A Phase I/II, Observer-blind, Randomised, Placebo-controlled Study to Assess Safety, Immunogenicity and Efficacy of GSK S. Aureus Candidate Vaccine When Administered to Healthy Adults (Dose-escalation) and to Adults 18 to 64 Years of Age With a Recent S. Aureus Skin and Soft Tissue Infection (SSTI)
Phase: PHASE2
Conditions: Infections, Soft Tissue
Sponsor: GlaxoSmithKline

Protocol Amendment 6
Study ID:  208833
Official Title of Study: A Phase I/II, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and efficacy of GSK S. aureus 
candidate vaccine when administered to healthy adults (dose escalation) and to 
adults 18 to 64 years of age with a recent S. aureus skin and soft tissue infection 
(SSTI)
NCT number: NCT04420221
Date of Document: 11-Oct-2022

CONFIDENTIAL 
208833 (STAPH AUREUS BIOCONJ-001 STG) 
Protocol Amendment 6 Final 
6 October 2022 
1 
 
Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA 
Rue de l’Institut 89,  
1330 Rixensart, Belgium 
Primary Study vaccine 
• 
GlaxoSmithKline (GSK) Biologicals 
Staphylococcus aureus candidate vaccine (S. 
aureus candidate vaccine [Sa-5Ag adjuvanted]) 
Other Study vaccine(s) 
• 
Placebo (Saline) 
• 
GlaxoSmithKline (GSK) Biologicals Sa-5Ag 
half dose non-adjuvanted 
• 
GlaxoSmithKline (GSK) Biologicals Sa-5Ag 
non-adjuvanted 
• 
GlaxoSmithKline (GSK) Biologicals Sa-5Ag 
half dose adjuvanted 
eTrack study number and 
abbreviated title 
208833 (STAPH AUREUS BIOCONJ-001 STG) 
Investigational New Drug 
(IND) number 
IND 19408 
EudraCT number 
2021-006215-29 
Date of protocol 
Final Version 1: 4 September 2019 
Date of protocol amendment 
Amendment 1 Final: 26 May 2020 
Amendment 2 Final: 2 April 2021 
Amendment 3 Final: 15 June 2021 
Amendment 4 Final: 30 November 2021 
Amendment 5 Final: 22 June 2022 
Amendment 6 Final: 6 October 2022 
Short title 
Safety, immunogenicity and efficacy of GSK S. 
aureus candidate vaccine (GSK3878858A) when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 64 years of age with a recent S. 
aureus skin and soft tissue infection (SSTI). 
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CONFIDENTIAL 
208833 (STAPH AUREUS BIOCONJ-001 STG) 
Protocol Amendment 6 Final 
6 October 2022 
2 
eTrack study number and 
abbreviated title 
208833 (STAPH AUREUS BIOCONJ-001 STG) 
Investigational New Drug 
(IND) number 
IND 19408 
EudraCT number 
2021-006215-29 
Title 
A Phase I/II, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity 
and efficacy of GSK S. aureus candidate vaccine 
when administered to healthy adults (dose-
escalation) and to adults 18 to 64 years of age with a 
recent S. aureus skin and soft tissue infection 
(SSTI). 
Co-ordinating author(s) 
(Amended 6 October 2022) 
 (Scientific Writer for GSK) 
Contributing authors 
(Amended 6 October 2022) 
• 
 (CSL) 
• 
 (SDL) 
• 
 (DMQL) 
• 
 (Study Statistician) 
• 
 (Lead Statistician) 
• 
 (CLS CRT-L) 
• 
 (Safety Physician) 
• 
 (Safety Scientist) 
• 
 (GRA) 
GSK Protocol WS v 16.0.1 
©2019 GSK group of companies or its licensor. 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

CONFIDENTIAL 
208833 (STAPH AUREUS BIOCONJ-001 STG) 
Protocol Amendment 6 Final 
6 October 2022 
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Protocol Amendment 6 Sponsor Signatory Approval  
eTrack study number and 
Abbreviated Title 
208833 (STAPH AUREUS BIOCONJ-001 STG) 
Investigational New Drug 
(IND) number 
IND 19408 
EudraCT number 
2021-006215-29 
Date of protocol amendment 
Amendment 6 Final: 6 October 2022  
Title 
A Phase I/II, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and 
efficacy of GSK S. aureus candidate vaccine when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 64 years of age with a recent S. aureus 
skin and soft tissue infection (SSTI). 
Sponsor signatory (Amended 
6 October 2022) 
Michele Pellegrini 
Clinical 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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208833 (STAPH AUREUS BIOCONJ-001 STG) 
Protocol Amendment 6 Final 
6 October 2022 
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Protocol Amendment 6 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 will comply with the terms of the site agreement. 
• 
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 vaccine(s) 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 subject. 
• 
To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s).  
• 
To co-operate with a representative of GSK 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 vaccine(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. 

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208833 (STAPH AUREUS BIOCONJ-001 STG) 
Protocol Amendment 6 Final 
6 October 2022 
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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 
course of 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 other documents 
required by regulatory agencies for this study. 

CONFIDENTIAL 
208833 (STAPH AUREUS BIOCONJ-001 STG) 
Protocol Amendment 6 Final 
6 October 2022 
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eTrack study number and 
Abbreviated Title 
208833 (STAPH AUREUS BIOCONJ-001 STG) 
Investigational New Drug 
(IND) number 
IND 19408 
EudraCT number 
2021-006215-29 
Date of protocol amendment 
Amendment 6 Final: 6 October 2022 
Title 
A Phase I/II, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and 
efficacy of GSK S. aureus candidate vaccine when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 64 years of age with a recent S. aureus 
skin and soft tissue infection (SSTI). 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 

CONFIDENTIAL 
208833 (STAPH AUREUS BIOCONJ-001 STG) 
Protocol Amendment 6 Final 
6 October 2022 
7 
SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA 
Rue de l’Institut 89, 1330 Rixensart, Belgium 
2. Sponsor Medical Expert for the Study 
Refer to the local study contact information document. 
3. Sponsor Study Monitor 
Refer to the local study contact information document. 
4. Sponsor Study Contact for Reporting of a Serious Adverse Event 
GSK Central Back-up Study Contact for Reporting SAEs: refer to protocol Section 
12.5.9.3  
Study Contact for Reporting SAEs: refer to the local study contact information 
document. 
5. GSK Central Safety Physician On-Call Contact information for Emergency 
Unblinding 
GSK Central Safety Physician and Back-up Phone contact: refer to protocol Section 
7.3.1. 

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208833 (STAPH AUREUS BIOCONJ-001 STG) 
Protocol Amendment 6 Final 
6 October 2022 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Table 1 
Document history 
Document 
Date 
Amendment 6 
6 October 2022 
Amendment 5 
22 June 2022 
Amendment 4 
30 November 2021 
Amendment 3 
15 June 2021 
Amendment 2 
2 April 2021 
Amendment 1 
26 May 2020 
Original Protocol 
4 September 2019 
Amendment 6: 6 October 2022 
Overall Rationale for the Amendment: The aim of this protocol amendment is to 
ensure consistency across the different protocol sections related to the interim 
efficacy analysis, with reference to the possibility to continue the enrolment up to 
the planned number of events needed for the key efficacy endpoint evaluation (i.e. 
 
 In 
addition, correction of typographical errors, and minor edits for clarification have 
been made (refer to Section 12.8.1 for information). 
List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief Rationale 
Synopsis; Section 5.2.2 
Update to clarify that “
 
 
 
 
of the targeted total number of 
culture confirmed cases of recurrent 
S. aureus SSTIs are observed…”
To ensure consistency across the 
different protocol sections related to 
the interim efficacy analysis 
Section 10.1.1 Hypotheses related 
to primary and secondary 
objectives 
Update to text linked to hypotheses 
related to primary and secondary 
objectives  
To ensure consistency across the 
different protocol sections related to 
the interim efficacy analysis 
Section 10.1.2 Sample size 
calculation 
Update to text linked to sample size 
calculation and clarification for the 
basis of assumptions  
To ensure consistency across the 
different protocol sections related to 
the interim efficacy analysis 
Section 10.3.7 Interim analyses 
Update to text linked to interim 
analyses 
To ensure consistency across the 
different protocol sections related to 
the interim efficacy analysis 
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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 7 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 8 
1. 
SYNOPSIS ............................................................................................................. 17 
2. 
SCHEDULE OF ACTIVITIES (SOA) ....................................................................... 29 
3. 
INTRODUCTION .................................................................................................... 37 
3.1. 
Study rationale ............................................................................................ 37 
3.2. 
Background ................................................................................................ 37 
3.2.1. 
Skin and soft tissue infections caused by S. aureus ..................... 37 
.................. 38 
3.3. 
Benefit/Risk assessment ............................................................................. 42 
3.3.1. 
Risk assessment .......................................................................... 43 
3.3.2. 
Benefit assessment ..................................................................... 44 
3.3.3. 
Overall Benefit: Risk conclusion ................................................... 44 
4. 
OBJECTIVE(S) AND ENDPOINT(S) ...................................................................... 44 
5. 
STUDY DESIGN .................................................................................................... 46 
5.1. 
Scientific rationale for study design ............................................................. 46 
5.2. 
Overall design ............................................................................................. 47 
5.2.1. 
Dose-Escalation safety lead-in healthy subjects (Phase I) ........... 49 
5.2.2. 
PoP in subjects with recent S. aureus SSTI Group 5a/b 
(Phase II) ..................................................................................... 54 
5.3. 
Number of subjects ..................................................................................... 58 
5.4. 
Subject and study completion ..................................................................... 59 
6. 
STUDY POPULATION ........................................................................................... 59 
6.1. 
Inclusion criteria for enrolment .................................................................... 59 
6.2. 
Exclusion criteria for enrolment ................................................................... 61 
6.2.1. 
Medical conditions ....................................................................... 61 
6.2.1.1. 
Subjects to be enrolled in the dose-escalation 
safety lead-in epochs .................................................. 61 
6.2.1.2. 
Subjects to be enrolled in the proof of principle 
epochs........................................................................ 62 
6.2.2. 
Prior/Concomitant therapy ........................................................... 63 
6.2.3. 
Prior/Concurrent clinical study experience ................................... 64 
6.2.4. 
Other exclusions .......................................................................... 64 
6.3. 
Criteria for temporary delay for enrolment and vaccination ......................... 64 
6.4. 
Screen and baseline failures ....................................................................... 65 
7. 
TREATMENTS ....................................................................................................... 66 
7.1. 
Treatments administered ............................................................................ 66 
7.2. 
Method of treatment assignment ................................................................. 68 
7.2.1. 
Subject identification .................................................................... 68 
7.2.2. 
Randomisation of treatment ......................................................... 68 
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7.2.2.1. 
Treatment allocation to the subject ............................. 68 
7.2.2.1.1. 
Study group and treatment 
number allocation ................................... 68 
7.2.2.1.2. 
Treatment number allocation for 
subsequent doses .................................. 69 
7.3. 
Blinding and unblinding ............................................................................... 69 
7.3.1. 
Emergency unblinding ................................................................. 70 
7.4. 
Handling, storage and replacement of study vaccine(s)/product(s) ............. 71 
7.4.1. 
Storage and handling of study vaccines ....................................... 71 
7.4.2. 
Replacement of unusable vaccine doses ..................................... 72 
7.5. 
Concomitant medication(s)/product(s) and concomitant vaccinations ......... 72 
7.5.1. 
Recording of concomitant medications/products and 
concomitant vaccinations ............................................................. 72 
7.5.2. 
Concomitant medications/products/vaccines that may lead 
to the elimination of a subject from per-protocol analyses ............ 73 
7.6. 
Intercurrent medical conditions that may lead to elimination of a 
subject from per-protocol analyses ............................................................. 74 
7.7. 
Contraindications to subsequent vaccine(s) administration ......................... 74 
7.8. 
Treatment after completion of the study ...................................................... 74 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 74 
8.1. 
General study aspects ................................................................................ 75 
8.2. 
Pre-vaccination procedures ........................................................................ 76 
8.2.1. 
Informed Consent ........................................................................ 76 
8.2.2. 
Collection of demographic data .................................................... 76 
8.2.3. 
Medical/vaccination history .......................................................... 76 
8.2.4. 
Physical examination ................................................................... 76 
8.2.5. 
Pregnancy test ............................................................................. 77 
8.2.6. 
Pre-vaccination body temperature ............................................... 77 
8.3. 
Case definition of recurrent S. aureus SSTI ................................................ 77 
8.4. 
Efficacy and/or immunogenicity assessments ............................................. 78 
8.4.1. 
Use of specified study materials .................................................. 78 
8.4.2. 
Biological samples ....................................................................... 79 
8.4.2.1. 
Sampling for efficacy assessments ............................. 79 
8.4.2.2. 
Blood sampling for immunogenicity response 
assessments .............................................................. 79 
8.4.3. 
Laboratory assays ....................................................................... 81 
8.4.3.1. 
Microbiology assessment for efficacy ......................... 81 
 
 ................... 81 
8.4.4. 
Immunological correlates of protection ......................................... 83 
8.5. 
Safety Assessments ................................................................................... 84 
8.5.1. 
Safety definitions ......................................................................... 84 
8.5.2. 
Time period and frequency for collecting AE and serious 
adverse event (SAE) information ................................................. 84 
8.5.3. 
Method of detecting AEs and SAEs ............................................. 87 
8.5.4. 
Reporting of serious adverse events, pregnancies, and 
other events ................................................................................. 87 
8.5.4.1. 
Contact information for reporting of serious 
adverse events (SAEs), pIMDs, pregnancies 
and study holding rules ............................................... 88 
8.5.4.2. 
Regulatory reporting requirements for SAEs .............. 88 
8.5.5. 
Follow-up of AEs and SAEs ......................................................... 88 
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8.5.6. 
Treatment of adverse events ....................................................... 89 
8.5.7. 
Clinical safety laboratory assessments ........................................ 89 
8.5.8. 
Subject card ................................................................................. 90 
8.6. 
Holding rules and safety monitoring ............................................................ 90 
8.6.1. 
Staggered vaccination ................................................................. 90 
8.6.2. 
Outcome of safety evaluation....................................................... 94 
8.6.3. 
Study holding rules ...................................................................... 94 
8.6.4. 
Risk assessment .......................................................................... 96 
8.6.5. 
Safety review team (SRT) ............................................................ 98 
8.6.6. 
Internal Safety Review Committee (iSRC) ................................... 99 
9. 
DISCONTINUATION CRITERIA ............................................................................. 99 
9.1. 
Discontinuation from the study .................................................................... 99 
9.2. 
Discontinuation of study vaccine(s) ........................................................... 100 
9.3. 
Lost to follow-up........................................................................................ 100 
10. STATISTICAL CONSIDERATIONS ...................................................................... 101 
10.1. 
Sample size determination ........................................................................ 101 
10.1.1. 
Hypotheses related to primary and secondary objectives .......... 101 
10.1.2. 
Sample size calculation ............................................................. 102 
10.2. 
Populations for analyses ........................................................................... 104 
10.3. 
Statistical analyses ................................................................................... 104 
10.3.1. 
Subjects disposition ................................................................... 104 
10.3.2. 
Demography and baseline characteristics analyses ................... 104 
10.3.3. 
Efficacy analyses ....................................................................... 105 
10.3.3.1. Case accountability: ................................................. 105 
10.3.4. 
Immunogenicity analyses ........................................................... 106 
10.3.5. 
Safety analyses ......................................................................... 107 
.................................................................... 107 
.................................................................... 107 
.................................................................... 108 
11. REFERENCES ..................................................................................................... 109 
12. APPENDICES ...................................................................................................... 113 
12.1. 
Appendix 1: Abbreviations, glossary of terms and trademarks .................. 113 
12.1.1. 
List of abbreviations ................................................................... 113 
12.1.2. 
Glossary of terms ....................................................................... 116 
12.2. 
Appendix 2: Clinical and safety laboratory tests ........................................ 119 
 
 ............ 119 
12.2.2. 
Laboratory assays for safety evaluation ..................................... 121 
12.3. 
Appendix 3: Clinical laboratories ............................................................... 122 
12.4. 
Appendix 4: Study governance considerations ......................................... 123 
12.4.1. 
Regulatory and ethical considerations ....................................... 123 
12.4.2. 
Financial disclosure ................................................................... 124 
12.4.3. 
Informed consent process .......................................................... 124 
12.4.4. 
Data protection .......................................................................... 125 
12.4.5. 
Publication policy ....................................................................... 125 
12.4.6. 
Dissemination of clinical study data ........................................... 125 
12.4.7. 
Data quality assurance .............................................................. 126 
12.4.8. 
Source documents ..................................................................... 127 
12.4.9. 
Study and site start and closure ................................................. 127 
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12.5. 
Appendix 5: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting .......................................... 128 
12.5.1. 
Definition of AE .......................................................................... 128 
12.5.1.1. AE Definition............................................................. 128 
12.5.1.2. Events Meeting the AE Definition ............................. 128 
12.5.1.3. Events NOT Meeting the AE Definition ..................... 129 
12.5.2. 
Definition of SAE ........................................................................ 129 
12.5.3. 
Solicited adverse events ............................................................ 130 
12.5.4. 
Unsolicited adverse events ........................................................ 131 
12.5.5. 
Adverse events of special interest (AESIs) ................................ 131 
12.5.5.1. Potential immune-mediated diseases ....................... 131 
12.5.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events .......................................................................... 134 
12.5.7. 
Events or outcomes not qualifying as adverse events or 
serious adverse events .............................................................. 134 
12.5.7.1. Pregnancy ................................................................ 134 
12.5.8. 
Detecting and recording adverse events, serious adverse 
events and pregnancies ............................................................. 135 
12.5.8.1. Time period for detecting and recording 
adverse events, serious adverse events and 
pregnancies .............................................................. 137 
12.5.8.2. Evaluation of adverse events and serious 
adverse events ......................................................... 138 
12.5.8.2.1. Active questioning to detect 
adverse events and serious 
adverse events ..................................... 138 
12.5.8.2.2. Assessment of adverse events ............. 139 
12.5.9. 
Reporting of serious adverse events, pregnancies, and 
other events ............................................................................... 142 
12.5.9.1. Prompt reporting of serious adverse events, 
pregnancies, and other events to GSK ..................... 142 
12.5.9.2. SAEs requiring expedited reporting to GSK .............. 142 
12.5.9.3. Back-up system in case the electronic 
reporting system does not work ................................ 143 
12.5.9.4. Completion and transmission of pregnancy 
reports to GSK .......................................................... 143 
12.5.9.5. Reporting of pIMDs to GSK ...................................... 143 
12.5.10. Updating of SAE, pregnancy, and AESI information after 
removal of write access to the subject’s eCRF ........................... 144 
12.5.11. Follow-up of adverse events, serious adverse events, and 
pregnancies ............................................................................... 144 
12.5.11.1. Follow-up of adverse events and serious 
adverse events ......................................................... 144 
12.5.11.1.1. Follow-up during the study .................... 144 
12.5.11.1.2. Follow-up after the subject is 
discharged from the study .................... 144 
12.5.11.2. Follow-up of pregnancies.......................................... 145 
12.6. 
Appendix 6: Contraceptive guidance and collection of pregnancy 
information ................................................................................................ 145 
12.6.1. 
Definitions .................................................................................. 145 
12.6.1.1. Woman of Childbearing Potential (WOCBP) ............. 145 

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12.6.1.1.1. Women in the following categories 
are not considered WOCBP .................. 145 
12.6.2. 
Contraception guidance ............................................................. 146 
12.6.3. 
Collection of pregnancy information ........................................... 147 
12.6.3.1. Female Subjects who become pregnant ................... 147 
12.7. 
Appendix 7: FDA Guidance for Industry: Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials (September 2007) ................................................. 147 
12.8. 
Appendix 8: Protocol Amendment History ................................................. 149 
12.8.1. 
Protocol Amendment 6 .............................................................. 149 
12.8.2. 
Protocol Amendment 5 .............................................................. 151 
12.8.3. 
Protocol Amendment 4 .............................................................. 158 
12.8.4. 
Protocol Amendment 3 .............................................................. 180 
12.8.5. 
Protocol Amendment 2 .............................................................. 184 
12.8.6. 
Protocol Amendment 1 .............................................................. 204 
 

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208833 (STAPH AUREUS BIOCONJ-001 STG) 
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LIST OF TABLES 
PAGE 
Table 1 
Document history ..................................................................................... 8 
Table 2 
Schedule of activities (dose-escalation safety lead-in epochs, 
Groups 1-3a/b) ....................................................................................... 29 
Table 3 
Schedule of activities (dose-escalation safety lead-in epochs, 
Group 4a/b) ............................................................................................ 31 
Table 4 
Schedule of activities (Group 5a/b, PoP screening epoch, PoP 
vaccination epochs) ............................................................................... 33 
Table 5 
Intervals between study visits (dose-escalation safety lead-in 
epochs) .................................................................................................. 36 
Table 6 
Intervals between study visits (PoP epochs) .......................................... 36 
........... 39 
........... 40 
Table 9 
Study objectives and endpoints .............................................................. 44 
Table 10 
Study groups, treatment and epochs foreseen in the study (dose-
escalation safety lead-in) ........................................................................ 51 
Table 11 
Study groups, treatment and epochs foreseen in the study (PoP 
epochs) .................................................................................................. 57 
Table 12 
Treatments administered ........................................................................ 66 
Table 13 
Contact information for emergency unblinding ....................................... 71 
Table 14 
Biological samples for efficacy assessment (PoP) .................................. 79 
........................ 80 
........................ 81 
Table 17 
Microbiology ........................................................................................... 81 
......................... 82 
......................... 82 
......................... 83 
Table 21 
Reporting periods for collecting safety information (dose-
escalation safety lead-in) ........................................................................ 85 
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Table 22 
Reporting periods for collecting safety information (PoP) ....................... 86 
Table 23 
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK ................................................................... 87 
Table 24 
Contact information for reporting of serious adverse events 
(SAEs), pIMDs, pregnancies and study holding rules ............................. 88 
Table 25 
Biological samples for haematology and chemistry assessments ........... 89 
Table 26 
Study holding rules ................................................................................. 95 
Table 27 
Protocol-Required Safety Laboratory Assessments ............................. 122 
Table 28 
GSK laboratories .................................................................................. 122 
Table 29 
Outsourced laboratories ....................................................................... 123 
Table 30 
Solicited local adverse events .............................................................. 130 
Table 31 
Solicited general adverse events .......................................................... 130 
Table 32 
Additional solicited general adverse events (PoP only) ........................ 130 
Table 33 
List of potential immune-mediated diseases (pIMDs) ........................... 132 
Table 34 
Intensity scales for solicited adverse events in adults ........................... 139 
Table 35 
Highly Effective Contraceptive Methods ............................................... 146 
Table 36 
FDA toxicity grading scales for hematology/ biochemistry 
parameters evaluated in the current study............................................ 148 
 

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LIST OF FIGURES 
PAGE 
Figure 1 
Overall design ........................................................................................ 20 
Figure 2 
Study design overview dose-escalation safety lead-in healthy 
subjects Groups 1-4a/b .......................................................................... 21 
Figure 3 
Study design overview PoP in subjects with a recent S. aureus 
SSTI Group 5a/b .................................................................................... 25 
Figure 4 
Overall design ........................................................................................ 48 
Figure 5 
Study design overview dose-escalation safety lead-in healthy 
subjects Groups 1-4a/b .......................................................................... 49 
Figure 6 
Study design overview PoP in subjects with a recent S. aureus 
SSTI ....................................................................................................... 54 
Figure 7 
Overview of staggered enrolment and safety evaluation (dose-
escalation safety lead-in) ........................................................................ 93 
Figure 8 
Overview of staggered enrolment and safety evaluation (PoP) .............. 93 
Figure 9 
Evaluations based on 6 subjects per group – Risk assessment 
curve for 1 formulation based on the proposed safety holding 
rules (dose-escalation safety lead-in steps) ............................................ 96 
Figure 10 
Evaluations based on 30 subjects per group – Risk assessment 
curve for 1 formulation based on the proposed safety holding 
rules (staggered step) ............................................................................ 97 
Figure 11 
Evaluations based on 200, 250, 300, 350 subjects per group – 
Risk assessment curve for 1 formulation based on the proposed 
safety holding rules (PoP full enrolment step) ........................................ 98 
Figure 12 
Sequence for evaluating both efficacy objectives in order to 
control the overall type I error below 7.5% (one-sided) and the 
power equal to 80% ............................................................................. 103 
 

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1. 
SYNOPSIS  
Indication: 
Active immunisation for the prevention of S. aureus infection (SSTI/Surgical Site 
Infection [SSI]/ Blood Stream Infection [BSI]) in adults aged 18 years or older. 
Rationale: 
The purpose of this seamless Phase I/II, first time in human - proof of principle (FTIH-
PoP) study is to assess safety and reactogenicity, to perform a preliminary evaluation of 
clinical efficacy and to explore immunogenicity of GSK Biologicals’ S. aureus vaccine 
compared to placebo (saline), both administered in a 2-dose schedule on Day 1 and Day 
61. 
There are no established correlates of protection for immunity against S. aureus 
infections, and therefore trials aimed at evaluating only safety and immunogenicity 
cannot currently predict vaccine efficacy. For this reason, an early evaluation of the 
efficacy of the candidate vaccine in this FTIH clinical trial is intended to provide an early 
reliable PoP that will serve to better guide future vaccine development. 
 
 
 
  
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
Descriptive: 
• 
To assess safety and 
reactogenicity of investigational 
S. aureus vaccine 
• 
Occurrence and intensity of solicited local and general AEs during 7 
days after each dose (i.e. day of vaccination and the 6 subsequent 
days) in all subjects by vaccination group. 
• 
Occurrence, intensity and relationship to vaccination of unsolicited 
AEs during 30 days after each dose (i.e. day of injection and the 29 
subsequent days) in all subjects by vaccination group. 
• 
Occurrence, intensity and relationship to vaccination of all SAEs in 
all subjects by vaccination group: 
− 
Groups 1 to 3 from Day 1 (day of vaccination) until Day 366. 
− 
Groups 4 and 5 from Day 1 (day of vaccination) until Day 426. 
• 
Occurrence, intensity and relationship to vaccination of all potential 
immune-mediated disease (pIMDs) during in all subjects by 
vaccination group. 
− 
Groups 1 to 3 from Day 1 (day of vaccination) until Day 366. 
− 
Groups 4 and 5 from Day 1 (day of vaccination) until Day 426. 
• 
Occurrence of haematological and biochemical laboratory 
abnormalities, and changes from the baseline values after 
vaccination: 
− 
In all subjects of Groups 1 to 3 on Day 8. 
− 
In all subjects of Group 4 on Days 8 and 68  (i.e. 7 days after 
dose 1 and dose 2), respectively. 
− 
Subjects in Group 5 Step 1 (i.e. first 40 subjects enrolled in the 
PoP) on Days 8 and 68  (i.e. 7 days after dose 1 and dose 2), 
respectively. 
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Objectives 
Endpoints 
Secondary 
Confirmatory: 
• 
To evaluate vaccine efficacy 
(VE) in the prevention of 
recurrent culture confirmed  
S. aureus SSTIs compared to 
placebo 
• 
Key secondary endpoint: Number of subjects with at least one 
culture confirmed case of recurrent S. aureus SSTI starting from Day 
75 (i.e.14 days after the second dose) up to 12 months after the 
second dose  
• 
Secondary endpoint: Number of subjects with at least one culture 
confirmed case of recurrent S. aureus SSTI starting from Day 15 (i.e. 
14 days after the first dose) up to 12 months after the second dose 
Ab = Antibody; AE = Adverse Event; CD = Cluster of Differentiation EAP = Exploratory Analysis Plan; 
 
;
 
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pIMDs = potential Immune-Mediated Disease; SAE = Serious Adverse Events; 
 SSTI = 
Skin and Soft Tissue Infection; VE = Vaccine Efficacy; 
 
 
Overall Design: 
This is a Phase I/II, placebo-controlled, observer-blind, randomised, multi-centric study. 
Figure 1 presents a high-level overview of the whole study design. More detailed figures 
are provided in the respective subsections for dose-escalation safety lead-in and PoP. 
The study will include the following epochs (see also Figure 2 and Figure 3): 
• 
Dose-escalation safety lead-in in healthy subjects 
− 
Screening epoch 
− 
Vaccination epoch 
• 
PoP in subjects with a recent S. aureus SSTI 
− 
Screening epoch 
− 
Vaccination epoch 
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Figure 1 
Overall design 
 
Grp = Group 
a/b = vaccine/placebo. 
Rando = Randomisation 
adj = adjuvanted 
SE = Safety evaluation by SRT/ iSRC chair (blinded review) or iSRC (unblinded review), for details refer to Section 8.6 
PoP = Proof of Principle 
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Dose-Escalation safety lead-in healthy subjects 
Figure 2 
Study design overview dose-escalation safety lead-in healthy subjects Groups 1-4a/b 
 
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CDISC is not calculating with Day 0, i.e. interval between Day –1 and Day 1 is 1 day. 
Grp = Group 
a/b =vaccine/placebo 
Rando = Randomisation 
adj = adjuvanted 
SE = Safety evaluation by SRT/ iSRC chair (blinded review) or iSRC (unblinded review), for details refer to Section 8.6 
PoP = Proof of Principle 
M = Month  
V = Vaccination 
BS-S = Blood Sample for Safety evaluation 
 
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Groups in dose-escalation safety lead-in epochs: 
• 
Group 1 Half dose non-adjuvanted (first group), 2 parallel groups:  
− 
Group 1a Half dose non-adj.: 1 dose of Sa-5Ag half dose, non-adjuvanted at 
Day 1 
− 
Group 1b Placebo: 1 dose of placebo (saline) at Day 1 
• 
Group 2 Full dose non-adjuvanted (second group), 2 parallel groups:  
− 
Group 2a Full dose non-adj.: 1 dose of Sa-5Ag full dose, non-adjuvanted at 
Day 1 
− 
Group 2b Placebo: 1 dose of placebo (saline) at Day 1 
• 
Group 3 Half dose adjuvanted (third group), 2 parallel groups:  
− 
Group 3a Half dose adj.: 1 dose of Sa-5Ag half dose, adjuvanted at Day 1 
− 
Group 3b Placebo: 1 dose of placebo (saline) at Day 1 
• 
Group 4 Full dose adjuvanted (fourth group), 2 parallel groups:  
− 
Group 4a Full dose adj.: A series of 2 doses of Sa-5Ag full dose, adjuvanted 
(S. aureus candidate vaccine, target vaccine formulation) given approximately 2 
months apart (Days 1 and 61) 
− 
Group 4b Placebo: A series of 2 doses of placebo (saline) given approximately  
2 months apart (Days 1 and 61) 
For each group, the enrolment of 8 subjects is planned as follows:  
• 
1 vaccinated subject + 1 subject receiving placebo (sentinel subjects). The 2 sentinel 
subjects in each group should be vaccinated on 2 different days. All the available 
safety data collected up to the Day 8 after vaccination visit from both subjects 
(including laboratory assessments at Day 8) will be evaluated. The Safety Review 
Team (SRT) and the internal Safety Review Committee (iSRC) Chair will evaluate 
safety data and confirm the start of the step below. Conditionally; unblinded data 
may be evaluated by iSRC and only after positive opinion of iSRC the next step can 
be started. 
• 
5 vaccinated subjects + 1 subject receiving placebo. All the available safety data 
collected up to the Day 8 after vaccination visit for the last vaccinated subject 
(including laboratory assessments at Day 8) will be evaluated. The SRT and the 
iSRC Chair will evaluate all the safety data available and confirm the start of the 
next step (subsequent group). Conditionally; unblinded data may be evaluated by 
iSRC and only after positive opinion of iSRC the next step can be started.  
All the unblinded data collected up to Day 8 after vaccination Visit 1 of the fourth 
group will be reviewed by iSRC.  
In addition to the above described steps, the fourth group (Full dose adjuvanted) will 
receive a second dose with an interval of approximately 2 months and subjects of all the 
groups will be followed until study end (i.e. for each subject approximately 12-14 
months). 

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After the iSRC review of the unblinded data collected up to the Day 8 after vaccination 
Visit 1 of the fourth group and prior to administering the second dose in that fourth 
group, the staggered enrolment for the PoP epochs of the first approximately 40 subjects 
in the vaccine target population (subjects with a recent S. aureus SSTI) can start. 
Vaccination will be performed with a staggered approach limited to approximately 40 
subjects (30 subjects receiving GSK S. aureus candidate vaccine and 10 receiving 
placebo) followed by an iSRC evaluation of the unblinded safety data up to Day 8 after 
vaccination (including laboratory assessments). 
For both the dose-escalation safety lead-in and the staggered enrolment for PoP of the 
first approximately 40 subjects, the investigator will not be permitted to start the 
administration of Dose 1 for the next group until receipt of the favourable outcome of the 
safety assessment committees evaluation (SRT/iSRC). In case more than 1 subject is to 
be vaccinated on the same day per site, subjects should be vaccinated sequentially at this 
site and at least 60 minutes apart as acute adverse reactions, such as anaphylactic shock, 
typically occur within 1 hour of vaccination (for holding rules refer to Section 8.6.3 and 
Table 26). Therefore, not vaccinating subjects in parallel and leaving at least 60 minutes 
between vaccinations of 2 consecutive subjects will ensure that, in the event of an acute 
adverse reaction, the site will be able to provide the required medical attention. The 2 
sentinel subjects of Groups 1 to 4 dose-escalation safety lead in should be vaccinated on 
2 different days.  

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PoP in subjects with recent S. aureus SSTI  
Figure 3 
Study design overview PoP in subjects with a recent S. aureus SSTI Group 5a/b 
 
Note: CDISC is not calculating with Day 0, i.e. interval between Day –30 and Day 1 is 30 days. 
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a/b = vaccine/placebo 
SE = Safety evaluation by iSRC (unblinded review), for details refer to Section 8.6 
Rando = Randomisation 
PoP = Proof of Principle 
SSTI = Skin and Soft Tissue Infection 
Vac = Vaccine 
Plac = Placebo 
M = Month  
V = Vaccination 
BS-S = Blood Sample for Safety evaluation.  
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In the PoP screening epoch, study subjects can be selected according to the following 
ways: 
1. Subjects with signs and symptoms of an ongoing skin infection and purulent lesion, 
i.e. SSTI, suspected to be caused by S. aureus will be enrolled after signing an 
informed consent form (ICF). Subjects with surgical site infections are not eligible 
for entry in this study. After demonstration of S. aureus positive culture, performed 
as a study procedure, and confirmation by investigator that S. aureus is the most 
likely cause of SSTI, subjects will continue in the study. Diagnosis (e.g. abscess or 
cellulitis) and body location will be collected in the eCRF. In addition, data related to 
S. aureus 
 
 and recorded in the eCRF. 
Specific treatment will be given in compliance with the standard medical practice for 
the management of S. aureus SSTIs and the choice and judgment of the most 
appropriate treatment will be applied by the investigator, outside the study 
procedures. After conclusion of the specific treatment for the skin lesion and after 
clinical resolution of the SSTI (e.g. no signs of ongoing infection such as swelling, 
erythema, pain or drainage), the first dose of S. aureus candidate vaccine or placebo 
will be administered. 
2. Subjects with an ongoing S. aureus SSTI (i.e. S. aureus is the most likely cause), as 
confirmed by positive culture performed outside the study procedures and not earlier 
than 30 days prior to ICF signature. Subjects with surgical site infections are not 
eligible for entry in this study. Diagnosis (e.g. abscess or cellulitis) and body location 
will be collected in the eCRF. In addition, S. aureus 
 
 
 and recorded in the eCRF. These subjects will be 
enrolled whether they have or have not already started specific treatment of the 
infection. In case they have not started the treatment, this will be then given in 
compliance with the standard medical practice for the management of S. aureus 
SSTIs and the choice and judgment of the most appropriate treatment will be applied 
by the investigator, outside the study procedures. After conclusion of the specific 
treatment for the skin lesion and after clinical resolution of the SSTI (e.g. no signs of 
ongoing infection such as swelling, erythema, pain or drainage), the first dose of S. 
aureus candidate vaccine or placebo will be administered.  
The enrolment in the PoP phase will also follow a staggered approach. Enrolment will be 
stopped as soon as 40 subjects have been vaccinated with the first dose of the GSK S. 
aureus candidate vaccine or placebo. Only subjects who already signed the ICF and 
entered the screening phase, at the time of enrolment hold, will be allowed to continue 
the study; therefore, approximately 40 subjects (30 subjects receiving GSK S. aureus 
candidate vaccine and 10 receiving placebo) will be evaluated for safety. After the iSRC 
evaluation of unblinded safety data collected up to the Day 8 after first dose (including 
laboratory assessments) for the last vaccinated subject of this staggered subset has shown 
lack of safety issues, the full enrolment of the remaining subjects in the PoP epochs will 
continue with a randomisation of a 1:1 ratio either to the GSK S. aureus candidate 
vaccine or to the placebo group. The study will follow a group sequential design with two 
analyses. 
 
