A Phase 2 Randomized, Active-controlled, Observer-blind Study to Assess the Safety, Reactogenicity, and Immunogenicity of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults Who Previously Received a Complete Primary Vaccination Series With or Without Booster Dose(s)
Phase: PHASE2
Conditions: SARS-CoV-2, COVID-19
Sponsor: GlaxoSmithKline

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1 
Clinical Study Protocol 
Primary Study 
Interventions  
CV0701 mRNA vaccine 
CV0601 mRNA vaccine  
CV0801 mRNA vaccine 
Other Study Intervention 
 
 
Study Identifier 
219075 (CV2 SARS-COV2-013 BST) 
EU CT Number 
2023-504596-25-00 
Approval date 
26 Sep 2023 
Title 
A Phase 2 randomized, active-controlled, observer-
blind study to assess the safety, reactogenicity, and 
immunogenicity of a booster dose of investigational 
COVID-19 mRNA vaccines in healthy adults who 
previously received a complete primary vaccination 
series with or without booster dose(s) 
Brief Title 
A study on the safety, reactogenicity, and immune 
response of a booster dose of investigational COVID-19 
mRNA vaccines in healthy adults 
Sponsor 
GlaxoSmithKline Biologicals S.A. 
Rue De L'Institut 89 
1330 Rixensart 
Belgium 
Sponsor Signatory 
Martin Gaudinski 
Clinical Project Lead 
Medical monitor name and contact can be found in local study contact 
information document 
©2023 GSK group of companies or its licensor. 
 
CCI
CCI

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PROTOCOL AMENDMENT 1 INVESTIGATOR AGREEMENT  
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments, with the terms of the clinical study agreement and with any other study 
conduct procedures and/or study conduct documents provided by GSK. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of and will comply with GCP and all applicable regulatory 
requirements. 
• 
That I will comply with the terms of the site agreement. 
• 
To comply with local bio-safety legislation. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study intervention and other study-related duties and functions as described 
in the protocol. 
• 
To supervise any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site. 
• 
To ensure that any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site are qualified to perform those study-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained on-site or 
elsewhere without the approval of GSK and the express informed consent of the 
participant. 
• 
To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s). 
• 
To co-operate with representative(s) of GSK in the monitoring and data management 
processes of the study with respect to data entry and resolution of queries about the 
data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the study. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator(s)’ ownership interest 
in the sponsor or the study intervention(s), and more generally about their financial 
ties with the sponsor. GSK will use and disclose the information solely for the 
purpose of complying with regulatory requirements. 

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Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study. 
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and all other documents 
required by regulatory agencies for this study. 

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Study identifier 
219075 (CV2 SARS-COV2-013 BST) 
EU CT Number 
2023-504596-25-00 
Approval Date 
26 Sep 2023 
Title 
A Phase 2 randomized, active-controlled, observer-
blind study to assess the safety, reactogenicity, and 
immunogenicity of a booster dose of investigational 
COVID-19 mRNA vaccines in healthy adults who 
previously received a complete primary vaccination 
series with or without booster dose(s) 
Investigator name 
 
 
 
Signature 
 
 
 
Date of signature 
(DD Month YYYY) 
 
 
 
 
 
name, function and title 
 
 
 
Signature 
 
 
 
Date of signature 
(DD Month YYYY) 
 
 
PPD

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE  
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 1 
26 Sep 2023 
Original Protocol 
04 May 2023 
Amendment 1 (26 Sep 2023) 
This amendment is considered substantial based on the criteria defined in EU Clinical 
Trial Regulation No 536/2014 of the European Parliament and the Council of the 
European Union because it significantly impacts the scientific value of the study. 
Overall rationale for the current Amendment:  
The objective of this amendment is to add a Part B to this Phase 2 study to provide 
exploratory safety and immunogenicity evidence of non-inferiority to our 
investigational vaccine stored at different conditions. The ongoing study described in 
the Protocol will herein be defined as Part A.  
List of main changes in the protocol and their rationale:  
Section # and 
title   
Description of change 
Brief rationale 
Title page; 
Study 
interventions 
The study intervention, 
“CV0801”, was added to 
the list of study 
intervention. 
To include the study intervention used 
for Phase 2 Part B. 
1.2. Schema 
A schema was added for 
the Part B study design. 
To summarize all the aspects of Part B 
design. 
1.3. Schedule of 
activities 
A new SoA for Part B 
participants has been 
developed. 
To ensure all protocol-mandated 
procedures of Part B are detailed.  
2.2. Study 
rationale 
The Part B study rationale 
has been added as a 
subsection. 
To explain the objective of Phase 2 Part 
B study. 
2.3. Benefit/risk 
assessment 
The study intervention 
CV0801 was added.  
To ensure the benefit/risk assessment is 
aligned with both Part A and Part B of 
the protocol.   
3. Objectives, 
endpoints, and 
estimands 
The immunogenecity and 
safety primary objectives 
and endpoints for Phase 
2 Part B have been added 
in a separate table. 
To ensure both Part A and Part B 
objectives and endpoints are reported.  

