A Phase I/II, Randomised, Controlled Study to Assess the Safety, Effectiveness and Immune Response of Meningococcal Combined ABCWY Vaccine When Administered to Healthy Adults (Phase I) and to Healthy Adolescents and Adults (Phase II)
Phase: PHASE1
Conditions: Infections, Meningococcal
Sponsor: GlaxoSmithKline

Protocol Amendment 4
Study ID:  212458
Official Title of Study: A Phase I/II, randomised, controlled study to assess the safety, 
effectiveness and immune response of meningococcal combined ABCWY vaccine when 
administered to healthy adults (Phase I) and to healthy adolescents and adults (Phase II)
NCTID: NCT04886154
Date of Document: 11 APR 2022

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Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA (GSK) 
Rue de l’Institut 89,  
1330 Rixensart, Belgium 
Primary study intervention 
and number 
GlaxoSmithKline Biologicals SA (GSK)’s combined 
meningococcal groups A, B, C, W and Y vaccine 
(GSK4023393A) 
Other study intervention(s) 
 
Phase I 
• 
Placebo 
Phase II 
• 
GSK’s meningococcal group B vaccine 
(Bexsero) 
• 
GSK’s combined meningococcal groups A, C, Y 
and W-135 conjugate vaccine (Menveo) 
• 
Placebo 
eTrack study number and 
abbreviated title 
212458 (MENACWY=
001 PRI) 
EudraCT number 
2020-004741-37 
Date of protocol 
Final: 11 January 2021 
Date of protocol amendment 
Amendment 1 Final: 7 May 2021 
Amendment 2 Final: 21 June 2021 
Amendment 3 Final: 29 September 2021 
Amendment 4 Final: 22 March 2022 
Title 
A Phase I/II, randomised, controlled study to assess 
the safety, effectiveness and immune response of 
meningococcal combined ABCWY vaccine when 
administered to healthy adults (Phase I) and to 
healthy adolescents and adults (Phase II). 
Brief title 
A study on the safety, effectiveness and immune 
response of meningococcal combined ABCWY 
vaccine in healthy adolescents and adults. 
Based on GlaxoSmithKline Biologicals SA Protocol WS v17.1 
© 2021 GSK group of companies or its licensor. 
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Protocol Amendment 4 Sponsor Signatory Approval 
eTrack study number and 
abbreviated title 
212458 (MENACWY=
001 PRI) 
EudraCT number 
2020-004741-37 
Date of protocol amendment  
Amendment 4 Final: 22 March 2022 
Title  
A Phase I/II, randomised, controlled study to assess 
the safety, effectiveness and immune response of 
meningococcal combined ABCWY vaccine when 
administered to healthy adults (Phase I) and to 
healthy adolescents and adults (Phase II). 
Sponsor signatory 
Daniela Toneatto,  
Clinical and Epidemiology Project Lead 
Signature 
 
 
 
Date 
 
Note: Not applicable if an alternative signature process (e.g. electronic signature or email 
approval) is used to get the sponsor approval. 
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Protocol Amendment 4 Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline (GSK) Biologicals SA. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements.  
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study intervention and other study-related duties and functions as described 
in the protocol. 
• 
To supervise any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site. 
• 
To ensure that any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site are qualified to perform those trial-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK and the express written informed consent of 
the participant and/or the participant’s legally acceptable representative (LAR).  
• 
To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s).  
• 
To co-operate with representative(s) of GSK in the monitoring process of the study 
and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the trial. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational intervention(s), and more generally about his/her 
financial ties with the sponsor. GSK will use and disclose the information solely for 
the purpose of complying with regulatory requirements. 
Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study.  
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and all other documents 
required by regulatory agencies for this study. 
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eTrack study number and 
abbreviated title 
212458 (MENACWY=
-001 PRI) 
EudraCT number 
2020-004741-37 
Date of protocol amendment 
Amendment 4 Final: 22 March 2022 
Title 
A Phase I/II, randomised, controlled study to assess 
the safety, effectiveness and immune response of 
meningococcal combined ABCWY vaccine when 
administered to healthy adults (Phase I) and to 
healthy adolescents and adults (Phase II). 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 
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SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA (GSK) 
2. Sponsor medical expert for the study 
Refer to the local study contact information document. 
3. Sponsor study monitor 
Refer to the local study contact information document. 
4. Sponsor study contact for reporting of a Serious Adverse Events (SAEs) 
GSK central back up study contact for reporting SAEs: refer to the protocol Section 
8.3.3.1.  
Study contact for reporting SAEs: refer to the local study contact information 
document. 
5. GSK Helpdesk for emergency unblinding  
Refer to the protocol section 6.3.5.4. 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Amendment 4 (22 March 2022) 
Overall rationale for the current Amendment: This protocol has been amended to add 
2 dosing schedules in the Phase II Sourcing part to support the finalization of assay 
development, further clinical testing, as well as assay stability monitoring and 
maintenance. 
Additional changes have been made to update the sample size, planned schedule of 
analyses and/or to improve the clarity of the text. Refer to Section 10.10.1 for details. 
List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
Section 1.3 Schedule of activities, Table 5, 
Table 6, Table 7, Table 8, Table 9 and 
Table10 
Section 3 Objectives and endpoints, Table 
11 
Section 4.1.2.2. (Study design) Phase II 
Sourcing 
Section 4.2 Scientific rationale for study 
design 
Section 6.1 Study intervention(s) 
administered 
Section 6.6 Continued access to study 
intervention after the end of the study 
Section 6.8 Concomitant therapy 
Section 8 Study assessments and 
procedures; Study procedures in special 
circumstances. 
Section 8.1.1.1 Blood sample 
Section 8.1.3 Immunological read-outs 
Section 8.3.1 Time period and frequency 
for collecting AE, SAE and other safety 
information 
Section 9.2.3: (Sample size determination) 
Phase II Sourcing 
Two (2) dosing schedules have 
been added in the Phase II 
Sourcing part. 
The wider dosing schedules have 
been included to support the 
finalization of assay development, 
further clinical testing, as well as 
assay stability monitoring and 
maintenance. 
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Section # and title 
Description of change 
Brief rationale 
Section 9.4.3 Primary endpoint(s) – Phase 
II (Sourcing) 
Section 9.4.6 Tertiary endpoint(s) – Phase 
II (Sourcing) 
Section 10.1.9.1 Study conclusions 
Section 10.3.8 Recording and follow-up of 
AEs, SAEs, AESIs and pregnancies 
Section 10.3.9.3 Medically attended visits 
Section 4.4 End of study definition 
Added a sentence to the 
definition for clarification. 
To explain that in case the date of 
last testing occurs prior to LSLV, 
the LSLV will be the EoS. 
Section 5.5 Criteria for temporarily 
delaying enrolment/ randomisation/ study 
intervention administration/blood sampling 
Section 10.3.9.5 Recording of AEs related 
to COVID-19 
Update has been done to the 
COVID-19 related wording in 
these sections. 
To align to the current COVID-19 
guidelines as per WHO and/or 
local regulations. 
Section 6.3.5 Blinding and unblinding 
Added wording to make clear 
that unblinding will be done 
phase wise. 
To clarify that the study will be 
unblinded after the completion of 
each Phase rather than at the end 
of the entire study.  
Section 9.5. Interim analyses 
The sequence of analyses and 
statistical considerations for 
interim analysis have been 
updated. 
The sequence of analyses has 
been presented in detail. 
 
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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 5 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 6 
1. 
PROTOCOL SUMMARY ........................................................................................ 18 
1.1. 
Synopsis ..................................................................................................... 18 
1.2. 
Schema ...................................................................................................... 18 
1.3. 
Schedule of Activities (SoA) ........................................................................ 19 
2. 
INTRODUCTION .................................................................................................... 33 
2.1. 
Study rationale ............................................................................................ 33 
2.2. 
Background ................................................................................................ 34 
2.3. 
Benefit/Risk assessment ............................................................................. 35 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 36 
4. 
STUDY DESIGN .................................................................................................... 42 
4.1. 
Overall design ............................................................................................. 42 
4.1.1. 
Phase I study design.................................................................... 42 
4.1.2. 
Phase II study design................................................................... 44 
4.1.2.1. 
Phase II: Formulation and Schedule-finding ............... 45 
4.1.2.2. 
Phase II: Sourcing ...................................................... 49 
4.2. 
Scientific rationale for study design ............................................................. 52 
4.3. 
Justification for dose ................................................................................... 53 
4.4. 
End of Study definition ................................................................................ 53 
5. 
STUDY POPULATION ........................................................................................... 54 
5.1. 
Inclusion criteria .......................................................................................... 54 
5.2. 
Exclusion criteria ......................................................................................... 55 
5.2.1. 
Medical conditions ....................................................................... 55 
5.2.2. 
Prior/Concomitant therapy ........................................................... 56 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 56 
5.2.4. 
Other exclusions .......................................................................... 57 
5.3. 
Lifestyle considerations ............................................................................... 57 
5.4. 
Screen failures ............................................................................................ 57 
5.5. 
Criteria for temporarily delaying enrolment/ randomisation/ study 
intervention administration/blood sampling ................................................. 57 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 58 
6.1. 
Study intervention(s) administered .............................................................. 58 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 65 
6.3. 
Measures to minimise bias: randomisation and blinding ............................. 65 
6.3.1. 
Participant identification ............................................................... 65 
6.3.2. 
Randomisation to study intervention ............................................ 65 
6.3.3. 
Intervention allocation to the participant ....................................... 65 
6.3.4. 
Allocation of participants to assay subsets ................................... 66 
6.3.5. 
Blinding and unblinding ................................................................ 66 
6.3.5.1. 
Phase I and Phase II (Sourcing) ................................. 66 
6.3.5.2. 
Phase II (Formulation and Schedule-finding) .............. 66 
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6.3.5.3. 
Unblinding .................................................................. 67 
6.3.5.4. 
Emergency unblinding ................................................ 67 
6.3.5.5. 
Unblinding prior to regulatory reporting of SAEs ......... 68 
6.4. 
Study intervention compliance .................................................................... 68 
6.5. 
Dose modification ....................................................................................... 68 
6.6. 
Continued access to study intervention after the end of the study ............... 68 
6.7. 
Treatment of overdose ................................................................................ 68 
6.8. 
Concomitant therapy ................................................................................... 69 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 70 
7.1. 
Discontinuation of study intervention ........................................................... 70 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration .............................................................................. 70 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 71 
7.3. 
Lost to follow-up .......................................................................................... 72 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 72 
8.1. 
Effectiveness and/or immunogenicity assessments .................................... 75 
8.1.1. 
Biological samples ....................................................................... 76 
8.1.1.1. 
Blood sample .............................................................. 76 
8.1.1.2. 
Urine sample .............................................................. 77 
8.1.2. 
Laboratory assays ....................................................................... 78 
 
 .............................................................. 79 
8.1.4. 
Clinical safety laboratory assessments ........................................ 82 
8.1.5. 
Immunological correlates of protection ......................................... 82 
8.2. 
Safety assessments .................................................................................... 82 
8.2.1. 
Pre-vaccination procedures ......................................................... 82 
8.2.1.1. 
Collection of demographic data .................................. 82 
8.2.1.2. 
Medical/vaccination history ......................................... 83 
8.2.1.3. 
General and symptom-directed physical 
examination ................................................................ 83 
8.2.1.4. 
Pregnancy test ........................................................... 83 
8.2.1.5. 
Warnings and precautions to vaccination ................... 84 
8.2.2. 
Study holding rules and safety monitoring .................................... 84 
8.2.2.1. 
Safety data review ...................................................... 84 
8.2.2.1.1. 
Safety evaluation .................................... 84 
8.2.2.1.2. 
Outcome of safety evaluation ................. 86 
8.2.2.1.3. 
Study holding rules ................................. 87 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and other 
safety reporting ........................................................................................... 89 
8.3.1. 
Time period and frequency for collecting AE, SAE and 
other safety information ............................................................... 89 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and 
other events ................................................................................. 95 
8.3.2.1. 
Clinically significant abnormal laboratory 
findings (Phase I)........................................................ 95 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies 
and other events .......................................................................... 95 
8.3.3.1. 
Contact information for reporting SAEs, AESIs, 
pregnancies and study holding rules .......................... 96 
8.3.4. 
Treatment of adverse events ....................................................... 97 
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8.3.5. 
Participant card ............................................................................ 97 
8.3.6. 
Medical device deficiencies.......................................................... 97 
8.3.6.1. 
Detection, follow-up and prompt reporting of 
medical device deficiency ........................................... 97 
8.3.6.2. 
Regulatory reporting of medical device 
deficiency when used as combination product ............ 97 
8.4. 
Pharmacokinetics ....................................................................................... 98 
8.5. 
Genetics and/or Pharmacogenomics .......................................................... 98 
8.6. 
Biomarkers ................................................................................................. 98 
8.7. 
Immunogenicity ........................................................................................... 98 
8.8. 
Health outcomes ......................................................................................... 98 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 98 
9.1. 
Statistical hypotheses ................................................................................. 98 
9.1.1. 
Phase I (Safety Lead-in) and Phase II (Sourcing) ........................ 98 
9.1.2. 
.. 98 
. 98 
. 99 
9.2. 
Sample size determination .......................................................................... 99 
9.2.1. 
Phase I (Safety Lead-in) .............................................................. 99 
9.2.2. 
Phase II (Formulation and Schedule-finding) ............................. 100 
. 100 
. 100 
9.2.3. 
Phase II (Sourcing) .................................................................... 101 
9.3. 
Analysis sets ............................................................................................. 102 
9.3.1. 
Criteria for elimination from analysis .......................................... 102 
9.4. 
Statistical analyses ................................................................................... 103 
9.4.1. 
Primary endpoint(s) – Phase I (Safety Lead-in) .......................... 103 
9.4.2. 
Primary endpoint(s) – Phase II (Formulation and 
Schedule-finding) ....................................................................... 104 
9.4.3. 
Primary endpoint(s) – Phase II (Sourcing) ................................. 106 
9.4.4. 
Secondary endpoint(s) – Phase II (Formulation and 
Schedule-finding) ....................................................................... 107 
............. 109 
............. 110 
............. 110 
............. 110 
............. 111 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................. 111 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations .......................................................................................... 111 
10.1.1. 
Regulatory and ethical considerations ....................................... 111 
10.1.2. 
Financial disclosure ................................................................... 112 
10.1.3. 
Informed consent process .......................................................... 112 
10.1.4. 
Data protection .......................................................................... 113 
10.1.5. 
Committees structure ................................................................. 113 
10.1.5.1. Responsibilities of the Investigator and IRB/EC ........ 113 
10.1.5.2. internal Safety Review Committee ............................ 114 
10.1.6. 
Dissemination of clinical study data ........................................... 115 
10.1.7. 
Data quality assurance .............................................................. 115 
10.1.8. 
Source documents ..................................................................... 116 
10.1.9. 
Study and site start and closure ................................................. 117 
10.1.9.1. Study conclusion ...................................................... 117 
10.1.10. Publication policy ....................................................................... 117 
10.2. 
Appendix 2: Clinical laboratory tests ......................................................... 118 
10.2.1. 
Protocol-required safety laboratory assessments ....................... 118 
10.2.2. 
Effectiveness and immunogenicity laboratory 
..... 118 
..... 119 
..... 119 
..... 119 
..... 120 
..... 120 
..... 120 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of AE ................ 121 
10.3.1. 
Definition of an Adverse Event (AE) ........................................... 121 
10.3.1.1. Events Meeting the AE Definition ............................. 121 
10.3.1.2. Events NOT Meeting the AE Definition ..................... 122 
10.3.2. 
Definition of an SAE ................................................................... 122 
10.3.3. 
Solicited events .......................................................................... 123 
10.3.4. 
Unsolicited adverse events ........................................................ 124 
10.3.5. 
Adverse events of special interest (AESIs) ................................ 124 
10.3.5.1. Potential immune-mediated diseases (pIMDs) .......... 124 
10.3.5.2. Other adverse events of special interest ................... 127 
10.3.5.2.1. Arthritis ................................................. 127 
10.3.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs .................................... 127 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs ................... 127 
10.3.7.1. Pregnancy ................................................................ 127 
10.3.8. 
Recording and follow-up of AEs, SAEs, AESIs and 
pregnancies ............................................................................... 128 
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10.3.8.1. Time period for collecting and recording AEs, 
SAEs, AESIs and pregnancies ................................. 129 
10.3.8.2. Follow-up of AEs, SAEs, AESIs, pregnancies 
or any other events of interest .................................. 130 
10.3.8.2.1. Follow-up during the study .................... 130 
10.3.8.2.2. Follow-up after the participant is 
discharged from the study..................... 130 
10.3.8.2.3. Follow-up of pregnancies ...................... 131 
10.3.8.3. Updating of SAE, AESI and pregnancy 
information after removal of write access to the 
participant’s eCRF .................................................... 131 
10.3.9. 
Assessment of intensity and toxicity ........................................... 131 
10.3.9.1. Assessment of intensity ............................................ 131 
10.3.9.2. Assessment of causality ........................................... 133 
10.3.9.3. Medically attended visits ........................................... 134 
10.3.9.4. Assessment of outcomes .......................................... 134 
10.3.9.5. Recording of AEs related to COVID-19 ..................... 134 
10.3.9.5.1. WHO Case Definition ............................ 135 
10.3.10. Reporting of SAEs, AESIs, pregnancies and other events ......... 136 
10.3.10.1. Events requiring expedited reporting to GSK ............ 136 
10.3.10.2. Back up system in case the electronic reporting 
system does not work ............................................... 137 
10.4. 
Appendix 4: FDA’s toxicity grading scale for healthy adult and 
adolescent volunteers enrolled in preventive vaccine clinical trials 
applied for this study ................................................................................. 137 
10.5. 
Appendix 5: Contraceptive guidance and collection of pregnancy 
information ................................................................................................ 138 
10.5.1. 
Definitions .................................................................................. 138 
10.5.1.1. Woman of Childbearing Potential (WOCBP) ............. 138 
10.5.1.1.1. Women not considered as women 
of childbearing potential ........................ 138 
10.5.2. 
Contraception guidance ............................................................. 139 
10.5.3. 
Collection of pregnancy information ........................................... 140 
10.5.3.1. Female participants who become pregnant .............. 140 
10.6. 
Appendix 6: Genetics ................................................................................ 140 
10.7. 
Appendix 7: Definition of medical device AE, adverse device effect 
(ADE), serious adverse device effect (SADE) and unanticipated 
SADE (USADE) ........................................................................................ 140 
10.7.1. 
Definition of medical device AE and adverse device effect 
(ADE) ......................................................................................... 140 
10.7.2. 
Definition of medical device SAE, SADE and USADE ................ 140 
10.7.3. 
Recording and reporting of medical device AE, ADEs, 
SADEs and USADE ................................................................... 141 
10.8. 
Appendix 8: Country-specific requirements ............................................... 141 
10.9. 
Appendix 9: Abbreviations and glossary of terms ...................................... 142 
10.9.1. 
List of abbreviations ................................................................... 142 
10.9.2. 
Glossary of terms ....................................................................... 144 
10.10. Appendix 10: Protocol Amendment history ............................................... 149 
10.10.1. Protocol amendment 4 ............................................................... 154 
10.10.2. Protocol amendment 3 ............................................................... 174 
10.10.3. Protocol amendment 2 ............................................................... 184 
10.10.4. Protocol amendment 1 ............................................................... 209 
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11. REFERENCES ..................................................................................................... 210 
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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities – Phase I ............................................................. 19 
Table 2 
Intervals between study visits/contacts –Phase I .................................... 21 
Table 3 
Schedule of activities – Phase II (Formulation and schedule-
finding) ................................................................................................... 22 
Table 4 
Intervals between study visits/contacts –Phase II (Formulation 
and schedule-finding) ............................................................................. 25 
Table 5 
Schedule of Activities – Phase II (Sourcing; 0, 1 month 
vaccination schedule) ............................................................................. 25 
Table 6 
Schedule of Activities – Phase II (Sourcing; 0, 2 month 
vaccination schedule) ............................................................................. 27 
Table 7 
Schedule of Activities – Phase II (Sourcing; 0, 6 month 
vaccination schedule) ............................................................................. 30 
Table 8 
Intervals between study visits/contacts – Phase II (Sourcing; 0, 1 
month vaccination schedule) .................................................................. 32 
Table 9 
Intervals between study visits/contacts – Phase II (Sourcing; 0, 2 
month vaccination schedule) .................................................................. 32 
Table 10 
Intervals between study visits/contacts – Phase II (Sourcing; 0, 6 
month vaccination schedule) .................................................................. 32 
Table 11 
Study objective(s) and endpoints ........................................................... 36 
Table 12 
Study groups, intervention and blinding – Phase I .................................. 44 
Table 13 
Study groups, intervention and blinding – Phase II (Formulation 
and Schedule-finding) ............................................................................ 48 
Table 14 
Study groups, intervention and blinding – Phase II (Sourcing) ................ 51 
Table 15 
Study intervention administered – Phase I ............................................. 59 
Table 16 
Study intervention administered – Phase II (Formulation and 
Schedule-finding) ................................................................................... 61 
Table 17 
Study intervention administered – Phase II (Sourcing) ........................... 63 
Table 18 
Contact information for emergency unblinding ....................................... 67 
Table 19 
Intervals between study visits/contacts during special 
circumstances – Phase I ........................................................................ 74 
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Table 20 
Intervals between study visits during special circumstances – 
Phase II Formulation and Schedule finding ............................................ 74 
Table 21 
Intervals between study visits/contacts during special 
circumstances – Phase II (Sourcing; 0,1 month vaccination 
schedule) ............................................................................................... 75 
Table 22 
Intervals between study visits/contacts during special 
circumstances – Phase II (Sourcing; 0,2 month vaccination 
schedule) ............................................................................................... 75 
Table 23 
Intervals between study visits/contacts during special 
circumstances – Phase II (Sourcing; 0,6 month vaccination 
schedule) ............................................................................................... 75 
Table 24 
Blood samples at Phase I ....................................................................... 76 
Table 25 
Blood samples at Phase II (Sourcing; 0,1 month vaccination 
schedule) ............................................................................................... 76 
Table 26 
Blood samples at Phase II (Sourcing; 0,2 and 0,6 month 
vaccination schedule) ............................................................................. 76 
Table 27 
Blood samples at Phase II (Formulation and schedule-finding) .............. 77 
Table 28 
Laboratory assays – Phase I and II ........................................................ 78 
Table 29 
Immunological read-outs – Phase II (Formulation and Schedule-
finding), 0_6 schedule: For 
 and 
Control groups........................................................................................ 79 
Table 30 
Immunological read-outs – Phase II (Formulation and Schedule-
finding), 0_2 schedule: 
 
groups .................................................................................................... 80 
Table 31 
Immunological read-outs – Phase II (Sourcing): 
 
 groups ................................................................... 81 
Table 32 
Study holding rules – Phase I ................................................................. 88 
Table 33 
Study holding rules – Phase II (Formulation and Schedule-
finding) ................................................................................................... 88 
Table 34 
Timeframes for collecting and reporting of safety information – 
Phase I ................................................................................................... 89 
Table 35 
Timeframes for collecting and reporting of safety information – 
Phase II (Formulation and schedule-finding) .......................................... 91 
Table 36 
Timeframes for collecting and reporting of safety information – 
Phase II (Sourcing; 0,1 month vaccination schedule) ............................. 92 
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Table 37 
Timeframes for collecting and reporting of safety information – 
Phase II (Sourcing; 0,2 month vaccination schedule) ............................. 93 
Table 38 
Timeframes for collecting and reporting of safety information – 
Phase II (Sourcing; 0,6 month vaccination schedule) ............................. 94 
Table 39 
Timeframes for submitting SAE, pregnancy and other events 
reports to GSK ....................................................................................... 96 
Table 40 
Contact information for reporting SAEs, AESIs, pregnancies and 
study holding rules ................................................................................. 96 
Table 41 
Power calculation to demonstrate superiority of 
 
compared to Control, for percentage of samples with bactericidal 
activity at 1:4 dilution ............................................................................ 100 
Table 42 
Power calculation to demonstrate non-inferiority for serogroups 
A, C, W and Y of 
compared to Control at 1 month 
after the second dose vs 1 month after a single dose ........................... 101 
Table 43 
Analysis sets ........................................................................................ 102 
Table 44 
Haematology and biochemistry tests – Phase I .................................... 118 
Table 45 
Solicited administration site events – Phase I and II ............................. 123 
Table 46 
Solicited systemic events – Phase I and II ............................................ 123 
Table 47 
List of potential immune-mediated diseases (pIMDs) ........................... 125 
Table 48 
Intensity scales for solicited events in adults and children of 10 
years of age or more ............................................................................ 131 
Table 49 
Laboratory abnormalities ...................................................................... 137 
Table 50 
Highly effective contraceptive methods ................................................ 139 
 
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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview – Phase I (Safety Lead-in) ................................. 43 
Figure 2 
Study design overview – Phase II (Formulation and Schedule-
finding) ................................................................................................... 46 
Figure 3 
Study design overview – Phase II (Sourcing) ......................................... 50 
Figure 4 
Step-wise approach for safety review in Phase I (Safety Lead-in) .......... 84 
Figure 5 
Step-wise approach for safety review in Phase II (Formulation 
and Schedule-finding) ............................................................................ 85 
 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Rationale: Neisseria meningitidis infections causing invasive meningococcal disease 
(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. Ninety 
percent of meningococcal meningitis and septicaemia are caused by only 5 N. 
meningitidis serogroups: A, B, C, W and Y. 
GSK is currently developing a MenABCWY combination vaccine intended to protect 
against IMD caused by all 5 meningococcal serogroups. 
The early clinical development plan consists of a seamless Phase I/II study. The first-
time-in-human (FTIH), Phase I part of this study will be conducted in healthy adults in a 
dose-escalating fashion with 2 formulations of the investigational 
 
 and will serve as a 
safety lead-in to the Phase II study.  
The Phase II part of the study will be conducted in 2 parts: The ‘formulation and 
schedule-finding’ part will follow in healthy adolescents and young adults and it is 
designed to select the vaccine formulation and the schedule to be tested in Phase III. The 
‘blood sourcing’ part will be conducted in healthy adults in order to collect sufficient 
serum samples for the development of assays to be used in the 
vaccine 
clinical development program. Phase II will assess the safety, the effectiveness and the 
immunogenicity of the above 2 formulations of the investigational 
 
vaccine. Bexsero (rMenB+OMV NZ, hereafter referred to as MenB) and Menveo 
(hereafter referred to as MenACWY) will be administered as control vaccines for 
assessing the response to serogroups B and ACWY, respectively. 
Objectives and endpoints: Refer to Table 11 for the study objectives and endpoints. 
1.2. 
Schema 
Refer to Figure 1, Figure 2 and Figure 3 in Section 4.1, Overall design. 
 
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1.3. 
Schedule of Activities (SoA) 
(Amended 22 March 2022) 
Table 1 
Schedule of Activities – Phase I 
Type of contact 
Visit Visit Visit 
PC 
Visit 
PC 
PC 
Notes 
Visit/Phone call no. 
V1 
V2 
V3 
T1 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 2 for visit windows] 
Day 1 Day 8 Day 
31 
Day 
38 
Day 
61 
Day 
151 
Day 
211 
Informed consent 
● 
 
 
 
 
 
 
Confirm consent form signed prior to any procedures. 
Before performing any study-related activities, check the randomisation 
system to ensure that enrolment is still open 
See Section 10.1.3 for details 
Check inclusion/exclusion criteria 
● 
 
○ 
 
 
 
 
Prior to administering each study intervention, the investigator must check 
eligibility criteria for subsequent vaccinations and criteria for delay of study 
intervention administration. 
See Sections 5.1 and 5.2 for inclusion and exclusion criteria 
Study group and treatment number allocation 
(randomisation) 
● 
 
 
 
 
 
 
See Section 6.3 for more information 
Treatment number allocation for subsequent doses 
 
 
○ 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
See Section 8.2.1.1 for more information 
Medical and vaccination history  
● 
 
 
 
 
 
 
See Section 8.2.1.2 for more information 
General physical examination  
○ 
 
 
 
 
 
 
Physical examination to be performed by a qualified health professional in 
accordance with local regulations and licensing requirements designated 
within the Delegation of Responsibility Log. 
See Section 8.2.1.3 for more information 
Symptom-directed physical examination 
 
○ 
○ 
 
○ 
 
 
Check contraindications, warnings and precautions 
to study intervention administration 
○ 
 
○ 
 
 
 
 
See Sections 7.1.1 and 8.2.1.5 for more information 
Check criteria for temporary delay for 
enrolment/study intervention administration/blood 
sampling 
○ 
○ 
○ 
 
○ 
 
 
See Section 5.5 for more information 
Urine pregnancy test for females 
● 
 
● 
 
 
 
 
See Section 8.2.1.4 for more information 
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Type of contact 
Visit Visit Visit 
PC 
Visit 
PC 
PC 
Notes 
Visit/Phone call no. 
V1 
V2 
V3 
T1 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 2 for visit windows] 
Day 1 Day 8 Day 
31 
Day 
38 
Day 
61 
Day 
151 
Day 
211 
Body temperature before study intervention 
administration 
● 
 
● 
 
 
 
 
Fever is defined as temperature 38.0°C/100.4°F. Preferred location for 
measuring temperature will be the oral cavity. If any other route is used for 
measuring temperature, this needs to be recorded in the eCRF 
Blood sampling for sourcing 
●^ 
 
●^ 
 
● 
 
 
Blood volume of approximately 80 mL will be collected at each blood sampling 
visit. 
See Section 8.1.1.1 for more information 
Blood sampling for safety laboratory evaluation  
●^ 
● 
 
 
 
 
 
Blood volume of ~7 mL will be collected. See Section 8.1.1.1 for more 
information 
Study intervention administration 
● 
 
● 
 
 
 
 
See Section 6.1 for more information 
Recording of administered study intervention 
number 
● 
 
● 
 
 
 
 
 
Post-injection assessment (30 minutes) 
● 
 
● 
 
 
 
 
See Section 10.3.8.1 for more information 
Distribution of eDiary  
○ 
 
○ 
 
 
 
 
 
Review of eDiary 
 
● 
● 
● 
● 
 
 
 
Return of eDiary 
 
 
 
 
● 
 
 
 
Recording of solicited AEs (Days 1–7 post-
vaccination)  
x 
 
x 
 
 
 
 
See Section 10.3.8 for more information 
Recording of unsolicited AEs (Days 1-30 post-
vaccination)* 
● 
● 
● 
● 
● 
 
 
See Section 10.3.8 for more information 
Record any concomitant medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
Timeframe for recording of concomitant medications/vaccinations is according 
to the recording period of the AEs for which they are being administered 
See Section 6.8 for more information 
Record any intercurrent medical conditions* 
 
● 
● 
● 
● 
● 
● 
See Section 9.3.1 for more information 
Recording of any AEs leading to vaccine/study 
withdrawal, SAEs, pregnancies and AESIs* 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording of SAEs related to study participation, or 
to a concurrent GSK medication/ vaccine 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs related to study participation, or to a concurrent GSK 
medication/vaccine begins from the time a participant signs the consent form 
to the study end. 
See Section 10.3.8 for more information 
Study (Phase I) Conclusion 
 
 
 
 
 
 
● 
Participants who terminate the study early are recommended to complete 
certain study-related procedures. 
See Section 4.4 and 10.1.9.1 for more information 
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● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. Documentation will be required in the source documents 
× is used to indicate a study procedure that will be documented in the eDiary  
^ Procedure to be performed prior to study intervention administration 
Abbreviation: PC, phone contact; V, clinic visit; T, telephone call; AE, adverse event; SAE, serious adverse event; AESI, adverse events of special interest. Note: All procedures to be 
performed prior to study intervention administration (as applicable). The study timepoints are the same for all groups, irrespective of the staggered enrolment (See Section 8.2.2.1).  
* Diagnosis of coronavirus 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 
Section 10.3 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 34). In addition, separate COVID-19 specific eCRF form(s) should be completed  
Note: Refer to Section 8 for information on study procedures during special circumstances 
Table 2 
Intervals between study visits/contacts –Phase I 
Interval 
Planned visit/ phone call interval  
Allowed interval range (visit window) 
Visit V1 → Visit V2  
7 days 
6 to 8 days (-1 to +1 days) 
Visit V1 → Visit V3 
30 days 
44 days (+14 days) 
Visit V3 → Telephone contact T1 
7 days 
6 to 8 days (-1 to +1 days) 
Visit V3 → Visit V4 
30 days 
25 to 44 days (-5 to +14 days) 
Visit V3 → Telephone contact T2 
120 days 
113 to 134 days (-7 to +14 days) 
Visit V3 → Telephone contact T3 
180 days 
173 to 194 days (-7 to +14 days) 
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Table 3 
Schedule of activities – Phase II (Formulation and schedule-finding) 
Type of contact 
Visit PC Visit PC 
Visit 
PC 
Visit Visit PC 
PC 
PC Visit 
Notes 
Visit/Phone call no. 
V1 
T1 
V2 
T2 
V3† 
TC†† 
V4 
V5 
T3 
T4 
T5 
V6 
Timepoint(s) 
[refer to Table 4 for visit windows] 
Day 
1 
Day  
8 
Day 
31 
Day 
91 
Day 
121 
Day 
121 
Day 
181 
Day 
211 
Day 
271 
Day 
361 
Day 
451 
Day 
541 
Groups 
All First 
45** All 
All ABCWY 
groups 
Control 
group 
All 
All 
All 
All 
All 
All 
 
Informed consent 
● 
 
 
 
 
 
 
 
 
 
 
 
Confirm consent form signed prior to any procedures. 
Before performing any study-related activities, check the 
randomisation system to ensure that enrolment is still open 
See Section 10.1.3 for details 
Informed assent, if applicable 
○ 
 
 
 
 
 
 
 
 
 
 
 
Confirm assent form (if applicable) signed prior to any 
procedures  
Check inclusion/exclusion criteria 
● 
 
 
 
○ 
 
○ 
 
 
 
 
 
Prior to administering each study intervention the 
investigator must check eligibility criteria for subsequent 
vaccination and criteria for delay of study intervention 
administration 
See Sections 5.1 and 5.2 for inclusion and exclusion criteria 
Study group and treatment number 
allocation (randomisation) 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 6.3 for more information 
Treatment number allocation for 
subsequent doses 
 
 
 
 
○ 
 
○ 
 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.1 for more information 
Medical and vaccination history  
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.2 for more information 
General physical examination  
○ 
 
 
 
 
 
 
 
 
 
 
 
Physical examination to be performed by a qualified health 
professional in accordance with local regulations and 
licensing requirements designated within the Delegation of 
Responsibility Log. 
See Section 8.2.1.3 for more information 
Symptom-directed physical examination 
 
 
○ 
 
○ 
 
○ 
○ 
 
 
 
○ 
Check contraindications, warnings and 
precautions to study intervention 
administration 
○ 
 
 
 
○ 
 
○ 
 
 
 
 
 
See Sections 7.1.1 and 8.2.1.5 for more information 
Check criteria for temporary delay for 
enrolment/study intervention 
administration/blood sampling 
○ 
 
○ 
 
○ 
 
○ 
○ 
 
 
 
○ 
See Section 5.5 for more information 
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Type of contact 
Visit PC Visit PC 
Visit 
PC 
Visit Visit PC 
PC 
PC Visit 
Notes 
Visit/Phone call no. 
V1 
T1 
V2 
T2 
V3† 
TC†† 
V4 
V5 
T3 
T4 
T5 
V6 
Timepoint(s) 
[refer to Table 4 for visit windows] 
Day 
1 
Day  
8 
Day 
31 
Day 
91 
Day 
121 
Day 
121 
Day 
181 
Day 
211 
Day 
271 
Day 
361 
Day 
451 
Day 
541 
Groups 
All First 
45** All 
All ABCWY 
groups 
Control 
group 
All 
All 
All 
All 
All 
All 
 
Urine pregnancy test for females of 
childbearing potential 
● 
 
 
 
● 
 
● 
 
 
 
 
 
See Section 8.2.1.4 for more information 
Body temperature before study intervention 
administration 
● 
 
 
 
● 
 
● 
 
 
 
 
 
Fever is defined as temperature 38.0°C/100.4°F. 
Preferred location for measuring temperature will be the oral 
cavity. If any other route is used for measuring temperature, 
this needs to be recorded in the eCRF 
Blood sampling 
●^ 
 
● 
 
 
 
 
● 
 
 
 
● 
Blood volume of approximately 15 mL will be collected at 
V1 (pre-vaccination) and V2 and approximately 30 mL at V5 
and V6. 
See Section 8.1.1.1 for more information 
Study intervention administration 
● 
 
 
 
● 
 
● 
 
 
 
 
 
See Section 6.1 for more information 
Recording of administered study 
intervention number 
● 
 
 
 
● 
 
● 
 
 
 
 
 
 
Post-injection assessment (30 minutes) 
● 
 
 
 
● 
 
● 
 
 
 
 
 
See Section 10.3.8.1 for more information 
Distribution of eDiary  
○ 
 
 
 
○ 
 
○ 
 
 
 
 
 
 
Review of eDiary 
 
● 
● 
 
 
 
●‡ 
● 
 
 
 
 
 
Return of eDiary 
 
 
 
 
 
 
 
● 
 
 
 
 
 
Recording of solicited AEs (Days 1–7 post-
vaccination) 
x 
 
 
 
x 
 
x 
 
 
 
 
 
See Section 10.3.8 for more information 
Recording of unsolicited AEs (Days 1-30 
post-vaccination) 
● 
● 
● 
 
● 
 
● 
● 
 
 
 
 
See Section 10.3.8 for more information 
Record any concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Timeframe for recording of concomitant 
medications/vaccinations is according to the recording 
period of the AEs for which they are being administered. 
See Section 6.8 for more information 
Record any intercurrent medical conditions 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● See Section 9.3.1 for more information 
Recording of any AEs leading to 
vaccine/study withdrawal, SAEs, 
pregnancies and AESIs* 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
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Type of contact 
Visit PC Visit PC 
Visit 
PC 
Visit Visit PC 
PC 
PC Visit 
Notes 
Visit/Phone call no. 
V1 
T1 
V2 
T2 
V3† 
TC†† 
V4 
V5 
T3 
T4 
T5 
V6 
Timepoint(s) 
[refer to Table 4 for visit windows] 
Day 
1 
Day  
8 
Day 
31 
Day 
91 
Day 
121 
Day 
121 
Day 
181 
Day 
211 
Day 
271 
Day 
361 
Day 
451 
Day 
541 
Groups 
All First 
45** All 
All ABCWY 
groups 
Control 
group 
All 
All 
All 
All 
All 
All 
 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs related to study participation, or to a 
concurrent GSK medication/vaccine begins from the time a 
participant signs the consent form to the study end. 
See Section 10.3.8 for more information 
Study Conclusion 
 
