthralgia 
0 
None 
1 
Mild: Arthralgia present but does not interfere with activity 
2 
Moderate: Arthralgia that interferes with normal activity 
3 
Severe: Arthralgia that prevents normal activity 
*Refer to the SoA (Table 3) for the definition of fever and the preferred location for temperature measurement 
Maximum Intensity of Local Injection Site Redness/Swelling/Induration 
The maximum intensity of local injection site redness/swelling/induration and fever will be scored as follows: 
 
Redness/swelling/induration 
Fever 
0: 
1 to 24 mm 
<38.0°C (100.4°F) 
1: 
25 to 50 mm 
≥38.0°C (100.4°F) to ≤38.9°C (102.1°F) 
2: 
51 to 100 mm 
>39.0°C (102.2°F) to ≤39.9°C (103.9°F) 
3: 
>100 mm 
>40.0°C (104°F) 
Maximum Intensity for Unsolicited AEs and SAEs 
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 

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judgment. 
The intensity should be assigned to 1 of the following categories: 
• 
1 (mild): An AE which is easily tolerated by the participant, causing minimal discomfort and not 
interfering with everyday activities. 
• 
2 (moderate): An AE which is sufficiently discomforting to interfere with normal everyday activities. 
• 
3 (severe): An AE which prevents normal, everyday activities (in a young child, such an AE would, for 
example, prevent attendance at school/kindergarten/daycare and would cause the parent(s)/LAR(s) to 
seek medical advice. In adults/adolescents, such an AE would, for example, prevent attendance at 
work/school and would necessitate the administration of corrective therapy. 
An AE that is assessed as Grade 3 (severe) should not be confused with an SAE. Grade 3 is a category used for 
rating the intensity of an event; and both AEs and SAEs can be assessed as Grade 3. An event is defined as 
“serious” when it meets 1 of the outcomes that define an SAE. 
 
Assessment of Causality 
All solicited administration-site and systemic events will be considered causally related to vaccination. 
The investigator must assess the relationship between study vaccines and the occurrence of each unsolicited 
AE/SAE using clinical judgment. Where several different vaccines/products were administered, the investigator 
should specify, when possible, if the unsolicited AE/SAE could be causally related to a specific vaccine/product 
(ie investigational, control/placebo or co-administered vaccine). When causal relationship to a specific vaccine 
cannot be determined, the investigator should indicate the unsolicited AE/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)/product will be considered and 
investigated. The investigator will also consult the IB and/or Summary of Product Characteristics and/or 
Prescribing Information for marketed products to determine his/her assessment. 
Causality should be assessed by the investigator using the following question: 
Is there a reasonable possibility that the unsolicited AE may have been caused by the study vaccine? 
• 
YES: There is a reasonable possibility that the study vaccine(s)/product contributed to the AE.  
• 
NO: There is no reasonable possibility that the AE is causally related to the administration of the study 
vaccine(s)/product. There are other, more likely causes and administration of the study 
vaccine(s)/product is not suspected to have contributed to the AE. 
If an event meets the criteria to be determined as “serious”, additional examinations/tests will be performed by 
the investigator 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)/product, if applicable. 
• 
Erroneous administration. 
• 
Other cause (specify).  
There may be situations when an SAE has occurred and the investigator has minimal information to include in the 
initial report to IQVIA. However, it is very important to record an assessment of causality for every event before 
submitting the Expedited Adverse Events Report to IQVIA.  
The causality assessment is 1 of the criteria used when determining regulatory reporting requirements. The 
investigator may change his/her opinion of causality after receiving additional information and update the SAE 
information accordingly. 

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Medically Attended Visits 
For each solicited and unsolicited symptom the participant experiences, the participant/participant’s 
parent(s)/LAR(s) will be asked if he/she/the participant received medical attention defined as hospitalization, or 
an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits. 
This information will be recorded in the eCRF. 
 
Assessment of Outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 
Reporting of SAEs, AESIs, Pregnancies, and Other Events 
Events Requiring Expedited Reporting to IQVIA 
• 
Once an investigator becomes aware that an SAE/AESI has occurred in a study participant, the investigator 
or investigator’s designee must complete information in the electronic Expedited AE Report WITHIN 
24 HOURS. The report will always be completed as thoroughly as possible with all available details of the 
event. The report allows to specify that the event is an AESI and whether it is serious or non-serious. 
• 
Even if the investigator does not have all information regarding an SAE/AESI, 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/AESI causality by ticking the “reviewed” 
box in the electronic Expedited AE Report within 72 hours of submission of the SAE/AESI. 
• 
Refer to Table 13 for the details on timeframes for reporting of SAEs/AESIs and pregnancies 
 
SAE/AESI/Pregnancy Reporting to IQVIA via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE/AESI/Pregnancy to IQVIA will be an EDC. 
• 
If the EDC is unavailable for more than 24 hours, then the study center will use the paper Expedited 
AE/Pregnancy Report (see details in the next section). 
• 
The study center will enter the SAE/AESI/pregnancy data into the EDC as soon as it become available. 
• 
After the study is completed at a given study center, the EDC will be taken offline to prevent the entry of 
new data or changes to existing data. 
• 
If a study center receives a report of a new SAE/AESI/pregnancy from a participant or receives updated data 
on a previously reported SAE/AESI/pregnancy after the EDC has been taken offline, then the study center 
can report this information on a paper Expedited AE/Pregnancy Report (see the next section) or to the 
Medical Monitor by telephone. 
• 
Contacts of the Medical Monitor for SAE/AESI/pregnancy reporting can be found in the study reference 
manual. 