 
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The subjects of the PoP vaccination and PoP follow-up epoch of the study will be 
evaluated in 2 parallel groups: 
•
Group 5a Vaccine: A series of 2 doses of S. aureus candidate vaccine (Sa-5Ag full
dose adjuvanted) given approximately 2 months apart (Days 1 and 61)
•
Group 5b Placebo: A series of 2 doses of placebo (saline) given approximately 2
months apart (Days 1 and 61)
The investigator will not be permitted to start the administration of the second dose in the 
staggered PoP subset (approximately 40 subjects) until receipt of the favourable outcome 
of the safety assessment performed by SRT and iSRC Chair, which needs to evaluate all 
the safety data available up to Day 68 (including laboratory assessments) related to the 
subjects of the fourth group (Full dose adjuvanted) of the dose-escalation safety lead-in 
step. Conditionally; unblinded data may be evaluated by iSRC and only after positive 
opinion of iSRC the next step (i.e. second dose of staggered PoP subset) can be started. 
Subjects in the PoP vaccination epoch will be followed with an overall duration of 
participation for each subject of approximately 14 months. 
Subjects will be monitored: 
•
For safety for the entire duration of the study.
•
For recurrence of SSTI starting from Day 1 up to 12 months after last dose.
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2. 
SCHEDULE OF ACTIVITIES (SOA)  
Table 2 
Schedule of activities (dose-escalation safety lead-in epochs, Groups 1-3a/b)  
Epoch 
Dose-escalation safety lead-in screening  
Dose-escalation safety lead-in vaccination  
Type of 
contact 
Group 1a/b Half dose non-adjuvanted 
Group 2a/b Full dose non-adjuvanted 
Group 3a/b Half dose adjuvanted 
V0-Grp1-3  
Screening  
V1-Grp1-3 V2-Grp1-3  V3-Grp1-3  
phone call 
V4-Grp1-3  
phone call 
V5-Grp1-3 
Time points 
Day –1* 
Day 1 
Day 8 
Day 31 
Day 181 
(M 6) 
Day 366 
(M 12) 
Sampling time points 
Pre-Vac1 
Informed consent by subjects  
● 
 
 
 
 
 
Check inclusion/exclusion criteria  
● 
 
 
 
 
 
Physical examination 
O 
● 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
Vaccine(s)/Product(s) 
Study group and treatment number allocation 
 
O 
 
 
 
 
Recording of administered treatment number 
 
● 
 
 
 
 
Vaccine administration 
 
● 
 
 
 
 
Safety assessments 
Medical history 
● 
 
 
 
 
 
History of administration of adjuvanted vaccine 
● 
 
 
 
 
 
Urine pregnancy test 
● 
 
 
 
 
 
Check contraindications and warnings and precautions to vaccination 
O 
O 
 
 
 
 
Pre-vaccination body temperature 
 
● 
 
 
 
 
Blood sampling for safety laboratory evaluation (6 mL) 
● 
 
● 
 
 
 
Record any concomitant medication/vaccination 
● 
● 
● 
● 
● 
● 
Record any intercurrent medical conditions 
● 
● 
● 
● 
● 
● 
Distribution of eDiaries and training 
 
O 
 
 
 
 
Review of eDiary data 
 
O 
O 
 
 
 
Return of eDiaries to the sites 
 
 
O 
 
 
 
Phone contact 
 
 
 
● 
● 
 
Recording of solicited adverse events  
 
O 
 
 
 
 
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Epoch 
Dose-escalation safety lead-in screening  
Dose-escalation safety lead-in vaccination  
Type of 
contact 
Group 1a/b Half dose non-adjuvanted 
Group 2a/b Full dose non-adjuvanted 
Group 3a/b Half dose adjuvanted 
V0-Grp1-3  
Screening  
V1-Grp1-3 V2-Grp1-3  V3-Grp1-3  
phone call 
V4-Grp1-3  
phone call 
V5-Grp1-3 
Time points 
Day –1* 
Day 1 
Day 8 
Day 31 
Day 181 
(M 6) 
Day 366 
(M 12) 
Sampling time points 
Pre-Vac1 
Recording of unsolicited adverse events   
 
● 
● 
● 
 
 
Occurrence of solicited AEs at the investigator’s site within 30 minutes 
post-vaccination observation 
 
● 
 
 
 
 
Reporting of pIMDs 
 
● 
● 
● 
● 
● 
Reporting of SAEs, pregnancies and pregnancy outcomes 
● 
● 
● 
● 
● 
● 
Study Conclusion  
 
 
 
 
 
● 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
*CDISC is not calculating with Day 0, i.e. interval between Day –1 and Day 1 is 1 day. 
a/b = vaccine/placebo 
pIMDs = potential Immune-Mediated Diseases 
SAE = Serious Adverse Event 
Vac = Vaccination 
M = Month 
V = Visit 

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Table 3 
Schedule of activities (dose-escalation safety lead-in epochs, Group 4a/b) 
Epoch 
Dose-escalation safety lead-
in screening  
Dose-escalation safety lead-in vaccination  
Type of contact 
Group 4a/b Full dose adjuvanted 
V0-Grp4  
Screening 
V1-Grp4 V2-Grp4 V3-Grp4  
phone 
call  
V4-
Grp4  
V5-
Grp4  
V6-Grp4  
phone 
call 
V7-Grp4  
phone 
call  
V8-Grp4 
Time points 
Day –1* 
Day 1 
Day 8 
Day 31 
Day 61  
Day 68 Day 91 
(M 3) 
Day 241 
(M 8)  
Day 426 
(M 14) 
Sampling time points 
Pre-
Vac1 
Pre-
Vac2  
Informed consent by subjects  
● 
 
 
 
 
 
 
 
 
Check inclusion/exclusion criteria  
● 
 
 
 
 
 
 
 
 
Physical examination 
O 
● 
 
 
● 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
Vaccine(s)/Product(s)  
Study group and treatment number allocation 
 
O 
 
 
 
 
 
 
 
Treatment number allocation for subsequent doses 
 
 
 
 
O 
 
 
 
 
Recording of administered treatment number 
 
● 
 
 
● 
 
 
 
 
Vaccine administration 
 
● 
 
 
● 
 
 
 
 
Safety assessments 
Medical history 
● 
 
 
 
 
 
 
 
 
History of administration of adjuvanted vaccine 
● 
 
 
 
 
 
 
 
 
Urine pregnancy test 
● 
 
 
 
● 
 
 
 
 
Check contraindications and warnings and precautions to vaccination 
O 
O 
 
 
O 
 
 
 
 
Pre-vaccination body temperature 
 
● 
 
 
● 
 
 
 
 
Blood sampling for safety laboratory evaluation (6 mL) 
● 
 
● 
 
● 
● 
 
 
 
Record any concomitant medication/vaccination 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record any intercurrent medical conditions 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Distribution of eDiaries and training 
 
O 
 
 
O*** 
 
 
 
 
Review of eDiary data 
 
O 
O 
 
O 
O 
 
 
 
Return of eDiaries to the sites 
 
 
 
 
 
O 
 
 
 
Phone contact 
 
 
 
● 
 
 
● 
● 
 
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Epoch 
Dose-escalation safety lead-
in screening  
Dose-escalation safety lead-in vaccination  
Type of contact 
Group 4a/b Full dose adjuvanted 
V0-Grp4  
Screening 
V1-Grp4 V2-Grp4 V3-Grp4  
phone 
call  
V4-
Grp4  
V5-
Grp4  
V6-Grp4  
phone 
call 
V7-Grp4  
phone 
call  
V8-Grp4 
Time points 
Day –1* 
Day 1 
Day 8 
Day 31 
Day 61  
Day 68 Day 91 
(M 3) 
Day 241 
(M 8)  
Day 426 
(M 14) 
Sampling time points 
Pre-
Vac1 
Pre-
Vac2  
Recording of solicited adverse events  
 
O 
 
 
O 
 
 
 
 
Recording of unsolicited adverse events   
 
● 
● 
● 
● 
● 
● 
 
 
Occurrence of solicited AEs at the investigator’s site within 30 minutes 
post-vaccination observation 
 
● 
 
 
● 
 
 
 
 
Reporting of pIMDs 
 
● 
● 
● 
● 
● 
● 
● 
● 
Reporting of SAEs, pregnancies and pregnancy outcomes 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Study Conclusion  
 
 
 
 
 
 
 
 
● 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
*CDISC is not calculating with Day 0, i.e. interval between Day –1 and Day 1 is 1 day. 
. 
***Remind subjects that the device is now ready to collect after Dose 2 data 
a/b = vaccine/placebo 
 
pIMDs = potential Immune-Mediated Diseases 
SAE = Serious Adverse Event 
Vac = Vaccination 
M = Month 
V = Visit 
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Table 4 
Schedule of activities (Group 5a/b, PoP screening epoch, PoP vaccination epochs)  
Epoch 
PoP 
screening  
PoP vaccination  
Type of contact 
V0  
V1  
V2 
Clinic visit or 
Phone calle  
V3 
 
V4  
Phone 
call 
V5  
V6 
Clinic visit or 
Phone call e  
V7  
V8  
Phone 
call 
V9  
Phone 
call 
V10  
Unscheduled 
visith 
Time points 
Day –30a 
Day 1  
Day 8 
Day 
15 
Day 31 
Day 
61  
Day 68 
Day 
75 
Day 91 
(M 3) 
Day 241 
(M 8)  
Day 426 
(M 14) 
 
Sampling time points 
Pre-
Vac1  
Pre-
Vac2  
Informed consent by subjects 
● 
 
 
 
 
 
 
 
 
 
 
 
Check inclusion/exclusion criteria  
● 
● 
 
 
 
 
 
 
 
 
 
 
Physical examination 
O 
● 
 
 
 
● 
 
 
 
 
 
 
Verification of clinical resolution of SSTI 
 
● 
 
 
 
 
 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
 
 
Vaccine(s)/Product(s)  
Study group and treatment number allocation 
 
O 
 
 
 
 
 
 
 
 
 
 
Treatment number allocation for subsequent doses 
 
 
 
 
 
O 
 
 
 
 
 
 
Recording of administered treatment number 
 
● 
 
 
 
● 
 
 
 
 
 
 
Vaccine administration 
 
● 
 
 
 
● 
 
 
 
 
 
 
Clinical Specimens for microbiology assessments 
Sampling of drainage for cultures performed in the 
study 
● 
 
 
 
 
 
 
 
 
 
 
●c 
Check of culture test report for SA-SSTI confirmation 
● 
 
 
 
 
 
 
 
 
 
 
● 
Safety assessments 
Medical history 
● 
● 
 
 
 
 
 
 
 
 
 
 
History of administration of adjuvanted vaccine 
● 
● 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
● 
● 
 
 
 
● 
 
 
 
 
 
 
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Epoch 
PoP 
screening  
PoP vaccination  
Type of contact 
V0  
V1  
V2 
Clinic visit or 
Phone calle  
V3 
 
V4  
Phone 
call 
V5  
V6 
Clinic visit or 
Phone call e  
V7  
V8  
Phone 
call 
V9  
Phone 
call 
V10  
Unscheduled 
visith 
Time points 
Day –30a 
Day 1  
Day 8 
Day 
15 
Day 31 
Day 
61  
Day 68 
Day 
75 
Day 91 
(M 3) 
Day 241 
(M 8)  
Day 426 
(M 14) 
 
Sampling time points 
Pre-
Vac1  
Pre-
Vac2  
Check contraindications and warnings and 
precautions to vaccination 
O 
O 
 
 
 
O 
 
 
 
 
 
 
Pre-vaccination body temperature 
 
● 
 
 
 
● 
 
 
 
 
 
 
Blood sampling for safety laboratory evaluation 
(6 mL) (PoP Step 1 subjects only)g 
 
● 
● 
 
 
● 
● 
 
 
 
 
 
Phone contact 
(PoP Step 2 subjects only) 
 
 
● 
 
 
 
● 
 
 
 
 
 
Record any concomitant medication/vaccination 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record any intercurrent medical conditions 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Distribution of eDiaries and training  
 
O 
 
 
 
Of 
 
 
 
 
 
 
Review of eDiary data 
 
O 
O 
 
 
 
O 
 
 
 
 
 
Return of eDiaries to the sites 
 
 
 
 
 
 
 
O 
 
 
 
 
Phone contact (all subjects) 
 
 
 
 
● 
 
 
 
● 
● 
 
 
Recording of solicited adverse events   
 
O 
 
 
 
O 
 
 
 
 
 
 
Recording of unsolicited adverse events   
 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
 
Occurrence of solicited AEs at the investigator’s site 
within 30 minutes post-vaccination observationi 
 
● 
 
 
 
● 
 
 
 
 
 
 
Reporting of pIMDs 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Reporting of SAEs, pregnancies and pregnancy 
outcomes 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Study Conclusion  
 
 
 
 
 
 
 
 
 
 
● 
 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
a CDISC is not calculating with Day 0, i.e. interval between Day –30 and Day 1 is 30 days. 
c SSTI must be amenable to microbiological culturing per standard clinical practice. 
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 e Visit 2 and 6: Clinical visit for PoP Step 1 subjects (i.e. first 40 subjects enrolled in the PoP) where 6 mL of whole blood for safety laboratory evaluation will be collected; Phone call 
for PoP Step 2 subjects (i.e. all those following subjects after the first 40 enrolled in the PoP Step 1).    
f Remind subjects that the device is now ready to collect after Dose 2 data.  
g The blood sampling for safety lab evaluation only (~6 mL to be drawn from PoP Step 1 subject only) should occur on Day 1 and Day 61 but, as an alternative, can be performed up to 
1 day before vaccine administration. 
hUnscheduled visits can occur at any time after first study vaccination and should happen as soon as possible after signs/symptoms onset 
iOccurrence of solicited AEs within 30 minutes post vaccination observation must be recorded in the eCRF 
a/b = vaccine/placebo 
 
 
pIMDs = potential Immune-Mediated Diseases 
SAE = Serious Adverse Event 
Vac = Vaccination 
M = Month 
V = Visit 
 
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Whenever possible, the investigator should arrange study visits within the intervals 
described in Table 5 and Table 6. 
Table 5 
Intervals between study visits (dose-escalation safety lead-in 
epochs) 
Groups 
Interval 
Optimal Length of 
interval  
Allowed 
interval 
Group 1a/b 
Group 2a/b 
Group 3a/b 
V0-Grp1-3 (Day -1)→ V1-Grp1-3 (Day 1) 
1 days  
0 - 3 days * 
V1-Grp1-3 (Day 1)→ V2-Grp1-3 (Day 8) 
7 days  
7 - 8 days  
V1-Grp1-3 (Day 1)→ V3-Grp1-3 (Day 31) 
30 days  
30 - 33 days  
V1-Grp1-3 (Day 1)→ V4-Grp1-3 (Month 6, Day 181) 
180 days  
180 - 190 days  
V1-Grp1-3 (Day 1)→ V5-Grp1-3 (Month 12, Day 
366) 
365 days  
365 - 380 days  
Group 4a/b V0-Grp4 (Day –1)→ V1-Grp4 (Day 1) 
1 days  
0 - 3 days * 
V1-Grp4 (Day 1)→ V2-Grp4 (Day 8) 
7 days  
7 - 8 days  
V1-Grp4 (Day 1)→ V3-Grp4 (Day 31) 
30 days  
30 - 33 days  
V1-Grp4 (Day 1)→ V4-Grp4 (Day 61) 
60 days  
60 - 67 days  
V4-Grp4 (Day 61)→ V5-Grp4 (Day 68) 
7 days  
7 - 9 days  
V4-Grp4 (Day 61)→ V6-Grp4 (Month 3, Day 91) 
30 days  
30 - 40 days  
V4-Grp4 (Day 61)→ V7-Grp4 (Month 8, Day 241) 
180 days  
180 - 190 days  
V4-Grp4 (Day 61→ V8-Grp4 (Month 14, Day 426) 
365 days  
365 - 380 days  
a/b = vaccine/placebo; GRP = Group; V = Visit 
Note: CDISC is not calculating with Day 0, i.e. interval between Day –1 and Day 1 is 1 day. 
*The minimum interval of 0 days means that screening and vaccination is on the same day and automatically the 
screening is then for this subject on Study Day 1. 
Table 6 
Intervals between study visits (PoP epochs)  
Group 5a/b 
Interval 
Length of 
interval  
Allowed interval 
All subjects 
V0 (Day -30 up to Day 1)→ V1 
(Day 1) 
up to 30 days   
0 - 30 days*  
V1 (Day 1)→V2 (Day 8) 
7 days  
7 - 9 days  
V1 (Day 1)→V3 (Day 15) 
14 days  
14 - 21 days  
V1 (Day 1)→V4 (Day 31) 
30 days  
30 - 37 days  
V1 (Day 1)→V5 (Day 61) 
60 days  
60 - 67 days  
V5 (Day 61)→V6 (Day 68) 
7 days  
7 - 9 days  
V5 (Day 61)→V7 (Day 75) 
14 days  
14 - 21 days  
V5 (Day 61)→V8 (Month 3, day 
91) 
30 days  
30 - 40 days  
V5 (Day 61)→V9 (Month 8, day 
241) 
180 days  
180 - 190 days  
V5 (Day 61)→V10 (Month 14, day 
426) 
365 days  
365 - 380 days  
a/b = vaccine/placebo; PoP = Proof of Principle; V = Visit 
Note: CDISC is not calculating with Day 0, i.e. interval between Day –30 and Day 1 is 30 days. 
* Vaccination should occur after clinical resolution of culture confirmed SSTI caused by S. aureus and must occur 
within 30 days from the date of skin drainage for microbiology assessment (done either outside or in the study) 

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3. 
INTRODUCTION 
3.1. 
Study rationale 
The purpose of this seamless Phase I/II first time in human - proof of principle (FTIH-
PoP) study is to evaluate safety and reactogenicity, to perform a preliminary evaluation of 
clinical efficacy and to explore immunogenicity of GSK Biologicals’ S. aureus vaccine 
compared to placebo (saline), both administered in a 2-dose schedule on Day 1 and Day 
61. 
There are no established correlates of protection for immunity against S. aureus 
infections, and therefore trials aimed at evaluating only safety and immunogenicity 
cannot currently predict vaccine efficacy. For this reason, an early evaluation of the 
efficacy of the candidate vaccine in this FTIH clinical trial is intended to provide an early 
reliable PoP that will serve to better guide future vaccine development. 
 
 
 
 
3.2. 
Background 
3.2.1. 
Skin and soft tissue infections caused by S. aureus 
S. aureus is a gram-positive bacterium causing a spectrum of illnesses varying from mild 
to life-threatening diseases and it is considered as a major cause of morbidity and 
mortality despite the availability of several anti-staphylococcal antibiotics. The clinical 
pattern of S. aureus infections includes: 
• 
SSTI (impetigo, cellulitis, furuncles, and abscesses)  
• 
Surgical wound infections  
• 
Bacteraemia including sepsis and septic shock  
• 
Respiratory tract infections (pneumonia including necrotizing pneumonia)  
• 
Musculoskeletal infections (arthritis, osteomyelitis, pyomyositis, necrotizing 
fasciitis)  
• 
Endocarditis 
• 
Device-related infections  
• 
Toxin-mediated illnesses 
There is a high medical need worldwide for a vaccine against S. aureus infections. It is a 
leading cause of surgical site infections (SSI), bloodstream infections (BSI), hospital-
acquired pneumonia (HAP), and community-acquired skin and soft tissue infections (CA-
SSTI) [Pozzi, 2017], [Lowy, 1998], [Knox, 2015]. It is among the species with highest 
antibiotic resistance and currently no vaccine is available on the market. 
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The World Health Organization [WHO, 2017]  and the Centre for Disease Control and 
Prevention [CDC, 2013] recently listed human pathogens with threatening drug-
resistance patterns with respectively global relevance or more specifically for the US: S. 
aureus is included in both lists. A recent assessment made by the European Medicines 
Agency (EMA) includes S. aureus as one of the major indicators as regards surveillance 
of antimicrobial resistance and antimicrobial consumption in humans [EFSA, 2017]. 
Standard of care for most infections is based on antibiotic therapy, which is not always 
sufficiently effective and leaves a considerable unmet medical need. 
 
 causes more than 11, 000 deaths per year in the US and more than 
5,400 deaths in EU [Pozzi, 2017].  
Infections significantly increase length of hospital stay. In EU 1,050,000 extra days of 
hospitalization, with extra costs of € 380 million annually have been reported [Kock, 
2010]. Recently bundle measures that included screening, decolonization, and targeted 
antibiotic prophylaxis of patients prior to surgery were shown to slightly, but 
significantly, reduce S. aureus post-operative infection rate in US hospitals [Schweizer, 
2015]. 
An efficacious vaccine would reduce the significant costs associated with bundle 
measures, could prevent the further increase of antibiotic resistance as well as all the 
infections not prevented by the bundles. 
The virulence of S. aureus involves the coordinated expression of a large number of 
surface and secreted proteins implicated in different aspects of pathogenesis [Cheng, 
2011], [Pozzi, 2015]. The ability of S. aureus to cause a wide variety of infections 
depends on the expression of numerous virulence factors. Moreover, S. aureus has 
evolved immune escape mechanisms as well as strategies to survive on inert surfaces 
(e.g., medical devices) and to persist in biofilms.  
In view of the complexity of S. aureus virulence mechanisms and of failed S. aureus 
vaccine attempts that targeted only one single virulence factor, a multi-component 
vaccine approach is considered essential [Daum, 2012]. 
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3.3. 
Benefit/Risk assessment 
Please refer to the current Investigator Brochure for the summary of potential risks and 
benefits of S. aureus candidate vaccine. 
The following section outlines the risk assessment and mitigation strategy for this study 
protocol. 
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3.3.1. 
Risk assessment 
Important/Potential/Identified/Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
GSK S. aureus candidate vaccine 
Theoretical risk of acquiring a vaccine-induced immune-
mediated disease after vaccination. 
No confirmed signals related to this potential risk have 
been identified to date. 
Close monitoring of potential immune-mediated diseases 
(pIMDs) in clinical development programs using adjuvants 
systems (AS). The potential risk of events of possible 
immune aetiology occurring is mentioned in the ICF. In 
addition, the ICF advises subjects to contact the study 
doctor or the study staff immediately, should they get any 
symptoms that they feel may be serious. 
Study Procedures 
Risk of blood sampling.  
Blood sampling associated risk of syncope, dizziness, 
infection at the site after or during venipuncture. 
Blood samples will be obtained by a trained professional 
and medical assistance will be available. The potential 
risk of feeling faint, or experiencing mild local pain, 
bruising, irritation or redness at the site where blood was 
taken, is mentioned in the ICF. The amount of blood to be 
taken for sampling will not be harmful to the subject’s 
health (see Table 2, Table 3, Table 4 and 
Section 8.4.2.2). 
Other 
Potential increase of mortality after S. aureus infection in 
subjects with low IL-2 and IL-17A before vaccination 
An increased mortality rate was seen in a vaccine study 
[McNeely, 2014] in subjects with low IL-2 and IL-17A 
before vaccination with iron-regulated surface 
determinant B (IsdB) staphylococcal vaccine who 
subsequently underwent cardio-thoracic surgery and 
experienced a S. aureus infection post-surgery. 
The composition of the GSK S. aureus candidate vaccine 
is different from the composition used in the study 
[McNeely, 2014], i.e. IsdB is not a component. Baseline 
values of IL-2 and IL17A will be measured and assessed 
together with safety data. 
Risk to receive placebo 
Subjects will have the risk of local reactions due to an 
injection without the benefit of efficacy. Placebo (saline) 
cannot be expected to have any effect on SSTI 
recurrences. 
Injection will be given by a trained professional and 
medical assistance will be available. The potential risk of 
feeling faint, or experiencing mild local pain, bruising, 
irritation, swelling, redness or other injection site reactions 
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3.3.2. 
Benefit assessment 
• 
Administration of the vaccine may reduce the risk of recurrences of S. aureus SSTIs. 
• 
Contribution to the process of developing a vaccine against treatment/antibiotic 
resistant S. aureus infections. 
• 
Medical evaluations/assessments associated with study procedures (i.e. physical 
examination). 
3.3.3. 
Overall Benefit: Risk conclusion 
The investigational GSK S. aureus candidate vaccine is currently in an early stage of 
clinical development with no vaccine efficacy demonstrated. With the measures taken to 
minimize the risks to subjects participating in this study, the potential risks are justified 
by the potential benefits linked to development of this vaccine.  
4. 
OBJECTIVE(S) AND ENDPOINT(S)  
Table 9 
Study objectives and endpoints  
Objectives 
Endpoints 
Primary 
Descriptive: 
• 
To assess safety and reactogenicity of 
investigational S. aureus vaccine 
• 
Occurrence and intensity of solicited local and general AEs 
during 7 days after each dose (i.e. day of vaccination and 
the 6 subsequent days) in all subjects by vaccination group. 
• 
Occurrence, intensity and relationship to vaccination of 
unsolicited AEs during 30 days after each dose (i.e. day of 
injection and the 29 subsequent days) in all subjects by 
vaccination group. 
• 
Occurrence, intensity and relationship to vaccination of all 
SAEs in all subjects by vaccination group: 
− 
Groups 1 to 3 from Day 1 (day of vaccination) until 
Day 366. 
− 
Groups 4 and 5 from Day 1 (day of vaccination) until 
Day 426. 
• 
Occurrence, intensity and relationship to vaccination of all 
potential immune-mediated disease (pIMDs) during in all 
subjects by vaccination group. 
− 
Groups 1 to 3 from Day 1 (day of vaccination) until 
Day 366. 
− 
Groups 4 and 5 from Day 1 (day of vaccination) until 
Day 426. 
− 
Occurrence of haematological and biochemical laboratory 
abnormalities, and changes from the baseline values after 
vaccination: 
− 
In all subjects of Groups 1 to 3 on Day 8. 
− 
In all subjects of Group 4 on Days 8 and 68  (i.e. 7 
days after dose 1 and dose 2), respectively. 
− 
Subjects in Group 5 Step 1 (i.e. first 40 subjects 
enrolled in the PoP)  on Days 8 and 68  (i.e. 7 days 
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Objectives 
Endpoints 
Secondary 
Confirmatory: 
• 
To evaluate vaccine efficacy (VE) in the 
prevention of recurrent culture 
confirmed S. aureus SSTIs compared to 
placebo 
• 
Key secondary endpoint: Number of subjects with at least 
one culture confirmed case of recurrent S. aureus SSTI 
starting from Day 75 (i.e.14 days after the second dose) up 
to 12 months after the second dose  
• 
Secondary endpoint: Number of subjects with at least one 
culture confirmed case of recurrent S. aureus SSTI starting 
from Day 15 (i.e. 14 days after the first dose) up to 12 
months after the second dose 
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Objectives 
Endpoints 
Ab = Antibody; AE = Adverse Event; CD = Cluster of Differentiation EAP = Exploratory Analysis Plan; 
 
 
 
pIMDs = potential Immune-Mediated Disease; SAE = Serious Adverse Events;
; SSTI = 
Skin and Soft Tissue Infection; VE = Vaccine Efficacy; 
 
 
5. 
STUDY DESIGN 
5.1. 
Scientific rationale for study design 
The rationale for the vaccine composition and dosage is provided in Section 3.2.2. 
This is a seamless Phase I/II self-contained study comprising of 2 phases: the study 
design comprises a combined FTIH evaluation and PoP demonstration aiming to provide 
an agile pathway from the concept to the clinical PoP.  
 
 
 the S. aureus vaccine candidate is a FTIH, considering that any new 
combination of antigens/adjuvants and vaccine technology are always considered as a 
new product from a safety perspective. For this reason, the study begins with a dose-
escalation safety lead-in phase in healthy subjects (Phase I). The dose-escalation safety 
lead-in phase will investigate half dose and full dose non-adjuvanted and adjuvanted 
vaccine with a staggered vaccination approach and includes safety review checkpoints by 
safety assessment committees (SRT/ iSRC). For details of study design refer to Section 
5.2; details about the internal safety evaluation by iSRC will be described in the iSRC 
Charter.  
The primary objective of this FTIH study is the assessment of safety and reactogenicity 
of the investigational S. aureus vaccine. 
Endpoints and statistical considerations of the secondary objective “vaccine efficacy 
(VE) in the prevention of recurrent culture confirmed S. aureus SSTIs compared to 
placebo” are based on the results of a study (207908 [EPI-STAPH-006 BOD DB]) which 
retrospectively reviewed the databases of three hospitals in the US that had available data 
on SSTI. The retrospective review focused on adult outpatients attending the outpatient 
and emergency departments and that were diagnosed with SSTI with the purpose of 
investigating the frequency of S. aureus SSTIs. 
 
. Since there 
is currently no licensed vaccine against S. aureus infections the comparator group will 
receive placebo (saline). 
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In the protocol ahead, Phase I is called as the dose-escalation safety lead-in or safety 
lead-in phase and Phase II is called as PoP phase. 
5.2. 
Overall design  
Figure 4 presents a high-level overview of the whole study design. More detailed figures 
are provided in the respective subsections for dose-escalation safety lead-in (Figure 5) 
and PoP (Figure 6). 

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Figure 4 
Overall design  
 
adj = adjuvanted 
Grp = Group 
a/b = vaccine/placebo 
Rando = Randomisation 
SE = Safety evaluation by SRT/ iSRC chair (blinded review) or iSRC (unblinded review), for details refer to Section 8.6 
PoP = Proof of Principle 
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5.2.1. 
Dose-Escalation safety lead-in healthy subjects (Phase I) 
Figure 5 
Study design overview dose-escalation safety lead-in healthy subjects Groups 1-4a/b 
 
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CDISC is not calculating with Day 0, i.e. interval between Day –1 and Day 1 is 1 day. 
Grp = Group 
a/b = vaccine/placebo 
adj = adjuvanted 
Rando = Randomisation 
SE = Safety evaluation by SRT/ iSRC chair (blinded review) or iSRC (unblinded review), for details refer to Section 8.6 
PoP = Proof of Principle 
M = Month  
V = Vaccination 
BS-S = Blood Sample for Safety evaluation 
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• 
Type of study: self-contained 
• 
Experimental design: Phase I, observer-blind, randomised, controlled, multi-centric 
study with staggered enrolment of subjects in 4 groups receiving different vaccine 
formulations in the dose-escalation safety lead-in epochs. 
• 
Duration of the study:  
− 
Dose-escalation safety lead-in screening epoch: Groups 1 to 4 screening starting 
at Visit 0 (Day –1) and ending just before the Visit 1 (Day 1). 
− 
Dose-escalation safety lead-in vaccination epoch: Groups 1 to 3 starting with 
vaccination at Visit1-Grp1-3 (Day 1) and ending just before the Visit5-Grp1-3 
(Month 12 [Day 366]). Group 4 starting with vaccination at Visit1-Grp4 (Day 1) 
and ending just before the Visit8-Grp4 (Month 14 [Day 426]). 
• 
Study groups: Table 10 
Table 10 
Study groups, treatment and epochs foreseen in the study (dose-
escalation safety lead-in) 
Study Groups  
Number 
of healthy 
subjects 
Age 
(Min-Max) 
Treatment name 
Epochs 
(Blinding) 
Dose-escalation 
safety lead-in 
screening  
(N/A ) 
Dose-escalation 
safety lead-in 
vaccination  
(observer-blind ) 
Group 1a Half dose 
non-adj  
6  
18 - 50 
years  
Sa-5Ag half dose 
non-adjuvanted  
●  
●  
Group 1b Placebo  
2  
Placebo  
●  
●  
Group 2a Full dose 
non-adj  
6  
18 - 50 
years  
Sa-5Ag full dose 
non-adjuvanted  
●  
●  
Group 2b Placebo  
2  
Placebo  
●  
●  
Group 3a Half dose adj  
6  
18 - 50 
years  
Sa-5Ag half dose 
adjuvanted  
●  
●  
Group 3b Placebo  
2  
Placebo  
●  
●  
Group 4a Full dose adj  
6  
18 - 50 
years  
Sa-5Ag full dose 
adjuvanted  
●  
●  
Group 4b Placebo  
2  
Placebo  
●  
●  
N/A = Not Applicable 
Note: For details regarding content and quantity of antigens and adjuvants refer to Table 12.  
• 
Control: placebo control. 
• 
Vaccination schedule(s): 
− 
Group 1 Half dose non-adjuvanted (first group), 2 parallel groups:  
o 
Group 1a Half dose non-adj.: 1 dose of Sa-5Ag half dose, non-adjuvanted 
at Day 1 
o 
Group 1b Placebo: 1 dose of placebo (saline) at Day 1 

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− 
Group 2 Full dose non-adjuvanted (second group), 2 parallel groups:  
o 
Group 2a Full dose non-adj.: 1 dose of Sa-5Ag full dose, non-adjuvanted 
at Day 1 
o 
Group 2b Placebo: 1 dose of placebo (saline) at Day 1 
− 
Group 3 Half dose adjuvanted (third group), 2 parallel groups:  
o 
Group 3a Half dose adj.: 1 dose of Sa-5Ag half dose, adjuvanted at Day 1 
o 
Group 3b Placebo: 1 dose of placebo (saline) at Day 1 
− 
Group 4 Full dose adjuvanted (fourth group), 2 parallel groups:  
o 
Group 4a Full dose adj.: A series of 2 doses of Sa-5Ag full dose, 
adjuvanted (S. aureus candidate vaccine, target vaccine formulation) given 
approximately 2 months apart (Days 1 and 61)  
o 
Group 4b Placebo: A series of 2 doses of placebo (saline) given 
approximately 2 months apart (Days 1 and 61) 
For each group, the enrolment of 8 subjects with an overall randomisation of a 3:1 
ratio either to the GSK S. aureus candidate vaccine or to the placebo group is 
planned (details are given below in bullet “Safety monitoring”).  
• 
Treatment allocation: randomised, subjects will be allocated to a study group using 
an automated, electronic System Built for Internet Randomisation (SBIR).  
• 
Blinding: not applicable for screening epoch, vaccination epoch is observer-blind.  
• 
Sampling schedule: Blood samples for laboratory safety evaluation and 
 
 
 will be drawn from all subjects. Blood samples will be 
collected at the timepoints as detailed in Table 2 and Table 3.  
• 
Data collection: standardised Electronic Case Report Form (eCRF). Solicited AEs 
will be collected using a subject Diary (electronic Diary [eDiary])  
• 
Safety monitoring: 
For each group in the dose-escalation safety lead-in, a staggered enrolment of 8 
subjects is planned as follows: 1 vaccinated subject + 1 subject receiving placebo 
(sentinel subjects) followed by 5 vaccinated subjects + 1 subject receiving placebo 
after safety assessment of safety data collected up to Day 8 (for details refer to 
Section 8.6). The 2 sentinel subjects in each group should be vaccinated on 2 
different days. 
The fourth group (Full dose adjuvanted) will receive a second vaccine/placebo dose 
with an interval of approximately 2 months and subjects of all the groups will be 
followed until study end (i.e. for 12 months after last vaccination for each subject).  
The investigator is not permitted to start the administration of Dose 1 for the next 
group and Dose 2 in the fourth group until receipt of the favourable outcome of the 
safety evaluation as described in Section 8.6.1. 
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During the whole study period, if the investigator becomes aware of a holding rule 
being met, he/she will suspend vaccination and will inform GSK immediately (e.g. in 
case of death or any life-threatening SAEs).  
Refer to Section 8.6 for detailed description of holding rules and safety monitoring. 
Refer to the iSRC Charter for details about the safety assessment committees 
evaluation. 

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5.2.2. 
PoP in subjects with recent S. aureus SSTI Group 5a/b (Phase II) 
Figure 6 
Study design overview PoP in subjects with a recent S. aureus SSTI  
 
a/b = vaccine/placebo 
SE = Safety evaluation by iSRC (unblinded), for details refer to Section 8.6 
PoP = Proof of rinciple 
SSTI = Skin and Soft Tissue Infection 
Rando = Randomization 
Vac = Vaccine 
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Plac = Placebo 
M = Month  
V = Vaccination 
BS-S = Blood Sample for Safety evaluation.  
Note: CDISC is not calculating with Day 0, i.e. interval between Day –30 and Day 1 is 30 days. 
 
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Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns. Therefore, adherence to the study design requirements, 
including those specified in the schedule of activities (Section 2), is essential and required 
for study conduct.  
• 
Type of study: self-contained 
• 
Experimental design: Phase II, observer-blind, randomised, controlled, group 
sequential, multi-centric study with 2 parallel groups in the PoP vaccination epoch. 
• 
Duration of the study: 
− 
PoP screening epoch: starting at Visit 0 and ending just before Visit 1.  
− 
PoP vaccination epoch: starting with vaccination at Visit 1 and ending just 
before Visit 10.  
In the PoP screening epoch, study subjects can be selected according to the following 
ways: 
1. Subjects with signs and symptoms of an ongoing skin infection and purulent lesion, 
i.e. SSTI, suspected to be caused by S. aureus will be enrolled after signing an 
informed consent form (ICF). Subjects with surgical site infections are not eligible 
for entry in this study. After demonstration of S. aureus positive culture, performed 
as a study procedure, and confirmation by investigator that S. aureus is the most 
likely cause of SSTI, subjects will continue in the study. Diagnosis (e.g. abscess or 
cellulitis) and body location will be collected in the eCRF. In addition, data related to 
S. aureus 
 
 and recorded in the eCRF. 
Specific treatment will be given in compliance with the standard medical practice for 
the management of S. aureus SSTIs and the choice and judgment of the most 
appropriate treatment will be applied by the investigator, outside the study 
procedures. After conclusion of the specific treatment for the skin lesion and after 
clinical resolution of the SSTI (e.g. no signs of ongoing infection such as swelling, 
erythema, pain or drainage), the first dose of S. aureus candidate vaccine or placebo 
will be administered. 
2. Subjects with an ongoing S. aureus SSTI (i.e. S. aureus is the most likely cause), as 
confirmed by positive culture, performed outside the study procedures and not earlier 
than 30 days prior to ICF signature. Subjects with surgical site infections are not 
eligible for entry in this study. Diagnosis (e.g. abscess or cellulitis) and body location 
will be collected in the eCRF. In addition, 
 
 
 and recorded in the eCRF. These subjects will be 
enrolled whether they have or have not already started specific treatment of the 
infection. In case they have not started the treatment, this will be then given in 
compliance with the standard medical practice for the management of S. aureus 
SSTIs and the choice and judgment of the most appropriate treatment will be applied 
by the investigator, outside the study procedures. After conclusion of the specific 
treatment for the skin lesion and after clinical resolution of the SSTI (e.g. no signs of 
ongoing infection such as swelling, erythema, pain or drainage), the first dose of S. 
aureus candidate vaccine or placebo will be administered.  
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The enrolment and vaccination in the PoP phase will also follow a staggered approach. 
Details are given below in bullet “Safety monitoring” and Section 8.6.1. The study will 
follow a group sequential design with two analyses. 
 
