A Phase 1, Open-label, Safety and Immunogenicity Study of a Booster Dose of the Investigational CV0501 mRNA COVID-19 Vaccine in Adults at Least 18 Years Old
Phase: PHASE1
Conditions: COVID-19, SARS-CoV-2
Sponsor: GlaxoSmithKline

C o nfi de nti al   
Pa g e 1 
 
C LI NI C A L S T U D Y P R O T O C O L  
 
A P h ase 1, O pe n -l a bel, S afet y a n d I m m u n o ge nicity St u d y of a B o oster D ose 
of t he I n vesti g ati o n al C V 0 5 01 m R N A C O VI D -19 Vacci ne i n A d ults at Le ast 
1 8 Ye ars Ol d  
 
P R O T O C O L 2 1 8 5 9 5 ( C V 2 S A R S - CO V 2 -0 1 2 B S T)  
S p o ns o r:  
Gla x o S mit h Kli n e Bi ol o gic als S A  
R u e d e l’I nstit ut 8 9, 1 3 3 0 Ri x e ns art, Bel gi u m  
S p o ns o r C o nt a ct:  
, M D, M P H 
C li nic al E pi d e mi ol o g y Pr oje ct Le a d 
G S K R o c k ville Ce nter f or Va c ci n es Res e arc h  
1 4 2 0 0 S h a d y Gr o ve R o a d  
R o c k ville, M D 2 0 8 5 0  
Tele p h o n e: 
 
P P D S afet y H otli ne:  
+ 1 -8 0 0 -2 0 1 -8 7 2 5  
Pr ot o c ol N u m be r:  
2 1 8 5 9 5  
A b bre vi ate d T itle: 
C V 2 S A R S -C O V 2 -0 1 2 B S T  
A me n d me nt N u m be r :  
2 
D ate of A me n d me nt  2 : 
2 6 J ul  2 0 2 2  
D ate of A me n d me nt  1 : 
2 3 J u n  2 0 2 2  
D ate of O ri gi n al Pr ot o c ol:  
2 0  A pr  2 0 2 2  
C o m p o u n d N a me:  
C V 0 5 0 1 m R N A v a c ci n e  
St u d y P h as e:  
1 
I N D N u m be r: 
2 8 4 6 2  
E u dr a C T N u m be r : 
2 0 2 2 -0 0 1 2 9 3 -5 8  
 
 
P P D
P P D

Confidential  
Page 2 
 
CONFIDENTIAL 
All financial and nonfinancial support for this study will be provided by GSK Biologicals 
SA. The concepts and information contained in this document or generated during the study 
are considered proprietary and may not be disclosed in whole or in part without the express 
written consent of GSK Biologicals SA. 
The study will be conducted according to the International Council for Harmonisation 
harmonised tripartite guideline E6(R2): Good Clinical Practice.  
 

Gla x o S mit h Kli ne Bi ol o gicals S A  
C V 0 5 0 1 Vacci ne 
Pr ot oc ol 2 1 8 5 9 5 ( C V 2 S A R S- C O V 2- 0 1 2 B S T) A me n d me nt 2 
2 6 J ul 2 0 2 2 
C o nfi de ntial  
Pa ge 3  
 
Pr ot oc ol A p pr o v al – S p o ns or Si g n at or y 
St u d y Title: 
A P hase 1, O pe n-la bel, Safet y a n d I m m u n o ge nicit y St u d y of a 
B o oster D ose of t he I n ves ti gati o nal C V 0 5 0 1 m R N A C O VI D- 1 9 
Vacci ne i n A d ults at Least 1 8 Years Ol d 
Pr ot oc ol N u m ber: 
2 1 8 5 9 5 
A b bre vi ate d Title: 
C V 2 S A R S- C O V 2- 0 1 2 B S T 
Pr ot oc ol D ate a n d 
Versi o n: 
2 6 J ul 2 0 2 2; A me n d me nt 2 
I N D N u m ber: 
2 8 4 6 2 
E u dr a C T 
N u m ber: 
2 0 2 2- 0 0 1 2 9 3- 5 8  
 
Pr ot oc ol acce pte d a n d a p pr o ve d b y: 
Cli nic al E pi de mi ol o g y Pr oject Le a d 
R os ha n Ra ma nat ha n, M D, M P H 
G S K R oc k ville Ce nter f or Vacci nes Researc h 
1 4 2 0 0 S ha d y Gr o ve R oa d 
R oc k ville, M D 2 0 8 5 0, U nite d States 
 
 
 
Si g nat ure
 
 
Date
 
 
 
 
2 6 J ul 2 0 2 2
P P D

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 4 
 
Declaration of Investigator 
I have read and understood all sections of the protocol titled “A Phase 1, Open-label, Safety 
and Immunogenicity Study of a Booster Dose of the Investigational CV0501 mRNA 
COVID-19 Vaccine in Adults at Least 18 Years Old” and the accompanying investigator’s 
brochure. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the Protocol Amendment 2, dated 26 Jul 2022, the International Council for 
Harmonisation harmonised tripartite guideline E6(R2): Good Clinical Practice and all 
applicable government regulations. I will not make changes to the protocol before consulting 
with GSK Biologicals SA or PPD or implement protocol changes without independent ethics 
committee approval except to eliminate an immediate risk to participants. I agree to 
administer study vaccine only to participants under my personal supervision or the 
supervision of a subinvestigator. 
I will not supply the study vaccine to any person not authorized to receive it. Confidentiality 
will be protected. Participant identity will not be disclosed to third parties or appear in any 
study reports or publications. 
I will not disclose information regarding this clinical investigation or publish results of the 
investigation without authorization from GSK Biologicals SA. 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Printed Name of Principal Investigator 
 
 
 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 5 
 
Table of Contents 
Table of Contents ........................................................................................................ 5 
List of Tables .............................................................................................................. 9 
List of Figures ............................................................................................................ 9 
List of Abbreviations and Definitions ........................................................................ 10 
Protocol Amendment Summary of Changes ............................................................... 13 
Protocol Synopsis ..................................................................................................... 15 
1 
Introduction ....................................................................................................... 24 
1.1 
Background Information ........................................................................... 24 
1.2 
Risk:Benefit Considerations ...................................................................... 26 
2 
Study Objectives and Endpoints ......................................................................... 29 
3 
Investigational Plan – Study Design ................................................................... 31 
3.1 
Part A Study Design .................................................................................. 32 
3.1.1 
Part A Dose Escalation Plan ........................................................ 33 
3.1.2 
Part A Study Schematic ............................................................... 34 
3.2 
Part B Study Design.................................................................................. 36 
3.3 
Scientific Rationale for Study Design ........................................................ 36 
3.3.1 
Starting Dose .............................................................................. 37 
3.3.2 
Dose Escalation .......................................................................... 38 
3.3.3 
Maximum Planned Dose ............................................................. 38 
3.3.4 
Low Dose Evaluation.................................................................. 39 
4 
Participant Selection and Withdrawal Criteria ..................................................... 40 
4.1 
Selection of Study Participants .................................................................. 40 
4.1.1 
Inclusion Criteria ........................................................................ 40 
4.1.2 
Exclusion Criteria ....................................................................... 41 
4.2 
Discontinuation From Study Intervention and/or Withdrawal From the Study
 ......................................................................................................... 43 
4.2.1 
Lost to Follow-Up ...................................................................... 44 
4.2.2 
Replacements ............................................................................. 45 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 6 
 
5 
Study Vaccines .................................................................................................. 46 
5.1 
Method of Assigning Participants to Study Vaccine Groups ........................ 46 
5.2 
Study Vaccine Administration ................................................................... 46 
5.3 
Identity of Investigational Product ............................................................. 47 
5.4 
Management of Clinical Supplies .............................................................. 48 
5.4.1 
Investigational Product Packaging and Storage ............................ 48 
5.4.2 
Investigational Product Accountability ........................................ 48 
5.4.3 
Other Supplies ............................................................................ 49 
5.5 
Overdose Management ............................................................................. 49 
5.6 
Blinding ................................................................................................... 50 
5.7 
Compliance With Study Vaccine................................................................ 50 
5.8 
Prior, Concomitant, and Rescue Therapies ................................................. 50 
5.8.1 
Prior and Concomitant Therapy ................................................... 50 
5.8.2 
Allowed Concomitant Therapy .................................................... 51 
5.8.3 
Rescue Medicine ........................................................................ 51 
5.9 
Study Holding Rules ................................................................................. 51 
6 
Study Assessments and Procedures ..................................................................... 54 
6.1 
Safety Assessments ................................................................................... 54 
6.1.1 
Adverse Events........................................................................... 55 
6.1.1.1 Definitions.................................................................................. 55 
6.1.1.1.1 
Adverse Events ............................................................... 55 
6.1.1.1.2 
Serious Adverse Events.................................................... 56 
6.1.1.1.3 
Suspected Unexpected Serious Adverse Reactions ............ 56 
6.1.1.1.4 
Adverse Events of Special Interest ................................... 56 
6.1.1.2 Eliciting and Documenting Adverse Events ................................. 57 
6.1.1.2.1 
Assessment of Intensity ................................................... 58 
6.1.1.2.2 
Assessment of Causality .................................................. 60 
6.1.1.3 Reporting Adverse Events ........................................................... 61 
6.1.1.3.1 
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest ................................... 61 
6.1.1.3.2 
Reporting Suspected Unexpected Serious Adverse Reactions
  ...................................................................................... 62 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 7 
 
6.1.1.4 Follow-Up of Participants Reporting Adverse Events ................... 62 
6.1.1.5 eDiary ........................................................................................ 63 
6.1.2 
SARS-CoV-2 Infection and COVID-19 Assessment and Definitions
 .................................................................................................. 63 
6.1.3 
Myocarditis and Pericarditis Assessment and Definitions ............. 65 
6.1.3.1 Surveillance for Asymptomatic Myocarditis and Pericarditis ........ 66 
6.1.4 
Clinical Safety Laboratory Assessments ...................................... 67 
6.1.5 
Physical Examinations ................................................................ 68 
6.1.6 
Vital Signs .................................................................................. 68 
6.2 
Pregnancy Reporting................................................................................. 69 
6.3 
Assessment of Immune Responses ............................................................ 69 
6.3.1 
Assessment of Humoral Immune Responses ................................ 70 
6.3.2 
Assessment of Cellular Immune Responses ................................. 70 
6.4 
Genetics ................................................................................................... 70 
7 
Statistical Considerations ................................................................................... 71 
7.1 
Statistical Hypothesis ................................................................................ 71 
7.2 
Sample Size Determination ....................................................................... 71 
7.3 
Analysis Sets ............................................................................................ 71 
7.4 
Description of Subgroups to Be Analyzed .................................................. 72 
7.5 
Statistical Analysis Methodology............................................................... 72 
7.5.1 
General Considerations ............................................................... 72 
7.5.2 
Analysis of the Primary Safety Endpoints .................................... 72 
7.5.3 
Analysis of Secondary Immunogenicity Endpoints....................... 73 
7.5.4 
Analyses of Exploratory Immunogenicity Endpoints .................... 73 
7.5.5 
Safety Analyses .......................................................................... 73 
7.5.6 
Other Analyses ........................................................................... 73 
7.6 
Handling of Missing Data ......................................................................... 74 
7.7 
Interim Analyses ....................................................................................... 74 
8 
Data Quality Assurance ...................................................................................... 75 
8.1 
Data Management ..................................................................................... 75 
9 
Ethics ................................................................................................................ 76 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 8 
 
9.1 
Independent Ethics Committee or Institutional Review Board .................... 76 
9.2 
Ethical Conduct of the Study ..................................................................... 76 
9.3 
Participant Information and eConsent ........................................................ 77 
10 Investigator’s Obligations .................................................................................. 78 
10.1 Confidentiality.......................................................................................... 78 
10.2 Data Protection ......................................................................................... 78 
10.3 Financial Disclosure and Obligations......................................................... 78 
10.4 Investigator Documentation ...................................................................... 79 
10.5 Study Conduct .......................................................................................... 79 
10.6 Adverse Events and Study Report Requirements ........................................ 79 
10.7 Investigator’s Final Report ........................................................................ 79 
10.8 Records Retention..................................................................................... 80 
10.9 Publications and Results Disclosures ......................................................... 80 
11 Study Management ............................................................................................ 81 
11.1 Safety Review Team ................................................................................. 81 
11.2 Monitoring ............................................................................................... 81 
11.2.1 
Monitoring of the Study .............................................................. 81 
11.2.2 
Inspection of Records ................................................................. 82 
11.3 Management of Protocol Amendments and Deviations ............................... 82 
11.3.1 
Modification of the Protocol........................................................ 82 
11.3.2 
Protocol Deviations .................................................................... 82 
11.4 Study Termination .................................................................................... 83 
11.5 Final Report.............................................................................................. 83 
12 References......................................................................................................... 85 
13 Appendices........................................................................................................ 88 
13.1 Appendix 1: Schedule of Events ................................................................ 88 
13.2 Appendix 2: Contraceptive Guidance and Pregnancy Information .............. 92 
13.3 Appendix 3: Bayesian Logistic Regression Model ..................................... 95 
13.4 Appendix 4: Potential Immune-mediated Diseases ..................................... 97 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 9 
 
13.5 Appendix 5: Grading for Laboratory Abnormalities ................................. 105 
13.6 Appendix 6: Protocol Amendment History............................................... 107 
 
List of Tables 
Table 2-1 
Study Objectives and Endpoints................................................................. 29 
Table 3-1 
Planned Cohorts, Dose Levels, Groups, and Sample Sizes for Part A .......... 32 
Table 3-2 
Dosing Scenarios for Participants Enrolled in Cohorts 4 and 5 .................... 33 
Table 3-3 
Planned Cohorts, Dose Levels, Groups, and Sample Sizes for Part B .......... 36 
Table 5-1 
Investigational Product Information ........................................................... 47 
Table 5-2 
Study Holding Rules ................................................................................. 52 
Table 6-1 
Intensity Scales for Solicited Symptoms..................................................... 59 
Table 13-1 
Schedule of Events .................................................................................... 89 
Table 13-2 
Hypothetical Data Scenarios for Determining Posterior Probabilities .......... 96 
Table 13-3 
List of Potential Immune-Mediated Diseases .............................................. 97 
Table 13-4 
Toxicity Grading for Serum Laboratory Abnormalities ............................. 106 
 
List of Figures 
Figure 3-1 
Part A Study Schematic ............................................................................. 35 
Figure 3-2 
Part B Study Schematic ............................................................................. 36 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 10 
 
List of Abbreviations and Definitions 
Abbreviation 
Definition 
Ab 
antibody  
AE 
adverse event 
AESI 
adverse event of special interest 
ANCOVA 
analysis of covariance 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
COVID-19 
coronavirus disease caused by SARS-CoV-2 
CV0501 
an investigational, monovalent, nucleoside-modified, mRNA 
COVID-19 vaccine targeting the Omicron variant of 
SARS-CoV-2 
D 
Day 
ECG 
electrocardiogram 
ECMO 
extracorporeal membrane oxygenation 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDiary 
electronic diary 
EOS 
end of study 
ET 
early termination 
FDA 
US Food and Drug Administration 
FSH 
follicle-stimulating hormone 
FTiH 
first-time-in human 
CCI
CCI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 11 
 
Abbreviation 
Definition 
GMI 
geometric mean increase 
GMT 
geometric mean titer 
GSK 
GlaxoSmithKline Biologicals SA 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
ICS 
intracellular cytokine staining  
IEC 
independent ethics committee 
IgG 
immunoglobulin G 
IND 
investigational new drug 
IM 
intramuscular(ly) 
IP 
investigational product 
IRB 
institutional review board 
IRT 
interactive response technology 
LNP 
lipid nanoparticle 
MAAE 
medically attended adverse event 
MedDRA 
Medical Dictionary for Regulatory Activities 
mRNA 
messenger ribonucleic acid 
NA 
not applicable 
N protein 
nucleocapsid protein 
PaO2/FiO2 
partial pressure of oxygen/fraction of inspired oxygen 
PBMC 
peripheral blood mononuclear cell 
pIMD 
potential immune-mediated disease 
PPI 
per protocol immunogenicity 
SAP 
statistical analysis plan 
RT-PCR 
reverse transcription polymerase chain reaction 
S protein 
spike protein 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 12 
 
Abbreviation 
Definition 
SAE 
serious adverse event 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SOE 
SOP 
schedule of events 
standard operating procedure 
SpO2 
blood oxygen saturation 
SRT 
Safety Review Team 
SUSAR 
suspected unexpected serious adverse reaction 
VRBPAC 
Vaccines and Related Biological Products Advisory Committee 
WHO 
World Health Organization 
WHODRUG 
World Health Organization Drug Dictionary 
WOCBP 
women of childbearing potential 
WT 
wild-type 
CCI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 13 
 
Protocol Amendment Summary of Changes 
DOCUMENT HISTORY 
Document 
Date 
Amendment 2 
26 Jul 2022 
Amendment 1 
23 Jun 2022 
Original Protocol 
20 Apr 2022 
 
Amendment 2, 26 Jul 2022: Current Amendment 
Rationale for Amendment 2: 
The rationale for Amendment 2 is to add a 12-lead ECG examination at screening, to 
facilitate a comprehensive cardiac safety assessment in the event of a participant’s abnormal 
Day 8 ECG examination.  
The summary of changes table provided here describes the important changes made in 
Amendment 2 relative to Amendment 1, including the sections modified and the 
corresponding rationales. The synopsis of Amendment 2 has been modified, as needed, to 
correspond to changes in the body of the protocol. Minor editorial, grammatical, and 
formatting corrections are not included in this summary table. 
Throughout the document, the protocol date and version were updated to reflect 
Amendment 2 and the title page was updated to reflect the protocol history.  
Summary of Important Changes from Amendment 1 to Amendment 2: 
Section Number and Name 
Description of Change 
Brief Rationale 
Section 3.1.1 (Part A Dose 
Escalation Plan) 
Section 11.1 (Safety Review 
Team) 
Removed references to an SRT 
charter 
The SRT charter has been 
retired. As per GSK process, the 
content contained within GSK 
SRT Charters is now 
documented in the GSK SOP, 
VQD-SOP-069378 Benefit-Risk 
Assessment at the Safety Review 
Team. 
Section 6.1.3.1 (Surveillance for 
Asymptomatic Myocarditis and 
Pericarditis) 
Section 13.1 (Appendix 1: 
Schedule of Events) 
Added a 12-lead ECG baseline 
examination at screening 
In the event of a participant’s 
abnormal Day 8 ECG 
examination, the screening ECG 
provides a baseline for 
comparison.  

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 14 
 
Section Number and Name 
Description of Change 
Brief Rationale 
Section 6.1.3 (Myocarditis and 
Pericarditis Assessment and 
Definitions) 
Section 6.1.3.1 (Surveillance for 
Asymptomatic Myocarditis and 
Pericarditis) 
 
Revised “PR-segment inversion” to 
“PR-segment depression” 
Revised to provide correct 
terminology: PR-segment 
depression may be indicative of 
pericarditis. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 15 
 
Protocol Synopsis 
Protocol Number: 218595 (CV2 SARS-CV0501-012 BST)  
Title: A Phase 1, Open-label, Safety and Immunogenicity Study of a Booster Dose of the 
Investigational CV0501 mRNA COVID-19 Vaccine in Adults at Least 18 Years Old  
Short Title: Phase 1 Safety and Immunogenicity Study of a Booster Dose of CV0501 mRNA 
COVID-19 Vaccine in Adults 
Sponsor: GlaxoSmithKline Biologicals SA, Rue de l’Institut 89, 1330 Rixensart, Belgium 
Study Phase: 1 
Proposed Indication: Prevention of COVID-19  
Rationale: Due to the ongoing COVID-19 pandemic and the need for vaccines to provide 
protection against COVID-19 caused by SARS-CoV-2 variants of concern, GSK and 
 are collaborating to develop the CV0501 mRNA vaccine. This is a Phase 1 FTiH 
study designed to evaluate the safety and immunogenicity of the GSK
 CV0501 
mRNA vaccine administered as a booster vaccination in previously vaccinated adults. The 
proposed study will guide selection of the optimal dose to be evaluated in Phase 2. 
 