 
 
 
 
 
 
 
 
 
 
● 
Participants who terminate the study early are 
recommended to complete certain study-related procedures 
See Section 4.4 and 10.1.9.1 for more information 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. Documentation will be required in the source documents.  
× is used to indicate a study procedure that will be documented in eDiary.  
^ Procedure to be performed prior to study intervention administration 
Abbreviation: PC, phone contact; V, clinic visit; T, telephone call; TC, Telephone call for Control group only; AE, adverse event; SAE, serious adverse event; AESI, adverse events of 
special interest.  
Note: All procedures to be performed prior to study intervention administration (as applicable). The study timepoints are the same for all groups, irrespective of the staggered enrolment 
(See Section 8.2.2.1) 
* Diagnosis of COVID-19 should be made in accordance with the World Health Organization case definitions. Cases should be reported as AEs or SAEs (refer to Section 10.3 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 35). In addition, separate COVID-19 specific eCRF form(s) should be completed. 
** The phone call at Day 8 is only for the first 45 participants (15 participants in 
, 5 participants in 
, 15 participants in 
, 5 participants in 
 and 5 participants in the Control groups). Refer to Section 4.1.2.1 and Figure 2 for details. 
† Visit V3 (at Day 121) is only applicable for 
 groups 
† †  TC (at Day 121) is only applicable for the Control group  
‡ Not applicable for Control group 
Note 1: If local regulations allow and quality of study procedures is maintained, participant(s) can be offered remote visits (e.g. home visits) for the collection of biological samples 
and/or study intervention administration (except for Visit V1 which will always be a clinic visit). These remote visits must be performed by qualified study staff/healthcare professionals 
(HCPs). Details of how these visits will be conducted are outlined in the study procedure manual (SPM). Refer to Section 8 (decentralised study procedures) for details 
Note 2: Refer to Section 8 for information on study procedures during special circumstances 
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Table 4 
Intervals between study visits/contacts –Phase II (Formulation and 
schedule-finding) 
Interval 
Planned visit interval  
Allowed interval range 
Visit V1 → Telephone contact T1*  
7 days 
6 to 8 days (-1 to +1 days) 
Visit V1 → Visit V2 
30 days 
25 to 44 days (-5 to +14 days) 
Visit V1 → Telephone contact T2 
90 days 
83 to 104 days (-7 to +14 days) 
Visit V2 → Visit V3/TC** 
90 days 
85 to 104 days (-5 to +14 days) 
Visit V3/TC** → Visit V4 
60 days 
55 to 74 days (-5 to +14 days) 
Visit V4 → Visit V5 
30 days 
25 to 44 days (-5 to +14 days) 
Visit V4 → Telephone contact T3 
90 days 
83 to 104 days (-7 to +14 days) 
Visit V4 → Telephone contact T4 
180 days 
173 to 194 days (-7 to +14 days) 
Visit V4 → Telephone contact T5 
270 days 
263 to 284 days (-7 to +14 days) 
Visit V4 → Visit V6 
360 days 
353 to 374 days (-7 to +14 days) 
T, Telephone contact; TC, Telephone contact for Control group only 
* The phone call (T1) at Day 8 is only for the first 45 participants (15 participants in 
, 5 participants in 
, 15 participants in
, 5 participants in 
 and 5 participants in the Control 
groups). 
** Visit for 
 groups (Visit V3) and telephone call 
for Control group (TC)  
Table 5 
Schedule of Activities – Phase II (Sourcing; 0, 1 month vaccination 
schedule) 
(Amended 22 March 2022) 
Type of contact 
Visit Visit Visit PC 
PC 
Notes 
Visit/Phone call no. 
V1 
V2 
V3 
T1 
T2 
Timepoint(s) 
 [refer to Table 8 for visit windows] 
Day 
1 
Day 
31 
Day 
61 
Day 
151 
Day 
211 
Informed consent 
● 
 
 
 
 
Confirm consent form signed prior to any 
procedures. 
Before performing any study-related activities, 
check the randomisation system to ensure that 
enrolment is still open 
See Section 10.1.3 for details 
Check inclusion/exclusion criteria 
● 
○ 
 
 
 
Prior to administering each study intervention, 
the investigator must check eligibility criteria for 
subsequent vaccinations and criteria for delay 
of study intervention administration. 
See Sections 5.1 and 5.2 for inclusion and 
exclusion criteria 
Study group and treatment number 
allocation (randomisation) 
● 
 
 
 
 
See Section 6.3 for more information 
Treatment number allocation for 
subsequent doses 
 
○ 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
See Section 8.2.1.1 for more information 
Medical and vaccination history  
● 
 
 
 
 
See Section 8.2.1.2 for more information 
General physical examination  
○ 
 
 
 
 
Physical examination to be performed by a 
qualified health professional in accordance with 
local regulations and licensing requirements 
designated within the Delegation of 
Responsibility Log. 
See Section 8.2.1.3 for more information 
Symptom-directed physical 
examination 
 
○ 
○ 
 
 
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Type of contact 
Visit Visit Visit PC 
PC 
Notes 
Visit/Phone call no. 
V1 
V2 
V3 
T1 
T2 
Timepoint(s) 
 [refer to Table 8 for visit windows] 
Day 
1 
Day 
31 
Day 
61 
Day 
151 
Day 
211 
Check contraindications, warnings 
and precautions to study intervention 
administration 
○ 
○ 
 
 
 
See Sections 7.1.1 and 8.2.1.5 for more 
information 
Check criteria for temporary delay for 
enrolment/study intervention 
administration/blood sampling 
○ 
○ 
○ 
 
 
See Section 5.5 for more information 
Urine pregnancy test for females 
● 
● 
 
 
 
See Section 8.2.1.4 for more information 
Body temperature before study 
intervention administration 
● 
● 
 
 
 
Fever is defined as temperature 
38.0°C/100.4°F. Preferred location for 
measuring temperature will be the oral cavity. If 
any other route is used for measuring 
temperature, this needs to be recorded in the 
eCRF 
Blood sampling 
●^ 
●^ 
● 
 
 
Blood volume of approximately 95 mL will be 
collected at each blood sampling visit. 
See Section 8.1.1.1 for more information 
Study intervention administration 
● 
● 
 
 
 
See Section 6.1 for more information 
Recording of administered study 
intervention number 
● 
● 
 
 
 
 
Post-injection assessment (30 
minutes) 
● 
● 
 
 
 
See Section 10.3.8.1 for more information 
Distribution of eDiary  
○ 
 
 
 
 
 
Review of eDiary 
 
● 
● 
 
 
 
Return of eDiary 
 
 
● 
 
 
 
Recording of solicited AEs (Days 1–7 
post-vaccination)  
x 
x 
 
 
 
See Section 10.3.8 for more information  
Recording of unsolicited AEs (Days 
1-30 post-vaccination) 
● 
● 
● 
 
 
See Section 10.3.8 for more information 
Record any concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
Timeframe for recording of concomitant 
medications/vaccinations is according to the 
recording period of the AEs for which they are 
being administered 
See Section 6.8 for more information 
Record any intercurrent medical 
conditions 
 
● 
● 
● 
● 
See Section 9.3.1 for more information 
Recording of any AEs leading to 
vaccine/study withdrawal, SAEs, 
pregnancies and AESIs* 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/ vaccine 
● 
● 
● 
● 
● 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine begins from the time a 
participant signs the consent form to the study 
end. 
See Section 10.3.8 for more information 
Study (Phase II, Sourcing) 
Conclusion 
 
 
 
 
● 
Participants who terminate the study early are 
recommended to complete certain study-related 
procedures. 
See Section 4.4 and 10.1.9.1 for more 
information 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. Documentation will 
be required in the source documents 
× is used to indicate a study procedure that will be documented in the eDiary  
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^ Procedure to be performed prior to study intervention administration 
Abbreviation: PC, phone contact; V, clinic visit; T, telephone call; AE, adverse event; SAE, serious adverse event; 
AESI, adverse events of special interest. Note: All procedures to be performed prior to study intervention administration 
(as applicable).  
* Diagnosis of coronavirus 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 Section 10.3 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 36). In addition, separate COVID-19 specific eCRF form(s) should be 
completed  
Note 1: If local regulations allow and quality of study procedures is maintained, participant(s) can be offered remote 
visits (e.g. home visits) for the collection of biological samples and/or study intervention administration (except for Visit 
V1 which will always be a clinic visit). These remote visits must be performed by qualified study staff/ HCPs. Details of 
how these visits will be conducted are outlined in the SPM. Refer to Section 8 (decentralised study procedures) for 
details 
Note 2: Refer to Section 8 for information on study procedures during special circumstances 
Table 6 
Schedule of Activities – Phase II (Sourcing; 0, 2 month vaccination 
schedule) 
(Amended 22 March 2022) 
Type of contact 
Visit PC Visit Visit Visit PC PC 
Notes 
Visit/Phone call no. 
V1 T1 V2 
V3 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 9 for visit 
windows] 
Day 
1 
Day 
31 
Day 
61 
Day 
76 
Day 
91 
Day 
181 
Day 
241 
Informed consent 
● 
 
 
 
 
 
 
Confirm consent form signed prior to 
any procedures. 
Before performing any study-related 
activities, check the randomisation 
system to ensure that enrolment is still 
open 
See Section 10.1.3 for details 
Check inclusion/exclusion 
criteria 
● 
 
○ 
 
 
 
 
Prior to administering each study 
intervention, the investigator must 
check eligibility criteria for subsequent 
vaccinations and criteria for delay of 
study intervention administration. 
See Sections 5.1 and 5.2 for inclusion 
and exclusion criteria 
Study group and treatment 
number allocation 
(randomisation) 
● 
 
 
 
 
 
 
See Section 6.3 for more information 
Treatment number allocation 
for subsequent doses 
 
 
○ 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
See Section 8.2.1.1 for more information 
Medical and vaccination 
history  
● 
 
 
 
 
 
 
See Section 8.2.1.2 for more information 
General physical examination  
○ 
 
 
 
 
 
 
Physical examination to be performed 
by a qualified health professional in 
accordance with local regulations and 
licensing requirements designated 
within the Delegation of Responsibility 
Log. 
See Section 8.2.1.3 for more information 
Symptom-directed physical 
examination 
 
 
○ 
○ 
○ 
 
 
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Type of contact 
Visit PC Visit Visit Visit PC PC 
Notes 
Visit/Phone call no. 
V1 T1 V2 
V3 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 9 for visit 
windows] 
Day 
1 
Day 
31 
Day 
61 
Day 
76 
Day 
91 
Day 
181 
Day 
241 
Check contraindications, 
warnings and precautions to 
study intervention 
administration 
○ 
 
○ 
 
 
 
 
See Sections 7.1.1 and 8.2.1.5 for more 
information 
Check criteria for temporary 
delay for enrolment/study 
intervention 
administration/blood sampling 
○ 
 
○ 
○ 
○ 
 
 
See Section 5.5 for more information 
Urine pregnancy test for 
females 
● 
 
● 
 
 
 
 
See Section 8.2.1.4 for more information 
Body temperature before study 
intervention administration 
● 
 
● 
 
 
 
 
Fever is defined as temperature 
38.0°C/100.4°F. Preferred location for 
measuring temperature will be the oral 
cavity. If any other route is used for 
measuring temperature, this needs to 
be recorded in the eCRF 
Blood sampling 
●^ 
 
 
● 
● 
 
 
Blood volume of approximately 95 mL 
will be collected at each blood sampling 
visit. 
See Section 8.1.1.1 for more information 
Study intervention 
administration 
● 
 
● 
 
 
 
 
See Section 6.1 for more information 
Recording of administered 
study intervention number 
● 
 
● 
 
 
 
 
 
Post-injection assessment (30 
minutes) 
● 
 
● 
 
 
 
 
See Section 10.3.8.1 for more 
information 
Distribution of eDiary  
○ 
 
 
 
 
 
 
 
Review of eDiary 
 
● 
 
● 
● 
 
 
 
Return of eDiary 
 
 
 
 
● 
 
 
 
Recording of solicited AEs 
(Days 1–7 post-vaccination)  
x 
 
x 
 
 
 
 
See Section 10.3.8 for more information  
Recording of unsolicited AEs 
(Days 1-30 post-vaccination) 
● 
● 
● 
● 
● 
 
 
See Section 10.3.8 for more information 
Record any concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
Timeframe for recording of concomitant 
medications/vaccinations is according 
to the recording period of the AEs for 
which they are being administered 
See Section 6.8 for more information 
Record any intercurrent 
medical conditions 
 
● 
● 
● 
● 
● 
● See Section 9.3.1 for more information 
Recording of any AEs leading 
to vaccine/study withdrawal, 
SAEs, pregnancies and AESIs* 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording of SAEs related to 
study participation, or to a 
concurrent GSK medication/ 
vaccine 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine begins from the 
time a participant signs the consent 
form to the study end. 
See Section 10.3.8 for more information 
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Type of contact 
Visit PC Visit Visit Visit PC PC 
Notes 
Visit/Phone call no. 
V1 T1 V2 
V3 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 9 for visit 
windows] 
Day 
1 
Day 
31 
Day 
61 
Day 
76 
Day 
91 
Day 
181 
Day 
241 
Study (Phase II, Sourcing) 
Conclusion 
 
 
 
 
 
 
● 
Participants who terminate the study 
early are recommended to complete 
certain study-related procedures. 
See Section 4.4 and 10.1.9.1 for more 
information 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
Documentation will be required in the source documents 
× is used to indicate a study procedure that will be documented in the eDiary  
^ Procedure to be performed prior to study intervention administration 
Abbreviation: PC, phone contact; V, clinic visit; T, telephone call; AE, adverse event; SAE, serious adverse 
event; AESI, adverse events of special interest. Note: All procedures to be performed prior to study 
intervention administration (as applicable).  
* Diagnosis of coronavirus 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 Section 10.3 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 36). In addition, separate COVID-19 specific 
eCRF form(s) should be completed  
Note 1: If local regulations allow and quality of study procedures is maintained, participant(s) can be offered 
remote visits (e.g. home visits) for the collection of biological samples and/or study intervention 
administration (except for Visit V1 which will always be a clinic visit). These remote visits must be performed 
by qualified study staff/ HCPs. Details of how these visits will be conducted are outlined in the SPM. Refer to 
Section 8 (decentralised study procedures) for details 
Note 2: Refer to Section 8 for information on study procedures during special circumstances 
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Table 7 
Schedule of Activities – Phase II (Sourcing; 0, 6 month vaccination 
schedule) 
(Amended 22 March 2022) 
Type of contact 
Visit PC Visit Visit Visit PC PC 
Notes 
Visit/Phone call no. 
V1 T1 V2 
V3 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 10 for visit 
windows] 
Day 
1 
Day 
31 
Day 
181 
Day 
196 
Day 
211 
Day 
301 
Day 
361 
Informed consent 
● 
 
 
 
 
 
 
Confirm consent form signed prior to 
any procedures. 
Before performing any study-related 
activities, check the randomisation 
system to ensure that enrolment is still 
open 
See Section 10.1.3 for details 
Check inclusion/exclusion 
criteria 
 
● 
 
○ 
 
 
 
 
Prior to administering each study 
intervention, the investigator must 
check eligibility criteria for subsequent 
vaccinations and criteria for delay of 
study intervention administration. 
See Sections 5.1 and 5.2 for inclusion 
and exclusion criteria 
Study group and treatment 
number allocation 
(randomisation) 
● 
 
 
 
 
 
 
See Section 6.3 for more information 
Treatment number allocation 
for subsequent doses 
 
 
○ 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
See Section 8.2.1.1 for more information 
Medical and vaccination 
history  
● 
 
 
 
 
 
 
See Section 8.2.1.2 for more information 
General physical examination  
○ 
 
 
 
 
 
 
Physical examination to be performed 
by a qualified health professional in 
accordance with local regulations and 
licensing requirements designated 
within the Delegation of Responsibility 
Log. 
See Section 8.2.1.3 for more information 
Symptom-directed physical 
examination 
 
 
○ 
○ 
○ 
 
 
Check contraindications, 
warnings and precautions to 
study intervention 
administration 
○ 
 
○ 
 
 
 
 
See Sections 7.1.1 and 8.2.1.5 for more 
information 
Check criteria for temporary 
delay for enrolment/study 
intervention 
administration/blood sampling 
○ 
 
○ 
○ 
○ 
 
 
See Section 5.5 for more information 
Urine pregnancy test for 
females 
● 
 
● 
 
 
 
 
See Section 8.2.1.4 for more information 
Body temperature before study 
intervention administration 
● 
 
● 
 
 
 
 
Fever is defined as temperature 
38.0°C/100.4°F. Preferred location for 
measuring temperature will be the oral 
cavity. If any other route is used for 
measuring temperature, this needs to 
be recorded in the eCRF 
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Type of contact 
Visit PC Visit Visit Visit PC PC 
Notes 
Visit/Phone call no. 
V1 T1 V2 
V3 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 10 for visit 
windows] 
Day 
1 
Day 
31 
Day 
181 
Day 
196 
Day 
211 
Day 
301 
Day 
361 
Blood sampling 
●^ 
 
 
● 
● 
 
 
Blood volume of approximately 95 mL 
will be collected at each blood sampling 
visit. 
See Section 8.1.1.1 for more information 
Study intervention 
administration 
● 
 
● 
 
 
 
 
See Section 6.1 for more information 
Recording of administered 
study intervention number 
● 
 
● 
 
 
 
 
 
Post-injection assessment (30 
minutes) 
● 
 
● 
 
 
 
 
See Section 10.3.8.1 for more 
information 
Distribution of eDiary  
○ 
 
 
 
 
 
 
 
Review of eDiary 
 
● 
 
● 
● 
 
 
 
Return of eDiary 
 
 
 
 
● 
 
 
 
Recording of solicited AEs 
(Days 1–7 post-vaccination)  
x 
 
x 
 
 
 
 
See Section 10.3.8 for more information  
Recording of unsolicited AEs 
(Days 1-30 post-vaccination) 
● 
● 
● 
● 
● 
 
 
See Section 10.3.8 for more information 
Record any concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
Timeframe for recording of concomitant 
medications/vaccinations is according 
to the recording period of the AEs for 
which they are being administered 
See Section 6.8 for more information 
Record any intercurrent 
medical conditions 
 
● 
● 
● 
● 
● 
● See Section 9.3.1 for more information 
Recording of any AEs leading 
to vaccine/study withdrawal, 
SAEs, pregnancies and AESIs* 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording of SAEs related to 
study participation, or to a 
concurrent GSK medication/ 
vaccine 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine begins from the 
time a participant signs the consent 
form to the study end. 
See Section 10.3.8 for more information 
Study (Phase II, Sourcing) 
Conclusion 
 
 
 
 
 
 
● 
Participants who terminate the study 
early are recommended to complete 
certain study-related procedures. 
See Section 4.4 and 10.1.9.1 for more 
information 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
Documentation will be required in the source documents 
× is used to indicate a study procedure that will be documented in the eDiary  
^ Procedure to be performed prior to study intervention administration 
Abbreviation: PC, phone contact; V, clinic visit; T, telephone call; AE, adverse event; SAE, serious adverse 
event; AESI, adverse events of special interest. Note: All procedures to be performed prior to study 
intervention administration (as applicable).  
* Diagnosis of coronavirus 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 Section 10.3 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 36). In addition, separate COVID-19 specific 
eCRF form(s) should be completed  
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Note 1: If local regulations allow and quality of study procedures is maintained, participant(s) can be offered 
remote visits (e.g. home visits) for the collection of biological samples and/or study intervention 
administration (except for Visit V1 which will always be a clinic visit). These remote visits must be performed 
by qualified study staff/ HCPs. Details of how these visits will be conducted are outlined in the SPM. Refer to 
Section 8 (decentralised study procedures) for details 
Note 2: Refer to Section 8 for information on study procedures during special circumstances 
Table 8 
Intervals between study visits/contacts – Phase II (Sourcing; 0, 1 month 
vaccination schedule) 
(Amended 22 March 2022) 
Interval 
Planned visit interval  
Allowed interval range (visit window) 
Visit V1 → Visit V2 
30 days 
44 days (+14 days) 
Visit V2 → Visit V3 
30 days 
25 to 44 days (-5 to +14 days) 
Visit V2 → Telephone contact T1 
120 days 
113 to 134 days (-7 to +14 days) 
Visit V2 → Telephone contact T2 
180 days 
173 to 194 days (-7 to +14 days) 
Table 9 
Intervals between study visits/contacts – Phase II (Sourcing; 0, 2 month 
vaccination schedule) 
(Amended 22 March 2022) 
Interval 
Planned visit interval  
Allowed interval range (visit window) 
Visit 1 → Telephone contact T1 
30 days 
23 to 44 days (-7 to +14 days) 
Visit V1 → Visit V2 
60 days 
74 days (+14 days) 
Visit V2 → Visit V3 
15 days 
10 to 22 days (-5 to +7 days) 
Visit V2 → Visit V4 
30 days 
25 to 51 days (-5 to +21 days) 
Visit V2 → Telephone contact T2 
120 days 
113 to 134 days (-7 to +14 days) 
Visit V2 → Telephone contact T3 
180 days 
173 to 194 days (-7 to +14 days) 
Table 10 
Intervals between study visits/contacts – Phase II (Sourcing; 0, 6 month 
vaccination schedule) 
(Amended 22 March 2022) 
Interval 
Planned visit interval  
Allowed interval range (visit window) 
Visit 1 → Telephone contact T1 
30 days 
23 to 44 days (-7 to +14 days) 
Visit V1 → Visit V2 
180 days 
194 days (+14 days) 
Visit V2 → Visit V3 
15 days 
10 to 22 days (-5 to +7 days) 
Visit V2 → Visit V4 
30 days 
25 to 51 days (-5 to +21 days) 
Visit V2 → Telephone contact T2 
120 days 
113 to 134 days (-7 to +14 days) 
Visit V2 → Telephone contact T3 
180 days 
173 to 194 days (-7 to +14 days) 
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2. 
INTRODUCTION 
2.1. 
Study rationale 
Neisseria meningitidis infections causing invasive meningococcal disease (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. Ninety percent of 
meningococcal meningitis and septicaemia are caused by only 5 N. meningitidis 
serogroups: A, B, C, W and Y.  
GSK has 2 established meningococcal vaccines against serogroups A, C, W, Y and B 
respectively, the quadrivalent meningococcal ACWY conjugate vaccine (Menveo) and 
the multi-component recombinant meningococcal B vaccine (Bexsero). The availability 
of a pentavalent meningococcal vaccine in a single administration would however reduce 
the number of injections, allow greater flexibility in dose administration schedules and 
increase the coverage for meningococcal disease caused by these serogroups worldwide. 
The 
drug component as well as the final pentavalent 
 
 have undergone pre-clinical 
testing in mice, rats and rabbits, to assess immunogenicity and breadth of MenB strain 
coverage, while a GLP toxicology study to assess local tolerability and systemic toxicity 
has been concluded. Results from the pre-clinical testing and toxicology study were 
favourable. Please refer to the current Investigator’s Brochure (IB) for information 
regarding the formulation and pre-clinical studies of 
 vaccine.  
The early clinical development plan consists of a seamless Phase I/II study. The first-
time-in-human (FTIH), Phase I part of this study will be conducted in healthy adults in a 
dose-escalating fashion with 2 formulations of the investigational 
 
 referred to hereafter 
as 
 respectively, and will serve as a safety lead-
in to the Phase II study part.  
The Phase II part of the study will be conducted in 2 parts: the ‘formulation and schedule-
finding’ part will follow in healthy adolescents and young adults and it is designed to 
select the vaccine formulation and the schedule to be tested in Phase III. The ‘blood 
sourcing’ part will be conducted in healthy adults in order to collect sufficient serum 
samples for the development of assays to be used in the 
 vaccine clinical 
development program. Phase II will assess the safety, the effectiveness and the 
immunogenicity of the above 2 formulations of the investigational 
 
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vaccine. Bexsero (rMenB+OMV NZ, hereafter referred to as MenB) and Menveo 
(hereafter referred to as MenACWY) will be administered as control vaccines for 
assessing the response to serogroups B and ACWY, respectively. 
2.2. 
Background 
Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis worldwide, 
capable of causing outbreaks and epidemics of invasive disease. 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. In healthy individuals, IMD can rapidly progress to serious clinical disease 
and may be associated with poor outcomes, including fatality in ~10% of cases. While 
the greatest IMD burden is in infants, there is a second peak of disease in adolescents and 
young adults. 
IMD occurs when the normally asymptomatically carried encapsulated gram-negative 
bacterium N. meningitidis enters the bloodstream, multiplies and causes sepsis. Once the 
blood-brain barrier is compromised, development of acute bacterial meningitis represents 
a neurological emergency and necessitates immediate diagnosis and treatment 
[Heckenberg, 2014].  
Ninety percent of meningococcal meningitis and septicaemia are caused by only 5 N. 
meningitidis serogroups: A, B, C, W and Y. The distribution of serogroups varies 
geographically and over time. While the disease burden of IMD in higher-income 
regions, such as Europe and Australia, is largely attributable to serogroup B, in the 
‘meningitis belt’ of sub-Saharan Africa, IMD is predominantly caused by serogroups A 
and W. In the United States (US), serogroups B, C and Y account for most IMD.  
The best option for the control of meningococcal disease is the use of effective vaccines 
that would include all 5 of the most common serogroups responsible for invasive disease. 
With evidence of meningococcal epidemiology changing over time and across 
geographies [Cohn, 2015; Halperin, 2012; Harrison, 2009], a vaccine with the broadest 
possible coverage is an important step toward a definitive and global solution for 
meningococcal disease prevention. Refer to Section 2.1 for details on GSK’ 
investigational 
 vaccine in development. 
GSK’s Meningococcal Groups A, C, Y and W-135 Conjugate Vaccine (Menveo) is a 
meningococcal oligosaccharide diphtheria CRM197 conjugate vaccine licensed for active 
immunisation to prevent IMD caused by N. meningitidis serogroups A, C, W, and Y. It 
contains a nontoxic mutant of diphtheria toxin (Corynebacterium diphtheriae Cross 
Reacting Material-197, CRM197) as the carrier protein and has been demonstrated to be 
highly immunogenic against serogroups A, C, W and Y and is well tolerated in all age 
groups. It has been licensed 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. 
The Meningococcal Group B Vaccine (Bexsero) contains 3 recombinant proteins [factor 
H binding protein (fHbp), Neisseria adhesin A (NadA), and Neisserial Heparin Binding 
Antigen (NHBA)], combined with Outer Membrane Vesicles (OMV) components from 
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the New Zealand outbreak strain NZ98/254. Bexsero is immunogenic against the 
majority of circulating meningococcal serogroup B strains and has acceptable 
reactogenicity and safety profiles when administered to individuals across age groups. 
The vaccine is currently approved in more than 40 countries worldwide. Although the 
meningococcal group B vaccine was developed for individuals aged 2 months and older, 
the actual age range for which this recommendation extends varies depending on the 
approval from different health authorities.  
Please refer to the current IB for information regarding pre-clinical studies of 
 vaccine. 
2.3. 
Benefit/Risk assessment 
Detailed information about the known and expected benefits and risks and expected 
adverse events of 
 vaccine can be found in the IB. 
Detailed information about the known and expected benefits and risks and expected 
adverse events of Bexsero (MenB) and Menveo (MenACWY) vaccine can be found in the 
Prescribing Information or Summary of Product Characteristics. 
As with all injectable vaccines, immediate systemic allergic reactions to vaccination can 
occur. In order to be able to treat participants with an immediate systemic allergic 
reaction to vaccination, all participants will need to remain under close observation for at 
least 30 minutes after each study intervention (as per the phase in which they are 
participating: Visit V1 and Visit V3 in Phase I, Visit V1, Visit V3^ and Visit V4 in Phase 
II Formulation and Schedule-Finding and Visit V1 and Visit V2 in Phase II Sourcing). 
Refer to Section 6.1. 
^ except for Control group participants who will have a phone call at this time point (TC). 
In terms of study procedures, blood sampling is associated with a risk of syncope, 
dizziness, local reactions and infection after or during venepuncture. For this reason, 
blood samples in this study will be obtained by a trained professional and medical 
assistance will be available. The potential risk of feeling faint, experiencing mild local 
pain, bruising, irritation or redness at the site where blood was taken, is mentioned in the 
Informed Consent Form.  
Benefit considerations include: 
• 
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.  
• 
Contributing to the process of developing new vaccines against N. meningitidis. 
• 
Medical evaluations/assessments associated with this study (e.g., physical 
examinations). 
Overall Benefit: Risk conclusion 
Considering the measures taken to minimise risk to participants participating in this study 
and since 
 vaccine is based on 2 of GSK’s meningococcal vaccines, 
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Menveo and Bexsero, with well-established safety profiles, the potential risks associated 
with it are justified by the anticipated benefits that may be afforded to participants 
receiving 
 vaccine. 
3. 
OBJECTIVES AND ENDPOINTS  
Table 11 
Study objective(s) and endpoints 
(Amended 22 March 2022) 
Objectives 
Endpoints 
Phase I – Safety lead-in, Dose escalation 
Primary 
To evaluate the safety and reactogenicity of the 2 
formulations (
) of the 
 
vaccine. 
• 
The frequencies and percentages of participants 
with solicited administration site and systemic 
events during the 7 days (including the day of 
vaccination) following each vaccination at Day 1 and 
Day 31 in all groups. 
• 
The frequencies and percentages of participants 
with any unsolicited AEs (including all SAEs, AEs 
leading to withdrawal, and AESIs) during the 30 
days (including the day of vaccination) following 
each vaccination at Day 1 and Day 31 in all groups. 
• 
The frequencies and percentages of participants 
with SAEs, AEs leading to withdrawal and AESIs 
throughout the study period in all groups (Day 1 
through Day 211). 
• 
The frequencies and percentages of participants 
with haematological and biochemical laboratory 
abnormalities, and changes from the baseline 
values, after the first vaccination at Day 8, in all 
groups. 
Phase II – Formulation and Schedule-finding 
Primary 
To demonstrate the superiority of the effectiveness of the 
 vaccine (
) when 
administered at 0,2- or 0,6-months schedule, compared to 
the MenB vaccine administered at 0,6-months schedule*. 
The percentages of samples with bactericidal serum 
activity using enc-hSBA against a panel of 110 randomly 
selected endemic US N. meningitidis serogroup B invasive 
disease strains at 1 month after the last vaccination (Day 
211, Month 7) in all groups.  
To demonstrate the immunological non-inferiority of the 
 vaccine 
) administered at 
0,2- or 0,6-months schedule compared to the MenACWY 
vaccine (single dose)*; †.  
The percentages of participants achieving a 4-fold rise** in 
hSBA titres against serogroups A, C, W and Y at 1 month 
after the 
• 
last 
 vaccination (Day 211, Month 7) 
for the ABCWY groups and, 
• 
MenACWY vaccination (Day 31, Month 1) in the 
Control group, 
relative to Day 1, Month 0 in 
, 
 and Control groups and relative to 3 
months pre-first 
 vaccination (Day 31, 
Month 1) in 
 
groups. 
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Objectives 
Endpoints 
To evaluate the safety and reactogenicity of the 
 vaccine (
), the MenB 
vaccine and the MenACWY vaccine. 
• 
The frequencies and percentages of participants 
with solicited administration site and systemic 
events during the 7 days (including the day of 
vaccination) following each vaccination at: 
• 
Day 1, Day 121 and Day 181 in the 
 
 groups, and 
• 
Day 1 and Day 181 in the Control group. 
• 
The frequencies and percentages of participants 
with any unsolicited AEs (including all SAEs, AEs 
leading to withdrawal, and AESIs) during the 30 
days (including the day of vaccination) following 
each vaccination at: 
• 
Day 1, Day 121 and Day 181 in the 
 
 groups, and 
• 
Day 1 and Day 181 in the Control group. 
• 
The frequencies and percentages of participants 
with SAEs, AEs leading to withdrawal and AESIs 
throughout the study period in all groups (Day 1 
through Day 541). 
Phase II –Sourcing 
Primary 
To evaluate the safety and reactogenicity of the 2 
formulations (
) of the 
 
vaccine. 
• 
The frequencies and percentages of participants 
with solicited administration site and systemic 
events during the 7 days (including the day of 
vaccination) following each vaccination at: 
• 
 Day 1 and Day 31 in 
 
 groups,  
• 
at Day 1 and Day 61 in 
 
 groups, and 
• 
at Day 1 and Day 181 in 
 
 groups. 
• 
The frequencies and percentages of participants 
with any unsolicited AEs (including all SAEs, AEs 
leading to withdrawal, and AESIs) during the 30 
days (including the day of vaccination) following 
each vaccination at: 
• 
Day 1 and Day 31 
 
 groups,  
• 
at Day 1 and Day 61 in 
 
 groups, and  
• 
at Day 1 and Day 181 in 
 
 groups. 
• 
The frequencies and percentages of participants 
with SAEs, AEs leading to withdrawal and AESIs 
throughout the study period: 
• 
Day 1 through Day 211 in 
 and 
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Objectives 
Endpoints 
 groups,  
• 
Day 1 through Day 241 in 
 
 groups, and 
• 
Day 1 through Day 361 in 
 
 groups). 
Phase II – Formulation and Schedule-finding  
Secondary 
To describe the distribution of participants by percentages 
of serogroup B invasive disease strains killed using enc-
hSBA at 1 month after the last vaccination of the 
 vaccine (
) administered at 
0,2 and 0,6-months schedule and of the MenB vaccine 
administered at 0,6-months schedule. 
The percentages of serogroup B invasive disease strains 
killed using enc-hSBA in each participant sample at 1 
month after the last vaccination (Day 211, Month 7) in all 
groups. 
To assess the immune response to the 
 
vaccine (
) administered at 0,2 and 0,6-
months schedule and to the MenB vaccine administered 
at 0,6-months schedule against serogroup B indicator 
strains.  
• 
The percentages of participants with hSBA titres 
≥LLOQ for each and all serogroup B indicator 
strains at:  
o 
Day 1, Month 0 in 
 
 and Control groups, 
o 
3 months pre-first 
 vaccination 
(Day 31, Month 1) in 
 
groups and, 
o 
1 month after the last vaccination (Day 211, 
Month 7) for all study groups. 
• 
The percentages of participants with 4-fold rise in 
hSBA titres** at 1 month after the last vaccination for 
all study groups (Day 211, Month 7), relative to:  
o 
Day 1, Month 0 for 
 
and Control groups and, 
o 
3 months pre-first 
 vaccination 
(Day 31, Month 1) for 
 
 groups. 
• 
hSBA GMTs against serogroup B indicator strains 
at:  
o 
Day 1, Month 0 in 
 
 and Control groups, 
o 
3 months pre-first 
 vaccination 
(Day 31, Month 1) in 
 
 groups and, 
o 
1 month after the last vaccination (Day 211, 
Month 7) for all study groups. 
• 
hSBA GMRs against serogroup B indicator strains at 
1 month after the last vaccination (Day 211, Month 
7) for all study groups relative to: 
o 
Day 1, Month 0 for 
 
 and Control groups and  
o 
3 months pre-first 
 vaccination 
(Day 31, Month 1) for 
 
 groups. 
To assess the immune response to the 
 
vaccine (
) administered at 0,2 and 0,6-
months schedule and to the MenACWY vaccine (single 
dose) against serogroups A, C, W and Y. 
• 
The percentages of participants with hSBA titres 
≥LLOQ for serogroups A, C, W and Y at:  
o 
Day 1, Month 0 in 
 
 and Control groups, 
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Objectives 
Endpoints 
o 
3 months pre-first 
 vaccination 
(Day 31, Month 1) in 
 
 groups,  
o 
1 month after the first 
 
vaccination (Day 31, Month 1) in the 
 groups, 
o 
1 month after the last 
 
vaccination (Day 211, Month 7) for all ABCWY 
groups and, 
o 
1 month after the MenACWY vaccination in 
the Control group (Day 31, Month 1). 
• 
The percentages of participants with 4-fold rise in 
hSBA titres** for serogroups A, C, W and Y at 1 
month after the first 
 vaccination (Day 
31, Month 1) relative to Day 1, Month 0 for 
 groups. 
• 
hSBA GMTs against serogroups A, C, W and Y at: 
o 
Day 1, Month 0 in 
 
 and Control group, 
o 
3 months pre-first 
 vaccination 
(Day 31, Month 1) in 
 
 groups, 
o 
1 month after the first 
 
vaccination (Day 31, Month 1) in the 
 groups, 
o 
1 month after the last 
 
vaccination (Day 211, Month 7) for all ABCWY 
groups and, 
o 
1 month after the MenACWY vaccination in 
the Control group (Day 31, Month 1). 
• 
hSBA GMRs against serogroups A, C, W and Y at 1 
month after: 
o 
the first 
vaccination (Day 31, 
Month 1) in the 
 
 groups, 
o 
the last 
 vaccination (Day 211, 
Month 7) for all ABCWY groups and 
o 
the MenACWY vaccination in the Control 
group (Day 31, Month 1), 
relative to Day 1, Month 0 for 
 
 and Control groups and 3 months 
pre-first 
 vaccination (Day 31, Month 
1) for 
 groups. 
• 
The total IgG as measured by ELISA GMCs against 
serogroups A, C, W and Y at:  
o 
Day 1, Month 0 in 
 
 and Control groups, 
o 
3 months pre- first 
 vaccination 
(Day 31, Month 1) in 
 
 groups, 
o 
1 month after the first 
 
vaccination in the 
 
 groups and after the 
MenACWY vaccination in the Control group 
(Day 31, Month 1) and, 
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C O N FI D E N TI A L  
2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
4 0  
O bj e cti v e s  
E n d p oi nt s  
o  
1 m o nt h aft er t h e l ast 
 
v acci n ati o n ( D ay 2 1 1, M o nt h 7) f or all A B C W Y 
gr o u ps.  
P h a s e II ( F or m ul ati o n a n d S c h e d ul e -fi n di n g) 
T erti ar y o bj e cti v e s  
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C O N FI D E N TI A L  
2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
4 1  
O bj e cti v e s  
E n d p oi nt s  
A b br evi ati o ns: A E, A dv ers e ev e nt; S A E, S eri o us a dv ers e ev e nt; A E SI, A dv ers e ev e nt of s p eci al i nt er est; E LI S A, 
e nzy m e -li nk e d i m m u n os or b e nt ass ay; G M C, g e o m etric m e a n c o nc e ntr ati o ns; e nc-h S B A, e n d o g e n o us c o m pl e m e nt 
h u m a n s er u m b act erici d al ass ay; G M T, g e o m etric m e a n titr e; G M R, g e o m etric m e a n r ati o; h S B A, h u m a n s er u m 
b act erici d al ass ay; L O D,  li mit of d et ecti o n; L L O Q, l o w er li mit of q u a ntit ati o n. 
N ot e 1: M e n B i m m u n e r es p o ns e will b e ass ess e d a g ai nst N. m e ni n giti dis  s er o gr o u p B i n dic at or str ai ns  
 
 
 
 
 
N ot e 2: Ev al u ati o n of t h e t erti ary o bj ectiv e s m ay or n ot b e p erf or m e d. If t h e t erti ary o bj ectiv es ar e ev al u at e d, it m ay b e 
ass ess e d i n a s u bs et of p artici p a nts usi n g r e m ai ni n g s er u m aft er t h e pri m ary a n d s ec o n d ary a n alys es h av e b e e n 
c o m pl et e d; n o a d diti o n al bl o o d s a m pl es will b e c oll ect e d fr o m p artici p a nts.  
* All st atistic al crit eri o n li nk e d t o ev al u ati o n of t h e o bj ectiv es c a n b e f o u n d i n S ecti o n 9. 4 . 
** F or t h e s er o gr o u p A C, W, Y a n d s er o gr o u p B ev al u ati o n s, t h e 4-f ol d ris e (f or s er o gr o u p B - p er e ac h i n dic at or str ai n) 
is d efi n e d as: 
-a p ost -v acci n ati o n h S B A titr e ≥1 6 f or p artici p a nts wit h a pr e -v acci n ati o n h S B A titr e < 4, 
-a p ost -v acci n ati o n h S B A titr e ≥4 ti m es t h e L L O Q f or p artici p a nts wit h a pr e -v acci n ati o n h S B A titr e ≥L O D b ut 
< L L O Q, a n d  
-a p ost -v acci n ati o n h S B A titr e ≥4 ti m es t h e pr e-v acci n ati o n h S B A titr e f or p artici p a nts wit h a pr e-v acci n ati o n h S B A 
titr e ≥L L O Q. 
† T h e pri m ary o bj ectiv e of i m m u n ol o gic al NI of t h e 
 v acci n e t o M e n A C W Y will b e ev al u at e d o nly i n 
p artici p a nts  wit h o ut a p r evi o us M e n A C W Y v acci n ati o n ( u n pri m e d). All ot h er pri m ary a n d s ec o n d ary o bj ectiv es will b e 
ev al u at e d i n p artici p a nts  wit h a n d wit h o ut pr evi o us M e n A C W Y v acci n ati o n ( pri m e d/ u n pri m e d).  
 