 
 
 
 
). It is estimated that then a total of 
approximately 500 to 600 subjects will be vaccinated in the PoP 
 
 
 
•
Primary Completion Date (PCD): Visit 10 (Month 14 [Day 426])
Refer to glossary of terms for the definition of PCD. 
•
End of Study (EoS): Last subject last visit (LSLV) (Visit 10).
Refer to glossary of terms for the definition of EoS. 
•
Study groups: Table 11
Table 11 
Study groups, treatment and epochs foreseen in the study (PoP 
epochs) 
Study 
Groups 
Number of 
subjects 
Age 
(Min-Max) 
Treatment name 
Epochs 
(Blinding) 
PoP screening 
(N/A) 
PoP vaccination 
(observer-blind) 
Group 5a 
Vaccine 
250* 
18 - 64 years 
Sa-5Ag full dose 
adjuvanted  
● 
●  
Group 5b 
Placebo 
250* 
18 - 64 years 
Placebo 
● 
●  
N/A = Not Applicable 
*Design of the study is event driven and it can be only estimated that approximately 250 to 300 subjects per study
group may be needed. Enrolment may continue until 27 events are reached.
•
Control: placebo control
•
Vaccination schedule(s):
−
Group 5a Vaccine: A series of 2 doses of S. aureus candidate vaccine (Sa-5Ag
full dose adjuvanted) given approximately 2 months apart (Days 1 and 61)
−
Group 5b Placebo: A series of 2 doses of placebo (saline) given approximately
2 months apart (Days 1 and 61)
•
Treatment allocation: randomised, subjects will be allocated to a study group using
an automated, electronic system (SBIR).
•
Blinding: not applicable for the screening epoch, and the vaccination epoch is
observer-blind
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• 
Sampling schedule:  
− 
Blood samples for laboratory safety evaluation will be drawn from the first 40 
subjects enrolled (i.e. subjects belonging to PoP Step 1) 
− 
Drainage samples will be taken from those subjects performing culture test  as 
study procedures at screening (i.e. Visit 0) and from all subjects with 
recurrences at the time of recurrence. 
• 
Data collection: standardised eCRF. Solicited AEs will be collected using a subject 
eDiary. 
• 
Safety monitoring: 
The enrolment and vaccination in the PoP phase will also follow a staggered 
approach. After safety assessment (for details refer to Section 8.6.1) of the first 
vaccination of the first approximately 40 subjects (randomised with a 3:1 ratio either 
to the GSK S. aureus candidate vaccine or to the placebo group) the full enrolment 
of the remaining subjects in the PoP phase will continue. The remaining subjects will 
be randomised with a 1:1 ratio either to the GSK S. aureus candidate vaccine or to 
the placebo group. 
Safety of the subjects in the PoP vaccination epoch will be monitored for the entire 
duration of the study with an overall duration of participation for each subject of 
approximately 14 months (i.e. 12 months after last vaccination). 
For both, PoP staggered enrolment/vaccination and the PoP full 
enrolment/vaccination, the investigator is not permitted to start the administration of 
Dose 1 for the next group and Dose 2 until receipt of the favorable outcome of the 
safety evaluation as described in Section 8.6.1. 
During the whole study period, if the investigator becomes aware of a holding rule 
being met, he/she will suspend vaccination and will inform GSK immediately (e.g. in 
case of death or any life-threatening SAEs).  
Refer to Section 8.6 for detailed description of holding rules and safety monitoring. 
Refer to the iSRC Charter for details about the safety assessment committees 
evaluation. 
5.3. 
Number of subjects 
Dose-escalation safety lead-in epochs: 
Approximately 32 subjects will be screened to achieve 32 randomised and 32 evaluable 
subjects for an estimated total of 8 evaluable subjects per treatment group. Withdrawals 
will not be replaced. 
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PoP epochs: 
The design of the PoP phase of the study is event driven. Vaccination of subjects with a 
randomisation of a 1:1 ratio either to the GSK S. aureus candidate vaccine or to the 
placebo group is planned until 
. It is 
estimated that a total of approximately 500 to 600 subjects will be vaccinated in the PoP. 
Approximately 1000 to 1200 subjects may be screened to achieve 500 to 600 randomised 
and evaluable subjects for an estimated total of 250 to 300 evaluable subjects per 
treatment group. Withdrawals will not be replaced. 
5.4. 
Subject and study completion 
A subject is considered to have completed the study if he/she returns for the concluding 
visit as described below:  
•
Dose-escalation safety lead-in:
−
Groups 1 to 3: Visit5-Grp1-3
−
Group 4: Visit8-Grp4
•
PoP:
−
All groups: Visit 10
Global completion of the study is required in order to provide sufficient subjects as 
defined in Section 10.1. 
6.
STUDY POPULATION
6.1. 
Inclusion criteria for enrolment
Deviations from inclusion criteria are not allowed because they can potentially jeopardise 
the scientific integrity, regulatory acceptability of the study or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential. 
All subjects must satisfy ALL the following criteria at study entry: 
•
Subjects who, in the opinion of the investigator, can and will comply with the
requirements of the protocol (e.g. completion of the diary cards, return for follow-up
visits).
•
Written or witnessed informed consent obtained from the subject prior to
performance of any study specific procedure.
•
Subject satisfying screening requirements.
•
Subjects who, after the nature of the study has been explained to them, have shown
adequate comprehension of the study procedures and knowledge of study.
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• 
A male or female: 
− 
Dose escalation and safety lead-in phase: Aged between 18 and 50 years of age, 
inclusive, at the time of first vaccination.  
− 
PoP phase: Aged between 18 and 64 years of age, inclusive, at the time of first 
vaccination.  
• 
Female subjects of non-childbearing potential may be enrolled in the study. Non-
childbearing potential is defined as pre-menarche, current bilateral tubal ligation or 
occlusion, hysterectomy, bilateral ovariectomy or post-menopause. Refer to Section 
12.6.1 for definitions of women of child-bearing potential, menarche and 
menopause. 
• 
Female subjects of childbearing potential may be enrolled in the study, if the subject 
(refer to Section 12.6.1.1 for definitions of woman of child bearing potential and 
adequate contraception): 
− 
has practiced adequate contraception for 30 days prior to vaccination, 
− 
has a negative pregnancy test on the day of enrolment, and 
− 
has agreed to continue adequate contraception during the entire treatment period 
and for 2 months after completion of the vaccination series. 
Additional inclusion criteria only for subjects to be enrolled in the dose-escalation 
safety lead-in screening epoch: 
• 
Healthy subjects as established by medical history, clinical examination and 
laboratory assessment.  
Additional inclusion criteria only for subjects to be enrolled in the PoP screening 
epoch: 
• 
Healthy subjects as established by medical history and clinical examination before 
entering into the study with an ongoing SSTI suspected to be caused by S. aureus, as 
diagnosed by investigator (before randomisation subjects have to be treated until 
clinical resolution of culture confirmed SSTI caused by S. aureus). SSTI must be 
amenable to microbiological culturing per standard clinical practice (i.e. recovery of 
drainage sample from abscess or suppurative cellulitis). 
OR 
• 
Healthy subjects as established by medical history and clinical examination before 
entering into the study with an ongoing S. aureus SSTI (i.e. S. aureus is the most 
likely cause), as confirmed by a S. aureus positive culture performed outside the 
study procedures and not earlier than 30 days prior to ICF signature. Before 
randomisation subjects have to be treated until clinical resolution of the culture 
confirmed SSTI caused by S. aureus. These subjects will be enrolled whether they 
have or have not already started specific treatment of the infection. In case they have 
not started the treatment, this will be then given in compliance with the standard 
medical practice for the management of S. aureus SSTIs and the choice and 
judgment of the most appropriate treatment will be applied by the investigator, 
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6.2. 
Exclusion criteria for enrolment 
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity, regulatory acceptability of the study or subject safety. 
Therefore, adherence to the criteria as specified in the protocol is essential. 
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study. 
6.2.1. 
Medical conditions 
6.2.1.1. 
Subjects to be enrolled in the dose-escalation safety lead-in epochs 
• 
Any active or ongoing illness at screening and the time of injection. 
• 
Body mass index (BMI) >40 kg/m2. 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccine. 
• 
Hypersensitivity to latex. 
• 
Recurrent history of uncontrolled neurological disorders or seizures. 
• 
History of any serious chronic or progressive disease according to the judgment of 
the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic 
disease). 
• 
History of potential immune-mediated disease (pIMD). 
Note: Please refer to Table 33 for a non-exhaustive list of pIMDs. If the subject has 
any condition on this list, they must be excluded unless the etiology is clearly 
documented to be non-immune-mediated. The investigator will exercise his/her 
medical and scientific judgement in deciding whether other diseases have an 
autoimmune origin and thus meet the exclusion criteria. 
• 
Clinical conditions that in the investigator’s opinion represent a contraindication to 
intramuscular vaccination and blood draws. 
• 
Known bleeding diathesis or any condition that may be associated with a prolonged 
bleeding time. 
• 
Any clinically significant* haematological (haemoglobin level, white blood cell, 
lymphocyte, neutrophil, eosinophil, platelet count and red blood cell count) and/or 
biochemical (alanine aminotransferase [ALT], aspartate aminotransferase [AST], 
creatinine) laboratory abnormality.  
*The investigator should use his/her clinical judgement to decide which 
abnormalities are clinically significant as follows: all Haematology/ Biochemistry 
parameters should be within local laboratory normal ranges for the subject to be 
eligible, unless the laboratory abnormalities are of Grade 1 (Refer to Appendix 7, 
Section 12.7) and considered not clinically significant by the investigator. See 
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6.2.1.2. 
Subjects to be enrolled in the proof of principle epochs  
Exclusion criteria to be considered at study entry: 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccine.  
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination, including human 
immunodeficiency virus (HIV) infection, hyper IgE syndrome and chronic 
granulomatous disease (no laboratory testing required).  
• 
Hypersensitivity to latex. 
• 
Major congenital defects, as assessed by the investigator. 
• 
Acute or chronic, clinically significant pulmonary, cardiovascular*, hepatic or renal 
functional abnormality, neoplasm, diabetes type 1 and uncontrolled diabetes type 2*, 
as determined by physical examination or laboratory screening tests.  
* Note: Well-controlled type 2 diabetes mellitus (HbA1c <7%) and well-controlled 
arterial hypertension (blood pressure <140/90 mmHg) can be considered for 
inclusion in the study. 
• 
Body mass index (BMI) >40 kg/m2. 
• 
Recurrent history of uncontrolled neurological disorders or seizures. 
• 
Any behavioural or cognitive impairment or psychiatric disease that, in the opinion 
of the investigator, may interfere with the subject's ability to participate in the study. 
• 
Clinical conditions that in the investigator’s opinion represent a contraindication to 
intramuscular vaccination and blood draws. 
• 
Known bleeding diathesis or any condition that may be associated with a prolonged 
bleeding time. 
• 
Individuals at risk for severe or life-threatening SSTIs (e.g., lymphatic or venous 
insufficiency, liver and kidney disease, IV drug use, etc.) 
• 
History of potential immune-mediated disease (pIMD). 
Note: Please refer to Table 33 for a non-exhaustive list of pIMDs. If the subject has 
any condition on this list, they must be excluded unless the etiology is clearly 
documented to be non-immune-mediated. The investigator will exercise his/her 
medical and scientific judgement in deciding whether other diseases have an 
autoimmune origin and thus meet the exclusion criteria. 
• 
Any other clinical condition that, in the opinion of the investigator, might pose 
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Exclusion criterion to be considered at time of vaccination: 
• 
Any clinically significant* haematological (haemoglobin level, white blood cell, 
lymphocyte, neutrophil, eosinophil, platelet count and red blood cell count) and/or 
biochemical (alanine aminotransferase [ALT], aspartate aminotransferase [AST], 
creatinine) laboratory abnormality at the time of vaccination.  
*The investigator should use his/her clinical judgement to decide which 
abnormalities are clinically significant as follows. All Haematology/ Biochemistry 
parameters should be within local laboratory normal ranges for the subject to be 
eligible, unless the laboratory abnormalities are of Grade 1 (Refer to Appendix 7, 
Section 12.7) and considered not clinically significant by the investigator. See 
Appendix 2, Section 12.2.2 for examples. 
• 
Microbiological test results of drainage suggest that the SSTI etiology could be other 
than infection with S. aureus (i.e. culture shows presence of another pathogen that in 
the investigator’s opinion could have caused the SSTI). 
6.2.2. 
Prior/Concomitant therapy 
The prior or concomitant therapies below are applicable as exclusion criteria for all 
subjects: 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study vaccine(s) during the period starting 30 days before the 
first dose of study vaccine(s)/placebo (Day -29 to Day 1), or planned use during the 
study period. 
• 
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 vaccine/placebo dose. For corticosteroids, this will mean 
prednisone ≥20 mg/day, or equivalent. Inhaled and topical steroids are allowed. 
• 
Cytotoxic therapy (e.g., medications used during cancer chemotherapy). 
• 
Administration of long-acting immune-modifying drugs at any time during the study 
period (e.g. infliximab).  
• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 3 months before the first dose of study vaccine or planned 
administration during the study period. 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol in the period starting 15 days before the first dose and ending 15 days after 
the last dose of vaccine(s) administration* with the exception of any non-adjuvanted 
influenza vaccine which may be administered ≥7 days before or after each study 
vaccination. 
*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 Product 
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6.2.3. 
Prior/Concurrent clinical study experience 
The prior or concurrent clinical study experiences below are applicable as exclusion 
criteria for all subjects: 
• 
Concurrently participating in another clinical study, at any time during the study 
period, in which the subject has been or will be exposed to an investigational or a 
non-investigational vaccine/product (drug or medical device). 
• 
History of having received a vaccine against S. aureus. 
6.2.4. 
Other exclusions 
The other conditions below are applicable as exclusion criteria for all subjects: 
• 
Pregnant or lactating female. 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions before 2 months after completion of the vaccination series. 
• 
History of chronic alcohol consumption and/or drug abuse. Chronic alcohol 
consumption is defined as: a prolonged period of frequent, heavy alcohol use; the 
inability to control drinking once it has begun; physical dependence manifested by 
withdrawal symptoms when the individual stops using alcohol; tolerance, or the need 
to use more and more alcohol to achieve the same effects; a variety of social and/or 
legal problems arising from alcohol use. 
• 
Any study personnel or immediate dependants, family, or household member. 
6.3. 
Criteria for temporary delay for enrolment and vaccination  
Dose-escalation safety lead-in: 
In the dose-escalation safety lead-in epochs time windows for the vaccination visits of 
first vaccination are too small to allow a delayed vaccination due to reasons mentioned 
below. They were only planned to allow sufficient time for the availability of results from 
haematology and chemistry laboratory evaluations before vaccination. For the first 
vaccination please refer to the exclusion criteria in Section 6.2.  
In Group 4a/b the second vaccination may be postponed within the allowed time interval 
until transient circumstances cited below have been resolved: 
• 
Subjects with haematological/biochemical values out of normal range which are 
expected to be temporary may be vaccinated at a later date within the allowed time 
interval. 
• 
Acute disease and/or fever at the time of vaccination. Fever is defined as temperature 
38.0°C/100.4°F. The preferred location for measuring temperature in this study will 
be the oral cavity. Subjects with a minor illness (such as mild diarrhoea, mild upper 
respiratory infection) without fever may be vaccinated at the discretion of the 
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• 
Use of antipyretics and/or analgesics and/or antibiotics within 3 days prior to 
vaccination. 
PoP: 
Vaccination for the PoP epochs may be postponed within the allowed time interval until 
transient circumstances cited below have been resolved: 
• 
Subjects with haematological/biochemical values out of normal range which are 
expected to be temporary may be vaccinated at a later date within the allowed time 
interval. 
• 
Acute disease and/or fever at the time of vaccination. Fever is defined as temperature 
38.0°C/100.4°F. The preferred location for measuring temperature in this study will 
be the oral cavity. Subjects with a minor illness (such as mild diarrhoea, mild upper 
respiratory infection) without fever may be vaccinated at the discretion of the 
investigator.  
• 
Use of antipyretics and/or analgesics and/or antibiotics within 3 days prior to 
vaccination. 
• 
Initial SSTI is not clinically resolved per medical judgment of the investigator (e.g. 
signs of ongoing infection are evident such as swelling, erythema, pain or drainage). 
6.4. 
Screen and baseline failures 
Screening failures are defined as subjects who sign the ICF but do not enter the 
vaccination epoch of the study.  
Dose-escalation safety lead-in: 
Screening failures will be replaced to achieve the planned number of 8 subjects per study 
group. 
PoP: 
Screening activities will continue at sites until the target number of events is reached.  
The following information will be collected in the eCRF for screening failures (dose-
escalation safety lead-in and PoP):  
• 
Informed consent. 
• 
Demographic data. 
• 
Inclusion/exclusion criteria. 
• 
Screening conclusion. 
• 
Concomitant medication/vaccination (if applicable). 
• 
SAEs related to study participation, to concomitant use of GSK products or any fatal 
SAEs (if applicable). 
• 
Microbiology results (PoP only) (if applicable). 

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7. 
TREATMENTS 
Study treatment is defined as a set of investigational product(s) or marketed product(s) or placebo intended to be administered to a subject. 
7.1. 
Treatments administered  
Table 12 
Treatments administered 
Study Treatment 
Name: 
Sa-5Ag half dose non-
adjuvanted  
Sa-5Ag full dose non-
adjuvanted  
Sa-5Ag half dose adjuvanted  
Sa-5Ag full dose adjuvanted * 
Placebo  
Study intervention 
name 
Study intervention 
formulation: 
Presentation 
Powder for solution 
for injection/ vial 
Solution 
for 
injection/ 
vial 
Powder for solution 
for injection/ vial 
Solution 
for 
injection/ 
vial 
Powder for 
solution for 
injection/ vial 
Suspension 
for 
suspension 
for injection/ 
vial 
Powder for 
solution for 
injection/ vial 
Suspension 
for 
suspension 
for injection/ 
vial 
Solution 
for 
injection/ 
vial or 
prefilled 
syringe****
** 
Type 
Study 
Co-
administrat
ion 
Study 
Co-
administrat
ion 
Study 
Co-
administratio
n 
Study 
Co-
administratio
n 
Control 
Product category 
Biological product 
Biological 
product 
Biological product 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Combinati
on product 
Route of 
Administration 
IM 
IM 
IM 
IM 
IM 
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Study Treatment 
Name: 
Sa-5Ag half dose non-
adjuvanted  
Sa-5Ag full dose non-
adjuvanted  
Sa-5Ag half dose adjuvanted  
Sa-5Ag full dose adjuvanted * 
Placebo  
Administration site: 
Location 
Deltoid  
Deltoid 
Deltoid  
Deltoid  
Deltoid  
Directionality  
Upper 
Upper 
Upper 
Upper 
Upper 
Laterality *** 
Non-dominant 
Non-dominant 
Non-dominant 
Non-dominant 
Non-
dominant 
Number of doses 
to be 
administered: 
1 
1 
1 
2**** 
1 or 2 **** 
Volume to be 
administered ***** 
0.5 mL 
0.5 mL 
0.5 mL 
0.5 mL 
at least 0.5 
mL 
Packaging and 
Labelling 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to 
SPM for 
more 
details 
Manufacturer 
 
 SPM = Study 
Procedures Manual 
Note: The half dosage and the full dosage derive from the same product obtained by resuspending the lyophilised product with different volumes (NaCl 
 
* S. aureus candidate vaccine 
  
*** 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 
**** The total number of doses is 1 or 2 depending on the study group, i.e. 2 doses only for subjects in group 4 dose-escalation safety lead-in treatment epoch and PoP treatment 
epoch  
***** Refer to the SPM for the volume after reconstitution 
****** The volume in the syringe may be between 0.6 mL and 0.8 mL. The full volume is to be injected. 
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After completing all prerequisite procedures prior to vaccination (refer to Section 7.7 
regarding the contraindications to subsequent vaccination), 1 dose of reconstituted study 
vaccine or placebo will be administered intramuscularly (IM) in the deltoid preferably of 
the non-dominant arm (refer to Table 12 for details regarding the treatment 
administered).  
If the investigator or delegate determines that the subject’s health on the day of 
administration temporarily precludes vaccine/placebo administration, the visit will be 
rescheduled within the allowed interval for this visit (refer to Table 5 and Table 6). 
The subjects will be observed closely for at least 60 minutes following the administration 
of vaccine/placebo, with appropriate medical treatment readily available in case of 
anaphylaxis and syncope. Occurrence of solicited AEs within 30 minutes post 
vaccination observation must be recorded in the eCRF (Table 4).  
7.2. 
Method of treatment assignment 
7.2.1. 
Subject identification 
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study, according to the range of subject identification 
numbers allocated to each study centre. 
7.2.2. 
Randomisation of treatment 
7.2.2.1. 
Treatment allocation to the subject 
The treatment numbers will be allocated by component.  
7.2.2.1.1. Study group and treatment number allocation  
Dose-escalation safety lead-in: 
For each group, the enrolment of 8 subjects is planned as follows:  
• 
1 vaccinated subject + 1 subject receiving placebo (sentinel subjects).  
The 2 sentinel subjects in each group should be vaccinated on 2 different days. 
• 
5 vaccinated subjects + 1 subject receiving placebo approximately 8 days after 
vaccination of the sentinel subjects (for safety evaluation and consequence on study 
progress refer to Section 8.6.1).  

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PoP: 
The target enrolment of subjects is event driven (
 
). The enrolment in the PoP phase will also follow a staggered 
approach:  
• 
The first approximately 40 subjects will be randomised with a 3:1 ratio (30 subjects 
receiving GSK S. aureus candidate vaccine and 10 receiving placebo). 
• 
The remaining subjects in the PoP epochs will be enrolled approximately 8 days after 
the last of the approximately 40 subjects  was vaccinated (for safety evaluation and 
consequence on study progress refer to Section 8.6.1). The subjects will be 
randomised with a 1:1 ratio either to receive the GSK S. aureus candidate vaccine or 
placebo until 
 (event driven 
design). It is estimated that a total of approximately 500 to 600 subjects will be 
vaccinated in the PoP but enrolment may continue until 27 events is reached (see 
Section 10.1.2). 
Allocation of the subject to a treatment number at the investigator site will be performed 
using a randomisation system on internet (SBIR). The randomisation algorithm will use a 
minimisation procedure (PoP only) accounting for site and for previous SSTIs yes or no 
within the last 12 months. Minimisation factors will have equal weight in the 
minimisation algorithm. 
After obtaining the signed and dated ICF from the subject and having checked the 
eligibility of the subject, the site staff in charge of the vaccine administration will access 
SBIR. Upon providing the subject identification number, the randomisation system will 
determine the study group and will provide the treatment number to be used for the first 
dose. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen. 
When SBIR is not available, please refer to the SBIR user guide or the Study Procedures 
Manual (SPM) for specific instructions. 
7.2.2.1.2. Treatment number allocation for subsequent doses  
For each dose subsequent to the first dose, the study staff in charge of the vaccine 
administration will access SBIR, provide the subject identification number, and the 
system will provide a treatment number consistent with the allocated study group. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen. 
7.3. 
Blinding and unblinding 
Subjects will be randomised at Visit 1 (Day 1) before vaccination (dose-escalation safety 
lead-in and PoP). 
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From that timepoint onwards, data will be collected in an observer-blind manner. By 
observer-blind, it is meant that during the course of the study, the vaccine(s) recipient and 
those responsible for the evaluation of any study endpoint (e.g. safety, reactogenicity, and 
efficacy) will all be unaware of which vaccine was administered. To do so, vaccine 
preparation and administration will be done by authorised medical personnel who will not 
participate in any of the study clinical evaluation assays. 
Each study site is responsible for having a blinding plan.  
Two teams of study personnel will hence be set up: 
• 
A team of unblinded personnel (responsible for the preparation and the 
administration of the vaccines/placebo) 
• 
A team of blinded personnel (responsible for the clinical evaluation of the subjects).  
Refer to the SPM for guidance on vaccine preparation and administration while 
maintaining the blind. 
• 
The laboratory in charge of the laboratory testing will be blinded to the treatment, 
and codes will be used to link the subject and study (without any link to the 
treatment attributed to the subject) to each sample. 
The SBIR will be programmed with blind-breaking instructions. In case of an emergency, 
the investigator has the sole responsibility for determining if unblinding of a subjects’ 
treatment assignment is warranted. Please refer to the Section 7.3.1 for details regarding 
emergency unblinding. 
7.3.1. 
Emergency unblinding  
Unblinding of a subject’s individual treatment code should occur only in the case of a 
medical emergency when knowledge of the treatment is essential for the clinical 
management or welfare of the subject. 
The emergency unblinding process consists of the automated Internet-based system 
(SBIR) that allows the investigator to have unrestricted, immediate and direct access to 
the subject’s individual study treatment. 
As back-up process, the investigator has the option of contacting a GSK Helpdesk (refer 
to Table 13) if he/she needs support to perform the unblinding (i.e. he/she cannot access 
the automated Internet-based system). 
Non-investigator physician (e.g. physician from emergency room) or subject/care 
giver/family member can also request emergency unblinding either via the investigator 
(preferred option) or via the GSK Helpdesk (back-up process). Contact details of 
investigator and GSK Helpdesk are reported in the patient/subject card. 

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Table 13 
Contact information for emergency unblinding  
GSK Helpdesk 
24 hours/7 days availability 
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 
For US 
Toll-free number: 1 844 446 3133 
GSK policy (which incorporates ICH E2A guidance, EU Clinical Trial Directive and US 
Federal Regulations) is to unblind the report of any SAE which is unexpected and 
attributable/suspected to be attributable to the study vaccine(s) prior to regulatory 
reporting. Vaccines Clinical Safety and Pharmacovigilance (VCSP) is responsible for 
unblinding the treatment assignment in accordance with the specified timeframes for 
expedited reporting of SAEs (refer to Section 12.5.9.2).  
A subject may continue in the study if that subject’s treatment assignment is unblinded.  
GSK VCSP staff may unblind the treatment assignment for any subject in case of 
Suspected Unexpected Serious Adverse Reaction (SUSAR) as well as in case of fatal or 
life-threatening cases. If the SAE requires that an expedited regulatory report be sent to 1 
or more regulatory agencies, a copy of the report, identifying the subject’s treatment 
assignment, may be sent to investigators in accordance with local regulations and/or GSK 
policy. 
7.4. 
Handling, storage and replacement of study 
vaccine(s)/product(s) 
7.4.1. 
Storage and handling of study vaccines 
The study vaccines must be stored at the respective label storage temperature conditions 
in a safe and locked place. Access to the storage space should be limited to authorised 
study personnel. The storage conditions will be assessed during pre-study activities under 
the responsibility of the sponsor study contact. The storage temperature should be 
continuously monitored with calibrated (if not validated) temperature monitoring 
device(s) and recorded. Refer to the Module on Clinical Trial Supplies in the SPM for 
more details on storage of the study vaccines. 
A temperature excursion is any temperature that is not in range of the label storage 
temperature conditions. Temperatures outside the range of label storage temperature 
conditions must be reported and/or documented. Temperature excursion impacting study 
vaccines must be reported and/or documented. 

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In the frame of the reporting, the lack/absence of temperature monitoring documentation 
from a device meeting GSK requirements has to be considered as a temperature 
excursion. 
Study vaccine(s) that are impacted by a temperature excursion may not be used and must 
be quarantined at label storage conditions until usage approval has been obtained 
from/via the local study contact (e.g. Site Monitor). 
Refer to the Module on Clinical Trial Supplies in the SPM for details and instructions on 
the temperature excursion reporting and usage decision process, packaging and 
accountability of the study vaccine(s). 
7.4.2. 
Replacement of unusable vaccine doses 
In addition to the vaccine doses provided for the planned number of subjects (including 
over-randomisation when applicable), at least 10% additional vaccine/placebo doses will 
be supplied to replace those that are unusable.  
The investigator will use SBIR to obtain the replacement dose number. The replacement 
numbers will be allocated by component. The system will ensure, in a blinded manner, 
that the replacement dose matches the formulation the subject was assigned to by 
randomisation. 
7.5. 
Concomitant medication(s)/product(s) and concomitant 
vaccinations 
7.5.1. 
Recording of concomitant medications/products and 
concomitant vaccinations 
At each study contact, the investigator or delegate should question the subject about any 
medications/products taken and vaccinations received by the subject. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF 
• 
All concomitant medications/products, except vitamins and dietary supplements, 
administered during a period of 30 days following the first (from Day 1 to Day 31) 
and the second (from Day 61 to Day 91) dose of study vaccine/placebo, as applicable 
according to the study group.  
• 
Any concomitant vaccination administered during the whole study period. 
• 
Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination). 
An anti-pyretic is considered to be prophylactic when it is given in the absence of 
fever and any other symptom, to prevent fever from occurring [fever is defined as 
temperature 38.0°C/100.4°F regardless the location of measurement]. The preferred 
location for measuring temperature in this study will be the oral cavity. 

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• 
Any concomitant medications/products/vaccines leading to the withdrawal or non-
eligibility of the subject from the study. Please refer to the Section 7.5.2 for further 
details. 
• 
Any concomitant medications/products/vaccines relevant to an SAE/pIMD to be 
reported as per-protocol or administered at any time during the study period for the 
treatment of an SAE/pIMDs. In addition, concomitant medications relevant to SAEs 
and pIMDs need to be recorded on the expedited Adverse Event report. 
• 
Any concomitant medications/product/vaccines aiming to prevent the occurrence of 
S. aureus SSTI. 
7.5.2. 
Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from per-protocol analyses 
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the subject from the study but may determine a subject’s evaluability in the 
per-protocol analysis. See Section 10.2 for populations to be analysed. 
For withdrawal of subjects from further vaccinations refer to Section 7.7 
(contraindications against subsequent vaccination). 
• 
Any investigational or non-registered product (drug or vaccine) other than the study 
vaccines used during the study period.  
• 
Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. more than 14 days in total) during the study period. For corticosteroids, this will 
mean prednisone 20 mg/day, or equivalent. Inhaled and topical steroids are 
allowed.  
• 
Long-acting immune-modifying drugs administered at any time during the study 
period (e.g. infliximab). 
• 
A vaccine not foreseen by the study protocol administered during the period starting 
15 days before the first dose and ending 15 days after the last dose of 
vaccine(s)/placebo administration*, with the exception of any non-adjuvanted 
influenza vaccine which may be administered ≥7 days before or after each study 
vaccination.  
*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 Product 
Information.  
• 
Immunoglobulins and/or any blood products administered during the study period. 
• 
Drug and/or alcohol abuse. 

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7.6. 
Intercurrent medical conditions that may lead to elimination 
of a subject from per-protocol analyses 
At each study visit subsequent to the vaccination visit, it must be verified if the subject 
has experienced or is experiencing any intercurrent medical condition that may lead to 
elimination from per-protocol analysis. If it is the case, the condition(s) must be recorded 
in the eCRF. 
Subjects may be eliminated from the per-protocol set for efficacy and immunogenicity if, 
during the study, they incur a condition that has the capability of altering their immune 
response (e.g. malignancies) or are confirmed to have an alteration of their initial immune 
status. 
7.7. 
Contraindications to subsequent vaccine(s) administration 
Prior to receipt of additional study vaccination, subjects must be evaluated to confirm that 
they are eligible for subsequent vaccination.  
If subjects meet any of the original exclusion criteria or the criteria listed below, they 
should not receive additional vaccinations. However, the subjects should be encouraged 
to continue other study procedures at the discretion of the investigator (Section 8.5.5). 
• 
Subjects who experience any serious adverse event judged to be possibly or probably 
related to study vaccine or non-study vaccines, including hypersensitivity reactions. 
• 
Subjects who develop any new condition which, in the opinion of the investigator, 
may pose additional risk to the subject if he/she continues to participate in the study. 
• 
Occurrence of a new pIMD or the exacerbation of an existing pIMD that, in the 
opinion of the investigator, exposes the subject to unacceptable risk from subsequent 
vaccination. In such cases, the investigator should use his/her clinical judgement 
prior to administering the next dose of the vaccine(s). Refer to Section 12.5.5.1 for 
the definition of pIMDs. 
7.8. 
Treatment after completion of the study 
Not applicable. 
8. 
STUDY ASSESSMENTS AND PROCEDURES  
Study procedures and their timing are summarised in Section 2, Schedule of Activities.  
Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns.  
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness, to determine if the subject(s) should discontinue study 
treatment. 

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Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for 
screening failure, as applicable.  
Procedures conducted as part of the subject’s routine clinical management (e.g. drainage, 
S. aureus confirmation) and obtained before signing of ICF may be utilised for screening 
or baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA. 
Under special circumstances, modification of specific study procedures may be 
implemented.  
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:  
• 
Safety follow-up may be made by a telephone call, other means of virtual contact or 
home visit, if appropriate. 
• 
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 . 
• 
Blood samples for safety assessment may be collected at a different location1 other 
than the study site or at participant’s home. Blood samples should not be collected if 
they cannot be processed in a timely manner or appropriately stored until the 
intended use.  
8.1. 
General study aspects 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects. 
                                                 
1 It is the investigator’s responsibility to identify an alternate location. The investigator should ensure that 
this alternate location meets 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. Refer to EMA 
Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic (version 
2, 27 March, 2020) for more details. 

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8.2. 
Pre-vaccination procedures 
8.2.1. 
Informed Consent 
The signed/witnessed informed consent of the subject must be obtained before study 
participation (at the screening visit). Refer to Section 12.4.3 for the requirements on how 
to obtain informed consent. 
8.2.2. 
Collection of demographic data 
Record demographic data such as month and year of birth, sex, race and ethnicity in the 
subject’s eCRF. 
8.2.3. 
Medical/vaccination history 
Obtain the subject’s medical/vaccination history by interview and/or review of the 
subject’s medical records and record any pre-existing conditions or signs and/or 
symptoms present in a subject at the screening visit and for the PoP also at Visit 1 prior to 
the first study vaccination in the eCRF. Take note of whether the subject has had a SSTI 
within 12 months preceding the initial infection at study entry. 
8.2.4. 
Physical examination 
At the screening visit and at each vaccination visit a complete physical examination will 
be performed for all subjects.  
Perform a physical examination of the subject, including assessment of resting vital 
signs: systolic/diastolic blood pressure, heart rate and respiratory rate after at least 10 
minutes of rest.  
Blood pressure and pulse measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
Physical examination at other visits will be performed only if the subject indicates during 
questioning that there might be some underlying pathology(ies) or if deemed necessary 
by the Investigator or delegate. 
Height and weight will be measured pre-vaccination, at visit 1. 
Collected information at the pre-vaccination visits needs to be recorded in the eCRF.  
If the investigator determines that the subject’s health on the day of vaccination 
temporarily precludes vaccination, the visit will be rescheduled within the allowed time 
interval for this visit (see Table 5 and Table 6). 
Treatment of any abnormality observed during this examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider. 

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8.2.5. 
Pregnancy test 
Female subjects of childbearing potential are to have a urine pregnancy test prior to any 
study vaccine administration. The study vaccine(s)/placebo may only be administered if 
the pregnancy test is negative.  
Note: Pregnancy test must be performed even if the subject is menstruating at the time of 
the study visit. 
8.2.6. 
Pre-vaccination body temperature 
The oral body temperature of each subjects needs to be measured prior to any study 
vaccine(s)/placebo administration. If the subject has fever [fever is defined as body 
temperature 38.0°C/100.4°F regardless the location of measurement] on the day of 
vaccination, the vaccination visit will be rescheduled within the allowed interval for this 
visit (see Section 6.3). 
8.3. 
Case definition of recurrent S. aureus SSTI 
Subjects that report signs or symptoms compatible with an SSTI are invited to present 
themselves for an ad-hoc visit. The investigator will assess whether the subject has an 
SSTI suspected to be caused by S. aureus, and whether the lesion is amenable to 
microbiological diagnostics (i.e. abscess with drainage or purulent cellulitis). Diagnosis 
(i.e. abscess or cellulitis) and body location will be collected in the eCRF. Samples for 
microbiological culture will be obtained whenever possible, and treatment will ensue 
according to the investigator’s clinical judgment. Provided that the episode is a new 
(recurrent) SSTI, rather than incomplete resolution of a previous SSTI per investigators 
judgment, the case will be assessed as follows. 
• 
If results from microbiological diagnostics in the investigator’s opinion suggest that 
S. aureus is the primary cause of the SSTI, then the case will be considered as a 
culture confirmed recurrence. 
• 
If results from microbiological diagnostics are inconclusive, or if no microbiological 
testing was performed, then the case will be considered as a suspected recurrence. 
• 
If results from microbiological diagnostics suggest that another pathogen is the 
primary cause of the SSTI, or if no microbiological testing was performed and the 
investigator considers other causes for the lesion to be equally or more probable than 
infection by S. aureus, then the case will not be reported unless it fulfils other 
reporting requirements (e.g. AE). 
Should the subject report an SSTI that has already occurred and resolved, e.g. because 
medical attention was sought elsewhere or not at all, the investigator will seek permission 
to obtain clinical records from the managing physician in order to evaluate the case per 
the above criteria. 

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8.4. 
Efficacy and/or immunogenicity assessments  
Please refer to the SPM for details on biospecimen management (handling, storage and 
shipment). 
Samples which will be sent to GSK laboratories or GSK designated laboratories will not 
be labelled with information that directly identifies the subject but will be coded with the 
identification number for the subject (subject number). 
It is also possible that future findings may make it desirable to use the samples acquired 
in this study for future research, not described in this protocol. Therefore, all subjects will 
be asked to give a specific consent to allow GSK or a contracted partner to use the 
samples for future research. Future research will be subject to the laws and regulations in 
the respective countries and will only be performed once an independent Ethics 
Committee or Review Board has approved this research.  
Information on further investigations and their rationale can be obtained from GSK. 
Any sample testing will be done in line with the consent of the individual subject. 
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s).  
The investigator is not allowed to do extra testing on samples including drainage samples 
outside of what has been agreed upon by the ethic committees. 
Collected samples will be stored for a maximum of 20 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with GSK. 
8.4.1. 
Use of specified study materials 
When materials are provided by GSK, it is MANDATORY that all clinical samples 
(including serum samples) be collected and stored exclusively using those materials in 
the appropriate manner. The use of other materials could result in the exclusion of the 
subject from the per-protocol analysis (see Section 10.2 for the definition of populations 
for analyses). The investigator must ensure that his/her personnel and the laboratory(ies) 
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under his/her supervision comply with this requirement. However, when GSK does not 
provide material for collecting and storing clinical samples, appropriate materials from 
the investigator’s site must be used. Refer to the Module on Clinical Trial Supplies in the 
SPM. 
8.4.2. 
Biological samples 
Refer to the Module on Biospecimen Management in the SPM for detailed instructions 
for the collection, handling and processing of the samples. 
8.4.2.1. 
Sampling for efficacy assessments 
Skin drainage samples will be collected from those subjects in the PoP performing 
culture test as a study procedure at screening (i.e. Day –30 [Visit 0]) and from all subjects 
at the time of their recurrence of SSTI (i.e. unscheduled visits).  
Drainage samples will not be stored. 
Table 14 
Biological samples for efficacy assessment (PoP)  
Sample type 
Quantity 
Unit 
Timepoint 
Subjects 
Drainage samples 
Depends on availability 
Day –30 (V0) 
 
 
 
Unscheduled* 
Subjects with SSTI who perform 
culture test as a study procedure at 
screening 
 
Subjects with suspected SA-SSTI 
V = Visit 
* Additionally, subjects with recurrent SSTI at the time of recurrence 
8.4.2.2. 
Blood sampling for immunogenicity response assessments  
Refer to the SPM for detailed information on sample collection and storage. 
The maximum amount of blood collected from each subject over the duration of the 
study, including any extra assessments that may be required, will not exceed 125 mL for 
subjects participating in the dose-escalation safety lead-in and will not exceed 274 mL for 
subjects participating in the PoP. 
Blood samples will be taken during certain study visits as specified in Section 2 Schedule 
of Activities (SoA). For more information regarding blood sampling for haematologal 
and chemistry evaluations refer to Section 8.5.7. 
• 
In the dose-escalation safety lead-in:  
− 
A volume of at least approximately 10 mL of whole blood (to provide at least 
3.3 mL of serum) should be drawn from all subjects for serum preparation at 
each pre-defined timepoint. After whole blood processing into serum, samples 
should be kept at –20°C (–4°F) or below until shipment.  
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8.4.3. 
Laboratory assays 
Please refer to Section 12.2 (Appendix 2) for a description of the haematology/chemistry 
and immunological assays performed in the study. Please refer to Section 12.3 
(Appendix 3) for the address of the clinical laboratories used for sample analysis. 
8.4.3.1. 
Microbiology assessment for efficacy 
Conventional bacteriological methods at the investigator’s institution and/or at a 
laboratory designated by GSK Biologicals will be used to study the skin infection 
aetiology, and in particular to demonstrate if S. aureus is the leading bacterial cause of 
the infection. (Table 17). The laboratories that will perform microbiology assessment 
listed in Table 17 are not yet identified. Each laboratory will be performing the 
microbiological evaluations according to their own routine clinical practices. 
Table 17 
Microbiology 
System 
Component 
Method 
Laboratory 
Skin drainage 
S. aureus identification 
 
Standard bacteriological 
methods 
Investigator’s institution and/ or at 
a laboratory designated by GSK 
Biologicals  
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8.4.4. 
Immunological correlates of protection 
No generally accepted immunological correlate of protection has been demonstrated so 
far for S. aureus. 
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8.5. 
Safety Assessments  
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. This includes the assessment 
of COVID-19 cases per the WHO definition [WHO, 2020]. The investigator and any 
designees remain responsible for following up AEs that are serious, considered related to 
the study treatment or the study, or that caused the subject to discontinue the this study.  
8.5.1. 
Safety definitions 
Please refer to Section 12.5 for safety definitions. 
8.5.2. 
Time period and frequency for collecting AE and serious adverse 
event (SAE) information  
An overview of the protocol-required reporting periods for AEs, SAEs, and pregnancies 
is given in Table 21 for dose-escalation safety lead-in and Table 22 for PoP. Refer to the 
Section 12.5.8.1 for details on the time period for recording safety information. 