 
CCI
CCI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 16 
 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary – Safety and Tolerability 
To evaluate the safety and tolerability of 
CV0501 at each dose level  
• 
Percentage of participants with each solicited 
local and systemic AE during 7 days after 
vaccination (ie, the day of study vaccination and 
6 subsequent days, Days 1 through 7)  
• 
Percentage of participants with abnormal 
laboratory findings for 8 days after study 
vaccination 
• 
Percentage of participants with unsolicited AEs 
for 28 days after study vaccination  
• 
Percentage of participants with MAAEs, SAEs, 
and AESIs from study vaccination through the 
end of the study (180 days after the study 
vaccine administration), each summarized 
separately 
Secondary – Immunogenicity  
To evaluate neutralizing Ab titers against 
SARS-CoV-2 WT, Omicron, and Delta 
variants following CV0501 booster 
vaccination in adult participants 
• 
GMTs of neutralizing Ab titers against 
pseudovirus bearing S protein from 
SARS-CoV-2 WT, Omicron, and Delta variants 
at each collection timepoint  
• 
GMI from baseline of neutralizing Ab titers 
against pseudovirus bearing S protein from 
SARS-CoV-2 WT, Omicron, and Delta variants 
at each collection time point  
To describe seroresponse to CV0501 based 
on neutralizing Ab titers against 
pseudoviruses bearing S protein from 
SARS-CoV-2 WT, Omicron, and Delta 
variants 
• 
Seroresponse rate 28 days after the booster dose 
(Day 29), based on neutralizing Ab titers against 
pseudoviruses bearing S protein from 
SARS-CoV-2 WT, Omicron, and Delta variants 
at each collection timepoint, with seroresponse 
defined as postboost titers ≥ 4× preboost titers.  
Note: Tertiary objectives and endpoints are included in the main protocol. 
 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 17 
 
Diagnosis and Main Criteria for Inclusion and Exclusion: The study will enroll healthy 
male and female adults, at least 18 years old, who have received at least 2 doses of mRNA 
COVID-19 vaccine
 
 with the last dose received at least 6 months prior to 
screening. Participants must be negative for SARS-CoV-2 infection (by RT-PCR test) at 
screening. Participants who have had close contact with anyone who had a confirmed SARS-
CoV-2 infection within 2 weeks before study vaccination will be excluded from study 
participation. 
Study Design:  
This open-label, dose escalation, FTiH Phase 1 study will evaluate the safety (including 
reactogenicity) and immunogenicity of a single booster dose of CV0501 vaccine in adults 
who have previously received at least 2 doses of an mRNA COVID-19 vaccine. 
Approximately 180 participants will be enrolled. The study will comprise two parts (Part A 
and Part B).  
The study duration per participant will be approximately 194 days from start of screening 
through EOS, including approximately 14 days for screening and approximately 180 days 
(6 months) for Day 1 vaccination and follow-up. There will be 6 protocol-scheduled visits: 
on Day 1 (vaccination day) and on Days 8, 15, 29, 91 and 181. In addition, there will be one 
protocol-scheduled telephone contact on Day 4 to query participants about solicited and 
unsolicited AEs occurring after study vaccination. 
Participants will be monitored for potential COVID-19 illness from Day 1 through the EOS 
(Day 181). Participants will be asked to contact the site if they experience any symptoms of 
COVID-19. An unscheduled visit may be performed to evaluate the potential infection. 
Alternatively, an investigator may utilize subject medical records from non-study care 
medical providers to verify whether a participant was infected with SARS-CoV-2. An 
CCI
CCI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 18 
 
additional unscheduled COVID-19 convalescent visit may be performed for all participants 
with confirmed COVID-19.  
Participants will also be required to document all AE symptoms and contact the site if 
necessary. An unscheduled visit may also be performed if an AE requires further evaluation. 
Safety data will be monitored on an ongoing basis by the investigator (or medically qualified 
designee) and sponsor to promptly identify and flag any event that potentially could trigger a 
stopping rule. If a stopping rule is triggered, study intervention administration and enrollment 
will pause and the SRT will review available safety data from all vaccinated participants. 
Participants who have already received vaccine will continue to attend follow-up visits as 
specified in the schedule of events.  
Part A: 
Participants in Cohorts 1 to 5 will be enrolled in a staggered manner to 1 of 5 cohorts with 
planned dose escalation of CV0501 from 12 µg up to 200 µg. Each cohort of Part A will 
evaluate a single-dose level of CV0501 vaccine and will include 2 age groups (younger 
adults, ≥ 18 to < 65 years old, and older adults, ≥ 65 years old). The dose levels for the 
groups in Cohorts 1-3 are fixed. The dose levels for the Cohorts 4 and 5 will be as 
recommended by the SRT, based on their review of all available safety data and dosing 
scenarios. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 19 
 
Planned Cohorts, Dose Levels, Groups, and Sample Sizes for Part A 
Cohort Vaccine 
Dose Level (µg) 
Group A 
Younger Adults 
≥18 to <65 Years Old 
(n range) 
Group B 
Older Adults 
≥65 Years Old 
(n range) 
Total 
Cohort  
Sample 
Size  
1 
CV0501 
12 
1a (min 10; max 20) 
1b (min 10; max 20) 
30 
2 
25 
2a (min 10; max 20) 
2b (min 10; max 20) 
30 
3 
50 
3a (min 10; max 20) 
3b (min 10; max 20) 
30 
4 
75 or 100* 
4a (min 10; max 20) 
4b (min 10; max 20) 
30 
5 
100, 150, or 200* 
5a (min 10; max 20) 
5b (min 10; max 20) 
30 
* 
Depending on the reactogenicity/safety findings from groups in Cohorts 1-3, the SRT may recommend 1 of 
3 prespecified dosing scenarios comprising these dose levels for groups in Cohorts 4 and 5. The dose level 
recommendations will be made independently for Groups A (younger participants) and B (older 
participants).  
The recruitment target will be a total of 30 participants per cohort in Cohorts 1 to 5. The 30 
participants will be distributed between the younger and older age groups. A minimum of 10 
participants per age group will be enrolled. A maximum of 20 participants may be enrolled in 
an individual age group.
 
 
Enrollment will be staggered, beginning with Group 1a (12 µg, younger adults). Initiation of 
enrollment in Group 1b (12 µg, older adults) will depend on SRT review of safety data up to 
Day 8 from a minimum of 10 participants in Group 1a.  
For both younger and older age groups, initiation of enrollment in the subsequent group at 
the next dose level for Cohorts 2-5 will depend on SRT review of safety data up to Day 8 
from a minimum of 10 participants, from the previous dose level in the same age group. The 
dose levels for the groups in Cohorts 1-3 are fixed. For each of the groups in Cohorts 4 and 5, 
the SRT may recommend a dose specified by 1 of the 3 dosing scenarios in the dosing 
scenario table (below), based on their review of all available safety data. The SRT will use 
the same approach, independently, to select the dose levels for older participants (Groups 4b 
and 5b) and younger participants (Groups 4a and 5a). 
CCI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 20 
 
Dosing Scenarios for Participants Enrolled in Cohorts 4 and 5 
Dosing Scenario 
Group 4a OR 4b 
Group 5a OR 5b 
#1 
75 µg 
100 µg 
#2 
100 µg 
150 µg 
#3 
100 µg 
200 µg 
 
While the SRT reviews safety data, enrollment in the same group will continue until the 
cohort is full. The SRT recommendation for each group could be to escalate to the next dose 
level or to stop the enrollment at the current dose. 
At each SRT meeting, a Bayesian logistic regression model will be used to predict 
unacceptable reactogenicity at the current or next dose level. A lower than 50% posterior 
probability that the percentage is above the maximum tolerable rate will be favorable to 
progression to the next higher dose. Based on the historical Phase 1 reactogenicity data from 
, the maximum 
tolerable rate for Grade 3 solicited adverse events has been set to 30%. The SRT may 
recommend dropping groups at any time during the study if an unfavorable safety profile is 
observed in that group or based on safety or immunogenicity data from other groups.  
Part B:  
Part B, designed to comprise 2 single age group cohorts, will start based on the first interim 
analysis of safety and immunogenicity, provided that the SRT assesses the 12 µg dose to be 
immunogenic and safe. The SRT may recommend dropping Cohorts 6 and 7 (Groups 6a and 
7a) based on immunogenicity data from the groups that received the 12 µg dose level. If the 
SRT determines that enrollment in Cohorts 6 and 7 may proceed, enrollment may proceed in 
parallel according to the table below.  
CCI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 21 
 
Planned Cohorts, Dose Levels, Groups, and Sample Sizes for Part B 
Cohort  
Vaccine  
Dose Level (µg)  
Group A  
≥18 to <65 Years Old  
Total Cohort   
Sample Size   
6  
CV0501 
3  
6a  
15 
7  
6  
7a  
15 
 
Study Duration:  
The study duration per participant will be approximately 194 days from start of screening 
through EOS, including approximately 14 days for screening and approximately 180 days 
(6 months) for Day 1 vaccination and follow-up.  
Safety Assessments:  
Safety will be assessed through the collection and evaluation of solicited AEs (for 7 days, the 
day of vaccination and 6 subsequent days); unsolicited AEs (for 28 days after study 
vaccination); and MAAEs, SAEs, and AESIs for the duration of the study. Local solicited 
AEs will include injection site pain, redness, and swelling and localized axillary, cervical or 
supraclavicular swelling or tenderness ipsilateral to the vaccination arm (lymphadenopathy). 
Systemic solicited AEs will include fever, fatigue, headache, chills, myalgia, and arthralgia. 
AESIs will include virologically confirmed COVID-19 disease, pIMDs, anaphylaxis or 
severe hypersensitivity within 24 hours after study vaccine administration, myocarditis, and 
pericarditis. Safety will also be assessed based on physical examinations, vital sign 
measurements, and clinical safety laboratory assessments (scheduled only at screening, 
Day 1, and Day 8). 
Assessment of Immune Responses:  
Blood samples will be collected to evaluate vaccine-induced neutralizing Ab levels, binding 
IgG Ab levels, and T-cell immune response.  
For assessment of humoral immune response, neutralizing Ab levels against pseudotyped 
virus displaying S protein from SARS-CoV-2 WT, Omicron, Delta, and potentially other 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 22 
 
relevant variants will be measured. Binding IgG Ab levels against SARS-CoV-2 WT S 
protein and SARS-CoV-2 S antigens from other variants will be measured.  
For assessment of cellular immune response, 
 
 
 
 
Investigational Product, Dosage, and Route of Administration:  
Study vaccine will be administered on Day 1 as a single IM injection in the deltoid area, 
preferably in the nondominant arm. The volume to be administered will vary by dose level 
over a potential range of 0.3 mL to 0.7 mL.  
The mRNA in the IP will encode the S protein of the Omicron SARS-CoV-2 variant.  
Sample Size:  
Approximately 180 healthy adult participants will be enrolled in the study as described in 
Study Design, above. 
 Statistical Methods:  
All analyses will be performed by treatment group, combining the younger and older adult 
participants together, unless specified otherwise. For categorical variables, frequencies and 
percentages will be presented. Continuous variables will be summarized using descriptive 
statistics (number of participants, mean, median, standard deviation, minimum, and 
maximum). For continuous immunogenicity variables, confidence interval and interquartile 
range will also be provided. 
For all safety endpoints, descriptive summary statistics will be provided for the Safety Set, 
which includes all participants vaccinated under this protocol. 
For the key immunogenicity endpoints, seroresponse rate with 95% CI, GMT of specific Ab 
with corresponding 95% CI at each timepoint and GMI of specific Ab with corresponding 
95% CI at each postbaseline timepoint over prevaccination baseline will be provided by 
group. The GMT, the GMI, and their 95% CIs in all cohorts will be analyzed using an 
CCI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 23 
 
ANCOVA with treatment and age group as fixed factors and prevaccination baseline value as 
a covariable. 
Interim Analyses:  
There are 2 planned interim analyses of safety and immunogenicity data. The first interim 
analysis will be performed after all participants in Cohorts 1, 2, and 3 have completed the 
Day 15 study visit. The second interim analysis will be performed after all participants in 
Cohorts 4 and 5 have completed the Day 15 study visit. 
 
 

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 2 4  
 
1  I ntr o d ucti o n 
1. 1 B ac k gr o u n d I nf or m ati o n  
T h e C O VI D -1 9 p a n d e mic c a us e d b y S A R S- C o V-2 vir us w as d e clare d b y t h e W H O o n 
1 1  Mar 2 0 2 0 ( W H O 2 0 2 0 ). As of 1 9 J a n 2 0 2 2, m ore t h a n 3 3 2 milli o n c as es h a ve b e e n 
re p orte d w orl d wi d e, le a di n g t o m ore t h a n 5. 5 milli o n d e at hs (W H O 2 0 2 2 ). To d ate, t h ere are 
m ulti ple lic e ns e d or c o n diti o n all y a p pr o ve d v a cci nes a v aila ble t h at rel y o n a v ariet y of 
v a c ci n e te c h n ol o gies. All c urre ntl y a v aila ble v a c ci n es are b as e d o n a nti g e ns fr o m t h e ori gi nal 
W u h a n strai n ( D 6 1 4; wil d -t y p e, h ere after referre d t o as “ W T”).  
H alf ( 5 0. 3 %) of t h e w orl d p o p u lati o n is f ull y v a c ci n ate d wit h a n y S A R S- C o V-2 v a c ci ne a n d 
a m o n g t his gr o u p, 1 0. 9 % h a v e re c ei v e d a b o oster or a d diti o nal d os e. Va c ci n ati o n rates v ar y 
star kl y b y c o u ntr y a n d re gi o n: t h e pr o p orti o n t h at w as f ull y v a c ci nate d i n t h e U S a n d Ca n a d a 
w as 6 2. 5 % a n d  7 8. 1 %, res p e cti vel y, v ers us 1 0. 1 % i n Afric a ( O ur Worl d i n D ata 2 0 2 2 ). 
Va c ci n e distri b uti o n is i n e q uita ble w orl d wi d e a n d t h e W H O c urre ntl y pri oritiz es pri m ar y 
s eries v a c ci n ati o n f or t his re as o n, t h o u g h o nl y a b o ut 2 0 % of all C O VI D -1 9 v a c ci n es are us e d 
as b o oster d os es ( W H O 2 0 2 1 ). A ut h orizi n g a d diti o n al v a cci n es t o o nl y b e us e d as b o oster 
d os es c o ul d h el p t h w art t h e s pre a d of O micr o n wit h o ut di v erti n g pri m ar y d os e res o urces 
fr o m p o p ulati o ns i n n e e d. 
Re al w orl d d ata fr o m Isra el a n d pres e nte d t o t h e F D A Va c ci n e s a n d Relate d Bi ol o gic al 
Pr o d u cts A d vis or y C o m mitte e ( V R B P A C) d e m o nstrate d t h at i m m u nit y t o S A R S - C o V-2 i n 
a d ults v a c ci n ate d wit h 2 d os es of t h e
v a c ci n e w a nes o v er 
ti m e a cr oss all a g e gr o u ps, is m ost pr o n o u n c e d a m o n g i n di vi d uals i n ol d er a d ults, a n d t h at 
b o oster d os es pr ote ct a g ai nst s e v ere C O VI D -1 9, i n cl u di n g a g ai nst t h e D elta v aria nt 
(Alr o y -Preis a n d Mil o 2 0 2 1 ). Bas e d o n t h es e a n d ot h er d ata, t h e V R B P A C v ote d 
u n a ni m o usl y t o re c o m m e n d t h at a b o oster d os e of  
b e a d mi nist ere d at le ast 6 
m o nt hs after c o m pleti o n of t h e pri m ar y s eries i n i n di vi d uals 6 5  y e ars of a g e a n d ol d er 
(F D A  2 0 2 1 ).  
Se v eral v aria nts of c o n c er n h a ve e m er g e d, i n cl u di n g D elta a n d m ore re c e ntl y O micr o n. T h e 
tra ns missi bilit y of O micr o n is esti m ate d t o b e hi g her t h a n D elta, a n d U K d ata h a v e i n dic ate d 
t h at t h e ris k of rei nfe cti o n a m o n g t h os e wit h a pri or C O VI D-1 9 i nfe cti o n is 3 -8 ti m es hi g h er 
fr o m O micr o n t h a n D elta. (U K H e alt h Se c urit y A g e n c y 2 0 2 1 ).  
C CI
C CI

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 2 5  
 
F or t h e w e e k e n di n g 1 8 D e c 2 0 2 1, t h e U S C D C esti m ate d t h at O m icr o n i nfe cti o ns w ere 
7 3. 2 % of all S A R S - C o V-2 i nfe cti o ns i n t h e U S, wit h D elta i nfe cti o ns at 2 3. 6 % ( C D C 
2 0 2 1 b ). F or t h e w e e k e n di n g 2 7 N o v 2 0 2 1, O micr o n h a d n ot b e e n d ete cte d i n t h e U S 
(M M W R 2 0 2 1 ), a n d D elta w as 9 9. 7 % of all S A R S- C o V-2 i nfe cti o ns.  
D ata p u b lis h e d i n Me d R xi v pre pri nt re p orts h a ve i n dic ate d t h at m R N A v a c ci n es e nc o di n g 
W T S pr otei n are s u bsta ntiall y less effe cti v e a g ai nst O micr o n t h a n a g ai nst D elta wit hi n t h e 1 
t o 3 m o nt hs f oll o wi n g t h e 2-d os e pri m ar y v a c ci n ati o n s eries, a n d t h e d ura bilit y of 
e ffe cti v e n ess o v er t h e n e xt 3 t o 6 m o nt hs is als o s u bsta ntiall y less a g ai nst O micr o n t h a n 
D elta ( A n dre ws et al 2 0 2 1 ; B u c h a n et al 2 0 2 1 ; H a ns e n et al 2 0 2 2 ; Ts e n g et al 2 0 2 2 ). T h e 
s a m e d ata a p p e ar t o i n dic ate a si milar p atter n of v a c ci ne effe cti v e ness a g ai nst O micr o n a n d 
D elta v aria nts f oll o wi n g a b o oster d os e of m R N A v a c ci n es e n c o di n g W T S pr otei n.  
Wit h t h e s ur g e i n O micr o n pre d o mi n a nc e w orl d wi d e, its gre ater tra ns missi bilit y, a n d a hi g h er 
ris k of S A R S- C o V-2 rei nfe cti o n wit h O micr o n, it is re as o n a ble t o a ntici p ate a n urg e nt n e e d 
f or b o oster s h ots t o e x p a n d i m m u nit y a gai nst O micr o n a n d a d diti o nal f ut ure v aria nts of 
c o n c er n.  
pre vi o usl y d e vel o p e d a n m R N A v a c ci n e  
 usi n g t h e u n m o difie d W T S 
pr otei n m R N A s e q u e n c e, f or w hic h v a cci n e s afet y a n d effic a c y are b ei n g e v al u ate d 
. I nteri m res ults fr o m t h e P h as e 2 b/ 3 trial of  
 s h owe d v ac ci ne 
effic a c y of 4 8 % a g ai nst C O VI D -1 9 of all s e v erities a cr oss all a g e gr o u ps a n d 1 5 differe nt 
vir us v aria nts (i n cl u di n g D elta, b ut b ef ore e m er g e n ce of O micr o n), wit h a n a c c e pta ble 
v a c ci n e s afet y pr ofile ( Kre ms ner  2 0 2 1 ). I n p artici p a nts 1 8 t o 6 0 y e ars of a g e, si g nific a nt 
v a c ci n e effic a c y w as d e m o nstrate d, w hic h i n cl u d e d 5 3 % effic a c y a g ai nst dis e ase of a n y 
s e v erit y, a n d 7 7 % effic a c y a g ai nst m o derate a n d s e v ere dis e ase. T h e vir us w as s e q u e n ce d i n 
2 0 4/ 2 2 8 a dj u dic ate d c as es ( 8 3 i n t h e  
 gr o u p a n d 1 4 5 i n t h e pla c e b o gr o u p) t o 
i d e ntif y t h e v aria nt c a usi n g t h e i nfe cti o n. A p pr o xi m atel y 8 6 % of s e q u e nc e d c as es w ere 
c a us e d b y eit h er v aria nts of c o nc er n ( ~ 5 1 %) or v aria nts of i nterest ( ~ 3 5 %). A p pr o xi m atel y 
3 % w ere attri b uta ble t o t h e W T S A R S - C o V-2 vir us, w hil e t h e re m ai ni n g 1 1 % w ere c a us e d 
b y less -i n v esti g ate d strai ns. C olle cti v el y, t h es e res ults d e m o nstrate d t h e n e e d f or pr ote cti o n 
a g ai nst e m er gi n g S A R S- C o V-2 v aria nts.  
C CI
C CI
C CI
C CI
C CI

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al  
Pa g e 2 6  
Se p aratel y, t h e  
 v a c ci ne w as teste d (al o n g wit h 6 ot h er C O VI D -1 9 v a c ci n es) as a 
si n gle-d os e b o oster after 2 d os es of eit h er 
 
 v a c ci n es (M u nr o et al 2 0 2 1 ). T h e  
 v a cci n e b o oste d 
i m m u nit y after b ot h pri m ar y s eries, as j u d g e d b y a nti-S I g G a n d n e utralizi n g ass a ys, alt h o u g h 
t o a less er e xte nt t h a n b o osti n g wit h eit h er t h e 
 
v a c ci n es.  
G S K a n d  
 are c olla b orati n g t o d e v el o p C V 0 5 0 1 , a m o difie d-n ucle oti d e m R N A 
v a c ci n e b as e d o n t h e s a m e L N P. platf or m as t h e  
v a c ci n e. T h e C V 0 5 0 1  m R N A 
e n c o d es S pr otei n fr o m t h e O micr o n v aria nt a n d h as b e e n o pti miz e d t o i m pr o v e i ntra c ell ular 
m R N A sta bilit y a n d tra nslati o n f or i n cre as e d a n d e xte n d e d pr otei n e x pressi o n, relati v e t o 
u n m o difie d S pr otei n m R N A ( Se cti o n  5. 3 ).  
T h e C V 0 5 0 1  v a c ci n e will b e i nte n d e d t o b e a d mi nistere d as a si n gle b o oster d os e f or a cti v e 
i m m u niz ati o n t o pre v e nt C O VI D -1 9 i n a d ults at le ast 1 8 y e ars ol d w h o h a ve pre vi o usl y 
re c ei v e d at le ast 2 d os es of a n m R N A C O VI D -1 9 v a c ci ne. T his P h as e 1 cli nic al st u d y is 
b ei n g i nitiate d t o e v al u ate t h e s afet y a n d i m m u n o g e nicit y of C V 0 5 0 1  as a b o oster v a cci n e 
o v er a ra n g e of d os e le v els i n a d ults at le ast 1 8  y e ars ol d.  
1. 2 Ris k: Be nefit C o nsi der ati o n s 
D etaile d i nf or m ati o n a b o ut t h e k n o w n a n d e x p e cte d ris ks of t h e C V 0 5 0 1  v ac ci ne is pr o vi d e d 
i n t h e c urre nt I B. I m p orta nt p ote ntial ris ks f or C V 0 5 0 1  v ac ci ne are t h e f oll o wi n g:  
•
H y p ers e nsiti vit y re a cti o ns, i n cl u di n g a n a p h yla xis
•
M y o c ar ditis
•
Peric ar ditis
•
Va c ci n e -ass o ciate d dis e as e e n h a n ce m e nt (a n i m p orta nt ris k f or all S A R S - C o V-2
v a c ci n es)
To miti g ate t h es e i m p orta nt p ote ntial ris ks, t h e f oll o wi n g ris k strate gies h a ve b e e n i n cl u de d 
i n t h e pr ot o c ol: 
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 2 7  
 