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Section # and 
title   
Description of change 
Brief rationale 
4.1. Overall 
study design  
The overall study design 
section has been divided 
in 2 subsections to 
describe Part A and Part 
B specific study design 
aspects.  
To ensure that the specificity of the 
study design is clearly explained for Part 
A and Part B.  
4.2 Scientific 
rationale for 
study design 
The section has been 
divided into 2 
subsections to describe 
Part A and Part B specific 
scientific rational 
aspects. 
To ensure that the specificity of the 
scientific rationale for study design is 
clearly explained for Part A and Part B. 
4.3. 
Justification of 
dose 
A rationale was provided 
for the choice of the 
CV0801 dose, as well as 
the objective for using 
alternative storage 
conditions.  
To explain why the dose and storage 
conditions chosen are important for the 
Part B study rationale. 
5.2 Exclusion 
criteria  
A new exclusion criterium 
has been added. 
To clarify that participants to Part A 
cannot be enrolled in Part B. 
6.1. Study 
interventions 
administered 
A table has been added to 
describe the study 
interventions 
administered to Part B 
participants. 
To ensure a detailed description of the 
Part B study interventions is included in 
the protocol.  
8 Study 
assessments 
and procedures 
and Section 8.2. 
Immunogenicity 
assessments 
Overall blood volumes 
that will be collected from 
each participant have 
been specified for Part A 
and Part B participants. 
Part B immunogenicity 
assessments have also 
been added in the 
relevant tables: biological 
samples, laboratory 
assays, and 
immunological reads-out. 
The tables have been 
modified to show Part A 
and Part B relevant 
information. 
To ensure clarity of the immunogenicity 
assessments that are to be performed in 
Part A and Part B . 

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Section # and 
title   
Description of change 
Brief rationale 
8.5 Committees 
structure 
Details about Part B have 
been added 
To explain frequency of committee 
review for both Part A and Part B. 
9 Statistical 
considerations 
Statistical information 
relevant to Part B has 
been added. The number 
of participants to be 
enrolled in Part B and the 
ratio of their distribution 
in the 3 groups of this 
Phase 2 study was 
provided.  
To ensure preliminary evidence of non-
inferiority between the different 
conditions can be provided with Part B 
of the study.  
9.4 Interim 
analysis 
Details about aggregate 
summaries have been 
added.  
To ensure the sharing of aggregate data 
to the SRT to assist with Regulatory 
interactions 
9.5 Sample size 
determination 
Details on Part B have 
been added. 
To define how sample size will be 
determined for Part A and Part B. 
 