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Table 21 
Reporting periods for collecting safety information (dose-escalation 
safety lead-in)  
Event 
Study group 
Pre-Vac Vac1 
 
 
 
Vac2 
 
 
 
Study 
Conclusion 
 
Half dose non-
adjuvanted 
Full dose non-
adjuvanted 
Half dose adjuvanted 
D–1* 
D1 
D7 
D30 
 
NA 
NA 
NA 
 
D366 
M12 
 
Full dose 
adjuvanted 
D–1* 
D1 
D7 
D30 
 
D61 D67 D90 
 
D426 
M14 
Solicited local 
and general AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs 
leading to 
withdrawal from 
the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to 
the study 
vaccine(s) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to 
study participation 
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
pIMDs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.  
** Unsolicited AEs/SAEs due to COVID-19 will be recorded according to the WHO case definition [WHO, 2020]. 
AEs = Adverse Events; SAEs = Serious Adverse Events; pIMDs = potential Immune-Mediated Diseases; Pre-Vac = 
Pre-Vaccination; Vac = Vaccination; D = Day; M = Month 

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Table 22 
Reporting periods for collecting safety information (PoP)  
Event 
Study group Pre-
Vac 
Vac1 
 
 
 
Vac2 
 
 
 
Study 
Conclusion 
 
Vaccine 
Placebo 
D–30* D1 
D7 
D30 
 
D61 D67 D90 
 
D426 
M14 
Solicited local and 
general AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading 
to withdrawal from 
the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to the 
study vaccine(s)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation or 
concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
pIMDs  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.  
** Unsolicited AEs/SAEs due to COVID-19 will be recorded according to the WHO case definition [WHO, 2020]. 
AEs = Adverse Events; SAEs = Serious Adverse Events; pIMDs= potential Immune-Mediated Diseases; Pre-Vac = 
Pre-Vaccination; Vac = Vaccination; D = Day; M = Month 
All SAEs will be recorded and reported via Expedited AE Reporting Form to the sponsor 
or designee immediately and under no circumstance should this exceed 24 hours after the 
investigator became aware of it, as indicated in Section 12.5 (Appendix 5). The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 

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A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Table 21 and Table 22. Investigators are not obligated to 
actively seek AEs or SAEs in former study subjects. However, if the investigator learns 
of any SAE, including a death, at any time after a subject has been discharged from the 
study, and he/she considers the event to be reasonably related to the study vaccine(s), the 
investigator will promptly notify the Study Contact for Reporting SAEs. 
8.5.3. 
Method of detecting AEs and SAEs 
The method of recording, evaluating, and assessing intensity, causality and outcome of 
AEs and SAEs and the procedures for completing and transmitting SAE reports are 
provided in Section 12.5.8. 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the subjects is the preferred method to inquire about 
AE occurrence.  
8.5.4. 
Reporting of serious adverse events, pregnancies, and other 
events 
SAEs, pregnancies and pIMDs that occur in the time period defined in Section 8.5.2 will 
be reported promptly to GSK within the timeframes described in Table 23 once the 
investigator determines that the event meets the respective protocol definition. 
Table 23 
Timeframes for submitting serious adverse event, 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 
pIMDs  
24 hours** ‡ 
electronic Expedited 
Adverse Events Report 
24 hours* 
Electronic Expedited Adverse 
Events Report 
* Timeframe allowed after receipt or awareness of the information. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of a pIMD. 
‡ The investigator will be required to confirm review of the SAE/pIMD causality within 72 hours of submission of the 
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8.5.4.1. 
Contact information for reporting of serious adverse events (SAEs), 
pIMDs, pregnancies and study holding rules 
Table 24 
Contact information for reporting of serious adverse events (SAEs), 
pIMDs, pregnancies and study holding rules 
Study contact for questions regarding SAEs, pIMDs, pregnancies and study holding rules  
Refer to the local study contact information document 
Study Contact for Reporting of study holding rules  
As soon as the investigator is aware that a holding rule is met, he/she must immediately inform the Local Medical 
Lead (LML).  
Back-up Study Contact for Reporting SAEs, pIMDs, pregnancies and study holding rules  
24 hours/7 days availability: 
GSK Clinical Safety & Pharmacovigilance 
Outside US 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 
8.5.4.2. 
Regulatory reporting requirements for SAEs 
Prompt notification of an SAE by the investigator to the sponsor is essential for meeting 
legal obligations and ethical responsibilities for the safety of subjects and the safety of a 
study treatment under clinical investigation.  
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study treatment under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (e.g. summary or listing of SAE) from the sponsor will review 
and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, if 
appropriate according to local requirements. 
8.5.5. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject at subsequent visits/contacts. All SAEs and pIMDs (serious and non-serious), will 
be followed until the event is resolved, stabilised, otherwise explained, or the subject is 
lost to follow-up. Further information on follow-up procedures is given in 
Section 12.5.11. 

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8.5.6. 
Treatment of adverse events 
Treatment of any AE is at the sole discretion of the investigator and according to current 
good medical practice. Any medication administered for the treatment of a SAE/pIMD 
should be recorded in Expedited Adverse Event Report of the subject’s eCRF (refer to 
Section 7.5). 
8.5.7. 
Clinical safety laboratory assessments 
In the dose-escalation safety lead-in and in the PoP Step 1 (i.e. first 40 subjects enrolled 
in the PoP): a volume of approximately 6 mL of whole blood should be drawn from all 
subjects for each analysis for haematology and chemistry assessments at each pre-defined 
timepoint (Table 25). Part of the whole blood will be processed into serum and will be 
managed according to local laboratory practices.  
Table 25 
Biological samples for haematology and chemistry assessments  
Sample type 
Quantity 
Unit 
Study group 
Timepoint 
Subjects 
Blood for 
haematology and 
chemistry 
~6 
mL 
1a/b Half dose non-adjuvanted 
2a/b Full dose non-adjuvanted 
3a/b Half dose adjuvanted 
Day –1 (V0-Grp1-3) 
Day 8 (V2-Grp1-3) 
All subjects 
4a/b Full dose adjuvanted 
Day –1 (V0-Grp4) 
Day 8 (V2-Grp4) 
Day 61 (V4-Grp4) 
Day 68 (V5-Grp4) 
All subjects 
~6 
mL 
5a/b vaccine/placebo 
Day 1 (V1) 
Day 8 (V2) 
Day 61 (V5) 
Day 68 (V6) 
PoP Step 1 (i.e. 
first 40 subjects 
enrolled in the 
PoP) 
V = Visit; Grp = Group; a/b = vaccine/placebo 
Refer to Section 12.2 (Appendix 2) for the list of clinical laboratory tests to be performed 
and to the SoA for the timing and frequency.  
The tests detailed in Appendix 2, Section 12.2 will be performed by the local laboratory 
at the investigator’s site. Results of tests will be needed before vaccination i.e. on the 
same of the blood draw day for PoP Step 1 or latest on the next day for dose-escalation 
safety lead-in (see also Section 6.2 exclusion criteria). 
• 
The investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the AE section of the 
eCRF. The laboratory reports must be filed with the source documents. 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 subject's condition. 
• 
All laboratory tests with values considered clinically significant abnormal during 
participation in the study or within 8 days after the last dose of study treatment 
should be repeated until the values return to normal or baseline or are no longer 
considered significantly abnormal by the investigator or medical monitor. Refer to 

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the Section 12.5.6 for clinical laboratory abnormal assessments qualified as AEs or 
SAEs. 
• 
If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified. 
All protocol-required laboratory safety assessments, as defined in Section 12.2 (Appendix 
2), must be conducted in accordance with the SPM and the SoA. 
8.5.8. 
Subject card 
Study subjects must be provided with the address and telephone number of the main site 
contact for information about the clinical study. 
The investigator (or designate) must therefore provide a “subject card” to each subject. In 
an emergency situation, this card serves to inform the responsible attending physician 
that the subject is in a clinical study and that relevant information may be obtained by 
contacting the investigator. 
Subjects must be instructed to keep subject cards in their possession at all times during 
the study duration. 
8.6. 
Holding rules and safety monitoring 
For both, the dose-escalation safety lead-in and PoP, the investigator will not be 
permitted to start the administration of Dose 1 for the next group until receipt of the 
favourable outcome of the safety assessment committees evaluation (SRT/iSRC), 
documented and provided in writing (scanned and emailed), authorising the investigator 
to proceed. The same applies for the administration of Dose 2 in the fourth group of the 
dose-escalation safety lead-in and for the administration of Dose 2 in the staggered 
enrolment of first 40 subjects of the PoP epoch.  
Refer to the iSRC Charter for details about the safety assessment committees evaluation.  
During the whole study period (dose-escalation safety lead-in and PoP) if the investigator 
becomes aware of a holding rule being met, he/she will suspend vaccination and will 
inform GSK immediately (e.g. in case of death or any life-threatening SAEs).  
8.6.1. 
Staggered vaccination 
A staggered enrolment approach of healthy subjects of the dose-escalation safety lead-in 
epochs is chosen and additionally a staggered enrolment of subjects in PoP epochs. The 
safety assessment committees (SRT/iSRC) will evaluate safety throughout the study and 
will decide at different steps about continuation of the study. 

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Staggered enrolment in dose-escalation safety lead-in epochs: 
Four groups receiving 4 different vaccine formulations will be included in the dose-
escalation safety lead-in epochs (for details see Section 5.2 and Figure 5). Subjects in the 
4 groups will be enrolled in 4 successive steps (see Figure 7), the next group can only be 
enrolled after safety assessment of the previous group and safety assessment committees 
(SRT/iSRC) approval. Additionally, for each step/group, a 2-substep staggered design is 
chosen (see Figure 7): 
• 
Substep a: 1 vaccinated subject + 1 subject receiving placebo (sentinel subjects). The 
2 sentinel subjects in each group should be vaccinated on 2 different days. All the 
available safety data collected up to the Day 8 after vaccination visit from both 
subjects (including laboratory assessments at Day 8) will be evaluated. The SRT and 
iSRC Chair will evaluate safety data and confirm the start of the step below. 
Conditionally; unblinded data may be evaluated by iSRC and only after positive 
opinion of iSRC the next step can be started. 
• 
Substep b: 5 vaccinated subjects + 1 subject receiving placebo. All the available 
safety data collected up to the Day 8 after vaccination visit for the last vaccinated 
subject (including laboratory assessments at Day 8) will be evaluated. The SRT and 
iSRC Chair will evaluate all the safety data available and confirm the start of the 
next step (subsequent group). Conditionally; unblinded data may be evaluated by 
iSRC and only after positive opinion of iSRC the next step can be started. 
All the unblinded data collected up to Day 8 after vaccination Visit 1 of the fourth 
group will be reviewed by iSRC.  
After the iSRC unblinded data review of dose 1 of the fourth group of the dose-escalation 
safety lead-in and prior to administering the second vaccine/placebo dose in that fourth 
group, the staggered enrolment of the first approximately 40 subjects in the PoP epochs 
in the vaccine target population (subjects with a recent S. aureus SSTIs) can start.  
The fourth group will receive a second vaccine/placebo dose with an interval of 
approximately 2 months and subjects of all the groups will be followed until study end 
(i.e. for each subject approximately 12 months after last vaccination). 
Staggered enrolment in PoP epochs (for details see Section 5.2 and Figure 6 and 
Figure 8): 
In a first step (PoP step 1) first dose of vaccination will be performed with a staggered 
approach. Enrolment will be stopped as soon as 40 subjects have been vaccinated with 
the first dose of the GSK S. aureus candidate vaccine or placebo. Only subjects who 
already signed the ICF and entered the screening phase, at the time of enrolment hold, 
will be allowed to continue the study; therefore, approximately 40 subjects (30 subjects 
receiving GSK S. aureus candidate vaccine and 10 receiving placebo) will be evaluated 
for safety. After iSRC evaluation of unblinded safety data collected up to the Day 8 after 
first dose (including laboratory assessments) for the last vaccinated subject of this 
staggered subset (step 1) has shown lack of safety issues, the PoP step 2, (full enrolment 
of the remaining subjects in the PoP epochs) will continue.  

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The investigator will not be permitted to start the administration of the second 
vaccine/placebo dose in the staggered PoP subset from step 1 (approximately 40 subjects) 
until receipt of the favourable outcome of the SRT and iSRC Chair, which needs to 
evaluate all the safety data available up to Day 68 (including laboratory assessments) 
related to the subjects of the fourth group (Full dose adjuvanted) of the last dose-
escalation safety lead-in step. Conditionally, unblinded data may be evaluated by iSRC 
and, only after positive opinion of iSRC, the next step (i.e. second dose of staggered PoP 
subset) can be started. 
All subjects will be closely observed at the site for a minimum of 60 minutes after 
vaccination. Occurrence of solicited AEs within 30 minutes post vaccination observation 
must be recorded in the CRF (Table 4).  
For both, the dose-escalation safety lead-in and PoP, the investigator is not permitted to 
start the administration of Dose 1 for the next group until receipt of the favourable 
outcome of the safety assessment committees evaluation (SRT/iSRC), documented and 
provided in writing (scanned and emailed), authorising the investigator to proceed 
(Figure 7 and Figure 8). The same applies for the administration of Dose 2 in the fourth 
group of the dose-escalation safety lead-in and for the administration of Dose 2 in the 
staggered enrolment of first 40 subjects of the PoP epoch.  
In case more than 1 subject is to be vaccinated on the same day per site, subjects should 
be vaccinated sequentially at this site and at least 60 minutes apart as acute adverse 
reactions, like anaphylactic shock, typically occur within 1 hour of vaccination (for 
holding rules refer to Section 8.6.3 and Table 26). Therefore, not vaccinating subjects in 
parallel and leaving at least 60 minutes between vaccinations of 2 consecutive subjects 
will ensure that, in the event of an acute adverse reaction, the site will be able to provide 
the required medical attention. The 2 sentinel subjects of Groups 1 to 4 of dose-escalation 
safety lead-in should be vaccinated on 2 different days. 

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Figure 7 
Overview of staggered enrolment and safety evaluation (dose-
escalation safety lead-in)  
 
* Safety reviews will take into account all safety data accumulated up to the specified timepoint 
Figure 8 
Overview of staggered enrolment and safety evaluation (PoP) 
 
* All safety reviews (i.e. SRTs/iSRCs) will take into account all safety data accumulated up to the specified timepoint  

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8.6.2. 
Outcome of safety evaluation 
• 
If no safety signal is observed, the favourable outcome of the safety evaluations will 
be documented and provided in writing (scanned and e-mailed), authorising the 
investigator to start vaccination of subjects with the subsequent dose as well as 
enrolment and vaccination of the remaining subjects in the next step of the study, as 
applicable. 
• 
In case the investigator becomes aware of holding rule(s) 1 is met, he/she should 
immediately inform GSK of the event (Refer to Table 24 for contact information). 
• 
If a safety signal is observed during the safety evaluations or if any of the holding 
rules 2a-c is met, the iSRC Chair (or his/her representative) is responsible for the 
urgent communication to GSK, including the rationale for the decision to put the 
vaccination on hold or not.  
• 
All site staff will be informed about that final decision (suspend or continue the 
study) by their local GSK contact. CRDL who is the primary contact will inform the 
local GSK contact.  
8.6.3. 
Study holding rules 
The safety holding rules are defined in Table 26. Holding rules 1 will be assessed by the 
investigator on a continuous basis irrespective of the number of subjects enrolled and 
meeting any of these holding rules will trigger a hold of vaccination irrespective of 
number of subjects enrolled and/or timing of the event relative to vaccination. Holding 
rules 2 will be assessed by the iSRC during the safety evaluations on unblinded data. 
Please refer to Appendix 7, Section 12.7 for the definition of the Toxicity Grading Scale 
for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Trials. 
These holding rules have been written under the assumption that the safety data from all 
subjects will be available. If the data from all subjects are not available (i.e. in case a 
subject 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 non-life-
threatening SAEs, missed visits due to vaccine-related AEs, Grade 1 and Grade 2 (Refer 
to Section 12.5.8.2.2) solicited and unsolicited AEs in the 7-day follow-up period and 
unsolicited AEs collected from Day 8 to Day 30 after vaccination. However, these data, if 
available, will also be reviewed by the safety assessment committee (SRT/iSRC as 
applicable) in order to allow for an overall assessment of the benefit/risk ratio of 
vaccination. 

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Table 26 
Study holding rules 
 
 
FTIH Dose-
escalation 
Safety Lead-In 
steps 1-4 
Staggered 
enrolment step of 
PoP vaccination 
epoch (PoP step 
1) 
Full enrolment 
step of PoP 
vaccination 
epoch (PoP 
step 2) 
Holding 
rule 
Event 
Number of 
subjects 
needed to 
trigger the 
hold 
Number and % of 
subjects needed 
to trigger the hold 
Number of 
subjects 
needed to 
trigger the hold 
1a 
Death or any life-threatening SAE 
≥ 1 
≥ 1 
≥ 1 
1b 
Any withdrawal from the study (by 
investigator or subject request) following a 
Grade 3 AE that cannot reasonably be 
attributed to a cause other than vaccination 
≥ 1 
≥ 1 
N/A 
1c 
Any local or general solicited AE leading to 
hospitalization, or fever >40°C (104°F) or 
necrosis at the injection site, within the 7-
day (Days 1-7) post-vaccination period 
≥ 1 
≥ 1 
N/A 
2a 
Any Grade 3 solicited local AE (lasting 48h 
or more) in an investigational group, within 
the 7-day (Day 1-7) post-vaccination period 
≥ 1 
≥ 6/30 or 20% 
N/A 
2b 
Any Grade 3 solicited general AE (lasting 
48h or more) in an investigational group, 
within the 7-day (Day 1-7) post-vaccination 
period 
≥ 1 
≥ 6/30 or 20% 
N/A 
2c 
Any Grade 3 unsolicited AE in an 
investigational group, that cannot 
reasonably be attributed to a cause other 
than vaccination, within the 7-day (Day 1-7) 
post-vaccination period or any Grade 3 
abnormality in pre-specified haematological 
or biochemical laboratory parameters in an 
investigational group within the 7-day (Day 
1-7) post-vaccination period * 
≥ 1 
≥ 6/30 or 20% 
N/A 
AE = Adverse Event; SAE = Serious Adverse Event; FTIH = First Time in Human; PoP = Proof of Principle; N/A = Not 
Applicable 
* Grading of laboratory parameters will be based on the FDA Guidance for Industry “Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (refer to Appendix 7, Section 12.7). 
Those laboratory parameters not included in the FDA Toxicity Grading Scale will not be graded. 
Holding rules 1a (in all steps), 1b and 1c (during the dose-escalation safety lead-In epoch and the PoP Step 1) will be 
monitored by the investigators on a continuous basis for as long as vaccination is ongoing in the study. Meeting any of 
these holding rules will trigger a hold of vaccination irrespective of the number of subjects vaccinated. 
Holding rules 2a, 2b and 2c are reviewed during unblinded review in the planned or ad-hoc iSRC. These rules will be 
applied only during the dose-escalation safety lead-In epoch and the staggered enrolment step of PoP vaccination 
epoch. Also in this case, different cut-offs are considered based on the sample size of the study group. 
For both, the dose-escalation safety lead-in and PoP, the investigator will not be 
permitted to start the administration of Dose 1 for the next group until receipt of the 
favourable outcome of the safety assessment committees evaluation (SRT/iSRC), 
documented and provided in writing (scanned and emailed), authorising the investigator 
to proceed. The same applies for the administration of Dose 2 in the fourth group of the 
dose-escalation safety lead-in and for the administration of Dose 2 in the staggered 
enrolment of first 40 subjects of the PoP epoch.  

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During the whole study period, if the investigator becomes aware of a holding rule being 
met, he/she will suspend vaccination and will inform GSK immediately. 
The below flow of communication has to be followed: 
• 
The concerned site staff must suspend the vaccination. 
• 
The concerned site staff must immediately inform their local contact defined in the 
Table 24. 
• 
Local Medical Lead (LML) will inform the other sites of his/her country, LMLs of 
other countries and the Clinical Research & Development Lead (CRDL). 
• 
All informed site staff will send back an e-mail 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.  
The detailed flow of communication will be described in the iSRC Charter. 
8.6.4. 
Risk assessment 
Figure 9, Figure 10 and Figure 11 give the probability of not meeting each holding rule 1 
and 2 for the subjects in 1 vaccine group.  
Figure 9 
Evaluations based on 6 subjects per group – Risk assessment curve 
for 1 formulation based on the proposed safety holding rules (dose-
escalation safety lead-in steps) 
 

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The Figure 9 illustrates that, with 6 subjects per study group: 
• 
Each holding rule 1a-c and 2a-c has more than 82% chance of being met for 
vaccination with a true incidence rate above 25% and has more than 53% chance of 
not being met for vaccination with a true incidence rate below 10%. 
Figure 10 
Evaluations based on 30 subjects per group – Risk assessment 
curve for 1 formulation based on the proposed safety holding rules 
(staggered step) 
 
The Figure 10 illustrates that, with 30 subjects per study group: 
• 
Each holding rule 1a-c has more than 78% chance of being met for vaccination with 
a true incidence rate above 5% and has more than 74% chance of not being met for 
vaccination with a true incidence rate below 1%. 
• 
Each holding rule 2a-c has more than 80% chance of being met for vaccination with 
a true incidence rate above 25% and more than 93% chance of not being met for 
vaccination with a true incidence rate below 10%. 

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Figure 11 
Evaluations based on 200, 250, 300, 350 subjects per group – Risk 
assessment curve for 1 formulation based on the proposed safety 
holding rules (PoP full enrolment step) 
 
The Figure 11 illustrates that, with 200-350 subjects per study group: 
• 
The holding rule 1a has a chance ranging from 3% (with 350 subjects) to 13% (with 
200 subjects) of not being met for vaccination with a true incidence rate below 1% 
and has more than 98% chance of being met for vaccination with a true incidence 
rate above 2%. 
8.6.5. 
Safety review team (SRT) 
The SRT is a GSK’s Central Committee responsible for on-going safety monitoring of 
the entire project and will meet on a regular basis throughout the duration of the study. In 
order to keep blinded all people involved in the conduct, cleaning and final analysis of 
the study, the SRT will monitor safety in a blinded manner. The GSK Biologicals’ SRT 
and iSRC chair will jointly review blinded safety data. If no potential holding rules (e.g. 
1a, 1b or 1c, Table 26) or safety concerns are identified during this blinded review, then 
review of unblinded data by iSRC team may not be required and study can proceed with 
the next step. Should there be any concerns that would require the evaluation of 
unblinded safety data, the iSRC will perform unblinded review of safety data and proceed 
as specified in the iSRC charter.  
Refer to the iSRC Charter for details about the safety assessment committees evaluation. 

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8.6.6. 
Internal Safety Review Committee (iSRC)  
As this will be the first time that the S. aureus candidate vaccine will be administered in 
humans, the study will enroll and vaccinate subjects in several steps (see also Figure 7 
and Figure 8). An iSRC authorised by the GSK’s VSMB will review unblinded data and 
holding rules have been established to ensure the safety of the subjects in the study. 
Conditional review of unblinded data by iSRC (i.e. in case of any safety concern, see also 
Section 8.6.5) can be performed after any step of the study, as applicable. Predefined 
unblinded review by iSRC will be performed on Day 8 after vaccination Visit 1 of the 
fourth group of dose-escalation safety lead-in and on Day 8 after vaccination Visit 1 of 
the last subject of the approximately first 40 subjects of staggered enrolment of the PoP. 
Details on safety assessment committees process is further described in the iSRC Charter. 
9. 
DISCONTINUATION CRITERIA 
9.1. 
Discontinuation from the study 
From an analysis perspective, a ‘withdrawal’ from the study refers to any subject who did 
not come back for the concluding visit/was not available for the concluding contact 
foreseen in the protocol.  
All data and samples collected until the date of withdrawal/last contact of the subject will 
be used for the analysis. 
A subject is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this subject from the date of withdrawal/last contact. 
Investigators will make attempts (3 telephone calls [e.g. once every 3 days] and a 
certified letter to the last known address or local equivalent methods) to contact those 
subjects who do not return for scheduled visits or follow-up. 
Primary reason for study withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject himself/herself, or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal: 
• 
Adverse events requiring expedited reporting (refer to Section 12.5.9.2 for details)  
• 
Unsolicited non-serious adverse event 
• 
Solicited adverse event 
• 
Protocol deviation  
• 
Withdrawal by subject, not due to an adverse event* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 

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• 
Sponsor study termination 
• 
Other (specify) 
*In case a subject is withdrawn from the study because he/she has withdrawn consent, the 
investigator will document the reason for withdrawal of consent, if specified by the 
subject, in the eCRF. 
Subjects who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from subjects who are withdrawn for other reasons. Investigators will 
follow subjects who are withdrawn from the study as result of a SAE/AE until resolution 
of the event (see Section 12.5.11). 
9.2. 
Discontinuation of study vaccine(s) 
A ‘withdrawal’ from the study vaccine(s) refers to any subject who does not receive the 
complete treatment, i.e. when no further planned dose is administered from the date of 
withdrawal. A subject withdrawn from the study vaccine(s) may continue further study 
procedures (e.g. safety, efficacy or immunogenicity) if planned in the study protocol, as 
deemed appropriate by the investigator.  
Primary reason relative to premature discontinuation of the study vaccine(s) will be 
documented on the Vaccine Administration page/screen of the eCRF. The investigator 
will document whether the decision to discontinue further vaccination was made by the 
subject himself/herself, or by the investigator, as well as which of the following possible 
reasons was responsible for withdrawal: 
• 
Adverse event requiring expedited reporting 
• 
Non-serious adverse event (specify) 
• 
Unsolicited non-serious adverse event 
• 
Solicited adverse event 
• 
Not willing to be vaccinated 
• 
Other (specify). 
9.3. 
Lost to follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a subject fails to return to the clinic for a required 
study visit: 
• 
The site must attempt to contact the subject and reschedule the missed visit as soon 
as possible and counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or should 
continue in the study. 

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• 
Before a subject is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, 
if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s 
medical record. 
• 
Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up and last day of 
actual contact be recorded on termination page.  
10. 
STATISTICAL CONSIDERATIONS 
10.1. 
Sample size determination 
10.1.1. 
Hypotheses related to primary and secondary objectives  
For the primary safety objective no statistical hypotheses are applicable.  
Two statistical hypotheses will be tested for the secondary efficacy objective. 
1. Null Hypothesis : Hazard Ratio (HR) ≥1 after the second vaccination  
Alternative Hypothesis: HR <1 
2. Null Hypothesis : Hazard Ratio (HR) ≥1 after the first vaccination  
Alternative Hypothesis: HR <1 
If the first hypothesis is statistically significant, also the second hypothesis will be tested 
in a sequential procedure. In case the first hypothesis is not significant no conclusions 
will be taken with respect to the second hypothesis. Both hypotheses will be tested using 
the log rank test. 
For the first hypothesis referring to the key efficacy endpoint two sequential analyses will 
be done following a Group Sequential Design using the O'Brien-Fleming spending 
function (with 48% and 100% of the total planned events). (Amended 6 October 2022) 
At the interim analysis the first hypothesis will be tested spending 1.61% alpha and 
8.83% beta ( this means a power equal to about 91%). At the final analysis the alpha will 
be 5.89% and the beta 11.17% (this means a power equal to about 89%). Overall after 
two sequential analyses the cumulative alpha will be 7.5% and the cumulative beta 20% 
(or power equal to 80%). 
The assumptions to test the first hypothesis on the HR after the second vaccination are:  
• 
to observe an HR (hazard ratio) equal or below to 0.39 
• 
a true incidence rate for the SSTI equal to 0.07 (starting to count the events two 
weeks after the second dose) 
• 
time to event follows an exponential distribution. 

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The second hypothesis of the secondary vaccine efficacy objective will be tested for all 
the events occurring after the first vaccination, with one-sided alpha equal to 5.89% and 
power 89% (both adjusted error values will be retrieved from the second group sequential 
test performed  on the first hypothesis). 
The following assumptions are made to test the hypothesis on the HR after the first dose 
of vaccine/placebo: 
• 
to observe an HR below 0.43 
• 
a true incidence rate equal to 0.12 (starting to count the events two weeks after the 
first dose)  
• 
time to event follows an exponential distribution 
The upper limit assumed for the HR equal to 0.43 allows to test the second hypothesis 
with alpha equal to 5,89% and power equal to 89%,  assuming the incidence rate equal to 
0.12, with the planned sample size for the first hypothesis (about 600 subjects).  
10.1.2. 
Sample size calculation  
The incidence rates of S. aureus SSTI (index cases and recurrences) at the selected study 
centre(s) are difficult to predict. For this reason, the study is designed as an event driven 
trial and includes 
. After the dose-escalation safety 
lead-in epoch and the PoP staggered enrolment step of PoP vaccination epoch are 
concluded and no safety issues are found, enrolment will continue with a randomisation 
of 1:1 ratio either to the S. aureus candidate vaccine or to the placebo group. It is 
estimated that approximately 500 to 600 subjects will be needed to achieve the 
 
. 
The key objective of clinical efficacy will be measured counting culture confirmed cases 
of recurrent S. aureus SSTIs occurring from 14 days after the second dose up to 12 
months after the second dose. Before the second dose has elicited a proper response (i.e. 
from Day 61 to Day 75) subjects will be also monitored for SSTI.  
The event driven design includes 
 (culture confirmed S. aureus SSTI 
recurrences) overall after the second dose to test the null hypothesis of no efficacy 
assuming an HR equal to 0.39 from Day 75 (14 days after the second vaccination) up to 
12 months after the second vaccination. 
The study sample size is not fixed and the enrolment will proceed until reaching the 
planned number of events necessary to evaluate the first statistical hypothesis of no 
efficacy (HR≥1) with an overall power equal to 80% and an overall one-sided alpha equal 
to 7.5%.  
A group sequential design with the O’Brien Fleming spending function is applied to the 
first hypothesis after the second vaccination, 
 
  
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After the final analysis for the first hypothesis a sequential procedure will be used in 
order to control the overall type I error for the efficacy objective: starting from the first 
hypothesis on the efficacy after the second dose, the second hypothesis on the efficacy 
after the first dose will be tested only if the efficacy after two doses will be demonstrated. 
Figure 12 
Sequence for evaluating both efficacy objectives in order to control 
the overall type I error below 7.5% (one-sided) and the power equal 
to 80%  
 
*All subjects who experience an SSTI recurrence at least two weeks after the second dose. If a subject experiences an 
event after the first and before the second dose the case will be not considered as first event after the second dose. If 
a subject experiences an event after the first and another after the second dose, only the case after the second dose 
will be considered as first event after the second dose. 
**The adjusted alpha for this hypothesis can only be given at the time of analysis as the adjustment is dependent on 
the alpha spent at the interim analysis. A more detailed decision tree will be given in the statistical analysis plan. 
***All subjects who experience an SSTI recurrence at least two weeks after the first dose.  
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10.2. 
Populations for analyses  
For purposes of analysis, the following analysis sets are defined: 
Analysis Set 
Description 
Screened 
All subjects who were screened for eligibility 
Enrolled  
All subjects who entered the study (who were randomized or received study 
intervention or underwent a post-screening study procedure). The allocation in a 
group will be done in function of the randomized intervention; non-randomized 
subjects will be part of a “Non randomized” group. Note: screening failures (who 
never passed screening even if rescreened) and subjects screened but never 
enrolled into the study (met eligibility but ultimately not enrolled) are excluded from 
the Enrolled analysis set as they did not enter the study. 
Exposed  
All subjects who received at least 1 dose of the study treatment. The allocation in a 
group is done in function of the administered treatment. 
Full Analysis Set (FAS) 
All subjects who received at least 1 dose of the study treatment and have post-
vaccination efficacy/ immunogenicity data  
Modified Full Analysis Set 
(mFAS) 
All subjects who received full study treatment course to which they are randomised 
and have post-vaccination efficacy/immunogenicity data 
Per-Protocol (PP) 
All subjects who received full study treatment course to which they are randomised 
and have post-vaccination data (mFAS) minus subjects with protocol deviations 
that lead to exclusion from PP 
Unsolicited Safety  
All subjects who received at least 1 dose of the study treatment (Exposed Set) that 
report unsolicited AEs/report not having unsolicited Aes 
Solicited Safety  
All subjects who received at least 1 dose of the study treatment (Exposed Set) who 
have solicited safety data in the period beginning 30 minutes after vaccination until 
7 days after vaccination. 
Solicited Safety 30m 
All subjects who received at least 1 dose of the study treatment (Exposed Set) who 
have solicited safety data during a period of 30 minutes after the vaccination. 
Overall Safety Set 
All subjects who received at least 1 dose of the study treatment (Exposed Set) who 
have solicited safety data including 30 minutes data and during a period of 7 days 
from the vaccination and/or report unsolicited Aes/report not having unsolicited Aes  
10.3. 
Statistical analyses 
10.3.1. 
Subjects disposition 
Number of screened, enrolled, vaccinated (at least 1 vaccination, full vaccination course) 
subjects, included in each group or in total for a given age category or for all age 
categories will be described. These might be additionally broken down by site.  
10.3.2. 
Demography and baseline characteristics analyses 
Demographic characteristics (age at first study vaccination in years, gender, race and 
ethnicity), SSTIs history (PoP only), will be summarised by overall and vaccine groups 
using descriptive statistics: 
• 
Frequency tables will be generated for categorical variables such as centre. 
• 
Mean, standard deviation, median, minimum and maximum will be provided for 
continuous data such as age, height, weight and body mass index (BMI). 

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Withdrawal status will be summarized by group using descriptive statistics: 
• 
The numbers of withdrawn subjects will be tabulated according to the reason for 
withdrawal 
• 
The number of subjects enrolled into the study as well as the number of subjects 
excluded from the per-protocol set (PPS) and mFAS will be tabulated. 
10.3.3. 
Efficacy analyses 
The primary efficacy analysis will be based on the mFAS. A supplementary analysis may 
be based on the PPS. 
10.3.3.1. 
Case accountability:  
Rules for SSTI cases: 
• 
All cases of SSTI will be reported, including multiple cases in the same subject. 
• 
The start date of a case is the date of the visit during which the diagnosis is done by a 
treating physician or equivalent licensed medical professional or based on medical 
records review by a study physician. 
• 
A new SSTI episode may be assessed by a study physician at site for any SSTI visit 
occurring after the clinical resolution of the previous SSTI and, if it does not 
represent a persistence of the previous episode as per medical judgement, it can be 
considered a new episode.  
Endpoint 
Statistical Analysis Methods 
Key 
secondary 
The analysis of efficacy will be based on the occurrence of the first case of SSTI anytime from 15 
Days after the administration of the second dose of the study vaccine up to 12 months. All 
subjects from the mFAS will contribute to the comparison between the treatment and the placebo 
groups. 
Time to occurrence of key secondary endpoint during the defined efficacy follow-up period will be 
compared between groups by calculating the respective Hazard ratio (methods will be detailed in 
the SAP).  
Vaccine (VE) will be defined as 1 minus the hazard ratio times 100: 
VE = (1 – hazard ratio) x 100 
Censoring will occur at the time of the last scheduled or medically attended visit without the 
occurrence of SSTI cases before the end of follow-up. Subjects who will complete the follow-up 
without events will be censored at 1 year. 
In order to check the statistical significance, 1-sided P-value for the log rank test will be 
calculated. 1-sided nominal type I error will be 1.61% at the interim analysis and 5.89% at the final 
analysis. The objective will be met if the 1-sided P-value calculated for the null hypothesis H0 = 
[occurrence SSTI VE =0%] is lower than defined 1-sided alpha level. 
Co-secondary 
The co- secondary endpoint will be analysed only if the statistical significance is demonstrated for 
the key secondary endpoint. 
For this analysis, the FAS will account for the first case of SSTI anytime from 15 Days after the 
administration of the first dose of the study vaccine up to 14 months. 
Time to occurrence of the co- secondary endpoint during the defined efficacy follow-up period will 
be compared between groups by calculating the respective Hazard ratio (methods will be detailed 
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Endpoint 
Statistical Analysis Methods 
In order to check the statistical significance, 1-sided P-value for the log rank test will be 
calculated. 1-sided nominal type I error will be 5.89%. (the nominal alpha level is equal to the key 
secondary at the final analysis, because we use a sequential procedure). The objective will be 
met if the 1-sided P-value calculated for the null hypothesis H0=[occurrence SSTI VE =0%] is 
lower than defined 1-sided alpha level. 
10.3.4. 
Immunogenicity analyses 
The main analysis set for immunogenicity will be the mFAS. 
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10.3.5. 
Safety analyses 
The primary analysis will be performed on the Solicited Safety and Unsolicited Safety 
sets. 
Endpoint 
Statistical Analysis Methods 
Primary 
Within groups assessment 
The overall incidence, with exact 95% confidence intervals (Cis) of any solicited AE (local or 
general), of at least 1 solicited local AE and of at least 1 solicited general AE during the 7-day 
(Day 1-7) period will be tabulated per study group and for each dose and overall. The same 
calculations will be performed for solicited Aes rated as grade 3 and fever >40°C/104°F. 
The overall incidence, with exact 95% confidence intervals (Cis) of any unsolicited AE, 
unsolicited Aes by MedDRA system organ class and by preferred term during the 30-day (Day 
1-30) follow-up post-vaccination period will be tabulated per study group and after each dose 
and overall. The same calculations will be performed for unsolicited Aes rated as grade 3 and 
fever >40°C/104°F, for unsolicited Aes causally related to vaccination and for grade 3 
unsolicited Aes causally related to vaccination. 
The number and percentages of subjects who experienced at least one SAE or any pIMD during 
the entire study period (Groups 1-3 Day 1-366, Groups 4 and 5 Day 1-426) will be reported. 
The percentage of subjects having haematology and biochemistry results below or above the 
normal laboratory ranges with the changes from the baseline values will be tabulated by time 
point for Group 1 to 4 and Group 5 Step 1. 
Duration will be presented.  
The verbatim reports of unsolicited symptoms will be reviewed by a GSK physician and the 
signs and symptoms will be coded according to the MedDRA Dictionary for Adverse Event 
Terminology.  
Serious adverse events and withdrawal due to adverse event(s) will be described in detail. 
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11. 
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Protalex. Safety Study of PRTX-100 With Methotrexate or Leflunomide to Treat Active 
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Health Emerg. 2017; 1: 25. 