 
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4. 
STUDY DESIGN 
(Amended 22 March 2022) 
4.1. 
Overall design 
This is a seamless Phase I/II multi-country, self-contained study comprising of 2 phases, 
in order to ensure the safety of participants. 
4.1.1. 
Phase I study design  
The Phase I safety lead-in will include 4 study groups (randomised 3:1), with a staggered 
enrolment (16 participants initially followed by 16 participants later) of a total of 32 
participants (Figure 1). 
• 
 Participants will receive the 
 vaccine in a 0,1-month 
schedule.  
• 
: Participants will receive a saline placebo in a 0,1-month schedule, as 
control group for 
 
• 
: Participants will receive the 
 vaccine in a 0,1-month 
schedule.  
• 
: Participants will receive a saline placebo in a 0,1-month schedule, as 
control group for 
 
For more detailed information on study groups and treatments administered, refer to 
Table 12 and Table 15. 
 
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Figure 1 
Study design overview – Phase I (Safety Lead-in) 
 
Abbreviation: N, number of participants; V, clinic visit; D, day; iSRC, internal safety review committee; PC, phone contact; BS, blood sample. 
Note 1: This figure represents the main aspects of the study design. Refer to Table 1, Schedule of activities, for details on all visits and contacts 
Note 2: Refer to Section 8 for information on study procedures during special circumstances. 
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A GSK internal Safety Review Committee (iSRC, composed of senior GSK experts, 
independent from the study team) will meet at pre-defined timepoints to perform 
unblinded review of safety data as described in Section 8.2.2.1.  
A total of 16 participants will be randomised with 3:1 ratio to 
 
groups (12 participants in the 
 group and 4 participants in the
 
group). A “go-no go” decision will be taken by the iSRC based on safety and 
reactogenicity data from these participants, as described in Section 8.2.2.1. If the decision 
is “go”, further visits and vaccination for these 2 groups will continue and recruitment of 
participants in groups 
 and 
 will start. 
Similarly, a total of 16 participants will be randomised with 3:1 ratio to 
 
 groups (12 participants in the 
 group and 4 participants in the 
 group). Again, a “go-no go” decision will be taken by the iSRC based on 
safety and reactogenicity data from these participants. If the decision is “go”, further 
visits and vaccination for these 2 groups will continue. Safety and reactogenicity data 
from these 2 groups post 2nd dose will be evaluated for a last “go” decision to enable the 
start of the Phase II.  
The schedule of activities in the Phase I is described in Table 1. 
Table 12 
Study groups, intervention and blinding – Phase I 
Study groups 
Number of 
participants 
Age 
(Min-Max) 
Study intervention(s)  
Blinding 
12 
18-40 yoa 
Observer-blinded 
12 
18-40 yoa 
4 
18-40 yoa 
NaCl 
4 
18-40 yoa 
NaCl 
Duration of the Phase I of the study: The intended duration of the Phase I of the study, 
per participant is approximately 7 months. 
Data collection: Standardised Electronic Case Report Form (eCRF). Solicited events will 
be collected using a participant diary (electronic Diary [eDiary]). 
Sampling schedule for Phase I of the study:  
• 
Blood sample: Refer to Section 8.1.1.1 for details on collection of blood samples. 
• 
Urine sample: Urine samples for pregnancy testing will be collected from female 
participants of childbearing potential at Visit 1 (Day 1) and Visit 3 (Day 31) prior to 
the study intervention. 
4.1.2. 
Phase II study design 
Phase II will start only after a positive outcome from the iSRC review of the safety data 
from participants receiving both vaccinations of the higher-dosage vaccine formulation in 
Phase I of the study. Phase II will be conducted in 2 parts: Formulation and Schedule-
finding and Blood sourcing with enrolment commencing parallelly to both these parts. 
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4.1.2.1. 
Phase II: Formulation and Schedule-finding 
Phase II (Formulation and Schedule-finding) will include 5 study groups, with a 
staggered enrolment (45 participants for safety lead-in and 955 participants thereafter) of 
a total of 1000 participants (Figure 2): 
• 
 Participants will receive 2 vaccinations of the 
 
vaccine in a (0,6-months) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,2-months) schedule.  
• 
 Participants will receive 2 vaccinations of the 
 
vaccine in a (0,6-months) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,2-months) schedule.  
The above 4 groups will also receive 1 injection of placebo, according to the schedule 
described in Figure 2. 
• 
Control: Participants will receive 2 vaccinations of MenB vaccine (Bexsero) in a 
(0,6-months) schedule and a single vaccination of MenACWY vaccine (Menveo).  
For more detailed information on study groups and treatments administered, refer to 
Table 13 and Table 16.  
The schedule of activities in Phase II (Formulation and Schedule-finding) of the study is 
described in Table 3. 
 
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Figure 2 
Study design overview – Phase II (Formulation and Schedule-finding)  
 
V2 D31
Month 1
V1 D1
Month 0
V5 D211
Month 7
V4 D181
Month 6
(N=191)
BS
BS
BS
BS
BS
BS
Randomization: 
1:1:1:1:1
N = 955
Placebo
Placebo
(N=191)
(N=191)
Control
(N=191)
BS
BS
Placebo
BS
MenB
MenACWY
V3/ TC# D121
Month 4
BS
BS
Placebo
BS
BS
BS
BS
MenB
V6 D541
Month 18
BS
BS
BS
BS
BS
(N=191)
N (Total) = 1000
Phase II: Formulation and Schedule-finding
V2 D31
Month 1
V1 D1
Month 0
V5 D211
Month 7
V4 D181
Month 6
(N=15)
(N=5)
BS
BS
BS
Randomization: 
3:1:3:1:1
N = 45
Placebo
Placebo
(N=15)
(N=5)
Control
(N=5)
BS
BS
BS
MenB
MenACWY
V3/ TC#  D121
Month 4
Placebo
MenB
V6 D541
Month 18
BS
Placebo
BS
BS
BS
BS
BS
BS
BS
BS
BS
BS
BS
i
S
R
C*
BS
BS
PC D8^
Month 0







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Abbreviation: N, number of participants; V, clinic visit; D, day; TC, Telephone contact for Control group only; iSRC, internal safety review committee; PC, phone contact; BS, blood 
sample. 
^ The phone call at Day 8 is only for the first 45 participants (15 participants in 
, 5 participants in 
 15 participants in 
 5 participants in 
 and 5 participants in the Control groups).  
* The outcome of the iSRC will impact the next study intervention at Month 4. The Month 1 blood sampling will proceed as planned. 
Note 1: Blood draw at Visit 6 Month 18 will be used only for assessment of tertiary objectives. 
Note 2: This figure represents the main aspects of the study design. Refer to Table 3 , Schedule of activities, for details on all visits and contacts 
Note 3: The Phase II (Formulation and Schedule-finding) is partially blinded. Study conduct and data collection in groups 
 
 will be observer-blind while in group Control it will be open-label. 
# Day 121 Month 4 is a visit for 
 groups (Visit V3) and is a telephone call for Control group (TC) 
Note 4: If local regulations allow and quality of study procedures is maintained, participant(s) can be offered remote visits (e.g. home visits) for the collection of biological samples 
and/or study intervention administration (except for Visit V1 which will always be a clinic visit). These remote visits must be performed by qualified study staff/ HCPs. Refer to the SoA 
(Table 3) for the timing of these visits. Details of how these visits will be conducted are outlined in the SPM. Refer to Section 8 (decentralised study procedures) for details 
Note 5: Refer to Section 8 for information on study procedures during special circumstances.  
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A total of 45 participants will be randomised with 3:1:3:1:1 ratio to the 5 groups (15 in 
the 
, 5 in the
 15 in the 
, 5 in the 
 and 5 in the Control group). A “go-no go” decision will be taken by the 
iSRC based on safety and reactogenicity data from these participants (Section 8.2.2.1).  
Note: The outcome of the iSRC will impact the next study intervention at Month 4. The 
Month 1 blood sampling will proceed as planned. 
If the decision is “go”, further vaccination at Month 4 and other study procedures 
following that will continue in these groups (as per the study design) along with 
continuing to recruit participants with a randomisation ratio of 1:1:1:1:1 (191 in each 
group) to reach the target total sample of 955 participants. Refer to Table 13 for total 
number of participants per group. 
Table 13 
Study groups, intervention and blinding – Phase II (Formulation and 
Schedule-finding) 
Study groups 
Number of 
participants 
Age 
(Min-Max)  
Study intervention(s) 
Blinding 
206 
10 – 25 yoa 
 
Observer-blinded 
NaCl 
196 
10 – 25 yoa 
 
NaCl 
206 
10 – 25 yoa 
 
NaCl 
196 
10 – 25 yoa 
 
NaCl 
Control 
196 
10 – 25 yoa 
MenACWY 
Open-label 
rMenB+OMV NZ 
Duration of the Phase II (Formulation and Schedule-finding) of the study: The 
intended duration of the Phase II of the study, per participant is approximately 18 months. 
Data collection: standardised eCRF. Solicited events will be collected using a participant 
diary (eDiary). 
Sampling schedule for Phase II (Formulation and Schedule-finding) of the study:  
• 
Blood sample: Refer to Section 8.1.1 for details on collection of blood samples. 
• 
Urine sample: Urine samples for pregnancy testing will be collected from female 
participants of childbearing potential at Visit 1 (Day 1), Visit 3 (Day 121) and Visit 4 
(Day 181) prior to the vaccination in the ABCWY groups and at Visit 1 (Day 1) and 
Visit 4 (Day 181) prior to the vaccination in the Control group. 
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4.1.2.2. 
Phase II: Sourcing 
(Amended 22 March 2022) 
The blood sourcing part of the Phase II study will include 2 groups (randomised 1:1), 
with a parallel enrolment of a total of 226* participants: 
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,1-month) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,1-month) schedule.  
* At the time of this protocol amendment (Protocol amendment 4), enrolment to these 2 
groups had been stopped. The total number of participants enrolled have been 
presented in Figure 3.  
Additionally, the Phase II sourcing part will include 4 more groups (randomised 
1:1:1:1), with a parallel enrolment of a total of 240 participants (Figure 3): 
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,2-month) schedule.  
• 
 Participants will receive 2 vaccinations of the 
 
vaccine in a (0,2-month) schedule. 
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,6-month) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,6-month) schedule. 
For more detailed information on study groups and treatments administered, refer to 
Table 14 and Table 17. 
The schedule of activities in the Phase II (sourcing) are described in Table 5, Table 6 
and Table 7. 
 
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Figure 3 
Study design overview – Phase II (Sourcing) 
 
 
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Abbreviation: N, number of participants; V, clinic visit; D, day, PC, phone contact; BS, blood sample. 
Note 1: This figure represents the main aspects of the study design. Refer to Table 5, Table 6 and Table 7, Schedule 
of activities, for details on all visits and contacts 
Note 2: If local regulations allow and quality of study procedures is maintained, participant(s) can be offered remote 
visits (e.g. home visits) for the collection of biological samples and/or study intervention administration (except for Visit 
V1 which will always be a clinic visit). These remote visits must be performed by qualified study staff/ HCPs. Refer to 
the SoA (Table 5, Table 6 and Table 7) for the timing of these visits. Details of how these visits will be conducted are 
outlined in the SPM. Refer to Section 8 (decentralised study procedures) for details 
Note 3: Refer to Section 8 for information on study procedures during special circumstances. 
Table 14 
Study groups, intervention and blinding – Phase II (Sourcing) 
Study groups 
Number of 
participants 
Age 
(Min-Max) 
Study intervention(s)  
Blinding 
107 
18-50 yoa 
 
Observer-
blinded* 
60 
60 
60 
60 
* Due to the different vaccination schedules in Phase II Sourcing, the study will be observer blind only in terms 
of the vaccine formulations. 
Duration of the Phase II (Sourcing) of the study: The intended duration of the Phase II 
(sourcing) of the study, per participant is: 
• 
approximately 7 months for the 
 and 
 groups, 
• 
approximately 8 months for the 
and 
 groups, 
and, 
• 
approximately 12 months for the 
 and 
groups. 
Data collection: Standardised Electronic Case Report Form (eCRF). Solicited events will 
be collected using a participant diary (electronic Diary [eDiary]). 
Sampling schedule for Phase II (Sourcing) of the study: 
• 
Blood sample: Refer to Section 8.1.1.1 for details on collection of blood samples. 
• 
Urine sample: Urine samples for pregnancy testing will be collected from female 
participants of childbearing potential prior to the study intervention (at the following 
timepoints): 
− 
at Visit 1 (Day 1) and Visit 2 (Day 31) for the 
 and 
 groups, 
− 
at Visit 1 (Day 1) and Visit 2 (Day 61) for the 
 and 
 groups, and, 
− 
at Visit 1 (Day 1) and Visit 2 (Day 181) for the 
 and 
 groups. 
The primary completion date for the study is the Day 541, Month 18 timepoint in Phase 
II. Refer to Section 9.4.6 for the planned interim analysis. 
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4.2. 
Scientific rationale for study design 
(Amended 22 March 2022) 
The investigational 
 vaccine is composed of 
 
 
 
 
 
As the investigational 
 vaccine has never been administered to humans, 
the study will follow a staggered design with 2 phases in order to assess the safety of the 
new vaccine first in a small group of healthy adults 18 through 40 years of age (Phase I), 
and subsequently in a small group of healthy adolescents and young adults aged 10 
through 25 years prior to proceeding with the full enrolment in Phase II. 
• 
The first part of the study [Phase I (Figure 1)] will serve as a safety lead-in to the 
Phase II part of the study. 
• 
The second part of the study [Phase II (Figure 2 and Figure 3] will only commence 
after demonstration of acceptable safety and reactogenicity in Phase I participants 
(Section 4.1.1). This Phase II will have 2 components – the formulation and 
schedule-finding part and the blood sourcing part. 
The 0,1-month schedule was selected for Phase I and Phase II (Sourcing) because the 
short time interval between vaccinations is conservative for the assessment of 
reactogenicity and safety.  
Furthermore, the 
 vaccine will also be administered according to a 
0,2month or 0,6month interval (wider dosing schedules) in the Phase II Sourcing part 
to support the finalization of assay development, further clinical testing, as well as 
assay stability monitoring and maintenance. For this reason, the total sample size of 
subjects in the Phase II Sourcing have been increased. 
The formulation and schedule-finding part of the Phase II is designed to assess safety, 
effectiveness and immunogenicity of 
 
 
. The 2-
dose schedule, as well as the interval between doses are based on the dosing schedule 
approved for Bexsero in adolescents and young adults. 
Menveo and Bexsero will be administered as comparators in Phase II, in line with the 
respective approved labels in this age group (
 
 
 
 in Phase I/II. 
Rationale for use of placebo: 
The placebo treatment (saline solution) is included in this study as: 
• 
a control for safety assessments (in Phase I), and, 
• 
to maintain the blinding (in Phase I and Phase II, Formulation and Schedule-finding). 
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C O N FI D E N TI A L  
2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
5 3  
4. 3.  
J u stifi c ati o n f or d o s e  
N o pre vi o us cli nical trials ha ve bee n p erf or me d wit h t he G S K 
 vacci ne 
ca n di date. T h e de vel o p m e nt of 
 v acci ne le v era ges t he e x perie nce 
gat h ere d fr o m t he 2  G S K vacci nes o n t he m ar ket, Bexser o  ( Me n B v acci ne) a n d Me nve o  
( Me n A C W Y vacci n e), f or w hic h si g nifica nt a m o u nt of n o n-cli nical, cli nical  a n d p ost -
mar keti n g d ata ha v e bee n ge n erat e d.  
4. 4.  
E n d of St u d y d efi niti o n  
( A me n de d 2 2  M arc h 2 0 2 2)  
A partici pa nt is c o nsi dere d t o ha ve c o m plet e d t he st u d y if he/s he ret ur ns f or t he last visit 
or is a vaila ble f or t he last sc he d ule d c o ntact / visit as descri be d i n t he pr ot oc ol  [Tele p h o ne 
T 3 i n P hase I, Visit V 6 i n P hase II, F or m ulati o n a n d Sc he d ule -fi n di n g a n d Tele p h o ne T 2 
or Tele p h o ne T 3  i n P hase II, S o urci n g ( as per t he gr o u p all oc ati o n)]. 
E n d of St u d y ( E o S):  Date of t he last testi n g/r ea di n g releas e d of t he H u ma n Bi ol o gical 
Sa m ples, relate d t o pri mar y a n d sec o n d ar y e n d p oi nts. E o S m ust be ac hie ve d n o later t ha n 
8 m o nt hs after L ast S u bje ct Last Visit ( L S L V)  ( L S L V = Da y 5 4 1, M o nt h 1 8  i n P hase II, 
f or m ulati o n a n d sc he d ule-fi n di n g). If t he c o m pletio n  of  testi n g occ ur s pr io r t he 
c om ple tio n  o f t he L S L V  t he latter d ate defi nes th e e n d of  st u dy visit. 
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5. 
STUDY POPULATION 
Adherence to the inclusion and exclusion criteria specified in the protocol is essential. 
Deviations from these criteria are not allowed because they can jeopardise the scientific 
integrity, regulatory acceptability of the study or safety of the participant. 
5.1. 
Inclusion criteria 
All participants must satisfy ALL the following criteria at study entry: 
Note: Prior to receipt of each study intervention, participants must be evaluated to 
confirm that they are eligible for subsequent vaccination. If participants do not meet any 
of the applicable inclusion criteria listed below, they should not receive additional study 
interventions. 
All inclusion criteria are applicable for both study phases, except where specified 
otherwise. 
• 
Participants and/or participants’ parent(s)/Legally Acceptable Representative(s) 
(LAR) who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of the eDiaries, return for follow-up 
visits). 
• 
Written or witnessed/thumb printed informed consent obtained from the participant 
or /parent(s)/LAR(s) of the participant prior to performance of any study specific 
procedure. 
• 
Written informed assent obtained from the participant (if applicable) prior to 
performing any study specific procedure. 
• 
Phase I only: A male or female between, and including, 18 and 40 years of age (i.e. 
40 years + 364 days) at the time of the first study intervention administration. 
• 
Phase II (Formulation and Schedule-finding) only: A male or female between, 
and including, 10 and 25 years of age (i.e. 25 years + 364 days) at the time of the 
first study intervention administration. 
• 
Phase II (Sourcing) only: A male or female between, and including, 18 and 50 
years of age (i.e. 50 years + 364 days) at the time of the first study intervention 
administration. 
• 
Participants who are either unvaccinated with MenACWY vaccine or have received 
a single previous dose of MenACWY vaccine can participate in the study, if they 
have received it at least 4 years prior to informed consent and assent as applicable 
(with the exception of meningococcal C vaccination, if the last dose of MenC was 
received at ≤24 months of age). 
• 
Healthy participants as established by medical history and clinical examination 
before entering into the study. 
• 
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. Refer to Section 
10.5.1 for definitions of menarche and menopause. 
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• 
Female participants of childbearing potential may be enrolled in the study, if the 
participant: 
− 
has practiced adequate contraception for 1 month prior to study intervention 
administration, and 
− 
has a negative pregnancy test on the day of study intervention administration, 
and 
− 
has agreed to continue adequate contraception during the entire treatment period 
and for 1 month after completion of the study intervention administration.  
Refer to Section 10.5.1 for definitions of woman of childbearing potential and 
adequate contraception 
5.2. 
Exclusion criteria 
All exclusion criteria are applicable for both study phases, except where specified 
otherwise. 
The following criteria should be checked at the time of study entry. The potential 
participant MAY NOT be included in the study if ANY exclusion criterion applies: 
5.2.1. 
Medical conditions 
• 
Current or previous, confirmed or suspected disease caused by N. meningitidis. 
• 
Household contact with and/or intimate exposure to an individual with laboratory 
confirmed N. meningitidis infection within 60 days of enrolment. 
• 
Progressive, unstable or uncontrolled clinical conditions. 
• 
Clinical conditions representing a contraindication to intramuscular vaccination and 
blood draws. 
• 
Are obese at enrolment (e.g. for participants from 20 years of age a body mass index 
(BMI) ≥ 30 kg/m2, for participants up to 19 years of age a BMI ≥ 95th percentile for 
age and gender or as applicable per country recommendations). 
• 
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, 
generalised tonic-clonic seizures, partial complex seizures, partial simple seizures). 
History of febrile convulsions should not lead to exclusion. 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study interventions. 
• 
Hypersensitivity, including allergy, to any component of vaccines, including 
diphtheria toxoid (CRM197) and latex medicinal products or medical equipment 
whose use is foreseen in this study.  
• 
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 
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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 (PO/IV/IM) for more than 14 
consecutive days within 3 months prior to study vaccination until the last blood 
sampling visit for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for 
Phase II (Formulation and Schedule-finding). This will mean prednisone 
equivalent ≥20 mg/day for adult participants/ ≥0.5 mg/kg/day with maximum of 
20 mg/day for paediatric participants. Inhaled and topical steroids are allowed.  
− 
Administration of antineoplastic and immunomodulating agents or radiotherapy 
within 90 days prior to study vaccination. 
− 
Administration of long-acting immune-modifying drugs at any time during the 
study period (e.g. infliximab). 
• 
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 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study intervention(s) during the period beginning 30 days 
before the first dose of study intervention(s) (Day -29 to Day 1), or their planned use 
during the study period. 
• 
Previous vaccination against any group B meningococcal vaccine at any time prior to 
informed consent and assent as applicable. 
• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 3 months before the administration of the first dose of 
study intervention(s) or planned administration until the last blood sampling visit for 
Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and 
Schedule-finding). 
• 
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 the first study intervention dose(s) until the last blood sampling visit 
for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation 
and Schedule-finding). For corticosteroids, this will mean prednisone equivalent 
≥20 mg/day for adult participants/ ≥0.5 mg/kg/day with maximum of 20 mg/day for 
paediatric participants. Inhaled and topical steroids are allowed. 
5.2.3. 
Prior/Concurrent clinical study experience 
• 
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 intervention (drug/invasive medical device). 
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5.2.4. 
Other exclusions 
• 
Pregnant or lactating female. 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions. 
• 
History of /current chronic alcohol abuse and/or drug abuse as determined by the 
investigator. 
• 
Any study personnel or immediate dependents, family, or household member. 
• 
Phase II (Formulation and Schedule-finding): Child in care. Please refer to the 
Glossary of terms for the definition of child in care. 
5.3. 
Lifestyle considerations 
Not applicable. 
5.4. 
Screen failures 
In the event that the individual is determined ineligible for study participation, he/she is 
considered a screen failure. A screen failure is an individual who consents to participate 
in this study but is not entered in the study/ randomised to a study intervention. 
The reason for screen failure must be documented in the Screening log. If the individual 
is determined to be eligible for the study, he/she will be enrolled into the study.  
5.5. 
Criteria for temporarily delaying enrolment/ randomisation/ 
study intervention administration/blood sampling  
(Amended 22 March 2022) 
Enrolment/randomisation/study intervention/blood sampling administration may be 
postponed within the permitted time interval until transient conditions cited below are 
resolved:  
• 
Acute disease and/or fever at the time of enrolment and/or study intervention 
administration. Refer to the SoA for definition of fever and preferred location for 
measuring temperature in this study.  
• 
Participants with a minor illness (such as mild diarrhoea, mild upper respiratory 
infection) without fever may be enrolled and/or dosed at the discretion of the 
investigator.  
• 
Significant acute illness within the previous 7 days of study intervention 
administration. 
• 
Receipt of systemic antibiotics within 3 days prior to blood sampling visit (this will 
defer blood draw). 
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• 
A positive test for current infection with COVID-19 prior to intervention 
administration. The testing should have been done using a molecular (polymerase 
chain reaction [PCR] or antigen test) approved by the country regulatory authorities. 
• 
Participants with known COVID-19 positive contacts and considered at risk of 
having contracted a COVID-19 infection according to local regulations. 
• 
Individuals who have received any other vaccines within 7 days (for inactivated 
vaccines) or 14 days (for live vaccines) prior to and following each vaccination up to 
Visit 3 for Phase I, up to Visit 4 for Phase II (Formulation and Schedule-finding) and 
up to Visit 2 for Phase II (Sourcing)*. 
* In case an emergency mass vaccination for an unforeseen public health threat (e.g.: 
a pandemic) is organised by the public health authorities, outside the routine 
immunisation program, the time period described above can be reduced if necessary 
for that vaccine provided it is licensed and used according to the local governmental 
recommendations and that the Sponsor notified accordingly. 
In case of seasonal influenza vaccination, 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. 
Under such circumstances, a participant may be considered eligible for study enrolment 
and randomisation and vaccination and/or blood sampling after the appropriate window 
for delay has passed and inclusion/exclusion criteria have been re-checked, and if the 
participant is confirmed to be eligible. 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY 
Refer to the Glossary of terms for the definition of study intervention. 
6.1. 
Study intervention(s) administered  
Refer to Section 4 for the study intervention administration schedule. 
 
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Table 15 
Study intervention administered – Phase I 
Study intervention name: 
Placebo 
Study intervention 
formulation† 
Sodium chloride (NaCl) 
(0.9%); Water for 
injections 
Dose Form/ Presentation 
Solution for injection 
/Syringe 
Product category 
Combination 
Combination 
Combination 
No of doses 
 
 
 
2 
- 
- 
- 
2 
- 
- 
- 
2 
- 
- 
2 
Volume to be 
administered^ 
Type  
Study  
Study  
Control 
Route of administration 
Intramuscular use 
Intramuscular use 
Intramuscular use 
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Study intervention name: 
Placebo 
Administration site 
 
 
 
• Location 
Deltoid 
Deltoid 
Deltoid 
• Laterality**  
Non-dominant 
Non-dominant 
Non-dominant 
Packaging, labelling and 
TM: 
Refer to SPM for details 
Manufacturer: 
GSK 
GSK 
GSK 
† The composition per dose is presented here 
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Table 16 
Study intervention administered – Phase II (Formulation and Schedule-finding) 
Study 
intervention  
Bexsero  
Menveo* 
Placebo 
(saline) 
Formulation† 
Sodium 
chloride 
(NaCl) 
(0.9%); Water 
for injections 
Dose Form/ 
Presentation 
Solution for 
injection/ 
Syringe 
Product 
category 
Combination 
Combination 
Combination 
Biological 
Combination 
2 
- 
- 
- 
1 
2 
- 
- 
- 
1 
- 
2 
- 
- 
1 
- 
2 
- 
- 
1 
Control 
- 
- 
2 
1 
 
Volume to be 
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Study 
intervention  
Bexsero  
Menveo* 
Placebo 
(saline) 
administered^  
Type  
Study 
Study 
Control 
Control 
Concomitant 
Route of 
administration 
Intramuscular use 
Intramuscular use 
Intramuscular use 
Intramuscular use 
Intramuscular 
use 
Administration 
site 
 
 
 
 
 
Location 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Laterality*** 
Non-dominant*** 
Non-dominant*** 
Non-dominant*** 
Dominant 
Non-
dominant*** 
Packaging, 
labelling and 
TM: 
Refer to SPM for details 
 
     
Manufacturer: 
GSK 
GSK 
GSK 
GSK 
GSK 
†The composition per dose is presented here. 
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Table 17 
Study intervention administered – Phase II (Sourcing) 
(Amended 22 March 2022) 
Study intervention name: 
Study intervention 
formulation† 
Dose Form/ Presentation 
Product category 
Combination  
Combination 
No of doses 
 
 
 
• 
2 
- 
• 
- 
2 
• 
2 
- 
• 
- 
2 
• 
2 
- 
• 
- 
2 
Volume to be 
administered^ 
Type  
Study  
Study  
Route of administration 
Intramuscular use 
Intramuscular use 
Administration site 
 
 
 