•  All p artici p a nts will re m ai n u n d er o bs er vati o n at t h e v a c ci n ati o n c e nter f or at le ast 
6 0  mi n utes after v a c ci n ati o n.  
•  I n di vi d u als wit h hist or y of h y p ers e nsiti vit y or s e v ere aller gic re a cti o n t o a n y pre vi o us 
v a c ci n e or a n y c o m p o n e nt of t h e I P are e x cl u de d fr o m t h e st u d y e nr oll m e nt a n d 
p artici p a nts will b e i nstr u cte d t o c o nta ct t h e st u d y site i m m e diatel y f or o c c urre nc e of 
a n y p ossi ble h y p ers e nsiti vit y re a cti o n wit hi n 1 d a y of v a c ci n ati o n.  
•  I n di vi d u als at i n cre as e d ris k of m y o c ar ditis or p eric ar ditis a n d i n di vi d uals wit h 
hist or y of m y o c ar ditis or p eric ar ditis are e x cl u d e d fr o m t h e st u d y e nr o ll m e nt. All 
p artici p a nts will b e e d u c ate d o n t h e  s y m pt o ms of m y o c ar ditis a n d p eric ar ditis a n d 
will re c ei v e g ui d a n c e o n c o nta cti n g st u d y p ers o n n el a n d s e e ki n g m e dic al c are if a n y 
of t h es e s y m pt o ms o c c ur. A n y p artici p a nts wit h s us p ecte d m y o c ar ditis or p eric ar ditis 
wit hi n 4 w e e ks after st u d y v a c ci n ati o n will b e e v al u ate d b y a c ar di ol o gist f or 
d efi niti v e dia g n osis a n d m a n a ge me nt.   
•  Partici p a nts will re c ei v e cl os e m e dic al s u per visi o n a n d m e dical ass ess me nts (e g, 
la b orat or y testi n g) d uri n g t h e st u d y. 
I n a d diti o n, v as o v a gal s y nc o pe a n d ot h er a n xiet y relate d re a cti o ns as a ps y c h o g e nic res p o ns e 
t o t h e n e e dle i nje cti o n c a n o c c ur f oll o wi n g or e v e n b ef ore a n y v a c ci nati o n. All p artici p a nts 
will t h eref ore re m ai n u n d er o bs er vati o n at t h e v a c ci n ati o n c e nter f or at le ast 6 0 mi n utes after 
v a c ci n ati o n.  
Partici p a nts are n ot e x p e cte d t o dire ctl y b e nefit fr o m st u d y p artici p ati o n. H o w e v er, t h eir 
p artici p ati o n i n t his st u d y will c o ntri b ute t o g e n erati n g i nf or m ati o n re gar di n g t h e v a cci n e 
platf or m b ei n g e v al u ate d a n d t h e p ote ntial f or t his c o nstr u ct t o b e f urt h er e v al uate d i n 
P h as e  2 a n d P h as e 3.  
D u e t o t h e la c k of e x p erie n c e i n h u m a n p artici p a nts, t h ere is c urre ntl y n ot e n o u g h 
i nf or m ati o n a v aila ble a b o ut t h e relati o ns hi p b et w e e n a d mi nistrati o n of t h e C V 0 5 0 1  m R N A 
i n v esti g ati o n al v a c ci ne a n d A Es. Alt h o u g h t h ere are n o cli nic al d ata a vaila ble o n t h e us e of 
C V 0 5 0 1  i n h u m a ns, av aila ble cli nic al d ata fr o m ot h er m R N A v a c ci n es usi n g a si milar 
m o difie d m R N A platf or m 
 a n d n o ncli nic al 
C CI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 28 
 
data using the unmodified mRNA 
 investigational vaccine guide the projection of 
expected AEs after vaccination. Based on this assessment, the anticipated AEs are expected 
to be manageable.  
The CV0501 vaccine is currently in an early stage of clinical development. As a result, 
vaccine efficacy, immunogenicity, and safety have not been demonstrated in humans. 
Considering the measures planned to be taken to minimize risk to participants in this Phase 1 
study, the potential risks associated with the investigational vaccine are considered 
acceptable. 
CCI

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 2 9  
 
2  St u d y O bjecti ves a n d E n d p oi nts  
T h e st u d y o bje cti v es a n d e n d p oi nts are d escri b e d i n  Ta b le  2- 1. 
Ta b le 2- 1 
St u d y O bje cti v es a n d E n d p oi nts  
P ri m ar y O bj ecti ves  
P ri m ar y E n d p oi nts  
T o e val uat e t he saf et y a n d 
t ol er a bilit y of C V 0 5 0 1 at eac h 
d ose l e vel  
• 
P er ce nt a ge of parti ci pa nts wit h eac h s oli cit e d l ocal a n d 
s yst e mi c A E d uri n g 7 da ys aft er vacci nati o n (i e, t he day 
of st u d y vacci nati o n a n d 6  s u bse q ue nt da ys, Da ys 1 
t hr o u g h 7)  
• 
P er ce nt a ge of parti ci pa nts wit h eac h a b n or m al cli ni cal 
saf et y l a b or at or y fi n di n g f or 8 da ys aft er st u d y 
vacci nati o n  
• 
P er ce nt a ge of parti ci pa nts wit h u ns oli cit e d A Es f or 2 8 
da ys aft er st u d y vacci nati o n  
• 
P er ce nt a ge of parti ci pa nts wit h M A A Es, A E SIs a n d 
S A Es f r o m st u d y vacci nati o n t hr o u g h t he e n d of t he 
st u d y (f or 1 8 0 da ys aft er t he st u d y vacci ne 
a d mi nistr ati o n), eac h s u m m ari ze d se par at el y  
S ec o n d ar y O bj ecti ves  
S ec o n d ar y E n d p oi nts  
T o e val uat e ne utr ali zi n g A b 
tit ers a gai nst S A R S-C o V -2 W T, 
O mi cr o n, a n d Delt a vari a nts 
f oll o wi n g C V 0 5 0 1 b o ost er 
vacci nati o n i n a d ult parti ci pa nts  
• 
G M Ts of ne utr ali zi n g A b a gai nst pse u d o vir us beari n g S 
pr ot ei n fr o m S A R S -C o V - 2 W T, O mi cr o n, a n d Delt a 
vari a nts at eac h c oll ecti o n ti m e p oi nt  
• 
G MI fr o m baseli ne of ne utr ali zi n g A b tit ers a gai nst 
pse u d o vir us beari n g S pr ot ei n fr o m S A R S -C o V -2 W T, 
O mi cr o n, a n d Delt a vari a nts at eac h c oll ecti o n ti m e 
p oi nt  
T o descri be ser or es p o nse t o 
C V 0 5 0 1 base d o n ne utr ali zi n g 
A b tit ers a gai nst pse u d o vir us es 
beari n g S pr ot ei n fr o m 
S A R S -C o V -2 W T, O mi cr o n, 
a n d Delt a vari a nts 
• 
S er or es p o nse r at e 2 8 da ys aft er t he b o ost er d ose ( Da y 
2 9), base d o n ne utr ali zi n g A b tit ers a gai nst 
pse u d o vir us es beari n g S pr ot ei n fr o m S A R S -C o V - 2 
W T, O mi cr o n, a n d Delt a vari a nts  at eac h c oll ecti o n 
ti m e p oi nt, wit h ser or es p o nse defi ne d as p ost b o ost tit ers 
≥ 4 ×  pr e b o ost tit ers.  
Terti ar y O bj ecti ves  
Terti ar y E n d p oi nts:  
C CI

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 3 0  
 
C CI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential 
Page 31 
3 Investigational Plan – Study Design 
This open-label, dose escalation FTiH Phase 1 study will evaluate the safety (including 
reactogenicity) and immunogenicity of a single booster dose of CV0501 vaccine in adults 
who have previously received at least 2 doses of an mRNA COVID-19 vaccine 
(Section 4.1.1). Approximately 180 participants will be enrolled. The study will comprise 
two parts (Part A and Part B).  
The study duration per participant will be approximately 194 days from start of screening 
through EOS, including approximately 14 days for screening and approximately 180 days 
(6 months) for Day 1 vaccination and follow-up. There will be 6 protocol-scheduled visits: 
on Day 1 (vaccination day) and on Days 8, 15, 29, 91 and 181. In addition, there will be one 
protocol-scheduled telephone contact on Day 4 to query participants about solicited and 
unsolicited AEs occurring after study vaccination. 
Participants will be monitored for potential COVID-19 illness from Day 1 through the EOS 
(Day 181). Participants will be asked to contact the site if they experience any symptoms of 
COVID-19 and will also be asked to report any positive SARS-CoV-2 diagnostic test.  
Participants will also be required to document all AE symptoms and contact the site if 
necessary. An unscheduled visit may also be performed if an AE requires further evaluation. 
Safety data will be monitored on an ongoing basis by the investigator (or medically qualified 
designee) and sponsor to promptly identify and flag any event that potentially could trigger a 
stopping rule. If a stopping rule is triggered, study intervention administration and enrollment 
will pause and the SRT will review available safety data from all vaccinated participants. 
Participants who have already received vaccine will continue to attend follow-up visits as 
specified in the schedule of events (Table 13-1). There are 2 planned interim analyses of 
safety and immunogenicity data (Section 7.7). 
CCI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 32 
 
3.1 Part A Study Design 
Participants in Cohorts 1 to 5 will be enrolled in a staggered manner to 1 of 5 cohorts with 
planned dose escalation of CV0501 from 12 µg up to 200 µg. Each cohort of Part A will 
evaluate a single dose level of CV0501 vaccine and will include 2 age groups (younger 
adults, ≥ 18 to < 65 years old, and older adults, ≥ 65 years old), as indicated in Table 3-1. The 
dose levels for the groups in Cohorts 1-3 are fixed. The dose levels for the Cohorts 4 and 5 
will be as recommended by the SRT, based on their review of all available safety data and 
dosing scenarios.  
Table 3-1 
Planned Cohorts, Dose Levels, Groups, and Sample Sizes for 
Part A 
Cohort Vaccine 
Dose Level (µg) 
Group A 
Younger Adults 
≥18 to <65 Years Old 
(n range) 
Group B 
Older Adults 
≥65 Years Old 
(n range) 
Total 
Cohort  
Sample Size  
1 
CV0501 
12 
1a (min 10; max 20) 
1b (min 10; max 20) 
30 
2 
25 
2a (min 10; max 20) 
2b (min 10; max 20) 
30 
3 
50 
3a (min 10; max 20) 
3b (min 10; max 20) 
30 
4 
75 or 100* 
4a (min 10; max 20) 
4b (min 10; max 20) 
30 
5 
100, 150, or 200* 
5a (min 10; max 20) 
5b (min 10; max 20) 
30 
*  
Depending on the reactogenicity/safety findings from groups in Cohorts 1-3, the SRT may recommend 1 of 
3 prespecified dosing scenarios comprising these dose levels for groups in Cohorts 4 and 5, as described in 
Section 3.1.1. The dose level recommendations will be made independently for Groups A (younger 
participants) and B (older participants). 
 
The recruitment target will be a total of 30 participants per cohort in Cohorts 1 to 5. The 30 
participants will be distributed between the younger and older age groups. A minimum of 10 
participants per age group will be enrolled. A maximum of 20 participants may be enrolled in 
an individual age group.
 
 
 
CCI

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al  
Pa g e 3 3  
3. 1. 1 P art A D ose Esc al ati o n Pl a n  
E nr oll m e nt will b e sta g g ere d, b e gi n ni n g wit h Gr o u p 1 a ( 1 2 µ g, y o u n ger a d ults). I nitiati o n of 
e nr oll m e nt i n Gr o u p 1 b ( 1 2 µ g, ol d er a d ults) will d e p e n d o n S R T re vie w of s afet y d ata u p t o 
D a y 8 fr o m a mi ni m u m of 1 0 p artici p a nts i n Gr o u p 1 a  (Fi g ure  3- 1, re d arr o w).  
F or b ot h y o u n g er a n d ol der a g e gr o u ps, i nitiati o n of e nr oll m e nt i n t h e s u bs e q ue nt gr o u p at 
t h e n e xt d os e le v el f or C o h orts 2- 5 will d e p e n d o n S R T re vie w of s afet y d ata  u p t o D a y 8 
fr o m a mi ni m u m of 1 0 p artici p a nts, fr o m t h e pre vi o us d os e le v el i n t h e s a m e a g e gr o u p 
(Fi g ure  3- 1, bla c k arr o ws). T h e d os e le v els f or t h e gr o u ps i n C o h orts 1 -3 are fi x e d. F or e a c h 
of t h e gr o u ps i n C o h orts 4 a n d 5, t h e S R T m a y re c o m m e n d a d os e s p e cifie d b y 1 of t h e 3 
d osi n g s c e n ari os i n  Ta b le  3- 2, b as e d o n t h eir re vie w of all a v aila ble s afet y d ata. T h e S R T will 
us e t h e s a m e a p pr o a c h, i n d e pe n d e ntl y, t o s ele ct t h e d os e le v el s f or ol d er p artici pa nts ( Gr o u ps 
4 b a n d 5 b) a n d y o u n g er p artici p a nts ( Gr o u ps 4 a a n d 5 a) . 
Ta ble  3- 2 
D osi n g Sc e n a ri os f o r P a rtici p a nts E nr olle d i n  C o h o rts 4 a n d 5  
D osi n g S ce n ari o  
G r o u p 4 a O R 4 b  
G r o u p 5 a O R 5 b  
# 1 
7 5 µ g  
1 0 0 µ g  
# 2  
1 0 0 µ g  
1 5 0 µ g  
# 3  
1 0 0 µ g  
2 0 0 µ g  
W hile t h e S R T  re vie ws s afet y d ata, e nr oll m e nt i n t h e s a m e gr o u p will c o nti n u e u ntil t h e 
c o h ort is f ull. T h e S R T re c o m m e n d ati o n f or e a c h gr o u p c o ul d b e t o es c alate t o t h e n e xt d os e 
le v el or t o st o p t h e e nr oll m e nt at t h e c urre nt d os e.  
At e a c h S R T m e eti n g, a  Ba y esia n l o gistic re gressi o n m o del ( Se cti o n  1 3. 3 ) will b e us e d t o 
pre dict u n a c c e pta ble re a ct o g e nicit y at t h e c urre nt or n e xt d os e le v el. A l o w er t h a n  5 0 % 
p osteri or pr o b a bilit y t h at t h e p erc e nta ge is a b o v e t h e m a xi m u m t olera ble rate will b e 
fa v ora ble t o pr o gressi o n t o t h e n e xt hi g her d os e. Bas e d o n t h e hist oric al P h as e 1 
re a ct o g e nicit y d ata fr o m 
v a c ci n e s, t h e m a xi m u m t olera ble rate f or Gra d e 3 s olicite d a d vers e e v e nts h as b e e n s et t o 
3 0 %. T h e S R T m a y re c o m m e n d dr o p pi n g gr o u ps at a n y ti m e d uri n g t h e st u d y if a n 
C CI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 34 
 
unfavorable safety profile is observed in that group or based on safety or immunogenicity 
data from other groups.  
3.1.2 Part A Study Schematic 
The study schematic of Part A is provided in Figure 3-1. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 35 
 
Figure 3-1 
Part A Study Schematic  
 
Note for Cohort 4 (Groups 4a and 4b) and Cohort 5 (Groups 5a and 5b): Depending on the reactogenicity/safety findings from groups in Cohorts 1-3, the SRT 
may prospectively recommend a dose of 75 µg or 100 µg for Groups 4a and 4b, and subsequently a dose of 100 µg, 150 µg or 200 µg for Groups 5a and 5b. 
The dose level recommendations will be made independently for Groups A (younger participants) and B (older participants).  
 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 36 
 
3.2 Part B Study Design 
Part B, designed to comprise 2 single age group cohorts (≥18 to <65 years old), will start 
based on the first interim analysis of safety and immunogenicity (Section 7.7), provided that 
the SRT assesses the 12 µg dose to be immunogenic and safe. The SRT may recommend 
dropping Cohorts 6 and 7 (Groups 6a and 7a) based on immunogenicity data from the groups 
that received the 12 µg dose level. If the SRT determines that enrollment in Cohorts 6 and 7 
may proceed, enrollment may proceed in parallel according to Table 3-3. 
Table 3-3 
Planned Cohorts, Dose Levels, Groups, and Sample Sizes for 
Part B 
Cohort  
Vaccine  
Dose Level (µg)  
Group A  
≥18 to <65 Years Old  
Total Cohort   
Sample Size   
6  
CV0501 
3  
6a  
15 
7  
6  
7a  
15 
 
The study schematic for Part B is provided in Figure 3-2. The SRT will review Day 8 safety 
data for all 15 participants in Groups 6a and 7a. 
Figure 3-2 
Part B Study Schematic 
 
Note: Initiation of enrollment for Groups 6a and 7a will be dependent on SRT review of safety and 
immunogenicity data from the first interim analysis (after all participants in Cohorts 1, 2, and 3 have 
completed the Day 15 study visit).  
3.3 Scientific Rationale for Study Design 
There is currently a critical unmet medical need for vaccines to prevent COVID-19 disease 
caused by the Omicron variant (B.1.1.529) of SARS-CoV-2. The transmissibility of Omicron 
variant is estimated to be higher than Delta, and preliminary clinical data indicate that the 
risk of reinfection among those with a prior COVID-19 infection is 3-8 times higher from 
Group 6a: CV0501 (3 µg, n=15)
18 – 64 years
M6 EOS
D1 Vac
D29
M3
D15
D8 SRT
Group 7a: CV0501 (6 µg, n=15)
18 – 64 years 
M6 EOS
D1 Vac
D29
M3
D15
D8 SRT

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 3 7  
 
O micr o n t h a n D elta. ( U K H e alt h Se c urit y A g e n c y 2 0 2 1 ). Alt h o u g h c urre nt F D A-a ut h oriz e d 
a n d lic e ns e d C O VI D -1 9 v a cci n es are hi g hl y effe cti v e, bre a kt hr o u g h c as es o c c ur. A t otal of 
1 0, 2 6 2 S A R S - C o V-2 v a c ci n e brea kt hr o u g h i nfe cti o ns h a d b ee n re p orte d fr o m 4 6 U S states 
a n d territ ories as of A pril 3 0, 2 0 2 1  (C D C 2 0 2 1c ). 
I n p art n ers hi p wit h 
 Gla x o S mit h Kli n e Bi ol o gic als S A ( G S K) is d e v el o pi n g a 
n e w C V 0 5 0 1  C O VI D-1 9 v a cci n e c o m prisi n g m o difie d -n u cle oti d e m R N A t h at e n c o des t h e 
O micr o n v aria nt S  pr otei n f or m ulate d wit h li pi d n a n o p articles ( L N Ps).  
T his is a P h as e 1 F Ti H st u d y d esi g n e d t o e v al u ate t h e s afet y, re a ct o ge nicit y, a n d 
i m m u n o g e nicit y of t h e G S K-
 C V 0 5 0 1  m o difie d m R N A v a cci n e e n c o di n g t h e 
O micr o n v aria nt t o pre v e nt C O VI D -1 9. T his st u d y will e v al u ate t h e C V 0 5 0 1  v a cci n e as a 
b o oster v a c ci n ati o n i n a h e alt h y a d ult p o p ulati o n of p artici p a nts w h o h a ve pre vi o usl y 
re c ei v e d at le ast 2 d os es of a n m R N A C O VI D -1 9 v a c ci ne . 
3. 3. 1 St arti n g D ose  
T h e starti n g d os e of C V 0 5 0 1  v a c ci n e ( 1 2 µ g) h as b e e n c h ose n b as e d o n a re p e at -d os e 
t o xicit y st u d y of 1 0 µ g or 2 0 µ g d os es of t h e 
 u n m o difie d S A R S- C o V-2 m R N A 
v a c ci n e,  
 ( Se cti o n  1. 1 ). Ple as e refer t o t h e c urre nt I B f or a d diti o n al d etails o n d ata 
fr o m n o n cli nic al t o xic ol o g y st u dies s u p p ort i nitiati o n of t h e starti n g d os e. 
Cli nic al s afet y d ata wit h  
 a n i n v esti g ati o n al L N P m R N A -b as e d v a c ci n e e n c o di n g 
t h e S A R S- C o V-2 S pi k e pr otei n of t h e W u h a n a n c estral is olate m a n ufact ure d b y 
 
f urt h er s u p p ort t h e starti n g d os e of 1 2 µ g f or t h e pres e nt st u d y.  
c o nsists of 
s e q u e n c e-o pti miz e d, c a p p e d a n d p ol y a d e n ylate d, c h e mic all y u n m o difie d m R N A. Va c ci n es 
c o ntai ni n g m o difie d m R N A, s u c h as C V 0 5 0 1 , are e x pe cte d t o h a v e less re a ct o g e nicit y t h a n 
v a c ci n es c o ntai ni n g u n m o difie d m R N A b e ca use m o difie d m R N A d o es n ot e n g a g e e n d oso mal 
a n d c yt os olic p atter n -re c o g niti o n re c e pt ors a n d s o pr o v o k e less i nfla m m ati o n. T h e re d u c e d 
i nfla m m ati o n is e x p e cte d t o yiel d a m ore fa v ora ble s afet y pr ofile.  
St u d y 
 is a n o n g oi n g P h as e 2 b/ 3, ra n d o miz e d, 
o bs er v er -bli n de d, pla c e b o -c o ntr olle d, m ultic e nter, cli nic al st u d y e v al u ati n g t h e effic ac y a n d 
s afet y of i n v esti g ati o n al C V n C o V v a c ci ne i n a d ults at le ast 1 8 y e ars ol d . I n t h e fi n al a n al ysis 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 3 8  
 
wit h d ata c ut off d ate of 1 7 J u n 2 0 2 1, 1 9, 7 8 3 p artici p a nts re c ei v e d at le ast 1 d os e of 1 2  µ g 
 a n d 1 9, 7 4 6 p artici pa nts at le ast 1 d os e of pla c e b o.  
Bas e d o n d ata fr o m t h e o n g oi n g 
 trial, t h e re a ct o ge nicit y pr ofile is c o nsi dere d 
a c c e pta ble wit h m ost s olicite d A Es b ei n g Gra d e 1  or Gra d e 2. A n y Gra d e 3 s olicite d A Es 
w ere tra nsie nt, wit h a m e dia n d urati o n of 1 d a y. L o c al re a cti o ns w ere m ore c o m m o n i n 
p artici p a nts re c ei vi n g  
 ( 8 4. 8 %) t h a n i n t h os e re c ei vi n g pla c e b o ( 2 4. 1 %). I n t h e 
 gr o u p, t h e m ost fre q ue ntl y re p orte d Grad e 3 l o c al re a cti o n after a n y d os e w as 
i nje cti o n site p ai n ( 1. 1 %). S olicite d s yste mic re a cti o ns w ere m ore c o m m o n i n p artici p a nts 
re c ei vi n g  
 ( 9 4.0 %) t h a n i n t h os e re c ei vi n g pla c e b o ( 6 3.5 %), wit h 2 6. 8 % a n d 3. 0 %, 
res p e cti v el y, re p orti n g Gra d e 3 s yste mic re a cti o ns. I n t h e  
 gr o u p, t h e m ost 
fre q u e ntl y re p orte d Gra d e 3 s yste mic re a cti o ns after a n y d ose w ere fati g u e ( 1 3. 4 %), c hills 
( 1 1. 0 %) a n d h e a d a c he ( 1 0. 9 %) (Kre ms n er 2 0 2 1 ). 
N o s afet y c o n c er ns relate d t o  
w ere i d e ntifie d f oll o wi n g a d mi nistrati o n  of 2 d os es 
of 1 2 µ g  
 gi v e n 2 8 d a ys a p art, t o a lar g e p o p ulati o n of p artici p a nts at le ast 1 8 y e ars 
ol d . 
3. 3. 2 D ose Esc al ati o n  
Es c alati o n t o t h e n e xt hi g h er d os e c o h ort f or e a c h a g e gr o u p will b e s u p p orte d b y cli nic al 
s afet y d ata fr o m a mi ni m u m of 1 0 a d ults i n t h e s a m e a g e gr o u p w h o re c ei v e d t h e pre vi o us 
d os e le v el. T h e d e cisi o n t o es c alate will b e b as e d o n re vie w b y t h e S R T as d es cri b e d i n 
Se cti o n  3. 1. 1 .  
3. 3. 3 M a xi m u m Pl a n ne d D ose  
T h e m a xi m u m pla n n e d d os e of C V 0 5 0 1 is 2 0 0 µ g i n t h e pres e nt st u d y. T h e rati o n ale f or 
e v al u ati n g d os es u p t o 2 0 0 µ g is b as e d o n t h e f oll o wi n g c o nsi derati o ns:  
•  T he o pti m al b o oste r d os e of C V 0 5 0 1  ne c ess a r y t o c o nfe r pr ote cti o n a g ai nst  
C O VI D -1 9 dis e as e c a us e d b y t he O mic r o n v a ri a nt ( B. 1. 1. 5 2 9) is u n k n o w n . T h e 
O micr o n v aria nt c o ntai ns at le ast 3 0 a mi n o a ci d s u bstit uti o ns, 1 5 of w hic h are i n t h e 
re c e pt or-bi n di n g d o m ai n ( C D C 2 0 2 1 a ). A c c u m ulati n g e vi d e n ce s u g gests t h at t h e 
O micr o n v aria nt c a n e v a de t h e i m m u ne pr ote cti o n c o nferre d b y v ac ci nes a n d n at ural 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 3 9  
 
i nfe cti o n (Se cti o n  1. 1 ). Bas e d o n li mite d d ata, c o n valesc e nt s era a n d a nti b o dies fr o m 
p ers o ns v a c ci n ate d wit h t h e m R N A C O VI D -1 9 v a cci n es m a n ufa ct ure d b y 
 w ere less effe cti v e at n e utralizi n g t h e O micr o n v aria nt 
c o m p are d t o W T vir us ( Se cti o n  1. 1 ). Ta k e n t o g et h er, t h es e d ata s u g gest t h at it is 
li k el y t h at hi g h er d os es c o ul d b e n ec essar y t o g e nerate a de q uate i m m u nit y t o c o nfer 
pr ote cti o n a g ai nst t h e O micr o n v aria nt.  
 