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TABLE OF CONTENTS  
PAGE  
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 5 
List of main changes in the protocol and their rationale: ........................................... 5 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................................ 13 
1. 
PROTOCOL SUMMARY ........................................................................................ 20 
1.1. 
Synopsis ..................................................................................................... 20 
1.2. 
Schema ...................................................................................................... 21 
1.3. 
Schedule of Activities .................................................................................. 23 
2. 
INTRODUCTION .................................................................................................... 27 
2.1. 
Background ................................................................................................ 27 
2.2. 
Study rationale ............................................................................................ 28 
2.2.1. 
Study rationale for Part A ............................................................. 28 
2.2.2. 
Study rationale for Part B ............................................................. 28 
2.3. 
Benefit/risk assessment .............................................................................. 29 
2.3.1. 
Risk assessment .......................................................................... 29 
2.3.2. 
Benefit assessment ..................................................................... 30 
2.3.3. 
Overall benefit/risk conclusion ..................................................... 30 
3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS ................................................... 31 
4. 
STUDY DESIGN .................................................................................................... 33 
4.1. 
Overall design ............................................................................................. 33 
4.1.1. 
Overall study design of Part A ...................................................... 33 
4.1.2. 
Overall design of Part B ............................................................... 34 
4.2. 
Scientific rationale for study design ............................................................. 35 
4.2.1. 
Scientific rationale for study design for Part A .............................. 35 
4.2.2. 
Scientific rationale for study design for Part B .............................. 35 
4.3. 
Justification for dose ................................................................................... 36 
4.4. 
End-of-study definition ................................................................................ 37 
5. 
STUDY POPULATION ........................................................................................... 37 
5.1. 
Inclusion criteria .......................................................................................... 37 
5.2. 
Exclusion criteria ......................................................................................... 38 
5.3. 
Lifestyle considerations ............................................................................... 39 
5.4. 
Screen failures ............................................................................................ 40 
5.5. 
Criteria for temporarily delaying administration of study intervention ........... 40 
6. 
STUDY INTERVENTIONS AND CONCOMITANT THERAPY ................................ 40 
6.1. 
Study interventions administered ................................................................ 40 
6.2. 
Preparation, handling, storage, and accountability ...................................... 42 
6.3. 
Assignment to study intervention ................................................................ 43 
6.4. 
Blinding ....................................................................................................... 43 
6.5. 
Study intervention compliance .................................................................... 44 
6.6. 
Dose modification ....................................................................................... 44 
6.7. 
Continued access to study intervention after the end of the study ............... 44 
6.8. 
Treatment of overdose ................................................................................ 44 
6.9. 
Prior and concomitant therapy .................................................................... 44 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 45 
7.1. 
Discontinuation of study intervention ........................................................... 45 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 45 
7.3. 
Lost to follow-up.......................................................................................... 46 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 46 
8.1. 
Administrative and general/baseline procedures ......................................... 47 
8.1.1. 
Demographics ............................................................................. 47 
8.1.2. 
Medical/vaccination history .......................................................... 47 
8.2. 
Immunogenicity assessments ..................................................................... 48 
8.2.1. 
Biological samples ....................................................................... 48 
8.2.2. 
Laboratory assays ....................................................................... 49 
8.2.3. 
Immunological read-outs .............................................................. 51 
8.3. 
Safety assessments .................................................................................... 51 
8.3.1. 
Physical examination ................................................................... 51 
8.3.2. 
Vital signs .................................................................................... 51 
8.3.3. 
Pregnancy testing ........................................................................ 52 
8.4. 
AEs, SAEs, and other safety reporting ........................................................ 52 
8.4.1. 
Time period and frequency for collecting AE, SAE, and 
other safety information ............................................................... 53 
8.4.2. 
Method of detecting AEs and SAEs ............................................. 54 
8.4.3. 
Follow-up of AEs and SAEs ......................................................... 54 
8.4.4. 
AESIs .......................................................................................... 54 
8.4.4.1. 
pIMDs ......................................................................... 55 
8.4.4.2. 
SARS-CoV-2 infection, COVID-19 assessment 
and definitions ............................................................ 59 
8.4.4.3. 
Myocarditis and pericarditis assessment and 
definitions ................................................................... 60 
8.4.5. 
Regulatory reporting requirements for SAEs, AESI and 
other events ................................................................................. 62 
8.4.6. 
Pregnancy ................................................................................... 62 
8.4.7. 
Contact information for reporting SAEs, AESIs, and 
pregnancies ................................................................................. 63 
8.4.8. 
Participant card ............................................................................ 63 
8.5. 
Committees structure .................................................................................. 63 
8.5.1. 
IDMC ........................................................................................... 63 
8.5.2. 
iDRC ............................................................................................ 64 
8.5.3. 
Safety Review Team (SRT) ......................................................... 64 
8.6. 
Pharmacokinetics ....................................................................................... 64 
8.7. 
Pharmacodynamics .................................................................................... 64 
8.8. 
Genetics ..................................................................................................... 64 
8.9. 
Biomarkers ................................................................................................. 64 
8.10. 
Immunogenicity assessments ..................................................................... 65 
8.11. 
Health economics or medical resource utilization and health 
economics .................................................................................................. 65 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 65 
9.1. 
Statistical hypothesis .................................................................................. 65 
9.2. 
Analysis sets ............................................................................................... 65 
9.3. 
Statistical analyses ..................................................................................... 66 
9.3.1. 
General considerations ................................................................ 66 