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Back-up SAE/AESI/Pregnancy Reporting to IQVIA via Paper (in Case of EDC Failure) 
• 
Facsimile transmission (fax) of the SAE/AESI/pregnancy paper Expedited AE/Pregnancy Report in case of 
EDC failure is the preferred method to transmit this information to the Medical Monitor. 
• 
In rare circumstances and in the absence of a fax equipment, notification by telephone is acceptable with a 
copy of the paper Expedited AE/Pregnancy Report sent by overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to complete and sign the 
Expedited AE/Pregnancy Report within the designated reporting timeframes. 
• 
Contacts of the Medical Monitor for SAE/AESI/pregnancy reporting can be found in the study reference 
manual. 
Definitions of Medical Device Adverse Events and Adverse Device Effects 
A Medical Device AE is: 
is any untoward medical occurrence, in a clinical study participant, users, or other persons, temporally associated 
with the use of study intervention whether or not considered related to a medical device. An AE can therefore be 
any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or 
exacerbated) temporally associated with the use of a medical device. This definition includes events related to the 
medical device or comparator and events related to the procedures involved. 
An Adverse Device Effect (ADE) is: 
Any AE related to the use of a medical device. This definition includes any AE resulting from: 
• 
insufficient or inadequate instructions for use (i.e., user error), or 
• 
any malfunction of a medical device, or 
• 
intentional misuse of the medical device. 
Definitions of a Medical Device SAE, Serious Adverse Device Effect, and Unexpected 
Serious Adverse Device Effect 
A Medical Device SAE is Any SAE that: 
 
Led to death  
 
Led to serious deterioration in the health of the participant, that either resulted in: 
• 
A life-threatening illness or injury. The term “life-threatening” in the definition of “serious” refers to an 
event in which the participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
• 
A permanent impairment of a body structure or a body function. 
• 
Inpatient or prolonged hospitalization. Planned hospitalization for a pre-existing condition, or a 
procedure required by the protocol, without serious deterioration in health, is not considered an SAE. 
• 
Medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to 
a body structure or a body function 
 
Led to fetal distress, fetal death or a congenital abnormality or birth defect 
 
Is a suspected transmission of any infectious agent via a medicinal product 

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A Serious Adverse Device Effect (SADE) is: 
• 
A SADE is defined as an ADE that has resulted in any of the consequences characteristic of a serious adverse 
event. 
• 
Any device deficiency that might have led to an SAE if appropriate action had not been taken, intervention 
had not occurred, or circumstances had been less fortunate. 
An Unanticipated SADE (USADE) is: 
• 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is a SADE that by its nature, 
incidence, severity or outcome has not been identified in the current version of the IB. 
 
Recording and Reporting of Medical Device AE, ADEs, SADEs and USADE 
• 
Any device deficiency must be reported to IQVIA within 24 hours after the investigator determines that 
the event meets the definition of a device deficiency. 
• 
E-mail/fax transmission of the paper “Medical device or combination product with device 
deficiency/incident report form” is the preferred method to transmit this information to IQVIA. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is acceptable 
with a copy of “Medical device or combination product with device deficiency/incident report form’ sent 
by overnight mail or courier service.” 
• 
Contacts of the Medical Monitor for medical device safety events reporting can be found in the study 
reference manual. 
• 
IQVIA will review all device deficiencies and determine and document in writing whether they could 
have led to an SAE. These device deficiencies will be reported to the regulatory authorities and 
IRBs/IECs as required by national regulations. 
 
 

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Appendix 5 
Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions 
Woman of Childbearing Potential 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
Women NOT Considered as Women of Childbearing Potential 
1. Premenarchal female*: 
a) Menarche is defined as an 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. 
b) If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
2. Premenopausal female with 1 of the following: 
a) Documented hysterectomy 
b) Documented bilateral salpingectomy 
c) Documented bilateral oophorectomy 
Note: Documentation can come from the study center staff: review of participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female: 
a) A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single follicle stimulating hormone measurement is 
insufficient. 
b) Females on HRT and whose menopausal status is in doubt will be required to use 1 of the 
non-hormonal highly effective contraception methods if they wish to continue their HRT 
during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment. 
*Note: If the childbearing potential changes after start of the study (e.g., a premenarchal female 
participant experiences menarche) or the risk of pregnancy changes (e.g., a female participant 
who is not heterosexually active becomes active), the participant must discuss this with the 
investigator, who should determine a highly effective method of contraception. If reproductive 
status is questionable, additional evaluation should be considered. 