T h e ra n g e of d os es t o b e teste d as a b o oster d os e i n t his P h as e 1 d os e es c alati o n st u d y 
i n a d ults, 3 µ g t o 2 0 0 µ g, bra c k ets t h e 3 0 µ g b o oster d ose a ut h oriz e d b y t h e F D A 
u n d er E U A f or t h e 
 
, t h e 5 0 µ g b o oster d os e a ut h oriz e d b y t h e F D A u n d er E U A f or t h e  
 
 a n d t h e 1 0 0 µ g pri m ar y v a cci n ati o n d os e f or t h e 
  
 
Ta k e n t o g et h er, t h es e d ata s u p p ort t h e e v al u ati o n of a ra n g e of d oses t o d eter mi ne t h e 
o pti m al s afe a n d i m m u n o ge nic d os e t o b e e v al uate d f urt h er. 
•  T he o pti m al d os e of C V 0 5 0 1  t h at c o ul d c o nfe r c r oss-pr ote cti o n a g ai nst 
n o n -O mic r o n v a ri a nts is u n k n o w n. As t h e C O VI D -1 9 p a n d e mic pr o gress es, n e w 
S A R S - C o V-2 v aria nts are li k el y t o e m er g e. Cr oss -pr ote cti o n a g ai nst S A R S- C o V- 2 
v aria nts n ot c o ntai n e d i n t h e v a c ci n e m a y b e c o m e i m p orta nt. F or t his re as o n, 
a d e q u ate d os e -fi n di n g is n e c ess ar y i n P h as e 1 t o h el p d eter mi n e t h e o pti m al d os e t h at 
c a n s afel y i n d u c e hi g h titers t h at c o ul d c o nfer cr oss -n e utralizi n g a cti vit y a g ai nst n e w 
a n d e m er gi n g v aria nts of c o n cer n.  
3. 3. 4 L o w D ose E v al u ati o n  
If t h e 1 2 µ g d os e le v el is d e m o nstrate d t o b e i m m u n o g e nic, t h e i m m u n o g e nicit y a n d s afety of 
l o w er d os e le v els ( 3 µ g a n d 6 µ g) of C V 0 5 0 1 will b e e v al u ate d. T h e s cie ntific rati o n ale f or 
testi n g t h es e a d diti o n al l o w er d os e le v els is t o e v al u ate w h et her C V 0 5 0 1 m R N A platf or m 
c o ul d b e o pti miz e d f or t h e d e v el o p me nt of m ulti v ale nt v a cci n e(s).  
C CI
C CI
C CI
C CI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 40 
 
4 Participant Selection and Withdrawal Criteria 
4.1 Selection of Study Participants 
Deviations from the inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability, or 
participant safety. Therefore, adherence to the eligibility criteria as specified in the protocol is 
essential. 
4.1.1 Inclusion Criteria 
A participant must meet all following criteria to be enrolled in this study: 
1. Must provide documented informed consent prior to any study procedures being 
performed  
2. Is capable of understanding and agrees to comply with planned study procedures and 
to be available for all study visits  
3. Has received at least 2 doses of 
 
, with the last dose of vaccine received at least 6 months prior to 
screening  
4. Negative for SARS-CoV-2 infection by RT-PCR test at screening 
5. Is a male or nonpregnant female ≥18 years old  
6. If the participant is a WOCBP, agrees to use at least 1 highly effective form of 
contraception for at least 30 days prior to the study vaccination up to 3 months after 
study vaccination. 
7. Agrees to refrain from blood or plasma donation from the first study vaccination 
through end of study. 
8. Has a body mass index of 18 to 40 kg/m2, inclusive, at screening. 
9. Is healthy or medically stable as determined by investigator judgment based on 
medical history, clinical laboratory tests, vital sign measurements, and physical 
examination findings 
CCI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 41 
 
4.1.2 Exclusion Criteria 
An individual who meets any of the following criteria will not be enrolled in the study: 
1. 
Participant is female and has a positive pregnancy test result at screening. 
2. 
Participant is female and is breastfeeding or will (re)start breastfeeding from the 
study vaccination to 3 months after vaccination.  
3. 
Has an acute febrile illness with temperature ≥38.0°C or ≥100.4°F within 72 hours 
before study vaccination. Individuals with suspected COVID-19 symptoms should 
be excluded and referred for medical care.  
4. 
Has a history of documented SARS-CoV-2 infection or COVID-19 within 6 months 
before screening. 
5. 
Has a documented medical history of HIV, hepatitis B or hepatitis C infection prior 
to screening, or a positive test for these conditions at screening.  
6. 
Any confirmed or suspected immunosuppressive or immunodeficient condition 
resulting from disease (eg, malignancy) or immunosuppressive/cytotoxic therapy 
(eg, medications used during cancer chemotherapy, organ transplantation or to treat 
autoimmune disorders). Chronic use (more than 14 continuous days) of any 
medication that may be associated with changes in immune function including, but 
not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone 
equivalent, allergy immunotherapy injections, immunoglobulin, interferon, 
immunomodulators, cytotoxic drugs, or other similar or toxic drugs within 6 months 
of the first study vaccination. Inclusion of persons who use low dose topical, 
ophthalmic, inhaled, or intranasal steroid preparations is permitted.  
7. 
History of myocarditis, pericarditis, or idiopathic cardiomyopathy, or presence of any 
medical condition that increases risk of myocarditis or pericarditis, including cocaine 
abuse, cardiomyopathy, endomyocardial fibrosis, hypereosinophilic syndrome, 
hypersensitivity myocarditis, eosinophilic granulomatosis with polyangiitis, 
persistent myocardial viral infection (eg, due to enterovirus or adenovirus), and 
celiac disease.  

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 42 
 
8. 
Has a new onset, clinically significant, abnormal biochemistry or hematology finding 
(defined as ≥Grade 1) at screening (adults with Grade 1 laboratory abnormalities that 
have been stable for at least 6 months before enrollment may be included in the 
study).  
9. 
Individuals with a history of autoimmune disease or an active autoimmune disease 
requiring therapeutic intervention, including but not limited to: systemic or 
cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, 
Guillain-Barré syndrome, multiple sclerosis, Sjögren’s syndrome, idiopathic 
thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell 
arteritis (temporal arteritis), Takayasu arteritis, granulomatosis with polyangiitis, 
psoriasis, and insulin-dependent diabetes mellitus (Type 1). 
10. Has an unstable chronic medical condition. This refers to a condition requiring a new 
medication or increase in dose of current medication(s) or a condition requiring 
hospitalization within 6 months prior to screening. 
11. Has a history of hypersensitivity or severe allergic reaction, including anaphylaxis, 
generalized urticaria, angioedema, and other significant reactions, to vaccines or to 
any component of the investigational product. 
12. Has received or plans to receive any licensed vaccine within 4 weeks before or 
4 weeks after study vaccination. Inactivated vaccines for influenza are permitted 
during the study if they are administered at least 14 days before or after study 
vaccination.  
13. Has had known close contact with anyone who had a confirmed SARS-CoV-2 
infection within 2 weeks before study vaccination. Rescreening of these participants 
permitted after quarantine period is complete. 
14. Has participated or plans to participate in another investigational study involving any 
investigational product or device within 6 months or 5 half-lives, whichever is 
longer, before the study vaccination through end of study. 
15. Has received or plans to receive immunoglobulins or any blood or blood products 
within 3 months before the first study vaccination through end of study.  

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 43 
 
16. Has a bleeding diathesis or condition associated with prolonged bleeding that would, 
in the opinion of the investigator, contraindicate intramuscular injection. 
17. Has a history of alcohol abuse or other recreational drug use (excluding cannabis) 
within 6 months before study vaccination.  
18. Has any abnormal skin condition or permanent body art (eg, tattoo) that would 
interfere with the ability to observe local reactions at the injection site.  
19. Has a medical disease or psychiatric condition that, in the opinion of the investigator, 
precludes study participation because it would place the individual at an 
unacceptable risk of injury, render the individual unable to meet the requirements of 
the protocol, or interfere with the individual's successful completion of the trial.  
20. Participant is an employee or family member of the investigator or study site 
personnel. 
4.2 
Discontinuation From Study Intervention and/or Withdrawal From 
the Study 
As this is a single-dose study, discontinuation from study intervention does not apply.  
Individual participants may withdraw from the study at any time at their own request for any 
reason without prejudice to their future medical care by the investigator or at the study site. 
The reasons for participants withdrawing from the study will be recorded in the eCRF. 
Participants will be informed of any new authorized or licensed booster vaccines that become 
available for prevention of COVID-19 during the study to support an informed choice for 
whether to continue or discontinue participation in the study. 
A participant may withdraw or be withdrawn from the study for any of the following reasons: 
• Participant request. 
• Investigator request. 
• The participant is noncompliant with the protocol. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 44 
 
• The participant has a serious or intolerable AE(s) that, in the investigator’s opinion, 
requires withdrawal from the study. 
• The participant is lost to follow-up. 
• Death. 
• The sponsor terminates the study. 
If a participant withdraws or is withdrawn from the study, ET procedures should be 
completed as indicated in the SOE (Table 13-1). Every effort will be made to continue to 
monitor the safety of participants who received a dose of IP and are withdrawn from the 
study. 
4.2.1 Lost to Follow-Up 
A participant 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 participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 2 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
participant’s medical record.  
• If the participant continues to be unreachable, he/she will be considered to have 
withdrawn from the study. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 45 
 
4.2.2 
Replacements 
Participants who withdraw may be replaced at the discretion of the sponsor after consultation 
with the SRT. Participants who are assigned to a group in error and not vaccinated may be 
replaced. Participants who withdraw for reasons connected to the study vaccine (eg, safety 
concerns after study vaccination) will not be replaced. 
If the investigator believes there is a reasonable justification to do so, all screening 
procedures may be repeated (maximum 1 rescreening per individual is allowed). Only results 
from the rescreening visit, if it occurs, will be taken into consideration and recorded in the 
eCRF. The participant can only be vaccinated once the investigator receives the results and 
confirms the eligibility criteria. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 46 
 
5 Study Vaccines 
5.1 Method of Assigning Participants to Study Vaccine Groups 
Participants in Part A will be assigned sequentially to a dose-level cohort by age group 
(Section 3.1). Participants in Part B will be randomly assigned on Day 1 to receive study 
vaccine by dose-level cohort.  
Interactive response technology will be used to administer the randomization schedule. 
Biostatistics will generate the randomization schedule using SAS software Version 9.4 or 
later (SAS Institute Inc, Cary, North Carolina) for IRT, which will link sequential participant 
randomization numbers to treatment codes. Note: If a participant is consented electronically, 
a participant number may be generated; however, that number will be updated to align with 
the IRT number after randomization is complete for consistency in each participant’s study 
records. 
5.2 Study Vaccine Administration 
Participants will receive 1 dose of IP on Day 1, in accordance with the study’s SOE 
(Table 13-1). The volume to be administered will vary by dose level over a potential range of 
0.3 mL to 0.7 mL; full details are described in the Pharmacy Manual.  
Study intervention should be administered intramuscularly into the deltoid muscle, preferably 
of the nondominant arm. The needle length recommendations for adults (by sex and weight) 
receiving an intramuscular injection in the deltoid muscle are as follows (CDC 2022b):  
• Men and women, < 70 kg (152 lb): 25 mm (1 inch) 
• Men, 70-118 kg (152-260 lb); Women, 70-90 kg (152-200 lb): 25-38 mm (1-1.5 inches) 
• Men, > 118 kg (260 lb); Women, > 90 kg (200 lb): 38 mm (1.5 inches)  
Standard vaccination practices must be observed, and vaccine must not be injected into blood 
vessels. Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.  

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 4 7  
 
A d mi nistrati o n of I P s h o ul d b e p erf or me d b y a n a p pr o priatel y q u alifie d, G C P -trai n e d, a n d 
v a c ci n e -e x perie nc e d m e m ber of t h e st u d y staff (e g, p h ysicia n, n urs e, p h ysicia n’s assista nt, 
n urs e pra ctiti o n er, p h ar m acis t, or m e dical assista nt) as all o w e d b y l o c al, state, a n d 
i nstit uti o n al g ui d a n c e. D etails of I P a d mi nistrati o n will b e re c or d e d i n t h e e C R F. 
Refer t o t h e P h ar m a c y Ma n u al f or a d diti o nal i nstr u cti o ns o n st u d y v a cci n e a d mi nistrati o n.  
5. 3 I de ntit y of I n vesti g ati o n al Pr o d uct 
I n v esti g ati o n al pr o d u ct i n t his P h as e 1 st u d y refers t o t h e C V 0 5 0 1  v a cci n e, w hic h is a 
f or m ulati o n of 
 
. t h at will b e a d mi nistere d d uri n g t h e st u d y.  
T h e I P i nf or m ati o n is pres e nt e d i n  Ta b le  5- 1. 
Ta ble  5- 1 
I n v esti g ati o n al Pr o d uct I nf o r m ati o n 
I nt er ve nti o n N a me  
C V 0 5 0 1   
T y p e  
Vacci ne  
D ose F or m ul ati o n  
M o difi e d m R N A  
U nit D ose St re n gt h(s)  
 μ g m R N A/ m L  
D os a ge Le vel(s )  
3, 6, 1 2, 2 5, 5 0, 7 5, 1 0 0, 1 5 0, 2 0 0 μ g  
R o ut e of A d mi nist r ati o n  
I ntr a m usc ul ar i nj ecti o n  
Dil u e nt  
0. 9 % s o di u m c hl ori de  
Use  
E x peri m e nt al  
I M P or NI M P  
I M P  
S o u rci n g  
Pr o vi de d ce ntr all y b y G S K Bi ol o gi cals S A or 
 
 
C CI
C CI
C CI
C CI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 48 
 
Packaging and Labeling  
IP will be provided in a glass vial as a sterile colloidal 
dispersion in a frozen liquid formulation as open-label 
supply. Each vial will be labeled as required per country 
requirement. 
Diluent (0.9% sodium chloride solution for injection) will be provided centrally by PPD in a glass or 
plastic vial as open-label supply. Each vial will be labeled as required per country requirement.  
Refer to the Pharmacy Manual for instructions on how to prepare and dispense the IP. 
Appropriately qualified and experienced study staff (eg, physician, nurse, physician’s 
assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist), as allowed by 
local, state, and institutional guidance, should prepare and dispense IP. A second staff 
member will verify the dispensing.  
5.4 Management of Clinical Supplies 
5.4.1 Investigational Product Packaging and Storage 
Investigational product will be supplied in vials that will require further dilution and 
preparation procedures; please refer to the Pharmacy Manual for additional packaging and 
preparation details. The IP must be stored in a secure, restricted freezer and kept at the 
temperature noted in the Pharmacy Manual at each stage of preparation for IM 
administration. 
Once prepared and diluted for IM administration, refer to the Pharmacy Manual for storage 
conditions. The investigator or designee must confirm appropriate temperature conditions 
have been maintained during transit for all IP received and any discrepancies are reported 
and resolved before use of the IP.  
Refer to the Pharmacy Manual for further details regarding storage and preparation 
requirements. 
5.4.2 Investigational Product Accountability 
The investigator will maintain accurate records of receipt of all IP, including dates of receipt. 
In addition, accurate records will be kept regarding when and how much IP is administered to 
each participant in the study. Only participants enrolled in the study may receive the IP and 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 49 
 
only authorized site personnel may supply or administer the IP. Reasons for departure from 
the expected dispensing regimen must also be recorded. At the completion of the study, to 
satisfy regulatory requirements regarding drug accountability, all IP will be reconciled and 
retained or destroyed according to applicable regulations. Further guidance and information 
for the final disposition of unused IP are provided in the Pharmacy Manual. 
5.4.3 Other Supplies 
Refer to the Pharmacy Manual for ancillary formulation preparation or injection materials 
that will be distributed by PPD to the study sites or that the study sites will need to procure.  
In addition, PPD will provide the following participant supplies to study sites: eDiary 
devices, rulers, thermometers, and informational cards describing solicited symptoms and 
symptoms of COVID-19.  
5.5 Overdose Management 
An overdose is any dose of study vaccine given to a participant that exceeds the planned dose 
for an individual participant within a given group.  
There is no specific treatment recommended for an overdose. 
Any overdose must be promptly reported to PPD within 24 hours. Overdose itself is not to be 
reported as an AE. However, any AEs associated with the overdose are to be reported in the 
relevant AE/SAE sections of the eCRF. 
In the event of an overdose, the investigator should: 
1. Contact the medical monitor immediately. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities for at 
least 3 days. Refer the participant to a higher level of care as clinically indicated. 
3. Document the quantity of the excess dose in the eCRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 50 
 
5.6 Blinding 
Allocation of participants to vaccine groups will proceed as described in Section 5.1. In the 
event of a quality assurance audit, auditors will be allowed access to study vaccine records at 
the study sites to verify that dispensing was performed accurately.  
In this open-label study, the study staff receiving, storing, dispensing, preparing, and 
administering the study interventions will be unblinded. Study and site personnel, including 
the investigator, study staff and participants will be unblinded.  
Preliminary reviews of available safety and immunogenicity data may be performed on an 
ongoing basis in an unblinded fashion. A statistical and programming team will perform 
2 planned interim analyses during the study (Section 7.7). Unblinded safety summaries will 
be provided to the SRT to inform study decisions for progressing enrollment between groups 
(Section 3.1.1). 
5.7 Compliance With Study Vaccine 
All participants will be vaccinated at the study site by the investigator or designee, under 
medical supervision. The date and time of study vaccine administration will be recorded in 
the source documents and in the eCRF. The dose of study vaccination and participant 
identification will be confirmed at the time of dosing by a member of the study site personnel 
other than the person administering the study vaccination.  
When the individual dose for a participant is prepared from a bulk supply, the preparation of 
the dose will be confirmed by a second member of the study site personnel.  
5.8 Prior, Concomitant, and Rescue Therapies 
5.8.1 Prior and Concomitant Therapy  
Use of all prior and concomitant medications and vaccinations within 6 months of screening 
will be recorded in the participant’s eCRF.  
All prior COVID-19 vaccines received (including those received more than 6 months before 
screening) and all COVID-19 vaccines received during the study will be recorded.  

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 51 
 
The minimum requirement is that drug name and the dates of administration are to be 
recorded. This will include all prescription drugs and vaccinations. In addition, any herbal 
products, vitamins, minerals, and over-the-counter medications taken within 2 weeks of study 
vaccination should also be recorded in the participant's eCRF. Any changes in concomitant 
medications also will be recorded in the participant’s eCRF throughout the study. 
5.8.2 Allowed Concomitant Therapy 
Any concomitant medication deemed necessary for the welfare of the participant during the 
study may be given at the discretion of the investigator. However, it is the responsibility of 
the investigator to ensure that details regarding the medication are recorded in full in the 
eCRF. 
Participants during this Phase 1 study will be allowed to receive a booster dose of a licensed 
or authorized COVID-19 vaccine, per national recommendations, if received at after the 
Day 29 visit. 
No concomitant medications will be provided by the sponsor or PPD. 
5.8.3 Rescue Medicine 
There are no known rescue medications for the IP; supportive care should be provided to 
participants as clinically indicated. 
5.9 Study Holding Rules 
The medical monitor, investigator, and SRT will continuously assess AEs against study 
holding rules (Table 5-2). 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 52 
 
Table 5-2 
Study Holding Rules 
Study Holding 
Rule 
Study Holding Rule Description 
Number of 
Participants Needed to 
Trigger a Study Hold 
1a 
Death or any life-threatening SAE regardless of causality 
≥1 
1b 
Any non-life-threatening SAE that cannot be reasonably 
attributed to a cause other than vaccination as per investigator 
or sponsor assessment 
≥1 
1c 
Necrosis at the injection site 
≥1 
1d 
Confirmed or suspect myocarditis or pericarditis events not 
clearly attributable to any cause other than study vaccine 
≥2 
2a 
Any same or similar Grade 3 related unsolicited events*, 
including but not limited to the identical MedDRA high-level 
term 
≥2 
2b 
Same Grade 3 solicited local or systemic AE in an 
investigational group 
≥3 
*  
Includes laboratory abnormalities of clinical relevance, symptomatic or not, as determined by the 
investigator.  
 