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12. 
APPENDICES 
12.1. 
Appendix 1: Abbreviations, glossary of terms and 
trademarks 
12.1.1. 
List of abbreviations 
AE: 
Adverse Event 
ANCOVA: 
Analysis of Covariance 
BSI: 
Blood Stream Infection 
CDC: 
Centers for Disease Control 
CI: 
Confidence Interval 
CLS: 
Clinical Laboratory Sciences 
CoP: 
Correlate of Protection 
DSSI: 
Deep Surgical Site Infection  
eCRF: 
electronic Case Report Form 
EMA: 
European Medicines Agency 
EoS: 
End of Study 
eTDF: 
Electronic Temperature excursion Decision Form 
EU: 
European Union 
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FAS: 
Full Analysis Set 
FDA: 
Food and Drug Administration, United States of America 
FTIH: 
First Time in Human 
GCP: 
Good Clinical Practice 
GSK: 
GlaxoSmithKline 
HR: 
Hazard Ratio 
IB: 
Investigator Brochure 
ICF: 
Informed Consent Form 
ICH: 
International Council on Harmonisation 
IEC: 
Independent Ethics Committee 
IMP: 
Investigational Medicinal Product 
IND: 
Investigational New Drug 
IRB: 
Institutional Review Board 
IsdB: 
Iron-regulated surface determinant B 
iSRC: 
Internal Safety Review Committee 
LLOQ: 
Lower Limit of Quantitation 
LOD: 
Limit of Detection 
LSLV: 
Last Subject Last Visit 
MACDP: 
Metropolitan Atlanta Congenital Defects Program 
MedDRA: 
Medical Dictionary for Regulatory Activities 
mFAS: 
Modified Full Analysis Set 
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PCD: 
Primary Completion Date 
pIMD: 
Potential Immune-Mediated Disease 
PoP: 
Proof of Principle 
PP: 
Per-protocol 
PRO: 
Patient Related Outcomes 
RRA: 
Recruitment/Randomisation Agreement 
SAE: 
Serious Adverse Event 
SBIR: 
Source data Base for Internet Randomisation  
SDV: 
Source Document Verification 
SmPC: 
Summary of Product Characteristics 
SPM: 
Study Procedures Manual 
SRT 
Safety Review Team 
SSI: 
Surgical Site Infection 
SSTI: 
Skin and Soft Tissue Infection 
US: 
United States of America 
VCSP: 
Vaccines Clinical Safety and Pharmacovigilance 
VE: 
Vaccine Efficacy 
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12.1.2. 
Glossary of terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use 
of a medicinal product, whether or not considered 
related to the medicinal product.  
An adverse event (AE) can therefore be any 
unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new 
or exacerbated) temporally associated with the use of a 
medicinal product. For marketed medicinal products, 
this also includes failure to produce expected benefits 
(i.e. lack of efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
trial, and only when the data are cleaned to an 
acceptable level of quality will appropriate personnel be 
unblinded or when required in case of a serious adverse 
event. In an observer-blind study, the subject and the site 
and sponsor personnel involved in the clinical evaluation 
of the subjects are blinded while other study personnel 
may be aware of the treatment assignment (see Section 
7.3 for details on observer-blinded studies).  
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. 
Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
End of Study (EoS)  
(Synonym of End of Trial) 
For studies with collection of human biological samples, 
the EoS is defined as last subject last visit (Visit 10).  
Epoch: 
Interval of time in the planned conduct of a study. An 
epoch is associated with a purpose (e.g. screening, 
randomisation, treatment, follow-up), which applies 
across all arms of a study. NOTE: Epoch is intended as a 
standardised term to replace: period, cycle, phase, stage.  

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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 (see Section 10.2 
for details on criteria for evaluability). 
Immunological correlate 
of protection: 
The defined immune response above which there is a 
high likelihood of protection in the absence of any host 
factors that might increase susceptibility to the 
infectious agent. 
Investigational vaccine: 
(Synonym of 
Investigational Medicinal 
Product) 
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorisation when used in a way different 
from the approved form, or when used for an 
unapproved indication, or when used to gain further 
information about an approved use.  
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 
Potential Immune-
Mediated Disease: 
Potential immune-mediated diseases (pIMDs) are a 
subset of AEs that include autoimmune diseases and 
other inflammatory and/or neurologic disorders of 
interest which may or may not have an autoimmune 
aetiology. 
Primary completion: date: The date that the final subject was examined or received 
an intervention for the purpose of final collection of data 
for all primary outcomes, whether the clinical trial was 
concluded according to the pre-specified protocol or was 
terminated. 
Protocol administrative 
change: 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study.  

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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 subjects, 
scope of the investigation, study design, or scientific 
integrity of the study. 
Randomisation: 
Process of random attribution of treatment to subjects in 
order to reduce bias of selection. 
Self-contained study: 
Study with objectives not linked to the data of another 
study. 
Site Monitor: 
An individual assigned by the sponsor who is 
responsible for assuring proper conduct of clinical 
studies at 1 or more investigational sites. 
Solicited adverse event: 
AEs to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the subject or an observer during 
a specified post-vaccination follow-up period. 
Source data: 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical 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 documents, data, and records (e.g. hospital 
records, clinical and office charts, laboratory notes, 
memoranda, subjects' 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, subject files, and records kept at the pharmacy, at 
the laboratories and at medico-technical departments 
involved in the clinical trial). 
Study vaccine/product: 
Any investigational vaccine/product being tested and/or 
any authorised use of a vaccine/product/placebo as a 
reference or administered concomitantly, in a clinical 
trial that evaluates the use of an investigational 
vaccine/product. 

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Sub-cohort: 
A group of subjects for whom specific study procedures 
are planned as compared to other subjects or a group of 
subjects who share a common characteristic (e.g. ages, 
vaccination schedule…) at the time of enrolment. 
Subject: 
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, either as a recipient 
of the vaccine(s) or as a control. 
Subject number: 
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study. 
Treatment: 
Term used throughout the clinical study to denote a set 
of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject. 
Treatment number: 
A number identifying a treatment to a subject, according 
to treatment allocation. 
Unsolicited adverse event: 
Any AE reported in addition to those solicited during the 
clinical study. Also, any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse 
event. 
12.2. 
Appendix 2: Clinical and safety laboratory tests 
CCI

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CCI

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12.2.2. 
Laboratory assays for safety evaluation 
The tests detailed in Table 27 will be performed by the local laboratory. Results of tests 
will be needed before vaccination i.e. latest on the next day for dose-escalation safety 
lead-in and on the same day for PoP Step 1 (see also requirements for inclusion or 
exclusion of subjects detailed in Section 6 of the protocol). 
Examples of clinically not significant abnormalities: (ULN = upper limit of normal; LLN 
= lower limit of normal) that can allow subjects to be enrolled: 
• 
WBC > ULN, if WBC remain stable over time i.e. maximum 10% change with 
respect to baseline (prior to the first vaccination). 
• 
Haemoglobin levels > the upper limit of the laboratory normal range (ULN). 
• 
RBC > ULN. 
• 
RBC < LLN and haemoglobin normal. 
• 
ALT or AST < LLN  
• 
If values out of normal ranges (Grade 1 considered clinically significant or above 
Grade 1) are observed (Refer to Appendix 7, Section 12.7), which are expected to be 
temporary (e.g., due to dehydration), the abnormal parameters can be re-assessed 
during a rescreening* visit but they must have returned to within local laboratory 
normal ranges for the subject to be eligible. If considered necessary by the 
investigator, related parameters outside of the panel can be (re-)tested in addition to 
the abnormal parameters (Haematology/Biochemistry). The subjects should be 
informed about the possibility of rescreening* in the informed consent form (ICF). 
* Rescreening of subjects in case of a transient clinical condition (e.g. previous 
screening failure due to non-S. aureus SSTI) at investigator discretion, is also 
possible. In such cases, the complete screening process should be reperformed. 
Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Section 6 of the protocol. 
The investigator is not allowed to do extra testing on samples outside of what has been 
agreed upon by the ethics committees. 
CCI

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Table 27 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Haematology 
Platelet Count  
RBC Count 
Haemoglobin 
WBC count with Differential: 
Neutrophils 
Lymphocytes 
Eosinophils 
Clinical Chemistry 
Creatinine 
Aspartate Aminotransferase (AST)/Serum Glutamic-Oxaloacetic 
Transaminase (SGOT) 
Alanine Aminotransferase (ALT)/Serum Glutamic-Pyruvic 
Transaminase (SGPT) 
Other Screening 
Tests 
Urine human chorionic gonadotropin (hCG) pregnancy test (as needed for women of 
childbearing potential)  
The results of each test carried out locally must be entered into the eCRF. 
RBC = Red Blood Cells; WBC = White Blood Cells 
NOTES: Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 
Pre-vaccination on Visit 0 (dose-escalation safety lead-in) and Visit 1 (PoP Step 1) 
haematology and chemistry evaluation will not be blinded since abnormal laboratory 
results will be an exclusion criterion (see Section 6.2.1). Visit Days 8, 61 and 68 
haematology and blood chemistry results will be blinded to study treatment. Unblinding 
is appropriate for safety issues, but unblinded data will only be reviewed by iSRC. Refer 
to the iSRC Charter for details about the safety assessment committees evaluation. 
12.3. 
Appendix 3: Clinical laboratories 
The laboratories (at the investigator’s institution and/or at a laboratory designated by 
GSK Biologicals) that will perform the microbiology assessments are not yet identified.  
A list of possible laboratories is given in Table 28 and Table 29. 
In addition, other laboratories than those listed below might also be used to perform the 
exploratory assays.  
Table 28 
GSK laboratories 
Laboratory* 
Address 
GSK Biological’s Clinical Laboratory Sciences, 
Rixensart  
Biospecimen Reception-B7/44 
Rue de l'Institut, 89 
B-1330 Rixensart 
Belgium  
GSK Biological’s Clinical Laboratory Sciences, 
Wavre-Nord Noir Epine 
Avenue Fleming, 20 
B-1300 Wavre 
Belgium 
GSK Vaccines S.r.l 
Preclinical R&D, Italy 
Via Fiorentina 1 
53100 Siena 
Italy 
*GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium or Wavre, Belgium. CLS may 
delegate testing to GSK Research laboratories in Siena, Italy or to an external laboratory. 

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Table 29 
Outsourced laboratories 
Laboratory 
Address 
Q2 Solutions Clinical Trials (UK) 
The Alba Campus Rosebank  
Livingston West Lothian, EH54 7EG Scotland,  
UK  
Q2 Solutions Clinical Trials (US) 
27027 Tourney Road, Suite 2E 
Valencia, CA 91355 
USA 
12.4. 
Appendix 4: Study governance considerations 
12.4.1. 
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, Informed Consent Form (ICF), 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 amendments to the protocol 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 subjects.  
• 
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. 
− 
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. 

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12.4.2. 
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 interests during the 
study and for 1 year after completion of the study. 
12.4.3. 
Informed consent process 
The investigator or his/her representative will explain the nature of the study to the 
subject or his/her legally authorised representative and answer all questions regarding the 
study.  
Subjects must be informed that their participation is voluntary.  
Freely given and written or witnessed/thumb printed informed consent must be obtained 
from each subject prior to participation in the study.  
The content of 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 informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was 
obtained. The authorised person obtaining the informed consent must also sign the ICF. 
Subjects 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 subject.  
Subjects who are rescreened are required to sign a new ICF. 
The ICF contains a specific section that addresses the use of remaining leftover samples 
for future use in accordance with SOP-GSKF-410. The investigator or authorised 
designee will inform each subject of the possibility of future use of left-over samples not 
related to the study/disease. Subjects will be told that they are free to refuse to participate 
and may withdraw their consent at any time and for any reason during the storage period. 
A separate tick box will be required to document a subject's agreement to allow any 
remaining leftover samples to be used for future use not related to the study/disease. 
Subjects who decline the use of left-over samples for objectives not related to the 
study/disease will tick the corresponding box. 

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12.4.4. 
Data protection 
Subject will be assigned a unique identifier by the sponsor. Any subject records or 
datasets that are transferred to the sponsor will contain the identifier only; subject’s 
names or any information which would make the subject identifiable will not be 
transferred.  
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  
The subject must be informed that his/her medical records 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 also ensure the protection of personal data of investigator and the site staff 
which will be collected within the framework and for the purpose of the study, in 
accordance with the Data Privacy Notice that will be sent to the site staff.  
12.4.5. 
Publication policy 
GSK aims to publish the results of this study in searchable, peer reviewed scientific 
literature. GSK will target to submit within 18 months from LSLV for interventional 
studies and from the completion of the analysis for non-interventional studies and follows 
the guidance from the International Committee of Medical Journal Editors. 
12.4.6. 
Dissemination of clinical study data 
The key design elements of this protocol will be posted on the GSK Clinical Study 
Register and on publicly accessible registers including ClinicalTrials.gov. Where 
required, protocol summaries will also be posted on national or regional clinical trial 
registers or databases (e.g. EudraCT database) in compliance with the applicable 
regulations. 
GSK also assures that results will be submitted to ClinicalTrials.gov within the required 
time frame, in compliance with the current regulations mentioned in the table below.  
At the time of study results posting, the full study protocol and statistical analysis plan 
will also be posted on ClinicalTrials.gov.  
In addition, for studies that are in scope of the EU Clinical Trial Directive, summaries of 
the results of GSK interventional studies (phase I-IV) in adult population will be posted 
within defined timelines on the publicly available EU Clinical Trial Register.  
If it is not possible to submit a summary of the results within the required timelines in the 
concerned EU member state, the summary of results shall be submitted as soon as it is 
available. In this case, the protocol shall specify when the results are going to be 
submitted, together with a justification.  

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Clinicaltrial.gov 
EU 
Protocol summary 
Before enrolment of subjects 
As per CTA submission/Before 
enrolment of subjects 
Results summary 
Within 12 months of PCD (Primary 
and safety endpoint results)/Within 
12 months of LSLV* (for secondary 
endpoint results) 
Within 6 months (for paediatric 
population studies)/Within 12 months 
(for adult population studies) of EoS*. 
* As defined in the study protocol. 
Under the framework of the SHARE initiative, anonymised patient-level data from GSK 
sponsored interventional studies that evaluate products will be made available within 6 
months of this publication to independent researchers whose research proposals have 
been approved by an independent panel. Requests for access may be made through 
www.clinicalstudydatarequest.com. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, 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 subjects, as appropriate. 
12.4.7. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents including source documents. The 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 documents for the trial may be added or reduced where justified (in advance of 
trial initiation) based on the 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.  
All subject data relating 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 CRF/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 subjects that supports the 
information entered in the eCRF.  
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies.  
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source data.  

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Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorised site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data should be traceable, should not 
obscure the original entry, and should be explained if necessary (e.g. via an audit trail). 
Safety and rights of subjects must be protected and study be conducted in accordance 
with the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
Quality tolerance limits (QTLs) will be pre-defined in the study management plan and 
will be monitored during the study.  
Trial records and source documents, including signed ICF, pertaining to the conduct of 
this study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (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.  
12.4.8. 
Source documents 
Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Investigator should maintain a record of the location(s) of 
their source documents.  
Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available. 
Definition of what constitutes source data and source documents can be found in the 
glossary of terms. 
12.4.9. 
Study and site start and closure 
First act of recruitment 
Start of study is defined as first subject first visit (FSFV) at a country-level. 
Study/Site termination  
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK, provided there is sufficient notice given 
to account for patient’s safe exit from study participation. Study sites regular closure will 
be 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 
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The investigator may initiate study site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study 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 subjects by the investigator 
• 
Discontinuation of further study treatment development 
• 
Total number of subjects included earlier than expected 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform 
the investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organisation(s) used in the study of the reason for termination or suspension, as specified 
by the applicable regulatory requirements. The investigator shall promptly inform the 
subject and should assure appropriate subject therapy and/or follow-up. 
12.5. 
Appendix 5: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting 
12.5.1. 
Definition of AE 
12.5.1.1. 
AE Definition 
An AE is any untoward medical occurrence in a clinical study subject, temporally 
associated with the use of a study treatment, whether or not considered related to the 
study treatment. 
NOTE: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study treatment. 
12.5.1.2. 
Events Meeting the AE Definition  
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study vaccine(s) administration even 
though they may have been present prior to the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
vaccine(s) or a concurrent medication (overdose per se should not be reported as an 
AE/SAE). 
• 
Signs, symptoms temporally associated with study vaccine(s) administration. 

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• 
Pre- or post-treatment events that occur as a result of protocol-mandated procedures 
(i.e. invasive procedures, modification of subject’s previous therapeutic regimen). 
• 
Medically attended visits related to adverse events (e.g. Hospital stays, physician 
visits and emergency room visits). 
AEs to be recorded as endpoints (solicited AEs) are described in Section 12.5.3. All other 
AEs will be recorded as UNSOLICITED AEs. 
 “Lack of efficacy" or "vaccination failure of expected pharmacological action" per se 
will not be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting from lack 
of efficacy will be reported as AE or SAE if they fulfil the definition of an AE or SAE.  
12.5.1.3. 
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 subject prior to the 
first study vaccination. These events will be recorded in the medical history section 
of the eCRF. 
12.5.2. 
Definition of SAE 
A SAE is any untoward medical occurrence that: 
a. 
Results in death, 
b. Is life-threatening, 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the subject was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, had it been more severe. 
c. 
Requires hospitalisation or prolongation of existing hospitalisation, 
Note: In general, hospitalisation signifies that the subject has been admitted at the 
hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or in an out-patient setting. Complications 
that occur during hospitalisation are also considered AEs. If a complication prolongs 
hospitalisation or fulfils any other serious criteria, the event will also be considered 
serious. When in doubt as to whether ‘hospitalisation’ occurred, or was necessary, 
the AE should be considered serious. 
Hospitalisation for elective treatment of a pre-existing condition (known or 
diagnosed prior to informed consent signature) that did not worsen from baseline is 
NOT considered an AE. 
d. Results in disability/incapacity, OR 

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Note: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhoea, influenza like illness, and accidental trauma (e.g. sprained 
ankle) which may interfere or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. 
Is a congenital anomaly/birth defect in the offspring of a study subject. 
f. 
Grade 4 laboratory abnormalities (Refer to Appendix 7, Section 12.7). 
Medical or scientific judgement should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalisation but may jeopardise 
the subject or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition. These should also be considered 
serious. Examples of such events are invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalisation. 
12.5.3. 
Solicited adverse events  
a. Solicited local (injection-site) adverse events 
The following local (injection-site) AEs will be solicited: 
Table 30 
Solicited local adverse events 
Adults 
Pain at injection site 
Redness at injection site 
Swelling at injection site 
b. Solicited general adverse events 
The following general AEs will be solicited: 
Table 31 
Solicited general adverse events 
Adults 
Fatigue 
Fever 
Nausea 
Vomiting 
Diarrhoea 
Abdominal pain 
Headache 
Table 32 
Additional solicited general adverse events (PoP only)  
Adults 
Myalgia 
Shivering 

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Note: subjects will be instructed to measure and record the oral body temperature in the 
evening. Should additional temperature measurements be performed at other times of 
day, subjects will be instructed to record the highest temperature in the eDiary. 
12.5.4. 
Unsolicited adverse events 
An unsolicited adverse event is an adverse event that was not solicited using a Subject 
Diary and that was spontaneously communicated by a subjects who has signed the 
informed consent. 
Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses 
requiring hospitalisation, or emergency room visit, or visit to/by a health care provider), 
or were of concern to the subjects. In case of such events, subjects will be instructed to 
contact the site as soon as possible to report the event(s). The detailed information about 
the reported unsolicited AEs will be collected by the qualified site personnel during the 
interview and will be documented in the subject’s records. 
Unsolicited AEs that are not medically attended nor perceived as a concern by subjects 
will be collected during interview with the subjects and by review of available medical 
records at the next visit. 
12.5.5. 
Adverse events of special interest (AESIs) 
12.5.5.1. 
Potential immune-mediated diseases 
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 33. For details regarding the reporting 
procedure refer to Section 12.5.9.2. 
However, the investigator will exercise his/her medical and scientific judgement in 
deciding 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. 
 

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Table 33 
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 anemia. 
• 
Autoimmune thrombocytopenia. 
• 
Antiphospholipid syndrome. 
• 
Pernicious anemia. 
• 
Autoimmune aplastic anemia. 
• 
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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When there is enough evidence to make any of the above diagnoses, the AE must be 
reported as pIMD. Symptoms, signs or conditions which might (or might not) represent 
the above diagnoses, should be recorded and reported as AEs but not as pIMD until the 
final or definitive diagnosis has been determined, and alternative diagnoses have been 
eliminated or shown to be less likely.  
12.5.6. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as adverse events or serious adverse events  
In absence of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, 
haematology, urinalysis) or other abnormal assessments (e.g. medical imaging) that are 
judged by the investigator to be clinically significant will be recorded as AE or SAE if 
they meet the definition of an AE or SAE (refer to Sections 12.5.1 and 12.5.2). Clinically 
significant abnormal laboratory findings or other abnormal assessments that are present at 
baseline and significantly worsen following the start of the study will also be reported as 
AEs or SAEs. However, clinically significant abnormal laboratory findings or other 
abnormal assessments that are associated with the disease being studied, unless judged by 
the investigator as more severe than expected for the subject’s condition, or that are 
present or detected at the start of the study and do not worsen, will not be reported as AEs 
or SAEs. 
The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant. 
12.5.7. 
Events or outcomes not qualifying as adverse events or serious 
adverse events 
12.5.7.1. 
Pregnancy 
Female subjects who are pregnant or lactating at the time of vaccination must not receive 
additional doses of study vaccine(s) but may continue other study procedures at the 
discretion of the investigator. 
While pregnancy is not considered an AE or SAE, any adverse pregnancy outcome or 
complication or elective termination of a pregnancy for medical reasons will be recorded 
and reported as an AE or a SAE. 
Note: The pregnancy should always be recorded on an electronic pregnancy report. 
The following should always be considered as SAE and will be reported as described in 
Sections 12.5.9.1 and 12.5.9.4: 
• 
Spontaneous pregnancy loss, including: 
− 
spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of 
gestation) 
− 
ectopic and molar pregnancy 

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− 
stillbirth (intrauterine death of foetus after 22 weeks of gestation). 
Note: the 22 weeks’ cut-off in gestational age is based on WHO-ICD 10 noted in the 
EMA Guideline on pregnancy exposure [EMA, 2006]. It is recognised that national 
regulations might be different. 
• 
Any early neonatal death (i.e. death of a live born infant occurring within the first 7 
days of life).  
• 
Any congenital anomaly or birth defect identified in the offspring of a study subject 
(either during pregnancy, at birth or later) regardless of whether the foetus is 
delivered dead or alive. This includes anomalies identified by prenatal ultrasound, 
amniocentesis or examination of the products of conception after elective or 
spontaneous abortion. 
Furthermore, any SAE occurring as a result of a post-study pregnancy AND considered 
by the investigator to be reasonably related to the study vaccine(s) will be reported to 
GSK as described in Section 12.5.9. While the investigator is not obligated to actively 
seek this information from former subjects, he/she may learn of a pregnancy through 
spontaneous reporting. 
12.5.8. 
Detecting and recording adverse events, serious adverse events 
and pregnancies  
An eDiary hereafter referred to as Subject eDiary will be used in this study to capture 
solicited adverse events. The subject should be trained on how and when to complete 
each field of the Subject eDiary. 
The subjects will be instructed to contact the investigator immediately should the subjects 
manifest any signs or symptoms they perceive as serious.  
Subject eDiary training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the Subject 
eDiary. 
• 
The same individual should complete the Subject eDiary throughout the course of 
the study. 
• 
The subject should be trained on how to self-measure local solicited adverse events 
and body temperature.  
• 
The measurement of solicited local adverse events is to be performed using the ruler 
provided by the site. 
• 
Subjects will be instructed to measure and record the oral body temperature in the 
evening. Should additional temperature measurements be performed at other times of 
day, subjects will be instructed to record the highest temperature in the Subject 
eDiary. 

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Subject eDiary assignment and use: 
• 
Each subject will be assigned a Subject eDiary and shown how to use the device – 
this will include how to access the eDiary, enter data to the eDiary screens, and how 
to charge and store the device.  
• 
The subject will self-select a numeric access code secret to themselves. The same 
individual should make the assessments and complete the Subject eDiary throughout 
the course of the study.  
• 
The subject will select an alarm time that suits their daily routines whilst ensuring 
compliance with protocol requirements. 
Subject eDiary instructions must ensure that the subject understands the following: 
• 
Timely completion of the Subject eDiary on a daily basis is a critical component to 
study participation. 
• 
The Subject eDiary will allow certain time windows for completion of each day’s 
observations. 
• 
The Subject eDiary employs the use of audio-visual alarms to ensure timely 
completion of data entry. 
• 
The trained and assigned user of the Subject eDiary must not share access codes with 
anyone. 
• 
A helpdesk will be provisioned for users of Subject eDiary in case of technical 
issues, though it must be stressed that the Helpdesk is not a replacement for standard 
medical care and no medical issues can be discussed with the agents. 
• 
The Subject eDiary itself must never be considered a substitute for direct medical 
care and any concerns must be communicated to site staff as soon as possible. 
• 
For all groups the Subject eDiary will be used to collect solicited AEs until 7 days 
after each dose (i.e. day of vaccination and the 6 subsequent days). For groups 1a/b-
3a/b of dose-escalation safety lead-in Subject eDiary will be returned on Day 8, for 
group 4a/b on Day 68 and for subjects in the PoP on Day 75 (groups 5a/b). 
• 
The subject will be contacted by the site staff on Day 31 (all groups), Day 91 (dose-
escalation safety lead-in Group 4 full dose adjuvanted and PoP both groups), Day 
181 (Groups 1-3: half dose non-adjuvanted, full dose non-adjuvanted, half dose 
adjuvanted) and Day 241 (dose-escalation safety lead-in Group 4 full dose 
adjuvanted and PoP both groups) via a scripted safety follow-up phone call. Subjects 
in PoP Step 2 will also be contacted on Day 8 and Day 68 via a scripted safety 
follow-up phone call. At, or in advance of applicable phone call the site will review 
the eDiary web-portal for responses entered by the subject in order to solicit 
additional information during the phone call e.g. related to unsolicited adverse 
events, concomitant vaccinations/medication and medically attended events. 
• 
Any new safety information reported during the safety follow-up phone call or site 
visits (including a solicited adverse event) cannot be entered into the Subject eDiary. 
Such information must be described in the source documents as a verbally-reported 
event. Any adverse event reported in this fashion must be described as an unsolicited 

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adverse event and therefore entered into the eCRF. This includes the assessment of 
COVID-19 cases per the WHO definition [WHO, 2020].  
12.5.8.1. 
Time period for detecting and recording adverse events, serious 
adverse events and pregnancies 
All solicited AEs during 7 days following administration of each dose of study vaccine(s) 
(Day 1 to Day 7 and Day 61 to Day 67) must be recorded in the eDiary, irrespective of 
intensity or whether or not they are considered vaccination-related. 
All other AEs during 30 days following administration of each dose of study vaccine(s) 
(Day 1 to Day 30 and Day 61 to Day 90) must be recorded in the appropriate section of 
the eCRF, irrespective of intensity or whether or not they are considered vaccination-
related. 
The time period for collecting and recording SAEs will begin at the first receipt of study 
vaccine(s) and will end 366 days following administration of the last dose of study 
vaccine(s) for each subject (i.e. the last study visit for each subject). See Section 12.5.9 
for instructions on reporting of SAEs. However, any SAEs assessed as related to study 
participation (e.g. study treatment, protocol-mandated procedures, invasive tests, or 
change in existing therapy) or related to a GSK product will be recorded from the time a 
subject consent to participate in the study. 
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the time of the first receipt of study vaccine(s). 
In addition to the above-mentioned reporting requirements and in order to fulfil 
international reporting obligations, SAEs that are related to study participation (i.e. 
protocol-mandated procedures, invasive tests, a change from existing therapy) or are 
related to a concurrent GSK medication/vaccine will be collected and recorded from the 
time the subject consents to participate in the study until she/he is discharged from the 
study. 
The time period for collecting and recording pregnancies will begin at the first receipt of 
study vaccine(s) and will end 366 days following administration of the last dose of study 
vaccine(s) (i.e. the last study visit for each subject). See Section 12.5.9 for instructions on 
reporting of pregnancies. 
The time period for collecting and recording of pIMDs will begin at the first receipt of 
study vaccine(s) and will end 366 days following administration of the last dose of study 
vaccine(s) (i.e. the last study visit for each subject). See Section 12.5.9.5 for instructions 
on reporting of pIMDs. 

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12.5.8.2. 
Evaluation of adverse events and serious adverse events 
12.5.8.2.1. Active questioning to detect adverse events and serious adverse 
events  
As a consistent method of collecting AEs, the subject should be asked a non-leading 
question such as: 
‘Have you felt different in any way since receiving the vaccine or since the previous 
visit?’ 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. This includes the assessment of COVID-19 cases per the WHO 
definition [WHO, 2020]. The investigator is not allowed to send photocopies of the 
subject’s medical records to GSK instead of appropriately completing the eCRF. 
However, there may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all subject identifiers will be blinded on the 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 and not the individual signs/symptoms. 

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12.5.8.2.2. Assessment of adverse events  
Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
Table 34 
Intensity scales for solicited adverse events in adults 
Adults 
Adverse Event 
Intensity grade 
Parameter 
Pain at injection site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing normal every day 
activities. 
 
2 
Moderate: Painful when limb is moved and interferes with every day 
activities. 
 
3 
Severe: Significant pain at rest. Prevents normal every day activities. 
Redness at injection site 
Record greatest surface diameter in mm 
Swelling at injection site 
Record greatest surface diameter in mm 
Temperature* 
 
Record temperature in °C/°F (with 1 decimal) 
Headache 
0 
Normal 
 
1 
Mild: Headache that is easily tolerated 
 
2 
Moderate: Headache that interferes with normal activity 
 
3 
Severe: Headache that prevents normal activity 
Fatigue 
0 
Normal 
 
1 
Mild: Fatigue that is easily tolerated 
 
2 
Moderate: Fatigue that interferes with normal activity 
 
3 
Severe: Fatigue that prevents normal activity 
Nausea 
0 
Normal 
 
1 
Mild: No interference with daily activity 
 
2 
Moderate: Interference with daily activity 
 
3 
Severe: Prevents daily activity 
Vomiting 
0 
Normal 
 
1 
Mild: 1-2 times in 24 hours 
 
2 
Moderate: 3-5 times in 24 hours 
 
3 
Severe: 6 or more times in 24 hours or requires intravenous hydration 
Diarrhoea 
0 
Normal 
 
1 
Mild: 2 - 3 loose stools in 24 hours 
 
2 
Moderate: 4 - 5 loose stools in 24 hours 
 
3 
Severe: 6 or more loose stools in 24 hours or requires intravenous 
hydration 
Abdominal pain 
0 
Normal 
 
1 
Mild: No interference with daily activity 
 
2 
Moderate: Interferes with daily activity 
 
3 
Severe: Prevents daily activity 
Myalgia 
0 
Normal 
 
1 
Mild: No interference with daily activity 
 
2 
Moderate: Interferes with daily activity 
 
3 
Severe: Prevents daily activity 
Shivering 
0 
Normal 
 
1 
Mild: No interference with daily activity 
 
2 
Moderate: Interferes with daily activity 
 
3 
Severe: Prevents daily activity 
*Fever is defined as temperature  38.0°C/100.4°F. The preferred location for measuring temperature in this study will 
be the oral cavity for adult subjects. 
If any of the solicited symptoms meet the SAE criteria they will reported as a SAE. 

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The maximum intensity of local injection site redness/swelling/fever will be scored at 
GSK as follows: 
0 
: 
< 25 mm diameter 
1 
: 
≥ 25 mm to ≤ 50 mm diameter 
2 
: 
> 50 mm to ≤ 100 mm diameter 
3 
: 
> 100 mm diameter 
Temperature will be scored at GSK Biologicals as follows: 
0 
: 
< 100.4°F (38.0°C)  
1 
: 
≥ 100.4°F (38.0°C) < 102.1°F (39.0°C) 
2 
: 
≥ 102.1°F (39.0°C)  104°F (40.0°C) 
3 
: 
> 104°F (40.0°C) 
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 subject, causing minimal 
discomfort and not interfering with everyday activities. 
2 (moderate) 
= 
An AE which is sufficiently discomforting to interfere with 
normal everyday activities. 
3 (severe) 
= 
An AE which prevents normal, everyday activities. Such an AE 
would, for example, prevent attendance at work/school and 
would necessitate the administration of corrective therapy. 
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. Grade 
3 is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets 1 of the pre-defined 
outcomes as described in Section 12.5.2. 
Grading of laboratory parameters will be based on the FDA Guidance for Industry 
“Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials” (Refer to Appendix 7, Section 12.7). Those 
laboratory parameters not included in the FDA Toxicity Grading Scale will not be 
graded. 
Assessment of causality 
The investigator is obligated to assess the relationship between study vaccine(s) and the 
occurrence of each AE/SAE using clinical judgement. In case of concomitant 
administration of multiple vaccines/products, if possible, the investigator should specify 
if the AE could be causally related to a specific vaccine/product administered (i.e. 
investigational, control/placebo or co-administered vaccine). When causal relationship to 
a specific vaccine(s) cannot be determined, the investigator should indicate the AE to be 
related to all products. 

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Alternative plausible causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study vaccine(s) will be considered and investigated. The investigator will also consult 
the IB and to determine his/her assessment. 
There may be situations when a SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important that the 
investigator always makes an assessment of causality for every event prior to submission 
of the Expedited Adverse Events Report to GSK. The investigator may change his/her 
opinion of causality in light of follow-up information and update the SAE information 
accordingly. The causality assessment is one of the criteria used when determining 
regulatory reporting requirements. 
All solicited local (injection site) and solicited general adverse events will be considered 
causally related to vaccination.  
Causality of all other AEs should be assessed by the investigator using the following 
question: 
Is there a reasonable possibility that the AE may have been caused by the study vaccine? 
YES 
: 
There is a reasonable possibility that the study vaccine(s) contributed to 
the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study vaccine(s). There are other, more likely 
causes and administration of the study vaccine(s) is not suspected to 
have contributed to the AE. 
If an event meets the criteria to be determined as ‘serious’ (see Section 12.5.2), additional 
examinations/tests will be performed by the investigator in order to determine ALL 
possible contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol-required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the vaccines, if applicable. 
• 
Erroneous administration. 
• 
Other cause (specify). 

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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). 
12.5.9. 
Reporting of serious adverse events, pregnancies, and other 
events 
12.5.9.1. 
Prompt reporting of serious adverse events, pregnancies, and other 
events to GSK 
SAEs that occur in the time period defined in Section 12.5.8 will be reported promptly to 
GSK within the timeframes described in Table 23, once the investigator determines that 
the event meets the protocol definition of a SAE. 
Pregnancies that occur in the time period defined in Section 12.5.8 will be reported 
promptly to GSK within the timeframes described in Table 23, once the investigator 
becomes aware of the pregnancy.  
pIMDs that occur in the time period defined in Section 12.5.8 will be reported promptly 
to GSK within the timeframes described in Table 23, once the investigator determines 
that the event meets the protocol definition of a pIMD. 
12.5.9.2. 
SAEs requiring expedited reporting to GSK 
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator (or designate) must complete the information in the electronic Expedited 
Adverse Events Report WITHIN 24 HOURS. The report will always be completed as 
thoroughly as possible with all available details of the event. Even if the investigator does 
not have all information regarding a SAE, the report should still be completed within 24 
hours. Once additional relevant information is received, the report should be updated 
WITHIN 24 HOURS. 
The investigator will always provide an assessment of causality at the time of the initial 
report. The investigator will be required to confirm the review of the SAE causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the SAE. 

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12.5.9.3. 
Back-up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designate) must 
complete, then date and sign a paper Expedited Adverse Events Report and fax it to the 
Study Contact for Reporting SAEs (refer to the Sponsor Information) or to GSK Clinical 
Safety and Pharmacovigilance department within 24 hours.  
This back-up system should only be used if the electronic reporting system is not working 
and NOT if the system is slow. As soon as the electronic reporting system is working 
again, the investigator (or designate) must complete the electronic Expedited Adverse 
Events Report within 24 hours. The final valid information for regulatory reporting will 
be the information reported through the electronic SAE reporting system.  
12.5.9.4. 
Completion and transmission of pregnancy reports to GSK  
Once the investigator becomes aware that a subject is pregnant, the investigator (or 
designate) must complete the required information onto the electronic pregnancy report 
WITHIN 24 HOURS. 
Note: Conventionally, the estimated gestational age (EGA) of a pregnancy is dated from 
the first day of the last menstrual period (LMP) of the cycle in which a woman conceives. 
If the LMP is uncertain or unknown, dating of EGA and the estimated date of delivery 
(EDD) should be estimated by ultrasound examination and recorded in the pregnancy 
report. 
12.5.9.5. 
Reporting of pIMDs to GSK  
Once a pIMD is diagnosed (serious or non-serious) in a study subject, the investigator (or 
designate) must complete the information in the electronic Expedited Adverse Events 
Report WITHIN 24 HOURS after he/she becomes aware of the diagnosis. The report 
allows specify that the event is a pIMD and whether it is serious or non-serious. The 
report will always be completed as thoroughly as possible with all available details of the 
event, in accordance with the pIMDs standard questionnaire provided. Even if the 
investigator does not have all information regarding a pIMD, the report should still be 
completed within 24 hours. Once additional relevant information is received, the report 
should be updated WITHIN 24 HOURS. 
The investigator will always provide an assessment of causality at the time of the initial 
report. The investigator will be required to confirm the review of the pIMD causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the pIMD. 
Refer to Section 12.5.9.3 for back-up system in case the electronic reporting system does 
not work. 

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12.5.10. 
Updating of SAE, pregnancy, and AESI information after removal 
of write access to the subject’s eCRF 
When additional SAE, pregnancy, or pIMD information is received after removal of the 
write access to the subject’s eCRF, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study Contact for Reporting SAEs (refer to the 
Sponsor Information) or to GSK Clinical Safety and Pharmacovigilance department 
within the designated reporting time frames specified in Table 23. 
12.5.11. 
Follow-up of adverse events, serious adverse events, and 
pregnancies 
12.5.11.1. Follow-up of adverse events and serious adverse events 
12.5.11.1.1. 
Follow-up during the study 
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject and provide additional relevant information on the subject’s condition to GSK 
(within 24 hours for SAEs; refer to Table 23). 
All SAEs and pIMDs (serious or non-serious) documented at a previous visit/contact and 
designated as not recovered/not resolved or recovering/resolving will be reviewed at 
subsequent visits/contacts until the last visit of the subject. 
All AEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until 30 
days after the last vaccination. 
12.5.11.1.2. 
Follow-up after the subject is discharged from the study 
The investigator will follow subjects: 
• 
with SAEs, pIMDs (serious or non-serious), or subjects withdrawn from the study as 
a result of an AE, until the event has resolved, subsided, stabilised, disappeared, or 
until the event is otherwise explained, or the subject is lost to follow-up.  
• 
with other non-serious AEs, until event has resolved, subsided, stabilized, 
disappeared, or until the event is otherwise explained, or if the subject is lost to 
follow-up. 
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to GSK using a paper/electronic Expedited Adverse 
Events Report and/or pregnancy report as applicable. 
GSK may request that the investigator performs or arranges the conduct of additional 
clinical examinations/tests and/or evaluations to elucidate as fully as possible the nature 
and/or causality of the AE or SAE. The investigator is obliged to assist. If a subject dies 

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during participation in the study or during a recognised follow-up period, GSK will be 
provided with any available post-mortem findings, including histopathology. 
12.5.11.2. Follow-up of pregnancies 
Pregnant subjects will be followed to determine the outcome of the pregnancy. At the end 
of the pregnancy, whether full-term or premature, information on the status of the mother 
and child will be forwarded to GSK using the electronic pregnancy report and the 
Expedited Adverse Events Report if applicable. Generally, the follow-up period doesn’t 
need to be longer than 6 to 8 weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is a 
SAE, it should always be reported as SAE. 
12.6. 
Appendix 6: Contraceptive guidance and collection of 
pregnancy information 
12.6.1. 
Definitions 
12.6.1.1. 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
12.6.1.1.1. Women in the following categories are not considered WOCBP 
• 
Premenarchal: 
Menarche is the onset of menses for the first time in a young female and is preceded 
by several changes associated with puberty including breast development and pubic 
hair growth. Menarche usually occurs within 1-2 years of breast development, 
thelarche. However, a young female can become pregnant before her first menses. 
Thus, a conservative definition of non-childbearing potential in a pre-menarcheal 
female is a young female who has not yet entered puberty as evidenced by lack of 
breast development (palpable glandular breast tissue). 
• 
Premenopausal female with ONE of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s: review of subject’s medical 
records, medical examination, or medical history interview. 