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Contraception Guidance 
Female participants of childbearing potential are eligible to participate if they agree to use an 
adequate contraception consistently and correctly according to the methods listed in the 
sponsor’s list of highly effective contraceptive methods provided in the table below.  
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent* 
Failure rate of <1% per year when used consistently and correctly.  
Combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Intravaginal  
• 
Transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Injectable  
Highly Effective Methods That Are User Independent* 
• 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device 
• 
Intrauterine hormone-releasing system 
• 
Bilateral tubal occlusion 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual 
partner of the woman of childbearing potential and the absence of sperm has been confirmed. If not, an additional 
highly effective method of contraception should be used.)  
Male partner sterilization prior to the female participant’s entry into the study, and this male is the sole partner for 
that participant, 
(The information on the male sterility can come from the study center personnel’s review of the participant’s 
medical records; medical examination and/or semen analysis, or medical history interview provided by her or her 
partner). 
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs 
to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.)  
* Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants in clinical studies.  
Female participants must practice adequate contraception for 30 days prior to vaccination, have a 
negative pregnancy test on the day of vaccination, and agree to continue adequate contraception 
during the entire intervention period and for 30 days after completion of the vaccination series. 

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Female Participants Who Become Pregnant 
Refer to the Sections 8.3.6 for information on detection, recording, reporting and follow-up of 
pregnancies. Any female participant who becomes pregnant during the study will discontinue 
study intervention. For a participant who becomes pregnant during the study, this information 
will be shared with the participant’s parent(s)/LAR(s) depending on the participant’s age as 
required by local regulations. 

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Appendix 6 
Country-specific Requirements  
To be confirmed. 

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Appendix 7 
Protocol Amendment History 
See the Summary of Changes for Protocol Amendment 3 directly before the Table of Contents. 
The history of Amendments 1 and 2 is provided below. 
Amendment 2 – 12 February 2021 
This amendment was considered substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for Amendment 2: 
The primary goal of Amendment 2 was to promote one of the secondary endpoints to co-
primary, which would allow to evaluate vaccine immunogenicity at 1 month after both the first 
and the second MenABCWY vaccinations (0,6-months). Also, considering that some of the 
study interventions are combination products constituted of a device and biologic product (pre-
filled syringes), the amended protocol provided instructions for collection of safety information 
related to the use of medical devices. 