• Location 
Deltoid 
Deltoid 
• Laterality* 
Non-dominant 
Non-dominant 
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Study intervention name: 
Packaging, labelling and 
TM: 
Refer to SPM for details 
Manufacturer: 
GSK 
GSK 
† The composition per dose is presented here 
Study participants must be observed closely for at least 30 minutes after the administration of the study intervention(s). Appropriate 
medical treatment must be readily available during the observation period in case of anaphylaxis, syncope.
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6.2. 
Preparation/Handling/Storage/Accountability 
The study intervention(s) must be stored in a secured place within the temperature range 
specified on the study intervention’s label. The storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s).  
Only authorised study personnel should be allowed access to the study intervention(s). 
Storage conditions will be assessed by a sponsor study contact during pre-study activities. 
Refer to the SPM for more details on storage and handling of the study intervention(s). 
6.3. 
Measures to minimise bias: randomisation and blinding  
6.3.1. 
Participant identification 
Participant identification numbers will be assigned sequentially to the individuals who 
have consented to participate in the study. Each study centre will be allocated a range of 
participant identification numbers. 
6.3.2. 
Randomisation to study intervention 
There are 2 randomisation processes for each participant in the study: 
• 
Randomisation to study intervention 
6.3.3. 
Intervention allocation to the participant 
In Phase I and Phase II (Sourcing), the randomisation algorithm will use a minimisation 
procedure accounting for the study.  
In Phase II (Formulation and Schedule-finding), the minimisation procedure will account 
for age category (10-17 years of age and 18-25 years of age) and previous MenACWY 
vaccination (priming) (Yes and No)*. 
It is recommended to have a balance between age category during enrolment in Phase II 
(Formulation and Schedule-finding). 
Once a participant identification number is allocated, the randomisation system will 
determine study group and will provide the study intervention number to be used for the 
first dose. The study intervention number(s) to be used for subsequent dosing will be 
provided by the same automated Internet-based system (SBIR). 
When SBIR is not available, please refer to the SBIR user guide or SPM for specific 
instructions. 
To allow GSK to take advantage of greater rates of recruitment in this multi-centre study 
and to reduce the overall study recruitment period, an over-randomisation of supplies will 
be prepared.  
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Refer to the SPM for additional information about the study intervention number 
allocation. 
Note: * Participants with and without a previous MenACWY vaccination (primed and 
unprimed). 
6.3.4. 
Allocation of participants to assay subsets 
Refer to Section 9 for details on the allocation as per the MenACWY priming and the 
analysis planned. Blood samples will be collected as detailed in Section 8.1.1.1. Refer to 
Section 10.2.1 for details on allocation of participants for safety laboratory assays. 
Refer to Section 8.1.3 for details on allocation of participants to assay subsets and Section 
10.2.2.1.1 for details on randomisation to strains for enc-hSBA testing. 
6.3.5. 
Blinding and unblinding 
(Amended 22 March 2022) 
6.3.5.1. 
Phase I and Phase II (Sourcing) 
(Amended 22 March 2022) 
Data will be collected in an observer-blind manner. To do so, study intervention(s) 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, efficacy). 
Note: Due to the different vaccination schedules in Phase II Sourcing, the study will be 
observer blind only in terms of the vaccine formulations 
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There 
will be no link between the study intervention and the identity of the participant. 
6.3.5.2. 
Phase II (Formulation and Schedule-finding) 
This phase is partially blinded. Data in the 4 ABCWY groups will be collected in an 
observer-blind manner. To do so, study intervention(s) 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, efficacy).  
Data in the Control group will be collected in an open-label manner i.e. study 
participants, investigator and site staff personnel will be aware of the treatment 
administered as 2 study interventions are administered at Visit V1. 
The laboratory in charge of the laboratory testing will be blinded to the treatment as well 
as to the subject number. There will be no link between the study intervention groups and 
the identity of the participant. In addition, for each sample, a different randomly selected 
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subject code will be used at each timepoint. This subject coding will prevent the testing 
laboratory personnel from linking the consecutive timepoints to a specific subject.  
Refer to the SPM for additional information about details on study blinding. 
6.3.5.3. 
Unblinding 
(Amended 22 March 2022) 
The participant, the site and sponsor personnel involved in the clinical evaluation of 
the participants will be unblinded to the treatment assigned at a Phase at completion of 
that particular Phase. 
Refer to Section 4.4 for the definition of study completion per participant. 
6.3.5.4. 
Emergency unblinding 
Unblinding a participant’s individual study intervention number should occur ONLY in 
case of a medical emergency when this information 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 via SBIR.  
The investigator may contact a GSK Helpdesk (refer to the Table 18) if he/she needs help 
to perform the unblinding process (i.e., if the investigator is unable to access the 
automated Internet-based system). 
A physician other than the investigator (e.g. an emergency room physician) or 
participant/care giver/family member may also request emergency unblinding either via 
the investigator (preferred option) or via the GSK Helpdesk (back up option). The 
subject/participant card provides contact information for the investigator, his/her back up 
and GSK Helpdesk. 
Table 18 
Contact information for emergency unblinding 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Phone: +32 2 656 68 04 
Fax: +32 2 401 25 75 
Email: rix.ugrdehelpdesk@gsk.com 
Refer to SPM for country-specific numbers 
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6.3.5.5. 
Unblinding prior to regulatory reporting of SAEs 
GSK policy requires unblinding of any unexpected SAE which is attributable/suspected 
to be attributable to the study intervention(s), prior to regulatory reporting. Vaccines 
Clinical Safety and Pharmacovigilance (VCSP) is responsible for unblinding the study 
intervention assignment within the timeframes defined for expedited reporting of SAEs 
(refer to the Section 10.3.10.1).  
In addition, GSK VCSP staff may unblind the intervention assignment for any participant 
with a Suspected Unexpected Serious Adverse Reaction (SUSAR) or a SAE that is fatal 
or life-threatening. For SAEs requiring expedited reporting to 1 or more regulatory 
agencies, a copy of the report containing participant’s intervention assignment may be 
sent to investigators in accordance with local regulations and/or GSK policy. 
6.4. 
Study intervention compliance 
When the study intervention is administered at the site, participants will receive it directly 
from the investigator or designee, under medical supervision. The date of administration 
of each study intervention dose in the clinic will be recorded in the source documents. 
6.5. 
Dose modification 
Not applicable. 
6.6. 
Continued access to study intervention after the end of the 
study 
(Amended 22 March 2022) 
During the study conclusion visit/contact (Telephone T3 in Phase I, Visit V6 in Phase II, 
Formulation and Schedule-finding and Telephone T2/ Telephone T3 in Phase II, 
Sourcing [as per group allocation]), 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 booster study/long-term study the 
reason for refusal will be documented, when available, in the participant’s eCRF. 
The investigator is encouraged to share the immunological assay results of non-
responders with the study participants/participants’ parent(s)/LAR(s). 
It is the responsibility of the investigator to determine the medical care of the non-
responder as per local/regional practices, such as re-vaccination. 
6.7. 
Treatment of overdose 
Not applicable. 
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6.8. 
Concomitant therapy 
(Amended 22 March 2022) 
At each study visit/contact, the investigator or his/her delegate should question the 
participant and/or the participant’s parent(s)/LAR(s) about all medications/products 
taken, and vaccinations received by the participant. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF: 
• 
All concomitant medication associated with an adverse event, including 
vaccines/products, except vitamins and dietary supplements, administered after the 
first dose of study intervention (Phase 1 and Phase II, Sourcing: Day 1 to Day 211 or 
Day 241 or Day 361 (as per the group allocation) and Phase II, Formulation and 
Schedule-finding: Day 1 to Day 541). 
• 
Any concomitant vaccination administered in the period starting 14 days before the 
first dose of study intervention and ending at the last study contact (Phase 1 and 
Phase II, Sourcing: -Day 14 to Day 211 or Day 241 or Day 361 (as per the group 
allocation) and Phase II, Formulation and Schedule-finding: Day -14 to Day 541). 
• 
All concomitant medication leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines. Refer to Sections 5.2.2 
and 9.3.1 for details. 
• 
All concomitant medication which may explain/cause/be used to treat SAE/Adverse 
Event of Special Interest (AESI) including vaccines/products, as defined in Sections 
8.3.1 and 10.3.8.2. These must also be recorded in the Expedited Adverse Event 
Report. 
• 
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 eCRF. 
• 
The use of analgesics to prevent (prophylactic use) and/or treat pain during the first 7 
days after vaccination to be recorded in the eCRF. 
• 
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 anti-pyretic is considered to be 
prophylactic when it is given in the absence of fever and any other symptom, to 
prevent fever from occurring [Refer to Table 1, Table 3 and Table 5 for definition of 
fever].  
• 
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 sampling (see Section 5.5, Criteria for temporary Delay of 
Vaccination). 
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The Local Medical Lead (LML) should be contacted if there are any questions regarding 
concomitant or prior therapy. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
‘Discontinuation’ of study intervention refers to any participant who has not received all 
planned doses of study intervention. A participant who discontinued study intervention 
may continue other study procedures (e.g. safety or immunogenicity), planned in the 
study protocol at the discretion of the investigator.  
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF as follows: 
• 
Adverse event requiring expedited reporting to GSK 
• 
Unsolicited non-serious adverse event  
• 
Solicited adverse event 
• 
Not willing to be vaccinated 
• 
Other (specify). 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration 
The eligibility for subsequent study intervention administration must be confirmed before 
administering any additional dose.  
Participants who meet any of the criteria listed below or criteria listed in sections 5.2.1 
and 5.2.2 should not receive additional doses of study intervention. Such participants 
should be encouraged to continue other study procedures, at the investigators’ discretion 
(Section 10.3.8.2). All relevant criteria for discontinuation of study intervention 
administration must be recorded in the eCRF.  
• 
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. 
• 
Anaphylaxis following the administration of study intervention(s). 
• 
Participants who experience any SAE judged to be possibly or probably related to 
study intervention or non-study concomitant vaccine/product, 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. 
• 
Any condition that in the judgement of the investigator would make intramuscular 
injection unsafe. 
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• 
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 doses of study intervention. Refer to Section 10.3.5 for the definition of 
AESIs. 
• 
Pregnancy (See Section 10.3.7.1). 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered to have withdrawn from the study if no new study procedure 
has been performed or no new information has been collected for him/her since the date 
of withdrawal/last contact. 
From an analysis perspective, a study ‘withdrawal’ refers to any participant who did not 
return for the concluding visit/was not available for the concluding contact planned in the 
protocol.  
Investigators will attempt to contact participants who do not return for scheduled visits or 
follow-up. 
All data and samples collected up to and including the date of withdrawal of/last contact 
with the participant will be included in the study analyses. Refer to Table 1, Table 3 and 
Table 5 for details.  
The primary reason for study withdrawal will be documented in the eCRF, based on the 
list below. The investigator will document whether the decision to withdraw a participant 
from the study was made by the participant himself/herself, by the participant’s 
parent(s)/LAR(s), or by the investigator, as well as which of the following possible 
reasons was responsible for withdrawal: 
• 
Adverse events requiring expedited reporting to GSK (Refer to Section 10.3.10.1 for 
the details) 
• 
Unsolicited non-serious adverse events 
• 
Solicited adverse event 
• 
Withdrawal by participant, not due to an adverse event* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 
• 
Sponsor study termination 
• 
Other (specify) 
*If a participant is withdrawn from the study because he/she/the participant’s 
parent(s)/LAR(s) has withdrawn consent and the reason for withdrawal was provided, the 
investigator must document this reason in the eCRF. 
Participants who are withdrawn from the study because of AEs/SAEs/AESIs/pregnancy 
must be clearly distinguished from participants who are withdrawn for other reasons. 
Investigator will follow participants who are withdrawn from the study due to an 
AE/SAE/AESI/pregnancy until the event is resolved (see Section 10.3.8.2). 
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A participant will be withdrawn if the participant’s treatment code is unblinded by the 
investigator or treating physician (Refer to Section 6.3.5.4). The primary reason for 
discontinuation (the event or condition which led to the unblinding) will be recorded in 
the eCRF. 
7.3. 
Lost to follow-up 
A participant will be considered ‘lost to follow-up’ if he/she fails to return for scheduled 
visits and cannot be contacted by the study site.  
Please refer to the SPM for a description of actions to be taken before considering the 
participant lost to follow-up. 
Study conclusion call/visit and discontinuation of individual sites or of the study as a 
whole is described in Section 10.1.9. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are only permitted when necessary for the management 
of immediate safety concerns for the participant.  
Immediate safety concerns should be discussed with the sponsor as soon as they occur or 
when the study team becomes aware of them. The purpose of this communication is to 
determine if the participant(s) should discontinue the study intervention. 
Study procedures and their timing are summarised in the SoA (Section 1.3).  
All screening evaluations must be completed and the results reviewed before confirming 
that potential participants meet all eligibility criteria. Refer to Sections 8.2.1.2 and 8.2.1.3 
for details on screening evaluations in this study. Note: The safety laboratory evaluations 
in Phase I are not part of the screening evaluation in this study. 
The investigator will maintain a 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. 
Procedures conducted as part of routine clinical management (e.g. haematologic profiles), 
and obtained before the participant/participant’s parent(s)/LAR(s) signed the Informed 
Consent Form (ICF), may be used for screening and/or for establishing a clinical baseline 
(provided the procedure met protocol specified criteria and was performed within the 
time frame defined in the SoA (Section 1.3). 
The SPM provides the investigator and site personnel with detailed administrative and 
technical information that does not impact participant safety. 
Decentralised study procedures (Phase II only): 
If local regulations allow and quality of study procedures is maintained, participant(s) can 
be offered remote visits (e.g. telemedicine, home visits) for the collection of biological 
samples and/or safety data/safety assessment(s)/study intervention administration. These 
remote visits must be performed by qualified study staff/healthcare professionals HCPs. 
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Refer to the Schedule of Activities for the timing of these visits. Details of how these 
visits will be conducted are outlined in the SPM. 
Following procedures can be performed remotely/ virtually (with the exception of Visit 1 
which is always a clinic visit). Refer to the Glossary of terms for definitions of 
telemedicine, remote and virtual visits: 
• 
Safety follow-up may be performed by telemedicine which will use secure video 
conferences, phone calls, and a web portal and/or mobile application as a way of 
communicating with the participant and monitoring the participant’s progress. In 
addition, qualified study staff/HCPs may also identify AEs and report them to the 
investigator for evaluation. 
• 
Biological samples may be collected remotely by qualified study staff/HCPs. 
Biological samples should be collected only if they can be processed in a timely 
manner and appropriately stored until the intended use.  
• 
Administration of study intervention can be performed remotely/at participant’s 
home by qualified study staff/HCPs if appropriate storage conditions for the study 
intervention can be ensured. Furthermore, appropriate medical treatment must be 
readily available during 30 minutes after dosing in case of anaphylaxis, syncope. 
Study procedures in special circumstances: 
(Amended 22 March 2022) 
During special circumstances (e.g., COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be applied. For the duration of such special circumstances, the 
following measures may be implemented for enrolled participants: 
• 
If the eDiary device was provided to the participant, it may be returned to the site by 
conventional mail after the end of the relevant data collection period (Visit 4 for 
Phase I, Visit 5 for Phase II, Formulation and Schedule-finding and Visit 3 for Phase 
II, Sourcing).  
• 
Biological samples may be collected at a different location* other than the study site 
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.  
• 
Phase II only (not applicable for Visit V1): Study visits may be performed at a 
different location* other than the study site (e.g. at participant’s home). For study 
visits involving blood draw, biological samples should not be collected if they cannot 
be processed in a timely manner or appropriately stored until the intended use.  
• 
If despite best efforts it is not possible to collect the biological samples within the 
interval pre-defined in the protocol (see Table 2 for Phase I, Table 4 for Phase II, 
Formulation and Schedule-finding and Table 8, Table 9 and Table 10 for Phase II, 
Sourcing), then the applicable intervals may be extended up to a maximum length of 
days as presented in Table 19 (Phase I), Table 20 (Phase II, Formulation and 
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Schedule-finding) and Table 21, Table 22 and Table 23 (Phase II, Sourcing), as 
applicable.  
• 
If despite best efforts it is not possible to administer the dose of study intervention as 
defined in the protocol (see Table 2 for Phase I, Table 4 for Phase II, Formulation 
and Schedule-finding and Table 8, Table 9 and Table 10 for Phase II, Sourcing), a 
maximum dose interval may be used as presented in Table 19 (Phase I) and Table 20 
(Phase II, Formulation and Schedule-finding) and Table 21, Table 22 and Table 23 
(Phase II, Sourcing), as applicable. 
* It is the investigator’s responsibility to identify an alternate location. The 
investigator should ensure that this alternate location meets International Council on 
Harmonisation (ICH) 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 staff at a site 
other than the designated study site.  
** In case of home visits (for Phase II only), the study procedures should be carried 
out by a qualified person/s as delegated by the Principal Investigator, provided that 
the compliance with protocol procedures are ensured. Refer to Schedule of Activities 
for the schedule of visits (see Table 3 and Table 5). 
Refer to local regulations on the conduct of clinical trials during the COVID-19 
pandemic for more details. 
Impact on the per protocol set for immunogenicity will be determined on a case by case 
basis. 
Table 19 
Intervals between study visits/contacts during special circumstances – 
Phase I 
Interval 
Length of interval  
Allowed interval (Visit window) 
Visit V3 → Visit V4 
30 days 
23 to 51 days (-7 to +21 days) 
Visit V3 → Telephone contact T2 
120 days 
113 to 141 days (-7 to +21 days) 
Visit 3 → Telephone contact T3 
180 days 
173 to 201 days (-7 to +21 days) 
Table 20 
Intervals between study visits during special circumstances – Phase II 
Formulation and Schedule finding 
Interval 
Length of interval  
Allowed interval (Visit window) 
Visit V1 → Visit V2 
30 days 
23 to 51 days (-7 to +21 days) 
Visit V1 → Telephone contact T2 
90 days 
83 to 111 days ( -7 to +21 days) 
Visit V2 → Visit V3/TC* 
90 days 
83 to 111 days (-7 to +21 days) 
Visit V3/TC* → Visit V4 
60 days 
53 to 81 days ( -7 to +21 days) 
Visit V4 → Visit V5 
30 days 
23 to 51 days (-7 to +21 days) 
Visit V4 → Telephone contact T3 
90 days 
83 to 111 days ( -7 to +21 days) 
Visit V4 → Telephone contact T4 
180 days 
173 to 201 days (-7 to +21 days) 
Visit V4  → Telephone contact 
T5 
270 days 
263 to 291 days (-7 to +21 days) 
Visit V4→Visit V6 
360 days 
353 to 381 days (-7 to +21 days) 
* Visit for 
 groups (Visit V3) and telephone call for 
Control group (TC) 
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Table 21 
Intervals between study visits/contacts during special circumstances – 
Phase II (Sourcing; 0,1 month vaccination schedule) 
Interval 
Length of interval  
Allowed interval (Visit window) 
Visit V2 → Visit V3 
30 days 
23 to 51 days (-7 to +21 days) 
Visit V2 → Telephone contact T1 
120 days 
113 to 141 days (-7 to +21 days) 
Visit V2 → Telephone contact T2 
180 days 
173 to 201 days (-7 to +21 days) 
Table 22 
Intervals between study visits/contacts during special circumstances – 
Phase II (Sourcing; 0,2 month vaccination schedule) 
Interval 
Length of 
interval  
Allowed interval (Visit window) 
Visit V2 → Visit V3 
15 days 
8 to 22 days (-7 to +7 days) 
Visit V2 → Visit V4 
30 days 
25 to 51 days (-5 to +21 days) 
Visit V2 → Telephone contact T2 
120 days 
113 to 141 days (-7 to +21 days) 
Visit V2 → Telephone contact T3 
180 days 
173 to 201 days (-7 to +21 days) 
Table 23 
Intervals between study visits/contacts during special circumstances – 
Phase II (Sourcing; 0,6 month vaccination schedule) 
Interval 
Length of 
interval  
Allowed interval (Visit window) 
Visit V2 → Visit V3 
15 days 
8 to 22 days (-7 to +7 days) 
Visit V2 → Visit V4 
30 days 
25 to 51 days (-5 to +21 days) 
Visit V2 → Telephone contact T2 
120 days 
113 to 141 days (-7 to +21 days) 
Visit V2 → Telephone contact T3 
180 days 
173 to 201 days (-7 to +21 days) 
8.1. 
Effectiveness and/or immunogenicity assessments  
Biological samples will be used for research planned in the protocol and for purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol.  
Findings in this or future studies may make it desirable to use samples acquired in this 
study for research not planned in this protocol. In this case, all participants in countries 
where this is allowed will be asked to give consent to allow GSK or a contracted partner, 
to use the samples for further research. The further research will be subject to prior 
Independent Ethics Committee/ Institutional Review Board (IEC/IRB) approval, if 
required by local legislation. 
Information on further research and its 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).  
By default, collected samples will be stored for a maximum of 20 years. This storage 
period begins when the last participant performs the last study visit. This timeline can be 
adapted based on local laws, regulations or guidelines requiring different timeframes or 
procedures. In all cases, the storage period should be aligned with participant’s consent. 
These additional requirements must be formally communicated to, discussed and agreed 
with GSK. 
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8.1.1. 
Biological samples 
8.1.1.1. 
Blood sample 
(Amended 22 March 2022) 
Phase I: An overall blood volume of approximately 240 mL per participant will be 
collected over the course of the Phase I part of the study. An additional 7 mL of blood 
will be collected at Visit V1 and Visit V2 from all participants for the safety laboratory 
evaluation. Refer to Table 24 for details. 
Table 24 
Blood samples at Phase I 
Sample 
type 
Quantity 
Unit 
Timepoint 
Subset name/ 
Group 
Day 
Blood 
Approximately 80 
mL 
Visit V1 
); 
All participants 
Day 1 
Blood 
Approximately 80 
mL 
Visit V3 (
); 
All participants 
Day 31 
Blood 
Approximately 80 
mL 
Visit V4 
 
All participants 
Day 61 
Blood 
Approximately 7 
mL 
Visit V1  
All participants 
Day 1 
Blood 
Approximately 7 
mL 
Visit V2 
All participants 
Day 8 
Pre-Vacc, Pre-vaccination timepoint; Post-Vacc, Post-vaccination timepoint 
Refer to Table 1 (SoA for Phase I) for details of visits. 
Phase II (sourcing): An overall blood volume of approximately 285 mL per participant 
will be collected over the course of the Phase II, Sourcing part of the study. Please refer 
to Table 25 and Table 26 for details. 
Table 25 
Blood samples at Phase II (Sourcing; 0,1 month vaccination schedule) 
Sample 
type 
Quantity 
Unit 
Timepoint 
Subset name/ 
Group 
Day 
Blood 
Approximately 95 
mL 
Visit V1 
); 
All participants 
Day 1 
Blood 
Approximately 95 
mL 
Visit V2 
 
All participants 
Day 31 
Blood 
Approximately 95 
mL 
Visit V3 (
 
All participants 
Day 61 
Pre-Vacc, Pre-vaccination timepoint; Post-Vacc, Post-vaccination timepoint 
Refer to Table 5 (SoA for Phase II, Sourcing) for details of visits. 
Table 26 
Blood samples at Phase II (Sourcing; 0,2 and 0,6 month vaccination 
schedule) 
Sample 
type 
Quantity 
Unit 
Timepoint 
Subset name/ Group 
Day 
Blood 
Approximately 95 
mL 
Visit V1 (
); 
All participants 
Day 1 
Blood 
Approximately 95 
mL 
Visit V3 
(
); 
Day 76 
Day 196 
Blood 
Approximately 95 
mL 
Visit V4  
 
Day 91 
Day 211 
Pre-Vacc, Pre-vaccination timepoint; Post-Vacc, Post-vaccination timepoint. 
Refer to Table 6 and Table 7(SoA for Phase II, Sourcing) for details of visits. 
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Note: the total number of participants (healthy adults) planned to be enrolled in the Phase 
I and Phase II (Sourcing) is required in order to collect sufficient serum samples for the 
development of assays to be used in the 
 vaccine clinical development 
program. All participants will be followed for safety up to 6 months after the last 
vaccination. 
Phase II (formulation and schedule-finding): In order to provide the necessary serum 
volume for the bactericidal assays (enc-hSBA and/ or hSBA), an overall blood volume of 
approximately 90mL, per participant, will be collected over the course of the Phase II 
step of the study. Please refer to Table 27 for details. 
Table 27 
Blood samples at Phase II (Formulation and schedule-finding) 
Sample 
type 
Quantity 
Unit 
Timepoint 
Subset name/ 
Group 
Day 
Blood 
Approximately 15 
mL 
Visit V1 (*) 
All participants 
Day 1 
Blood 
Approximately 15 
mL 
Visit V2 (**) 
All participants 
Day 31 
Blood 
Approximately 30 
mL 
Visit V5 (
 
All participants 
Day 211 
Blood 
Approximately 30 
mL 
Visit V6 (^) 
All participants 
Day 541 
* Pre-vaccination (Pre-Vacc) for 
 and Control groups 
** Pre-vacc timepoint for
 groups. For rest of the groups, 
 
 and Control, this is post-vaccination (post-Vacc 1) timepoint 
^ Blood sample will be used only for assessment of tertiary objectives 
Note: in case of local regulations limiting the amount of blood to be taken in the younger population (e.g 10-12 years of 
age and/or at the lower bound of the percentile of the growth chart), a reduced amount of blood volume could be drawn 
at Phase II, Visit 5 and Visit 6. In this population every effort must be done to collect at least 25mL of blood volume, 
samples will be analysed according to priority ranking provided in Table 29 and Table 30. 
Refer to Table 3 (SoA for Phase II, Formulation and Schedule-finding) for details of visits. 
Insufficient blood volume may lead to test cancellation and jeopardise the statistical 
power. Hence, every effort must be done to collect blood volume as per protocol 
requirements. 
Note 1: Blood samples are taken from all participants in Phase I and II irrespective of the 
testing status to maintain the blind of the study. Refer to Section 8.1 for details on how the 
unused/ left-over samples will be used. 
Note 2: Check criteria for blood draw delay as specified in Section 5.5. A topical 
anaesthetic (e.g. EMLA adhesives or cream) may be used at the site of blood sample 
draw, according to local practice in order to minimise pain. 
8.1.1.2. 
Urine sample 
Urine samples for pregnancy testing will be collected from female participants of 
childbearing potential prior to the study intervention. Refer to Section 4.1 and 8.2.1.4 for 
details. 
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C O N FI D E N TI A L  
2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
7 8  
8. 1. 2.  
L a b or at or y a s s a y s  
( A me n de d 2 2  M arc h 2 0 2 2)  
All la b orat or y testi n g will be perf or m e d at G S K la b orat or y or i n a la b orat or y desi g nat e d 
b y G S K. Refer t o Secti o n 8. 1. 1. 1  f or details o n bl o o d sa m pli n g. 
Effecti ve n ess of t he 
 a nti ge ns  of t he 
 vacci ne will be e val uate d 
wit h ser u m bacteri ci dal assa y s usi n g e n d o ge n o us s o urce of h u m a n c o m ple me nt (e nc-
h S B A), o n a p a nel of 1 1 0 U S re pres e ntati ve N. me ni n giti dis  ser o gr o u p B i n vasi ve disease 
strai ns. I m m u n o ge ni cit y of t he vacci ne a gai nst ser o gr o u ps A, B, C, W a n d Y will be 
e val uate d wit h t he ser u m bacterici d al assa y usi n g e x o ge n o us s o urce of h u ma n 
c o m ple me nt ( h S B A). A n 
 m ulti ple x ass ay will 
be use d t o e val uat e t he ser ot y pe -s pecific I g G res p o nses t o A, C, W, a n d Y. 
T a bl e 2 8  
L a b or at or y a s s a y s –  P h a s e I a n d II 
Ple as e refer t o t he Secti o n 1 0. 2  f or a brief descri pti o n of t he ass a ys perf or me d i n the  
st u d y.  
T he a d dresses of cli nic al l a b or at ories use d f or s a m ple a n al ysis are pr o vi de d i n a 
se p ar ate d oc u me nt acc o m p a n yi n g t his st u d y pr ot oc ol. 
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GSK clinical laboratories have established a Quality System supported by procedures. 
The activities of GSK clinical laboratories are audited regularly for quality assessment by 
an internal (sponsor-dependent) but laboratory-independent Quality Department. 
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C O N FI D E N TI A L  
2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
8 0  
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C O N FI D E N TI A L  
2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
8 1  
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C O N FI D E N TI A L  
2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
8 2  
8. 1. 4.  
Cli ni c al s af et y l a b o r at or y a s s e s s m e nt s 
Refer t o  t he Secti o n 1 0. 2. 1  f or t he list of cli nical la b orat or y safet y assess me nts re q uire d 
b y t he pr ot oc ol. T hese assess me nts m us t be c o n d ucte d acc or di n g t o t he cli nical 
la b orat or y ma n u al a n d t h e S o A. 
8. 1. 5.  
I m m u n ol o gi c al c orr el at e s of pr ot e cti o n 
N o ge nerall y acce pte d i m m u n ol o gical c orrelate of pr otecti o n has bee n de m o nstrate d s o 
far a gai nst N. me ni n giti dis  ser o gr o u ps A, B, W, a n d Y.  
A n h S B A titre ≥4 is a ge nerall y acce pte d c orrelat e of pr otecti o n a gai nst I M D ca use d b y 
N. me ni n giti dis  ser o gr o u p C. 
T he i m m u n ol o gical ass a y res ults will be c o m m u nicate d t o t he i n vesti gat or w he n rea d y 
a n d a vaila ble.  Refer t o S ecti o n 6. 6  f or det ails re gar di n g tr eat me nt f or n o n-res p o n ders. 
8. 2.  
S af et y a s s e s s m e nt s  
T he i n vesti gat or a n d his/ her desi g nees are res p o nsi ble f or detecti n g, d o c u me nti n g, a n d 
re p orti n g e ve nts t hat meet the defi niti o n of a n A E , A E SI or S A E. T he i n vesti gat or a n d 
desi g nees are res p o nsi ble f or f oll o wi n g u p A Es t h at are s eri o us, c o nsi dere d relate d t o t he 
st u d y i nter ve nti o n or t he st u d y, or t hat ca use d t he partici pa nt’s wit h dra wal fr o m t he st u d y 
i nter ve nti o n or s t u d y. 
8. 2. 1.  
Pr e -v a c ci n ati o n pr o c e d ur e s  
8. 2. 1. 1.  
C oll e cti o n of d e m o gr a p hi c d at a  
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Prior to study enrolment, demographic data will be collected from the participant, 
including date of birth (Phase I and Phase II (Sourcing): year; Phase II (Formulation and 
Schedule-finding): month and year), gender, race, ethnicity, weight, and height, and 
recorded in the participant’s eCRF. 
For Phase II (Formulation and Schedule-finding) only: At Visit V1 in the Control 
group, the participant receives 2 injections, one in either arm. Therefore, in order to 
associate the solicited events reported to the vaccine administered in that arm, the 
dominant arm (left or right) will be recorded in the eCRF (Table 16). 
8.2.1.2. 
Medical/vaccination history 
Obtain the participant’s medical/vaccination history by interviewing the 
participant/parent(s)/LAR(s) and/or review of the participant’s medical records. Record 
any pre-existing conditions, signs and/or symptoms present prior to the first dose of study 
intervention in the eCRF. 
8.2.1.3. 
General and symptom-directed physical examination 
A general physical examination is to be performed by a qualified healthcare practitioner. 
“Qualified health care practitioner” refers to any licensed or certified healthcare 
professional who is permitted by institutional policy to perform protocol-required 
procedures, and who is identified within the Delegation of Responsibility Log. The 
physical examination will include examination of organ systems that are relevant to the 
investigator based on medical history and review of systems and a measurement of heart 
rate, blood pressure, and temperature.  
These data will be written in the source document. Should the physical assessment reveal 
any abnormal values or events, these must be documented in the eCRF Adverse Events 
Form. 
Physical examination at each study visit subsequent to the first study intervention visit, 
will be performed only if the participant / participant’s parent(s)/LAR(s) indicates during 
questioning that there might be some underlying pathology(ies) or if deemed necessary 
by the Investigator or delegate. 
If the investigator determines that the participant’s health on the day of vaccination 
temporarily precludes vaccination, the visit will be rescheduled. 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. 
8.2.1.4. 
Pregnancy test 
Female participants of childbearing potential must perform a urine pregnancy test before 
the administration of any dose of study intervention. Pregnancy testing must be done 
even if the participant is menstruating at the time of the study visit. The study 
intervention may only be administered if the pregnancy test is negative.  
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Refer to the Section 10.5.3.1 for the information on study continuation for participants 
who become pregnant during the study. 
8.2.1.5. 
Warnings and precautions to vaccination 
Warnings and precautions to administration of study intervention must be checked at 
each visit with planned administration of study intervention. 
Refer to the approved product label/package insert of Bexsero and Menveo.  
8.2.2. 
Study holding rules and safety monitoring 
Safety monitoring is specified in the endpoints (Section 9.4) as well as in Table 1 (for 
Phase I), Table 3 (for Phase II, Formulation and Schedule-finding) and Table 5 (for Phase 
II, Sourcing). 
8.2.2.1. 
Safety data review  
8.2.2.1.1. Safety evaluation 
For Phase I of the study, a staggered enrolment of healthy volunteers will be performed, 
as described in Figure 4. 
Figure 4 
Step-wise approach for safety review in Phase I (Safety Lead-in) 
 
Abbreviation: N, number of participants; V, clinic visit; D, day; iSRC, internal safety review committee; PC, phone 
contact; BS, blood sample. 
Note: This is a simplified study design aimed to show the safety review in Phase I. To see the detailed study design, 
refer to Figure 1 
An iSRC, composed of senior GSK experts independent from the study team, will meet at 
pre-defined timepoints to perform safety monitoring through unblinded review of safety 
data. 
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The following step-wise approach will be followed for the safety evaluation during the 
Phase I Safety Lead-in: 
• 
Step 1: Following the first vaccination in 
 (12 participants) and 
4 participants) groups, all available safety data from all participants 
collected up to Day 8 will be evaluated by the iSRC. The iSRC will be responsible 
for making the first “go-no go” decision based on unblinded data. If a “go” decision 
is made, the enrolment in groups 
 will start and the 
administration of the second vaccination will take place in groups 
 
.  
• 
Step 2: Following the first vaccination in 
 (12 participants) and 
 (4 participants) groups, all available safety data from all participants 
collected up to Day 8 will be evaluated by the iSRC. The iSRC will be responsible 
for making the second “go-no go” decision based on unblinded data. If a “go” 
decision is made, the administration of the second vaccination will take place for 
participants in groups 
.  
• 
Step 3: Following the second vaccination in 
 groups at 
Day 31, all available safety data from all participants collected up to Day 38 will be 
evaluated by the iSRC. The iSRC will be responsible for making the third “go-no 
go” decision based on unblinded data. If a “go” decision is made, the Phase II 
enrolment will start parallelly for the 2 parts: Phase II (sourcing) and Phase II 
(formulation and schedule-finding). 
For Phase II, Formulation and Schedule-finding part of the study, a staggered enrolment 
of healthy volunteers will be performed, as described in Figure 5, for the iSRC safety 
evaluation of the first 45 enrolled participants (Phase II safety lead-in). 
Figure 5 
Step-wise approach for safety review in Phase II (Formulation and 
Schedule-finding) 
  
(N=191)
Randomization: 
1:1:1:1:1
N = 955
(N=191)
(N=191)
Control
(N=191)
(N=191)
N (Total) = 1000
Refer to Study design figure for details*
Phase II: Formulation and Schedule-finding
V2 D31
Month 1
V1 D1
Month 0
V5 D211
Month 7
V4 D181
Month 6
(N=15)
(N=5)
BS
BS
BS
Randomization: 
3:1:3:1:1
N = 45
Placebo
Placebo
(N=15)
(N=5)
Control
(N=5)
BS
BS
BS
MenB
MenACWY
V3/ TC #D121
Month 4
Placebo
MenB
V6 D541
Month 18
BS
Placebo
BS
BS
BS
BS
BS
BS
BS
BS
BS
BS
BS
i
S
R
C
BS
BS
PC D8^
Month 0






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Abbreviation: N, number of participants; V, clinic visit; D, day; TC, Telephone contact for Control group only; iSRC, 
internal safety review committee; PC, phone contact; BS, blood sample. 
^ The phone call at Day 8 is only for the first 45 participants (15 participants in 
 5 participants in 
, 15 participants in 
, 5 participants in 
and 5 participants in the Control 
groups) 
# Day 121 Month 4 is a visit for 
 groups (Visit V3) 
and is a telephone call for Control group (TC) 
Note: This is a simplified study design aimed to show the safety review in Phase II (Formulation and Schedule-finding). 
To see the detailed study design, refer to Figure 2 (*) 
The following step-wise approach will be followed for the safety evaluation during the 
Phase II (Formulation and Schedule-finding): 
• 
A total of 45 participants will be randomised with 3:1:3:1:1 ratio to the 5 groups (15 
in the 
, 5 in the 
, 15 in the 
, 5 in the 
 and 5 in the Control group). A “go-no go” decision will be taken by 
the iSRC based on safety and reactogenicity data collected up to Day 8 from these 
participants (Section 8.2.2.1).  
• 
If the decision is “go”, the enrolment in all groups will continue with a 
randomisation ratio of 1:1:1:1:1 to the target total sample of 1000 participants and 
the administration of the second vaccination at Month 4 will take place in the 40 
participants in 
 
 groups (as per study design).  
Unblinded safety data to be reviewed by the iSRC include clinical safety laboratory data 
(only for Phase I), solicited administration site and systemic post-vaccination events, 
unsolicited AEs, AESIs, and SAEs. Additional safety data may be reviewed and 
monitored by the iSRC whenever applicable. 
Continuous monitoring during the study by the study team will allow for ad-hoc iSRC 
reviews and/or enrolment hold if any safety concern is identified or a substantial trend 
emerges outside of the scheduled unblinded safety reviews. Holding rules will be 
introduced to ensure a well-controlled exposure to the investigational candidate vaccine 
and to prevent participants from being exposed to any unnecessary safety risks (refer to 
Section 8.2.2.1.3). 
8.2.2.1.2. Outcome of safety evaluation 
If no safety signal is observed during the iSRC reviews, the favourable outcome of the 
safety evaluations will be documented and provided in a written way, authorising the 
investigator to start the administration of the subsequent dose of study intervention to 
participants, as well as enrolment and study intervention administration to the remaining 
participants in the next step of the study. 
If a safety signal is observed during the safety evaluations or if any of the holding rules 
2a-c is met (Table 32), the iSRC Chair (or his/her representative) is responsible for the 
urgent communication within GSK, including the rationale for the decision to put the 
study intervention administration on hold or not. Details about the procedures to be 
followed in case of safety signal or if a holding rule 2 (a-c) is met will be documented in 
the iSRC Charter. 
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The Clinical Research & Development Lead (CRDL) who is the primary study contact 
will inform the local GSK contact. All site staff will be informed about the final decision 
whether to suspend, modify or continue the conduct of the study on all groups or on 
selected groups by their local GSK contact. 
8.2.2.1.3. Study holding rules 
Holding rules are defined to ensure well-controlled exposure to the investigational 
product and they will apply to study participants in the Phase I Safety Lead-in and to the 
first 45 study participants enrolled in the formulation and schedule-finding Phase II part. 
The holding rules will hence serve as criteria to point attention to safety signals and 
require escalation within GSK, in order to decide whether other participants can be 
exposed. However, medical judgement considering all available safety data at the time of 
safety review should be the basis for decision to continue the study or not at each step. 
The safety holding rules are defined in the Table 32 (Phase I) and Table 33 (Phase II, 
Formulation and Schedule-finding). If the investigator becomes aware of holding rule 1a-
d being met (for Phase I) and holding rule 1a (for Phase II, Formulation and Schedule-
finding during the safety lead-in step), he/she will suspend administering the study 
intervention and will inform GSK immediately (e.g. in case of death or any life-
threatening SAEs). 
Holding rules 2a-c will be assessed by the iSRC during the safety evaluations on 
unblinded data. 
These holding rules have been written under the assumption that the safety data from all 
participants will be available. If the data from all participants are not available (i.e. in 
case a participant is lost to follow-up), then the holding rules will be assessed on a pro-
rata basis. 
Of note, no formal holding rules will be applied for other safety data such as missed visits 
due to study intervention related AEs, Grade 1 and Grade 2 solicited and unsolicited AEs 
in the 7-day follow-up period and unsolicited AEs collected from Day 8 to Day 30 after 
study intervention administration. However, if available, these data will also be reviewed 
by the iSRC to allow an overall assessment of the benefit/risk ratio of study intervention 
administration. 
The iSRC can also meet ad-hoc during the entire safety lead-in phase (Phase I). 
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Table 32 
Study holding rules – Phase I  
Holding 
rule 
Event 
Number or % of 
participants needed to 
trigger the hold 
1a 
Death or any life-threatening SAE regardless of causality 
≥ 1 
1b 
Any non-life-threatening SAE that can be reasonably attributed to the 
vaccination 
≥ 1 
1c 
Any withdrawal from the study (by investigator or participant request) 
following a Grade 3 AE that can be reasonably attributed to the vaccination. 
≥ 1 
1d 
Fever >40°C (104°F) OR any solicited administration site and/or systemic 
events leading to hospitalisation, OR necrosis at the injection site, each 
with an event onset within the 7-day (Day 1-7) post-vaccination period  
≥ 1 
2a 
Any Grade 3 solicited administration site event (lasting 48h or more) in 
the investigational group, with an event onset within the 7-day (Day 1-7) 
post-vaccination period 
≥ 20% 
2b 
Any Grade 3 solicited systemic event (lasting 48h or more) in an 
investigational group, with an event onset within the 7-day (Day 1-7) post-
injection period 
≥ 20% 
2c 
Any Grade 3 unsolicited AE in an investigational group, that can be 
reasonably attributed to the vaccination, with an event onset within the 7-
day (Day 1-7) post-injection period OR Any Grade 3 abnormality in pre-
specified haematological or biochemical laboratory parameters* in an 
investigational group with an event onset within the 7-day (Day 1-7) post-
vaccination period  
≥ 20% 
Abbreviations: AE, adverse event; SAE, serious adverse event.  
* Please refer to FDA Toxicology Grading Scale for the definition of the Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials [FDA, 2007; Refer to Section 10.4, Appendix 4] 
Table 33 
Study holding rules – Phase II (Formulation and Schedule-finding) 
Holding 
rule 
Event 
Number or % of 
participants needed to 
trigger the hold 
1a 
Death or any life-threatening SAE regardless of causality 
≥ 1 
2a 
Any Grade 3 solicited administration site event (lasting 48h or 
more) in the investigational group, with an event onset within the 7-day 
(Day 1-7) post-vaccination period 
≥ 20% 
2b 
Any Grade 3 solicited systemic event (lasting 48h or more) in an 
investigational group, with an event onset within the 7-day (Day 1-7) 
post-injection period 
≥ 20% 
2c 
Any Grade 3 unsolicited AE in an investigational group, that can be 
reasonably attributed to the vaccination, with an event onset within the 
7-day (Day 1-7) post-injection period  
≥ 20% 
Abbreviations: AE, adverse event; SAE, serious adverse event;  
The investigator is not permitted to begin dosing study participants in subsequent steps 
(Phase I or Phase II Formulation and Schedule-finding) until the receipt of favourable 
written documentation of iSRC safety evaluations.  
If the investigator becomes aware of a holding rule being met, he/she must suspend 
administration of the study intervention and inform GSK immediately (holding rules 1a-
d). Refer to Table 40 for contact information.  
The following communication sequence must be followed: 
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• 
The concerned site staff must put enrolment and study intervention administration on 
hold. 
• 
The concerned site staff must immediately inform their local contact defined in the 
Table 40. 
• 
The LML will inform the other sites of his/her country, LMLs of other countries and 
the CRDL. 
• 
All informed site staff will send back an email to their local contact to acknowledge 
receipt of the information. 
• 
GSK Central will further evaluate the case with the iSRC and will take the decision 
to stop or to restart the vaccination. CRDL who is the primary contact will inform 
the local GSK contact. All site staff will be informed about that final decision by 
their local GSK contact. 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
other safety reporting 
8.3.1. 
Time period and frequency for collecting AE, SAE and other 
safety information  
(Amended 22 March 2022) 
An overview of the protocol-required reporting periods for AEs, SAEs, AESIs and 
pregnancies is given in Table 34 for Phase I and Table 35 for Phase II. Refer to the 
Section 10.3.8.1 for details on the time period for recording safety information. 
Table 34 
Timeframes for collecting and reporting of safety information – Phase I 
Event 
On 
V1* 
 
V1 
 
 
V3 
 
V4 
 
PC 
Phase I 
conclusion 
 
D1*** 
D7 
D31 
D37 
D61 
 
D151 
D 211 (PC) 
Solicited administration site 
and systemic events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to withdrawal 
from the study** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Event 
On 
V1* 
 
V1 
 
 
V3 
 
V4 
 
PC 
Phase I 
conclusion 
 
D1*** 
D7 
D31 
D37 
D61 
 
D151 
D 211 (PC) 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AESIs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies**  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.; V: Visit; D: Day, M: Month; PC=Phone call 
** Including COVID-19 infection-related AEs; Recording of unsolicited AEs is only from Day 1 to Day 30 post-
vaccination 
*** Except SAEs related to study participation or concurrent GSK medication/vaccine, all other safety data will be 
collected starting from Visit 1 after vaccine administration 
 