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• 
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 1 
of the non-hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrolment. 
12.6.2. 
Contraception guidance 
• 
Female subjects of childbearing potential are eligible to participate if they agree to 
use an adequate contraception consistently and correctly according to the methods 
listed in GSK list of highly effective contraceptive methods provided in Table 35.  
Table 35 
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  
• 
oral 
• 
injectable  
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 subject’s entry into the study, and this male is the sole partner for 
that subject, 
(The information on the male sterility can come from the site personnel’s review of the subject’s medical records; 
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 subject.)  
NOTES:  
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 subjects in clinical studies.  

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12.6.3. 
Collection of pregnancy information 
12.6.3.1. 
Female Subjects who become pregnant 
• 
Investigator will collect pregnancy information on any female subject, who becomes 
pregnant while participating in this study.  
• 
Information will be recorded on the appropriate form and submitted to GSK within 
24 hours of learning of a subject's pregnancy.  
• 
Subject will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on subject and neonate, which will be 
forwarded to GSK. Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.  
• 
Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.  
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE.  
• 
A spontaneous abortion is always considered to be an SAE and will be reported as 
such. 
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to GSK 
as described in Section 12.5.9. While the investigator is not obligated to actively 
seek this information in former study subjects, he or she may learn of an SAE 
through spontaneous reporting.  
Any female subject who becomes pregnant while participating will be discontinued 
from study treatment and followed-up until the final outcome.  
12.7. 
Appendix 7: FDA Guidance for Industry: Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled 
in Preventive Vaccine Clinical Trials (September 2007) 
Tables for Laboratory Abnormalities 
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. 

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Table 36 
FDA toxicity grading scales for hematology/ biochemistry 
parameters evaluated in the current study  
Serum * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4)** 
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  
* 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 characterization of the 
laboratory abnormalities as Potentially Life-Threatening (Grade 4). For example, a low sodium value that falls within a 
Grade 3 parameter (125-129 mE/L) should be recorded as a Grade 4 hyponatremia event if the subject had a new 
seizure associated with the low sodium value. 
*** “ULN” is the upper limit of the normal range. 
Hematology * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-Threatening 
(Grade 4) 
Hemoglobin (Female) - gm/dL  
11.0 – 12.0  
9.5 – 10.9  
8.0 – 9.4  
< 8.0 
Hemoglobin (Female)  
change from baseline value - 
gm/dL  
Any decrease 
– 1.5  
1.6 – 2.0  
2.1 – 5.0  
> 5.0 
Hemoglobin (Male) - gm/dL  
12.5 – 13.5  
10.5 – 12.4  
8.5 – 10.4  
< 8.5 
Hemoglobin (Male)  
change from baseline value – 
gm/dL  
Any decrease 
– 1.5  
1.6 – 2.0  
2.1 – 5.0  
> 5.0 
WBC Increase - cell/mm
3 
10 800 – 
15 000  
15 001 – 
20 000  
20 001 – 
25 000  
> 25 000 
WBC Decrease - cell/mm
3 
2 500 – 3 500  1 500 – 2 499  
1 000 – 1 
499  
< 1 000 
Lymphocytes Decrease - 
cell/mm
3 
750 – 1 000  
500 – 749  
250 – 499  
< 250 
Neutrophils Decrease - 
cell/mm
3 
1 500 – 2 000  1 000 – 1 499  
500 – 999  
< 500 
Eosinophils - cell/mm
3 
650 – 1 500  
1 501 - 5 000  
> 5 000  
Hypereosinophilic 
Platelets Decreased - 
cell/mm
3 
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. 
** “ULN” is the upper limit of the normal range. 

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12.8. 
Appendix 8: 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 
Amendment 6 
6 October 2022 
Amendment 5 
22 June 2022 
Amendment 4 
30 November 2021 
Amendment 3 
15 June 2021 
Amendment 2 
2 April 2021 
Amendment 1 
26 May 2020 
Protocol Version 1  
4 September 2019 
12.8.1. 
Protocol Amendment 6 
Overall Rationale for the Amendment: The aim of this protocol amendment is to 
ensure consistency across the different protocol sections related to the interim 
efficacy analysis, with reference to the possibility to continue the enrolment up to 
the planned number of events needed for the key efficacy endpoint evaluation (i.e. 
 and in case futility or efficacy criteria are 
met at the interim analysis based 
. In 
addition, removal of previous GSK logo, correction of typographical errors, and 
minor edits for clarification have been made (refer to Section 12.8.1 for 
information). 
List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief Rationale 
Synopsis; Section 5.2.2 
Section 10.1.1 Hypotheses related 
to primary and secondary 
Update to text linked to hypotheses 
related to primary and secondary 
To ensure consistency across the 
different protocol sections related to 
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Section # and Name 
Description of Change 
Brief Rationale 
objectives 
objectives  
the interim efficacy analysis 
Section 10.1.2 Sample size 
calculation 
Update to text linked to sample size 
calculation and clarification for the 
basis of assumptions  
To ensure consistency across the 
different protocol sections related to 
the interim efficacy analysis 
In the following sections, deleted text is indicated in strikethrough and changed text in 
bold italics: 
In the Title page: 
 
Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA 
Rue de l’Institut 89,  
1330 Rixensart, Belgium 
 
Co-ordinating author(s) 
 (Scientific 
Writer for GSK) 
Contributing authors 
• 
 (CRDLCSL) 
• 
 (SDL) 
• 
 (ODMDMQL)  
In the Sponsor Signatory page: 
Sponsor signatory 
Michele Pellegrini 
Clinical & Epidemiology Project Lead 
In the Synopsis: 
In Section 5.2.2 PoP in subjects with recent S. aureus SSTI Group 5a/b (Phase II): 
The study will follow a group sequential design with two analyses. 
 
 
 
. 
PPD
PPD
PPD
PPD
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In Section 10.2. Sample size calculation: 
12.8.2. 
Protocol Amendment 5 
Overall Rationale for the Amendment:The aim of this protocol amendment is to add 
that during study conduct a presentation of the placebo in a prefilled syringe (PFS) may 
be used. In addition, correction of typographical error, minor edits for clarification, and 
the alignment of some sections to the current Company protocol template have also been 
made (refer to Section 12.8.1 for information). 
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List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief Rationale 
Section 7 Treatment 
An additional presentation of 
placebo (saline line) has been 
added 
Considering that current placebo 
presentation (Hollister Saline in vial) 
is expected to be discontinued in 
future, placebo (saline solution) in 
prefilled syringe presentation has 
been added as it might replace in 
future current vial presentation 
Section 10.2. Population for 
analyses 
Changed the definition of the 
enrolled set 
To remove screening failures from 
the enrolled set  
Section 10.2. Population for 
analyses 
Added screened set within the 
population for analyses  
A specific analytical set comprising of 
all subjects that were screened for 
eligibility  
In the following sections, deleted text is indicated in strikethrough and changed text in 
bold italics: 
In the Title page: 
Co-ordinating author(s) 
 (Scientific Writer) 
 
 (Scientific Writer for GSK) 
Contributing authors 
• 
 (CRDL) 
• 
 (SDL) 
• 
 (ODM) 
• 
 (Study Statistician) 
 
 (Study Statistician) 
• 
 (Lead Statistician) 
• 
 (CLS CRT-L) 
• 
 (Safety Physician) 
• 
 (Safety Scientist) 
• 
 (GRA) 
• 
 (LML) 
• 
 (Lead VDL) 
The following change in units: 
From ml to mL has been applied throughout the Protocol. This change has been indicated 
as black bold italics. 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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In Section 2 Schedule of Activities (SOA), Table 4: 
g The blood sampling for safety lab evaluation only (~6 mL to be drawn from PoP Step 1 subject only) should occur on 
Day 1 and Day 61 but, as an alternative, can be performed up to 1 day before vaccine administration. 
hUnscheduled visits can occur at any time after first study vaccination and should happen as soon as possible 
after signs/symptoms onset 
iOccurrence of solicited AEs within 30 minutes post vaccination observation must be recorded in the eCRF 
In Section 2 Schedule of Activities (SOA), Table 6: 
* Vaccination should occur after clinical resolution of culture confirmed SSTI caused by S. aureus and must occur 
within 30 days from the date of skin drainage for microbiology assessment (done either outside or in the 
study) 
In Section 6.2.1.1 Subjects to be enrolled in the dose-escalation safety lead-in epochs 
*The investigator should use his/her clinical judgement to decide which 
abnormalities are clinically significant as follows: all Haematology/ Biochemistry 
parameters should be within local laboratory normal ranges for the subject to be 
eligible, unless the laboratory abnormalities are of Grade 1 (Refer to Appendix 7, 
Section 12.7) and considered not clinically significant by the investigator. See 
Appendix 2, Section 12.2.2 12.2 for examples. 
In Section 6.2.1.2 Subjects to be enrolled in the proof of principle epochs 
*The investigator should use his/her clinical judgement to decide which 
abnormalities are clinically significant as follows: all Haematology/ Biochemistry 
parameters should be within local laboratory normal ranges for the subject to be 
eligible, unless the laboratory abnormalities are of Grade 1 (Refer to Appendix 7, 
Section 12.7) and considered not clinically significant by the investigator. See 
Appendix 2, Section 12.2.2 12.2 for examples. 

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In Section 7.1 Treatments Administered, (Table 12) 
Study Treatment 
Name: 
Sa-5Ag half dose non-
adjuvanted  
Sa-5Ag full dose non-
adjuvanted  
Sa-5Ag half dose adjuvanted  
Sa-5Ag full dose adjuvanted * 
Placebo  
Study intervention 
name 
Study intervention 
formulation: 
Presentation 
Powder for solution 
for injection/ vial 
Solution 
for 
injection/ 
vial 
Powder for solution 
for injection/ vial 
Solution 
for 
injection/ 
vial 
Powder for 
solution for 
injection/ vial 
Suspension 
for 
suspension 
for injection/ 
vial 
Powder for 
solution for 
injection/ vial 
Suspension 
for 
suspension 
for injection/ 
vial 
Solution 
for 
injection/ 
vial or 
prefilled 
syringe***
*** 
Type 
Study 
Co-
administrat
ion 
Study 
Co-
administrat
ion 
Study 
Co-
administratio
n 
Study 
Co-
administratio
n 
Control 
Product category 
Biological product 
Biological 
product 
Biological product 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Combinati
on 
product 
Route of 
Administration 
IM 
IM 
IM 
IM 
IM 
Administration site: 
Location 
Deltoid  
Deltoid 
Deltoid  
Deltoid  
Deltoid  
Directionality  
Upper 
Upper 
Upper 
Upper 
Upper 
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Study Treatment 
Name: 
Sa-5Ag half dose non-
adjuvanted  
Sa-5Ag full dose non-
adjuvanted  
Sa-5Ag half dose adjuvanted  
Sa-5Ag full dose adjuvanted * 
Placebo  
Laterality *** 
Non-dominant 
Non-dominant 
Non-dominant 
Non-dominant 
Non-
dominant 
Number of doses 
to be 
administered: 
1 
1 
1 
2**** 
1 or 2 **** 
Volume to be 
administered ***** 
0.5 mL 
0.5 mL 
0.5 mL 
0.5 mL 
at least 
0.5 mL 0.5 
mL 
Packaging and 
Labelling 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to 
SPM for 
more 
details 
Manufacturer 
 
 SPM = Study 
Procedures Manual 
Note: The half dosage and the full dosage derive from the same product obtained by resuspending the lyophilised product with different volumes (NaCl 
). 
* S. aureus candidate vaccine 
  
*** 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 
**** The total number of doses is 1 or 2 depending on the study group, i.e. 2 doses only for subjects in group 4 dose-escalation safety lead-in treatment epoch and PoP treatment 
epoch  
***** Refer to the SPM for the volume after reconstitution 
****** The volume in the syringe may be between 0.6 mL and 0.8 mL. The full volume is to be injected. 
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In Section 7.1 Treatments Administered 
The subjects will be observed closely for at least 60 minutes following the administration 
of vaccine/placebo, with appropriate medical treatment readily available in case of 
anaphylaxis and syncope. Occurrence of solicited AEs within 30 minutes post 
vaccination observation must be recorded in the eCRF (Table 4).  
In Section 8.6.1. Staggered vaccination 
Occurrence of solicited AEs within 30 minutes post vaccination observation must be 
recorded in the CRF (Table 4).  
In Section 8.6.3. Study holding rules 
Of note, no formal holding rules will be applied for other safety data such as non-life-
threatening SAEs, missed visits due to vaccine-related AEs, Grade 1 and Grade 2 (Refer 
to Section 12.5.8.2.2) solicited and unsolicited AEs in the 7-day follow-up period and 
unsolicited AEs collected from Day 8 to Day 30 after vaccination. However, these data, if 
available, will also be reviewed by the safety assessment committee (SRT/iSRC as 
applicable) in order to allow for an overall assessment of the benefit/risk ratio of 
vaccination. 
In Section 10.2. Populations for analyses 
Screened 
All subjects who were screened for eligibility 
Enrolled  
All subjects who entered the study (who were randomized or received study 
intervention or underwent a post-screening study procedure). The allocation 
in a group will be done in function of the randomized intervention; non-
randomized subjects will be part of a “Non randomized” group. Note: 
screening failures (who never passed screening even if rescreened) and 
subjects screened but never enrolled into the study (met eligibility but 
ultimately not enrolled) are excluded from the Enrolled analysis set as they 
did not enter the study. 
All subjects who sign informed consent  
Randomized 
All subjects who sign informed consent and are randomized to the treatment group 
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In Section 12.3. Clinical laboratories Table 28 
Laboratory* 
Address 
GSK Biological’s Clinical Laboratory Sciences, 
Rixensart  
Biospecimen Reception-B7/44 
Rue de l'Institut, 89 
B-1330 Rixensart 
Belgium  
GSK Biological’s Clinical Laboratory Sciences, 
Wavre-Nord Noir Epine 
Avenue Fleming, 20 
B-1300 Wavre 
Belgium 
GSK Vaccines S.r.l 
Preclinical R&D, Italy 
Via Fiorentina 1 
53100 Siena 
Italy 
*GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium or Wavre, Belgium. 
CLS may delegate testing to GSK Research laboratories in Siena, Italy or to an external laboratory. 
In Section 12.3. Clinical laboratories Table 29 
Laboratory 
Address 
Q2 Solutions Clinical Trials (UK) 
The Alba Campus Rosebank  
Livingston West Lothian, EH54 7EG Scotland,  
UK  
Q2 Solutions Clinical Trials (US) 
27027 Tourney Road, Suite 2E 
Valencia, CA 91355 
USA 
Nexelis Impfstoffforschung 
(Marburg, Germany) 
Emil-von-Behring-Str. 76 
35041 Marburg 
Germany 
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In Section 12.5.2. Definition of SAE 
Grade 4 laboratory abnormalities (Refer to Appendix 7, Section 12.7). 
In Section 12.5.8.2.2. Assessment of adverse events 
Grading of laboratory parameters will be based on the FDA Guidance for Industry 
“Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials” (Refer to Appendix 7, Section 12.7). Those 
laboratory parameters not included in the FDA Toxicity Grading Scale will not be 
graded. 
12.8.3. 
Protocol Amendment 4 
Overall Rationale for the Amendment: The aim of this protocol amendment is to 
facilitate the enrolment of subjects with S. aureus SSTIs for the PoP phase (Phase II) of 
the study, by extending the allowed upper age limit from 50 to 64 years, allowing 
enrolment of subjects with well-controlled type 2 diabetes mellitus and/or arterial 
hypertension, and extending the interval between S. aureus SSTI microbiological 
diagnosis and signature of the informed consent from 14 days to 30 days. In addition, 
correction of typographical error, minor edits for clarification, and the alignment of some 
sections to the current Company protocol template have also been made (refer to Section 
12.8.1 for information). 
List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief Rationale 
Title page and signature pages 
(short title and title) 
Synopsis, Figure 1 and Figure 3 
Section 5.2 Overall design, Figure 
4 
Section 5.2.2 PoP in subjects with 
recent S. aureus SSTI Group 5a/b 
(Phase II),Figure 6, Table 11 
Section 6.1 Inclusion criteria for 
enrolment 
The age range has been extended 
from 18 to 50 years of age to 18 to 
64 years of age  
To facilitate the enrolment of subjects 
with S. aureus SSTIs for the PoP 
phase (Phase II) of the study. 
Synopsis (including Figure 3) 
Section 2 Schedule of Activities, 
Table 4 and footnote 
Section 2 Schedule of Activities, 
Table 7 and footnote 
Section 5.2.2 PoP in subjects with 
recent S. aureus SSTI Group 5a/b 
(Phase II): Figure 6 and footnote, 
The time interval between S. Aureus 
SSTI microbiological diagnosis and 
the signing of the informed consent 
form has been extended from 14 to 
30 days in the PoP screening phase 
To facilitate the enrolment of subjects 
with S. aureus SSTIs for the PoP 
phase (Phase II) of the study. 

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Section # and Name 
Description of Change 
Brief Rationale 
duration of the study, and sampling 
schedule 
Section 6.1 Inclusion criteria for 
enrolment, Additional inclusion 
criteria only for subjects to be 
enrolled in the PoP screening 
epoch 
Section 8.4.2.1 Sampling for 
efficacy assessments and Table 14 
Section 8.5.2 Time period and 
frequency for collecting AE and 
serious adverse event (SAE) 
information, Table 22 Reporting 
periods for collecting safety 
information (PoP) 
Section 6.2.1.2 Subjects to be 
enrolled in the proof of principle 
(PoP) epochs, Exclusion criteria to 
be considered at study entry 
Wording was added to clarify that 
subjects with well-controlled type 2 
diabetes mellitus (defined as HbA1c 
<7%) and well-controlled 
hypertension (defined as blood 
pressure < 140/90 mmHg) may be 
considered for enrolment in the 
study 
To facilitate the enrolment of subjects 
with S. aureus SSTIs for the PoP 
phase (Phase II) of the study. 
Section 8.5.4 Reporting of serious 
adverse events, pregnancies, and 
other events, Table 23 Timeframes 
for submitting serious adverse 
event, pregnancy and other events 
reports to GSK 
Section 12.5.9.4 Completion and 
transmission of pregnancy reports 
to GSK 
Section12.6.3.1 Female subjects 
who become pregnant 
Change the timeframe for submitting 
pregnancy reports to GSK from 2 
weeks to 24 hours and correct the 
footnote 
To update the timeframe for 
submitting pregnancy reports to GSK 
to align with current Company 
requirements 
In the following sections, deleted text is indicated in strikethrough and changed text in 
bold italics: 
In the Title page: 
EudraCT number 
2021-006215-29 
Short title  
Safety, immunogenicity and efficacy of GSK S. 
aureus candidate vaccine (GSK3878858A) when 
administered to healthy adults (dose-escalation) and 

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to adults 18 to 6450 years of age with a recent S. 
aureus skin and soft tissue infection (SSTI). 
Title 
A Phase I/II, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and 
efficacy of GSK S. aureus candidate vaccine when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 6450 years of age with a recent S. 
aureus skin and soft tissue infection (SSTI). 
Co-ordinating author(s) 
 and 
 (Scientific Writers) 
 (Scientific Writer for GSK) 
Contributing authors 
• 
 and 
 
(CLS CRT-L) 
 
• 
 (LDL)  
• 
 (DPL) 
 (Lead 
VDL) 
In Protocol Amendment 4 Sponsor signatory approval: 
EudraCT number 
2021-006215-29 
Title 
A Phase I/II, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and 
efficacy of GSK S. aureus candidate vaccine when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 6450 years of age with a recent S. 
aureus skin and soft tissue infection (SSTI). 
In Protocol Amendment 4 Investigator agreement: 
• 
That I will comply with the terms of the site agreement. 
EudraCT number 
2021-006215-29 
Title 
A Phase I/II, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and 
efficacy of GSK S. aureus candidate vaccine when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 6450 years of age with a recent S. 
aureus skin and soft tissue infection (SSTI). 
In Synopsis: 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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Overall design, Figure 1 Overall design 
 
PoP in subjects with recent S. aureus SSTI: 
Figure 3 
Study design overview PoP in subjects with a recent S. aureus SSTI 
Group 5a/b: 
 
Note: CDISC is not calculating with Day 0, i.e. interval between Day –30 and Day 1 is 30 days. 
Group 5a/b
PoP second
vaccination
Group 1a/b (only 1 
vaccination): 
Half dose non-
adj/Placebo 
Dose-escalation 
safety lead-in epoch 
Healthy subjects 
18-50 years
N=8/Rando 3:1
Group 2a/b (only 1 
vaccination): 
Full dose non-
adj/Placebo
Group 3a/b (only 1 
vaccination): 
Half dose 
adj/Placebo
SE
SE
SE
Group 4a/b first 
vaccinatiion :
Full dose 
adj/Placebo
Group 5a/b first vaccination:
PoP staggered enrolment/vaccination
(vaccine/placebo; rando 3:1)
Group 5a/b first vaccinatiion
PoP enrolment/vaccination
(vaccine/placebo;
rando 1:1)
N= 40
PoP
Subjects with recent 
history of S. aureus 
SSTI 18-5064 years 
Group 4a/b 
second
vaccination: 
Full dose 
adj/Placebo
SE
SE
SE
SE
SE
SE
SE
N=8
N= 8
N=8
N=8
Unscheduled clinic visit(s) may occur in case of recurrence of SSTI 
Step 1: PoP staggered enrolment/vaccination
(vaccine/placebo; rando 3:1)
Skin Drainage
SE
Step 2: PoP enrolment/vaccination
(vaccine/placebo; rando 1:1)
PoP
(Group 5a/b)
Subjects with 
recent history of 
S. aureus SSTI
18-6450 years 
N= 40
Vaccination epoch
Screening epoch

Visit 9 
M 8 
BS-S
BS-S
BS-S


Visit 0 Day -14
30 Screening
Skin 
Drainage
Visit 3 
Day 15
Visit 10 
M 14
Visit 2
Day 8
Visit 5 
Day 61
Visit 7
Day 75
Visit 8 
M 3
Visit 6 
Day 68
Visit 1 
Day 1 
Visit 4 
Day 31
Second vaccination

Visit 9 
M 8 
BS-S
BS-S
BS-S
BS-S


Visit 0 Day -14
30 Screening
Skin 
Drainage
Visit 3 
Day 15
Visit 10 
M 14
Visit 2
Day 8
Visit 5 
Day 61
Visit 7
Day 75
Visit 8 
M 3
Visit 6 
Day 68
Visit 1 
Day 1 
Visit 4 
Day 31
Second vaccination
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In the PoP screening epoch, study subjects can be selected according to the following 
ways: 
1. Subjects with signs and symptoms of an ongoing skin infection and purulent lesion, 
i.e. SSTI, suspected to be caused by S. aureus will be enrolled after signing an 
informed consent form (ICF). Subjects with surgical site infections are not eligible 
for entry in this study. Subjects with surgical site infections are not included in the 
target population. After demonstration of S. aureus positive culture, performed as a 
study procedure, and confirmation by investigator that S. aureus is the most likely 
cause of SSTI, subjects will continue in the study. Diagnosis (e.g. abscess or 
cellulitis) and body location will be collected in the eCRF. In addition, data related to 
S. aureus 
 
 and recorded in the eCRF. 
Specific treatment will be given in compliance with the standard medical practice for 
the management of S. aureus SSTIs and the choice and judgment of the most 
appropriate treatment will be applied by the investigator, outside the study 
procedures. After conclusion of the specific treatment for the skin lesion and after 
clinical resolution of the SSTI (e.g. no signs of ongoing infection such as swelling, 
erythema, pain or drainage), the first dose of S. aureus candidate vaccine or placebo 
will be administered.  
2. Subjects with an ongoing S. aureus SSTI (i.e. S. aureus is the most likely cause), as 
confirmed by positive culture performed outside the study procedures and not earlier 
than 1430 days prior to ICF signature. Subjects with surgical site infections are not 
eligible for entry in this study. Diagnosis (e.g. abscess or cellulitis) and body 
location will be collected in the eCRF. In addition, S. aureus 
 
 
 and recorded in the eCRF. These subjects will be 
enrolled whether they have or have not already started specific treatment of the 
infection. In case they have not started the treatment, this will be then given in 
compliance with the standard medical practice for the management of S. aureus 
SSTIs and the choice and judgment of the most appropriate treatment will be applied 
by the investigator, outside the study procedures. After conclusion of the specific 
treatment for the skin lesion and after clinical resolution of the SSTI (e.g. no signs of 
ongoing infection such as swelling, erythema, pain or drainage),  the first dose of S. 
aureus candidate vaccine or placebo will be administered. 
In Section 2 Schedule of Activities (SOA), Table 2: 
Safety assessments 
Medical history 
History of administration of adjuvanted vaccine 
Urine pregnancy test 
Check contraindications and warnings and precautions to vaccination 
Pre-vaccination body temperature 
Blood sampling for safety laboratory evaluation (6 mL) 
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In Section 2 Schedule of Activities (SOA), Table 3: 
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In Section 2 Schedule of Activities (SOA), Table 4 and footnote: 
Table 4 
Schedule of activities (Group 5a/b, PoP screening epoch, PoP vaccination epochs) 
Epoch 
PoP 
screening  
PoP vaccination  
Type of contact 
V0  
V1  
V2 
Clinic visit or 
Phone calle  
V3 
 
V4  
Phone 
call 
V5  
V6 
Clinic visit or 
Phone call e  
V7  
V8  
Phone 
call 
V9  
Phone 
call 
V10  
Unscheduled 
visit 
Time points 
Day –30a 
Day 1  
Day 8 
Day 
15 
Day 31 
Day 
61  
Day 68 
Day 
75 
Day 91 
(M 3) 
Day 241 
(M 8)  
Day 426 
(M 14) 
 
Sampling time points 
Pre-
Vac1  
Pre-
Vac2  
Informed consent by subjects 
● 
 
 
 
 
 
 
 
 
 
 
 
Check inclusion/exclusion criteria  
● 
● 
 
 
 
 
 
 
 
 
 
 
Physical examination 
O 
● 
 
 
 
● 
 
 
 
 
 
 
Verification of clinical resolution of SSTI 
 
● 
 
 
 
 
 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
 
 
Vaccine(s)/Product(s)  
Study group and treatment number allocation 
 
O 
 
 
 
 
 
 
 
 
 
 
Treatment number allocation for subsequent doses 
 
 
 
 
 
O 
 
 
 
 
 
 
Recording of administered treatment number 
 
● 
 
 
 
● 
 
 
 
 
 
 
Vaccine administration 
 
● 
 
 
 
● 
 
 
 
 
 
 
Clinical Specimens for microbiology assessments 
Sampling of drainage for cultures performed in the 
study 
● 
 
 
 
 
 
 
 
 
 
 
●c 
Check of culture test report for SA-SSTI confirmation 
● 
 
 
 
 
 
 
 
 
 
 
● 
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Epoch 
PoP 
screening  
PoP vaccination  
Type of contact 
V0  
V1  
V2 
Clinic visit or 
Phone calle  
V3 
 
V4  
Phone 
call 
V5  
V6 
Clinic visit or 
Phone call e  
V7  
V8  
Phone 
call 
V9  
Phone 
call 
V10  
Unscheduled 
visit 
Time points 
Day –30a 
Day 1  
Day 8 
Day 
15 
Day 31 
Day 
61  
Day 68 
Day 
75 
Day 91 
(M 3) 
Day 241 
(M 8)  
Day 426 
(M 14) 
 
Sampling time points 
Pre-
Vac1  
Pre-
Vac2  
Safety assessments 
Medical history 
● 
● 
 
 
 
 
 
 
 
 
 
 
History of administration of adjuvanted vaccine 
● 
● 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
● 
● 
 
 
 
● 
 
 
 
 
 
 
Check contraindications and warnings and 
precautions to vaccination 
O 
O 
 
 
 
O 
 
 
 
 
 
 
Pre-vaccination body temperature 
 
● 
 
 
 
● 
 
 
 
 
 
 
Blood sampling for safety laboratory evaluation 
(6 mL) (PoP Step 1 subjects only)g 
 
● 
● 
 
 
● 
● 
 
 
 
 
 
Phone contact 
(PoP Step 2 subjects only) 
 
 
● 
 
 
 
● 
 
 
 
 
 
Record any concomitant medication/vaccination 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record any intercurrent medical conditions 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Distribution of eDiaries and training  
 
O 
 
 
 
Of 
 
 
 
 
 
 
Review of eDiary data 
 
O 
O 
 
 
 
O 
 
 
 
 
 
Return of eDiaries to the sites 
 
 
 
 
 
 
 
O 
 
 
 
 
Phone contact (all subjects) 
 
 
 
 
● 
 
 
 
● 
● 
 
 
Recording of solicited adverse events   
 
O 
 
 
 
O 
 
 
 
 
 
 
Recording of unsolicited adverse events   
 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
 
Occurrence of solicited AEs at the investigator’s site 
within 30 minutes post-vaccination observation 
 
● 
 
 
 
● 
 
 
 
 
 
 
Reporting of pIMDs 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Reporting of SAEs, pregnancies and pregnancy 
outcomes 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Study Conclusion  
 
 
 
 
 
 
 
 
 
 
● 
 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 

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a CDISC is not calculating with Day 0, i.e. interval between Day –30 and Day 1 is 30 days. 
. 
c SSTI must be amenable to microbiological culturing per standard clinical practice. 
e Visit 2 and 6: Clinical visit for PoP Step 1 subjects (i.e. first 40 subjects enrolled in the PoP) where 6 ml of whole blood for safety laboratory evaluation will be collected; Phone call for 
PoP Step 2 subjects (i.e. all those following subjects after the first 40 enrolled in the PoP Step 1).    
f Remind subjects that the device is now ready to collect after Dose 2 data.  
g The blood sampling for safety lab evaluation only (~6 mL to be drawn from PoP Step 1 subject only) should occur on Day 1 but, as an alternative, can be performed up to 
1 day before vaccine administration. 
a/b = vaccine/placebo 
pIMDs = potential Immune-Mediated Diseases 
SAE = Serious Adverse Event 
Vac = Vaccination 
M = Month 
V = Visit 
C
C
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In Section 2 Schedule of Activities (SOA), Table 7 and footnote: 
Table 7 
Intervals between study visits (PoP epochs) 
Group 5a/b 
Interval 
Length of 
interval  
Allowed interval 
Subjects with S. aureus positive 
culture, performed as a study 
procedure 
V0 (Day –14)→V1 (Day 1) 
14 days  
14 - 29 days*  
Subjects with S. aureus positive 
culture performed outside or in 
the study procedures 
All subjects 
V0 (Day -3014 up to Day 1) 
→V1 (Day 1) 
up to 30 14 
days   
0 - 2930 days*  
V1 (Day 1)→V2 (Day 8) 
7 days  
7 - 9 days  
V1 (Day 1)→V3 (Day 15) 
14 days  
14 - 21 days  
V1 (Day 1)→V4 (Day 31) 
30 days  
30 - 37 days  
V1 (Day 1)→V5 (Day 61) 
60 days  
60 - 67 days  
V5 (Day 61)→V6 (Day 68) 
7 days  
7 - 9 days  
V5 (Day 61)→V7 (Day 75) 
14 days  
14 - 21 days  
V5 (Day 61)→V8 (Month 3, 
day 91) 
30 days  
30 - 40 days  
V5 (Day 61)→V9 (Month 8, 
day 241) 
180 days  
180 - 190 days  
V5 (Day 61)→V10 (Month 14, 
day 426) 
365 days  
365 - 380 days  
Note: CDISC is not calculating with Day 0, i.e. interval between Day –3014 and Day 1 is 3014 days. 
In Section 3.2.2 GSK Biologicals Staphylococcus aureus candidate vaccine: 
 
 
 
 
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In Section 5.2 Overall design, Figure 4: 
Figure 4 
Overall design 
 
In Section 5.2.2 PoP in subjects with recent S. aureus SSTI Group 5a/b (Phase II): 
Figure 6 
Study design overview PoP in subjects with a recent S. aureus SSTI 
and footnote: 
 
Note: CDISC is not calculating with Day 0, i.e. interval between Day –3014 and Day 1 is 3014 days. 
Duration of the study:  
− 
PoP screening epoch: starting at Visit 0 (Day –14) and ending just before Visit 
1(Day 1). 
− 
PoP vaccination epoch: starting with vaccination at Visit 1 (Day 1) and ending 
just before Visit 10 (Month 14 [Day 426]). 
Group 5a/b
PoP second
vaccination
Group 1a/b (only 1 
vaccination): 
Half dose non-
adj/Placebo 
Dose-escalation 
safety lead-in epoch 
Healthy subjects 
18-50 years
N=8/Rando 3:1
Group 2a/b (only 1 
vaccination): 
Full dose non-
adj/Placebo
Group 3a/b (only 1 
vaccination): 
Half dose 
adj/Placebo
SE
SE
SE
Group 4a/b first 
vaccinatiion :
Full dose 
adj/Placebo
Group 5a/b first vaccination:
PoP staggered enrolment/vaccination
(vaccine/placebo; rando 3:1)
Group 5a/b first vaccinatiion
PoP enrolment/vaccination
(vaccine/placebo;
rando 1:1)
N= 40
PoP
Subjects with recent 
history of S. aureus 
SSTI 18-5064 years 
Group 4a/b 
second
vaccination: 
Full dose 
adj/Placebo
SE
SE
SE
SE
SE
SE
SE
N=8
N= 8
N=8
N=8
Unscheduled clinic visit(s) may occur in case of recurrence of SSTI 
Step 1: PoP staggered enrolment/vaccination
(vaccine/placebo; rando 3:1)
Skin Drainage
SE
Step 2: PoP enrolment/vaccination
(vaccine/placebo; rando 1:1)
PoP
(Group 5a/b)
Subjects with 
recent history of 
S. aureus SSTI
18-6450 years 
N= 40
Vaccination epoch
Screening epoch

Visit 9 
M 8 
BS-S
BS-S
BS-S
BS-S


Visit 0 Day -14
30 Screening
Skin 
Drainage
Visit 3 
Day 15
Visit 10 
M 14
Visit 2
Day 8
Visit 5 
Day 61
Visit 7
Day 75
Visit 8 
M 3
Visit 6 
Day 68
Visit 1 
Day 1 
Visit 4 
Day 31
Second vaccination

Visit 9 
M 8 
BS-S
BS-S
BS-S
BS-S


Visit 0 Day -14
30 Screening
Skin 
Drainage
Visit 3 
Day 15
Visit 10 
M 14
Visit 2
Day 8
Visit 5 
Day 61
Visit 7
Day 75
Visit 8 
M 3
Visit 6 
Day 68
Visit 1 
Day 1 
Visit 4 
Day 31
Second vaccination
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In the PoP screening epoch, study subjects can be selected according to the following 
ways: 
1. Subjects with signs and symptoms of an ongoing skin infection and purulent lesion, 
i.e. SSTI, suspected to be caused by S. aureus will be enrolled after signing an 
informed consent form (ICF). Subjects with surgical site infections are not eligible 
for entry in this study. After demonstration of S. aureus positive culture, performed 
as a study procedure, and confirmation by investigator that S. aureus is the most 
likely cause of SSTI, subjects will continue in the study. Diagnosis (e.g. abscess or 
cellulitis) and body location will be collected in the eCRF. In addition, data related to 
S. aureus 
 
 and recorded in the eCRF. 
Specific treatment will be given in compliance with the standard medical practice for 
the management of S. aureus SSTIs and the choice and judgment of the most 
appropriate treatment will be applied by the investigator, outside the study 
procedures. After conclusion of the specific treatment for the skin lesion and after 
clinical resolution of the SSTI (e.g. no signs of ongoing infection such as swelling, 
erythema, pain or drainage), the first dose of S. aureus candidate vaccine or placebo 
will be administered.  
2. Subjects with an ongoing S. aureus SSTI (i.e. S. aureus is the most likely cause), as 
confirmed by positive culture, performed outside the study procedures and not earlier 
than 1430 days prior to ICF signature. Subjects with surgical site infections are not 
eligible for entry in this study. Diagnosis (e.g. abscess or cellulitis) and body 
location will be collected in the eCRF. In addition, S. aureus 
 
 
 and recorded in the eCRF. These subjects will be 
enrolled whether they have or have not already started specific treatment of the 
infection. In case they have not started the treatment, this will be then given in 
compliance with the standard medical practice for the management of S. aureus 
SSTIs and the choice and judgment of the most appropriate treatment will be applied 
by the investigator, outside the study procedures. After conclusion of the specific 
treatment for the skin lesion and after clinical resolution of the SSTI (e.g. no signs of 
ongoing infection such as swelling, erythema, pain or drainage), the first dose of S. 
aureus candidate vaccine or placebo will be administered.  
Study groups, Table 11: 
Table 11: Study groups, treatment and epochs foreseen in the study (PoP epochs) 
Study 
Groups 
Number of 
subjects 
Age 
(Min-Max) 
Treatment name 
Epochs 
(Blinding) 
PoP screening  
(N/A) 
PoP vaccination  
(observer-blind) 
Group 5a 
Vaccine  
250* 
18 – 64 50 
years  
Sa-5Ag full dose 
adjuvanted  
●  
●  
Group 5b 
Placebo  
250* 
18 - 64 50 
years  
Placebo  
●  
●  
N/A = Not Applicable 
*Design of the study is event driven and it can be only estimated that approximately 250 to 300 subjects per study 
group may be needed. Enrolment may continue until 
 are reached. 
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Sampling schedule: 
• 
Drainage samples will be taken from those subjects performing culture test  as study 
procedures at screening (i.e. Day –14 [Visit 0]) and from all subjects with 
recurrences at the time of recurrence. 
In Section 6.1 Inclusion criteria for enrolment: 
• 
A male or female: 
− 
Dose escalation and safety lead-in phase: Aged between 18 and 50 years of 
age, inclusive, at the time of first vaccination.  
− 
PoP phase: Aged between 18 and 64 years of age, inclusive, at the time of first 
vaccination.  
• 
Female subjects of non-childbearing potential may be enrolled in the study. Non-
childbearing potential is defined as pre-menarche, current bilateral tubal ligation or 
occlusion, hysterectomy, bilateral ovariectomy or post-menopause. Refer to Section 
12.6.1 for definitions of women of child-bearing potential, menarche and 
menopause. 
In Section 6.1 Inclusion criteria for enrolment, Additional inclusion criteria only for 
subjects to be enrolled in the PoP screening epoch: 
• 
Healthy subjects as established by medical history and clinical examination before 
entering into the study with an ongoing S. aureus SSTI (i.e. S. aureus is the most 
likely cause), as confirmed by a S. aureus positive culture performed outside the 
study procedures and not earlier than 3014 days prior to ICF signature. 
In Section 6.2.1.2 Subjects to be enrolled in the proof of principle epochs, Exclusion 
criteria to be considered at study entry: 
• 
Acute or chronic, clinically significant pulmonary, cardiovascular*, hepatic or renal 
functional abnormality, neoplasm, diabetes type 1 and uncontrolled diabetes type 2*, 
as determined by physical examination or laboratory screening tests.  
* Note: Well-controlled type 2 diabetes mellitus (HbA1c <7%) and well-controlled 
arterial hypertension (blood pressure <140/90 mmHg) can be considered for 
inclusion in the study. 
In Section 6.2.2 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 vaccine/placebo dose. For corticosteroids, this will mean 
prednisone ≥205 mg/day, or equivalent. Inhaled and topical steroids are allowed. 
 