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Description of Changes in Amendment 2: 
Section # and 
Name 
Description of Change 
Brief Rationale 
Substantial Changes 
1.1 Synopsis 
The following secondary endpoint was promoted to co-primary and labeled 
“Family 1”: 
Objectives 
Endpoints 
Immunological non-inferiority: 
MenABCWY vs. MenACWY 
(Family 1): 
To demonstrate the immunological 
non-inferiority of the MenABCWY 
vaccine, compared to MenACWY 
vaccine given to healthy 
participants, previously primed 
with a MenACWY vaccine, as 
measured by the percentages of 
participants achieving a 4-fold rise 
in hSBA titers against 
N. meningitidis serogroups A, C, 
W, and Y, at 1 month after the 
second MenABCWY vaccination 
(0,6-months) and 1 month after the 
MenACWY vaccination (single 
dose). 
The percentages of participants 
with a 4-fold rise in hSBA titers 
against N. meningitidis serogroups 
A, C, W, and Y at 1 month after 
the second vaccination for the 
ABCWY group (Day 211, Month 
7), and 1 month after the single 
MenACWY vaccination for the 
ACWY group (Day 31, Month 1) 
relative to baseline (Day 1, Month 
0). 
The original primary endpoint was changed to co-primary and was labeled 
“Family 2”: 
Objectives 
Endpoints 
To promote one of the 
secondary endpoints to co-
primary, which will allow to 
evaluate vaccine 
immunogenicity at 1 month 
after both the first and the 
second MenABCWY 
vaccinations (0, 6-months) 
 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Immunological non-inferiority: 
MenABCWY vs. MenACWY 
(Family 2) 
To demonstrate the immunological 
non-inferiority of the MenABCWY 
vaccine, compared to MenACWY 
vaccine given to healthy 
participants, previously primed 
with a MenACWY vaccine, as 
measured by the percentages of 
participants achieving a 4-fold rise 
in hSBA titers against N. 
meningitidis serogroups A, C, W, 
and Y, at 1 month after the first 
MenABCWY vaccination (0,6-
months) and 1 month after the 
MenACWY vaccination (single 
dose). 
The percentages of participants 
with a 4-fold rise in hSBA titers 
against N. meningitidis serogroups 
A, C, W, and Y at 1 month after 
the first vaccination for the 
ABCWY group (Day 31, 
Month 1), and 1 month after the 
single dose of MenACWY 
vaccination for the ACWY group 
(Day 31, Month 1), relative to 
baseline (Day 1, Month 0). 
1.3 Schedule of 
Activities 
In the footnote for Table 3 (formerly Table 1 in the original protocol) 
“Schedule of Activities”, the following footnotes were added: 
1 
Home visits are always allowed if deemed suitable and are 
conducted according to local regulations. 
To allow additional flexibility 
to perform study visits. 
9 
Frequency or urine pregnancy tests can be established at the site 
according to local regulations. 
Numbering of the footnotes shifted accordingly. 
The cross-reference to the footnote 1 was added to the row “Days 
post-vaccination” 
The cross-reference to the footnote 9 was added to the row “Urine 
To reflect local requirements on 
pregnancy testing. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
pregnancy test for females of childbearing potential” 
3.0 OBJECTIVES 
AND 
ENDPOINTS 
Table 6 “Study Objectives and Endpoints” was revised to reflect the 
changes made in the same table in Synopsis. 
For consistency. 
5.1 Inclusion 
Criteria 
The following text was revised as follows (the new text is bold): 
4. Previous vaccination with 1 dose of MenACWY vaccine at an age of 10 
years or older, with an interval of at least 4 years and not more than 6 years 
(intended as up to 6 years and 364 days) between the previous 
MenACWY vaccine and enrollment (informed consent and assent [as 
applicable]) into this study. 
For clarity. 
The following sentence was added: 
Frequency or urine pregnancy tests can be established at the site according 
to local regulations. 
To incorporate local 
requirement on pregnancy 
testing. 
5.2.1 Medical 
Conditions  
5.2.2 
Prior/Concomitan
t Therapy 
The exclusion criteria #7 and #14 were revised as follows (the new text is 
bold; the deleted text is crossed out): 
For corticosteroids (oral/intravenous/intramuscular), with mean prednisone 
≥20 mg/day (for adult participants), or ≥0.5 mg/kg/day, or ≥20 mg/day 
whichever is the maximum dose for pediatric participants, or equivalent. 
For corticosteroids, this will mean prednisone equivalent ≥20 mg/day 
for adult participants and ≥0.5 mg/kg/day with maximum ≥20 mg/day 
for pediatric participants. 
For clarity. 
6.1 Study 
Interventions 
Administered 
In Table 8 (formerly Table 6) “Study Interventions Administered”, the 
following rows (shown in bold) were added: 
Study 
Interventio
MenABC
WY 
Menveo  
Bexsero 
Placebo 
The new row with “Product 
type” was added to identify 
combination products. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
n Name 
Product 
type 
Combinat
ion 
Biological 
Combinat
ion 
Combinat
ion 
Type 
Study 
Control 
Additiona
l 
Additiona
l 
6.3.5.1  
Blinding 
The following text was revised as follows (the new text is bold; the deleted 
text is crossed out): 
The laboratory in charge of the sample testing will be blinded to the 
intervention assignment. Codes will be used to link the participant and 
study (without any link to the intervention attributed to the participant) to 
each sample. 
The laboratory in charge of the laboratory testing will be blinded to 
the treatment, subject and visit number, and codes will be used to link 
the subject, visit and study (without any link to the treatment 
attributed to the subject) to each sample. 
For clarity. 
6.7 
Criteria for 
Temporary Delay 
for Enrollment 
and/or 
Vaccination 
and/or Blood 
Sampling 
The following text was revised as follows (the new text is bold): 
Under such circumstances, a participant may be considered eligible for 
study enrollment and/or vaccination after the appropriate window for delay 
described above, or as defined by local health authorities, has passed 
and inclusion/exclusion criteria have been re-checked, and if the participant 
is confirmed to be eligible. 
For clarity. 
8.1.2 Laboratory 
Assays 
In the footnote for Table 10 (formerly Table 8) “Laboratory Assays”, the 
text was revised as follows (the added text is bold; the deleted text is 
crossed out): 
To reflect the fact that Nexelis 
acquired CLS in Germany. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
GSK Biologicals laboratory refers to the Clinical Laboratory Sciences 
(CLS) in Rixensart, Belgium; or Wavre, Belgium or Marburg, Germany. 
CLS may delegate testing to GSK Research laboratories in Siena, Italy, or 
to Nexelis in Marburg, Germany, or to an other external laboratoryies. 
8.3.6.1 Time 
Period and 
Frequency for 
Collecting AE and 
SAE Information 
The following text was added: 
Any solicited AE that has not resolved within 30 days post-vaccination and 
is reported during clinic visits or safety follow-up calls will be entered into 
the subject’s eCRF as an unsolicited AE. It will also be included in the 
subject’s source documents at the site by the investigator/site staff as a 
verbally reported event. It will not be included in the Subject eDiary. These 
AEs will be analyzed as unsolicited AEs (i.e., in the Unsolicited Safety 
Set). 
For clarity and to align with 
other MenABCWY protocols 
8.3.8 Medical 
Device 
Deficiencies 
The new section “Medical Device Deficiencies” was added, with the 
following subsections included (only the subsections headers are shown; 
see the content of these sections in the body of the protocol amendment): 
8.3.8.1 Detection, Follow-up and Prompt Reporting of Medical Device 
Deficiency 
8.3.8.2 Regulatory Reporting of Medical Device Deficiency When Used 
as Combination Product  
Given that the study 
interventions (MenABCWY 
and Bexsero) are combination 
products constituted of a device 
and biologic product (pre-filled 
syringes), the language 
regarding combination 
products, collection and 
reporting of safety events 
related to medical devices in 
accordance with the FDA 
guidelines, was added. 
9.1 Statistical 
Hypotheses 
The text was revised as follows (the added content is bold; the deleted text 
is crossed out): 
Statistical considerations were 
revised to accommodate 