Study holding rules 1a, 1b, and 1c will be assessed by the investigators on a continuous basis. 
Study holding rules will lead to a hold of the vaccination in the entire study. Study holding 
rules 1d, 2a and 2b will be assessed by the SRT on an ongoing basis. A triggered study 
holding rule will lead to a hold of vaccination in the entire study. 
If the sponsor confirms that a stopping rule has been met, the following actions will be taken: 
1. The SRT (Section 11.1) will review all available safety data whenever any of the 
study holding rules are met. The SRT will recommend to the sponsor whether a 
cohort or group should be permanently stopped, modified, or continued unchanged. 
Medical judgment, considering all available safety data at the time of review, should 
be the basis for a recommendation to continue the study or not. 
2. The stopping rule will pause enrollment and study intervention administration for all 
dose levels and age groups.  
3. For all vaccinated participants, all other routine study activities, including ongoing 
data entry, reporting of AEs, participant reactogenicity eDiary completion, blood 
sample collection and participant follow-up will continue during the pause. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 53 
 
4. Ethical and regulatory authorities will be notified per local requirements. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 54 
 
6 Study Assessments and Procedures 
Before any study procedures are performed, all potential participants will be consented using 
an IRB/IEC-approved ICF. Additional procedural details related to the ICF, including 
educating participants on the symptoms and means of reporting suspected myocarditis or 
pericarditis, are provided in Section 9.3. Study assessments will be performed in an 
outpatient setting at qualified study sites.  
Refer to the SOE Table 13-1 for the full list of visits and assessments. Due to the ongoing 
pandemic, safety follow-up may be completed via televisits, as permitted by country 
regulations. 
6.1 Safety Assessments 
Safety will be assessed through the collection and evaluation of solicited and unsolicited AEs 
(Section 6.1.1.1.1), MAAEs (Section 6.1.1.1.1), SAEs (Section 6.1.1.1.2), and AESIs 
(Section 6.1.1.1.4). Safety will also be assessed by physical examinations, vital sign 
measurements, and clinical safety laboratory assessments.  
All suspected cases of COVID-19 in study participants will be diagnosed and clinically 
evaluated, which may require unscheduled study site visits and additional SARS-CoV-2 
laboratory testing (Section 6.1.2). Participant COVID-19 diagnosis and clinical evaluation 
may be performed by an outside medical provider following local standard of care. 
All suspected or confirmed cases of myocarditis or pericarditis will be diagnosed and 
clinically evaluated (Section 6.1.3).  
Any abnormal laboratory test results or other safety assessments (eg, physical examinations, 
vital sign measurements), including those that worsen from baseline or are clinically 
significant in the medical and scientific judgment of the investigator, are to be recorded as 
AEs or SAEs as applicable. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 55 
 
6.1.1 Adverse Events 
6.1.1.1 Definitions 
6.1.1.1.1 
Adverse Events 
The investigator is responsible for reporting all AEs that are observed or reported during the 
study, regardless of their relationship to the IP or their clinical significance. 
An AE is defined as any untoward medical occurrence in a participant enrolled into this study 
regardless of its causal relationship to the IP. Participants will be instructed to contact the 
investigator at any time after enrollment if any symptoms develop. 
A solicited AE is defined as an AE that is recorded by participants in an eDiary from Day 1 
through Day 7 in response to specific questions (Section 6.1.1.5). After study vaccination all 
participants will be instructed to record local and systemic solicited AE symptoms in an 
eDiary. Local solicited AEs will include injection site pain, redness, and swelling and 
lymphadenopathy (localized axillary, cervical or supraclavicular swelling or tenderness 
ipsilateral to the vaccination arm). Systemic solicited AEs will include fever, fatigue, 
headache, chills, myalgia, and arthralgia. Solicited local and systemic AEs will be used to 
assess reactogenicity and will be assigned a grade as described in Section 6.1.1.2.1. Any such 
AEs starting more than 7 days after vaccination will be captured as unsolicited AEs. 
An unsolicited AE is defined as any AE that is volunteered from the participant. Unsolicited 
AEs will be monitored for 28 days after vaccination. 
An MAAE is defined as an AE that results in a visit to a medical professional (eg, 
telemedicine visits, physician’s office visits, urgent care visits, emergency room visits, or 
hospitalization). 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 56 
 
6.1.1.1.2 
Serious Adverse Events 
An SAE is defined as any event that: 
• Results in death 
• Is immediately life-threatening 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
• Is an important medical event that may not result in death, be life-threatening, or 
require hospitalization but, based upon appropriate medical judgment, jeopardizes the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. All events of myocarditis and 
pericarditis will be considered important medical events and SAEs (Section 6.1.3).  
6.1.1.1.3 
Suspected Unexpected Serious Adverse Reactions 
A SUSAR is defined as a serious adverse reaction, the nature or severity of which is not 
consistent with the applicable product information (eg, IB for an unapproved IP). 
6.1.1.1.4 
Adverse Events of Special Interest 
An AESI (serious or nonserious) is defined as an AE or SAE of scientific and medical 
concern specific to the sponsor’s product or program, for which ongoing monitoring and 
rapid communication by the investigator to the sponsor could be appropriate (ICH E2F; 
CIOMS VI). 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 57 
 
For this study, prespecified AESIs will include the following events: 
• Virologically confirmed COVID-19 (see Section 6.4 for definition) 
• Potential immune-mediated disorders (Section 13.4) 
• Anaphylaxis or severe hypersensitivity within 24 hours after study vaccine 
administration 
• Myocarditis 
• Pericarditis  
Refer to Section 6.1.1.3.1 for reporting AESIs. 
6.1.1.2 Eliciting and Documenting Adverse Events 
Adverse events will be reported throughout the study. Nonserious AEs will be reported from 
the time of the administration of IP until 28 days after the administration of IP; SAEs will be 
reported from the time the participant signs the ICF until exit from the study. 
If the investigator learns of any SAE, including a death, at any time after a participant has 
been discharged from the study, and he/she considers the event to be reasonably related to the 
IP, the investigator must notify PPD Pharmacovigilance within 24 hours of learning of the 
event (Section 6.1.1.3.1). 
At every study visit, participants will be asked a standard nonleading question to elicit any 
medically related changes in their well-being. 
In addition to participant observations, AEs identified from any study data (eg, laboratory 
values, physical examination findings) or identified from review of other documents (eg, 
participant eDiaries) that are relevant to participant safety will be documented on the AE 
page in the eCRF. 
As described in Section 6.1.1.1.1, participant eDiaries will be used to collect solicited AEs. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 58 
 
6.1.1.2.1 
Assessment of Intensity 
The intensity, or severity, of an AE refers to the extent to which an AE affects the 
participant’s daily activities.  
Solicited AEs will be graded in intensity by the participant. 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 judgment. 
The intensity of the following solicited events will be assessed as described in Table 6-1. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 59 
 
Table 6-1 
Intensity Scales for Solicited Symptoms 
Event 
Intensity 
Grade 
Parameter 
Pain at administration site 
0 
None 
1 
Mild: Any pain neither interfering with nor preventing normal everyday 
activities 
2 
Moderate: Painful when limb is moved and interferes with everyday 
activities 
3 
Severe: Significant pain at rest. Prevents normal everyday activities 
Redness at administration site 
0 
<2.5 cm 
1 
2.5 – 5 cm 
2 
5.1 – 10 cm 
3 
>10 cm 
Swelling at administration site 
0 
<2.5 cm 
1 
2.5 – 5 cm and does not interfere with activity 
2 
5.1 – 10 cm or interferes with activity 
3 
>10 cm or prevents daily activity 
Lymphadenopathya 
0 
None 
1 
Mild: No interference with activity 
2 
Moderate: Some interference with daily activity or requires repeated use 
of non-narcotic pain reliever 
3 
Severe: Prevents daily activity or requires use of narcotic pain reliever 
Temperatureb 
0 
<38.0°C or <100.4°F 
1 
38.0 – 38.4°C or 100.4 – 101.1°F 
2 
38.5 – 38.9°C or 101.2 – 102.0°F 
3 
>38.9°C or >102.0°F 
Headache 
0 
Normal 
1 
Mild: Headache that is easily tolerated 
2 
Moderate: Headache that interferes with normal activity 
3 
Severe: Headache that prevents normal activity 
Fatigue 
0 
Normal 
1 
Mild: Fatigue that is easily tolerated 
2 
Moderate: Fatigue that interferes with normal activity 
3 
Severe: Fatigue that prevents normal activity 
Myalgia 
0 
Normal 
1 
Mild: No interference with daily activity 
2 
Moderate: Interferes with daily activity 
3 
Severe: Prevents daily activity 
Arthralgia 
0 
Normal 
1 
Mild: No interference with daily activity 
2 
Moderate: Interferes with daily activity 
3 
Severe: Prevents daily activity 
Chills 
0 
None 
1 
Mild sensation of cold; shivering; chattering of teeth 
2 
Moderate tremor of the entire body; narcotics indicated 
3 
Severe or prolonged, not responsive to narcotics 
a. 
Defined as localized axillary, cervical or supraclavicular swelling or tenderness ipsilateral to the vaccination arm. 
b. 
Refer to Section 6.1.4 for the definition of fever.  

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 60 
 
The intensity of AEs will be assigned to one of the following categories: 
• Grade 1 (Mild): An AE that is easily tolerated by the participant, causing minimal 
discomfort, and not interfering with everyday activities. 
• Grade 2 (Moderate): An AE that is sufficiently discomforting to interfere with normal 
everyday activities. 
• Grade 3 (Severe): An AE that prevents normal, everyday activities. In adults, such an 
AE would, for example, prevent attendance at work and would necessitate the 
administration of corrective therapy. 
An AE that is assessed as Grade 3 (severe) should not be confused with an SAE. Grade 3 is a 
category used for rating the intensity of an event; and both AEs and SAEs can be assessed as 
Grade 3. An event is defined as “serious” when it meets the definition of an SAE 
(Section 6.1.1.1.2). 
Refer to Section 6.1.2 for grading of laboratory-associated AEs. 
Changes in the severity of an AE should be documented to allow an assessment of the 
duration of the event at each level of intensity. Adverse events characterized as intermittent 
do not require documentation of onset and duration of each episode. 
6.1.1.2.2 
Assessment of Causality 
The investigator’s assessment of an AE’s relationship to the IP is part of the documentation 
process, but it is not a factor in determining what is or is not reported in the study. If there is 
any doubt as to whether a clinical observation is an AE, the event should be reported. 
The relationship or association of the IP in causing or contributing to the AE will be 
characterized using the following classification and criteria: 
YES: 
There is a reasonable possibility that the IP contributed to the AE. 
NO: 
There is no reasonable possibility that the AE is causally related to the 
administration of IP. There are other, more likely causes and administration of 
IP is not suspected to have contributed to the AE. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 61 
 
6.1.1.3 Reporting Adverse Events 
All AEs reported or observed during the study will be recorded on the AE page in the eCRF. 
Information to be collected includes, but is not limited to, the following: 
• Event term 
• Investigator-specified assessment of severity and causality to IP 
• Seriousness/grade 
• Time of onset of the event 
• Time of resolution of the event 
• Any required treatment or evaluations 
• Outcome 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, 
reactions to concurrent medications, or progression of disease states must also be reported. 
All AEs will be followed to adequate resolution. MedDRA will be used to code all AEs. 
Any medical condition that is present at the time that the participant is screened but does not 
deteriorate should not be reported as an AE. However, if it deteriorates at any time during the 
study, it should be recorded as an AE. 
6.1.1.3.1 
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest 
Any AE that meets the definition of an SAE (Section 6.1.1.1.2) must be reported to PPD 
Pharmacovigilance within 24 hours after site personnel first learn of the event. Events should 
be captured electronically in the EDC system; however, if the EDC is unavailable, a backup 
paper option is available and this form can be faxed to the fax number listed below. 
 
SAE Hotline:  
+1-800-201-8725 
 
Fax:  
 
+1-888-488-9697 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 62 
 
Any AE that meets AESI criteria (Section 6.1.1.1.4) must be reported to PPD 
Pharmacovigilance within 24 hours after site personnel first learn of the event.  
If the EDC is unavailable and a faxed form is used to report an SAE or AESI, the site should 
update the EDC with exactly the same information reported on paper (by fax) as soon as 
possible after the EDC becomes available again.  
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of an IP under clinical investigation. The sponsor will 
comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information from the sponsor will review and then file it as appropriate and 
will notify the IRB/IEC according to local requirements.  
6.1.1.3.2 
Reporting Suspected Unexpected Serious Adverse Reactions 
The sponsor will promptly evaluate all SUSARs against cumulative product experience to 
identify and expeditiously communicate possible new safety findings to investigators, 
IRB/IECs, and applicable health authorities based on applicable legislation. 
Reporting requirements will also be based on the investigator’s assessment of causality and 
seriousness, with allowance for upgrading by the sponsor as needed.  
Cases of myocarditis or pericarditis (as defined in Section 6.1.3) occurring in temporal 
association with vaccination of study participants within 4 weeks after vaccination will be 
reported as SUSARs, as required by 21 CFR 312.32. 
6.1.1.4 Follow-Up of Participants Reporting Adverse Events 
All AEs must be reported in detail on the appropriate page in the eCRF and followed to 
satisfactory resolution, until the investigator deems the event to be chronic or not clinically 
significant, the event is considered stable, or the participant is lost to follow-up. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 63 
 
6.1.1.5 eDiary 
An eDiary will be used after study vaccination for participants to record solicited local 
injection site and systemic AEs during the 7 days after study vaccination for reactogenicity 
assessment. Study site personnel will instruct the participants on use of the eDiary. The site 
staff will review the eDiary data at Days 4 and 8. 
Participants will be instructed to contact the study site as needed at any time point during the 
study with safety concerns. Any AE that meets the definition of an SAE (Section 6.1.1.1.2) 
must be reported to PPD Pharmacovigilance immediately (ie, within 24 hours) after site 
personnel first learn of the event (Section 6.1.1.3.1). 
6.1.2 SARS-CoV-2 Infection and COVID-19 Assessment and Definitions 
Vaccine efficacy will not be evaluated in this study, but all laboratory-confirmed 
asymptomatic SARS-CoV-2 infections should be reported by the participant and documented 
as AEs, while virologically confirmed cases of COVID-19 are reported as AESIs 
(Section 6.1.1.1.4). Participant COVID-19 diagnosis and clinical evaluation may be 
performed by an outside medical provider following local standard of care. Any available 
isolate genotyping results will also be requested. Participants will be instructed to inform the 
investigator in the event of a positive SARS-CoV-2 diagnostic test. Serology testing for 
SARS-CoV-2 N protein will be performed prevaccination and postvaccination to monitor for 
undetected SARS-CoV-2 infections at the time points specified in the SOE (Table 13-1). 
All participants with suspected COVID-19 may have an unscheduled visit for suspected 
COVID-19, as detailed in the SOE (Table 13-1). At this visit, participants will undergo the 
following assessments:  
• Medical history  
• SARS-CoV-2 RT-PCR (nasopharyngeal or mid-turbinate swab)  
• Physical examination  
• Vital sign measurements 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 64 
 
• Review of adverse events  
• Concomitant medication/vaccination 
Participants with confirmed COVID-19 may have an unscheduled COVID-19 convalescent 
visit as detailed in the SOE (Table 13-1). At this visit, participants will undergo the following 
assessments:   
• Medical history 
• Physical examination  
• Vital sign measurements  
• COVID-19 evaluation  
• Review of adverse events 
• Concomitant medication/vaccination 
To complete the COVID-19 evaluation, the investigator will review the history of the 
participants, including medical records to define the severity of COVID-19. Alternatively, an 
investigator may utilize participant medical records from non-study care medical providers to 
verify whether a participant was infected with SARS-CoV-2. 
Any confirmed cases of SARS-CoV-2 infection or COVID-19 during the study will be 
assigned one of the following definitions: 
Asymptomatic 
SARS-CoV-2 
infection: 
Laboratory-confirmed SARS-CoV-2 N protein seroconversion 
without any of the following symptoms: fever or chills, cough, 
shortness of breath or difficulty breathing, fatigue, muscle or body 
aches, headache, new loss of taste or smell, sore throat, congestion 
or runny nose, nausea or vomiting, diarrhea 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 65 
 
COVID-19: 
Virologically confirmed SARS-CoV-2 by RT-PCR with 1 or more 
of the following symptoms: fever or chills, cough, shortness of 
breath or difficulty breathing, fatigue, muscle or body aches, 
headache, new loss of taste or smell, sore throat, congestion or 
runny nose, nausea or vomiting, diarrhea 
Severe COVID-19: 
Virologically confirmed SARS-CoV-2 infection with any 1 of the 
following: 
• Clinical signs at rest indicative of severe systemic illness 
(respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, 
SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 
< 300 mm Hg) 
• Respiratory failure (defined as needing high-flow oxygen, 
noninvasive ventilation, mechanical ventilation, or ECMO) 
• Evidence of shock (systolic blood pressure <90 mmHg, 
diastolic blood pressure <60 mmHg, or requiring vasopressors) 
• Significant acute renal, hepatic, or neurologic dysfunction 
• Admission to a hospital or an intensive care unit 
• Death 
6.1.3 Myocarditis and Pericarditis Assessment and Definitions 
All suspected or confirmed cases of myocarditis or pericarditis will be diagnosed and 
clinically evaluated.  
Participants reporting acute chest pain, shortness of breath, or other symptoms of myocarditis 
or pericarditis within 4 weeks after vaccination must be evaluated by a cardiologist with 
evaluation and management following current practice guidelines (eg, American Heart 
Association or local standard of care). Functional cardiac evaluation (eg, stress test 
echocardiogram) to detect potential late onset of cardiac function impairment must also be 
performed. Suspected myocarditis includes (but is not necessarily limited to) the following: 
• New ECG abnormality that a cardiologist judges consistent with probable or possible 
myocarditis or pericarditis, including the following: 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 66 
 
o Sustained atrial or ventricular arrhythmias 
o Second degree Mobitz Type II or worse atrioventricular block, new bundle 
branch block 
o Diffuse ST-segment elevation or PR-segment depression, compatible with 
pericarditis  
• An abnormal troponin I value that is confirmed abnormal on repeat testing 
Participants will have safety follow-up until resolution of symptoms and/or of abnormal test 
findings. 
6.1.3.1 Surveillance for Asymptomatic Myocarditis and Pericarditis 
At the Day 8 visit, all participants will be assessed by 12-lead ECG for evidence of 
asymptomatic myocarditis or pericarditis, based on evidence that rare cases of myocarditis or 
pericarditis have occurred most frequently within 7 days of vaccination (CDC 2022a). All 
participants will also have a 12-lead ECG examination at screening to provide a baseline for 
comparison. 
Asymptomatic acute myocarditis/pericarditis is defined as electrocardiographic changes 
suggestive of acute myocardial injury occurring in an asymptomatic participant within 
4 weeks after administration of a COVID-19 mRNA vaccine, if other causes of acute cardiac 
disease are excluded. Electrocardiogram changes suggestive of acute myocardial injury and 
consistent with probable or possible myocarditis or pericarditis would include sustained atrial 
or ventricular arrhythmias, second degree Mobitz Type II or worse atrioventricular block, 
new bundle branch block, or diffuse ST-segment elevation or PR-segment depression. If any 
of these ECG changes are detected at the surveillance ECG occurring at the Day 8 visit, the 
findings will be reviewed by a cardiologist. If a diagnosis of myocarditis or pericarditis is 
confirmed, then the subject will be further evaluated and receive cardiology consultation, 
including cardiac enzyme assessment, echocardiography, or other assessments deemed 
clinically warranted by the treating clinician. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 67 
 
6.1.4 Clinical Safety Laboratory Assessments 
The following laboratory assessments will be performed at the time points specified in the 
SOE (Table 13-1): 
Hematology: 
Basophils, eosinophils, erythrocytes (red blood cells), hemoglobin, 
leukocytes (white blood cells), lymphocytes, monocytes, 
neutrophils, and platelets 
Chemistry: 
Alanine aminotransferase, alkaline phosphatase, aspartate 
aminotransferase, total and direct bilirubin, blood urea nitrogen, 
and creatinine  
SARS-CoV-2: 
• SARS-CoV-2 N protein serology (Ab) prevaccination and 
postvaccination to monitor for asymptomatic SARS-CoV-2 
infections  
• SARS-CoV-2 RT-PCR (nasopharyngeal or mid-turbinate swab) 
HIV/HBV/HCV 
• Hepatitis B surface antigen test 
• HIV 4th generation antigen/Ab test 
• Anti-HCV Ab test (and RNA test if anti-HCV Ab positive)  
Other analyses: 
Female participants of childbearing potential:  
β-human chorionic gonadotropin (serum test at screening; urine test 
at additional time points)  
Serum FSH, to confirm postmenopausal status per Appendix 13.2 
The clinical safety laboratory assessments will be performed by a local or central laboratory 
as detailed in the Laboratory Manual. Screening laboratory tests may be repeated once for 
enrollment requirements.  
The investigator must review the laboratory reports, document this review, and record any 
clinically relevant changes occurring during the study. If the laboratory reports are not 

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 6 8  
 
tra nsferre d ele ctr o nic all y, t h e v al u es m ust b e file d wit h t h e s o urc e i nf or mati o n (i n cl u di n g 
refere n c e ra n g es). A n y cli nic all y rele va nt la b orat or y res ults s h o ul d b e re p orte d as a n A E or 
S A E a n d gra d e d wit h t h e A E i nte nsit y gra di n g s c ale ( Se cti o n  6. 1.1. 2. 1 ).  
All la b orat or y tests wit h v al u es c o nsi dere d cli nic all y si g nifica ntl y a n d a b n or mal d uri n g 
p artici p ati o n i n t h e st u d y s h o ul d b e e v al uate d f or t h e eti ol o g y a n d s h o ul d b e re p eate d u ntil 
t h e v al u es ret ur n t o n or m al or b as eli n e or are n o l o n ger c o nsi d ere d cli nic all y si g nific a nt b y 
t h e i n v esti g at or or m e dic al m o nit or. If s u c h v al u es d o n ot ret ur n t o n or m al/ b as eli n e wit hi n a 
p eri o d of ti m e j u d g e d re as o na ble b y t h e i n v esti g at or, t h e s p o ns or s h o ul d b e n otifie d.  
All p r ot o c ol-re q uire d la b orat or y ass ess me nts m ust b e c o n d u cte d i n a c c or d a nc e wit h t h e 
La b orat or y Ma n u al. If la b orat or y v al u es fr o m n o n -pr ot o c ol -s p ecifie d la b orat or y ass ess m e nts 
p erf or m e d at t h e l o c al st u d y site la b orat or y re q uire a c h a n ge i n p artici p a nt m a n a ge m e nt or 
are c o nsi d ere d cli nic all y si g nific a nt b y t h e i n v esti g at or, t h e n t h e res ults m ust b e re c or d e d i n 
t h e e C R F. 
A m a xi m u m of 1 2 0 m L of bl o o d will b e c olle cte d p er p artici p a nt p er visit. T his m a y i n cl u d e 
5 0  m L of bl o o d c olle cte d at 3 visits f or p artici p a nt s i n Part A e nr olle d at sites 
 
 T h e m a xi m u m a m o u nt of bl o o d c olle cte d 
o v er t h e 6 -m o nt h d urati o n of t h e st u d y is a p pr o xi m atel y 5 0 0  m L . Re p e at or u ns c h e d ule d 
s a m ples m a y b e ta k e n f or s afet y re as o ns or f or te c h nic al iss u es wit h t h e s a m ples.  
6. 1. 5 P h ysic al E x a mi n ati o ns  
A c o m plete p h ysic al e x a mi nati o n i n cl u di n g h ei g ht a n d w ei g ht will b e p erf or m e d at s cre e ni n g 
as i n dic ate d i n t h e S O E (Ta b le  1 3 - 1). S y m pt o m-dire cte d p h ysic al e x a mi n ati o ns will b e 
p erf or m e d as cli nic all y i n dic ate d at s u bs e q u e nt visits.  
6. 1. 6 Vit al Si g ns  
Vital si g n m e as ure m e nts will b e p erf or m e d at t h e ti m e p oi nts i n dic ate d i n t h e S O E 
(Ta b le  1 3 - 1). Vital si g ns will b e m e as ure d i n a sitti n g p ositi o n after at le ast 5 mi n utes of rest 
a n d will i n cl u d e te m p erat ure, p uls e, o x y g e n s at urati o n  by p uls e o xi metr y , res pirati o n rate, 
s yst olic a n d diast olic bl o o d press ure. Vital si g n m e as ure m e nts s h o ul d b e c olle cte d b ef ore a n d 
after st u d y v a c ci n ati o n o n D a y  1. Vital si g n m e as ure m e nts s h o ul d als o b e p erf or m e d b ef ore 
C CI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 69 
 
any scheduled blood collection. Per standard clinical practice, vital sign measurements may 
be repeated per investigator discretion. 
Body temperature will be measured throughout the study. Participants who are febrile 
(temperature ≥38.0°C or ≥100.4°F) before study vaccination should be rescheduled for study 
vaccination within the relevant window period of screening. 
6.2 Pregnancy Reporting 
Any pregnancy that occurs during study participation must be reported using the PPD paper 
pregnancy report form (Section 13.2) faxed to the same fax number as may be used for 
backup SAE reports (Section 6.1.1.3.1). To ensure participant safety, site personnel must 
report each pregnancy to PPD within 24 hours of learning of its occurrence. The pregnancy 
must be followed to determine outcome (including spontaneous miscarriage, elective 
termination, normal birth, or congenital abnormality) and status of mother and child, even if 
the participant was discontinued from the study. Pregnancy complications and elective 
terminations for medical reasons must be reported as an AE or SAE. Spontaneous 
miscarriages must be reported as an SAE. 
Any SAE occurring in association with a pregnancy, brought to the investigator’s attention 
after the participant has completed the study, and considered by the investigator as possibly 
related to the study vaccine, must be promptly reported to PPD as described in 
Section 6.1.1.3.1. 
6.3 Assessment of Immune Responses 
Humoral and cellular immunogenicity assessments will be performed at sponsor-designated 
laboratories as detailed in the Study Manual. Blood samples will be collected at the time 
points indicated in the SOE (Table 13-1).  
 