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In Section 7.1 Treatments administered, Table 12: 
Table 12 
Treatments administered 
Study Treatment 
Name: 
Sa-5Ag half dose non-
adjuvanted  
Sa-5Ag full dose non-
adjuvanted  
Sa-5Ag half dose adjuvanted  
Sa-5Ag full dose adjuvanted * 
Placebo  
Study intervention 
Vaccine(s)/ 
Product(s) name 
Study intervention 
Vaccine(s) / 
Product(s) 
formulation: 
Presentation 
Lyophilized form in 
vial Powder for 
solution for 
injection/ vial 
Solution 
for 
injection/ 
Liquid in 
vial 
Lyophilized form in 
vial Powder for 
solution for 
injection/ vial 
Solution 
for 
injection/ 
Liquid in 
vial 
Lyophilized form 
in vial Powder 
for solution for 
injection/ vial 
Liquid in  
Suspension 
for 
suspension 
for 
injection/ 
vial 
Lyophilized 
form in vial 
Powder for 
solution for 
injection/ vial 
Liquid in  
Suspension 
for 
suspension 
for injection/ 
vial 
Solution 
for 
injection/ 
Liquid in 
vial  
Type 
Study 
Co-
administr
ation 
Study 
Co-
administr
ation 
Study 
Co-
administrati
on 
Study 
Co-
administrati
on 
Control 
Product category 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Biological 
product 
Route of 
Administration 
IM 
IM 
IM 
IM 
IM 
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Study Treatment 
Name: 
Sa-5Ag half dose non-
adjuvanted  
Sa-5Ag full dose non-
adjuvanted  
Sa-5Ag half dose adjuvanted  
Sa-5Ag full dose adjuvanted * 
Placebo  
Administration site: 
Location 
Deltoid  
Deltoid 
Deltoid  
Deltoid  
Deltoid  
Directionality  
Upper 
Upper 
Upper 
Upper 
Upper 
Laterality *** 
Non-dominant 
Non-dominant 
Non-dominant 
Non-dominant 
Non-
dominant 
Number of doses 
to be 
administered: 
1 
1 
1 
2**** 
1 or 2 **** 
Volume to be 
administered ***** 
0.5 ml 
0.5 ml 
0.5 ml 
0.5 ml 
0.5 ml 
Packaging and 
Labelling 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to 
SPM for 
more 
details 
Manufacturer 
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In Section 7.3.1 Emergency unblinding, Table 13: 
GSK Helpdesk 
24 hours/7 days availability 
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  
For US 
Toll-free number: 1 844 446 3133877 870 0019 
In Section 7.5.2 Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from per-protocol analyses 
• 
Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. more than 14 days in total) during the study period. For corticosteroids, this will 
mean prednisone 205 mg/day, or equivalent. Inhaled and topical steroids are 
allowed. 
In Section 8.3 Case definition of recurrent S.aureus SSTI: 
• 
If results from microbiological diagnostics in the investigator’s opinion suggest that 
S. aureus is the primary cause of the SSTI, then the case will be considered as a 
culture confirmed recurrence. 
• 
If results from microbiological diagnostics are inconclusive, or if no microbiological 
testing was performed, then the case will be considered as a suspected recurrence. 
In Section 8.4.2.1 Sampling for efficacy assessments: 
Skin drainage samples will be collected from those subjects in the PoP performing 
culture test as a study procedure at screening (i.e. Day –1430 [Visit 0]) and from all 
subjects at the time of their recurrence of SSTI (i.e. unscheduled visits).  
Drainage samples will not be stored. 
Table 14 
Biological samples for efficacy assessment (PoP)  
Sample type 
Quantity 
Unit 
Timepoint 
Subjects 
Drainage samples 
Depends on availability 
Day –1430 (V0) 
 
 
 
Unscheduled* 
Subjects with SSTI who perform 
culture test as a study procedure at 
screening 
 
Subjects with suspected SA-SSTI 
V = Visit 
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* Additionally, subjects with recurrent SSTI at the time of recurrence 
In Section 8.4.2.2 Blood sampling for immunogenicity response assessments: 
The maximum amount of blood collected from each subject over the duration of the 
study, including any extra assessments that may be required, will not exceed 125 ml mL 
for subjects participating in the dose-escalation safety lead-in and will not exceed 274 ml 
mL for subjects participating in the PoP. 
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In Section 8.5.2 Time period and frequency for collecting AE and serious adverse 
event (SAE) information, Table 22 
Table 22 
Reporting periods for collecting safety information (PoP)  
Event 
Study group 
Pre-
Vac 
Vac1 
 
 
 
Vac2 
 
 
 
Study Conclusion 
 
Vaccine 
Placebo 
D–30* D1 
D7 
D30 
 
D61 D67 D90 
 
D426 
M14 
In Section 8.5.4 Reporting of serious adverse events, pregnancies, and other events, 
Table 23 Timeframes for submitting serious adverse event, pregnancy and other 
events reports to GSK 
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Table 23 
Timeframes for submitting serious adverse event, 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 2 
weeks* 
electronic pregnancy report 
24 hours 2 
weeks* 
electronic pregnancy report 
pIMDs  
24 hours** ‡ 
electronic Expedited 
Adverse Events Report 
24 hours* 
Electronic Expedited Adverse 
Events Report 
* Timeframe allowed after receipt or awareness of the information. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of a pIMD. 
‡ The investigator will be required to confirm review of the SAE/pIMD causality by ticking the ‘reviewed’ box in the 
electronic Expedited Adverse Events Report within 72 hours of submission of the SAE/pIMD. 
In Section 10.3.3.1 Case accountability: 
Endpoint 
Statistical Analysis Methods 
Key 
secondary 
The analysis of efficacy will be based on the occurrence of the first case of SSTI anytime from 15 
Days after the administration of the second dose of the study vaccine up to 12 months. All 
subjects from the mFAS will contribute to the comparison between the treatment and the placebo 
groups. 
Time to occurrence of key secondary endpoint during the defined efficacy follow-up period will be 
compared between groups by calculating the respective Hazard ratio (methods will be detailed in 
the SAP).  
Vaccine (VE) will be defined as 1 minus the hazard ratio times 100: 
VE = (1 – hazard ratio) x 100 
Censoring will occur at the time of the last scheduled or medically attended visit without the 
occurrence of SSTI cases before the end of follow-up. Subjects who will complete the follow-up 
without events will be censored at 1 year. 
In order to check the statistical significance, 1-sided P-value for the log rank test will be 
calculated. 1-sided nominal type I error will be 1.61% at the interim analysis and 5.89% at the final 
analysis. The objective will be met if the 1-sided P-value calculated for the null hypothesis H0 = 
[occurrence SSTI VE =≥0%] is lower than defined 1-sided alpha level. 
Co-secondary 
The co- secondary endpoint will be analysed only if the statistical significance is demonstrated for 
the key secondary endpoint. 
For this analysis, the mFAS will account for the first case of SSTI anytime from 15 Days after the 
administration of the first dose of the study vaccine up to 14 months. 
Time to occurrence of the co- secondary endpoint during the defined efficacy follow-up period will 
be compared between groups by calculating the respective Hazard ratio (methods will be detailed 
in the SAP). 
In order to check the statistical significance, 1-sided P-value for the log rank test will be 
calculated. 1-sided nominal type I error will be 5.89%. (the nominal alpha level is equal to the key 
secondary at the final analysis, because we use a sequential procedure). The objective will be 
met if the 1-sided P-value calculated for the null hypothesis H0=[occurrence SSTI VE =≥0%] is 
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In Section 10.3.4 Immunogenicity analyses 
Endpoint 
Statistical Analysis Methods 
In Section 12.1.1 List of abbreviations: 
LOD: 
Limit of Detection 
LLOQ: 
Lower Limit of Quantitation 
In Section 12.2.2 Laboratory assays for safety evaluation: 
• 
If values out of normal ranges (Grade 1 considered clinically significant or above 
Grade 1) are observed, which are expected to be temporary (e.g., due to 
dehydration), the abnormal parameters can be re-assessed during a rescreening* visit 
but they must have returned to within local laboratory normal ranges for the subject 
to be eligible. If considered necessary by the investigator, related parameters outside 
of the panel can be (re-)tested in addition to the abnormal parameters 
(Haematology/Biochemistry). The subjects should be informed about the possibility 
of rescreening* in the informed consent form (ICF). 
* Rescreening of subjects with previous screening failure due to non-S. aureus 
SSTI is also possible. In such cases, the complete screening process should be 
reperformed. 
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In Section 12.4.4 Data protection: 
GSK will also ensure the protection of personal data of investigator and the site staff 
which will be collected within the framework and for the purpose of the study, in 
accordance with the Data Privacy Notice that will be sent to the site staff.  
In Section 12.4.9 Study and site start and closure: 
Heading: Section 12.4.9 Study and site start and closure 
First act of recruitment 
Start of study is defined as first subject first visit (FSFV) at a country-level. 
Study/Site termination  
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK, provided there is sufficient notice given 
to account for patient’s safe exit from study participation. Study sites regular closure will 
be 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 sufficient notice is given 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 subjects by the investigator 
• 
Discontinuation of further study treatment development 
• 
Total number of subjects included earlier than expected 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform 
the investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organisation(s) used in the study of the reason for termination or suspension, as 
specified by the applicable regulatory requirements. The investigator shall promptly 
inform the subject and should assure appropriate subject therapy and/or follow-up.  
The investigator will: 
• 
Review data collected to ensure accuracy and completeness. 
• 
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In Section 12.5.8 Detecting and recording adverse events, serious adverse events and 
pregnancies: 
Subject eDiary training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the Subject 
eDiary. This individual may not be the subject, but if a person other than the subject 
enters information into the Subject eDiary, this must be documented in the subject’s 
source record. Any individual that makes entries into the Subject eDiary must receive 
training on completion of the Subject eDiary at the time of the visit when Subject eDiary 
is dispensed. This training must be documented in the subject’s source record. 
Subject eDiary assignment and use: 
• 
Each subject will be assigned a Subject eDiary and shown how to use the device – 
this will include how to access the eDiary, performing test data entry on sample 
questions enter data into the eDiary screens, and how to charge and store the 
device. 
In Section 12.5.9.4 Completion and transmission of pregnancy reports to GSK: 
Once the investigator becomes aware that a subject is pregnant, the investigator (or 
designate) must complete the required information onto the electronic pregnancy report 
WITHIN 2 WEEKS 24 HOURS. 
In Section 12.6.2 Contraception guidance, Table 35 Highly Effective Contraceptive 
Methods and footnote: 
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 ovulationb  
• 
oral 
• 
intravaginal  
• 
transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulationb  
• 
oral 
• 
injectable  
Highly Effective Methods That Are User Independent  
• 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulationb 
• 
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 subject’s entry into the study, and this male is the sole partner for 
that subject, 
(The information on the male sterility can come from the site personnel’s review of the subject’s medical records; 
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 subject.)  

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NOTES:  
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 subjects in clinical studies.  
b Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy of the 
contraceptive method. In this case 2 highly effective methods of contraception should be utilised during the treatment 
period and for at least 30 days after the last dose of study treatment  
In Section 12.6.3.1 Female subjects who become pregnant: 
• 
Information will be recorded on the appropriate form and submitted to GSK within 
24 hours 2 weeks of learning of a subject's pregnancy.  
12.8.4. 
Protocol Amendment 3 
Overall Rationale for the Amendment: The sponsor is updating the clinical research 
phase of the study from Phase I toPhase I/II to account for the design of the study which, 
in its Proof of Principle epoch, aims to also generate evidence on the efficacy of the 
vaccine to prevent recurrences of Skin and Soft Tissue Infections due to Staphylococcus 
aureus in the target population. 
List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief Rationale 
Title page and signature pages 
Synopsis 
Section 3.1, Study rationale 
Section 5.1, Scientific rationale for 
study design 
Section 5.2, Overall design 
The phase has been modified from 
Phase I to Phase I/II. 
Change to account for the design of 
the study which,  in its Proof of 
Principle epoch,.aims to also 
generate evidence on the efficacy of 
the vaccine to prevent recurrences of 
Skin and Soft Tissue Infections due 
to Staphylococcus aureus in the 
target population  
Section 8.5.4.1, Contact 
information for reporting of serious 
adverse events (SAEs), pIMDs, 
pregnancies and study holding 
rules 
The contact phone numbers and e-
mail address for non-US sites were 
added. 
Change needed to allow other 
countries, outside the US, to 
potentially support screening and 
enrolment of participants of the POP 
part of the study . 
Detailed description of Protocol Amendment 3: 
In the following sections, deleted text is indicated in strikethrough and changed text in 
bold italics: 
In the Title page: 
Title 
A Phase I/II, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and 
efficacy of GSK S. aureus candidate vaccine when 
administered to healthy adults (dose-escalation) and 

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to adults 18 to 50 years of age with a recent S. aureus 
skin and soft tissue infection (SSTI). 
Co-ordinating author(s) 
 and 
 (Scientific Writers) 
and
 (Scientific writer for GSK) 
In Protocol Amendment 3 Sponsor signatory approval and Protocol Amendment 3 
Investigator agreement: 
Title 
A Phase I/II, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and 
efficacy of GSK S. aureus candidate vaccine when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 50 years of age with a recent S. aureus 
skin and soft tissue infection (SSTI). 
In Synopsis: 
Rationale: The purpose of this seamless Phase I/II, first time in human - proof of 
principle (FTIH-PoP) study is to assess safety and reactogenicity, to perform a 
preliminary evaluation of clinical efficacy and to explore immunogenicity of GSK 
Biologicals’ S. aureus vaccine compared to placebo (saline), both administered in a 2-
dose schedule on Day 1 and Day 61. 
Overall design: This is a Phase I/II, placebo-controlled, observer-blind, randomised, 
multi-centric study. 
In Section 3.1, Study rationale: 
The purpose of this seamless Phase I/II first time in human - proof of principle (FTIH-
PoP) study is to evaluate safety and reactogenicity, to perform a preliminary evaluation of 
clinical efficacy and to explore immunogenicity of GSK Biologicals’ S. aureus vaccine 
compared to placebo (saline), both administered in a 2-dose schedule on Day 1 and Day 
61. 
In Section 5.1, Scientific rationale for study design: 
The rationale for the vaccine composition and dosage is provided in Section 3.2.2. 
This is a seamless Phase I/II self-contained study comprising of 2 phases: The the 
study design comprises a combined FTIH evaluation and PoP demonstration aiming to 
provide an agile pathway from the concept to the clinical PoP. 
PPD
PPD
PPD
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). For details of study design refer to Section 
5.2; details about the internal safety evaluation by iSRC will be described in the iSRC 
Charter.  
The primary objective of this FTIH study is the assessment of safety and reactogenicity 
of the investigational S. aureus vaccine. 
Endpoints and statistical considerations of the secondary objective “vaccine efficacy 
(VE) in the prevention of recurrent culture confirmed S. aureus SSTIs compared to 
placebo” are based on the results of a study (207908 [EPI-STAPH-006 BOD DB]) which 
retrospectively reviewed the databases of three hospitals in the US that had available data 
on SSTI. The retrospective review focused on adult outpatients attending the outpatient 
and emergency departments and that were diagnosed with SSTI with the purpose of 
investigating the frequency of S. aureus SSTIs. 
The PoP phase (Phase II) is designed as an event driven study and subjects will be 
enrolled until 
. Since there 
is currently no licensed vaccine against S. aureus infections the comparator group will 
receive placebo (saline). 
In the protocol ahead, Phase I is called as the dose-escalation safety lead-in or safety 
lead-in phase and Phase II is called as PoP phase. 
In Section 5.2, Overall design: 
5.2.1 Dose-Escalation safety lead-in healthy subjects (Phase I) 
5.2.2. PoP in subjects with recent S. aureus SSTI Group 5a/b (Phase II) 
• 
Experimental design: Phase I II, observer-blind, randomised, controlled, group 
sequential, multi-centric study with 2 parallel groups in the PoP vaccination epoch. 
In Section 8.4.2.2, Blood sampling for immunogenicity response assessments: 
The maximum amount of blood collected from each subject over the duration of the 
study, including any extra assessments that may be required, will not exceed 125 ml for 
subjects participating in the dose-escalation safety lead-in and will not exceed 310 274 ml 
for subjects participating in the PoP. 
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In Section 8.5.4.1, Contact information for reporting of serious adverse events 
(SAEs), pIMDs, pregnancies and study holding rules: 
Table 25 
Contact information for reporting of serious adverse events (SAEs), 
pIMDs, pregnancies and study holding rules 
Study contact for questions regarding SAEs, pIMDs, pregnancies and study holding rules 
Refer to the local study contact information document 
Study Contact for Reporting of study holding rules  
As soon as the investigator is aware that a holding rule is met, he/she must immediately inform the Local Medical 
Lead (LML).  
Back-up Study Contact for Reporting SAEs, pIMDs, pregnancies and study holding rules  
24 hours/7 days availability: 
GSK Clinical Safety & Pharmacovigilance 
Outside US 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 
In Section 11, References: 
WHO. Global Surveillance for human infection with coronavirus disease (COVID-19). 
Interim guidance. https://www.who.int/publications-detail/global-surveillance-for-
human-infection-with-novel-coronavirus-(2019-ncov). Accessed May 15, 2020  
WHO. Public health surveillance for COVID-19. Interim guidance: December 2020; . 
https://www.who.int/publications/i/item/who-2019-nCoV-surveillanceguidance-2020.8 
Accessed June 15, 2021. 

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12.8.5. 
Protocol Amendment 2 
Overall Rationale for the Amendment: The main reasons for this protocol amendment 
have been to simplify the study procedures for the proof of principle (PoP) phase, 
including those related to the screening of subjects and to outline specific measures 
related to an emergency mass vaccination for an unforeseen public health threat (e.g.: a 
pandemic) that may be applicable during the subjects’ participation in the study. 
Additionally, some minor corrections have been made as well. 
List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief Rationale 
Synopsis and Section 
5.2 Overall design 
Section 2: Schedule of 
activities 
Section 6.1: Inclusion 
criteria 
To allow also subjects with 
documented recent SA-SSTI, as 
diagnosed  outside the study 
procedures by external laboratories, 
the possibility to have access to the 
screening procedures for study 
eligibility in the PoP phase. 
To maximize the possibility to enrol the target 
population of the PoP phase in the context of 
Covid-19 pandemic. 
Synopsis and Section 
5.2 Overall design  
Section 2: Schedule of 
activities 
To restrict the collection of blood 
samples for safety evaluation to the 
first 40 subjects enrolled in the proof 
of principle (PoP) phase (i.e. 
staggered enrollment, Step 1). 
To change Visits 2 and 6 for PoP Step 
2 participants from clinic visits to 
safety phone calls, as no other 
invasive procedures were foreseen, 
apart the safety blood draws. 
To simplify study procedures in the context of 
Covid-19 pandemic, and considering that 
holding rules related to laboratory 
abnormalities were not applicable for subjects 
belonging to PoP Step 2, blood sample for 
safety will be collected for PoP Step 1 subjects 
only and will not be collected PoP Step 2.  
 
Section 6.2.2: 
Prior/Concomitant 
therapy 
Specific measures related to 
vaccination against  emergency mass 
vaccination that may be applicable 
during the subjects’ participation in the 
study 
To add instructions on how to manage 
possible emergency mass vaccinations done 
outside the study 
Synopsis and Section 4: 
Objectives and 
endpoints  
 
Section 2: Schedule of 
activities 
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Detailed description of Protocol Amendment 2: 
In the following sections, deleted text is indicated in strikethrough and changed text in 
bold italics: 
In the Title page: 
Primary Study vaccine 
• 
GlaxoSmithKline (GSK) Biologicals 
Staphylococcus aureus candidate vaccine (S. 
aureus candidate vaccine [Sa-5Ag adjuvanted]) 
Co-ordinating author(s) 
• 
 and 
 (Scientific 
Writers) and 
 (Scientific 
Writer for GSK) 
Contributing authors 
• 
 (CRDL) 
• 
 (Study Statistician) 
• 
 (GRA) 
• 
 (GRA) 
In Protocol Amendment 2 Sponsor Signatory Approval: 
Note: Not applicable if an alternative signature process (e.g. electronic signature or 
email approval) is used to get the sponsor approval. 
In the whole document: 
Covid-19 has been written as COVID-19 
In Synopsis and Section 4: Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
Descriptive: 
• 
To assess safety and reactogenicity of 
investigational S. aureus vaccine 
• 
Occurrence and intensity of solicited local and general AEs 
during 7 days after each dose (i.e. day of vaccination and 
the 6 subsequent days) in all subjects by vaccination group. 
• 
Occurrence, intensity and relationship to vaccination of 
unsolicited AEs during 30 days after each dose (i.e. day of 
injection and the 29 subsequent days) in all subjects by 
vaccination group. 
• 
Occurrence, intensity and relationship to vaccination of all 
SAEs in all subjects by vaccination group: 
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Objectives 
Endpoints 
− 
Groups 1 to 3 from Day 1 (day of vaccination) until 
Day 366. 
− 
Groups 4 and 5 from Day 1 (day of vaccination) until 
Day 426. 
• 
Occurrence, intensity and relationship to vaccination of all 
potential immune-mediated disease (pIMDs) during in all 
subjects by vaccination group. 
− 
Groups 1 to 3 from Day 1 (day of vaccination) until 
Day 366. 
− 
Groups 4 and 5 from Day 1 (day of vaccination) until 
Day 426. 
• 
Occurrence of haematological and biochemical laboratory 
abnormalities, and changes from the baseline values after 
vaccination, in all subjects by vaccination group on Days 8, 
and 68 (i.e. 7 days after dose 1 and dose 2), respectively: 
− 
In all subjects of Groups 1 to 3 on Day 8. 
− 
In all subjects of Group 4 on Days 8 and 68  (i.e. 7 
days after dose 1 and dose 2), respectively. 
− 
Subjects in Group 5 Step 1 (i.e. first 40 subjects 
enrolled in the PoP) on Days 8 and 68  (i.e. 7 days 
after dose 1 and dose 2), respectively. 
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In Synopsis and Section 5.2 Overall design – Figure 3 Study design overview PoP in 
subjects with a recent S. aureus SSTI Group 5a/b 
 
 
 
In the PoP screening epoch, study subjects can will be selected according to the 
following ways: 
3. based on Subjects with signs and symptoms of an ongoing skin infection and 
purulent lesion, i.e. SSTI, suspected to be caused by S. aureus. Subjects will then be 
enrolled after signing an informed consent form (ICF). After demonstration of S. 
aureus positive culture, performed as a study procedure, and confirmation by 
investigator that S. aureus is the most likely cause of SSTI, subjects will continue in 
the study. Diagnosis (e.g. abscess or cellulitis) and body location will be collected 
in the eCRF. In addition,  data related to S. aureus 
 
 
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 and recorded in the eCRF. Specific treatment will be 
given in compliance with the standard medical practice for the management of S. 
aureus SSTIs and the choice and judgment of the most appropriate treatment will be 
applied by the investigator, outside the study procedures. After conclusion of the 
specific treatment for the skin lesion and after clinical resolution of the SSTI (e.g. no 
signs of ongoing infection such as swelling, erythema, pain or drainage), the first 
dose of S. aureus candidate vaccine or placebo will be administered.  
4. Subjects with an ongoing S. aureus SSTI (i.e. S. aureus is the most likely cause), 
as confirmed by positive culture performed outside the study procedures and not 
earlier than 14 days prior to ICF signature. Diagnosis (e.g. abscess or cellulitis) 
and body location will be collected in the eCRF. In addition, S. aureus 
 
 
 and recorded in the eCRF. These 
subjects will be enrolled whether they have or have not already started specific 
treatment of the infection. In case they have not started the treatment, this will be 
then given in compliance with the standard medical practice for the management 
of S. aureus SSTIs and the choice and judgment of the most appropriate treatment 
will be applied by the investigator, outside the study procedures. After conclusion 
of the specific treatment for the skin lesion and after clinical resolution of the 
SSTI (e.g. no signs of ongoing infection such as swelling, erythema, pain or 
drainage), the first dose of S. aureus candidate vaccine or placebo will be 
administered. 
In Section 2 Schedule of activities (SoA): 
Table 5 
Schedule of activities (Group 5a/b, PoP screening epoch, PoP 
vaccination epochs) 
Epoch 
PoP 
screening 
PoP vaccination  
Type of contact 
V0  
V1  
V2 
Clinic 
visit 
or 
Phone 
call e 
V3  
V4  
Phone 
call 
V5  
V6 
Clinic 
visit 
or 
Phone 
call e 
V7  
V8  
Phone 
call 
V9  
Phone 
call 
V10 Unscheduled 
visit 
Time points 
Day –14a 
Day 
1  
Day 8 Day 
15 
Day 
31 
Day 
61  Day 68 Day 
75 
Day 
91 (M 
3) 
Day 
241 
(M 8)  
Day 
426 
(M 
14) 
 
Sampling time points 
Pre-
Vac1 
Pre-
Vac2 
Informed consent by 
subjects 
● 
 
 
 
 
 
 
 
 
 
 
 
Check 
inclusion/exclusion 
criteria  
● 
● 
 
 
 
 
 
 
 
 
 
 
Physical examination 
O 
● 
 
 
 
● 
 
 
 
 
 
 
Verification of clinical 
resolution of SSTI 
 
● 
 
 
 
 
 
 
 
 
 
 
Collect demographic 
data 
● 
 
 
 
 
 
 
 
 
 
 
 
Vaccine(s)/Product(s)  
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Epoch 
PoP 
screening 
PoP vaccination  
Type of contact 
V0  
V1  
V2 
Clinic 
visit 
or 
Phone 
call e 
V3  
V4  
Phone 
call 
V5  
V6 
Clinic 
visit 
or 
Phone 
call e 
V7  
V8  
Phone 
call 
V9  
Phone 
call 
V10 Unscheduled 
visit 
Time points 
Day –14a 
Day 
1  
Day 8 Day 
15 
Day 
31 
Day 
61  Day 68 Day 
75 
Day 
91 (M 
3) 
Day 
241 
(M 8)  
Day 
426 
(M 
14) 
 
Sampling time points 
Pre-
Vac1 
Pre-
Vac2 
Study group and 
treatment number 
allocation 
 
O 
 
 
 
 
 
 
 
 
 
 
Treatment number 
allocation for 
subsequent doses 
 
 
 
 
 
O 
 
 
 
 
 
 
Recording of 
administered treatment 
number 
 
● 
 
 
 
● 
 
 
 
 
 
 
Vaccine administration 
 
● 
 
 
 
● 
 
 
 
 
 
 
Clinical Specimens for microbiology assessments 
Sampling of drainage 
for cultures performed 
in the study 
● 
 
 
 
 
 
 
 
 
 
 
●c 
Check of culture test 
report for SA-SSTI 
confirmation  
● 
 
 
 
 
 
 
 
 
 
 
● 
Safety assessments 
Medical history 
● 
● 
 
 
 
 
 
 
 
 
 
 
History of administration 
of adjuvanted vaccine 
● 
● 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
● 
● 
 
 
 
● 
 
 
 
 
 
 
Check contraindications 
and warnings and 
precautions to 
vaccination 
O 
O 
 
 
 
O 
 
 
 
 
 
 
Pre-vaccination body 
temperature 
 
● 
 
 
 
● 
 
 
 
 
 
 
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Epoch 
PoP 
screening 
PoP vaccination  
Type of contact 
V0  
V1  
V2 
Clinic 
visit 
or 
Phone 
call e 
V3  
V4  
Phone 
call 
V5  
V6 
Clinic 
visit 
or 
Phone 
call e 
V7  
V8  
Phone 
call 
V9  
Phone 
call 
V10 Unscheduled 
visit 
Time points 
Day –14a 
Day 
1  
Day 8 Day 
15 
Day 
31 
Day 
61  Day 68 Day 
75 
Day 
91 (M 
3) 
Day 
241 
(M 8)  
Day 
426 
(M 
14) 
 
Sampling time points 
Pre-
Vac1 
Pre-
Vac2 
Blood sampling for 
safety laboratory 
evaluation (6 ml) (PoP 
Step 1 subjects only) 
 
● 
● 
 
 
● 
● 
 
 
 
 
 
Phone contact 
(PoP Step 2 subjects 
only) 
 
 
● 
 
 
 
● 
 
 
 
 
 
Record any concomitant 
medication/vaccination 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record any intercurrent 
medical conditions 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Distribution of eDiaries 
and training  
 
O 
 
 
 
Of 
 
 
 
 
 
 
Review of eDiary data 
 
O 
O 
O 
O 
O 
O 
O 
 
 
 
 
Return of eDiaries to 
the sites 
 
 
 
 
 
 
 
O 
 
 
 
 
Phone contact (all 
subjects) 
 
 
 
 
● 
 
 
 
● 
● 
 
 
Recording of solicited 
adverse events   
 
O 
 
 
 
O 
 
 
 
 
 
 
Recording of unsolicited 
adverse events   
 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
 
Occurrence of solicited 
AEs at the investigator’s 
site within 30 minutes 
post-vaccination 
observation 
 
● 
 
 
 
● 
 
 
 
 
 
 
Reporting of pIMDs 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Reporting of SAEs, 
pregnancies and 
pregnancy outcomes 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Study Conclusion  
 
 
 
 
 
 
 
 
 
 
● 
 
Note: The double-line borders indicate analyses which will be performed on all data obtained up to those time points. 
* aCDISC is not calculating with Day 0, i.e. interval between Day –14 and Day 1 is 14 days. 
*** c If possible.SSTI must be amenable to microbiological culturing per standard clinical practice. 
***** e Visit 2 and 6: Clinical visit for PoP Step 1 subjects (i.e. first 40 subjects enrolled in the PoP) where 6 ml 
of whole blood for safety laboratory evaluation will be collected; Phone call for PoP Step 2 subjects (i.e. all 
those following subjects after the first 40 enrolled in the PoP Step 1.  
****** f Remind subjects that the device is now ready to collect after Dose 2 data.  
 
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Table 7 
Intervals between study visits (PoP epochs)  
Group 5a/b 
Interval 
Length of interval  
Allowed interval 
Subjects 
with S. 
aureus 
positive 
culture, 
performed 
as a study 
procedure 
V0 (Day –14)→V1 (Day 1) 
14 days  
14 - 29 days*  
Subjects 
with S. 
aureus 
positive 
culture 
performed 
outside the 
study 
procedures 
V0 (Day -14 up to Day 1)→V1 (Day 1) 
up to 14 days   
0 - 29 days*  
All 
subjects 
V1 (Day 1)→V2 (Day 8) 
7 days  
7 - 9 days  
V1 (Day 1)→V3 (Day 15) 
14 days  
14 - 21 days  
V1 (Day 1)→V4 (Day 31) 
30 days  
30 - 37 days  
V1 (Day 1)→V5 (Day 61) 
60 days  
60 - 67 days  
V5 (Day 61)→V6 (Day 68) 
7 days  
7 - 9 days  
V5 (Day 61)→V7 (Day 75) 
14 days  
14 - 21 days  
V5 (Day 61)→V8 (Month 3, day 91) 
30 days  
30 - 40 days  
V5 (Day 61)→V9 (Month 8, day 241) 
180 days  
180 - 190 days  
V5 (Day 61)→V10 (Month 14, day 426) 
365 days  
365 - 380 days  
a/b = vaccine/placebo; PoP = Proof of Principle; V = Visit 
Note: CDISC is not calculating with Day 0, i.e. interval between Day –14 and Day 1 is 14 days. 
* Vaccination should occur after clinical resolution of culture confirmed SSTI caused by S. aureus  
In Section 5.2: Overall design 
• 
Sampling schedule:  
− 
Blood samples for laboratory safety evaluation and will be drawn from the first 
40 subjects enrolled (i.e. subjects belonging to PoP Step 1). 
− 
Drainage samples will be taken from all those subjects performing culture test  
as study procedures at screening (i.e. Day –14 [Visit 0]) and from all subjects 
with recurrences at the time of recurrence. 
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In Section 6.1: Inclusion criteria for enrolment: 
Additional inclusion criteria only for subjects to be enrolled in the PoP screening 
epoch: 
• 
Healthy subjects as established by medical history and clinical examination before 
entering into the study with an ongoing SSTI suspected to be caused by S. aureus, as 
diagnosed by investigator (before randomisation subjects have to be treated until 
clinical resolution of culture confirmed SSTI caused by S. aureus). SSTI must be 
amenable to microbiological culturing per standard clinical practice (i.e. recovery of 
drainage sample from abscess or suppurative cellulitis). 
OR 
• 
Healthy subjects as established by medical history and clinical examination before 
entering into the study with an ongoing S. aureus SSTI (i.e. S. aureus is the most 
likely cause), as confirmed by a S. aureus positive culture performed outside the 
study procedures and not earlier than 14 days prior to ICF signature. Before 
randomisation subjects have to be treated until clinical resolution of the culture 
confirmed SSTI caused by S. aureus. These subjects will be enrolled whether they 
have or have not already started specific treatment of the infection. In case they 
have not started the treatment, this will be then given in compliance with the 
standard medical practice for the management of S. aureus SSTIs and the choice 
and judgment of the most appropriate treatment will be applied by the investigator, 
outside the study procedures.  
In Section 6.2 Exclusion criteria; Section 6.2.2 Prior/Concomitant therapy 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol in the period starting 15 days before the first dose and ending 15 days after 
the last dose of vaccine(s) administration* with the exception of any non-adjuvanted 
influenza vaccine which may be administered ≥7 days before or after each study 
vaccination. 
*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 Product 
Information. 
In Section 6.4: Screen and baseline failures 
PoP: 
Screening activities will continue at sites until the target number of events is reached. 
The following information will be collected in the eCRF for screening failures (dose-
escalation safety lead-in and PoP):  
• 
Informed consent. 
• 
Demographic data. 

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• 
Inclusion/exclusion criteria. 
• 
Screening conclusion. 
• 
Concomitant medication/vaccination (if applicable). 
• 
SAEs related to study participation, to concomitant use of GSK products or any fatal 
SAEs (if applicable). 
• 
Microbiology results (PoP only) (if applicable). 
In Section 7.5.2: Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from per-protocol analyses 
• 
A vaccine not foreseen by the study protocol administered during the period starting 
15 days before the first dose and ending 15 days after the last dose of 
vaccine(s)/placebo administration*, with the exception of any non-adjuvanted 
influenza vaccine which may be administered ≥7 days before or after each study 
vaccination.  
*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 Summary of 
Product Characteristics (SmPC) or Prescribing Product Information and according to 
the local governmental recommendations and provided a written approval of the 
Sponsor is obtained. 
In Section 8.4.2.1: Sampling for efficacy assessments 
Skin drainage samples will be collected from all screened subjects with SSTI in the PoP 
at the screening visit and during the study in subjects with SSTI recurrences at 
unscheduled visits those subjects in the PoP performing culture test as a study 
procedure at screening (i.e. Day –14 [Visit 0]) and from all subjects at the time of their 
recurrence of SSTI (i.e. unscheduled visits). 
Drainage samples will not be stored. 
Table 15 
Biological samples for efficacy assessment (PoP) 
Sample type 
Quantity 
Unit 
Timepoint 
Subjects 
Drainage samples 
Depends on availability 
Day –14 (V0) 
 
Unscheduled* 
Subjects with SSTI who perform 
culture test as a study procedure 
at screening 
 
Subjects with suspected SA-SSTI 
V = Visit 
* Additionally, subjects with recurrent SSTI at the time of recurrence 

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In Section 8.4.3.1: Microbiology assessment for efficacy 
Table 18 
Microbiology 
System 
Component 
Method 
Laboratory 
Skin drainage 
S. aureus identification 
Standard bacteriological 
methods 
Investigator’s institution and/ or at 
a laboratory designated by GSK 
Biologicals  
In Section 8.4.3.2: Assays for immunogenicity assessments 
In Section 8.5.7: Clinical safety laboratory assessments: 
In the dose-escalation safety lead-in and in the PoP Step 1 (i.e. first 40 subjects enrolled 
in the PoP): a volume of approximately 6 ml of whole blood should be drawn from all 
subjects for each analysis for haematology and chemistry assessments at each pre-defined 
timepoint (Table 26). Part of the whole blood will be processed into serum and will be 
managed according to local laboratory practices.  
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Table 26 
Biological samples for haematology and chemistry assessments 
Sample type 
Quantity 
Unit 
Study group 
Timepoint 
Subjects 
Blood for haematology and 
chemistry 
~6 
ml 
1a/b Half dose non-
adjuvanted 
2a/b Full dose non-
adjuvanted 
3a/b Half dose adjuvanted 
Day –1 (V0-Grp1-3) 
Day 8 (V2-Grp1-3) 
All 
subjects 
4a/b Full dose adjuvanted 
Day –1 (V0-Grp4) 
Day 8 (V2-Grp4) 
Day 61 (V4-Grp4) 
Day 68 (V5-Grp4) 
All 
subjects 
~6 
ml 
5a/b vaccine/placebo 
Day 1 (V1) 
Day 8 (V2) 
Day 61 (V5) 
Day 68 (V6) 
All 
subjects 
PoP 
Step 1 
(i.e. first 
40 
subjects 
enrolled 
in the 
PoP) 
V = Visit; Grp = Group; a/b = vaccine/placebo 
Refer to Section 12.2 (Appendix 2) for the list of clinical laboratory tests to be performed 
and to the SoA for the timing and frequency.  
The tests detailed in Appendix 2, Section 12.2 will be performed by the local laboratory 
at the investigator’s site. Results of tests will be needed before vaccination i.e. on the 
same of the blood draw day for PoP Step 1 or latest on the next day for dose-escalation 
safety lead-in (see also Section 6.2 exclusion criteria). 

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In Section 8.6.1: Staggered vaccination (under Section 8.6: Holding rules and safety 
monitoring): 
Figure 6 
Overview of staggered enrolment and safety evaluation (dose-
escalation safety lead-in) 
 
 
* Safety reviews will take into account all safety data accumulated up to the specified timepoint 

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Figure 7 
Overview of staggered enrolment and safety evaluation (PoP) 
 
 
* All safety reviews (i.e. SRTs/iSRCs) will take into account all safety data accumulated up to the specified 
timepoint  
In Section 8.6.2: Outcome of safety evaluation: 
If no safety signal is observed, the favourable outcome of the safety evaluations will be 
documented and provided in writing (scanned and e-mailed), authorising the investigator 
to start vaccination of subjects with the subsequent dose as well as enrolment and 
vaccination of the remaining subjects in the next step of the study, as applicbale 
applicable. 