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First Co-Primary Immunogenicity Objective (Family 1) 
The first co-primary immunogenicity objective is to demonstrate the 
immunological non inferiority (NI) of the antibody response to 
MenABCWY vaccine, compared to MenACWY vaccine given to healthy 
participants, previously primed with MenACWY, as measured by 
percentage of participants with 4-fold rise in hSBA titer against each of the 
N. meningitidis serogroups A, C, W, and Y, at 1 month after the first 
second MenABCWY vaccination and 1 month after the MenACWY 
vaccination (single dose). This translates to the following hypotheses: 
H0: 
(p1_MenABCWY(i) – p1_MenACWY(i) ≤−10% 
vs. 
H1: 
(p1_MenABCWY(i) – p1_MenACWY(i) >−10% 
Where  p1_MenABCWY(i) denotes the percentages of participants with 4-
fold rise in hSBA titers for serogroups i=A, C, W, and Y, 1 month after the 
first second vaccination of MenABCWY group and p1_MenACWY(i) 
denotes the percentages of participants with 4-fold rise in hSBA titers for 
serogroups i=A, C, W, and Y, 1 month after the single vaccination of 
MenACWY group. 
NI criterion: Non-inferiority will be demonstrated if the lower limit of 
the two-sided 95% CI for the percent difference in the 4-fold rise in 
hSBA titers (p_MenABCWY– p_MenACWY) is above −10% for each 
serogroup A, C, W, and Y. 
Second Co-Primary Secondary Immunogenicity Objective (Family 2) 
The secondary co-primary immunogenicity objective is to demonstrate the 
immunological NI of the antibody response to MenABCWY vaccine, 
compared to MenACWY vaccine given to healthy participants, previously 
primed with MenACWY, as measured by percentage of participants with 4-
fold rise in hSBA titer against each of the N. meningitidis serogroups A, C, 
W, and Y, at 1 month after the second first MenABCWY vaccination and 1 
month after the MenACWY vaccination (single dose). This translates to the 
additional analyses required in 
the study due to promotion of 
one of the secondary endpoints 
to co-primary.  
Identifiers “Family 1” and 
“Family 2” were added for 
referencing testing strategy for 
the 2 co-primary endpoints. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
following hypotheses: 
H0: 
(p2_MenABCWY(i) – p2_MenACWY(i) ≤−10% 
vs. 
H1: 
(p2_MenABCWY(i) – p2_MenACWY(i) >−10% 
Where  p2_MenABCWY(i) denotes the percentages of participants with 4-
fold rise in hSBA titers for serogroups i=A, C, W, and Y, 1 month after the 
second first vaccination of MenABCWY group and p2_MenACWY(i) 
denotes the percentages of participants with 4-fold rise in hSBA titers for 
serogroups i=A, C, W, and Y, 1 month after the single vaccination of 
MenACWY group. 
NI criterion: Non-inferiority will be demonstrated if the lower limit of 
the two-sided 95% CI for the percent difference in the 4-fold rise in 
hSBA titers (p_MenABCWY– p_MenACWY) is above −10% for each 
serogroup A, C, W, and Y. 
9.2 Sample Size 
Determination 
The text was revised as follows (the added content is bold; the deleted text 
is crossed out): 
Table 14  Power to Demonstrate Immunological Non-inferiority for 
Serogroups A, C, W, and Y of MenABCWY Compared to 
MenACWY (Primary) 
Serogro
up 
4-fold 
Rate 
MenAC
WY, % 
4-fold 
Rate 
MenAB
CWY, 
% 
NI 
Margin, 
% 
Actual 
Margin, 
% 
Power, 
% 
n, 
Group 
A 
95 
91 
−10 
−4 
96.00 
542 
C 
95 
93 
−10 
−2 
99.95 
542 
W 
95 
91 
−10 
−4 
96.00 
542 