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Table 35 
Timeframes for collecting and reporting of safety information – Phase II (Formulation and schedule-finding) 
Event 
On 
V1* 
 
V1 
 
V2 
 
V3# 
 
 
 
V4 
 
V5 
 
PC 
V6 
Study Conclusion 
 
D1*** 
D7 
D31 
D121 
D127 
D151 
 
D181 
D 187 
D 211 
 
D361 
D541 
Solicited administration site 
and systemic events  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to withdrawal 
from the study** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AESIs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.; V: Visit; D: Day, M: Month; PC = Phone call 
#Solicited AEs and unsolicited AEs will be collected only for 
 groups at Visit V3 (Control group will have a phone 
call at this time point (TC) where other safety follow-up will be done) 
** Including COVID-19 infection-related AEs; Recording of unsolicited AEs is only from Day 1 to Day 30 post-vaccination 
*** Except SAEs related to study participation or concurrent GSK medication/vaccine, all other safety data will be collected starting from Visit 1 after vaccine administration 
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Table 36 
Timeframes for collecting and reporting of safety information – Phase II 
(Sourcing; 0,1 month vaccination schedule) 
Event 
On 
V1* 
 
V1 
 
 
V2 
 
 
V3 
 
PC 
Study 
conclusion 
 
D1*** 
D7 
D31 
D37 
 
D61 
 Day 151 
D 211 
(PC) 
Solicited administration 
site and systemic events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to withdrawal 
from the study** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AESIs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies**  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.; V: Visit; D: Day, M: Month; PC=Phone call 
** Including COVID-19 infection-related AEs; Recording of unsolicited AEs is only from Day 1 to Day 30 post-
vaccination) 
*** Except SAEs related to study participation or concurrent GSK medication/vaccine, all other safety data will be 
collected starting from Visit 1 after vaccine administration 
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Table 37 
Timeframes for collecting and reporting of safety information – Phase II 
(Sourcing; 0,2 month vaccination schedule) 
Event 
On 
V1* 
 
V1 
 
PC 
 
V2 
 
 
V3 
 
V4 
 
PC 
Study 
conclusion 
 
D1*** D7 
D31 
D61 D67  
D76 
 
D91 
 Day 181 
D 241 
(PC) 
Solicited 
administration site 
and systemic 
events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to 
withdrawal from the 
study** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AESIs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies**  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.; V: Visit; D: Day, M: Month; PC=Phone call 
** Including COVID-19 infection-related AEs; Recording of unsolicited AEs is only from Day 1 to Day 30 post-
vaccination) 
*** Except SAEs related to study participation or concurrent GSK medication/vaccine, all other safety data will 
be collected starting from Visit 1 after vaccine administration 
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Table 38 
Timeframes for collecting and reporting of safety information – Phase II 
(Sourcing; 0,6 month vaccination schedule) 
Event 
On 
V1* 
 
V1 
 
PC 
 
V2 
 
 
V3 
 
V4 
 
PC 
Study 
conclusion 
 
D1*** D7 
D31 
D181 D187  D196  D211  Day 301 D 361(PC) 
Solicited 
administration site 
and systemic events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to 
withdrawal from the 
study** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AESIs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies**  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.; V: Visit; D: Day, M: Month; PC=Phone call 
** Including COVID-19 infection-related AEs; Recording of unsolicited AEs is only from Day 1 to Day 30 post-
vaccination) 
*** Except SAEs related to study participation or concurrent GSK medication/vaccine, all other safety data will 
be collected starting from Visit 1 after vaccine administration 
The investigator or designee will record and immediately report all SAEs to the sponsor 
via the Expedited AE Reporting Form. Reporting should, under no circumstances, occur 
later than 24 hours after the investigator becomes aware of an SAE, as indicated in 
Section 10.3.10. The investigator will submit any updated SAE data to the sponsor 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 34. Investigators are not obligated to actively seek AEs 
or SAEs from 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 intervention, the 
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investigator will promptly notify the study contact for reporting SAEs mentioned in the 
Table 40. 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and other 
events  
Detection and recording of AE/SAE/AESI/pregnancies are detailed in Section 10.3.8.  
Assessment of AE/SAE intensity, causality and outcome are described in Section 10.3.9.  
Open-ended and non-leading verbal questioning of participants/participants’ 
parent(s)/LAR(s) is the preferred method of acquiring information related to an 
AE/SAE/AESI/pregnancy. 
8.3.2.1. 
Clinically significant abnormal laboratory findings (Phase I) 
The investigator must review the laboratory report, document that he/she did so, and 
record any clinically relevant changes occurring during the study in the AE section of the 
eCRF. Clinically significant abnormal laboratory findings are those which are not 
associated with an underlying disease, unless judged by the investigator to be more 
severe than expected for the participant’s condition. 
• 
All clinically significant abnormal laboratory test values reported for participants in 
Phase I at Visit V1 and Visit V2 should be repeated until the values return to 
normal/baseline, or until they are no longer considered significantly abnormal by the 
investigator or LML. Refer to the Section 10.3.6 for more information on clinically 
abnormal laboratory assessments that qualify as an AE or SAE. 
• 
If such values do not return to normal/baseline after an interval judged reasonable by 
the investigator, the aetiology of the abnormal value should be identified and the 
sponsor notified. 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies and 
other events  
Once an investigator (or designee) becomes aware that a study participant has 
experienced an SAE/AESI/pregnancy, it must be reported to GSK using the required 
documentation and within the timeframes mentioned in Table 39. This is essential for 
meeting GSK legal obligations and ethical responsibilities for participant safety and the 
safety of a study intervention under clinical investigation. 
For SAEs/AESIs, the investigator must always provide an assessment of causality at the 
time of the initial report, as defined in the Section 10.3.9.2. 
Local regulatory requirements and sponsor policy for preparation of an investigator 
safety report of Suspected Unexpected Serious Adverse Reactions (SUSAR) must be 
followed. These reports will be forwarded to investigators as necessary. 
The sponsor has the legal responsibility to notify local authorities/regulatory agencies 
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about the safety of an investigational study intervention. The sponsor will comply with 
country-specific regulatory requirements related to safety reporting to the regulatory 
authority, IRB/IEC and investigators. 
Please refer to the Section 10.3.10 for further details regarding the reporting of 
SAEs/AESIs/pregnancies. 
Table 39 
Timeframes for submitting SAE, pregnancy and other events reports to 
GSK  
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡‡ 
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
Pregnancies 
24 hours* 
electronic pregnancy report  
24 hours* 
electronic pregnancy report 
AESIs  
24 hours**, ‡‡  
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of an AESI  
‡‡ The investigator will be required to confirm review of the SAE/AESI causality within 72 hours of submission of the 
SAE/AESI 
8.3.3.1. 
Contact information for reporting SAEs, AESIs, pregnancies and study 
holding rules 
Table 40 
Contact information for reporting SAEs, AESIs, pregnancies and study 
holding rules 
Study contact for questions regarding 
SAEs, AESIs, pregnancies  
Study contact for reporting of study 
holding rules  
Refer to the local study contact 
information document 
As soon as the investigator is aware that a 
holding rule is met, he/she must 
immediately inform the LML.  
Back up study contact for reporting 
SAEs, AESIs, pregnancies  
Available 24/24 hours and 7/7 days: 
Back up study contact for escalation of 
holding rules  
If applicable, refer to the local study 
contact information document. 
GSK Clinical Safety & 
Pharmacovigilance 
 
Outside US & Canada sites: 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: Rix.CT-safety-
vac@gsk.com 
US sites only: 
Fax: 1 610 787 7053 
 
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8.3.4. 
Treatment of adverse events 
Any medication administered for the treatment of an SAE/AESI should be recorded in 
the eCRF (refer to the Section 10.3.10.1). 
8.3.5. 
Participant card 
The investigator (or 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 always keep the 
participant card in his/her/their possession for the duration of the study. In an emergency, 
this card serves to inform the responsible attending physician/LAR/family member that 
the participant is in a clinical study and that relevant information may be obtained by 
contacting the investigator or his/her back up. 
8.3.6. 
Medical device deficiencies 
The study interventions (
, Bexsero and placebo) are combination products 
constituted of a device and biologic product (e.g., pre-filled syringes). Refer to Glossary 
of terms for the definition of a combination product and a medical device deficiency. 
8.3.6.1. 
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 GSK. This applies to any 
medical device provided for the conduct of the study.  
Device deficiencies will be reported to GSK within 24 hours after the investigator 
determines that the event meets the protocol definition of a device deficiency. Refer to 
Section 10.7 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 related of the device deficiency to the incident. Follow-up 
applies to all participants, including those who discontinue study intervention or the 
study. 
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator and reported to GSK within 24 hours. 
8.3.6.2. 
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 to GSK. GSK has a legal responsibility to notify 
appropriate regulatory authorities and other entities about safety information linked to 
medical devices being used in clinical studies. Refer to section  10.7.3 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. 
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8.4. 
Pharmacokinetics 
Pharmacokinetics are not evaluated in this study. 
8.5. 
Genetics and/or Pharmacogenomics 
Not applicable. 
8.6. 
Biomarkers 
Not applicable. 
8.7. 
Immunogenicity 
Refer to Section 8.1. 
8.8. 
Health outcomes 
Not applicable. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
9.1.1. 
Phase I (Safety Lead-in) and Phase II (Sourcing) 
There is no hypothesis for Phase I. 
9.1.2. 
Phase II (Formulation and Schedule-finding)  
9.1.2.1. 
Superiority of vaccine effectiveness of the 
 vaccine 
 
) when administered at 0,2- or 0,6-m schedule compared to the 
Control vaccine (MenB) 
For demonstration of superiority of the Vaccine effectiveness (VE), defined as the 
percentage of samples with bactericidal serum activity at 1:4 dilution using enc-hSBA 
against a panel of 110 randomly selected endemic US N. meningitidis serogroup B 
invasive disease strains, of 
 vaccine compared to Control vaccine (MenB) 
the following hypothesis will be tested: 
Null hypothesis: 
H0: π
 – π Control ≤ 5% 
vs. 
Alternative hypothesis: 
H1: π
 – π Control > 5% 
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Where: π 
 and π Control represent the percentages of samples with 
bactericidal serum activity using enc-hSBA against a randomly selected panel of endemic 
US N. meningitidis serogroup B invasive disease strains at 1 month after the last 
vaccination in the ABCWY groups and in the Control group and 5% is the superiority 
margin for the difference in percentages of samples with bactericidal serum activity 
between ABCWY and Control groups. Superiority of 
 to Control vaccine 
(MenB) will be demonstrated if the Lower Limit (LL) of the 2-sided 97.5% Confidence 
Interval (CI) for the group difference in percentages of samples with bactericidal serum 
activity against a randomly selected panel is above 5%. 
9.1.2.2. 
Immunological non-inferiority of 
 vaccine
 
when administered at 0,2- or 0,6-m schedule compared to the Control 
vaccine (MenACWY) 
For demonstration of non-inferiority of 
 vaccine versus Control vaccine 
(MenACWY – in participants without a previous MenACWY vaccination (unprimed)), 
the following non-inferiority hypotheses will be tested simultaneously for each of the 4 
serogroups A, C, W, and Y: 
Null hypothesis: 
H0: π 
 – π Control ≤ -10% 
vs. 
Alternative hypothesis: 
H1: π 
 – π Control > -10% 
Where: π 
 represents the percentages of participants with a 4-fold rise 1 
month after the last vaccination in the groups receiving 
 and π Control 
represents the percentages of participants with a 4-fold rise 1 month after the first 
vaccination in the Control group (participants receiving MenACWY without a previous 
MenACWY vaccination (unprimed)); and -10% is the non-inferiority margin for the 
difference in 4-fold rise between groups receiving 
 and Control group. 
Immunological non-inferiority of 
 vaccine to Control (MenACWY) will 
be demonstrated if the LL of the 2-sided 97.5% CI for the group difference in percentages 
of participants achieving a 4-fold rise in hSBA titres is above -10% for each serogroup. 
9.2. 
Sample size determination 
Participants who withdraw from the study will not be replaced. 
9.2.1. 
Phase I (Safety Lead-in)  
Thirty-two (32) participants are to be enrolled in the 4 arms of Phase I of the study; 12 
each in the 
 groups and 4 each in the 
 
 groups. 
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9.2.2. 
Phase II (Formulation and Schedule-finding)  
A thousand (1000) participants are to be enrolled in 5 arms of Phase II of the study, 206 
participants for both 
 arms and 196 participants for 
 and Control arms. 
 
 
 
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The formulation and schedule for future clinical development of the 
 
vaccine will be selected taking also into considerations the results of the Phase II 
secondary endpoints, following the success of the primary objectives. 
9.2.3. 
Phase II (Sourcing) 
(Amended 22 March 2022) 
One hundred and seven (107) participants have been enrolled in 2 arms of Phase II 
(Sourcing) of the study, in 
 group (1:1 
randomisation). At the time of this amendment (Protocol amendment 4) enrolment to 
these groups was stopped. 
Two hundred and forty (240) participants are to be enrolled in 4 arms, 60 participants 
each in 
 
groups (1:1:1:1 randomization). 
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9.3.1. 
Criteria for elimination from analysis 
If the participant meets one of the criteria listed in the Section 7.1.1, he/she may be 
eliminated from per protocol analysis. 
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9.4. 
Statistical analyses 
9.4.1. 
Primary endpoint(s) – Phase I (Safety Lead-in) 
Primary Endpoint 
Statistical Analysis Methods 
Safety 
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Primary Endpoint 
Statistical Analysis Methods 
9.4.2. 
Primary endpoint(s) – Phase II (Formulation and Schedule-
finding)  
(Amended 22 March 2022) 
Primary Endpoint 
Statistical Analysis Methods 
Superiority of 
effectiveness 
Immunological non-
inferiority 
Safety 
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Primary Endpoint 
Statistical Analysis Methods 
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9.4.3. 
Primary endpoint(s) – Phase II (Sourcing) 
(Amended 22 March 2022) 
Primary Endpoint 
Statistical Analysis Methods 
Safety 
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Primary Endpoint 
Statistical Analysis Methods 
9.4.4. 
Secondary endpoint(s) – Phase II (Formulation and Schedule-
finding) 
Secondary Endpoint 
Statistical Analysis Methods 
Description of the 
distribution of B 
strains killed  
Immune response to 
serogroup B 
indicator strains 
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Secondary Endpoint 
Statistical Analysis Methods 
Immune response to 
serogroups A,C,W 
and Y 
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C O N FI D E N TI A L  
2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
1 0 9  
9. 4. 5.  
T erti ar y e n d p oi nt( s) –  P h a s e II ( F or m ul ati o n a n d S c h e d ul e -
fi n di n g)  
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
10.1.1. 
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 Good Clinical Practice (GCP) Guidelines 
− 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF or Informed Assent Form (IAF), 
Investigator Brochure, 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.  
• 
GSK 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/EC. 
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− 
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 site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
10.1.2. 
Financial disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interest prior 
initiation of the centre and for providing an update of Financial Disclosure if their 
financial interest changes at any point during their participation in a study and for 1 year 
after completion of the study. 
10.1.3. 
Informed consent process 
The investigator or his/her representative must fully explain the nature of the study to the 
participant/participant’s parent(s) or his/her LAR(s) and answer all questions regarding 
the study.  
Participants/participants’ parent(s)/LAR(s) must be informed that their participation is 
voluntary.  
Freely given and written/witnessed/thumb printed informed consent must be obtained 
from each participant and/or each participant’s parent(s)/LAR(s)/witness (per phase: 
Phase I, Phase II, Sourcing or Phase II, Formulation and Schedule-finding) and 
participant informed assent (for Phase II, Formulation and Schedule-finding), as 
appropriate, prior to participation in the study.  
The content of the informed consent form must meet the requirements of 21 CFR 50, 
local regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB/IEC or study centre. 
The medical record must include a statement that written or witnessed/thumb printed 
informed consent was obtained before the participant was enrolled in the study and the 
date the consent was obtained. The authorised person obtaining the informed consent 
must also sign the ICF.  
Participants must be re-consented to the most current version of the ICF(s) or an ICF 
addendum during their participation in the study.  
A copy of the ICF(s) must be provided to the participants/participants’ parent(s)/LAR(s).  
Participants who are rescreened are required to sign a new ICF. 
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Phase II (Formulation and Schedule-finding): 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 summarises the study and includes a consent 
statement and documents that the participant agrees to continue participating in the study. 
Phase II (Formulation and Schedule-finding): The study investigator is encouraged to 
obtain assent from the minor in addition to the consent provided by the LAR(s) when a 
minor can assent to decisions about his/her participation in a study. The investigator is 
also accountable for determining a minor’s capacity to assent to participation in a 
research study according to the local laws and regulations. 
10.1.4. 
Data protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records 
or datasets transferred to the sponsor will contain only the identifier. Name and any other 
information which would identify the participant will not be transferred.  
The participants/participants’ parent(s)/LAR(s) must be informed that: 
• 
His/her personal/their child’s study-related data will be used by the sponsor in 
accordance with local data protection law.  
• 
 His/her medical records/their child’s may be examined by Clinical Quality 
Assurance auditors or other authorised personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
GSK will ensure protection of the personal data of the investigator and site staff which is 
collected within the framework of and for the purpose of the study, in accordance with 
the Data Privacy Notice that will be sent to the site staff.  
The participants/participants’ parent(s)/LAR(s) must be notified about their rights 
regarding the use of their personal data in accordance with the data privacy section of the 
ICF. 
10.1.5. 
Committees structure 
10.1.5.1. 
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 Good Clinical Practice E6 (R1), Section 3 [ICH, 1997]. A signed 
and dated statement that the protocol and informed consent have been approved by the 
IRB/EC must be given to GSK before study initiation. Prior to study start and at any time 
the protocol is 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 GSK monitors, auditors, GSK Clinical 
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Quality Assurance representatives, designated agents of GSK, IRBs/ECs, and regulatory 
authorities as required. If an inspection of the clinical site is requested by a regulatory 
authority, the investigator must inform GSK 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 subjects 
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(s), and their study-related duties and functions. 
• 
Ensuring that appropriately trained healthcare professionals who can perform all 
study-related medical decisions and for ensuring appropriate medical care of subjects 
experiencing any AE related to the study. 
• 
If permission to do so is given by the subject and/or parent(s)/legal guardian(s), 
ensuring that the subject’s primary healthcare provider is informed of the subject’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/favourable 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an 
immediate hazard(s) to study subjects, or when the change(s) involves only logistical or 
administrative aspects of the study (e.g., change in monitor(s), change of telephone 
number(s)). 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 subjects without prior IRB/IEC 
approval/favourable 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: 
i. 
to the IRB/IEC for review and approval/favourable opinion,  
ii. to the Sponsor for agreement and, if required, 
iii. to the regulatory authority(ies). 
10.1.5.2. 
internal Safety Review Committee 
Refer to Section 8.2.2 for details. 
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10.1.6. 
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 
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/ study 
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 trial 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. GSK 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. 
GSK will provide the investigator with the randomisation codes for their site only after 
completion of the full statistical analysis. 
GSK intends to make anonymised patient-level data from this trial 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 trial 
participants are used to maximum effect in the creation of knowledge and understanding. 
10.1.7. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents, including source documents (see Glossary of terms for the exact definition of 
essential and source documents). The document storage system used during the trial and 
for archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval.  
Essential trial documents may be added or removed where justified (in advance of trial 
initiation) based on their importance and relevance to the trial. When a copy is used to 
replace an original document (e.g. source documents, CRF), the copy should fulfil the 
requirements for certified copies (see Glossary of terms for the exact definition of 
certified copies).  
All participant data related to the study will be recorded on printed or electronic CRF 
unless transmitted to the sponsor or designee 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 trial records 
that include all pertinent observations on each of the site’s trial participants (see Glossary 
of terms for the exact definition of source documents) that supports information entered 
in the eCRF.  
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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 for such review and inspection.  
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source data (see Glossary of terms for the exact definition of 
source data).  
Study monitors will perform ongoing source data verification to confirm that data entered 
in the eCRF by authorised site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data must be traceable, not obscure 
the original entry, and be fully explained if necessary (e.g. via an audit trail). The safety 
and rights of participants must be protected, and the study conducted in accordance with 
the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
Quality tolerance limits (QTLs) will be pre-defined in the Statistical analysis plan to 
identify systematic issues that can impact participant safety and/or the reliability of study 
results. These pre-defined parameters will be monitored during the study. Important 
deviations from the QTLs and remedial actions taken will be summarised in the Clinical 
Study Report (CSR). 
Trial records and source documents pertaining to the conduct of this study, including 
signed ICFs, must be retained by the investigator for 25 years from issuance 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 of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor.  
10.1.8. 
Source documents 
Source documents provide evidence to establish the existence of the participant and 
substantiate the integrity of collected data. The investigator should maintain a record of 
the location(s) of their source documents.  
Data transcribed into the eCRF from source documents must be consistent with those 
source documents; any 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. 
Definitions of what constitutes source data and documents can be found in the Glossary 
of terms. 
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10.1.9. 
Study and site start and closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at its sole discretion, provided there is sufficient notice given to 
account for all participants safe exit from study.  
Regular closure of study sites will occur upon study completion. A study site is 
considered closed when all required data/documents and study supplies have been 
collected and a study site closure visit has been performed.  
The investigator may initiate study site closure at any time, provided there is reasonable 
cause and enough notice in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor 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. 
10.1.9.1. 
Study conclusion 
(Amended 22 March 2022) 
At Phase I conclusion phone call (Day 211), Phase II (Formulation and Schedule-finding) 
conclusion visit (study conclusion; Visit 6, Day 541) and Phase II (Sourcing) conclusions 
phone call (Day 211 in 
 groups, Day 241 in 
 groups and Day 361 in 
 
 groups), the investigator will: 
• 
Review data collected to ensure accuracy and completeness 
• 
Complete the Study Conclusion screen in the eCRF 
10.1.10. 
Publication policy 
GSK aims to submit the results of the study for publication in searchable, peer reviewed 
scientific literature within 18 months from the LSLV for interventional studies and 
follows the guidance from the International Committee of Medical Journal Editors 
(ICMJE). 
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10.2. 
Appendix 2: Clinical laboratory tests 
10.2.1. 
Protocol-required safety laboratory assessments 
Haematology and biochemistry assays for safety assessment will be performed in all 
participants in Phase I, in the investigator’s laboratory using standard procedures as per 
local practice (refer to Table 44 and Table 1). 
Table 44 
Haematology and biochemistry tests – Phase I 
System 
Discipline 
Component 
Method 
Scale 
Laboratory 
Whole 
blood 
Haematology 
Leukocytes (White 
Blood Cells)  
Per contract laboratory’s 
procedures 
Quantitative  
Investigator’s 
institution/laboratory 
Neutrophils* 
Per contract laboratory’s 
procedures 
Quantitative  
Lymphocytes* 
Per contract laboratory’s 
procedures 
Quantitative  
Basophils* 
Per contract laboratory’s 
procedures 
Quantitative  
Monocytes* 
Per contract laboratory’s 
procedures 
Quantitative  
Eosinophils* 
Per contract laboratory’s 
procedures 
Quantitative  
Haemoglobin 
Per contract laboratory’s 
procedures 
Quantitative 
Platelets  
Per contract laboratory’s 
procedures 
Quantitative 
Erythrocytes (Red 
Blood Cells)  
Per contract laboratory’s 
procedures 
Quantitative  
Serum 
Biochemistry 
Alanine 
Aminotransferase 
(ALT) 
Per contract laboratory’s 
procedures 
Quantitative  
Investigator’s 
institution/laboratory 
Aspartate 
Aminotransferase 
(AST) 
Per contract laboratory’s 
procedures 
Quantitative  
Creatinine 
Per contract laboratory’s 
procedures 
Quantitative 
* For White Blood Cell (WBC) differential count. 
The tests detailed in Table 44 will be performed by the local laboratory.  
10.2.2. 
Effectiveness and immunogenicity laboratory assessments 
The tests detailed in Table 28 will be performed at GSK or at a laboratory designated by 
GSK where the assays are available for the intended use.  
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol. 
A urine pregnancy test will be conducted as needed for women of childbearing potential 
(refer to Section 8.1.1.2). 
The investigator is not allowed to do extra testing on samples outside of what has been 
agreed upon by the ethic committees. 
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10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of 
AE 
10.3.1. 
Definition of an Adverse Event (AE)  
An AE is any untoward medical occurrence (an unfavourable/unintended sign – including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical 
study participant that is temporally associated with the study intervention. The AE may or 
may not be considered related to the study intervention. 
10.3.1.1. 
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 administration of the study 
intervention even though they may have been present before study start. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug, disease or other 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either the 
study intervention or a concurrent medication. 
• 
Signs or symptoms temporally associated with administration of the study 
intervention. 
• 
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 to be recorded as solicited AEs are described in the Section 10.3.3. All other 
AEs will be recorded as UNSOLICITED AEs. 
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10.3.1.2. 
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 before 
the first dose of study intervention. These events will be recorded in the medical 
history section of the eCRF.  
• 
Hospitalisation for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from baseline. 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
10.3.2. 
Definition of an SAE 
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 hospitalisation or prolongation of existing hospitalisation 
Note: In general, hospitalisation 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 out-patient setting. 
Complications that occur during hospitalisation are also considered AEs. The 
event will also be considered serious if a complication prolongs hospitalisation or 
fulfils any other serious criteria. When in doubt as to whether ‘hospitalisation’ 
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, diarrhoea, influenza like illness, and accidental 
trauma (e.g. sprained ankle) which may interfere or prevent everyday life functions 
but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect in the offspring of a study participant 
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f. 
Abnormal pregnancy outcomes (e.g. spontaneous abortion, foetal death, stillbirth, 
congenital anomalies, ectopic pregnancy). 
g. Other situations 
Medical or scientific judgement must be exercised in deciding whether reporting is 
appropriate in other situations. Important medical events that may not be 
immediately life-threatening or result in death or hospitalisation but may 
jeopardise the participant or require medical or surgical intervention to prevent one 
of the other outcomes listed in the above definition should 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; and 
convulsions that do not result in hospitalisation. 
10.3.3. 
Solicited events 
a. Solicited administration site events 
The following administration site events will be solicited: 
Table 45 
Solicited administration site events – Phase I and II 
All age groups 
Injection site Pain  
Erythema 
Swelling  
Induration 
b. Solicited systemic events 
The following systemic events will be solicited: 
Table 46 
Solicited systemic events – Phase I and II 
All age groups 
fever [body temperature ≥ 38.0°C] 
nausea 
fatigue 
myalgia 
arthralgia 
headache 
Note: participants/participants’ parent(s)/LAR(s) will be instructed to measure and record 
the oral* temperature in the evening. If additional temperature measurements are taken at 
other times of the day, participants/participants’ parent(s)/LAR(s) will be instructed to 
record the highest temperature in the eDiary. 
* Preferred location for measuring temperature will be the oral cavity. In case the 
participant/ participant’s parent(s)/LAR(s) use any other route for measuring temperature, 
this needs to be recorded in the eDiary. 
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10.3.4. 
Unsolicited adverse events 
An unsolicited adverse event is an adverse event that was not included in a list of 
solicited events using a Participant Diary. Unsolicited events must have been 
spontaneously communicated by a participant/participant’s parent(s)/LAR(s) who has 
signed the informed consent. Unsolicited AEs include both serious and non-serious AEs. 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalisation, or an emergency room visit, or visit to/by a health care 
provider). The participants/participant’s parent(s)/LAR(s) will be instructed to contact the 
site as soon as possible to report medically attended event(s), 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 site personnel 
and documented in the participant’s records. 
Unsolicited AEs that are not medically attended or perceived as a concern by the 
participant/participant’s parent(s)/LAR(s) will be collected during an interview with the 
participants/participant’s parent(s)/LAR(s) and by review of available medical records at 
the next visit. 
10.3.5. 
Adverse events of special interest (AESIs) 
Adverse events of special interest are pre-defined (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 
characterise and understand it. 
10.3.5.1. 
Potential immune-mediated diseases (pIMDs) 
Potential immune-mediated diseases (pIMDs) 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 aetiology. AEs that need to be recorded and 
reported as pIMDs include those listed in the Table 47. 
The investigator must exercise his/her medical/scientific judgement 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 preferred terms (PTs) and PT codes corresponding 
to the below diagnoses will be available to investigators at study start. 
 
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Table 47 
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 e.g.: 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 and dermatitis 
herpetiformis). 
• 
Lichen planus. 
• 
Sweet’s syndrome. 
• 
Localised Scleroderma 
(Morphoea). 
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Vasculitis 
Blood disorders 
Others 
• 
Large vessels vasculitis including:  
• 
Giant Cell Arteritis (Temporal Arteritis), 
• 
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. 
• 
Autoimmune haemolytic anaemia. 
• 
Autoimmune thrombocytopenia. 
• 
Antiphospholipid syndrome. 
• 
Pernicious anaemia. 
• 
Autoimmune aplastic anaemia. 
• 
Autoimmune neutropenia. 
• 
Autoimmune pancytopenia. 
• 
Autoimmune glomerulonephritis 
including: 
• 
IgA nephropathy,  
• 
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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10.3.5.2. 
Other adverse events of special interest 
10.3.5.2.1. Arthritis 
Cases of arthritis are defined according to the following ad-hoc definition: 
• 
Presence of a physical exam findings of swelling, redness, heat, or limitation in 
range of motion and/or 
• 
Presence of a 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 
MedDRA 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 characterise this AESI. 
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) lead to one 
of the above diagnoses, should be recorded and reported as AEs but not as AESI until the 
final or definitive diagnosis has been made, and alternative diagnoses eliminated or 
shown to be less likely.  
10.3.6. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs  
In the absence of a diagnosis, abnormal laboratory findings assessments or other 
abnormal results the investigator considers clinically significant will be recorded as an 
AE or SAE, if they meet the definition of an AE or SAE (refer to the Sections 10.3.1 and 
10.3.2).  
The investigator must exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding, or other abnormal assessment is clinically 
significant. 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs  
10.3.7.1. 
Pregnancy 
Female participants who become pregnant after the first study intervention dose must not 
receive subsequent doses of the study intervention but may continue other study 
procedures at the discretion of the investigator. 
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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. Please refer to the Section 10.3.2 for definition of 
SAE.  
10.3.8. 
Recording and follow-up of AEs, SAEs, AESIs and pregnancies 
(Amended 22 March 2022) 
The participants/participants’ parent(s)/LAR(s) will be instructed to contact the 
investigator immediately should they experience any signs or symptoms they perceive as 
serious.  
When an AE/SAE occurs, it is the investigator’s responsibility to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) related to 
the event. The investigator will then record all relevant information regarding an AE/SAE 
on the eCRF. The investigator may not send photocopies of the participant’s medical 
records to GSK instead of appropriately completing the eCRF.  
There may be instances when copies of medical records for certain cases are requested by 
GSK. In this case, all participant identifiers will be blinded on copies of the medical 
records prior to submission to GSK. 
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 instead of individual signs/symptoms. 
An Electronic Diary (eDiary), hereafter referred to as Participant Diary, 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 the Participant Diary. 
Anyone who measures administration site or systemic events and who will record the 
event in the Participant Diary should be trained on using the Diary. This training must be 
documented in the participant’s source record. If any individual other than the 
participant/participant’s parent(s)/LAR(s) is making entries in the Participant Diary, their 
identity must be documented in the Participant Diary/participant’s source record. 
Note (Phase II, Formulation and Schedule-finding part only): eDiaries may be filled in by 
a minor participant under the supervision of the participant’s parent(s)/LAR(s) provided 
the minor is capable of assessing and reporting the information to be recorded on the 
eDiary. The ultimate accountability for completion of the eDiary remains with the 
participant’s parent(s)/LAR(s). The investigator should discuss this accountability with 
the participant’s parent(s)/LAR(s).  
• 
Verify completed eDiaries during discussions with the participant/participant’s 
parent(s)/LAR(s) on: 
− 
Visit V3 (Day 31) and Visit V4 (Day 61) – Phase I 
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− 
Visit V2 (Day 31), Visit V4 (Day 181) and Visit V5 (Day 211) – Phase II, 
Formulation and Schedule finding, 
 
 groups 
− 
Visit V2 (Day 31) and Visit V5 (Day 211) – Phase II, Formulation and Schedule 
finding, Control group 
− 
Visit V2 (Day 31) and Visit V3 (Day 61) – Phase II, Sourcing, 
 
 groups. 
− 
Phone call (T1, Day 31), Visit V3 (Day 76) and Visit 4 (Day 91) – Phase II, 
Sourcing, 
 groups. 
− 
Phone call (T1, Day 31), Visit V3 (Day 196) and Visit 4 (Day 211) - Phase II, 
Sourcing, 
 groups. 
Collect eDiaries on Visit 4 (Day 61) for Phase I participants, Visit 5 (Day 211) for 
Phase II (Formulation and Schedule-finding) participants and Visit 3/4 (V3, Day 61 
for 
 groups, V4, Day 91 for 
 
 groups and V4, Day 211 in 
 
 groups) for Phase II (Sourcing) participants. 
Note (Phase II, Formulation and Schedule-finding only): If the eDiary has been filled 
in by a minor participant, the investigator or delegate should verify the reported 
information during a discussion with the minor participant preferably in the presence 
of his/her parent(s)/LAR(s). 
• 
Any unreturned eDiaries will be sought from the participant/participant’s 
parent(s)/LAR(s) through telephone call(s) or any other convenient procedure. 
The investigator or delegate will transcribe the required information into the eCRF in 
English.  
Refer to the SPM for more information regarding the use of eDiary.  
10.3.8.1. 
Time period for collecting and recording AEs, SAEs, AESIs and 
pregnancies 
All post-study intervention immediate reactions observed within the observational period 
of at least 30 minutes after each injection, including signs or symptoms of anaphylaxis, 
allergic phenomena (such as rashes, itching, or other allergic manifestations), solicited 
events, unsolicited events and body temperature, will be recorded in the eCRF. 
All solicited events that occur during 7 days (including the day of vaccination) following 
administration of each dose of study intervention (Day 1 to Day 7) must be recorded into 
the eDiary, irrespective of intensity. All other AEs occurring within this time frame 
should be recorded into the appropriate section of the eCRF, irrespective of their intensity 
or whether or not they are considered related to the study intervention. 
Solicited events that are ongoing after the 7-day reporting period may continue to be 
recorded in the eDiary until resolution or up to 30 days post-vaccination (ie, recording 
period for unsolicited AEs) whichever occurs first and do not need to be entered as an AE 
CI
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in the AE eCRF or the participant’s source document. Any solicited event 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 participant’s eCRF as an unsolicited AE. It will 
also be included in the participant’s source documents at the site by the investigator/site 
staff as a verbally reported event. These events will be analysed as unsolicited AEs. 
Any solicited event that meets any of the following criteria must also be entered into 
participants’ source documents and as an AE on the Adverse Event eCRF: 
• 
Solicited administration site or systemic events 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 events that otherwise meets the definition of 
SAE (see Section 10.3.2) or an AESI (See Section 10.3.5). 
All other AEs occurring within this time frame should be recorded into the appropriate 
section of the eCRF, irrespective of their intensity or whether or not they are considered 
related to the study intervention. 
Refer to Table 34, Table 35 and Table 36 for the time period for collecting and recording 
unsolicited AEs, SAEs, AESIs and pregnancies.  
10.3.8.2. 
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, the investigator 
is required to proactively follow each participant at subsequent visits/contacts. All SAEs 
and non-serious AEs of special interest (as defined in the Section 10.3.5), will be 
followed until the event is resolved, stabilised, otherwise explained, or the participant is 
lost to follow-up. 
Other non-serious AEs must be followed until last visit/contact of the participant or until 
the participant is lost to follow-up. 
10.3.8.2.1. 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 last 
visit/contact of the participant. 
If a participant dies during their participation in the study or during a recognised follow-
up period, GSK will be provided with any available post-mortem findings, including 
histopathology. 
10.3.8.2.2. Follow-up after the participant is discharged from the study 
The investigator will provide any new or updated relevant information to GSK on a 
previously reported SAE/AESI using an electronic Expedited Adverse Events Report 
and/or pregnancy report as applicable. The investigator is obliged to perform or arrange 
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for the conduct of supplemental clinical examinations/tests and/or evaluations to 
elucidate the nature and/or causality of the SAE/AESI as fully as possible. 
10.3.8.2.3. 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 GSK using electronic pregnancy report and the 
Expedited AEs Report if applicable. Generally, the follow-up period does not need to be 
longer than 6 to 8 weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is an 
SAE, it should always be reported as such. 
Furthermore, if the investigator becomes aware of any SAE occurring as a result of a 
post-study pregnancy AND it is considered by the investigator to be reasonably related to 
the study intervention, he/she must report this information to GSK as described in the 
Section 10.3.10. 
10.3.8.3. 
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 write access to 
the participant’s eCRF is removed, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study contact for reporting SAEs (refer to the 
Section 8.3.3.1) or to GSK VCSP department within the defined reporting time frames 
specified in the Table 39. 
10.3.9. 
Assessment of intensity and toxicity 
10.3.9.1. 
Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
Table 48 
Intensity scales for solicited events in adults and children of 10 years 
of age or more 
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 
every day activities. 
 