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In Section 8.6.3: Study holding rules 
Table 27 
Study holding rules  
 
 
FTIH Dose-
escalation 
Safety Lead-
In steps 1-4 
Staggered 
enrolment step 
of PoP 
vaccination 
epoch (PoP 
step 1) 
Full enrolment 
step of PoP 
vaccination 
epoch (PoP 
step 2) 
Holding 
rule 
Event 
Number of 
subjects 
needed to 
trigger the 
hold 
Number and % 
of subjects 
needed to 
trigger the hold 
Number of 
subjects 
needed to 
trigger the hold 
1a 
Death or any life-threatening SAE 
≥ 1 
≥ 1 
≥ 1 
1b 
Any withdrawal from the study (by 
investigator or subject request) following a 
Grade 3 AE that cannot reasonably be 
attributed to a cause other than vaccination 
≥ 1 
≥ 1 
N/A 
1c 
Any local or general solicited AE leading to 
hospitalization, or fever >40°C (104°F) or 
necrosis at the injection site, within the 7-day 
(Days 1-7) post-vaccination period 
≥ 1 
≥ 1 
N/A 
2a 
Any Grade 3 solicited local AE (lasting 48h or 
more) in an investigational group, within the 
7-day (Day 1-7) post-vaccination period 
≥ 1 
≥ 6/30 or 20% 
N/A 
2b 
Any Grade 3 solicited general AE (lasting 48h 
or more) in an investigational group, within 
the 7-day (Day 1-7) post-vaccination period 
≥ 1 
≥ 6/30 or 20% 
N/A 
2c 
Any Grade 3 unsolicited AE in an 
investigational group, that cannot reasonably 
be attributed to a cause other than 
vaccination, within the 7-day (Day 1-7) post-
vaccination period or any Grade 3 
abnormality in pre-specified haematological 
or biochemical laboratory parameters in an 
investigational group within the 7-day (Day 1-
7) post-vaccination period * 
≥ 1 
≥ 6/30 or 20% 
N/A 
AE = Adverse Event; SAE = Serious Adverse Event; FTIH = First Time in Human; PoP = Proof of Principle; N/A = Not 
Applicable 
* Grading of laboratory parameters will be based on the FDA Guidance for Industry “Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (refer to Appendix 7, Section 12.7). 
Those laboratory parameters not included in the FDA Toxicity Grading Scale will not be graded. 
Holding rules 1a (in all steps), 1b and 1c (during the dose-escalation safety lead-In epoch and the PoP Step 1) 
will be monitored by the investigators on a continuous basis for as long as vaccination is ongoing in the study. Meeting 
any of these holding rules will trigger a hold of vaccination irrespective of the number of subjects vaccinated. 
Holding rules 2a, 2b and 2c are reviewed during unblinded review in the planned or ad-hoc iSRC. These rules will be 
applied only during the dose-escalation safety lead-In epoch and the staggered enrolment step of PoP vaccination 
epoch. Also in this case, different cut-offs are considered based on the sample size of the study group. 

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In Section 10.3.3.1 Case accountability (under Section 10.3.3: Efficacy analyses): 
Endpoint 
Statistical Analysis Methods 
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In Section 10.3.5: Safety analyses: 
Endpoint 
Statistical Analysis Methods 
Primary 
Within groups assessment 
The overall incidence, with exact 95% confidence intervals (CIs) of any solicited AE (local or 
general), of at least 1 solicited local AE and of at least 1 solicited general AE during the 7-day 
(Day 1-7) period will be tabulated per study group and for each dose and overall. The same 
calculations will be performed for solicited AEs rated as grade 3 and fever >40°C/104°F. 
The overall incidence, with exact 95% confidence intervals (CIs) of any unsolicited AE, 
unsolicited AEs by MedDRA system organ class and by preferred term during the 30-day (Day 
1-30) follow-up post-vaccination period will be tabulated per study group and after each dose 
and overall. The same calculations will be performed for unsolicited AEs rated as grade 3 and 
fever >40°C/104°F, for unsolicited AEs causally related to vaccination and for grade 3 
unsolicited AEs causally related to vaccination. 
The number and percentages of subjects who experienced at least one SAE or any pIMD during 
the entire study period (Groups 1-3 Day 1-366, Groups 4 and 5 Day 1-426) will be reported. 
The percentage of subjects having haematology and biochemistry results below or above the 
normal laboratory ranges with the changes from the baseline values will be tabulated by time 
point for Group 1 to 4 and Group 5 Step 1. 
Duration will be presented.  
The verbatim reports of unsolicited symptoms will be reviewed by a GSK physician and the 
signs and symptoms will be coded according to the MedDRA Dictionary for Adverse Event 
Terminology.  
Serious adverse events and withdrawal due to adverse event(s) will be described in detail. 
In Section 11: References 
EMA Guideline on the exposure to medicinal products during pregnancy: need for 
post-authorisation data (Doc. Ref. EMEA/CHMP/313666/2005 ) ‘adopted at Community 
level in May 2006);  
https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guideline-
exposure-medicinal-products-during-pregnancy-need-post-authorisation-data_en.pdf 
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_g
uideline/2009/11/WC500011303.pdf. Accessed January 17, 2019 31 March 2021 
In Section 12.1.1: List of abbreviations 
PP: 
Per-protocol 
PP: 
Per-protocol 
In Section 12.2.2 Laboratory assays for safety evaluation 
The tests detailed in Table 28 will be performed by the local laboratory. Results of tests 
will be needed before vaccination i.e. latest on the next day for dose-escalation safety 
lead-in and on the same day for PoP Step 1 (see also requirements for inclusion or 
exclusion of subjects detailed in Section 6 of the protocol). 
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Pre-vaccination on Visit 0 (dose-escalation safety lead-in) and Visit 1 (PoP Step 1) 
haematology and chemistry evaluation will not be blinded since abnormal laboratory 
results will be an exclusion criterion (see Section 6.2.1). 
In Section 12.3 Appendix 3: Clinical laboratories: 
Table 29 
GSK laboratories 
Laboratory 
Address 
GSK Biological’s Clinical Laboratory Sciences, 
Rixensart  
Biospecimen Reception-B7/44 
Rue de l'Institut, 89 
B-1330 Rixensart 
Belgium  
GSK Biological’s Clinical Laboratory Sciences, 
Wavre-Nord Noir Epine 
Avenue Fleming, 20 
B-1300 Wavre 
Belgium 
GSK Vaccines GmbH 
Clinical Laboratory Sciences, Marburg, 
Germany 
Emil-von-Behring-Str. 76 
35041 Marburg 
Germany 
GSK Vaccines S.r.l 
Preclinical R&D, Italy 
Via Fiorentina 1 
53100 Siena 
Italy 
Table 30 
Outsourced laboratories 
Laboratory 
Address 
Q2 Solutions Clinical Trials (UK) 
The Alba Campus Rosebank  
Livingston West Lothian, EH54 7EG Scotland,  
UK  
Q2 Solutions Clinical Trials (US) 
27027 Tourney Road, Suite 2E 
Valencia, CA 91355 
USA 
Nexelis Impfstoffforschung 
(Marburg, Germany) 
Emil-von-Behring-Str. 76 
35041 Marburg 
Germany 
In Section 12.4.2 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 at the end of the study. Investigators are responsible 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.  
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 
interests during the study and for 1 year after completion of the study. 

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In Section 12.4.7: Data quality assurance 
Quality tolerance limits (QTLs) will be pre-defined in the study management plan and 
will be monitored during the study. 
In Section 12.5.8: Detecting and recording adverse events, serious adverse events 
and pregnancies 
The subject will be contacted by the site staff on Day 31 (all groups), Day 91 (dose-
escalation safety lead-in Group 4 full dose adjuvanted and PoP both groups), Day 181 
(Groups 1-3: half dose non-adjuvanted, full dose non-adjuvanted, half dose adjuvanted) 
and Day 241 (dose-escalation safety lead-in Group 4 full dose adjuvanted and PoP both 
groups) via a scripted safety follow-up phone call. Subjects in PoP Step 2 will also be 
contacted on Day 8 and Day 68 via a scripted safety follow-up phone call. At, or in 
advance of applicable phone call the site will review the eDiary web-portal for responses 
entered by the subject in order to solicit additional information during the phone call e.g. 
related to unsolicited adverse events, concomitant vaccinations/medication and medically 
attended events. 
In Section 12.6.2 Contraception guidance 
Table 36 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly.  
Progestogen-only hormonal contraception associated with inhibition of ovulationb 
• 
oral 
• 
injectable  

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12.8.6. 
Protocol Amendment 1 
Overall Rationale for the Amendment 1 is to make some minor corrections, remove the 
 
, and to comply with selected 
recommendations from Center for Biologics Evaluation and Research (CBER). This 
protocol amendment 1 outlines also measures that may be applicable during special 
circumstances (e.g., CovidOVID-19 pandemic), to protect participant’s welfare and 
safety, and promote data integrity. 
List of main changes in the protocol and their rationale: 
Section # and 
Name 
Description of Change 
Brief Rationale 
Cover page 
Sponsor 
signature page 
Investigator 
signature page 
To swap the identifiers “short title” and 
“title”. 
To add the IND number. 
Identifiers have been corrected,as applicable and 
the IND number has been added. 
2. Schedule of 
activities (SOA) 
Simplification of study procedures. 
5.1. Scientific 
rationale for 
study design 
To address CBER’s comment 
5.2. Overall 
design 
5.3. Number of 
subjects 
7.2.2.1.1. Study 
group and 
treatment 
number 
allocation 
8. Study 
assessment 
and procedures 
To add information related to study 
procedures conduction during special 
circumstances (e.g. CovidOVID-19 
pandemic). 
Adds alternative ways to conduct study procedures  
8.4.2.2. Blood 
sampling for 
immunogenicity 
response 
assessments 
Simplification of study procedures  
10.1.1. 
Hypotheses 
related to 
primary and 
secondary 
objectives 
To change the number of total planned 
events for the final efficacy analysis and 
the percentage of events for the interim 
To change alpha and beta of the first and 
second hypotheses for interim and final 
analysis. 
To change the hazard ratio (HR).  
To address CBER’s comment 
10.1.2. Sample 
size calculation 
To address CBER’s comment 
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Section # and 
Name 
Description of Change 
Brief Rationale 
10.2. 
Populations for 
analyses 
To add the overall safety set. 
To split the solicited safety set in: i) 
solicited safety set until 30 minutes after 
vaccination, ii) solicited safety set 
including only subjects with data from 30 
minutes until 7 days after vaccination. 
To generate data requires for public disclosure and 
improve the display of the solicited AEs data. 
 
10.3.3.1. Case 
accountability 
To change alpha and beta for interim and 
final analysis according changes in 
Section 10.1.1. 
To address CBER’s comment 
12.5.3. 
Solicited 
adverse events 
Added a Table 33 to add the general 
adverse events myalgia and shivering to 
be solicited for the PoP population. 
To address CBER’s comment  
12.5.8.2.2. 
Assessment of 
adverse events 
Updated Table 35 to add the solicited 
general adverse events myalgia and 
shivering. 
To address CBER’s comment. 
12.5.8.2.2. 
Assessment of 
adverse events 
Fever grading scale revised as follows: 
grade 1: ≥ 38.0°C and < 39.0°C, grade 2: 
≥ 39.00°C and ≤ 40.0°C, grade 3: > 
40.0°C. 
To correct a  typo 
Detailed description of Protocol Amendment 1: 
In the following sections, deleted text is indicated in strikethrough and changed text in 
bold italics: 
Coverpage 
Investigational New Drug 
(IND) number 
To be done IND 19408 
Date of protocol 
Final Version 1: 04 September 2019 
Date of protocol 
amendment/administrative 
change 
Amendment 1 Final: 26 May 2020 
Short tTitle 
Safety, immunogenicity and efficacy of GSK S. 
aureus candidate vaccine (GSK3878858A) when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 50 years of age with a recent S. aureus 
skin and soft tissue infection (SSTI). 
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Short tTitle 
A Phase I, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and 
efficacy of GSK S. aureus candidate vaccine when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 50 years of age with a recent S. aureus 
skin and soft tissue infection (SSTI). 
Contributing authors 
• 
 (CRDL) 
• 
 (CRDL) 
• 
 (SDL) 
• 
 (ODM) 
• 
 (Lead Statistical Analyst) 
• 
 (Lead Statistician) 
• 
 (CTSM, Vaccine supply) 
• 
 (CLS CRT-L) 
• 
 (Safety Physician) 
• 
 (Safety Scientist) 
• 
 (GRA) 
• 
 (LDL)  
• 
 (LML) 
• 
 (DPL) 
Protocol Amendment 1 Sponsor Signatory Approval 
IND number 
Tobe done IND 19408 
Date of protocol 
Final Version 1: 04 September 2019 
Date of protocol 
amendment/administrative 
change 
Amendment 1 Final: 26 May 2020 
Short tTitle  
A Phase I, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and 
efficacy of GSK S. aureus candidate vaccine when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 50 years of age with a recent S. aureus 
skin and soft tissue infection (SSTI). 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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Protocol Amendment 1 Investigator Agreement 
IND number 
Tobe done IND 19408 
Date of protocol 
Final Version 1: 04 September 2019 
Date of protocol 
amendment/administrative 
change 
Amendment 1 Final: 26 May 2020 
Short tTitle  
A Phase I, observer-blind, randomised, placebo-
controlled study to assess safety, immunogenicity and 
efficacy of GSK S. aureus candidate vaccine when 
administered to healthy adults (dose-escalation) and 
to adults 18 to 50 years of age with a recent S. aureus 
skin and soft tissue infection (SSTI). 
Section 1. 
SYNOPSIS 
Objectives and Endpoints:  
Objectives 
Endpoints 
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Objectives 
Endpoints 
Ab = Antibody; AE = Adverse Event; CD = Cluster of Differentiation EAP = Exploratory Analysis Plan; 
 
 
 
 pIMDs = potential Immune-Mediated Disease; SAE = Serious Adverse Events; 
 
; SSTI = Skin and Soft Tissue Infection; VE = Vaccine Efficacy;  
 
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Section 1. 
SYNOPSIS 
Synopsis Figure 1 
Overall design 
 
Grp = Group 
a/b = vaccine/placebo. 
Rando = Randomisation 
adj = adjuvanted 
SE = Safety evaluation by SRT/ iSRC chair (blinded review) or iSRC (unblinded review), for details refer to Section 8.6 
PoP = Proof of Principle 
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Synopsis Figure 3 
Study design overview PoP in subjects with a recent S. aureus SSTI Group 5a/b 
 
Note: CDISC is not calculating with Day 0, i.e. interval between Day –14 and Day 1 is 14 days. 
a/b = vaccine/placebo 
SE = Safety evaluation by iSRC (unblinded review), for details refer to Section 8.6 
Rando = Randomisation 
PoP = Proof of Principle 
SSTI = Skin and Soft Tissue Infection 
Vac = Vaccine 
Plac = Placebo 
M = Month  
V = Vaccination 
BS-S = Blood Sample for Safety evaluation 
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The enrolment in the PoP phase will also follow a staggered approach. Enrolment will be 
stopped as soon as 40 subjects have been vaccinated with the first dose of the GSK S. 
aureus candidate vaccine or placebo. Only subjects who already signed the ICF and 
entered the screening phase, at the time of enrolment hold, will be allowed to continue 
the study; therefore, approximately 40 subjects (30 subjects receiving GSK S. aureus 
candidate vaccine and 10 receiving placebo) will be evaluated for safety. After the iSRC 
evaluation of unblinded safety data collected up to the Day 8 after first dose (including 
laboratory assessments) for the last vaccinated subject of this staggered subset has shown 
lack of safety issues, the full enrolment of the remaining subjects in the PoP epochs will 
continue with a randomisation of a 1:1 ratio either to the GSK S. aureus candidate 
vaccine or to the placebo group. 
 
 
 
 
 
 
 
 
 
 
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Section 2 
SCHEDULE OF ACTIVITIES 
Table 3 
Schedule of activities (dose-escalation safety lead-in epochs, Groups 1-3a/b) 
Epoch 
Dose-escalation safety lead-in screening  
Dose-escalation safety lead-in vaccination  
Type of 
contact 
Group 1a/b Half dose non-adjuvanted 
Group 2a/b Full dose non-adjuvanted 
Group 3a/b Half dose adjuvanted 
V0-Grp1-3  
Screening  
V1-Grp1-3 V2-Grp1-3  V3-Grp1-3  
phone call 
V4-Grp1-3  
phone call 
V5-Grp1-3 
Time points 
Day –1* 
Day 1 
Day 8 
Day 31 
Day 181 
(M 6) 
Day 366 
(M 12) 
Sampling time points 
Pre-Vac1 
Informed consent by subjects  
● 
 
 
 
 
 
Check inclusion/exclusion criteria  
● 
 
 
 
 
 
Physical examination 
O 
● 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
Vaccine(s)/Product(s) 
Study group and treatment number allocation 
 
O 
 
 
 
 
Recording of administered treatment number 
 
● 
 
 
 
 
Vaccine administration 
 
● 
 
 
 
 
Safety assessments 
Medical history 
● 
 
 
 
 
 
History of administration of adjuvanted vaccine 
● 
 
 
 
 
 
Urine pregnancy test 
● 
 
 
 
 
 
Check contraindications and warnings and precautions to vaccination 
O 
O 
 
 
 
 
Pre-vaccination body temperature 
 
● 
 
 
 
 
Blood sampling for safety laboratory evaluation (6 ml) 
● 
 
● 
 
 
 
Record any concomitant medication/vaccination 
● 
● 
● 
● 
● 
● 
Record any intercurrent medical conditions 
● 
● 
● 
● 
● 
● 
Distribution of eDiaries and training 
 
O 
 
 
 
 
Review of eDiary data 
 
O 
O 
 
 
 
Return of eDiaries to the sites 
 
 
O 
 
 
 
Phone contact 
 
 
 
● 
● 
 
Recording of solicited adverse events  
 
O 
 
 
 
 
Recording of unsolicited adverse events   
 
● 
● 
● 
 
 
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Epoch 
Dose-escalation safety lead-in screening  
Dose-escalation safety lead-in vaccination  
Type of 
contact 
Group 1a/b Half dose non-adjuvanted 
Group 2a/b Full dose non-adjuvanted 
Group 3a/b Half dose adjuvanted 
V0-Grp1-3  
Screening  
V1-Grp1-3 V2-Grp1-3  V3-Grp1-3  
phone call 
V4-Grp1-3  
phone call 
V5-Grp1-3 
Time points 
Day –1* 
Day 1 
Day 8 
Day 31 
Day 181 
(M 6) 
Day 366 
(M 12) 
Sampling time points 
Pre-Vac1 
Occurrence of solicited AEs at the investigator’s site within 30 minutes 
post-vaccination observation 
 
● 
 
 
 
 
Reporting of pIMDs 
 
● 
● 
● 
● 
● 
Reporting of SAEs, pregnancies and pregnancy outcomes 
● 
● 
● 
● 
● 
● 
Study Conclusion  
 
 
 
 
 
● 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
*CDISC is not calculating with Day 0, i.e. interval between Day –1 and Day 1 is 1 day. 
. 
a/b = vaccine/placebo 
 
pIMDs = potential Immune-Mediated Diseases 
SAE = Serious Adverse Event 
Vac = Vaccination 
M = Month 
V = Visit 
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Table 5 
Schedule of activities (Group 5a/b, PoP screening epoch, PoP vaccination epochs) 
Epoch 
PoP 
screening  
PoP vaccination  
Type of contact 
V0  
V1  
V2  
V3  
V4  
Phone 
call 
V5  
V6  
V7  
V8  
Phone 
call 
V9  
Phone 
call 
V10  
Unscheduled 
visit 
Time points 
Day –14* 
Day 1  Day 
8 
Day 
15 
Day 31 
Day 61  Day 
68 
Day 
75 
Day 91 (M 
3) 
Day 241 
(M 8)  
Day 426 
(M 14) 
 
Sampling time points 
Pre-
Vac1  
Pre-
Vac2  
Informed consent by subjects 
● 
 
 
 
 
 
 
 
 
 
 
 
Check inclusion/exclusion criteria  
● 
● 
 
 
 
 
 
 
 
 
 
 
Physical examination 
O 
● 
 
 
 
● 
 
 
 
 
 
 
Verification of clinical resolution of SSTI 
 
● 
 
 
 
 
 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
 
 
Vaccine(s)/Product(s)  
Study group and treatment number allocation 
 
O 
 
 
 
 
 
 
 
 
 
 
Treatment number allocation for subsequent doses 
 
 
 
 
 
O 
 
 
 
 
 
 
Recording of administered treatment number 
 
● 
 
 
 
● 
 
 
 
 
 
 
Vaccine administration 
 
● 
 
 
 
● 
 
 
 
 
 
 
Clinical Specimens for microbiology assessments 
Sampling of drainage for culture 
● 
 
 
 
 
 
 
 
 
 
 
●*** 
Safety assessments 
Medical history 
● 
● 
 
 
 
 
 
 
 
 
 
 
History of administration of adjuvanted vaccine 
● 
● 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
● 
● 
 
 
 
● 
 
 
 
 
 
 
Check contraindications and warnings and precautions to 
vaccination 
O 
O 
 
 
 
O 
 
 
 
 
 
 
Pre-vaccination body temperature 
 
● 
 
 
 
● 
 
 
 
 
 
 
Blood sampling for safety laboratory evaluation (6 ml) 
 
● 
● 
 
 
● 
● 
 
 
 
 
 
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Epoch 
PoP 
screening  
PoP vaccination  
Type of contact 
V0  
V1  
V2  
V3  
V4  
Phone 
call 
V5  
V6  
V7  
V8  
Phone 
call 
V9  
Phone 
call 
V10  
Unscheduled 
visit 
Time points 
Day –14* 
Day 1  Day 
8 
Day 
15 
Day 31 
Day 61  Day 
68 
Day 
75 
Day 91 (M 
3) 
Day 241 
(M 8)  
Day 426 
(M 14) 
 
Sampling time points 
Pre-
Vac1  
Pre-
Vac2  
Record any concomitant medication/vaccination 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record any intercurrent medical conditions 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Distribution of eDiaries and training  
 
O 
 
 
 
O***** 
 
 
 
 
 
 
Review of eDiary data 
 
O 
O 
O 
O 
O 
O 
O 
 
 
 
 
Return of eDiaries to the sites 
 
 
 
 
 
 
 
O 
 
 
 
 
Phone contact 
 
 
 
 
● 
 
 
 
● 
● 
 
 
Recording of solicited adverse events   
 
O 
 
 
 
O 
 
 
 
 
 
 
Recording of unsolicited adverse events   
 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
 
Occurrence of solicited AEs at the investigator’s site within 30 
minutes post-vaccination observation 
 
● 
 
 
 
● 
 
 
 
 
 
 
Reporting of pIMDs 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Reporting of SAEs, pregnancies and pregnancy outcomes 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Study Conclusion  
 
 
 
 
 
 
 
 
 
 
● 
 
Note: The double-line borders indicate analyses which will be performed on all data obtained up to those time points. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
*CDISC is not calculating with Day 0, i.e. interval between Day –14 and Day 1 is 14 days. 
 
***If possible. 
 
*****Remind subjects that the device is now ready to collect after Dose 2 data. 
a/b = vaccine/placebo 
 
pIMDs = potential Immune-Mediated Diseases 
SAE = Serious Adverse Event 
Vac = Vaccination 
M = Month 
V = Visit 
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Section 4. 
OBJECTIVE(S) AND ENDPOINT(S) 
Table 10 
Study objectives and endpoints 
Objectives 
Endpoints 
Ab = Antibody; AE = Adverse Event; CD = Cluster of Differentiation EAP = Exploratory Analysis Plan; 
 
 
 pIMDs = potential Immune-Mediated Disease; SAE = Serious Adverse Avent;
 
 SSTI = Skin and Soft Tissue Infection; VE = Vaccine Efficacy; 
Section 5.1. 
Scientific rationale for study design 
The PoP phase is designed as an event driven study and subjects will be enrolled 
 
 Since there is currently 
no licensed vaccine against S. aureus infections the comparator group will receive 
placebo (saline). 
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Section 5.2 
Overall design 
Figure 1 
Overall design 
 
adj = adjuvanted 
Grp = Group 
a/b = vaccine/placebo 
Rando = Randomisation 
SE = Safety evaluation by SRT/ iSRC chair (blinded review) or iSRC (unblinded review), for details refer to Section 8.6 
PoP = Proof of Principle 
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Figure 3 
Study design overview PoP in subjects with a recent S. aureus SSTI 
 
Note: CDISC is not calculating with Day 0, i.e. interval between Day –14 and Day 1 is 14 days. 
a/b = vaccine/placebo 
SE = Safety evaluation by iSRC (unblinded), for details refer to Section 8.6 
PoP = Proof of Principle 
SSTI = Skin and Soft Tissue Infection 
Rando = Randomization 
Vac = Vaccine 
Plac = Placebo 
M = Month  
V = Vaccination 
BS-S = Blood Sample for Safety evaluation 
 
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The enrolment and vaccination in the PoP phase will also follow a staggered approach. 
Details are given below in bullet “Safety monitoring” and Section 8.6.1. The study will 
follow a group sequential design with two analyses. An event driven interim analysis will 
be performed when 50% 
 
 
 
 
 (event driven design). It is estimated that then a total of 
approximately 500 to 600 subjects will be vaccinated in the 
 
 
Table 12 
Study groups, treatment and epochs foreseen in the study (PoP 
epochs) 
Study 
Groups 
Number of 
subjects 
Age 
(Min-Max) 
Treatment name 
Epochs 
(Blinding) 
PoP screening  
(N/A) 
PoP vaccination  
(observer-blind) 
Group 5a 
Vaccine  
250* 
18 - 50 years  
Sa-5Ag full dose 
adjuvanted  
●  
●  
Group 5b 
Placebo  
250* 
18 - 50 years  
Placebo  
●  
●  
N/A = Not Applicable 
*Design of the study is event driven and it can be only estimated that approximately 250 to 300 subjects per study 
group may be needed. 
. 
• 
Data collection: standardised eCRF. Solicited AEs will be collected using a subject 
eDiary.) 
Section 5.3. 
Number of subjects 
PoP epochs: 
The design of the PoP phase of the study is event driven. Vaccination of subjects with a 
randomisation of a 1:1 ratio either to the GSK S. aureus candidate vaccine or to the 
placebo group is planned 
 It is 
estimated that a total of approximately 500 to 600 subjects will be vaccinated in the PoP. 
Section 7.2.2.1.1. 
Study group and treatment number allocation 
PoP: 
 
 The enrolment in the PoP phase will also follow a staggered 
approach:  
• 
The remaining subjects in the PoP epochs will be enrolled approximately 8 days after 
the last of the approximately 40 subjects  was vaccinated (for safety evaluation and 
consequence on study progress refer to Section 8.6.1). The subjects will be 
randomised with a 1:1 ratio either to receive the GSK S. aureus candidate vaccine or 
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placebo until 
 (event driven 
design). It is estimated that a total of approximately 500 to 600 subjects will be 
vaccinated in the PoP 
 (see 
Section 10.1.2). 
Section 7.3.1. Emergency unblinding 
Table 14 
Contact information for emergency unblinding 
GSK Helpdesk 
24 hours/7 days availability 
The Helpdesk is available by phone, fax and email 
Phone: +32 2 656 68 04 
For Canada, US and Puerto Rico 
Toll-free number: 877 870 0019 
Fax: +32 2 401 25 75 
email: rix.ugrdehelpdesk@gsk.com 
Section 8. 
STUDY ASSESSMENTS AND PROCEDURES 
Under special circumstances, modification of specific study procedures may be 
implemented:  
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:  
• 
Safety follow-up may be made by a telephone call, other means of virtual contact 
or home visit, if appropriate. 
• 
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. 
• 
Blood samples for safety assessment may be collected at a different location2 other 
than the study site or at participant’s home. Blood samples should not be collected 
if they cannot be processed in a timely manner or appropriately stored until the 
intended use.  
                                                 
2 It is the investigator’s responsibility to identify an alternate location. The investigator should ensure 
that this alternate location meets 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. Refer to EMA 
Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic 
(version 2, 27 March, 2020) for more details. 
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Section 8.4. 
Efficacy/immunogenicity assessments 
Refer also to the Amendment 1 Investigator Agreement, where it is noted that the 
investigator cannot perform any other biological assays except those described in the 
protocol or its amendment(s). 
Section 8.4.2.2. 
Blood sampling for immunogenicity response assessments  
Refer to the SPM for detailed information on sample collection and storage. 
The maximum amount of blood collected from each subject over the duration of the 
study, including any extra assessments that may be required, will not exceed 125 ml for 
subjects participating in the dose-escalation safety lead-in and will not exceed 370310 ml 
for subjects participating in the PoP. 
Section 8.5. 
Safety Assessments 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. This includes the assessment 
of Covid-19 cases per the WHO definition [WHO, 2020]. 
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Table 22 
Reporting periods for collecting safety information (dose-escalation 
safety lead-in) 
Event 
Study group 
Pre-
Vac 
Vac1 
 
 
 
Vac2 
 
 
 
Study 
Conclusion 
 
Half dose non-
adjuvanted 
Full dose non-
adjuvanted 
Half dose 
adjuvanted 
D–1* 
D1 
D7 
D30 
 
NA 
NA 
NA 
 
D366 
M12 
 
Full dose 
adjuvanted 
D–1* 
D1 
D7 
D30 
 
D61 D67 
D90 
 
D426 
M14 
Solicited local and 
general AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading 
to withdrawal from 
the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to the 
study vaccine(s) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation or 
concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
pIMDs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.  
** Unsolicited AEs/SAEs due to Covid-19 will be recorded according to the WHO case definition [WHO, 2020]. 
AEs = Adverse Events; SAEs = Serious Adverse Events; pIMDs = potential Immune-Mediated Diseases; Pre-Vac = 
Pre-Vaccination; Vac = Vaccination; D = Day; M = Month 

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Table 23 
Reporting periods for collecting safety information (PoP) 
Event 
Study group Pre-
Vac 
Vac1 
 
 
 
Vac2 
 
 
 
Study 
Conclusion 
 
Vaccine 
Placebo 
D–14* D1 
D7 
D30 
 
D61 D67 D90 
 
D426 
M14 
Solicited local and 
general AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading 
to withdrawal from 
the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to the 
study vaccine(s)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation or 
concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
pIMDs  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained.  
** Unsolicited AEs/SAEs due to Covid-19 will be recorded according to the WHO case definition [WHO, 2020]. 
AEs = Adverse Events; SAEs = Serious Adverse Events; pIMDs= potential Immune-Mediated Diseases; Pre-Vac = 
Pre-Vaccination; Vac = Vaccination; D = Day; M = Month 

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Figure 9 
Sequence for evaluating both efficacy objectives in order to control 
the overall type I error below 7.5% (one-sided) ) and the power equal to 80% 
 
Figure 9 
Sequence for evaluating both efficacy objectives in order to control the 
overall type I error below 7.5% (one-sided) ) and the power equal to 80% 
 
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Section 10.2. Populations for analyses 
Analysis Set 
Description 
Enrolled  
All subjects who sign informed consent  
Randomized 
All subjects who sign informed consent and are randomized to the treatment 
group 
Exposed  
All subjects who received at least 1 dose of the study treatment. The allocation 
in a group is done in function of the administered treatment. 
Full Analysis Set (FAS) 
All subjects who received at least 1 dose of the study treatment and have post-
vaccination efficacy/ immunogenicity data  
Modified Full Analysis Set 
(mFAS) 
All subjects who received full study treatment course to which they are 
randomised and have post-vaccination efficacy/immunogenicity data 
Per-Protocol (PP) 
All subjects who received full study treatment course to which they are 
randomised and have post-vaccination data (mFAS) minus subjects with 
protocol deviations that lead to exclusion from PP 
Unsolicited Safety  
All subjects who received at least 1 dose of the study treatment (Exposed Set) 
that report unsolicited AEs/report not having unsolicited AEs 
Solicited Safety  
All subjects who received at least 1 dose of the study treatment (Exposed Set) 
who have solicited safety data in the period beginning 30 minutes after 
vaccination until 7 days after vaccination. 
Solicited Safety 30m 
All subjects who received at least 1 dose of the study treatment (Exposed 
Set) who have solicited safety data during a period of 30 minutes after the 
vaccination. 
Overall Safety Set 
All subjects who received at least 1 dose of the study treatment (Exposed 
Set) who have solicited safety data including 30 minutes data and during a 
period of 7 days from the vaccination and/or report unsolicited AEs/report 
not having unsolicited AEs   
Section 10.3.3.1. 
Case accountability: 
Endpoint 
Statistical Analysis Methods 
Key 
secondary 
The analysis of efficacy will be based on the occurrence of the first case of SSTI anytime from 15 
Days after the administration of the second dose of the study vaccine up to 12 months. All 
subjects from the mFAS will contribute to the comparison between the treatment and the placebo 
groups. 
Time to occurrence of key secondary endpoint during the defined efficacy follow-up period will be 
compared between groups by calculating the respective Hazard ratio (methods will be detailed in 
the SAP).  
Vaccine (VE) will be defined as 1 minus the hazard ratio times 100: 
VE = (1 – hazard ratio) x 100 
Censoring will occur at the time of the last scheduled or medically attended visit without the 
occurrence of SSTI cases before the end of follow-up. Subjects who will complete the follow-up 
without events will be censored at 1 year. 
In order to check the statistical significance, 1-sided P-value for the log rank test will be 
calculated. 1-sided nominal type I error will be 1.612.04% at the interim analysis and 5.8946% at 
the final analysis. The objective will be met if the 1-sided P-value calculated for the null 
hypothesis H0 = [occurrence SSTI VE ≥0%] is lower than defined 1-sided alpha level. 
Co-secondary 
The co- secondary endpoint will be analysed only if the statistical significance is demonstrated for 
the key secondary endpoint. 
For this analysis, the mFAS will account for the first case of SSTI anytime from 15 Days after the 
administration of the first dose of the study vaccine up to 14 months. 
Time to occurrence of the co- secondary endpoint during the defined efficacy follow-up period will 
be compared between groups by calculating the respective Hazard ratio (methods will be detailed 
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Endpoint 
Statistical Analysis Methods 
In order to check the statistical significance, 1-sided P-value for the log rank test will be 
calculated. 1-sided nominal type I error will be 5.8946%. (the nominal alpha level is equal to the 
key secondary at the final analysis, because we use a sequential procedure). The objective will 
be met if the 1-sided P-value calculated for the null hypothesis H0=[occurrence SSTI VE ≥0%] is 
lower than defined 1-sided alpha level. 
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Section 11. 
REFERENCES 
WHO. Global Surveillance for human infection with coronavirus disease (COVID-19). 
Interim guidance. Last update in March 2020; https://www.who.int/publications-
detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-ncov). 
Accessed May 15, 2020. 
Section 12.5.3. 
Solicited adverse events 
b. Solicited general adverse events 
Table 33 
Additional solicited general adverse events (PoP only)  
Adults 
Myalgia 
Shivering 
Section 12.5.8. 
Detecting and recording adverse events, serious adverse events 
and pregnancies 
Subject eDiary training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the Subject 
eDiary. This individual may not be the subject, but if a person other than the subject 
enters information into the Subject eDiary, this person’s identity must be documented in 
the subject’s source recordSubject eDiary. Any individual that makes entries into the 
Subject eDiary must receive training on completion of the Subject eDiary at the time of 
the visit when Subject eDiary is dispensed. This training must be documented in the 
subject’s source record. 
Subject eDiary instructions must ensure that the subject understands the following: 
• 
Any new safety information reported during the safety follow-up phone call or site 
visits (including a solicited adverse event) cannot be entered into the Subject eDiary. 
Such information must be described in the source documents as a verbally-reported 
event. Any adverse event reported in this fashion must be described as an unsolicited 
adverse event and therefore entered into the eCRF. This includes the assessment of 
Covid-19 cases per the WHO definition [WHO, 2020]. 
CCI

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Section 12.5.8.2.1. 
Active questioning to detect adverse events and serious adverse 
events 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. This includes the assessment of Covid-19 cases per the WHO 
definition [WHO, 2020]. The investigator is not allowed to send photocopies of the 
subject’s medical records to GSK instead of appropriately completing the eCRF. 
However, there may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all subject identifiers will be blinded on the copies of 
the medical records prior to submission to GSK. 
Section 12.5.8.2.2. 
Assessment of adverse events 
Table 35 
Intensity scales for solicited adverse events in adults 
Adults 
Adverse Event 
Intensity grade 
Parameter 
Pain at injection site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing 
normal every day activities. 
 
2 
Moderate: Painful when limb is moved and interferes with 
every day activities. 
 
3 
Severe: Significant pain at rest. Prevents normal every 
day activities. 
Redness at injection site 
Record greatest surface diameter in mm 
Swelling at injection site 
Record greatest surface diameter in mm 
Temperature* 
 
Record temperature in °C/°F (with 1 decimal) 
Headache 
0 
Normal 
 
1 
Mild: Headache that is easily tolerated 
 
2 
Moderate: Headache that interferes with normal activity 
 
3 
Severe: Headache that prevents normal activity 
Fatigue 
0 
Normal 
 
1 
Mild: Fatigue that is easily tolerated 
 
2 
Moderate: Fatigue that interferes with normal activity 
 
3 
Severe: Fatigue that prevents normal activity 
Nausea 
0 
Normal 
 
1 
Mild: No interference with daily activity 
 
2 
Moderate: Interference with daily activity 
 
3 
Severe: Prevents daily activity 
Vomiting 
0 
Normal 
 
1 
Mild: 1-2 times in 24 hours 
 
2 
Moderate: 3-5 times in 24 hours 
 
3 
Severe: 6 or more times in 24 hours or requires 
intravenous hydration 
Diarrhoea 
0 
Normal 
 
1 
Mild: 2 - 3 loose stools in 24 hours 
 
2 
Moderate: 4 - 5 loose stools in 24 hours 
 
3 
Severe: 6 or more loose stools in 24 hours or requires 
intravenous hydration 
Abdominal pain 
0 
Normal 
 
1 
Mild: No interference with daily activity 

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Adults 
Adverse Event 
Intensity grade 
Parameter 
 
2 
Moderate: Interferes with daily activity 
 
3 
Severe: Prevents daily activity 
Myalgia 
0 
Normal 
 
1 
Mild: No interference with daily activity 
 
2 
Moderate: Interferes with daily activity 
 
3 
Severe: Prevents daily activity 
Shivering 
0 
Normal 
 
1 
Mild: No interference with daily activity 
 
2 
Moderate: Interferes with daily activity 
 
3 
Severe: Prevents daily activity 
*Fever is defined as temperature  38.0°C/100.4°F. The preferred location for measuring temperature in this study will 
be the oral cavity for adult subjects. 
If any of the solicited symptoms meet the SAE criteria they will reported as a SAE. 
Temperature will be scored at GSK Biologicals as follows: 
0 
: 
< 100.4°F (38.0°C)  
1 
: 
≥ 100.4°F (38.0°C)  < 102.1°F (39.0°C) 
2 
: 
≥ 102.1°F (39.0°C)  104°F (40.0°C) 
3 
: 
> 104°F (40.0°C) 
Possible contributing factors include: 
• 
Lack of efficacy of the vaccine(s)/product(s) (delete as applicable), if applicable. 

Signature Page for  208833 TMF-15034175 v1.0
Signature Page for TMF-15034175 v1.0
Reason for signing: Approved
Name:
Role: Approver
Date of signature: 11-Oct-2022 07:21:14 GMT+0000
PPD