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Y 
95 
93 
−10 
−2 
99.95 
542 
Global 
 
 
 
92.00 
n = number of participants; NI = Non-inferiority 
For each serogroup: NI limit is −10% 
Family 1: For the secondary immunogenicity objective, it is assumed 
Assuming that MenABCWY and MenACWY groups will induce a 4-fold 
rise in about 95% of the participants for each of the 4 serogroups (Table 
15), and Uusing a 1-sided score test (Miettinen, 1985), non-inferiority 
margin of −10% and actual margin of 0%, an estimated number of 
evaluable participants (n = 225 and 542 for MenABCWY and MenACWY, 
respectively) and individual powers of 99.87% for each A, C, W, and Y 
serogroup test, will give a global power of 99.48% to demonstrate 
non-inferiority of MenABCWY versus MenACWY. 
Family 2: Assuming that MenACWY group will induce a 4-fold rise in 
about 95% of the participants for each of the 4 serogroups; 
MenABCWY will induce a 4-fold rise in about 91% of the participants 
for A and W serogroups, and 93% of the participants for C and Y 
serogroups; and, using a 1-sided score test (Miettinen, 1985), non-
inferiority margin of −10% and actual margins as given in Table 14, an 
estimated evaluable participants (n=542) and individual powers of 
96.00%, 99.95%, 96.00%, and 99.95% for each A, C, W, and Y 
serogroup test, will give a global power of 91% to demonstrate NI of 
MenABCWY versus MenACWY. 
Table 15   Power to Demonstrate Immunological Non-inferiority for 
Serogroups A, C, W, and Y of MenABCWY Compared to 
MenACWY (Secondary) 

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125 
Serogrou
p 
4-fold 
Rate 
MenAC
WY, % 
4-fold 
Rate 
MenABC
WY, % 
NI 
Margi
n, % 
Actual 
Margin
, % 
Power, 
% 
n,  
ABCWY/A
CWY 
A 
95 
95 
−10 
0 
99.87 
225/542 
C 
95 
95 
−10 
0 
99.87 
225/542 
W 
95 
95 
−10 
0 
99.87 
225/542 
Y 
95 
95 
−10 
0 
99.87 
225/542 
Global  
 
 
 
99.48 
n = number of participants; NI = Non-inferiority 
For each serogroup: Non-inferiority limit is −10% 
For the multiplicity adjustment, all hypotheses will be ranked into two 
families according to the following power of test: 
Table 14 Power to Demonstrate Immunological Non-inferiority for 
Serogroups A, C, W, and Y of MenABCWY Compared to 
MenACWY (Primary) 
Serogro
up 
4-fold 
rate  
MenAC
WY 
4-fold 
rate 
MenABC
WY 
NI 
margi
n 
Actual 
margin Power 
N  
ABCWY/ 
ACWY 
Family 1: NI, 2-sided score test (Miettinen and Nurminen, 1985) 
A 
95% 
95% 
-10% 
0% 
99.87% 225  
C 
95% 
95% 
-10% 
0% 
99.87% 225  
W 
95% 
95% 
-10% 
0% 
99.87% 225  
Y 
95% 
95% 
-10% 
0% 
99.87% 225  
Family 2: NI, 2-sided score test (Miettinen and Nurminen, 1985) 
A 
95% 
91% 
-10% 
-4% 
96.00% 542 
C 
95% 
93% 
-10% 
-2% 
99.95% 542 
W 
95% 
91% 
-10% 
-4% 
96.00% 542 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Y 
95% 
93% 
-10% 
-2% 
99.95% 542 
Global Power 
91.00%   
n = number of participants; NI = non-inferiority 
Considering that approximately 10% of the selected participants might 
withdraw or not be evaluable for the immunogenicity objectives, the target 
sample size to be analyzed is 853 participants (603 and 250 participants for 
ACWY and ABCWY respectively). 
Considering that approximately 10% of the selected participants might 
withdraw or not be evaluable for the immunogenicity objectives, the 
target sample size to be analyzed will be 270 participants per group 
and 603 participants per group for the first co-primary and the second 
co-primary objectives respectively. 
Evaluable means all participants included in the set for the statistical 
analysis defined in Section 9.3. The sample size calculation was performed 
in PASS 12 (Hintze, 2013). The global power for all 4 strains across 
Family 1 and Family 2 is the product of individual powers. 
9.3 Populations 
for Analyses 
The text in the table was revised as follows: 
Participant who agreed/participant for whom parent(s)/LAR(s) agreed to 
participate in a clinical study after completion of the informed consent 
process, who meet screening/eligibility criteria and randomized or received 
study intervention or undergone an invasive procedure. 
9.4.1 General 
Considerations 
The following bullet point list item was revised as follows (the added 
content is bold; the deleted text is crossed out): 
• 
No multiplicity adjustment is foreseen as NI is considered achieved 
when the criterion is met for all 4 strains. This is applicable for both 
primary and secondary NI objectives. Fixed sequential testing 