 
 
 
CCI

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 7 0  
 
 
 
6. 3. 1 Assess me nt of H u m or al I m m u ne Re s p o nses 
6 . 3. 2 Assess me nt of Cell u l ar I m m une Res p o nses  
6. 4 Ge netics 
H u m a n g e n etics will n ot b e ass ess e d i n t his st u d y.  
C CI
C CI
C CI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 71 
 
7 Statistical Considerations 
Statistical analysis will be performed using SAS software Version 9.4 or later. Details of the 
statistical analyses, methods, and data conventions are described in the SAP. No formal 
significance testing will be performed. 
7.1 
Statistical Hypothesis 
There is no hypothesis testing in this study; where statistical methods are applied, the 
emphasis will be on estimation with 95% CIs. 
7.2 Sample Size Determination 
The sample size is based on clinical considerations to inform dose regimen decisions for 
continued clinical development.  
Approximately 180 participants will be enrolled in this Phase 1 study, 5 dose-level cohorts 
(Cohorts 1 to 5) each comprising 2 age groups. Cohorts 6 and 7 will comprise 1 age group 
(younger adults). With 30 participants in each cohort, there is a 78.5% probability to observe 
at least 1 AE if the incidence rate is 5% and a 95.8% probability to observe at least 1 AE if 
the incidence rate is 10%. With 30 participants in each cohort, a 10% unevaluable rate for 
immunogenicity results, and a standard deviation of 0.45 for log10-transformed increase from 
Day 1, the ratio of the upper limit of a 2-sided 95% CI and the point estimate of GMI is 1.5. 
The sample size in Cohorts 6 and 7 is based on clinical feasibility rather than on statistical 
rationale. With 15 participants in each cohort, there is a 79.4% probability to observe at least 
one AE if the true incidence rate is 10%. 
7.3 Analysis Sets 
The following analysis sets will be used in the statistical analyses:  
• Enrolled Set: All eligible participants who gave informed consent, regardless of the 
participants’ treatment status in the study. 
• Safety Set: All participants who receive 1 dose of IP. The Safety Set will be used for 
all analyses of safety. Data are analyzed according to treatment received. The Safety 
Set will be used for safety analyses. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 72 
 
• Per Protocol Immunogenicity Set: The PPI Set includes all eligible participants who 
received a dose of study IP per protocol and who have values for predose and Day 15 
neutralizing Ab titers against pseudovirus bearing S protein from the Omicron variant 
of SARS-CoV-2. Results from a blood sample deviating from the dosing or blood 
sampling schedule (Table 13-1) and results from a blood sample after intercurrent 
conditions that may interfere with immunogenicity (eg, laboratory-confirmed 
SARS-CoV-2 infections or immunosuppressive or immunodeficient conditions) or 
after a prohibited concomitant medication/vaccination (COVID-19 vaccination) will 
be excluded from the PPI Set. The analysis will be done according to the dose that 
participants received at Visit 1. The PPI Set will be used for the immunogenicity 
analyses. 
7.4 Description of Subgroups to Be Analyzed 
Subgroup analyses for safety and immunogenicity endpoints may be performed in selected 
groups and will be described in the SAP. 
7.5 Statistical Analysis Methodology 
7.5.1 General Considerations 
All analyses will be performed by treatment group, combining the younger and older adult 
participants together, unless specified otherwise. For categorical variables, frequencies and 
percentages will be presented. Continuous variables will be summarized using descriptive 
statistics (number of participants, mean, median, standard deviation, minimum, and 
maximum). 
7.5.2 Analysis of the Primary Safety Endpoints 
The primary safety endpoints as detailed in Section 2 will be analyzed as described in the 
SAP. Laboratory abnormalities will be graded for severity following the FDA toxicity 
grading table (Section 13.5). For all safety endpoints, descriptive summary statistics will be 
provided for the Safety Set. Safety data listings will also be provided. 
Refer to Section 13.3 for details on Bayesian logistic regression used during the safety 
monitoring of the study. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 73 
 
In addition to the planned summary of SAEs throughout the study, any SAEs that are 
reported will also be summarized within 28 days of study vaccine administration. 
7.5.3 Analysis of Secondary Immunogenicity Endpoints 
The secondary endpoints detailed in Section 2 will be analyzed as described in the SAP. 
Listings will be provided, and graphical presentations will be considered as needed. In 
addition to descriptive statistics for continuous variables (Section 7.5.1), confidence intervals 
and interquartile ranges will also be provided for continuous immunogenicity variables.  
Seroresponse rate with 95% CI, GMT of specific Ab with corresponding 95% CI at each 
timepoint and GMI from baseline of specific Ab with corresponding 95% CI at each 
postbaseline timepoint over pre-injection baseline will be provided by group. The GMT, the 
GMI, and their 95% CI in all cohorts will be analyzed using an ANCOVA with treatment and 
age group as fixed factors and prevaccination baseline value as a covariable. 
7.5.4 Analyses of Exploratory Immunogenicity Endpoints 
The exploratory endpoints detailed in Section 2 will be analyzed as described in the SAP. For 
continuous immunogenicity variables, summary statistics, CIs, and interquartile ranges will 
be provided. Immunogenicity data listings will also be provided and graphical presentations 
will be considered as needed.  
7.5.5 Safety Analyses 
Safety and reactogenicity are the primary study objectives; thus, refer to Section 7.5.2 for the 
analysis description. 
7.5.6 Other Analyses 
Summary statistical analyses will be provided for demographics and vital signs at baseline. 
Subgroup analysis for safety and immunogenicity endpoints may be performed in selected 
groups and will be described in the SAP. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 74 
 
7.6 Handling of Missing Data 
Details regarding handling of missing safety, reactogenicity, and immunogenicity data will be 
described in the SAP. 
7.7 Interim Analyses 
There are 2 planned interim analyses of safety and immunogenicity data for at least 
neutralizing Ab titers against SARS-CoV-2 WT, Omicron, and Delta variant pseudoviruses. 
The first interim analysis will be performed after all participants in Cohorts 1, 2, and 3 have 
completed the Day 15 study visit. The second interim analysis will be performed after all 
participants in Cohorts 4 and 5 have completed the Day 15 study visit. Details of these 
interim analyses will be described in the SAP. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 75 
 
8 Data Quality Assurance 
This study will be conducted according to the ICH E6(R2) risk and quality processes 
described in the applicable procedural documents. The quality management approach to be 
implemented in this study will be documented and will comply with the current ICH 
guidance on quality and risk management. The sponsor assumes accountability for actions 
delegated to other individuals (eg, contract research organizations). 
8.1 Data Management 
As part of the responsibilities assumed by participating in the study, the investigator agrees to 
maintain adequate case histories for the participants treated as part of the research under this 
protocol. The investigator agrees to maintain accurate eCRFs and source documentation as 
part of the case histories. These source documents may include eDiary information, 
laboratory reports, etc. 
Investigative site personnel will enter participant data into an EDC system. The analysis data 
sets will be a combination of these data and data from other sources (eg, laboratory data). 
Clinical data management will be performed in accordance with applicable PPD standards 
and data cleaning procedures to ensure the integrity of the data (eg, removing errors and 
inconsistencies in the data). Adverse event terms will be coded using MedDRA, an internal 
validated medical dictionary, and concomitant medications will be coded using WHODRUG. 
After database lock, each study site will receive electronic files of study media (eCRF data) 
from PPD, including full discrepancy and audit history. Additionally, electronic files of all of 
the study site’s data from the study will be created and sent to GSK Biologicals SA for 
storage. PPD will maintain a duplicate copy in their electronic records. In all cases, 
participant initials will not be collected or transmitted to the sponsor.  

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 76 
 
9 Ethics 
9.1 Independent Ethics Committee or Institutional Review Board 
Federal regulations and the ICH guidelines require that approval be obtained from an 
IRB/IEC before human participation in research studies. Before study onset, the protocol, 
informed consent, advertisements to be used for the recruitment of study participants, and 
any other written information regarding this study to be provided to the participant must be 
approved by the IRB/IEC. Documentation of all IRB/IEC approvals and of the IRB/IEC 
compliance with ICH harmonised tripartite guideline E6(R2): GCP will be maintained by the 
site and will be available for review by the sponsor or its designee. 
The IRB/IEC approval should be signed by the IRB/IEC chairman or designee and must 
identify the IRB/IEC name and address, the clinical protocol by title or protocol number or 
both, and the date approval or a favorable opinion was granted. 
The investigator is responsible for providing written summaries of the progress and status of 
the study at intervals not exceeding 1 year or otherwise specified by the IRB/IEC. The 
investigator must promptly supply the sponsor or its designee, the IRB/IEC, and, where 
applicable, the institution, with written reports on any changes significantly affecting the 
conduct of the study or increasing the risk to participants. 
9.2 Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki, ICH GCP, and all applicable regulations. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 77 
 
9.3 Participant Information and eConsent 
Documented informed consent, in compliance with regulatory authority regulations and US 
Title 21 CFR Part 50, shall be obtained from each participant before entering the study or 
performing any unusual or nonroutine procedure that involves risk to the participant. Consent 
may be collected through a digital method or remote solution if allowed by country and site 
regulations. Informed consent will ideally be obtained via eConsent with a backup paper 
consent option if needed. If any institution-specific modifications to study-related procedures 
are proposed or made by the site, the consent should be reviewed by the sponsor or its 
designee or both before IRB/IEC submission. Once reviewed, the consent will be submitted 
by the investigator to the IRB/IEC for review and approval before the start of the study. If the 
ICF is revised during the course of the study, all active participants must be reconsented 
using the revised form. 
Before recruitment and enrollment, each prospective participant will be given a full 
explanation of the study, be allowed to read the approved ICF, and have any questions 
answered. As part of the consent process, participants will be provided with educational 
materials describing the symptoms of myocarditis and pericarditis and guidance on 
contacting study personnel and seeking medical care if any of these symptoms occur. Once 
the investigator is assured that the participant understands the implications of participating in 
the study, the participant will be asked to give consent to participate in the study by signing 
the ICF via eConsent or a backup paper option. The authorized person obtaining the informed 
consent also documents this on the ICF. 
The ICF will contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research (if applicable) and explain/address the exploratory 
research portion of the study. Participant medical records need to state that documented 
informed consent was obtained. 
For eConsent, the original signed version of the ICF is retained within the eConsent platform, 
and downloaded versions are provided to the participant and for the investigator records. In 
the event a backup paper consent is used, the investigator shall retain the signed original 
ICF(s) and give a copy of the signed original form to the participant. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 78 
 
10 Investigator’s Obligations 
The following administrative items are meant to guide the investigator in the conduct of the 
study but may be subject to change based on industry and government standard operating 
procedures, working practice documents, or guidelines. Changes will be reported to the 
IRB/IEC but will not result in protocol amendments. 
10.1 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain participant confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the written 
permission of the participant, except as necessary for monitoring and auditing by the sponsor, 
its designee, the FDA, or the IRB/IEC. 
The investigator and all employees and coworkers involved with this study may not disclose 
or use for any purpose other than performance of the study any data, record, or other 
unpublished, confidential information disclosed to those individuals for the purpose of the 
study. Prior written agreement from the sponsor or its designee must be obtained for the 
disclosure of any said confidential information to other parties. 
10.2 Data Protection 
All personal data collected related to participants, investigators, or any person involved in the 
study, which may be included in the sponsor’s databases, shall be treated in accordance with 
local data protection law.  
Data collected must be adequate, relevant, and not excessive, in relation to the purposes for 
which they are collected. Each category of data must be properly justified and in line with the 
study objective. 
10.3 Financial Disclosure and Obligations 
Investigators are required to provide financial disclosure information to allow the sponsor to 
submit the complete and accurate certification or disclosure statements required under 
21 CFR 54. In addition, the investigator must provide to the sponsor a commitment to 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 79 
 
promptly update this information if any relevant changes occur during the course of the 
investigation and for 1 year after the completion of the study. 
Neither the sponsor nor PPD is financially responsible for further testing or treatment of any 
medical condition that may be detected during the screening process. In addition, in the 
absence of specific arrangements, neither the sponsor nor PPD is financially responsible for 
further treatment of the participant’s disease. 
10.4 Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 
Section 8.2 and Title 21 of the CFR by providing all essential documents. 
10.5 Study Conduct 
The investigator agrees that the study will be conducted according to the principles of ICH 
E6(R2). The investigator will conduct all aspects of this study in accordance with all 
national, state, and local laws or regulations. Study information from this protocol will be 
posted on publicly available clinical trial registers before enrollment of participants begins. 
The investigator agrees to conduct the study as outlined in this protocol in accordance with 
ICH E6(R2) and all applicable guidelines and regulations. 
10.6 Adverse Events and Study Report Requirements 
The investigator agrees to submit reports of SAEs to the sponsor and/or IRB/IEC according 
to the timeline and method outlined in the protocol. In addition, the investigator agrees to 
submit annual reports to the study site IRB/IEC as appropriate. 
10.7 Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the 
institution; the investigator/institution should provide the IRB/IEC with a summary of the 
study’s outcome and the sponsor and regulatory authority(ies) with any reports required. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 80 
 
10.8 Records Retention 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the IP. These documents should be retained for a 
longer period, however, if required by the applicable regulatory requirements or by an 
agreement with the sponsor. It is the responsibility of the sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained. No records 
may be transferred to another location or party without written notification to the sponsor. 
10.9 Publications and Results Disclosures 
During or after completion of the study, the data may be considered for reporting at a 
scientific meeting, publication in a scientific journal, or other public format. The procedures 
and timing for reporting at a scientific meeting, publication in a scientific journal, or other 
public format will be in accordance with GSK policy and the sponsor has final approval 
authority over all such issues. In these cases, the sponsor will be responsible for these 
activities and will work with the investigators to determine how the manuscript(s) is written 
and edited, the number and order of authors, the publication to which it will be submitted, 
and other related issues. 
Data are the property of the sponsor and cannot be published without prior authorization 
from the sponsor, but data and publication thereof will not be unduly withheld. 

Gl ax o S mit h Kli ne Bi ol o gic als S A   
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S - CO V2 -0 1 2 B S T) A men d ment 2  
2 6 J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 8 1  
 
1 1  St u d y M a n a ge me nt  
T h e st u d y a d mi nistrati v e str u ct ure will i n cl u d e a n S R T, a c o ntra ct res e arc h or g a niz ati o n 
( P P D, p art of T h er m o Fis h er Scie ntific), a n d t hir d p art y v e n d ors.  
1 1. 1 S afet y Re vie w Te a m  
T h e S R T will b e a n i nter n al te a m, wit h re pres e ntati v es fr o m b ot h G S K a n d  
.  T h e r ole 
of t h e S R T i n d e ci di n g d os e es c alati o n is d es cri b e d i n Se cti o n  3. 1. 1 . I n a d diti o n, t h e S R T will 
re vie w s afet y a n d i m m u n o ge nicit y d ata d uri n g t h e pla n n e d i nteri m a n al ys es a n d w h e ne ver 
a n y st u d y h ol di n g r ules are m et ( Se cti o n  5. 9 ). T h e S R T m a y als o re c o m m e n d t o p er m a n e ntl y 
st o p e nr oll m e nt i n a gr o u p. Gr o u ps m a y b e dr o p pe d at a n y ti m e d uri n g t h e st u d y if a n 
u nfa v ora ble s afet y pr ofile is o bs er ve d i n t h at gr o u p or b as e d o n s afet y or i m m u n o g e nicit y 
d ata fr o m ot h er gr o u ps. T h e S R T will re vie w i nteri m a n al ysis d ata.  
Bas e d o n S R T re vie w a n d re c o m m e n dati o ns, t h e s p o ns or m a y dr o p d os e gr o u ps at a n y ti m e 
d uri n g t h e st u d y if a n u nfa v ora ble s afet y pr ofile is o bs er ve d i n t h at gr o u p or b as e d o n s afet y 
or i m m u n o g e nicit y d ata fr o m ot h er gr o u ps.  
1 1. 2 M o nit ori n g 
1 1. 2. 1 
M o nit ori n g of t he St u d y  
T his st u d y will b e m o nit ore d a c c or di n g t o a n a p pr o v e d m o nit ori n g pla n b as e d o n t h e 
o bje cti v es, p ur p os e, d esi g n, a n d c o m ple xit y of t h e st u d y. T h e i n v esti g at or will all o c ate 
a d e q u ate ti m e f or all m o nit ori n g visits a n d b et w e e n visits t o fa cilitate t h e re q uire m e nts of t h e 
st u d y a n d st u dy ti m eli n es. T h e i n v esti g at or will als o e ns ure t h at t h e m o nit or or ot h er 
c o m plia n c e or q u alit y ass ura n ce re vie wer is gi v e n dire ct a c c ess t o all st u d y -relate d 
d o c u m e nts a n d st u d y -relate d fa cilities (e g, p h ar m ac y, dia g n ostic la b orat or y), p h o ne, fa x, a n d 
i nter n et a n d h as a d e q u ate s p a ce t o c o n d u ct t h e m o nit ori n g visit, if c o n d u cte d o n site. Site 
m o nit ori n g is c o n d u cte d t o e ns ure t h at t h e ri g hts of h u m a n p artici p a nts are pr ote cte d, t h at t h e 
st u d y is i m ple m e nte d i n a c c or da n ce wit h t h e pr ot o c ol a n d/ or ot h er o p erati n g pr o c e d ures, a n d 
t h at t h e st u d y us es hi g h q u alit y d ata c olle cti o n pr o cess es. T h e m o nit or will e v al u ate st u d y 
pr o c ess es b as e d o n P P D sta n d ar ds, I C H E 6, a n d all a p plic a ble, re g ulat or y g ui deli n es.  
C CI

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 82 
 
Monitoring details describing the strategy (eg, risk-based initiatives in operations and quality, 
such as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or onsite monitoring), are provided in the monitoring 
plan. 
11.2.2 
Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, 
audits, IRB/IEC review, and regulatory inspections by providing direct access to all study 
records. In the event of an audit, the investigator agrees to allow the sponsor, representatives 
of the sponsor, or a regulatory agency (eg, FDA or other regulatory agency) access to all 
study records. 
The investigator should promptly notify the sponsor and PPD of any audits scheduled by any 
regulatory authorities and promptly forward copies of any audit reports received to the 
sponsor. 
11.3 Management of Protocol Amendments and Deviations 
11.3.1 
Modification of the Protocol 
Any changes in the required procedures defined in this protocol, except those necessary to 
remove an apparent, immediate hazard to the participants, must be reviewed and approved by 
the sponsor or designee. Amendments to the protocol (including emergency changes) must be 
submitted in writing to the investigator’s IRB/IEC, along with any applicable changes to the 
ICF, for approval before participants can be enrolled into an amended protocol. 
11.3.2 Protocol Deviations 
A deviation from the protocol is an unintended or unanticipated departure from the 
procedures or processes approved by the sponsor and the IRB/IEC and agreed to by the 
investigator. A significant deviation occurs when there is nonadherence to the protocol or to 
local regulations or ICH GCP guidelines that may or may not result in a significant, 
additional risk to the participant or impacts the integrity of study data. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 83 
 
The investigator or designee must document and explain in the participant’s source 
documentation any deviation from the approved protocol. The investigator may implement a 
deviation from, or a change of, the protocol to eliminate an immediate hazard/safety risk to 
study participants without prior IRB/IEC approval. As soon as possible after such an 
occurrence, the implemented deviation or change, the reasons for it, and any proposed 
protocol amendments should be submitted to the IRB/IEC for review and approval, to the 
sponsor for agreement, and to the regulatory authorities, where required. 
In order to keep deviations from the protocol to a minimum, the investigator and relevant site 
personnel will be trained in all aspects of study conduct by the sponsor/sponsor 
representative. This training will occur either as part of the investigator meeting or site 
initiation. Ongoing training may also be performed throughout the study during routine site 
monitoring activities. 
11.4 Study Termination 
Although GSK Biologicals SA has every intention of completing the study, GSK Biologicals 
SA reserves the right to discontinue the study at any time for clinical or administrative 
reasons. 
The end of the study is defined as the date on which the last participant completes the last 
visit (includes follow-up visit). 
If the study is prematurely terminated or suspended, the sponsor or investigator shall 
promptly inform the investigators, the IRB/IECs, the regulatory authorities, and any contract 
research organization(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 participant and should assure appropriate participant therapy and/or follow-up. 
11.5 Final Report 
Whether the study is completed or prematurely terminated, the sponsor will ensure that the 
final data are summarized and provided to the regulatory agency(ies) as required by the 
applicable regulatory requirement(s). The sponsor will also ensure that the clinical study 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 84 
 
reports in marketing applications (as applicable) meet the standards of the ICH harmonised 
tripartite guideline E3: Structure and content of clinical study reports.  
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results. 
Upon completion of the final report, the sponsor will provide the investigator with the 
summary of the study results. The investigator is encouraged to share a summary of the 
results with the study participants, as appropriate. The study results will be posted on 
publicly available clinical trial registers. 