3 
Severe: Significant pain at rest. Prevents normal every day 
activities. 
Erythema at administration site 
Greatest surface diameter in mm 
Swelling at administration site 
Greatest surface diameter in mm  
Induration at administration site 
Greatest surface diameter in mm 
Temperature* 
 
Temperature in °C/°F (with 1 decimal) 
Nausea 
0 
Normal 
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Adults/Child (10 years)  
Event 
Intensity grade 
Parameter 
 
1 
Mild: Nausea that is easily tolerated 
 
2 
Moderate: Nausea that interferes with normal activity 
 
3 
Severe: Nausea 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 
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 
* Refer to the SoA for the definition of fever and the preferred location for temperature measurement. 
The maximum intensity of local injection Site Induration, Swelling, Erythema will be 
scored at GSK as follows: 
0 
: 
1 – 24 mm 
1 
: 
25 – 50 mm 
2 
: 
51 – 100 mm 
3 
: 
>100 mm 
The maximum intensity of fever will be scored at GSK as follows: 
0 
: 
< 38.0°C (100.4℉) 
1 
: 
≥ 38.0 (100.4°F) - 38.9°C (102.1°F) 
2 
: 
≥ 39.0 (102.2°F) - 39.9°C (103.9°F) 
3 
: 
≥ 40.0°C (104.0°F)  
The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgement. 
The intensity should be assigned to 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 /a day-care centre and would cause the 
parent(s)/LAR(s) to seek medical advice. In adults/adolescents, 
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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 pre-defined 
outcomes as described in the Section 10.3.2. 
10.3.9.2. 
Assessment of causality 
All solicited administration site and systemic events will be considered causally related to 
administration of the study intervention. The complete list of these events is provided in 
Table 45 and Table 46.  
The investigator must assess the relationship between study intervention and the 
occurrence of each unsolicited AE/SAE using clinical judgement. Where several different 
interventions were administered, the investigator should specify, when possible, if the 
unsolicited AE/SAE could be causally related to a specific intervention. When a causal 
relationship to a specific study intervention cannot be determined, the investigator should 
indicate the unsolicited AE/SAE to be related to all interventions. 
Alternative possible causes, such as the natural history of underlying disease, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study intervention will be considered and investigated. The investigator will also consult 
the IB and/or SmPC and/or Prescribing Information for marketed products to assist in 
making 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 intervention? 
YES 
: 
There is a reasonable possibility that the study intervention contributed 
to the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study intervention. There are other, more likely 
causes and administration of the study intervention is not suspected to 
have contributed to the AE. 
If an event meets the criteria to be determined ‘serious’ (see Section 10.3.2), 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. 
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• 
Protocol-required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the study intervention, if applicable. 
• 
An error in study intervention 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 GSK. However, it is very important to 
record an assessment of causality for every event before submitting the Expedited AEs 
Report to GSK.  
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. 
10.3.9.3. 
Medically attended visits 
(Amended 22 March 2022) 
For each solicited and unsolicited AE the participant experiences (Refer to Table 34, 
Table 35, Table 36, Table 37 and Table 38), the participant/participant’s 
parent(s)/LAR(s) will be asked if he/she/the participant received medical attention 
(defined as hospitalisation, or an otherwise unscheduled visit to or from medical 
personnel for any reason, including emergency room visits). This information will be 
recorded in the eDiary/ eCRF.  
10.3.9.4. 
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). 
10.3.9.5. 
Recording of AEs related to COVID-19 
(Amended 22 March 2022) 
For COVID-19 infection-related AEs, sites should follow routine AE/SAE processes as 
outlined in the protocol, using the following terms according to World Health 
Organization (WHO) defined case definitions: 
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• 
Suspected COVID-19 case 
• 
Probable COVID-19 case 
• 
Confirmed COVID-19 case [WHO, 2020] 
Note: Due to the rapid evolution of the COVID-19 pandemic situation, it is important 
to adhere to the most recent guidelines released by WHO. Please refer to the WHO 
website for the latest guidance. 
10.3.9.5.1. WHO Case Definition 
• 
Suspected COVID-19 case 
A. A person who meets the clinical AND epidemiological criteria 
Clinical criteria: 
− 
Acute onset of fever AND cough OR acute onset of ANY THREE OR MORE 
of the following signs or symptoms: fever, cough, general weakness/fatigue, 
headache, myalgia, sore throat, coryza, dyspnoea, anorexia/nausea/vomiting, 
diarrhoea, altered mental status  
AND 
Epidemiological criteria: 
− 
Residing or working in an area with high risk of transmission of virus: closed 
residential settings, humanitarian settings such as camp and camp-like settings 
for displaced persons; anytime within the 14 days prior to symptom onset OR 
residing to travel to an area with community transmission anytime within the 14 
days prior to symptom onset OR working in any health care setting, including 
within health facilities or within the community; anytime within the 14 days 
prior to symptom onset 
OR 
B. A patient with severe acute respiratory illness (SARI: acute respiratory infection 
with history of fever or measured fever of ≥38.0°C, and cough; with onset within the 
last 10 days; and requires hospitalisation) 
• 
Probable COVID-19 case  
A. A patient who meets clinical criteria above AND is a contact of a probable or 
confirmed case, or epidemiologically linked to a cluster with at least one confirmed 
case 
OR 
B. A suspect case with chest imaging showing findings suggestive of COVID-19 
disease* 
− 
* Typical chest imaging findings suggestive of COVID-19 include the 
following: 
− 
Chest radiography: hazy opacities, often rounded in morphology, with 
peripheral and lower lung distribution 
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− 
Chest computed tomography (CT): multiple bilateral ground glass opacities, 
often rounded in morphology, with peripheral and lower lung distribution 
− 
Lung ultrasound: thickened pleural lines, B lines (multifocal, discrete, or 
confluent), consolidative patterns with or without air bronchograms 
OR 
C. A person with recent anosmia (loss of smell) or ageusia (loss of taste) in the 
absence of any other identified cause.  
OR 
D. Death, not otherwise explained, in an adult with respiratory distress preceding 
death AND was a contact of a probable or confirmed case or epidemiologically 
linked to a cluster with at least one confirmed case. 
• 
Confirmed COVID-19 case [WHO, 2020] 
A person with laboratory confirmation of COVID-19 infection, irrespective of 
clinical signs and symptoms. See “Laboratory testing for 2019 novel coronavirus 
(2019-nCoV) in suspected human cases” [WHO, 2019] for details. 
10.3.10. 
Reporting of SAEs, AESIs, pregnancies and other events 
10.3.10.1. Events requiring expedited reporting to GSK 
Once an investigator becomes aware that an SAE has occurred, the investigator (or 
designee) must complete information in the electronic Expedited AEs Report WITHIN 
24 HOURS, even if the investigator does not have complete information on the SAE. It 
must be completed as thoroughly as possible, with all available details of the event.  
The SAE report must be updated WITHIN 24 HOURS of the receipt of updated 
information on the SAE. The investigator will always provide an assessment of causality 
at the time of the initial report. 
Refer to the Table 39 for the details on timeframes for reporting of SAEs/ AESIs/ 
pregnancies. 
The investigator will be required to confirm the review of SAE causality within 72 hours 
of submission of the SAE. 
Fax transmission is the preferred method of forwarding the paper Expedited AEs Report 
to the study contact for reporting SAEs (refer to the Table 40). In the absence/dysfunction 
of fax equipment, the study contact for reporting SAEs must be notified by telephone 
within 24 hours. As soon as the fax equipment is working again, the investigator (or 
designee) must fax the report to the study contact for reporting SAEs, within 24 hours.  
Refer to the Section 10.3.10.2 for information on back up systems in case the electronic 
reporting system does not work. 
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10.3.10.2. Back up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designee) must fax a 
completed, dated and signed paper Expedited AEs Report to the study contact for 
reporting SAEs (refer to the SPONSOR INFORMATION) or to GSK VCSP department 
within 24 hours of becoming aware of the SAE.  
Investigator (or designee) must complete the electronic Expedited AEs Report within 24 
hours after the electronic reporting system is working again. The information reported 
through the electronic SAE reporting system will be considered valid for regulatory 
reporting purposes. 
10.4. 
Appendix 4: FDA’s toxicity grading scale for healthy adult 
and adolescent volunteers enrolled in preventive vaccine 
clinical trials applied for this study 
The laboratory values provided in the tables below serve as guidelines and are dependent 
upon institutional normal parameters. Institutional normal reference ranges should be 
provided to demonstrate that they are appropriate. 
Table 49 
Laboratory abnormalities 
 
Mild (Grade 1) 
Moderate (Grade 
2) 
Severe (Grade 
3) 
Potentially life-
threatening 
(Grade 4)** 
Serum* 
Creatinine – mg/dL 
1.5 – 1.7 
1.8 – 2.0 
2.1 – 2.5 
>2.5 or requires 
dialysis 
Liver function tests – ALT, AST 
increase by factor 
1.1 – 2.5 x 
ULN*** 
2.6 – 5.0 x ULN 
5.1 – 10 x ULN 
>10 x ULN 
Haematology* 
Haemoglobin (Female) - gm/dL 
11.0 – 12.0 
9.5 – 10.9 
8.0 – 9.4 
< 8.0 
Haemoglobin (Female)  
change from baseline value - 
gm/dL  
Any decrease 
– 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
Haemoglobin (Male) - gm/dL  
12.5 – 13.5 
10.5 – 12.4 
8.5 – 10.4 
< 8.5 
Haemoglobin (Male)  
change from baseline value – 
gm/dL  
Any decrease 
– 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
WBC Increase - cell/mm3 
10,800 – 
15,000 
15,001 – 20,000 
20,001 – 25, 000 
> 25,000 
WBC Decrease - cell/mm3 
2,500 – 3,500 
1,500 – 2,499 
1,000 – 1,499 
< 1,000 
Lymphocytes Decrease - 
cell/mm3 
750 – 1,000 
500 – 749 
250 – 499 
< 250 
Neutrophils Decrease - cell/mm3 
1,500 – 2,000 
1,000 – 1,499 
500 – 999 
< 500 
Eosinophils - cell/mm3 
650 – 1500 
1501 - 5000 
> 5000 
Hypereosinophilic 
Platelets Decreased - cell/mm3 
125,000 – 
140,000 
100,000 – 124,000 
25,000 – 99,000 
< 25,000 
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate. 
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterisation of the 
laboratory abnormalities as Potentially Life-Threatening (Grade 4). 
***ULN is the upper limit of the normal range. 
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10.5. 
Appendix 5: Contraceptive guidance and collection of 
pregnancy information 
10.5.1. 
Definitions 
(Amended 22 March 2022) 
10.5.1.1. 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
10.5.1.1.1. Women not considered as women of childbearing potential 
• 
Premenarchal 
Menarche is the first onset of menses in a young female. Menarche is normally 
preceded by several changes associated with puberty including breast development 
and pubic hair growth.  
Additional evaluation should be considered if a participant’s fertility status is unclear 
(e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention. 
• 
Premenopausal female with ONE of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
− 
Current bilateral tubal ligation or occlusion 
Note: Documentation can come from the site personnel’s: review of participant’s medical 
records, medical examination, or medical history interview. 
• 
Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 12 
months of amenorrhea, a single FSH measurement is insufficient. 
• 
Females on HRT and whose menopausal status is in doubt will be required to use a 
non-hormonal, highly effective contraception method if they wish to continue their 
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrolment. 
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10.5.2. 
Contraception guidance 
• 
Female participants of childbearing potential are eligible to participate if they agree 
to use a highly effective contraceptive method consistently and correctly according 
to the methods listed in GSK’s list of highly effective contraceptive methods (Table 
50).  
Table 50 
Highly effective contraceptive methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
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 
• 
injectable  
• 
oral 
Highly Effective Methods That Are User Independent  
• 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
Vasectomised partner  
(A vasectomised partner is a highly effective contraception method provided that the partner 
is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used.)  
Male partner sterilisation 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 site 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.)  
a 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 
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10.5.3. 
Collection of pregnancy information 
10.5.3.1. 
Female participants who become pregnant 
Refer to the Sections 8.3.1, 8.3.2, 10.3.8.1 and 10.3.8.3 for further information on 
detection, recording, reporting and follow-up of pregnancies. 
Any female participant who becomes pregnant during the study will discontinue study 
intervention or be withdrawn from the study.  
10.6. 
Appendix 6: Genetics 
Not applicable. 
10.7. 
Appendix 7: Definition of medical device AE, adverse device 
effect (ADE), serious adverse device effect (SADE) and 
unanticipated SADE (USADE) 
10.7.1. 
Definition of medical device AE and adverse device effect (ADE) 
• 
Medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether considered related to a medical device or not. An AE can 
therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated 
with the use of a 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 an 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. 
10.7.2. 
Definition of medical device SAE, SADE and USADE 
A medical device SAE is any serious adverse event that: 
a. 
Led to death  
b. 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. 
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• 
A permanent impairment of a body structure or a body function. 
• 
Inpatient or prolonged hospitalisation. Planned hospitalisation 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. 
c. 
Led to foetal distress, foetal death or a congenital abnormality or birth defect 
d. Is a suspected transmission of any infectious agent via a medicinal product. 
Serious Adverse Device Effect (SADE) definition 
• A SADE is defined as an adverse device effect 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 or circumstances had been less fortunate. 
Unanticipated SADE (USADE) definition 
• 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is a 
serious adverse device effect that by its nature, incidence, severity or outcome has 
not been identified in the current version of the IB. 
10.7.3. 
Recording and reporting of medical device AE, ADEs, SADEs and 
USADE 
• 
Any device deficiency must be reported to GSK within 24 hours after the 
investigator determines that the event meets the definition of a device deficiency. 
• 
E-mail/Facsimile transmission of the paper ‘Medical device or combination product 
with device deficiency/incident report form’ is the preferred method to transmit this 
information to the sponsor. 
• 
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 for reporting can be found in Section 8.3.3.1. 
• 
GSK will review all device deficiencies, 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. 
10.8. 
Appendix 8: Country-specific requirements 
Not applicable. 
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10.9. 
Appendix 9: Abbreviations and glossary of terms 
10.9.1. 
List of abbreviations  
ADE: 
Adverse Device Effect 
AE: 
Adverse Event 
AESI: 
Adverse event of special interest 
ANOVA: 
Analysis of variance 
BMI: 
Body mass index 
CLS: 
Clinical Laboratory Sciences 
COVID-19: 
Coronavirus disease-2019 
CRDL:  
Clinical Research & Development Lead 
CRM197: 
Corynebacterium diphtheriae Cross Reacting Material-197 
CSR: 
Clinical Study Report 
eCRF: 
electronic Case Report Form 
eDiary: 
Electronic Diary 
Enc-hSBA: 
Endogenous Complement Human Serum Bactericidal Assay 
EoS: 
End of Study 
EU: 
European Union 
fHbp: 
factor H binding protein 
FTIH: 
First-time in human 
GCP: 
Good Clinical Practice 
GMC: 
Geometric Mean Concentration 
GMR: 
Geometric Mean Ratio 
GSK: 
GlaxoSmithKline Biologicals SA 
HCP: 
Qualified study staff/healthcare professionals 
hSBA: 
Human Serum Bactericidal Assay 
IAF: 
Informed Assent Form 
IB: 
Investigator Brochure 
ICF: 
Informed Consent Form 
ICH: 
International Council on Harmonisation 
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IDMC: 
Independent Data Monitoring Committee 
IEC: 
Independent Ethics Committee 
IMD: 
Invasive Meningococcal Disease 
IRB: 
Institutional Review Board 
iSRC: 
Internal Safety Review Committee 
LAR: 
Legally Acceptable Representative 
LLOQ: 
Lower limit of quantitation 
LML 
Local Medical lead 
LOD: 
Limit of detection 
LSLV: 
Last Participant Last Visit 
MedDRA: 
Medical Dictionary for Regulatory Activities 
N. meningitidis: 
Neisseria meningitidis 
NadA: 
Neisseria Adhesin A 
NHBA: 
Neisserial Heparin Binding Antigen 
pIMD: 
Potential Immune-Mediated Disease 
PorA: 
Porin A 
QTL 
Quality Tolerance Limit 
SADE: 
Serious Adverse Device Effect 
SAE: 
Serious Adverse Event 
SBIR: 
Source data Base for Internet Randomisation  
SmPC: 
Summary of Product Characteristics 
SPM: 
Study Procedures Manual 
US: 
United States 
USADE 
Unanticipated Serious Adverse Device Effect 
VE: 
Vaccine effectiveness 
WHO: 
World Health Organization 
WOCBP 
Woman of Childbearing Potential 
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10.9.2. 
Glossary of terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the 
use of a medicinal product, whether or not considered 
related to the medicinal product.  
An adverse event (AE) can therefore be any 
unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new 
or exacerbated) temporally associated with the use of a 
medicinal product. For marketed medicinal products, 
this also includes failure to produce expected benefits 
(i.e. lack of efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the trial 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 
trial, and only when the data are cleaned to an 
acceptable level of quality will appropriate personnel be 
unblinded or when required in case of a serious adverse 
event.  
For Phase I and Phase II Sourcing: In an observer-
blind study, the participant, the site and sponsor 
personnel involved in the clinical evaluation of the 
participants are blinded while other study personnel may 
be aware of the treatment assignment.  
For Phase II Formulation and Schedule-finding: 
Partially-blind is to be used for study designs with 
different blinding levels between different groups, e.g. 
double-blinded consistency lots which are open with 
respect to the control group. 
Certified copy: 
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. 
Child in care: 
A child who has been placed under the control or 
protection of an agency, organisation, institution or 
entity by the courts, the government or a government 
body, acting in accordance with powers conferred on 
them by law or regulation. The definition of a child in 
care can include a child cared for by foster parents or 
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living in a care home or institution, provided that the 
arrangement falls within the definition above. The 
definition of a child in care does not include a child who 
is adopted or has an appointed legal guardian. 
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: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrolled participant 
‘Enrolled’ means a 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 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 of the protocol for the definition 
of ‘enrolled set’ 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. 
eTrack: 
GSK’s tracking tool for clinical trials. 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per protocol analysis. 
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(s) or marketed product(s) or 
placebo intended to be administered to a participant. 
Intervention number: 
A number identifying an intervention to a participant, 
according to intervention allocation. 
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Investigational vaccine: 
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorisation when used in a way different 
from the approved form, or when used for an 
unapproved indication, or when used to gain further 
information about an approved use.  
Synonym: Investigational Medicinal Product 
Investigator 
A person responsible for the conduct of the clinical trial 
at a trial site. If a trial is conducted by a team of 
individuals at a trial site, the investigator is the 
responsible leader of the team and may be called the 
Principal Investigator.  
The investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified 
individual or party to perform those trial-related duties 
and functions. 
Legally acceptable 
representative 
An individual, judicial or other body authorised under 
applicable law to consent on behalf of a prospective 
participant to the participant's participation in the 
clinical trial. 
The terms legal representative or legally authorised 
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. 
Participant: 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or who 
participates in the clinical study as a recipient of the 
study intervention (vaccine(s)/product(s)/control). 
Synonym: subject 
Participant number: 
A unique identification number assigned to each 
participant who consents to participate in the study. 
Primary completion date: 
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 trial was concluded according to the pre-
specified protocol or was terminated. 
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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. 
Protocol administrative 
change: 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study.  
Remote visit: 
Refers to the visit conducted in the place other than the 
study site. 
Randomisation: 
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. 
Site Monitor: 
An individual assigned by the sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
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 follow-up period following study 
intervention administration. 
Source data: 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data 
are contained in source documents (original records or 
certified copies). 
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 
certified after verification as being accurate copies, 
microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, participant files, and records 
kept at the pharmacy, laboratories and at medico-
technical departments involved in the clinical trial). 
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Study intervention: 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
Sub-cohort: 
A group of participants for whom specific study 
procedures are planned as compared to other participants 
or a group of participants who share a common 
characteristic (e.g. ages, vaccination schedule, etc.) at 
the time of enrolment. 
Telemedicine: 
Telemedicine refers to the use of information 
technologies and electronic communications to provide 
clinical services to patients virtually. The digital 
transmission of medical imaging, virtual medical 
diagnosis and evaluations, and video consultations with 
specialists are all examples of telemedicine. 
Unsolicited adverse event: 
Any AE reported in addition to those solicited during the 
clinical study. Also, any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse 
event. 
Virtual visit: 
Refers to study visits conducted using multimedia or 
technological platforms. 
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10.10. 
Appendix 10: Protocol Amendment history 
The Protocol Amendment Summary of Changes Table for the current amendment 
is located directly before the Table of Contents (TOC). 
DOCUMENT HISTORY 
Document 
Date of Issue 
Protocol Amendment 4 
22 March 2022 
Protocol Amendment 3 
29 September 2021 
Protocol Amendment 2 
21 June 2021 
Protocol Amendment 1 
7 May 2021 
Original Protocol  
11 January 2021 
 
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Amendments summary of changes table: 
Document 
Date of issue 
Section # and title 
Description of change 
Brief rationale 
Protocol Amendment 1 
7 May 2021 
Section 1.3, Schedule of activities 
 
Section 8.1.1.1, Biological samples 
The blood volume for safety assessment 
needs to change to approximately 7 mL 
from approximately 6 mL. 
In order to avoid collecting lower volume of 
blood, it was determined that the blood 
sample tubes should be filled to capacity. 
Protocol Amendment 2 
21 June 2021 
Section 2.3, Benefit/Risk assessment 
Section 4.1.2.1, Phase II formulation and 
schedule-finding 
Section 4.2, Scientific rationale for study 
design 
Section 5.1, Inclusion criteria 
Section 6.1, Study intervention(s) 
administered (Table 12) 
Section 8.2.1.5, Warnings and 
precautions to vaccination 
Section 8.2.21, Safety data review 
The Tdap vaccine (Boostrix) has been 
removed from the study design of Phase II 
Formulation and schedule-finding. It has 
been replaced by placebo as applicable. 
To avoid potential confounding factors that 
might impact selection of dosage and 
schedule for further development which is 
one of the primary aims of the study. 
 
 
Section 4.1.2.1, Phase II formulation and 
schedule-finding 
Section 6.3.5, Blinding and unblinding 
The blinding for Phase II formulation and 
schedule-finding has been changed to 
‘partially-blind’ from ‘observer-blind’ 
(ABCWY groups = observer-blind; Control 
group = open-label). 
The section on Blinding has been updated 
accordingly. 
Note: The blinding has been removed from 
the study title as it differs between the 
phases in the study. 
Since Tdap vaccine has been removed, the 
4 groups administering 
 
vaccine in different dosages and schedules 
are observer-blind; however the Control 
group receiving MenACWY and MenB 
vaccines at Visit V1 will be open-label. 
Protocol Amendment 2 
21 June 2021 
Section 4.1.2.1, Phase II: Formulation 
and Schedule-finding 
Section 8.2.2.1, Safety data review: 
Section 9.2, Sample size determination, 
9.2.2, Phase II (Formulation and 
Schedule-finding) 
Section 9.2.2.1, Superiority of vaccine 
effectiveness of the 
 
The number of participants in Phase II 
Formulation and Schedule-finding has been 
increased to 1000 from 885 (45 in Step 1 
and 955 in Step 2). 
Due to the split in the alpha (for parallel 
testing of  
 dose), the 
sample size has been increased to maintain 
the power of the analysis. 
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Document 
Date of issue 
Section # and title 
Description of change 
Brief rationale 
vaccine 
) when 
administered at 0,2- or 0,6-m schedule 
compared to the Control vaccine (MenB) 
Section 9.2.2.2, Immunological non-
inferiority of 
 vaccine 
 when administered at 
0,2- or 0,6-m schedule compared to the 
Control vaccine (MenACWY) 
 
 
Section 4.1.2.2, Phase II Sourcing 
Section 9.2.3, Phase II (Sourcing) 
The number of participants in Phase II 
sourcing have been increased to 226 from 
126 earlier. 
To support the assay development. 
 
 
Section 6.1, Study intervention(s) 
administered  
Section 8.3.6, Medical device 
deficiencies 
Section 10.7: Appendix 6: Definition of 
medical device AE, adverse device effect 
(ADE), serious adverse device effect 
(SADE) and unanticipated SADE 
(USADE) 
Product category included 
 
Implementation of wording on medical 
device deficiency for combination products 
for Post Marketing Safety Reporting.  
In line with the FDA Combination Product 
Post Marketing Safety Reporting guidance. 
Protocol Amendment 2 
21 June 2021 
Section 1.3, Schedule of activities 
Section 10.3.8.1, Time period for 
collecting and recording AEs, SAEs, 
AESIs and pregnancies 
Details on post-injection assessment have 
been added. 
To clarify on the data to be collected during 
the post-injection assessment period. 
 
 
Section 3, Objectives and endpoints 
(Table 7) 
Section 8.1.2, Laboratory assays 
Section 8.1.3, Immunological read-outs 
Section 10.2.2.2.1, MenB serum 
bactericidal assays – 
 and 
Bexsero 
 
 
Section 8.3.3, Regulatory reporting 
requirements for SAEs, pregnancies and 
other events 
The timeframe for submitting pregnancy 
report to GSK is now 24 hours (changed 
from 2 weeks). 
Changed in line with the pregnancy reporting 
guidelines for Vaccine studies. 
 
 
Section 2.3, Benefit/Risk assessment 
The Tdap vaccine (Boostrix) has been 
removed from the study design of Phase II 
To avoid potential confounding factors that 
might impact selection of dosage and 
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Document 
Date of issue 
Section # and title 
Description of change 
Brief rationale 
Section 4.1.2.1, Phase II formulation and 
schedule-finding 
Section 4.2, Scientific rationale for study 
design 
Section 5.1, Inclusion criteria 
Section 6.1, Study intervention(s) 
administered (Table 12) 
Section 8.2.1.5, Warnings and 
precautions to vaccination 
Section 8.2.21, Safety data review 
Formulation and schedule-finding. It has 
been replaced by placebo as applicable. 
schedule for further development which is 
one of the primary aims of the study. 
Protocol Amendment 3 
29 September 
2021 
Section 1.3 Schedule of activities, Table 
3 
Section 1.3 Schedule of activities, Table 
4 
Section 2.3 Benefit/Risk assessment 
Section 3 Objectives and endpoints, 
Table 7 
Section 4.1.2.1 Phase II: Formulation and 
Schedule-finding 
Section 6.1 Study intervention(s) 
administered, Table 12 
Section 8 Study assessments and 
procedures, Table 16 
Section 8.2.2.1.1 Safety evaluation 
Section 8.3.1 Time period and frequency 
for collecting AE, SAE and other safety 
information, Table 28 
Section 10.3.8 Recording and follow-up 
of AEs, SAEs, AESIs and pregnancies 
In the Phase II Formulation and Schedule 
finding, the participants in the Control group 
will have no study intervention at Visit V3 
(Month 4). This visit (Visit V3) has been 
replaced by a phone call (TC). Applicable 
changes made in all sections noted here. 
Refer to Section 10.10.1 for details. 
Since the Control group is open-label, 
administration of placebo at Visit V3 (Month 
4) is not required. Therefore this group will 
not have any study intervention administered 
at this timepoint. This visit has been replaced 
by a phone call. 
 
 
Section 1.3 Schedule of activities,  
Table 1, Table 3, Table 5 
Section 8.1.1.1 Blood sample 
The word ‘approximately’ added when 
referring to overall volume 
To align with the fact that individual volumes 
are presented as ‘approximately xx mL’, this 
word has been added to the overall blood 
volume as well. 
 
 
Section 8.3.1 Time period and frequency 
for collecting AE, SAE and other safety 
information, Table 27, Table 28, Table 29 
Footnote added to clarify the follow-up for 
unsolicited AEs post-vaccination 
Since the way the shading of the table is 
done may lead to misinterpretation regarding 
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Document 
Date of issue 
Section # and title 
Description of change 
Brief rationale 
the follow-up period for unsolicited AEs, the 
footnote has been added for clarification. 
 
 
Section 9.1.2.1 Superiority of vaccine 
effectiveness of the 
 
vaccine
 when 
administered at 0,2- or 0,6-m schedule 
compared to the Control vaccine (MenB) 
Section 9.1.2.2 Immunological non-
inferiority of 
 vaccine 
 when administered at 
0,2- or 0,6-m schedule compared to the 
Control vaccine (MenACWY) 
Section 9.4.2 Primary endpoint(s) – 
Phase II (Formulation and Schedule-
finding) 
The confidence interval for the primary 
immunogenicity objectives associated with 
phase II formulation and schedule-finding 
has been changed to 97.5% CI (from 95% 
CI). 
In the statistical analyses of the study, the 
alpha has been split due to the decision to 
parallelly test the 2 formulations (
 
). Therefore, the confidence interval 
for the evaluation of primary endpoints 
should be presented as 97.5%. 
 
 
Section 9.2, Sample size determination 
The following sentence added: Participants 
who withdraw from the study will not be 
replaced 
Clarification added to make it clear that 
withdrawals will not be replaced in the study. 
 
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10.10.1. 
Protocol amendment 4 
Detailed description of current Protocol amendment: New text is shown in bold italics 
and deleted text is shown in strikethroughs. 
In Section 1.3 Schedule of activities (SoA) 
Table 5 
Schedule of Activities – Phase II (Sourcing; 0, 1 month vaccination 
schedule) 
Table 6 
Schedule of Activities – Phase II (Sourcing; 0, 2 month vaccination 
schedule) 
Type of contact 
Visit PC Visit Visit Visit PC PC 
Notes 
Visit/Phone call no. 
V1 T1 V2 
V3 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 9 for visit 
windows] 
Day 
1 
Day 
31 
Day 
61 
Day 
76 
Day 
91 
Day 
181 
Day 
241 
Informed consent 
● 
 
 
 
 
 
 
Confirm consent form signed prior to 
any procedures. 
Before performing any study-related 
activities, check the randomisation 
system to ensure that enrolment is still 
open 
See Section 10.1.3 for details 
Check inclusion/exclusion 
criteria 
● 
 
○ 
 
 
 
 
Prior to administering each study 
intervention, the investigator must 
check eligibility criteria for subsequent 
vaccinations and criteria for delay of 
study intervention administration. 
See Sections 5.1 and 5.2 for inclusion 
and exclusion criteria 
Study group and treatment 
number allocation 
(randomisation) 
● 
 
 
 
 
 
 
See Section 6.3 for more information 
Treatment number allocation 
for subsequent doses 
 
 
○ 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
See Section 8.2.1.1 for more information 
Medical and vaccination 
history  
● 
 
 
 
 
 
 
See Section 8.2.1.2 for more information 
General physical examination  
○ 
 
 
 
 
 
 
Physical examination to be performed 
by a qualified health professional in 
accordance with local regulations and 
licensing requirements designated 
within the Delegation of Responsibility 
Log. 
See Section 8.2.1.3 for more information 
Symptom-directed physical 
examination 
 
 
○ 
○ 
○ 
 
 
Check contraindications, 
warnings and precautions to 
study intervention 
administration 
○ 
 
○ 
 
 
 
 
See Sections 7.1.1 and 8.2.1.5 for more 
information 
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Type of contact 
Visit PC Visit Visit Visit PC PC 
Notes 
Visit/Phone call no. 
V1 T1 V2 
V3 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 9 for visit 
windows] 
Day 
1 
Day 
31 
Day 
61 
Day 
76 
Day 
91 
Day 
181 
Day 
241 
Check criteria for temporary 
delay for enrolment/study 
intervention 
administration/blood sampling 
○ 
 
○ 
○ 
○ 
 
 
See Section 5.5 for more information 
Urine pregnancy test for 
females 
● 
 
● 
 
 
 
 
See Section 8.2.1.4 for more information 
Body temperature before study 
intervention administration 
● 
 
● 
 
 
 
 
Fever is defined as temperature 
38.0°C/100.4°F. Preferred location for 
measuring temperature will be the oral 
cavity. If any other route is used for 
measuring temperature, this needs to 
be recorded in the eCRF 
Blood sampling 
●^ 
 
 
● 
● 
 
 
Blood volume of approximately 95 mL 
will be collected at each blood sampling 
visit. 
See Section 8.1.1.1 for more information 
Study intervention 
administration 
● 
 
● 
 
 
 
 
See Section 6.1 for more information 
Recording of administered 
study intervention number 
● 
 
● 
 
 
 
 
 
Post-injection assessment (30 
minutes) 
● 
 
● 
 
 
 
 
See Section 10.3.8.1 for more 
information 
Distribution of eDiary  
○ 
 
 
 
 
 
 
 
Review of eDiary 
 
● 
 
● 
● 
 
 
 
Return of eDiary 
 
 
 
 
● 
 
 
 
Recording of solicited AEs 
(Days 1–7 post-vaccination)  
x 
 
x 
 
 
 
 
See Section 10.3.8 for more information  
Recording of unsolicited AEs 
(Days 1-30 post-vaccination) 
● 
 
● 
 
 
 
 
See Section 10.3.8 for more information 
Record any concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
Timeframe for recording of concomitant 
medications/vaccinations is according 
to the recording period of the AEs for 
which they are being administered 
See Section 6.8 for more information 
Record any intercurrent 
medical conditions 
 
● 
● 
● 
● 
● 
● See Section 9.3.1 for more information 
Recording of any AEs leading 
to vaccine/study withdrawal, 
SAEs, pregnancies and AESIs* 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording of SAEs related to 
study participation, or to a 
concurrent GSK medication/ 
vaccine 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine begins from the 
time a participant signs the consent 
form to the study end. 
See Section 10.3.8 for more information 
Study (Phase II, Sourcing) 
Conclusion 
 
 
 
 
 
 
● 
Participants who terminate the study 
early are recommended to complete 
certain study-related procedures. 
See Section 4.4 and 10.1.9.1 for more 
information 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
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○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
Documentation will be required in the source documents 
× is used to indicate a study procedure that will be documented in the eDiary  
^ Procedure to be performed prior to study intervention administration 
Abbreviation: PC, phone contact; V, clinic visit; T, telephone call; AE, adverse event; SAE, serious adverse 
event; AESI, adverse events of special interest. Note: All procedures to be performed prior to study 
intervention administration (as applicable).  
* Diagnosis of coronavirus 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 Section 10.3 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 36). In addition, separate COVID-19 specific 
eCRF form(s) should be completed  
Note 1: If local regulations allow and quality of study procedures is maintained, participant(s) can be offered 
remote visits (e.g. home visits) for the collection of biological samples and/or study intervention 
administration (except for Visit V1 which will always be a clinic visit). These remote visits must be performed 
by qualified study staff/ HCPs. Details of how these visits will be conducted are outlined in the SPM. Refer to 
Section 8 (decentralised study procedures) for details 
Note 2: Refer to Section 8 for information on study procedures during special circumstances 
Table 7 
Schedule of Activities – Phase II (Sourcing; 0, 6 month vaccination 
schedule) 
Type of contact 
Visit PC Visit Visit Visit PC PC 
Notes 
Visit/Phone call no. 
V1 T1 V2 
V3 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 10 for visit 
windows] 
Day 
1 
Day 
31 
Day 
181 
Day 
196 
Day 
211 
Day 
301 
Day 
361 
Informed consent 
● 
 
 
 
 
 
 
Confirm consent form signed prior to 
any procedures. 
Before performing any study-related 
activities, check the randomisation 
system to ensure that enrolment is still 
open 
See Section 10.1.3 for details 
Check inclusion/exclusion 
criteria 
● 
 
○ 
 
 
 
 
Prior to administering each study 
intervention, the investigator must 
check eligibility criteria for subsequent 
vaccinations and criteria for delay of 
study intervention administration. 
See Sections 5.1 and 5.2 for inclusion 
and exclusion criteria 
Study group and treatment 
number allocation 
(randomisation) 
● 
 
 
 
 
 
 
See Section 6.3 for more information 
Treatment number allocation 
for subsequent doses 
 
 
○ 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
See Section 8.2.1.1 for more information 
Medical and vaccination 
history  
● 
 
 
 
 
 
 
See Section 8.2.1.2 for more information 
General physical examination  
○ 
 
 
 
 
 
 
Physical examination to be performed 
by a qualified health professional in 
accordance with local regulations and 
licensing requirements designated 
within the Delegation of Responsibility 
Log. 
See Section 8.2.1.3 for more information 
Symptom-directed physical 
examination 
 
 
○ 
○ 
○ 
 
 
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Type of contact 
Visit PC Visit Visit Visit PC PC 
Notes 
Visit/Phone call no. 
V1 T1 V2 
V3 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 10 for visit 
windows] 
Day 
1 
Day 
31 
Day 
181 
Day 
196 
Day 
211 
Day 
301 
Day 
361 
Check contraindications, 
warnings and precautions to 
study intervention 
administration 
○ 
 
○ 
 
 
 
 
See Sections 7.1.1 and 8.2.1.5 for more 
information 
Check criteria for temporary 
delay for enrolment/study 
intervention 
administration/blood sampling 
○ 
 
○ 
○ 
○ 
 
 
See Section 5.5 for more information 
Urine pregnancy test for 
females 
● 
 
● 
 
 
 
 
See Section 8.2.1.4 for more information 
Body temperature before study 
intervention administration 
● 
 
● 
 
 
 
 
Fever is defined as temperature 
38.0°C/100.4°F. Preferred location for 
measuring temperature will be the oral 
cavity. If any other route is used for 
measuring temperature, this needs to 
be recorded in the eCRF 
Blood sampling 
●^ 
 
 
● 
● 
 
 
Blood volume of approximately 95 mL 
will be collected at each blood sampling 
visit. 
See Section 8.1.1.1 for more information 
Study intervention 
administration 
● 
 
● 
 
 
 
 
See Section 6.1 for more information 
Recording of administered 
study intervention number 
● 
 
● 
 
 
 
 
 
Post-injection assessment (30 
minutes) 
● 
 
● 
 
 
 
 
See Section 10.3.8.1 for more 
information 
Distribution of eDiary  
○ 
 
 
 
 
 
 
 
Review of eDiary 
 
● 
 
● 
● 
 
 
 
Return of eDiary 
 
 
 
 
● 
 
 
 
Recording of solicited AEs 
(Days 1–7 post-vaccination)  
x 
 
x 
 
 
 
 
See Section 10.3.8 for more information  
Recording of unsolicited AEs 
(Days 1-30 post-vaccination) 
● 
 
● 
 
 
 
 
See Section 10.3.8 for more information 
Record any concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
Timeframe for recording of concomitant 
medications/vaccinations is according 
to the recording period of the AEs for 
which they are being administered 
See Section 6.8 for more information 
Record any intercurrent 
medical conditions 
 
● 
● 
● 
● 
● 
● See Section 9.3.1 for more information 
Recording of any AEs leading 
to vaccine/study withdrawal, 
SAEs, pregnancies and AESIs* 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording of SAEs related to 
study participation, or to a 
concurrent GSK medication/ 
vaccine 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine begins from the 
time a participant signs the consent 
form to the study end. 
See Section 10.3.8 for more information 
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Type of contact 
Visit PC Visit Visit Visit PC PC 
Notes 
Visit/Phone call no. 
V1 T1 V2 
V3 
V4 
T2 
T3 
Timepoint(s) 
 [refer to Table 10 for visit 
windows] 
Day 
1 
Day 
31 
Day 
181 
Day 
196 
Day 
211 
Day 
301 
Day 
361 
Study (Phase II, Sourcing) 
Conclusion 
 
 
 
 
 
 
● 
Participants who terminate the study 
early are recommended to complete 
certain study-related procedures. 
See Section 4.4 and 10.1.9.1 for more 
information 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
Documentation will be required in the source documents 
× is used to indicate a study procedure that will be documented in the eDiary  
^ Procedure to be performed prior to study intervention administration 
Abbreviation: PC, phone contact; V, clinic visit; T, telephone call; AE, adverse event; SAE, serious adverse 
event; AESI, adverse events of special interest. Note: All procedures to be performed prior to study 
intervention administration (as applicable).  
* Diagnosis of coronavirus 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 Section 10.3 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 36). In addition, separate COVID-19 specific 
eCRF form(s) should be completed  
Note 1: If local regulations allow and quality of study procedures is maintained, participant(s) can be offered 
remote visits (e.g. home visits) for the collection of biological samples and/or study intervention 
administration (except for Visit V1 which will always be a clinic visit). These remote visits must be performed 
by qualified study staff/ HCPs. Details of how these visits will be conducted are outlined in the SPM. Refer to 
Section 8 (decentralised study procedures) for details 
Note 2: Refer to Section 8 for information on study procedures during special circumstances 
Table 8 
Intervals between study visits/contacts – Phase II (Sourcing; 0, 1 month 
vaccination schedule) 
Table 9 
Intervals between study visits/contacts – Phase II (Sourcing; 0, 2 month 
vaccination schedule) 
Interval 
Planned visit interval  
Allowed interval range (visit window) 
Visit 1 → Telephone contact T1 
30 days 
23 to 44 days (-7 to +14 days) 
Visit V1 → Visit V2 
60 days 
74 days (+14 days) 
Visit V2 → Visit V3 
15 days 
10 to 22 days (-5 to +7 days) 
Visit V2 → Visit V4 
30 days 
25 to 51 days (-5 to +21 days) 
Visit V2 → Telephone contact T2 
120 days 
113 to 134 days (-7 to +14 days) 
Visit V2 → Telephone contact T3 
180 days 
173 to 194 days (-7 to +14 days) 
Table 10 
Intervals between study visits/contacts – Phase II (Sourcing; 0, 6 month 
vaccination schedule) 
Interval 
Planned visit interval  
Allowed interval range (visit window) 
Visit 1 → Telephone contact T1 
30 days 
23 to 44 days (-7 to +14 days) 
Visit V1 → Visit V2 
180 days 
194 days (+14 days) 
Visit V2 → Visit V3 
15 days 
10 to 22 days (-5 to +7 days) 
Visit V2 → Visit V4 
30 days 
25 to 51 days (-5 to +21 days) 
Visit V2 → Telephone contact T2 
120 days 
113 to 134 days (-7 to +14 days) 
Visit V2 → Telephone contact T3 
180 days 
173 to 194 days (-7 to +14 days) 
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In Section 3, Objectives and endpoints: 
Table 11 
Study objective(s) and endpoints 
Phase II –Sourcing 
Primary 
To evaluate the safety and reactogenicity of the 2 
formulations (
) of the 
 
vaccine. 
• 
The frequencies and percentages of participants 
with solicited administration site and systemic 
events during the 7 days (including the day of 
vaccination) following each vaccination at Day 1 and 
Day 31 in all groups: 
• 
 Day 1 and Day 31 in 
 
 groups,  
• 
at Day 1 and Day 61 in 
 
 groups, and 
• 
at Day 1 and Day 181 in 
 
 groups. 
• 
The frequencies and percentages of participants 
with any unsolicited AEs (including all SAEs, AEs 
leading to withdrawal, and AESIs) during the 30 
days (including the day of vaccination) following 
each vaccination at Day 1 and Day 31 in all groups: 
• 
Day 1 and Day 31 
 
 groups,  
• 
at Day 1 and Day 61 in ABCWY50S_02 and 
 groups, and  
• 
at Day 1 and Day 181 in 
 
groups. 
• 
The frequencies and percentages of participants 
with SAEs, AEs leading to withdrawal and AESIs 
throughout the study period in all groups (Day 1 
through Day 211): 
• 
Day 1 through Day 211 in 
 
 groups,  
• 
Day 1 through Day 241 in 
 
 groups, and 
• 
Day 1 through Day 361 in 
 
 groups). 
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In Section 4.1.2.2 Phase II Sourcing 
The blood sourcing part of the Phase II study will include 2 groups (randomised 1:1), 
with a parallel enrolment of a total of 226* participants (Figure 3): 
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,1-month) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,1-month) schedule.  
* At the time of this protocol amendment (Protocol amendment 4), enrolment to these 2 
groups had been stopped. The total number of participants enrolled have been 
presented in Figure 3.  
Additionally, the Phase II sourcing part will include 4 more groups (randomised 
1:1:1:1), with a parallel enrolment of a total of 240 participants (Figure 3): 
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,2-month) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,2-month) schedule. 
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,6-month) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,6-month) schedule. 
 