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Section # and 
Name 
Description of Change 
Brief Rationale 
with full alpha propagation in pre-ordered hypotheses families 
(Family 1 and Family 2, as defined in Section 9.1) will be 
applied. 
9.4.3.1 
Immunological 
Non-inferiority of 
MenABCWY vs. 
MenACWY 
The following text was revised as follows (the added content is bold; the 
deleted text is crossed out): 
Statistical method (Family 1): For each of the serogroups A, C, W, and Y, 
the percentages of participants with 4-fold rise (refer to Section 9.4.1), and 
the corresponding exact 2-sided 95% CIs based on Clopper-Pearson 
method (Clopper and Pearson, 1934) will be calculated for each study 
group at 1 month after the first second vaccination. The standardized 
asymptotic CIs between group differences in percentages will be derived 
using the method of Miettinen and Nurminen (Miettinen, 1985). 
The following text was added: 
Statistical method (Family 2): For each of the serogroups A, C, W, and Y, 
the percentages of participants with 4-fold rise (refer to Section 9.4.1), and 
the corresponding exact 2-sided 95% CIs based on Clopper-Pearson 
method (Clopper and Pearson, 1934) will be calculated for each study 
group at 1 month after the first vaccination. The standardized asymptotic 
CIs between group differences in percentages will be derived using the 
method of Miettinen and Nurminen (Miettinen, 1985). 
NI criterion: Non-inferiority will be demonstrated if, the lower limit of 2-
sided 95% CI for the percent difference in 4-fold rise in hSBA titers 
(p1_MenABCWY − p1_MenACWY) is above −10%, for each serogroup 
A, C, W, and Y. 
9.4.4 Secondary 
Endpoints 
Section 9.4.4.1 “Immunological Non-Inferiority of MenABCWY vs. 
MenACWY” was deleted with all its content. 
Numbering of subsequent subsections in Section 9.4.4. shifted accordingly. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Appendix 1  
Abbreviations 
and Glossary of 
Terms 
 
New abbreviations added: 
ADE 
SADE 
USADE 
New terms added: 
Combination product 
Medical device deficiency 
New terms added to support 
changes in the protocol text 
regarding combination products 
and device deficiencies. 
The following definitions were removed from the Glossary of Terms: 
Adverse event 
Adverse event of special interest 
Removed to avoid redundancy: 
both terms are defined in 
Appendix 4. 
Appendix 2 
Regulatory, 
Ethical, and 
Study Oversight 
Considerations 
 
In the subsection “Informed Consent and Assent Process”, the following 
text was added: 
Re-consent must be obtained in accordance with local laws and regulations 
for participants who become legally emancipated during the study, i.e. 
reach the legal age of consent. The participant can provide consent by 
signing/witnessing/thumb printing an ICF, similar to that provided to the 
parent(s)/LAR(s) at study start, which summarizes the study and includes a 
consent statement and documents that the participant agrees to continue 
participating in the study. 
As an additional consideration 
for consent process applicable 
to the study population. 
The subheading “Study and Study Center Start and Closure” was renamed 
to “Study and Study Center Start and Closure” 
In the subsection “Study and Study Center Closure”, the following text was 
For clarity. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
added. 
An additional item in the list of reasons for study closure: 
• Total number of participants included earlier than expected 
An addditional paragraph: 
If the study is prematurely terminated or suspended, IQVIA shall promptly 
inform the investigators, the IECs/IRBs, the regulatory authorities, for the 
reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the 
participants and should assure appropriate participant therapy and/or 
follow-up. 
Appendix 4 
Adverse Events: 
Definitions and 
Procedures for 
Recording, 
Evaluating, 
Follow-up, and 
Reporting 
In the section “Potential Immune-Mediated Diseases (pIMDs)”, the 
following text was removed: 
If pIMDs are the only AESIs collected during the study, this should be 
explicitly mentioned in this section and the term “AESI” can be replaced by 
“pIMD” throughout the document. 
Adapt the following list of pIMDs based on the discussion with the project 
Safety Physician if more disorders need to be considered. 
To correct the error as this text 
played administrative role and 
was not part of the content of 
the section. 
The table heading was revised as follows (the removed text is crossed out): 
 Assessment of Intensity and Toxicity 
To correct the error, as toxicity 
assessment methods are not 
described in the associated 
table. 
The following information was added (only the paragraph headers are 
shown; see the added content in the body of the appendix): 
Definitions of Medical Device Adverse Events and Adverse Device 
Effects 
Definitions of a Medical Device SAE, Serious Adverse Device Effect, 
To provide instructions on 
identifying, recording, and 
reporting of device-related 
safety events 