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 85 
 
12 References 
Alroy-Preis S, Milo R. Booster protection against confirmed infections and severe disease - 
data from Israel. [Internet]. 2021 [cited 2022 Jan 20]. Available from: 
https://www.fda.gov/media/152205/download. 
Andrews N, Stowe J, Kirsebom F, et al. Effectiveness of COVID-19 vaccines against the 
Omicron (B.1.1.529) variant of concern. [Internet]. 2021 [cited 2022 Jan 20]. Available from: 
https://www.medrxiv.org/content/10.1101/2021.12.14.21267615v1. 
Buchan SA, Chung H, Brown KA, et al. Effectiveness of COVID-19 vaccines against 
Omicron or Delta infection. [Internet]. 2021 [cited 2022 Jan 21]. Available from: 
https://www.medrxiv.org/content/10.1101/2021.12.30.21268565v1. 
Centers for Disease Control (CDC 2021a). Science brief: Omicron (B.1.1.529) variant. 
[Internet]. 2021 [cited 2022 Jan 21]. Available from: https://www.cdc.gov/coronavirus/2019-
ncov/science/science-briefs/scientific-brief-omicron-variant.html. 
Centers for Disease Control (CDC 2021b). Variant proportions (12/12/2021 – 12/18/2021). 
[Internet]. [cited 2021 Dec 21]. Available from: https://covid.cdc.gov/covid-data-
tracker/#circulatingVariants.  
Centers for Disease Control (CDC 2021c). COVID-19 vaccine breakthrough infections 
reported to CDC – United States, January 1 – April 30, 2021. [Internet]. [cited 2022 Feb 02]. 
Available from: https://www.cdc.gov/mmwr/volumes/70/wr/mm7021e3.htm. 
Centers for Disease Control (CDC 2022a). Clinical considerations: myocarditis and 
pericarditis after receipt of mRNA COVID-19 vaccines among adolescents and young adults. 
[Internet]. [cited 2022 Jun 20]. Available from: https://www.cdc.gov/vaccines/covid-
19/clinical-considerations/myocarditis.html.  
Centers for Disease Control (CDC 2022b). Vaccine recommendations and guidelines of the 
ACIP. [Internet]. [cited 2022 Jun 22]. Available from: 
https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/administration.html#t6_2.  

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 86 
 
Department of Health and Human Services (DHHS), Food and Drug Administration, Center 
for Biologics Evaluation and Research (US). Guidance for industry. Toxicity grading scale 
for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials. 
September 2007 [cited 2021 Jul 09]. Available from: 
https://www.fda.gov/media/73679/download.  
Food and Drug Administration, Center for Biologics Evaluation and Research (FDA 2021). 
Summary minutes 167th Vaccines and Related Biological Products Advisory Committee 
September 17, 2021. 2021 [cited 2022 Jan 20]. Available from: 
https://www.fda.gov/media/152597/download. 
Food and Drug Administration, Center for Biologics Evaluation and Research (FDA 2022). 
Moderna COVID-19 Vaccine fact sheet for healthcare providers. [Internet]. 2022 [cited 
2022 Jan 21]. 35 p. Available from: https://www.fda.gov/media/144637/download. 
Hansen CH, Schelde AB, Moustsen-Helm IR, et al. Vaccine effectiveness against SARS-
CoV-2 infection with the Omicron or Delta variants following a two-dose or booster 
BNT162b2 or mRNA-1273 vaccination series: A Danish cohort study. [Internet]. 2022 [cited 
2022 Jan 21]. Available from: 
https://www.medrxiv.org/content/10.1101/2021.12.20.21267966v2.full.pdf. 
Kremsner PG, Guerrero RAA, Arana E, et al. Efficacy and Safety of the CVnCoV 
SARS-CoV-2 mRNA Vaccine Candidate: Results from Herald, a Phase 2b/3, Randomised, 
Observer-Blinded, Placebo-Controlled Clinical Trial in Ten Countries in Europe and Latin 
America. [Preprint from The Lancet]. 2021 [cited 2021 09 Sep]. Available from: 
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3911826  
MMWR. SARS-CoV-2 B.1.1.529 (Omicron) Variant — United States, December 1–8, 2021. 
Morb Mortal Wkly Rep 2021;70:1731-1734. [cited 2021 Dec 21]. Available from: 
https://www.cdc.gov/mmwr/volumes/70/wr/mm7050e1.htm?s_cid=mm7050e1_w.  
Munro APS, Janani L, Cornelius V, et al. Safety and immunogenicity of seven COVID-19 
vaccines as a third dose (booster) following 2 doses of ChAdOx1 nCov-19 or BNT162b2 in 
the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. Lancet 
2021;398(10318):2258-76.  

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 87 
 
Our World in Data. Coronavirus (COVID-19) Vaccinations. [Internet]. 2022 [cited 
2022 Jan 17]. Available from: https://ourworldindata.org/covid-vaccinations.  
Pfizer-BioNTech. Emergency Use Authorization fact sheet for healthcare providers 
administering vaccine. [Internet]. 2022 [cited 2022 Jan 21]. Available from: 
https://www.cvdvaccine-us.com/. 
Roth N, Schӧn J, Hoffmann D, et al. CV0501, an enhanced mRNA-based SARS-CoV-2 
vaccine candidate, supports higher protein expression and improved immunogenicity in rats. 
[Internet]. 2021 [cited 2021 Jul 07]. Available from: 
https://www.biorxiv.org/content/10.1101/2021.05.13.443734v1.full.pdf  
Tseng HF, Ackerson BK, Luo Y, et al. Effectiveness of mRNA-1273 against SARS-CoV-2 
omicron and delta variants. [Internet]. 2022 [cited 2022 Jan 21]. Available from: 
https://www.medrxiv.org/content/10.1101/2022.01.07.22268919v1.full.pdf. 
UK Health Security Agency. SARS-CoV-2 variants of concern and variants under 
investigation in England. 10 Dec 2021 [cited 2021 Dec 17]. Available from: 
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data
/file/1040076/Technical_Briefing_31.pdf. 
World Health Organization (WHO). WHO Director-General’s opening remarks at the media 
briefing on COVID-19 – 11 March 2020 [Internet]. 2020 [cited 2021 Jun 11]. Available from: 
https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-
media-briefing-on-covid-19---11-march-2020  
World Health Organization (WHO). Interim statement on booster doses for COVID-19 
vaccination. [Internet]. 2021 [cited 2022 Jan 22]. Available from: 
https://www.who.int/news/item/22-12-2021-interim-statement-on-booster-doses-for-covid-
19-vaccination---update-22-december-2021. 
World Health Organization (WHO). WHO coronavirus (COVID-19) dashboard. [Internet]. 
2022 [cited 2022 Jan 19]. Available from: https://covid19.who.int/  

GlaxoSmithKline Biologicals SA  
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-COV2-012 BST) Amendment 2 
26 Jul 2022 
Confidential  
Page 88 
 
13 Appendices 
13.1 Appendix 1: Schedule of Events 

Gl ax o S mit h Kli ne Bi ol o gic als S A  
 
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S -C V0 5 0 1 -0 1 2 B S T) A men d me nt 2  
 
X X J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 8 9  
 
Ta ble  1 3 - 1 
Sc he d ule of E v e nts  
 
Sc r e e ni n g a 
D 1  
D 4  
D 8  
D 1 5  
D 2 9  
D 9 1  
D 1 8 1 
( E O S) 
 
E T   
Visit  
U nsc he d ule d 
Visit f o r 
S us pe ct e d 
C O VI D 1 9  
U nsc he d ule d 
C O VI D -1 9 
C o n v alesc e nt 
Visit  
Wi n d o w  
D – 1 4  t o – 1  
0  
± 1  
± 1  
± 3  
± 3  
± 5  
± 7  
N A  
N A  
N A  
Visit  
1  
2  
P h o ne  
3  
4  
5  
6  
7  
N A  
N A  
N A  
I nf or m e d c o ns e nt 
X  
 
 
 
 
 
 
 
 
 
 
I n cl usi o n/e x cl usi o n 
X  
 
 
 
 
 
 
 
 
 
 
Re as s es s st u d y v a c ci n e eli gi bilit y b 
 
X  
 
 
 
 
 
 
 
 
 
De m o gr a p hics  
X  
 
 
 
 
 
 
 
 
 
 
M e dic al hist or y (i n cl u di n g v a c ci n ati o n 
hist or y)  
X 
 
 
 
 
 
 
 
 
 
 
Pr e g n a n c y testc 
X  
X  
 
 
 
 
 
 
 
 
 
P h ysic al e x a mi n ati o n f 
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Vital si g n m e as ur e m e nts g  
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Vir al s cr e e ni n g as s a ys h  
X  
 
 
 
 
 
 
 
 
 
 
He m at ol o g y a n d s er u m c h e mistr y h  
X  
X d 
 
X  
 
 
 
 
 
 
 
Gr o u p as si g n m e nt f or Part A/ 
Ra n d o miz ati o n f or Part B  
 
X 
 
 
 
 
 
 
 
 
 
I nitiate e Diar y f or s olicite d A Es i 
 
X  
 
 
 
 
 
 
 
 
 
1 2 -le a d E C G  e x a mi n ati o n  
X  
 
 
X  
 
 
 
 
 
 
 
Site staff r e vie w of e Diar y  
 
 
X  
X  
 
 
 
 
 
 
 
C O VI D -1 9 as s es s m e nt k  
 
 
 
 
 
 
 
 
 
X k 
X k 
C CI
C CI
C CI
C CI

Gl ax o S mit h Kli ne Bi ol o gic als S A  
 
C V 0 5 0 1  Va c ci ne  
Pr ot o col 2 1 8 5 9 5 ( C V2  S A R S -C V0 5 0 1 -0 1 2 B S T) A men d me nt 2  
 
X X J ul  2 0 2 2  
C o nfi de nti al   
Pa g e 9 0  
 
N ote: D u e t o t h e o n g oi n g p a n d e mic, s af et y f oll o w -u p m a y b e c o m plete d via tele visits, as p er mitte d b y c o u ntr y r e g ulati o ns.   
a.  If t h e i n v esti gat or b elie v es t h er e is a r e as o n a ble j ustific ati o n t o d o s o, all s cr e e ni n g pr o c e d ur es m a y b e r e p e ate d ( m a xi m u m 1  r es cr e e ni n g p er p artici p a nt is 
all o we d). O nl y r es ults fr o m t h e r es cr e e ni n g visit, if it o c c urs, will b e ta k e n i nt o c o nsi d er ati o n a n d r e c or d e d i n t h e e C R F. T h e p artici p a nt  c a n o nl y b e v a c ci n ate d 
o n c e t h e i n v esti gat or r e c ei v es t h e r es ults a n d c o nfir ms t h e e li gi bilit y criteria.  
b. Pri or t o st u d y v a c ci n e a d mi nistr ati o n, p artici p a nts will b e r e as s es s e d f or d e v el o p m e nt of a n y n e w c o n diti o n t h at w o ul d b e c o nsi d er e d e x cl usi o nar y i n cl u di n g a c ute 
ill n es s or pr e g n a n c y. As s es s m e nt will b e b as e d o n pr e g n a n c y test r es ults, p artici p a nt-r e p orte d s y mpt o m ol o g y, vital si g n m e as ur e m e nts, a n d p h ysic al e x a mi n ati o n 
fi n di n gs.  
c.  
A s er u m pr e g n a n c y test will b e p erf or m e d at s cr e e ni n g i n W O C B P.  A uri n e pr e g n a n c y test b y di pstic k will b e p erf or m e d pri or t o  st u d y v a c ci n ati o n. Ne gativ e 
c o nfir m ati o n is r e q uir e d pri or t o st u d y v a c ci n e a d mi nistr ati o n. Pr e g n a n c y test m a y b e r e p e ate d at a n u ns c h e d ule d visit p er in v esti gat or’s dis cr eti o n.  
d. 
O n Da y 1, t h e bl o o d s a m ple s h o ul d b e c olle cte d b ef ore  st u d y v a c ci n e a d mi nistr ati o n.  
e.  
f. 
A c o m plete p h ysic al e x a mi n ati o n i n cl u di n g h ei g ht a n d wei g ht will  b e p erf or m e d at s cr e e ni n g. S y m pt o m -dir e cte d p h ysic al e x a mi n ati o ns will b e p erf or m e d as 
cli nic all y i n dic ate d at s u bs e q u e nt visits.  
g.  
Vital si g n m e as ur e m e nts (te m p er at ur e, p uls e  r ate, o x y ge n s at ur ati o n  b y p uls e o xi m etr y , r es pir ati o n r ate, a n d bl o o d pr es s ur e) s h o ul d b e c olle cte d b ef or e a n d after 
st u d y v a c ci n ati o n o n D 1. Vital s i g n m e as ur e m e nts s h o ul d b e p erf or m e d b ef or e a n y s c h e d ule d bl o o d c olle cti o n. Partici p a nts w h o ar e f e brile (te m p er at ur e ≥3 8. 0° C 
or ≥1 0 0. 4° F) b ef or e st u d y v a c ci n ati o n o n D 1 s h o ul d b e r es c h e d ule d f or st u d y v a c ci n ati o n wit hi n t h e r ele v a nt wi n d o w p eri o d.  
h. 
Cli nic al s af et y la b or at or y testi n g will i n cl u d e h e m at ol o g y a n d s er u m c h e mistr y. Scr e e ni n g la b or at or y tests m a y b e r e p e ate d o n c e f or e n r oll m e nt r e q uir e m e nts. At 
u ns c h e d ule d visits, cli nic al s af et y la b or at or y testi n g m a y b e p erf or m e d p er i n v esti gat or’s dis creti o n.  Vir al s cr e e ni n g as s a ys i n cl u d e HI V 1/ 2 A nti ge n/ A b, h e p atitis 
B s urf a c e a nti ge n ( H Bs A g) a n d h e p atitis C vir us a nti b o dies ( H C V A bs).  T esti n g f or  H C V R N A will b e p erf or m e d  i n p artici p a nts w h o test p ositi v e f or H C V A b. 
i. 
A n e Diar y will b e i nitiate d f or d ail y r e c or di n g b y t h e p artici p a nt of s olicite d l o c al a n d s yste mic a d v ers e e v e nts.  
j. 
S olicite d l o c al a n d s yste mic A Es will b e c olle cte d d uri n g t h e  7 d a ys after st u d y v a c ci n ati o n v ia e Diaries. U ns olicite d A Es will b e c olle cte d f or 2 8 d a ys after st u d y 
v a c ci n ati o n. S A Es, M A A Es, a n d A E SIs will b e c olle cte d f or t h e d ur ati o n of t h e st u d y.  
k. 
All s us p e cte d c as es of C O VI D -1 9 i n st u d y p artici p a nts will b e dia g n os e d a n d cli nic all y e v al u ate d  a c c or di n g t o t h e d efi niti o ns pr o vi d e d i n Se cti o n  6. 1. 2 . S u c h 
p artici p a nts m a y h a v e  u ns c h e d ule d st u d y site visits a n d n as o p h ary n ge al R T -P C R testi n g f or S A R S -C o V -2. A n u ns c h e d ule d visit m a y  b e p erf or m e d f or 
p artici p a nts r e p orti n g s y m pt o ms c o nsiste nt wit h C O VI D -1 9. A n i nitial visit s h o ul d b e s c h e d ule d u p o n r e p ort of s y m pt o m o ns et, pr efer a bl y wit hi n 3 d a ys of 
s y m pt o m o ns et. Alter n ati v el y, a n i n v esti gat or m a y utiliz e p artici p a nt m e dic al r e c or ds fr o m n o n -st u d y c ar e m e dic al  pr o vi d ers t o v erif y w h et h er a p artici p a nt was 
i nf e cte d wit h S A R S-C o V -2.  A n a d diti o n al u ns c h e d ule d, C O VI D -1 9 c o n v alesc e nt visit will b e pr ef er a bl y c o n d u cte d wit hi n t h e m o nt h after t h e p artici p a nt is 
C CI

GlaxoSmithKline Biologicals SA 
 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
 
XX Jul 2022 
Confidential  
Page 91 
 
confirmed with COVID-19. At the convalescent visit, the investigator will seek medical records documenting any treatments and hospitalizations related to 
COVID-19.  

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 92 
 
13.2 Appendix 2: Contraceptive Guidance and Pregnancy Information 
Definitions: 
Woman of Childbearing Potential 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of IP, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP: 
1. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, Müllerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
2. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. 
o A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy. However, in the absence of 12 months of 
amenorrhea, confirmation with more than 1 FSH measurement >40 IU/L 
(or mIU/mL) is required.  

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 93 
 
• Females on HRT and whose menopausal status is in doubt will be required to use 
one of the nonestrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment. 
Contraception Guidance: 
This contraception guidance is applicable to WOCBP in a heterosexual relationship (ie, this 
guidance does do not apply to participants in a same-sex relationship).  
True abstinence is 100% of time no sexual intercourse (male’s penis enters the female’s 
vagina). Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods, 
and withdrawal are not acceptable methods of contraception).  
Acceptable forms of primary contraception include monogamous relationship with a 
vasectomized partner who has been vasectomized for 180 days or more prior to the 
participant’s study vaccination, intrauterine devices, birth control pills, tubal ligation, and 
injectable/implantable/insertable hormonal birth control products.  
WOCBP must use at least 1 highly effective form of contraception for at least 30 days prior 
to study vaccination to 3 months after study vaccination. 
Collection of Pregnancy Information from Female Participants Who Become Pregnant 
• The investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. The initial information will be 
recorded on the PPD paper pregnancy report form and faxed to the same fax number 
as may be used for backup SAE reports within 24 hours of learning of a participant's 
pregnancy.  
• The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate, and 
the information will be forwarded to the sponsor. 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 the procedure. 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 94 
 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE.  
• A spontaneous abortion (occurring at <22 weeks gestational age) or still birth 
(occurring at >22 weeks gestational age) is always considered to be an SAE and will 
be reported as such.  
• Any poststudy pregnancy-related SAE considered reasonably related to the IP by the 
investigator will be reported to the sponsor as described in Section 6.1.1.3. While the 
investigator is not obligated to actively seek this information in former study 
participants, he or she may learn of an SAE through spontaneous reporting. 
• Any female participant who becomes pregnant while participating in the study will 
discontinue the IP. 
 
 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 95 
 
13.3 Appendix 3: Bayesian Logistic Regression Model 
A Bayesian logistic regression model will be used to determine posterior probabilities of 
unacceptable reactogenicity (Grade 3 solicited AEs) at the current or next dose level in 
Part A, as described below: 
logit(p(d)) = (α + β1*log(d/d*)) + β2 (indicator of OA) 
where 
• 
p(d) represents the probability of having a Grade 3 event at dose d, 
• 
logit(p) = ln(p/(1-p)), 
• 
d* = 50 µg is the reference dose,  
• 
α is an intercept parameter, reflecting the expected logit value at the 50 µg reference 
dose level,  
• 
β1 is a dose effect, 
• 
β2 is an age group effect. 
The prior for α and ln(β1) is a mixture of 2 bivariate normal distributions: 
1. 80% weight for α ≈ normal (mean=-0.8473, var=1) and ln(β1) ≈ normal  
(mean=-0.0556, var=1), reflecting a rate of 30% at 50 µg, and 10% at 12 µg). 
2. 20% weight for α≈ normal (mean=-0.4055, var=1) and ln(β1) ≈ normal 
(mean=0.10612, var=1), reflecting an intolerable dose (ie, a rate of 40% at 50 µg and 
12% at 12 µg). 
The prior β2 is half normal (mean=0, variance=0.25, β2<0 to reflect lower reactogenicity in 
older age group [OA]). 
The covariance between priors is assumed to be zero. 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 96 
 
A greater than 50% posterior probability that the rate at a current or next dose is greater than 
30% will inform the SRT in their decision to continue at the current or next dose. This will be 
applied by each dose and age group. 
Hypothetical scenarios for determining posterior probabilities based on combined younger 
age group and older age group data are presented in Table 13-2. 
Table 13-2 
Hypothetical Data Scenarios for Determining Posterior 
Probabilities 
Scenario 
Dose (µg) 
#Events 
#Participants CD – P(OD) Next Dose ND – P(TD) ND – P(OD) 
1 
12 
0 
30 
0 
25 
0.984 
0.016 
25 
0 
30 
0 
50 
0.860 
0.1442 
50 
0 
30 
0 
100 
0.917 
0.083 
100 
0 
30 
0 
200 
0.984 
0.016 
200 
0 
30 
0 
- 
- 
- 
2 
12 
0 
30 
- 
25 
0.984 
0.016 
25 
4 
30 
0.01 
50 
0.633 
0.367 
50 
6 
30 
0.097 
100 
0.352 
0.648* 
100 
8 
30 
0.407 
200 
0.1717 
0.829* 
200 
15 
30 
0.992* 
- 
- 
- 
*Stopping rule met, ie, ND – P(OD) >0.5 
CD = current dose; NA = not applicable; ND = next dose; P(TD) = probability of target dose; and P(OD) = probability of 
overdose. 
In this evaluation, the age effect was not considered in the model. 
When fitting the model, 0 events (#events) are replaced by 1 event (ie, assume 1 event in the younger adult group); this is 
done to prevent results from being overinfluenced by rates of events (=0%) being on the boundary of the parameter space.  
Rows in red should not be in the table, since the stopping rule would have been met at the previous dose; however, the rows 
are included for illustration purposes only. 
NOTE: It should be noted that the Bayesian model may be applied in a small number of exposed participants since it 
will be applied at each SRT review.  
 