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Figure 3 
Study design overview – Phase II (Sourcing) 
 
 
 
 
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Note 1: This figure represents the main aspects of the study design. Refer to Table 5, Table 6 and Table 7, Schedule 
of activities, for details on all visits and contacts 
Note 2: If local regulations allow and quality of study procedures is maintained, participant(s) can be offered remote 
visits (e.g. home visits) for the collection of biological samples and/or study intervention administration (except for Visit 
V1 which will always be a clinic visit). These remote visits must be performed by qualified study staff/ HCPs. Refer to 
the SoA (Table 5, Table 6 and Table 7) for the timing of these visits. Details of how these visits will be conducted are 
outlined in the SPM. Refer to Section 8 (decentralised study procedures) for details 
Table 14 
Study groups, intervention and blinding – Phase II (Sourcing) 
Study groups 
Number of 
participants 
Age 
(Min-Max) 
Study intervention(s)  
Blinding 
113 
113 
107 
18-50 yoa 
 
Observer-
blinded* 
60 
60 
60 
60 
* Due to the different vaccination schedules in Phase II Sourcing, the study will be observer blind only in terms 
of the vaccine formulations. 
Duration of the Phase II (Sourcing) of the study: The intended duration of the Phase II 
(sourcing) of the study, per participant is: 
• 
approximately 7 months for the 
 and 
 groups, 
• 
approximately 8 months for the 
 and 
 groups, 
and, 
• 
approximately 12 months for the 
 and 
 groups. 
Data collection: Standardised Electronic Case Report Form (eCRF). Solicited events will 
be collected using a participant diary (electronic Diary [eDiary]). 
Sampling schedule for Phase II (Sourcing) of the study: 
• 
Blood sample: Refer to Section 8.1.1.1 for details on collection of blood samples. 
• 
Urine sample: Urine samples for pregnancy testing will be collected from female 
participants of childbearing potential at Visit 1 (Day 1) and Visit 2 (Day 31) prior to 
the study intervention (at the following timepoints): 
− 
at Visit 1 (Day 1) and Visit 2 (Day 31) for the 
 
 groups, 
− 
at Visit 1 (Day 1) and Visit 2 (Day 61) for the 
 
 groups, and, 
− 
at Visit 1 (Day 1) and Visit 2 (Day 181) for the 
 
 groups. 
In Section 4.2 Scientific rationale for study design: 
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• 
The second part of the study [Phase II (Figure 2 and Figure 3] will only commence 
after demonstration of acceptable safety and reactogenicity in Phase I participants 
(Section 4.1.1). This Phase II will have 2 components – the formulation and 
schedule-finding part and the blood sourcing part. 
The 0,1-month schedule was selected for Phase I and Phase II (Sourcing) because the 
short time interval between vaccinations is conservative for the assessment of 
reactogenicity and safety.  
Furthermore, the 
 vaccine will also be administered according to a 
0,2month or 0,6month interval (wider dosing schedules) in the Phase II Sourcing part 
to support the finalization of assay development, further clinical testing, as well as 
assay stability monitoring and maintenance. For this reason, the total sample size of 
subjects in the Phase II Sourcing have been increased. 
In Section 4.4 End of study definition: 
A participant is considered to have completed the study if he/she returns for the last visit 
or is available for the last scheduled contact/ visit as described in the protocol [Telephone 
T3 in Phase I, Visit V6 in Phase II, Formulation and Schedule-finding and Telephone T2 
or Telephone T3 in Phase II, Sourcing (as per the group allocation)]. 
End of Study (EoS): Date of the last testing/reading released of the Human Biological 
Samples, related to primary and secondary endpoints. EoS must be achieved no later than 
8 months after Last Subject Last Visit (LSLV) (LSLV = Day 541, Month 18 in Phase II, 
formulation and schedule-finding). If the completion of testing occurs prior the 
completion of the LSLV the latter date defines the end of study visit. 
In Section 5.5, Criteria for temporarily delaying enrolment/ randomisation/ study 
intervention administration/blood sampling: 
• 
Significant acute illness within the previous 7 days of study intervention 
administration. 
• 
A positive test for current infection with COVID-19 prior to intervention 
administration. The testing should have been done using a molecular (polymerase 
chain reaction [PCR] or antigen test) approved by the country regulatory authorities. 
• 
Participants with known COVID-19 positive contacts and considered at risk of 
having contracted a COVID-19 infection according to local regulations. 
In Section 6.1, Study intervention(s) administered: 
Table 17 
Study intervention administered – Phase II (Sourcing) 
Study intervention name: 
No of doses 
 
 
 
2 
- 
- 
2 
2 
- 
- 
2 
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Study intervention name: 
2 
- 
- 
2 
In Section 6.3.5 Blinding and unblinding: 
6.3.5.1 Phase I and Phase II (Sourcing) 
Data will be collected in an observer-blind manner. To do so, study intervention(s) 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, efficacy). 
Note: Due to the different vaccination schedules in Phase II Sourcing, the study will be 
observer blind only in terms of the vaccine formulations 
6.3.5.3 Unblinding 
The participant, the site and sponsor personnel involved in the clinical evaluation of 
the participants will be unblinded to the treatment assigned at a Phase at completion of 
that particular Phase. 
Refer to Section 4.4 for the definition of study completion per participant. 
In Section 6.6, Continued access to study intervention after the end of the study: 
During the study conclusion visit/contact (Telephone T3 in Phase I, Visit V6 in Phase II, 
Formulation and Schedule-finding and Telephone T2/ Telephone T3 in Phase II, 
Sourcing [as per group allocation]), 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 booster study/long-term study the 
reason for refusal will be documented, when available, in the participant’s eCRF. 
In Section 6.8 Concomitant therapy: 
• 
All concomitant medication associated with an adverse event, including 
vaccines/products, except vitamins and dietary supplements, administered after the 
first dose of study intervention (Phase 1 and Phase II, Sourcing: Day 1 to Day 211 or 
Day 241 or Day 361 (as per the group allocation) and Phase II, Formulation and 
Schedule-finding: Day 1 to Day 541). 
• 
Any concomitant vaccination administered in the period starting 14 days before the 
first dose of study intervention and ending at the last study contact (Phase 1 and 
Phase II, Sourcing: -Day 14 to Day 211 or Day 241 or Day 361 (as per the group 
allocation) and Phase II, Formulation and Schedule-finding: Day -14 to Day 541). 
In Section 8, Study assessments and procedures: 
Study procedures in special circumstances: 
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• 
If despite best efforts it is not possible to collect the biological samples within the 
interval pre-defined in the protocol (see Table 2 for Phase I, Table 4 for Phase II, 
Formulation and Schedule-finding and Table 8, Table 9 and Table 10 for Phase II, 
Sourcing), then the applicable intervals may be extended up to a maximum length of 
days as presented in Table 19 (Phase I), Table 20 (Phase II, Formulation and 
Schedule-finding) and Table 21, Table 22 and Table 23 (Phase II, Sourcing), as 
applicable.  
• 
If despite best efforts it is not possible to administer the dose of study intervention as 
defined in the protocol (see Table 2 for Phase I, Table 4 for Phase II, Formulation 
and Schedule-finding and Table 8, Table 9 and Table 10 for Phase II, Sourcing), a 
maximum dose interval may be used as presented in Table 19 (Phase I) and Table 20 
(Phase II, Formulation and Schedule-finding) and Table 21, Table 22 and Table 23 
(Phase II, Sourcing), as applicable. 
Table 21 
Intervals between study visits/contacts during special circumstances – 
Phase II (Sourcing; 0,1 month vaccination schedule) 
Table 22 
Intervals between study visits/contacts during special circumstances – 
Phase II (Sourcing; 0,2 month vaccination schedule) 
Interval 
Length of 
interval  
Allowed interval (Visit window) 
Visit V2 → Visit V3 
15 days 
8 to 22 days (-7 to +7 days) 
Visit V2 → Visit V4 
30 days 
25 to 51 days (-5 to +21 days) 
Visit V2 → Telephone contact T2 
120 days 
113 to 141 days (-7 to +21 days) 
Visit V2 → Telephone contact T3 
180 days 
173 to 201 days (-7 to +21 days) 
Table 23 
Intervals between study visits/contacts during special circumstances – 
Phase II (Sourcing; 0,6 month vaccination schedule) 
Interval 
Length of 
interval  
Allowed interval (Visit window) 
Visit V2 → Visit V3 
15 days 
8 to 22 days (-7 to +7 days) 
Visit V2 → Visit V4 
30 days 
25 to 51 days (-5 to +21 days) 
Visit V2 → Telephone contact T2 
120 days 
113 to 141 days (-7 to +21 days) 
Visit V2 → Telephone contact T3 
180 days 
173 to 201 days (-7 to +21 days) 
In Section 8.1.1.1 Blood sample 
Phase II (sourcing): An overall blood volume of approximately 285 mL per participant 
will be collected over the course of the Phase II, Sourcing part of the study. Please refer 
to Table 25 and Table 26 for details. 
Table 25 
Blood samples at Phase II (Sourcing; 0,1 month vaccination schedule) 
Sample 
type 
Quantity 
Unit 
Timepoint 
Subset name/ 
Group 
Day 
Blood 
Approximately 95 
mL 
Visit V1 (
); 
All participants 
Day 1 
Blood 
Approximately 95 
mL 
Visit V2 (
 
All participants 
Day 31 
Blood 
Approximately 95 
mL 
Visit V3 (
 
All participants 
Day 61 
Pre-Vacc, Pre-vaccination timepoint; Post-Vacc, Post-vaccination timepoint 
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2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
1 6 6  
R ef er t o T a bl e 5  ( S o A f or P h as e II, S o urci n g) f or d et ails of visits.  
T a ble 2 6  
Bl o o d s a m ples at P h ase II ( S o urci n g; 0, 2 a n d 0, 6 m o nt h v acci n ati o n 
sc he d ule) 
S a m pl e 
t y p e 
Q u a ntit y  
U nit  
Ti m e p oi nt  
S u b s et n a m e/ Gr o u p  
D a y  
Bl o o d  
A p pr o xi m at el y 9 5  
m L  
Vi sit V 1 
; 
All p arti ci p a nt s  
D a y 1  
Bl o o d  
A p pr o xi m at el y 9 5  
m L  
Vi sit V 3  
(
); 
D a y 7 6  
D a y 1 9 6  
Bl o o d  
A p pr o xi m at el y 9 5  
m L  
Vi sit V 4  
(
 
D a y 9 1  
D a y 2 1 1  
Pr e -V a c c, Pre -v a c ci n ati o n ti m e p oi nt; P o st -Va c c, P o st -v a c ci n ati o n ti m e p oi nt . 
R ef er t o T a bl e 6  a n d T a bl e 7( S o A f or P h a s e II, S o urci n g) f or d et ail s of vi sit s. 
I n secti o n 8. 1. 2 L a b or at or y ass a ys: 
Effecti ve n ess of t he  
 a nti ge ns of t he 
 vacci ne will be e val uate d 
wit h ser u m bacteri ci dal assa ys usi n g e n d o ge n o us s o urce of h u m a n c o m ple me nt (e nc -
h S B A), o n a p a nel of 1 1 0 U S re pres e ntati ve N. me ni n giti dis  ser o gr o u p B i n vasi ve disease 
strai ns. I m m u n o ge ni cit y of t he vacci ne a gai nst ser o gr o u ps A, B, C, W a n d Y will be 
e val uate d wit h t he ser u m bacterici d al assa y usi n g e x o ge n o us s o urce of h u ma n 
c o m ple me nt ( h S B A). A n  e nz y me-li n ke d i m m u n os or be nt assa y ( E LI S A) or a n y ot h er 
E LI S A -li ke tec h n ol o g y
 m ulti ple x ass ay will be 
use d t o e val uate t he s er ot y p e -s pecifi c I g G res p o ns es t o A, C, W, a n d Y. 
T a ble 2 8  
L a b or at or y ass a ys –  P h ase I a n d II  
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C O N FI D E N TI A L  
2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
1 6 7  
I n Secti o n 8. 1. 3, I m m u n ol o gic al re a d -o uts : 
Ta ble 2 9  
I m m u n ol o gical r ea d-o uts –  P hase II ( F or m ulati o n a n d Sc he d ule-fi n di n g), 0 _ 6 
sc he d ule: F or 
 a n d C o ntr ol gr o u ps 
Ta ble 3 1  
I m m u n ol o gical r ea d-o uts –  P hase II ( S o urci n g): 
 
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In Section 8.3.1, Time period and frequency for collecting AE, SAE and other safety 
information: 
Table 36 
Timeframes for collecting and reporting of safety information – Phase II 
(Sourcing 0,1 month vaccination schedule) 
Table 37 
Timeframes for collecting and reporting of safety information – Phase II 
(Sourcing; 0,2 month vaccination schedule) 
Event 
On 
V1* 
 
V1 
 
 
V2 
 
 
V3 
 
V4 
 
PC 
Phase II, 
Sourcing 
conclusion 
 
D1*** D7 
D61 
D67  
D76 
 
D91 
 
Day 181 
D 241 
(PC) 
Solicited 
administration site 
and systemic events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to 
withdrawal from the 
study** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AESIs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies**  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.; V: Visit; D: Day, M: Month; PC=Phone call 
** Including COVID-19 infection-related AEs; Recording of unsolicited AEs is only from Day 1 to Day 30 post-
vaccination) 
*** Except SAEs related to study participation or concurrent GSK medication/vaccine, all other safety data will 
be collected starting from Visit 1 after vaccine administration 
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Table 38 
Timeframes for collecting and reporting of safety information – Phase II 
(Sourcing; 0,6 month vaccination schedule) 
Event 
On 
V1* 
 
V1 
 
 
V2 
 
 
V3 
 
V4 
 
PC 
Study 
conclusion 
 
D1*** D7 
D181 D187  D196  
D211 
 
Day 301 D 361(PC) 
Solicited 
administration site 
and systemic events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to 
withdrawal from the 
study** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AESIs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies**  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.; V: Visit; D: Day, M: Month; PC=Phone call 
** Including COVID-19 infection-related AEs; Recording of unsolicited AEs is only from Day 1 to Day 30 post-
vaccination) 
*** Except SAEs related to study participation or concurrent GSK medication/vaccine, all other safety data will 
be collected starting from Visit 1 after vaccine administration 
In Section 9.2.3, Phase II (Sourcing): 
Two hundred and twenty-six (226) One hundred and seven (107) participants are to be 
have been enrolled in 2 arms of Phase II (Sourcing) of the study, 113 participants each in 
 group (1:1 randomisation). At the time of this 
amendment (Protocol amendment 4) enrolment to these groups was stopped. 
Two hundred and forty (240) participants are to be enrolled in 4 arms, 60 participants 
each in 
 
groups (1:1:1:1 randomization). 
In Section 9.3, Analysis sets: 
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In Section 9.4.3, Primary endpoint(s) – Phase II (Sourcing) 
Primary Endpoint 
Statistical Analysis Methods 
Safety 
 
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In Section 10.1.9.1, Study conclusions: 
At Phase I conclusion phone call (Day 211), Phase II (Formulation and Schedule-finding) 
conclusion visit (study conclusion; Visit 6, Day 541) and Phase II (Sourcing) conclusions 
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phone call (Day 211 in 
 
 groups and Day 361 in 
 
 groups), the investigator will: 
• 
Review data collected to ensure accuracy and completeness 
• 
Complete the Study Conclusion screen in the eCRF 
In Section 10.3.8, Recording and follow-up of AEs, SAEs, AESIs and pregnancies: 
• 
Verify completed eDiaries during discussions with the participant/participant’s 
parent(s)/LAR(s) on: 
− 
Visit V3 (Day 31) and Visit V4 (Day 61) – Phase I 
− 
Visit V2 (Day 31), Visit V4 (Day 181) and Visit V5 (Day 211) – Phase II, 
Formulation and Schedule finding, 
 
 groups 
− 
Visit V2 (Day 31) and Visit V5 (Day 211) – Phase II, Formulation and Schedule 
finding, Control group 
− 
Visit V2 (Day 31) and Visit V3 (Day 61) – Phase II, Sourcing, 
 
 groups. 
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− 
Phone call (T1, Day 31), Visit V3 (Day 76) and Visit 4 (Day 91) – Phase II, 
Sourcing,
 groups. 
− 
Phone call (T1, Day 31), Visit V3 (Day 196) and Visit 4 (Day 211) - Phase II, 
Sourcing, 
 groups. 
Collect eDiaries on Visit 4 (Day 61) for Phase I participants, Visit 5 (Day 211) for Phase 
II (Formulation and Schedule-finding) participants and Visit 3/4 (V3, Day 61 for 
 groups, V4, Day 91 for 
 
 groups and V4, Day 211 in 
 
groups) for Phase II (Sourcing) participants. 
In Section 10.3.9.3, Medically attended visits: 
For each solicited and unsolicited AE the participant experiences (Refer to Table 34, 
Table 35, Table 36, Table 37 and Table 38), the participant/participant’s 
parent(s)/LAR(s) will be asked if he/she/the participant received medical attention 
(defined as hospitalisation, or an otherwise unscheduled visit to or from medical 
personnel for any reason, including emergency room visits). This information will be 
recorded in the eDiary/ eCRF. 
In Section 10.3.9.5, Recording of AEs related to COVID-19: 
For COVID-19 infection-related AEs, sites should follow routine AE/SAE processes as 
outlined in the protocol, using the following terms according to World Health 
Organization (WHO) defined case definitions: 
• 
Suspected COVID-19 case 
• 
Probable COVID-19 case 
• 
Confirmed COVID-19 case [WHO, 2020] 
Note: Due to the rapid evolution of the COVID-19 pandemic situation, it is important 
to adhere to the most recent guidelines released by WHO. Please refer to the WHO 
website for the latest guidance. 
• 
Confirmed COVID-19 case [WHO, 2020] 
A person with laboratory confirmation of COVID-19 infection, irrespective of 
clinical signs and symptoms. See “Laboratory testing for 2019 novel coronavirus 
(2019-nCoV) in suspected human cases” [WHO, 2019] for details 
In Section 10.5.1.1.1, Women not considered as women of childbearing potential: 
• 
Premenopausal female with ONE of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
− 
Current bilateral tubal ligation or occlusion 
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10.10.2. 
Protocol amendment 3 
Detailed description of current Protocol amendment: New text is shown in bold italics 
and deleted text is shown in strikethroughs. 
In Section 1.3 Schedule of activities, Table 1, Schedule of Activities – Phase I: 
Type of contact 
Visit Visit Visit PC Visit PC PC Notes 
Visit/Phone call no. 
V1 V2 V3 T1 V4 T2 T3 
Timepoint(s) 
 [refer to Table 2 for visit 
windows] 
Day 
1 
Day 
8 
Day 
31 
Day 
38 Day 
61 
Day 
151 
Day 
211 
Blood sampling for sourcing 
●^ 
 
●^ 
 
● 
 
 
Blood volume of approximately 80 mL will be 
collected at each blood sampling visit. 
See Section 8.1.1.1 for more information 
In Section 1.3 Schedule of activities, Table 2, Intervals between study visits/contacts 
–Phase I: 
Interval 
Planned visit/ phone call interval  
Allowed interval range (visit window) 
Visit V3 → Telephone contact T1 
6 7 days 
5 6 to 7 8 days (-1 to +1 days) 
In Section 1.3 Schedule of activities, Table 3, Schedule of Activities – Phase II 
(Formulation and schedule-finding): 
Type of contact 
Visit PC Visit PC 
Visit 
PC 
Visit Visit PC PC PC Visit 
Notes 
Visit/Phone call no. 
V1 
T1 
V2 T2 
V3† 
TC†† 
V4 V5 T3  T4  T5  V6 
Timepoint(s) 
[refer to Table 4 for visit 
windows] 
Day 
1 
Day  
8** 
Day 
31 
Day 
91 Day 121 
Day 121 Day 
181 
Day 
211 
Day 
271 
Day 
361 
Day 
451 
Day 
541 
Groups 
All First 
45** All All ABCWY 
groups 
Control 
group 
All All All All All All 
 
Informed consent 
● 
 
 
 
 
 
 
 
 
 
 
 
Confirm consent form 
signed prior to any 
procedures. Before 
performing any study-
related activities, check the 
randomisation system to 
ensure that enrolment is 
still open 
See Section 10.1.3 for 
details 
Informed assent, if 
applicable 
○ 
 
 
 
 
 
 
 
 
 
 
 
Confirm assent form (if 
applicable) signed prior to 
any procedures  
Check inclusion/exclusion 
criteria 
● 
 
 
 
○ 
 
○ 
 
 
 
 
 
Prior to administering each 
study intervention the 
investigator must check 
eligibility criteria for 
subsequent vaccination 
and criteria for delay of 
study intervention 
administration 
See Sections 5.1 and 5.2 
for inclusion and exclusion 
criteria 
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Type of contact 
Visit PC Visit PC 
Visit 
PC 
Visit Visit PC PC PC Visit 
Notes 
Visit/Phone call no. 
V1 
T1 
V2 T2 
V3† 
TC†† 
V4 V5 T3  T4  T5  V6 
Timepoint(s) 
[refer to Table 4 for visit 
windows] 
Day 
1 
Day  
8** 
Day 
31 
Day 
91 Day 121 
Day 121 Day 
181 
Day 
211 
Day 
271 
Day 
361 
Day 
451 
Day 
541 
Groups 
All First 
45** All All ABCWY 
groups 
Control 
group 
All All All All All All 
 
Study group and treatment 
number allocation 
(randomisation) 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 6.3 for more 
information 
Treatment number 
allocation for subsequent 
doses 
 
 
 
 
○ 
 
○ 
 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.1 for 
more information 
Medical and vaccination 
history  
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.2 for 
more information 
General physical 
examination  
○ 
 
 
 
 
 
 
 
 
 
 
 
Physical examination to be 
performed by a qualified 
health professional in 
accordance with local 
regulations and licensing 
requirements designated 
within the Delegation of 
Responsibility Log. 
See Section 8.2.1.3 for 
more information 
Symptom-directed physical 
examination 
 
 
○ 
 
○ 
 
○ 
○ 
 
 
 
○ 
Check contraindications, 
warnings and precautions 
to study intervention 
administration 
○ 
 
 
 
○ 
 
○ 
 
 
 
 
 
See Sections 7.1.1 and 
8.2.1.5 for more 
information 
Check criteria for 
temporary delay for 
enrolment/study 
intervention 
administration/blood 
sampling 
○ 
 
○ 
 
○ 
 
○ 
○ 
 
 
 
○ 
See Section 5.5 for more 
information 
Urine pregnancy test for 
females of childbearing 
potential 
● 
 
 
 
● 
 
● 
 
 
 
 
 
See Section 8.2.1.4 for 
more information 
Body temperature before 
study intervention 
administration 
● 
 
 
 
● 
 
● 
 
 
 
 
 
Fever is defined as 
temperature 
38.0°C/100.4°F. 
Preferred location for 
measuring temperature will 
be the oral cavity. If any 
other route is used for 
measuring temperature, 
this needs to be recorded 
in the eCRF 
Blood sampling 
●^ 
 
● 
 
 
 
 
● 
 
 
 
● 
Blood volume of 
approximately 15 mL will 
be collected at V1 (pre-
vaccination) and V2 and 
approximately 30 mL at 
V5 and V6. 
See Section 8.1.1.1 for 
more information 
Study intervention 
administration 
● 
 
 
 
● 
 
● 
 
 
 
 
 
See Section 6.1 for more 
information 
Recording of administered 
study intervention number 
● 
 
 
 
● 
 
● 
 
 
 
 
 
 
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Type of contact 
Visit PC Visit PC 
Visit 
PC 
Visit Visit PC PC PC Visit 
Notes 
Visit/Phone call no. 
V1 
T1 
V2 T2 
V3† 
TC†† 
V4 V5 T3  T4  T5  V6 
Timepoint(s) 
[refer to Table 4 for visit 
windows] 
Day 
1 
Day  
8** 
Day 
31 
Day 
91 Day 121 
Day 121 Day 
181 
Day 
211 
Day 
271 
Day 
361 
Day 
451 
Day 
541 
Groups 
All First 
45** All All ABCWY 
groups 
Control 
group 
All All All All All All 
 
Post-injection assessment 
(30 minutes) 
● 
 
 
 
● 
 
● 
 
 
 
 
 
See Section 10.3.8.1 for 
more information 
Distribution of eDiary  
○ 
 
 
 
○ 
 
○ 
 
 
 
 
 
 
Review of eDiary 
 
● 
● 
 
 
 
●‡ 
● 
 
 
 
 
 
Return of eDiary 
 
 
 
 
 
 
 
● 
 
 
 
 
 
Recording of solicited AEs 
(Days 1–7 post-
vaccination) 
x 
 
 
 
x 
 
x 
 
 
 
 
 
See Section 10.3.8 for 
more information 
Recording of unsolicited 
AEs (Days 1-30 post-
vaccination) 
● 
● 
● 
 
● 
 
● 
● 
 
 
 
 
See Section 10.3.8 for 
more information 
Record any concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Timeframe for recording of 
concomitant 
medications/vaccinations is 
according to the recording 
period of the AEs for which 
they are being 
administered. 
See Section 6.8 for more 
information 
Record any intercurrent 
medical conditions 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● See Section 9.3.1 for more 
information 
Recording of any AEs 
leading to vaccine/study 
withdrawal, SAEs, 
pregnancies and AESIs* 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for 
more information 
Recording of SAEs related 
to study participation, or to 
a concurrent GSK 
medication/vaccine 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs related 
to study participation, or to 
a concurrent GSK 
medication/vaccine begins 
from the time a participant 
signs the consent form to 
the study end. 
See Section 10.3.8 for 
more information 
Study Conclusion 
 
 
 
 
 
 
 
 
 
 
 
● 
Participants who terminate 
the study early are 
recommended to complete 
certain study-related 
procedures 
See Section 4.4 and 
10.1.9.1 for more 
information 
TC, Telephone contact for Control group only 
† Visit V3 (at Day 121) is only applicable for 
 
groups 
† †  TC (at Day 121) is only applicable for the Control group 
‡ Not applicable for Control group 
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In Section 1.3 Schedule of activities, Table 4, Intervals between study visits/contacts 
–Phase II (Formulation and schedule-finding): 
Interval 
Planned visit interval  
Allowed interval range 
Visit V1→Telephone contact T1*  
7 days 
6 to 8 days (-1 to +1 days) 
Visit V2 →Visit V3/TC** 
90 days 
85 to 104 days (-5 to +14 days) 
Visit V3/TC** → Visit V4 
60 days 
55 to 74 days (-5 to +14 days) 
Visit V4 → Telephone contact T3  
90 days 
83 to 104 days (-7 to +14 days) 
Visit V4 → Telephone contact T4  
180 days 
173 to 194 days (-7 to +14 days) 
Visit V4 → Telephone contact T5  
270 days 
263 to 284 days (-7 to +14 days) 
TC, Telephone contact for Control group only 
* The phone call (T1) at Day 8 is only for the first 45 participants (15 participants in 
, 5 
participants in
, 15 participants in 
 5 participants in 
 and 5 
participants in the Control groups). 
** Visit for 
 groups (Visit V3) and telephone 
call for Control group (TC) 
In Section 1.3 Schedule of activities, Table 5, Schedule of Activities – Phase II 
(Sourcing): 
Type of contact 
Visit Visit Visit 
PC 
PC 
Notes 
Visit/Phone call no. 
V1 V2 
V3 
T1 
T2 
Timepoint(s) 
 [refer to Table 6 for visit windows] 
Day 
1 
Day 
31 
Day 
61 
Day 
151 
Day 
211 
Blood sampling 
●^ 
●^ 
● 
 
 
Blood volume of approximately 95 mL will be 
collected at each blood sampling visit. 
See Section 8.1.1.1 for more information 
In Section 2.3 Benefit/Risk assessment 
As with all injectable vaccines, immediate systemic allergic reactions to vaccination can 
occur. In order to be able to treat participants with an immediate systemic allergic 
reaction to vaccination, all participants will need to remain under close observation for at 
least 30 minutes after each study intervention (as per the phase in which they are 
participating: Visit V1 and Visit V3 in Phase I, Visit V1, Visit V3^ and Visit V4 in Phase 
II Formulation and Schedule-Finding and Visit V1 and Visit V2 in Phase II Sourcing). 
Refer to Section 6.1. 
^ except for Control group participants who will have a phone call at this time point 
(TC). 
In Section 3, Table 7, Study objective(s) and endpoints 
Objectives 
Endpoints 
Phase II – Formulation and Schedule-finding 
Primary 
To evaluate the safety and reactogenicity of the 
 vaccine (
), the MenB vaccine and the 
MenACWY vaccine. 
• 
The frequencies and percentages of participants 
with solicited administration site and systemic 
events during the 7 days (including the day of 
vaccination) following each vaccination at: 
• 
Day 1, Day 121 and Day 181 in the 
 
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Objectives 
Endpoints 
 
groups, and 
• 
Day 1 and Day 181 in the Control group. 
• 
The frequencies and percentages of participants 
with any unsolicited AEs (including all SAEs, AEs 
leading to withdrawal, and AESIs) during the 30 
days (including the day of vaccination) following 
each vaccination at: 
• 
Day 1, Day 121 and Day 181 in the 
 
 
groups, and 
• 
Day 1 and Day 181 in the Control group. 
• 
The frequencies and percentages of participants 
with SAEs, AEs leading to withdrawal and AESIs 
throughout the study period in all groups (Day 1 
through Day 541). 
Note 1: MenB immune response will be assessed against N. meningitidis serogroup B indicator strains
 
In Section 4.1.2.1, Phase II: Formulation and Schedule-finding: 
Control: Participants will receive 2 vaccinations of MenB vaccine (Bexsero) in a (0,6-
months) schedule and a single vaccination of MenACWY vaccine (Menveo). They will 
also receive 1 injection of placebo. 
Figure 2 
Study design overview – Phase II (Formulation and Schedule-finding) 
 
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TC, Telephone contact for Control group only 
# Day 121 Month 4 is a visit for 
 groups (Visit 
V3) and is a telephone call for Control group (TC) 
If the decision is “go”, further vaccination at Month 4 and other study procedures 
following that will continue in these groups (as per the study design) along with 
continuing to recruit participants with a randomisation ratio of 1:1:1:1:1 (191 in each 
group) to reach the target total sample of 955 participants. Refer to Table 9 for total 
number of participants per group.  
Urine sample: Urine samples for pregnancy testing will be collected from female 
participants of childbearing potential at Visit 1 (Day 1), Visit 3 (Day 121) and Visit 4 
(Day 181) prior to the vaccination in the ABCWY groups and at Visit 1 (Day 1) and 
Visit 4 (Day 181) prior to the vaccination in the Control group. 
In Section 6.1, Table 12, Study intervention administered – Phase II (Formulation 
and Schedule-finding) 
Study 
intervention  
Bexsero  
Menveo* 
Placebo 
(saline) 
Product 
category 
Combination 
Combination 
Combination 
Biological 
Combination 
2 
- 
- 
- 
1 
2 
- 
- 
- 
1 
- 
2 
- 
- 
1 
- 
2 
- 
- 
1 
Control 
- 
- 
2 
1 
1 
Laterality*** 
Non-dominant*** 
Non-dominant*** 
Non-
dominant*** 
Dominant 
Non-
dominant*** 
In Section 8, Table 16, Intervals between study visits during special circumstances – 
Phase II (Formulation and Schedule finding) 
V2 D31
Month 1
V1 D1
Month 0
V5 D211
Month 7
V4 D181
Month 6
(N=191)
BS
BS
BS
BS
BS
BS
Randomization: 
1:1:1:1:1
N = 955
Placebo
Placebo
(N=191)
(N=191)
Control
(N=191)
BS
BS
Placebo
BS
MenB
MenACWY
V3/ TC# D121
Month 4
BS
BS
Placebo
BS
BS
BS
BS
MenB
V6 D541
Month 18
BS
BS
BS
BS
BS
(N=191)
N (Total) = 1000
Phase II: Formulation and Schedule-finding
V2 D31
Month 1
V1 D1
Month 0
V5 D211
Month 7
V4 D181
Month 6
(N=15)
(N=5)
BS
BS
BS
Randomization: 
3:1:3:1:1
N = 45
Placebo
Placebo
(N=15)
(N=5)
Control
(N=5)
BS
BS
BS
MenB
MenACWY
V3/ TC#  D121
Month 4
Placebo
MenB
V6 D541
Month 18
BS
Placebo
BS
BS
BS
BS
BS
BS
BS
BS
BS
BS
BS
i
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R
C*
BS
BS
PC D8^
Month 0