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130 
Section # and 
Name 
Description of Change 
Brief Rationale 
and Unexpected Serious Adverse Device Effect 
Recording and Reporting of Medical Device AE, ADEs, SADEs and 
USADE 
Appendix 5 
Contraceptive 
Guidance and 
Collection of 
Pregnancy 
Information 
In the table “Highly Effective Contraceptive Methods”, subheading 
“Highly Effective Contraceptive Methods That Are User Dependent”, the 
text was updated as follows (the added text is bold): 
Progestogen-only hormonal contraception associated with inhibition of 
ovulation 
• 
Oral 
• 
Injectable 
The oral contraception method 
was considered acceptable as 
discussed for V72_72 Phase III 
study. The oral contraception 
method will allow enrollment of 
more potential participants into 
the study. 
In the table “Highly Effective Contraceptive Methods”, subheading 
“Highly Effective Methods That Are User Independent”, the following item 
was aligned with other items on the list with an added bullet point: 
• 
Implantable progestogen-only hormonal contraception associated 
with inhibition of ovulation 
To correct the formatting error 
that affected accuracy on the 
content. 
Administrative Changes 
Title Page 
Original text:  
Amendment Number: Amendment 1 
New Text:  
Amendment Number: 2 
Original date: 31 August 2020 
New date: 12 February 2021 
To reflect the change in the 
protocol version 
Page Headers 
Original text: 
Protocol 213171 (MENABCWY-019) – Amendment 2 
To reflect the change in the 
protocol version 

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Protocol 213171 (MENABCWY-019) – Amendment 3 
 
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Section # and 
Name 
Description of Change 
Brief Rationale 
New text: 
Protocol 213171 (MENABCWY-019) – Amendment 3 
Appendix 7 
Protocol 
Amendment 
History 
The new appendix added to include the summaries of changes from 
previous protocol amendments, 1 and 2. 
To retain the history of previous 
protocol amendments 
Appendix 8  
Signature of 
Investigator 
The number of the appendix changed from 7 to 8. 
Due to addition of Appendix 
“Protocol Amendment History” 
Original text: 
VERSION: Amendment 2 
New text: 
VERSION: Amendment 3 
To reflect the change in the 
protocol version 
Additional 
administrative 
changes 
Page numbers, Table of Contents, Table of Tables were updated. Table 
numbering shifted. Relevant editorial changes were also made (e.g., 
internal cross-references, formatting). 
Updates were made according 
to the changes in the content of 
the document 
Amendment 1 - 31 August 2020 
This amendment was considered to be non-substantial based on the criteria set forth in Article 10(a) of Directive 2001/20/EC of the 
European Parliament and the Council of the European Union because it neither significantly impacted the safety or physical/mental 
integrity of subjects nor the scientific value of the study. 
Overall Rationale for the Amendment: 
This protocol was amended to correct the volume of normal saline which comprised the placebo used in this study. 
Description of Changes in Amendment 1: 

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Section # and 
Name 
Description of Change 
Brief Rationale 
6.1 
Study 
Interventions 
Administered 
Table 8 was updated to reflect the following changes: 
Dose form; Placebo: changed from “Suspension for 
injection” to “Solution for Injection” 
Vaccines(s)/ Product Formulation; Placebo: Sodium 
chloride (NaCl) (0.9%) Water for injections was 
added and NaCl, water for injections q.s. 0.5 ml was 
deleted  
Volume to be administered; Placebo: Changed from 
0.5mL to 0.65mL 
Footnote 11 was added: The volume of the saline 
PFS may be between 0.6 mL and 0.8 mL. The full 
volume is to be injected 
Change in placebo volume from 0.5 mL to 0.65 mL 
to be aligned with the Certificate of Analysis. 
 

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Appendix 8 
Signature of Investigator 
PROTOCOL TITLE:  A phase IIIB, randomized, controlled, observer-blind study to evaluate 
safety and immunogenicity of GSK’s Meningococcal ABCWY vaccine when administered in 
healthy adolescents and adults, previously primed with MenACWY vaccine 
PROTOCOL NO: 
213171 (MENABCWY-019) 
VERSION:  
 
Amendment 3 
This protocol is a confidential communication of GlaxoSmithKline Biological SA (GSK). 
I confirm that I have read this protocol, I understand it, and I will work according to this 
protocol. I will also work consistently with the ethical principles that have their origin in the 
Declaration of Helsinki and that are consistent with Good Clinical Practices and the applicable 
laws and regulations. Acceptance of this document constitutes my agreement that no unpublished 
information contained herein will be published or disclosed without prior written approval from 
GSK. 
Instructions to the Investigator:  Please SIGN and DATE this signature page. PRINT your name, title, and the name of the study 
center in which the study will be conducted. Return the signed copy to IQVIA. 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
 
 
Signature of Investigator:      ___________________________          Date:  ________________ 
Printed Name:                         ___________________________ 
Investigator Title:                   ___________________________ 
 
Name/Address of Center:       ___________________________ 
 
 
 
 
___________________________ 
 
 
 
 
___________________________