 
 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 97 
 
13.4 Appendix 4: Potential Immune-mediated Diseases 
Potential immune-mediated diseases 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 etiology. Adverse events that need to be recorded and reported as pIMDs 
include those listed in Table 13-3. 
However, the investigator will exercise their medical and scientific judgment in deciding 
whether other diseases have an autoimmune origin (that is pathophysiologically involving 
systemic or organ-specific pathogenic autoantibodies) and should also be recorded as a 
pIMD. 
When there is enough evidence to make any of the diagnoses mentioned in Table 13-3, the 
AE must be reported as a pIMD. Symptoms, signs, or conditions which might (or might not) 
represent the above diagnoses, should be recorded and reported as AEs but not as pIMDs 
until the final or definitive diagnosis has been determined, and alternative diagnoses have 
been eliminated or shown to be less likely. 
In order to facilitate the documentation of pIMDs in the eCRF, a pIMD standard 
questionnaire will be available to investigators. 
Once a pIMD is diagnosed (serious or nonserious) in a study participant, the investigator (or 
designate) must complete, date, and sign an electronic Expedited Adverse Events Report. 
Table 13-3 
List of Potential Immune-Mediated Diseases 
Medical Concept 
Additional Notes 
Blood disorders and coagulopathies 
Antiphospholipid syndrome 
 
Autoimmune aplastic anemia 
 
Autoimmune hemolytic anemia • 
Includes warm antibody hemolytic anemia and cold antibody 
hemolytic anemia 
Autoimmune 
lymphoproliferative syndrome 
(ALPS) 
 
Autoimmune neutropenia  
 
Autoimmune pancytopenia 
 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 98 
 
Medical Concept 
Additional Notes 
Autoimmune 
thrombocytopenia 
• 
Frequently used related terms include: “autoimmune 
thrombocytopenic purpura”, “idiopathic thrombocytopenic purpura 
(ITP)”, “idiopathic immune thrombocytopenia”, “primary immune 
thrombocytopenia”. 
Evans syndrome 
 
Pernicious anemia 
 
Thrombosis with 
thrombocytopenia syndrome 
(TTS) 
 
Thrombotic thrombocytopenic 
purpura 
• 
Also known as “Moschcowitz-syndrome” or “microangiopathic 
hemolytic anemia” 
Cardio-pulmonary inflammatory disorders 
Idiopathic 
Myocarditis/Pericarditis 
Including but not limited to: 
• 
Autoimmune / Immune-mediated myocarditis 
• 
Autoimmune / Immune-mediated pericarditis 
• 
Giant cell myocarditis 
Idiopathic pulmonary fibrosis 
Including but not limited to: 
• 
Idiopathic interstitial pneumonia (frequently used related terms 
include “Interstitial lung disease”, “Pulmonary fibrosis”, “Immune-
mediated pneumonitis”) 
• 
Pleuroparenchymal fibroelastosis (PPFE) 
Pulmonary alveolar proteinosis 
(PAP) 
• 
Frequently used related terms include: “pulmonary alveolar 
lipoproteinosis”, “phospholipidosis” 
Endocrine disorders 
Addison’s disease 
 
Autoimmune / Immune-
mediated thyroiditis  
Including but not limited to: 
• 
Hashimoto thyroiditis (autoimmune hypothyroidism, lymphocytic 
thyroiditis) 
• 
Atrophic thyroiditis  
• 
Silent thyroiditis  
• 
Thyrotoxicosis 
Autoimmune diseases of the 
testis and ovary 
• 
Includes autoimmune oophoritis, autoimmune ovarian failure and 
autoimmune orchitis 
Autoimmune hyperlipidemia 
 
Autoimmune hypophysitis 
 
Diabetes mellitus type I 
 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 99 
 
Medical Concept 
Additional Notes 
Grave's or Basedow’s disease 
• 
Includes Marine Lenhart syndrome and Graves' ophthalmopathy, 
also known as thyroid eye disease (TED) or endocrine 
ophthalmopathy 
Insulin autoimmune syndrome 
 
Polyglandular autoimmune 
syndrome 
• 
Includes Polyglandular autoimmune syndrome type I, II, and III 
Eye disorders 
Ocular Autoimmune / 
Immune-mediated disorders 
Including but not limited to: 
• 
Acute macular neuroretinopathy (also known as acute macular outer 
retinopathy) 
• 
Autoimmune / Immune-mediated retinopathy  
• 
Autoimmune / Immune-mediated uveitis, including idiopathic 
uveitis and sympathetic ophthalmia  
• 
Cogan's syndrome: an oculo-audiovestibular disease 
• 
Ocular pemphigoid 
• 
Ulcerative keratitis 
• 
Vogt-Koyanagi-Harada disease 
Gastrointestinal disorders 
Autoimmune / Immune-
mediated pancreatitis 
 
Celiac disease 
 
Inflammatory Bowel disease  
Including but not limited to:  
• 
Crohn’s disease  
• 
Microscopic colitis  
• 
Terminal ileitis 
• 
Ulcerative colitis  
• 
Ulcerative proctitis 
Hepatobiliary disorders 
Autoimmune cholangitis 
 
Autoimmune hepatitis 
 
Primary biliary cirrhosis 
 
Primary sclerosing cholangitis 
 
Musculoskeletal and connective tissue disorders  
Gout 
• 
Includes gouty arthritis 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 100 
 
Medical Concept 
Additional Notes 
Idiopathic inflammatory 
myopathies 
Including but not limited to: 
• 
Dermatomyositis 
• 
Inclusion body myositis 
• 
Immune-mediated necrotizing myopathy 
• 
Polymyositis 
Mixed connective tissue 
disorder 
 
Polymyalgia rheumatica 
(PMR) 
 
Psoriatic arthritis (PsA) 
 
Relapsing polychondritis 
 
Rheumatoid arthritis  
Including but not limited to: 
• 
Rheumatoid arthritis-associated conditions 
• 
Juvenile idiopathic arthritis 
• 
Palindromic rheumatism 
• 
Still's disease 
• 
Felty’s syndrome 
Sjögren’s syndrome 
 
Spondyloarthritis 
Including but not limited to:  
• 
Ankylosing spondylitis 
• 
Juvenile spondyloarthritis 
• 
Keratoderma blenorrhagica 
• 
Psoriatic spondylitis  
• 
Reactive Arthritis (Reiter's Syndrome) 
• 
Undifferentiated spondyloarthritis 
Systemic lupus erythematosus  
• 
Includes Lupus associated-conditions (eg, Cutaneous lupus 
erythematosus, Lupus nephritis) or complications such as shrinking 
lung syndrome (SLS) 
Systemic scleroderma 
(systemic sclerosis) 
• 
Includes Reynolds syndrome (RS), systemic sclerosis with diffuse 
scleroderma and systemic sclerosis with limited scleroderma (also 
known as CREST syndrome) 
Neuroinflammatory/neuromuscular disorders 
Acute disseminated 
encephalomyelitis (ADEM) and 
Includes the following: 
• 
Acute necrotizing myelitis 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 101 
 
Medical Concept 
Additional Notes 
other inflammatory 
demyelinating variants  
• 
Bickerstaff's brainstem encephalitis  
• 
Disseminated necrotizing leukoencephalopathy (also known as 
Weston-Hurst syndrome, acute hemorrhagic leuko-encephalitis, or 
acute necrotizing hemorrhagic encephalomyelitis)  
• 
Myelin oligodendrocyte glycoprotein antibody-associated disease 
• 
Neuromyelitis optica (also known as Devic’s disease) 
• 
Noninfective encephalitis / encephalomyelitis / myelitis 
• 
Postimmunization encephalomyelitis  
Guillain-Barré syndrome 
(GBS) 
• 
Includes variants such as Miller Fisher syndrome and the acute 
motor and sensory axonal neuropathy (AMSAN) 
Idiopathic cranial nerve 
palsies/paresis and 
inflammations (neuritis) 
Including but not limited to: 
• 
Cranial nerve neuritis (eg, optic neuritis) 
• 
Idiopathic nerve palsies/paresis (eg, Bell’s palsy) 
• 
Melkersson-Rosenthal syndrome 
• 
Multiple cranial nerve palsies/paresis  
Multiple sclerosis (MS) 
Includes the following: 
• 
Clinically isolated syndrome (CIS)  
• 
Malignant MS (the Marburg type of MS)  
• 
Primary-progressive MS (PPMS) 
• 
Radiologically isolated syndrome (RIS) 
• 
Relapsing-remitting MS (RRMS) 
• 
Secondary-progressive MS (SPMS) 
• 
Uhthoff's phenomenon  
Myasthenia gravis 
• 
Includes ocular myasthenia and Lambert-Eaton myasthenic 
syndrome 
Narcolepsy 
• 
Includes narcolepsy with or without presence of unambiguous 
cataplexy 
Peripheral inflammatory 
demyelinating neuropathies 
and plexopathies 
Including but not limited to: 
• 
Acute Brachial Radiculitis (also known as Parsonage-Turner 
Syndrome or neuralgic amyotrophy) 
• 
Antibody-mediated demyelinating neuropathy 
• 
Chronic idiopathic axonal polyneuropathy (CIAP) 
• 
Chronic Inflammatory Demyelinating Polyradiculoneuropathy 
(CIDP), including atypical CIDP variants (eg, multifocal acquired 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 102 
 
Medical Concept 
Additional Notes 
demyelinating sensory and motor neuropathy also known as Lewis-
Sumner syndrome) 
• 
Multifocal motor neuropathy (MMN)  
Transverse myelitis (TM) 
• 
Includes acute partial transverse myelitis (APTM) and acute 
complete transverse myelitis (ACTM) 
Renal disorders 
Autoimmune / Immune-
mediated glomerulonephritis  
Including but not limited to: 
• 
IgA nephropathy 
• 
IgM nephropathy 
• 
C1q nephropathy 
• 
Fibrillary glomerulonephritis 
• 
Glomerulonephritis rapidly progressive 
• 
Membranoproliferative glomerulonephritis 
• 
Membranous glomerulonephritis 
• 
Mesangioproliferative glomerulonephritis 
• 
Tubulointerstitial nephritis and uveitis syndrome 
Skin and subcutaneous tissue disorders 
Alopecia areata 
 
Autoimmune / Immune-
mediated blistering dermatoses  
Including but not limited to:  
• 
Bullous Dermatitis 
• 
Bullous Pemphigoid  
• 
Dermatitis herpetiformis  
• 
Epidermolysis bullosa acquisita (EBA)  
• 
Linear IgA-mediated bullous dermatosis (LABD), also known as 
Linear IgA disease 
• 
Pemphigus  
Erythema multiforme 
 
Erythema nodosum 
 
Reactive granulomatous 
dermatitis  
Including but not limited to 
• 
Interstitial granulomatous dermatitis 
• 
Palisaded neutrophilic granulomatous dermatitis 
Lichen planus 
• 
Includes lichen planopilaris 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 103 
 
Medical Concept 
Additional Notes 
Localized Scleroderma 
(Morphoea) 
• 
Includes Eosinophilic fasciitis (also called Shulman syndrome) 
Psoriasis 
 
Pyoderma gangrenosum 
 
Stevens-Johnson Syndrome 
(SJS) 
 
Including but not limited to:  
• 
Toxic Epidermal Necrolysis (TEN)  
• 
SJS-TEN overlap 
Sweet’s syndrome 
• 
Includes Acute febrile neutrophilic dermatosis 
Vitiligo 
 
Vasculitis 
Large vessels vasculitis  
Including but not limited to: 
• 
Arteritic anterior ischemic optic neuropathy (AAION or arteritic 
AION) 
• 
Giant cell arteritis (also called temporal arteritis)  
• 
Takayasu's arteritis  
Medium sized and/or small 
vessels vasculitis  
Including but not limited to: 
• 
Anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis 
(type unspecified)  
• 
Behcet's syndrome  
• 
Buerger’s disease (thromboangiitis obliterans) 
• 
Churg–Strauss syndrome (allergic granulomatous angiitis)  
• 
Erythema induratum (also known as nodular vasculitis) 
• 
Henoch-Schonlein purpura (also known as IgA vasculitis) 
• 
Microscopic polyangiitis 
• 
Necrotizing vasculitis 
• 
Polyarteritis nodosa 
• 
Single organ cutaneous vasculitis, including leukocytoclastic 
vasculitis, hypersensitivity vasculitis and acute hemorrhagic edema 
of infancy (AHEI) 
• 
Wegener's granulomatosis  
Other (including multisystemic) 
Anti-synthetase syndrome 
 
Capillary leak syndrome 
• 
Frequently used related terms include: “systemic capillary leak 
syndrome (SCLS)” or “Clarkson's Syndrome” 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 104 
 
Medical Concept 
Additional Notes 
Goodpasture syndrome 
• 
Frequently used related terms include: “pulmonary renal syndrome” 
and “anti-Glomerular Basement Membrane disease (anti-GBM 
disease)” 
Immune-mediated 
enhancement of disease 
• 
Includes vaccine-associated enhanced disease (VAED and 
VAERD). Frequently used related terms include “vaccine-mediated 
enhanced disease (VMED)”, “enhanced respiratory disease (ERD)”, 
“vaccine-induced enhancement of infection”, “disease 
enhancement”, “immune enhancement”, and “antibody-dependent 
enhancement (ADE)” 
Immunoglobulin G4 related 
disease 
 
Langerhans' cell histiocytosis 
 
Multisystem inflammatory 
syndromes 
Including but not limited to: 
• 
Kawasaki’s disease 
• 
Multisystem inflammatory syndrome in adults (MIS-A) 
• 
Multisystem inflammatory syndrome in children (MIS-C)  
Overlap syndrome 
 
Raynaud’s phenomenon 
 
Sarcoidosis 
• 
Includes Löfgren syndrome 
Susac's syndrome 
 
 
 
 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 105 
 
13.5 Appendix 5: Grading for Laboratory Abnormalities 
Laboratory abnormalities will be graded for severity using the following FDA toxicity 
grading table (DHHS 2007). Clinically relevant laboratory abnormalities (Grades 1-3) will be 
reported as AEs. All Grade 4 laboratory abnormalities will be reported as SAEs.  

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 106 
 
Table 13-4 
Toxicity Grading for Serum Laboratory Abnormalities 
Parameter 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially 
Life-Threatening 
(Grade 4) 
Hematology (Whole Blood) 
Hemoglobin (g/dL) - Female 
11.0 – 12.0 
9.5 – 10.9 
8.0 – 9.4 
<8.0 
Hemoglobin (g/dL) – Female 
Change from Baseline Value 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
>5.0 
Hemoglobin (g/dL) - Male 
12.5 – 13.5 
10.5 – 12.4 
8.5 – 10.4 
<8.5 
Hemoglobin (g/dL) - Male 
Change from Baseline Value 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
>5.0 
Platelets Decrease (cell/mm3) 
125,000 – 140,000 
100,000 – 124,000 
25,000 – 99,000 
<25,000 
WBC Increase (cell/mm3) 
10,800 – 15,000 
15,001 – 20,000 
20,001 – 25,000 
>25,000 
WBC Decrease (cell/mm3) 
2500 – 3500 
1500 – 2499 
1000 – 1499 
<1000 
Lymphocytes Decrease (cell/mm3) 
750 – 1000 
500 – 749 
250 – 499 
<250 
Neutrophils Decrease (cell/mm3) 
1500 – 2000 
1000 – 1499 
500 – 999 
<500 
Eosinophils (cell/mm3) 
650 – 1500 
1501 – 5000 
>5000 
Hypereosinophilic 
Biochemistry (Serum) 
Alkaline phosphatase (increase by 
factor) 
1.1 – 2.0 x ULN 
2.1 – 3.0 x ULN 
3.1 – 10 x ULN 
> 10 x ULN 
ALT (increase by factor) 
1.1 – 2.5 × ULN 
2.6 – 5.0 × ULN 
5.1 – 10 × ULN 
>10.0 × ULN 
AST (increase by factor) 
1.1 – 2.5 × ULN 
2.6 – 5.0 × ULN 
5.1 – 10 × ULN 
>10.0 × ULN 
Bilirubin – when accompanied by 
any increase in Liver Function 
Test (increase by factor) 
1.1 – 1.25 x ULN 
1.26 – 1.5 x ULN 
1.51-1.75 x ULN 
> 1.75 x ULN 
Bilirubin – when Liver Function 
Test is normal (increase by factor) 
1.1 – 1.5 x ULN 
1.6 – 2.0 x ULN 
2.0 – 3.0 x ULN 
> 3.0 x ULN 
BUN (mg/dL) 
23 – 26 
27 – 31 
>31 
Requires dialysis 
Creatinine (mg/dL) 
1.5 – 1.7 
1.8 – 2.0 
2.1 – 2.5 
>2.5 or requires 
dialysis 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; ULN = upper limit of the 
normal range; WBC = white blood cells. 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 107 
 
13.6 Appendix 6: Protocol Amendment History 
The document history table for this protocol and the Protocol Amendment Summary of 
Changes Table for the current Amendment 2 is located directly before the Protocol Synopsis. 
A description of Amendment 1 is presented in this appendix. 
Amendment 1, 23 Jun 2022 
Rationale for Amendment 1: 
The main purposes of Amendment 1 are to respond to requests from regulatory authorities, to 
correct a typographical error in the wording of the primary safety endpoint, and to further 
align the trial parameters with best medical practices and previous practices in similar trials.  
The summary of changes table provided here describes the important changes made in 
Amendment 1 relative to the original protocol, including the sections modified and the 
corresponding rationales. The synopsis of Amendment 1 has been modified, as needed, to 
correspond to changes in the body of the protocol. Minor editorial, grammatical, and 
formatting corrections are not included in this summary table. 
Throughout the document, the protocol date and version were updated to reflect 
Amendment 1 and the title page was updated to reflect the protocol history.  
Summary of Important Changes from the Original Protocol to Amendment 1: 
Section Number and Name 
Description of Change 
Brief Rationale 
Section 1.2 (Risk:Benefit 
Considerations) 
Section 6 (Study Assessments and 
Procedures) 
Section 9.3 (Participant 
Information and eConsent) 
Added language describing 
increased education and guidance to 
participants regarding myocarditis 
and pericarditis 
Response to FDA request for 
increased risk mitigation for 
myocarditis and pericarditis 
Section 2 (Study Objectives and 
Endpoints)  
Corrected the primary safety 
endpoint to read: Percentage of 
participants with abnormal 
laboratory findings drawn 8 days 
after study vaccination 
To correct a typographical error 
in the number of days 

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 108 
 
Section Number and Name 
Description of Change 
Brief Rationale 
Section 3 (Study Design) 
Section 13.1 (Appendix 1: 
Schedule of Events)  
Increased the length of the 
screening period from 7 to 14 days, 
resulting in an increased study 
duration per participant from 187 to 
194 days 
To allow investigators more time 
to assess eligibility of 
participants and enhance study 
management 
Section 3 (Study Design) 
Section 6.1 (Safety Assessments) 
Section 6.1.2 (SARS-CoV-2 
Infection and COVID-19 
Assessment and Definitions) 
Section 13.1 (Appendix 1: 
Schedule of Events, footnote k) 
Clarified that participants will be 
asked to report any positive 
SARS-CoV-2 diagnostic test results 
and that investigators may verify 
SARS-CoV-2 infection from 
records of an outside medical 
provider 
To improve surveillance for 
SARS-CoV-2 infections during 
the study and to expedite 
infected participant access to 
medical care while limiting their 
travel and resulting exposure to 
the general population while 
infected 
Section 4.1.1 (Inclusion Criteria) 
In criterion 8, increased the upper 
limit of body mass index from 32 to 
40 kg/m2 
To broaden eligibility to better 
reflect the target patient 
population without expected 
increased risk to participants 
Section 4.1.2 (Exclusion Criteria) 
In criterion 12, removed the phrase, 
“including a COVID-19 vaccine” 
Response to Australian 
regulatory authority request to 
clarify criterion 12. The 
inclusion criteria and 
Section 5.8.2 of the protocol 
adequately describe the allowed 
intervals between COVID-19 
vaccination and vaccination with 
IP 
Section 5.2 (Study Vaccine 
Administration) 
Inserted recommendations for 
needle length by sex and weight 
To address revision of inclusion 
criterion 8, included guidance on 
recommended needle length  
Section 5.9 (Study Holding Rules) 
Timing windows for study holding 
rules 1c and 2a were eliminated, 
and a new study holding rule for 
myocarditis or pericarditis (1d) was 
established  
Response to FDA request to 
widen the scope of study holding 
rules 
Section 6.1 (Safety Assessments) 
Section 6.1.3 (Myocarditis and 
Pericarditis Assessment and 
Definitions) 
Added specifications for diagnosing 
and evaluating cases of suspected or 
confirmed myocarditis or 
pericarditis  
Response to FDA request for 
increased risk mitigation for 
myocarditis and pericarditis  

GlaxoSmithKline Biologicals SA 
CV0501 Vaccine 
Protocol 218595 (CV2 SARS-CV0501-012 BST) Amendment 2 
XX Jul 2022 
Confidential  
Page 109 
 
Section Number and Name 
Description of Change 
Brief Rationale 
Section 6.1.1.1.2 (Serious Adverse 
Events) 
Clarified that all events of 
myocarditis and pericarditis will be 
considered important medical 
events and SAEs 
Response to FDA request for 
increased risk mitigation for 
myocarditis and pericarditis 
Section 6.1.1.3.2 (Reporting 
Suspected Unexpected Serious 
Adverse Reactions) 
Added that cases of myocarditis or 
pericarditis occurring in temporal 
association with vaccination of 
study participants within 4 weeks 
after vaccination will be reported as 
SUSARs, as required by 21 CFR 
312.32 
Response to FDA request for 
increased risk mitigation for 
myocarditis and pericarditis 
Section 6.1.3.1 (Surveillance for 
Asymptomatic Myocarditis and 
Pericarditis) 
Section 13.1 (Appendix 1: 
Schedule of Events) 
Added a 12-lead ECG examination 
to the assessments conducted at the 
Day 8 visit, with cardiologist 
follow-up if findings of myocarditis 
or pericarditis are suspected or 
confirmed 
To enhance surveillance for 
asymptomatic myocarditis and 
pericarditis and respond to FDA 
request for increased risk 
mitigation for myocarditis and 
pericarditis  
Section 13.2 (Appendix 2: 
Contraceptive Guidance and 
Pregnancy Information) 
Added tubal ligation to the list of 
acceptable forms of primary 
contraception 
To provide clarity to 
Investigators on acceptable 
forms of primary contraception 
and to enhance study 
management at study sites