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C O N FI D E N TI A L  
2 1 2 4 5 8 ( M E N A C W Y =
-0 0 1 P RI)  
Pr ot o c ol A m e n d m e nt 4  Fi n al  
2 2  M ar c h 2 0 2 2  
1 8 0  
I nt er v al 
L e n gt h of i nt er v al  
All o w e d i nt er v al ( Vi sit wi n d o w)  
Visit V 1 → Visit V 2  
3 0 d ays  
2 3 t o 5 1 d ays ( -7 t o + 2 1 d ays)  
Visit V 1  → T el e p h o n e c o nt act T 2  
9 0 d ays  
8 3 t o 1 1 1 d ays ( -7 t o + 2 1 d ays)  
Visit V 2 →Visit V 3 / TC * 
9 0 d ays  
8 3 t o 1 1 1 d ays ( -7 t o  + 2 1 d ays)  
Visit V 3 / TC * → Visit V 4  
6 0 d ays  
5 3 t o 8 1 d ays ( -7 t o + 2 1 d ays)  
Visit V 4 → Visit V 5  
3 0 d ays  
2 3 t o 5 1 d ays ( -7 t o + 2 1 d ays)  
Visit V 4 → T el e p h o n e c o nt act  T 3   
9 0 d ays  
8 3 t o 1 1 1 d ays ( -7 t o + 2 1 d ays)  
Visit V 4 → T el e p h o n e c o nt act T 3  T 4  
1 8 0 d ays  
1 7 3 t o 2 0 1 d ays ( -7 t o + 2 1 d ays)  
Visit V 4 → T el e p h o n e c o nt act T 4  T 5  
2 7 0 d ays  
2 6 3 t o 2 9 1 d ays ( -7 t o + 2 1 d ays)  
Visit V 4 →Visit V 6  
3 6 0 d ays  
3 5 3 t o 3 8 1 d ays ( -7 t o + 2 1 d ays)  
* Vi sit f or 
gr o u p s ( Vi sit V 3) a n d t el e p h o n e 
c all f or C o ntr ol gr o u p ( T C ) 
I n Secti o n 8. 1. 1. 1, Bl o o d s a m ple 
P h ase I:  A n o v erall bl o o d v ol u me of a p pr o xi m ately  2 4 0 m L p er partici pa nt will be 
c ollecte d o ver t he c o urs e of t he P hase I p art of t he st u d y.  
P h ase II (s o urci n g): A n o verall bl o o d v ol u me of a p pr o xi m ately  2 8 5 m L p er partici p a nt 
will be c ollecte d o ver t he c o urse of t he P h ase II, S o urci n g p art of t he st u d y.  
P h ase II (f or m ul ati o n a n d sc he d ule -fi n di n g): I n or der t o pr o vi de t he n ecessar y ser u m 
v ol u me f or t he bacterici d al assa ys (e n c -h S B A a n d/ or h S B A), a n o v erall bl o o d v ol u me of 
a p pr o xi m ately  9 0 m L, per partici pa nt, will be c oll ecte d o ver t he c o urse of t he P hase II 
ste p of t he st u d y. 
I n Secti o n 8. 1. 3, T a ble 2 4 I m m u n ol o gic al re a d-o uts –  P h ase II ( S o urci n g): All 
p artici p a nts:  
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In Section 8.2.2.1.1 Safety evaluation: 
Figure 5 Step-wise approach for safety review in Phase II (Formulation and 
Schedule-finding) 
 
 
TC, Telephone contact for Control group only 
# Day 121 Month 4 is a visit for 
 groups (Visit 
V3) and is a telephone call for Control group (TC) 
The following step-wise approach will be followed for the safety evaluation during the 
Phase II (Formulation and Schedule-finding): 
• 
If the decision is “go”, the enrolment in all groups will continue with a 
randomisation ratio of 1:1:1:1:1 to the target total sample of 1000 participants and 
the administration of the second vaccination at Month 4 will take place in the 40 
participants in 
 
groups (as per study design).  
(N=191)
Randomization: 
1:1:1:1:1
N = 955
(N=191)
(N=191)
Control
(N=191)
(N=191)
N (Total) = 1000
Refer to Study design figure for details*
Phase II: Formulation and Schedule-finding
V2 D31
Month 1
V1 D1
Month 0
V5 D211
Month 7
V4 D181
Month 6
(N=15)
(N=5)
BS
BS
BS
Randomization: 
3:1:3:1:1
N = 45
Placebo
Placebo
(N=15)
(N=5)
Control
(N=5)
BS
BS
BS
MenB
MenACWY
V3/ TC #D121
Month 4
Placebo
MenB
V6 D541
Month 18
BS
Placebo
BS
BS
BS
BS
BS
BS
BS
BS
BS
BS
BS
i
S
R
C
BS
BS
PC D8^
Month 0






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In Section 8.3.1, Table 27, Timeframes for collecting and reporting of safety 
information – Phase I: 
** Including COVID-19 infection-related AEs; Recording of unsolicited AEs is only from Day 1 to Day 30 post-
vaccination  
 In Section 8.3.1, Table 28, Timeframes for collecting and reporting of safety 
information – Phase II (Formulation and schedule-finding) 
Event 
On 
V1* 
 
V1 
 
V2 
 V3# 
 
 
 
V4 
 
V5 
 
PC 
V6 
Study 
Conclusion 
#Solicited AEs and unsolicited AEs will be collected only for 
 
 groups at Visit V3 (Control group will have a phone call at this time point (TC) where other 
safety follow-up will be done) 
** Including COVID-19 infection-related AEs; Recording of unsolicited AEs is only from Day 1 to Day 30 post-
vaccination 
In Section 8.3.1, Table 29, Timeframes for collecting and reporting of safety 
information – Phase II (Sourcing): 
** Including COVID-19 infection-related AEs; Recording of unsolicited AEs is only from Day 1 to Day 30 post-
vaccination  
In Section 9.1.2.1 Superiority of vaccine effectiveness of the 
 vaccine 
(
) when administered at 0,2- or 0,6-m schedule compared to the 
Control vaccine (MenB) 
Superiority of 
 to Control vaccine (MenB) will be demonstrated if the 
Lower Limit (LL) of the 2-sided 95% 97.5% Confidence Interval (CI) for the group 
difference in percentages of samples with bactericidal serum activity against a randomly 
selected panel is above 5%. 
In Section 9.1.2.2 Immunological non-inferiority of 
 vaccine 
 
 when administered at 0,2- or 0,6-m schedule compared to the Control 
vaccine (MenACWY) 
Immunological non-inferiority of 
 vaccine to Control (MenACWY) will 
be demonstrated if the LL of the 2-sided 95% 97.5% CI for the group difference in 
percentages of participants achieving a 4-fold rise in hSBA titres is above -10% for each 
serogroup. 
In Section 9.2 Sample size determination 
Participants who withdraw from the study will not be replaced. 
In Section 9.4.2 Primary endpoint(s) – Phase II (Formulation and Schedule-finding) 
Primary Endpoint 
Statistical Analysis Methods 
Superiority of 
effectiveness 
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Primary Endpoint 
Statistical Analysis Methods 
Immunological non-
inferiority 
Safety  
In Section 10.3.8 Recording and follow-up of AEs, SAEs, AESIs and pregnancies: 
• 
Verify completed eDiaries during discussions with the participant/participant’s 
parent(s)/LAR(s) on: 
− 
Visit 3 (Day 31) and Visit 4 (Day 61) – Phase I 
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− 
Visit 2 (Day 31), Visit 4 (Day 181) and Visit 5 (Day 211) – Phase II, 
Formulation and Schedule finding, 
 
 groups 
− 
Visit 2 (Day 31) and Visit 5 (Day 211) – Phase II, Formulation and Schedule 
finding, Control group 
− 
Visit 2 (Day 31) and Visit 3 (Day 61) – Phase II, Sourcing. 
10.10.3. 
Protocol amendment 2 
Detailed description of current Protocol amendment: New text is shown in bold italics 
and deleted text is shown in strikethroughs. 
In the Title page: 
Other study intervention(s) 
Phase I 
• 
Placebo 
Phase II 
• 
GSK’s meningococcal group B vaccine 
(Bexsero) 
• 
GSK’s combined meningococcal groups A, C, Y 
and W-135 conjugate vaccine (Menveo) 
• 
GSK’s combined reduced antigen content 
diphtheria-tetanus toxoids and acellular pertussis 
vaccine (Tdap) (Boostrix) 
• 
Placebo 
Detailed title in Title page, Protocol Amendment 2 Sponsor Signatory Approval and 
Protocol Amendment 2 Investigator Agreement: 
Title 
A Phase I/II, observer-blind, randomised, controlled 
study to assess the safety, effectiveness and immune 
response of meningococcal combined ABCWY 
vaccine when administered to healthy adults (Phase 
I) and to healthy adolescents and adults (Phase II). 
In Section 1.3, Schedule of activities (Table 1, Table 3 and Table 5): 
Post-injection assessment (30 
minutes) 
(as per Table) 
See Section 10.3.8.1 for more information 
^ Procedure to be performed prior to study intervention administration 
In Section 2.2, Background: 
The Meningococcal Group B Vaccine (Bexsero) contains
 
 
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 Bexsero is immunogenic against the 
majority of circulating meningococcal serogroup B strains and has acceptable 
reactogenicity and safety profiles when administered to individuals across age groups. 
The vaccine is currently approved in more than 40 countries worldwide. Although the 
meningococcal group B vaccine was developed for individuals aged 2 months and older, 
the actual age range for which this recommendation extends varies depending on the 
approval from different health authorities. 
In Section 2.3, Benefit/Risk assessment: 
Detailed information about the known and expected benefits and risks and expected 
adverse events of Bexsero (MenB), and Menveo (MenACWY) and Boostrix (Tdap) 
vaccine can be found in the Prescribing Information or Summary of Product 
Characteristics. 
As with all injectable vaccines, immediate systemic allergic reactions to vaccination 
can occur. In order to be able to treat participants with an immediate systemic allergic 
reaction to vaccination, all participants will need to remain under close observation for 
at least 30 minutes after each study intervention (as per the phase in which they are 
participating: Visit V1 and Visit V3 in Phase I, Visit V1, Visit V3 and Visit V4 in Phase 
II Formulation and Schedule-Finding and Visit V1 and Visit V2 in Phase II 
Sourcing). Refer to Section 6.1. 
In terms of study procedures, blood sampling is associated with a risk of syncope, 
dizziness, local reactions and infection after or during venepuncture. For this reason, 
blood samples in this study will be obtained by a trained professional and medical 
assistance will be available. The potential risk of feeling faint, experiencing mild local 
pain, bruising, irritation or redness at the site where blood was taken, is mentioned in the 
Informed Consent Form. Appropriate medical treatment will be readily available. 
In Section 3, Objectives and endpoints: 
Note 1: MenB immune response will be assessed against N. meningitidis serogroup B 
indicator strains 
 
 
 
 
 
 
 
In Section 4.1.2.1, Phase II: Formulation and Schedule-finding: 
Phase II (Formulation and Schedule-finding) will include 5 study groups, with a 
staggered enrolment (45 participants for safety lead-in and 840 955 participants 
thereafter) of a total of 885 1000 participants (Figure 2): 
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• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,6-months) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,2-months) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,6-months) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,2-months) schedule.  
The above 4 groups will also receive 1 vaccination each of the combined tetanus, 
diphtheria, and pertussis (Tdap, Boostrix) vaccine and injection of placebo, according to 
the schedule described in Figure 2. 
• 
Control: Participants will receive 2 vaccinations of MenB vaccine (Bexsero) in a 
(0,6-months) schedule and a single vaccination of MenACWY vaccine (Menveo). 
They will also receive 1 vaccination of Tdap injection of placebo. 
For more detailed information on study groups and treatments administered, Refer to 
Table 9 and Table 12.  
The schedule of activities in Phase II (Formulation and Schedule-finding) of the study is 
described in Table 3. 
 
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Abbreviation: N, number of participants; V, clinic visit; D, day; iSRC, internal safety review committee; PC, phone 
contact; BS, blood sample. 
^ The phone call at Day 8 is only for the first 45 participants (15 participants in 
, 5 participants in 
, 15 participants in 
, 5 participants in 
 and 5 participants in the Control 
groups).  
* The outcome of the iSRC will impact the next study intervention at Month 4. The Month 1 blood sampling will proceed 
as planned 
Note 1: Blood draw at Visit 6 Month 18 will be used only for assessment of tertiary objectives. 
Note 2: This figure represents the main aspects of the study design. Refer to Table 3, Schedule of activities, for details 
on all visits and contacts 
Note 3: The Phase II (Formulation and Schedule-finding) is partially blinded. Study conduct and data collection 
in groups 
 will be observer-blind while in 
group Control it will be open-label. 
Note 3 4: If local regulations allow and quality of study procedures is maintained, participant(s) can be offered remote 
visits (e.g. home visits) for the collection of biological samples and/or study intervention administration (except for Visit 
V1 which will always be a clinic visit). These remote visits must be performed by qualified study staff/ HCPs. Refer to 
the SoA (Table 3) for the timing of these visits. Details of how these visits will be conducted are outlined in the SPM. 
Refer to Section 8 (decentralised study procedures) for details 
Note 4 5: Refer to Section 8 for information on study procedures during special circumstances. 
If the decision is “go”, further vaccination at Month 4 and other study procedures 
following that will continue in these groups along with continuing to recruit participants 
with a randomisation ratio of 1:1:1:1:1 (168 191 in each group) to reach the target total 
sample of 840 955 participants. Refer to Table 9 for total number of participants per 
group. 
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Table 9 
Study groups, intervention and blinding – Phase II (Formulation and 
Schedule-finding) 
Study groups 
Number of 
participants 
Age 
(Min-Max)  
Study intervention(s) 
Blinding 
183 206 
10 – 25 yoa 
 
Observer-blinded 
Tdap 
NaCl 
173 196 
10 – 25 yoa 
 
Tdap 
NaCl 
183 206 
10 – 25 yoa 
 
Tdap 
NaCl 
173 196 
10 – 25 yoa 
 
Tdap 
NaCl 
Control 
173 196 
10 – 25 yoa 
MenACWY 
Observer-blinded 
Open-label 
rMenB+OMV NZ 
Tdap NaCl 
In Section 4.1.2.1, Phase II: Sourcing: 
The blood sourcing part of the Phase II study will include 2 groups (randomised 1:1), 
with a parallel enrolment of a total of 126 226 participants (Figure 3): 
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,1-month) schedule.  
• 
: Participants will receive 2 vaccinations of the 
 
vaccine in a (0,1-month) schedule.  
For more detailed information on study groups and treatments administered, Refer to 
Table 10 and Table 13. 
The schedule of activities in the Phase II (sourcing) is described in Table 5. 
Figure 3 
Study design overview – Phase II (Sourcing) 
 
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Table 10 
Study groups, intervention and blinding – Phase II (Sourcing) 
Study groups 
Number of 
participants 
Age 
(Min-Max) 
Study intervention(s)  
Blinding 
 
63 113 
18-40 50 yoa 
 
Observer-blinded 
 
63 113 
18-40 50 yoa 
 
In Section 4.2, Scientific rationale for study design: 
The Tdap vaccine is indicated for the booster immunisation against tetanus, diphtheria 
and pertussis as a single dose in individuals 10 years of age and older. It is a non-
investigational study vaccine, administered to maintain the blinding of the Phase II of the 
study (along with placebo). 
In Section 5.1, Inclusion criteria: 
• 
Phase I and Phase II (Sourcing) only: A male or female between, and including, 18 
and 40 years of age (i.e. 40 years + 364 days) at the time of the first study 
intervention administration. 
• 
Phase II (Sourcing) only: A male or female between, and including, 18 and 50 
years of age (i.e. 50 years + 364 days) at the time of the first study intervention 
administration. 
• 
Phase II (Formulation and Schedule-finding) only: Participants who have 
received previous doses of tetanus, diphtheria, and pertussis vaccine can participate 
in the study if they have received it at least 5 years prior to informed consent (and 
assent, as applicable). 
In Section 5.2 Exclusion criteria, in Section 5.2.1, Medical conditions: 
• 
Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive 
days within 3 months prior to study vaccination until the last blood sampling visit for 
Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation and 
Schedule-finding). This will mean for adult participants prednisone or equivalent  
20 mg/day, and for paediatric participants 0.5 mg/kg/day or 20 mg/day, 
whichever is the maximum dose. This will mean prednisone equivalent ≥20 mg/day 
 
(N=113)
 
(N=113)
V1 D1
Month 0
V2D31
Month 1
V3 D61
Month 2
PC D211
Month 7
Phase II: Blood sourcing
Randomization: 
1:1
N (total) = 226
BS
BS
BS

BS
BS
BS

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for adult participants/ ≥0.5 mg/kg/day with maximum of 20 mg/day for paediatric 
participants. Inhaled and topical steroids are allowed.  
In Section 5.2 Exclusion criteria, in Section 5.2.2, Prior/Concomitant therapy: 
• 
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 the first study intervention dose(s) until the last blood sampling visit 
for Phase I and Phase II (Sourcing) and Visit 5 (Day 211) for Phase II (Formulation 
and Schedule-finding). For corticosteroids, this will mean for adult participants 
prednisone or equivalent  20 mg/day, and for paediatric participants 0.5 mg/kg/day 
or 20 mg/day, whichever is the maximum dose prednisone equivalent ≥20 mg/day 
for adult participants/ ≥0.5 mg/kg/day with maximum of 20 mg/day for paediatric 
participants. Inhaled and topical steroids are allowed. 
In Section 5.5, Criteria for temporarily delaying enrolment/ randomisation/ study 
intervention administration/blood sampling: 
* In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a 
pandemic) is organised by the public health authorities, outside the routine immunisation 
program, the time period described above can be reduced if necessary for that vaccine 
provided it is licensed and used according to its Prescribing Information and according to 
the local governmental recommendations and provided a written approval of that the 
Sponsor is obtained notified accordingly. 
In Section 6.1, Study intervention(s) administered: 
Table 11 
Study intervention administered – Phase I 
Study 
intervention 
name: 
Placebo 
Type  
Biologic product  
Biologic product  
Not 
applicable  
Product 
category 
Combination 
Combination 
Combination 
Type of 
intervention 
Study  
Study  
Control 
 
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Table 12 
Study intervention administered – Phase II (Formulation and Schedule-finding) 
Study 
interve
ntion  
Bexsero  
Menveo* 
Boostrix (Ex-
US 
formulation)3 
Boostrix (US 
formulation)3 
Placebo 
(saline) 
Formul
ation† 
Sodium 
chloride 
(NaCl) 
(0.9%); 
Water for 
injections 
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Study 
interve
ntion  
Bexsero  
Menveo* 
Boostrix (Ex-
US 
formulation)3 
Boostrix (US 
formulation)3 
Placebo 
(saline) 
Dose 
Form/ 
Present
ation 
Solution for 
injection/ 
Syringe 
Type 
Biologic product 
Biologic product 
Biologic 
product 
Biologic product 
Biologic product 
Not 
applicable 
Produc
t 
categor
y 
Combination 
Combination 
Combination 
Biological 
 
Combinatio
n 
No of doses 
2 
- 
- 
- 
1 
1 
2 
- 
- 
- 
1 
1 
- 
2 
- 
- 
1 
1 
- 
2 
- 
- 
1 
1 
Control 
- 
 
2 
1 
1 
- 1 
Volume 
to be 
admini
stered^  
Type of 
interve
Study 
Study 
Control 
Control 
Concomitant 
Concomitant 
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Study 
interve
ntion  
Bexsero  
Menveo* 
Boostrix (Ex-
US 
formulation)3 
Boostrix (US 
formulation)3 
Placebo 
(saline) 
ntion 
Route 
of 
admini
stration 
Intramuscular use 
Intramuscular use 
Intramuscular 
use 
Intramuscular use 
Intramuscular use 
Intramuscula
r use 
Admini
stration 
site 
 
 
 
 
 
 
Locatio
n 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Lateralit
y*** 
Non-dominant*** 
Non-dominant*** 
Non-
dominant*** 
Dominant 
Non-dominant*** 
Dominant 
Non-
dominant 
Packag
ing, 
labellin
g and 
TM: 
Refer to SPM for details 
Manufa
cturer: 
GSK 
GSK 
GSK 
GSK 
GSK 
GSK 
3 The US formulation of Boostrix will be administered to participants included in the study in US. In all other countries, participants will receive the ex-US formulation of the same 
vaccine 
*** (Not for Visit 1 in Control group) 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 
 
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Table 13 
Study intervention administered – Phase II (Sourcing) 
Study intervention name: 
Type 
Biologic product 
Biologic product 
Product category 
Combination  
Combination 
Type of intervention 
Study  
Study  
In Section 6.3.2, Randomisation to study intervention: 
There are 2 randomisation processes for each participant in the study: 
• 
Randomisation to study intervention 
• 
 
In Section 6.3.3, Intervention allocation to the participant: 
It is recommended to have a balance between age category during enrolment in Phase 
II (Formulation and Schedule-finding). 
In Section 6.3.4, Allocation of participants to assay subsets: 
Refer to Section 9 for details on the allocation as per the MenACWY priming and the 
analysis planned. Blood samples will be collected as detailed in Section 8.1.1.1. Refer to 
Section 10.2.1 for details on allocation of participants for safety laboratory assays. 
Refer to Section 8.1.3 for details on allocation of participants to assay subsets and 
 
Note: The following section has only been moved from 6.3.4 to 10.2.2.1.1 therefore 
not presented as new text. 
In Section 6.3.5, Blinding and unblinding: 
6.3.5.1 
Phase I and Phase II (Sourcing) 
Data will be collected in an observer-blind manner. To do so, study intervention(s) 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, efficacy). 
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There 
will be no link between the study intervention and the identity of the participant. 
6.3.5.2 
Phase II (Formulation and Schedule-finding) 
This phase is partially blinded. Data in the 4 ABCWY groups will be collected in an 
observer-blind manner. To do so, study intervention(s) 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, 
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1 9 5  
effic a cy). D at a i n t he C o ntr ol gr o u p will be c ollecte d i n a n o pe n -l a bel m a n ner i.e. st u dy 
p artici p a nts, i nvesti g at or a n d site st aff pers o n nel will be a w are of t he tre at m e nt 
a d mi nistere d as 2 st u dy i nterve nti o ns are a d mi nistere d at Visit V 1.  
T he l a b or at ory i n c h ar ge of t he l a b or at ory testi n g will be bli n de d t o t he tre at m e nt as 
well as t o t he s u bject n u m ber. T here will be n o li n k bet wee n t he st u dy i nterve nti o n 
gr o u ps a n d t he i de ntity of t he p artici p a nt. I n a d diti o n, f or e ac h s a m ple, a differe nt 
r a n d o mly selecte d s u bject c ode will be use d at e ac h ti m e p oi nt. T his s u bject c o di n g will 
preve nt t he testi n g l a b or at ory pers o n nel fr o m li n ki n g t he c o nsec utive ti me p oi nts t o a 
s pecific s u bject.  
Refer t o t he S P M f or a d diti o n al i nf or m ati o n a b o ut det ails o n st u dy bli n di n g.  
I n Secti o n 8. 1. 1. 1, Bl o o d s a m ple:  
T a ble 2 0  
Bl o o d s a m ples at P h ase II ( F o r m ul ati o n a n d sc he d ule -fi n di n g) 
S a m pl e 
t y p e 
Q u a ntit y  
U nit  
Ti m e p oi nt  
S u b s et n a m e/ 
Gr o u p  
D a y  
Bl o o d  
A p pr o xi m at el y 1 5  
m L  
Visit V1 (*)  
All p artici p a nts  
D ay 1  
Bl o o d  
A p pr o xi m at el y  1 5  
m L  
Visit V2 (**)  
All  p artici p a nts  
D ay 3 1  
Bl o o d  
A p pr o xi m at el y  3 0  
m L  
Visit V5 ( Post -Vacc 2)  
All p artici p a nts  
D ay 2 1 1  
Bl o o d  
A p pr o xi m at el y  3 0  
m L  
Visit V6 (^)  
All p artici p a nts  
D ay 5 4 1  
I n Secti o n 8. 1. 2, L a b or at or y ass a ys: 
T a ble 2 1  
L a b or at or y ass a ys –  P h ase I a n d II  
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1 9 6  
I n Secti o n 8. 2. 1. 1, C ollecti o n of de m o gr a p hic d at a: 
F or P hase II ( F or m ulati o n a n d Sc he d ule -fi n di n g) o nl y: At Visit V 1 i n t he C o ntr ol gr o u p, 
t he partici pa nt recei ves 2 i njecti o ns, o ne i n eit her ar m. T heref ore, i n or der t o ass ociate t he 
s olicite d e ve nts re p ort e d t o t he vacci ne a d mi nistere d i n t hat ar m, t he d o mi na nt ar m (left 
or ri g ht) will be rec or de d i n t he e C R F ( Ta ble 1 2).  
I n Secti o n 8. 2. 1. 5, W ar ni n gs a n d prec a uti o ns t o v acci n ati o n: 
Refer t o t he a p pr o ve d pr o d uct la bel/ pac ka ge i nsert of Be xser o a n d  Me n ve o. a n d B o ostrix . 
I n Secti o n 8. 2. 2. 1, S afet y d at a re vie w: 
Ste p 3: F oll o wi n g t he sec o n d vacci nati o n i n 
 gr o u ps at Da y 
3 0  3 1 , all a vaila ble safet y dat a fr o m all partici pa nts c ollecte d u p t o Da y 3 8 will be 
e val uate d b y t he i S R C.  
Fi g ure 5  
Ste p -wise a p pr o ac h f or s afet y re vie w i n P h ase II ( F o r m ul ati o n a n d 
Sc he d ule -fi n di n g) 
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If the decision is “go”, the enrolment in all groups will continue with a randomisation 
ratio of 1:1:1:1:1 to the target total sample of 885 1000 participants and the 
administration of the second vaccination at Month 4 will take place in the 45 participants 
as per their group allocation. 
Continuous monitoring during the study by the study team will allow for ad-hoc iSRC 
reviews and/or enrolment hold if any safety concern is identified or a substantial trend 
emerges outside of the scheduled unblinded safety reviews. 
In Section 8.2.2.1.2, Outcome of safety evaluation 
If a safety signal is observed during the safety evaluations or if any of the holding rules 
2a-c is met (Table 25), the iSRC Chair (or his/her representative) is responsible for the 
urgent communication to within GSK, including the rationale for the decision to put the 
study intervention administration on hold or not. 
In Section 8.2.2.1.3, Study holding rules: 
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Table 26 
Study holding rules – Phase II (Formulation and Schedule-finding) 
Holding 
rule 
Event 
Number or % of 
participants needed to 
trigger the hold 
1a 
Death or any life-threatening SAE regardless of causality 
≥ 1 
2a 
Any Grade 3 solicited administration site event (lasting 48h or 
more) in the investigational group, with an event onset within the 7-day 
(Day 1-7) post-vaccination period 
≥ 20% 
2b 
Any Grade 3 solicited systemic event (lasting 48h or more) in an 
investigational group, with an event onset within the 7-day (Day 1-7) 
post-injection period 
≥ 20% 
2c 
Any Grade 3 unsolicited AE in an investigational group, that can be 
reasonably attributed to the vaccination, with an event onset within the 
7-day (Day 1-7) post-injection period  
≥ 20% 
Abbreviations: AE, adverse event; SAE, serious adverse event; TBD, To be determined. 
In Section 8.3.1, Time period and frequency for collecting AE, SAE and other safety 
information  
Table 27 
Timeframes for collecting and reporting of safety information – Phase I 
Event 
On 
V1* 
 
V1 
V2 
 
V3 
PC 
V4 
 
PC 
Phase I 
conclusion 
 
D1*** 
D7 
D31 
D37 
D61 
 
D151 
D 211 (PC) 
In Section 8.3.3,  
Table 30 
Timeframes for submitting SAE, pregnancy and other events reports to 
GSK  
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours*  
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
Pregnancies 
2 weeks 24 
hours* 
electronic pregnancy report  
2 weeks 24 
hours* 
electronic pregnancy report 
AESIs  
24 hours**, ‡‡  
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of an AESI  
‡‡ The investigator will be required to confirm review of the SAE/AESI causality by ticking the ‘reviewed’ box in the 
electronic Expedited Adverse Events Report within 72 hours of submission of the SAE/AESI 
In Section 8.3.4, Treatment of adverse events: 
Any medication administered for the treatment of an SAE/AESI should be recorded in 
the Expedited Adverse Event Report of the participant’s eCRF screen (refer to the 
Section 10.3.10.1). 
Section 8.3.6, Medical device deficiencies has been added: 
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Section 8.3.6 Medical device deficiencies 
The study interventions (
  Bexsero and placebo) are combination 
products constituted of a device and biologic product (e.g., pre-filled syringes). Refer to 
Glossary of terms for the definition of a combination product and a medical device 
deficiency. 
8.3.6.1. 
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 GSK. This applies to 
any medical device provided for the conduct of the study.  
Device deficiencies will be reported to GSK within 24 hours after the investigator 
determines that the event meets the protocol definition of a device deficiency. Refer to 
Section 10.7 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 related of the device deficiency to the incident. Follow-up 
applies to all participants, including those who discontinue study intervention or the 
study. 
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator and reported to GSK within 24 hours. 
8.3.6.2. 
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 to GSK. GSK has a legal responsibility to notify 
appropriate regulatory authorities and other entities about safety information linked to 
medical devices being used in clinical studies. Refer to section  10.7.3 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. 
In Section 9.2, Sample size determination, 9.2.2, Phase II (Formulation and 
Schedule-finding): 
Eight hundred and eighty-five (885) A thousand (1000) participants are to be enrolled in 
5 arms of Phase II of the study, 183 206 participants for both 
 
 arms and 173 196 participants for 
 and 
Control arms. It is assumed that 15% of the participants will drop out or will not 
contribute to an evaluable result for the primary endpoints resulting in about 150 170 
evaluable participants per arm. 
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In Section 9.2.2.1, Superiority of vaccine effectiveness of the 
 vaccine 
(
) when administered at 0,2- or 0,6-m schedule compared to the 
Control vaccine (MenB) 
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In Section 9.2.3, Phase II (Sourcing): 
One Two hundred and twenty-six (126 226) participants are to be enrolled in 2 arms of 
Phase II (Sourcing) of the study, 63 113 participants each in 
 
 group (1:1 randomisation). 
In Section 9.4.2, Primary endpoint(s) – Phase II (Formulation and Schedule-
finding): 
Primary Endpoint 
Statistical Analysis Methods 
Superiority of 
effectiveness 
In Section 9.4.4, Secondary endpoint(s) – Phase II (Formulation and Schedule-
finding): 
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Secondary Endpoint 
Statistical Analysis Methods 
Description of the 
distribution of B 
strains killed  
Immune response to 
serogroup B 
indicator strains 
Immune response to 
serogroups A,C,W 
and Y serogroups 
 
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Secondary Endpoint 
Statistical Analysis Methods 
 
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T erti ar y E n d p oi nt  
St ati sti c al A n al y si s M et h o d s  
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In Section 10.1.4, Data protection: 
GSK will ensure protection of the personal data of the investigator and site staff which is 
collected within the framework of and for the purpose of the study, in accordance with 
the Data Privacy Notice that will be sent to the site staff. 
The bullet format has been removed for the above as it is an independent statement. 
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In Section 10.3.8.1, Time period for collecting and recording AEs, SAEs, AESIs and 
pregnancies: 
All post-study intervention immediate reactions observed within the observational 
period of at least 30 minutes after each injection, including signs or symptoms of 
anaphylaxis, allergic phenomena (such as rashes, itching, or other allergic 
manifestations), solicited events, unsolicited events and body temperature, will be 
recorded in the eCRF. 
All solicited events that occur during 7 days (including the day of vaccination) following 
administration of each dose of study intervention (Day 1 to Day 7) must be recorded into 
the eDiary, irrespective of intensity. All other AEs occurring within this time frame 
should be recorded into the appropriate section of the eCRF, irrespective of their 
intensity or whether or not they are considered related to the study intervention. 
In Section 10.3.9.3, Medically attended visits: 
For each solicited and unsolicited AE the participant experiences (Refer to Table 27, 
Table 28 and Table 29), the participant/participant’s parent(s)/LAR(s) will be asked if 
he/she/the participant received medical attention (defined as hospitalisation, or an 
otherwise unscheduled visit to or from medical personnel for any reason, including 
emergency room visits). This information will be recorded in the eDiary/ eCRF. 
In Section 10.3.10.1, Events requiring expedited reporting to GSK: 
The investigator will be required to confirm the review of SAE causality within 72 
hours of submission of the SAE. 
Added:  
Section 10.7, Appendix 7: Definition of medical device AE, adverse device effect 
(ADE), serious adverse device effect (SADE) and unanticipated SADE (USADE) 
10.7.1 
Definition of medical device AE and adverse device effect (ADE) 
• 
Medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether considered related to a medical device or not. An AE can 
therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a 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 an 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. 
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10.7.2 Definition of medical device SAE, SADE and USADE 
A medical device SAE is any serious adverse event that: 
a. Led to death  
b. 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 hospitalisation. Planned hospitalisation 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. 
c. 
Led to foetal distress, foetal death or a congenital abnormality or birth defect 
d. Is a suspected transmission of any infectious agent via a medicinal product. 
Serious Adverse Device Effect (SADE) definition 
• A SADE is defined as an adverse device effect 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 or circumstances had been less fortunate. 
Unanticipated SADE (USADE) definition 
• 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is a 
serious adverse device effect that by its nature, incidence, severity or outcome 
has not been identified in the current version of the IB. 
10.7.3 
Recording and reporting of medical device AE, ADEs, SADEs and USADE 
• 
Any device deficiency must be reported to GSK within 24 hours after the 
investigator determines that the event meets the definition of a device deficiency. 
• 
E-mail/Facsimile transmission of the paper ‘Medical device or combination 
product with device deficiency/incident report form’ is the preferred method to 
transmit this information to the sponsor. 
• 
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. 
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• 
Contacts for reporting can be found in Section 8.3.3.1. 
GSK will review all device deficiencies, 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. 
In Section 10.9.1, List of abbreviations  
ADE: 
Adverse Device Effect 
SADE: 
Serious Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
In Section 10.9.2, Glossary of terms 
Blinding: 
A procedure in which 1 or more parties to the trial 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 
trial, and only when the data are cleaned to an 
acceptable level of quality will appropriate personnel be 
unblinded or when required in case of a serious adverse 
event.  
For Phase I and Phase II Sourcing: In an observer-
blind study, the participant, the site and sponsor 
personnel involved in the clinical evaluation of the 
participants are blinded while other study personnel may 
be aware of the treatment assignment.  
For Phase II Formulation and Schedule-finding: 
Partially-blind is to be used for study designs with 
different blinding levels between different groups, e.g. 
double-blinded consistency lots which are open with 
respect to the control group. 
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. 
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10.10.4. 
Protocol amendment 1 
Detailed description of the Protocol amendment (Amendment 1): This is a country-
specific protocol amendment pertaining to Phase 1 part (conducted in Australia) of this 
seamless Phase I/II study. The blood tubes which are required for collection of blood 
samples for safety laboratory evaluation in Phase 1 hold a maximum volume of 7 mL and 
it is not possible to measure 6 mL volume in these tubes. Therefore in order to avoid the 
risk of collecting lower volume of blood, this protocol has been amended to document the 
change in the blood sample volume for the safety laboratory evaluation (from 6 mL to 
7 mL). 
New text is shown in bold italics and deleted text is shown in strikethroughs. 
In Section 1.3, Schedule of Activities, under Table 1 Schedule of Activities – Phase I 
Table 1 
Schedule of Activities – Phase I 
Type of contact 
Visit Visit Visit PC Visit PC PC 
Notes 
Visit/Phone call no. 
V1 V2 V3 T1 V4 T2 T3 
Timepoint(s) 
 [refer to Table 2 for visit windows] 
Day 
1 
Day 
8 
Day 
31 
Day 
38 
Day 
61 
Day 
151 
Day 
211 
Blood sampling for safety 
laboratory evaluation  
● 
● 
 
 
 
 
 
Blood volume of ~6 ~7 mL will be collected. See 
Section 8.1.1.1 for more information 
In Section 8.1.1.1, Blood Sample: 
Phase I: An overall blood volume of 240 mL per participant will be collected over the 
course of the Phase I part of the study. An additional 6 7 mL of blood will be collected at 
Visit V1 and Visit V2 from all participants for the safety laboratory evaluation. Refer to 
Table 18 for details. 
Table 18 
Blood samples at Phase I 
Sample 
type 
Quantity 
Unit 
Timepoint 
Subset name/ 
Group 
Day 
Blood 
Approximately 80 
mL 
Visit V1 
; 
All participants 
Day 1 
Blood 
Approximately 80 
mL 
Visit V3 (
 
All participants 
Day 31 
Blood 
Approximately 80 
mL 
Visit V4 (
 
All participants 
Day 61 
Blood 
Approximately 6 7 
mL 
Visit V1  
All participants 
Day 1 
Blood 
Approximately 6 7 
mL 
Visit V2 
All participants 
Day 8 
Pre-Vacc, Pre-vaccination timepoint; Post-Vacc, Post-vaccination timepoint 
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11. 
REFERENCES 
Cohn A and MacNeil J. The Changing Epidemiology of Meningococcal Disease. Infect 
Dis Clin North Am. 2015; 29(4):667-77.  
Halperin SA, Bettinger JA, Greenwood B, Harrison LH, Jelfs J, Ladhani SN, et al. The 
changing and dynamic epidemiology of meningococcal disease. Vaccine. 2012; 30 Suppl 
2:B26-B36.  
Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal disease. 
Vaccine. 2009;27 Suppl 2: B51-B63. 
Heckenberg S, Brouwer M, van de Beek D. Bacterial Meningitis. Handbook of Clinical 
Neurology (121) Chapter 93. 2014. 
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 two rates. Statistics in Medicine 
1985; 4(2):213-26. 
US Food and Drug Administration (FDA). Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials: Guidance for 
industry, 2007. Center for Biologics Evaluation and Research - 2005D-0155. 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/toxicity-
grading-scale-healthy-adult-and-adolescent-volunteers-enrolled-preventive-vaccine-
clinical (Accessed on 18 September 2020). 
Welsch A et al. Breadth of coverage against a panel of 110 invasive disease isolates, 
immunogenicity and safety for 2 and 3 doses of an investigational MenABCWY vaccine 
in US adolescents – Results from a randomized, controlled, observer-blind phase II study. 
Vaccine 2018; 36(35):5309-5317. 
World Health Organization (WHO). Laboratory testing for 2019 novel coronavirus 
(2019-nCoV) in suspected human cases. Interim guidance. WHO, 2019 [cited 11-SEP-
2019] Available from: https://www.who.int/publications/i/item/10665-331501 
World Health Organization (WHO). WHO COVID-19 Case Definition. WHO, 2020 
[cited 11-SEP-2019] Available from: https://www.who.int/publications/i/item/WHO-
2019-nCoV-Surveillance_Case_Definition-2020.1 
World Health Organization (WHO). Coronavirus disease (COVID-19) pandemic. 
WHO website. Accessed on 18 March 2022. 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019. 
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Signature Page for  212458 TMF-14522581 v1.0
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Date of signature: 11-Apr-2022 11:45:07 GMT+0000
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