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9.3.2. 
Primary endpoints analysis .......................................................... 66 
9.3.3. 
Secondary endpoints analyses .................................................... 66 
9.3.4. 
Tertiary endpoints analyses ......................................................... 66 
9.4. 
Interim analyses .......................................................................................... 67 
9.5. 
Sample size determination .......................................................................... 67 
9.5.1. 
Part A .......................................................................................... 67 
9.5.2. 
Part B .......................................................................................... 67 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 68 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight considerations .......... 68 
10.1.1. 
Regulatory and ethical considerations ......................................... 68 
10.1.2. 
Financial disclosure ..................................................................... 69 
10.1.3. 
Informed consent process ............................................................ 69 
10.1.4. 
Recruitment strategy .................................................................... 69 
10.1.5. 
Data protection ............................................................................ 70 
10.1.6. 
Dissemination of clinical study data ............................................. 70 
10.1.7. 
Data quality assurance ................................................................ 71 
10.1.8. 
Source documents ....................................................................... 72 
10.1.9. 
Publication policy ......................................................................... 72 
10.2. 
Appendix 2: Clinical laboratory tests ........................................................... 72 
10.3. 
Appendix 3: AEs and SAEs: Definitions and procedures for 
recording, evaluating, follow-up, and reporting ............................................ 73 
10.3.1. 
Definition of AE ............................................................................ 73 
10.3.2. 
Definition of SAE .......................................................................... 74 
10.3.3. 
Solicited AEs ............................................................................... 75 
10.3.4. 
Unsolicited AEs............................................................................ 75 
10.3.5. 
Definition of MAAE ....................................................................... 76 
10.3.6. 
Recording, assessment, and follow-up of AEs, SAEs, 
MAAEs, AESIs, and pregnancies ................................................. 76 
10.3.6.1. AE and SAE recording ................................................ 76 
10.3.6.2. Time period for collecting and recording AEs, 
SAEs, MAAEs, AESIs and pregnancies ...................... 77 
10.3.6.3. Assessment of intensity .............................................. 78 
10.3.6.4. Assessment of causality ............................................. 79 
10.3.6.5. Assessment of outcomes............................................ 80 
10.3.6.6. Follow-up of AEs, SAEs, AESIs, pregnancies 
or any other events of interest .................................... 80 
10.3.6.7. Updating of SAE, AESI, and pregnancy 
information after removal of write-access to the 
participant’s eCRF ...................................................... 81 
10.3.6.8. Reporting of SAEs, AESIs and pregnancies ............... 81 
10.3.7. 
Study and site start and closure ................................................... 82 
10.4. 
Appendix 4: Contraceptive and barrier guidance ......................................... 83 
10.4.1. 
Definitions .................................................................................... 83 
10.4.1.1. Women of childbearing potential................................. 83 
10.4.1.2. Women of non-childbearing potential ......................... 83 
10.4.2. 
Contraception guidance ............................................................... 84 
10.5. 
Appendix 5: Protocol amendment history .................................................... 84 
11. REFERENCES ....................................................................................................... 85 
 

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LIST OF TABLES  
PAGE 
Table 1 
Schedule of activities for Part A .............................................................. 23 
Table 2 
Schedule of activities for Part B .............................................................. 25 
Table 3 
Intervals between study visits for Part A ................................................. 27 
Table 4 
Intervals between study visits for Part B ................................................. 27 
Table 5 
Objectives and endpointsfor Part A ........................................................ 31 
Table 6 
Objectives and endpointsfor Part B ........................................................ 33 
Table 7 
Study intervention administered for Part A ............................................. 41 
Table 8 
Study intervention for Part B .................................................................. 42 
Table 9 
Biological samples ................................................................................. 49 
Table 10 
Laboratory assays .................................................................................. 50 
Table 11 
Immunological read-outs ........................................................................ 51 
Table 12 
Collection and reporting of safety information ......................................... 53 
Table 13 
List of pIMDs .......................................................................................... 55 
Table 14 
Timeframes for submitting SAE, pregnancy and other events 
reports to GSK ....................................................................................... 62 
Table 15 
Contact information for reporting SAEs, AESIs, and pregnancies .......... 63 
Table 16 
Intensity scales for solicited events ........................................................ 78 
Table 17 
Highly effective contraceptive methods .................................................. 84 
 

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LIST OF FIGURES  
PAGE 
Figure 1 
Part A: Study design overview ................................................................ 21 
Figure 2 
Part B: Study design overview ................................................................ 22 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS  
Abbreviation 
Definition 
Ab 
Antibody 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ANCOVA 
Analysis of covariance 
CI 
Confidence interval 
COVID-19 
Coronavirus disease 2019 
CRO 
Contract research organization 
CV0601 
Monovalent modified-nucleoside LNP encapsulated mRNA 
COVID-19 vaccine candidate encoding the 
 
 spike proteins of the 
 variants 
CV0701 
Bivalent modified-nucleoside LNP encapsulated mRNA 
COVID-19 vaccine candidate encoding the 
 
strain spike and 
 spike proteins 
CV0801 
Monovalent modified-nucleoside LNP encapsulated mRNA 
COVID-19 vaccine encoding the 
 spike 
protein with the 
 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
eDiary 
Electronic diary 
EMA 
European Medicines Agency 
EoS 
End-of-study 
EoSL 
End of shelf life 
ES 
Exposed Set 
FDA 
Food and Drug Administration 
FSH 
Follicule-stimulating hormone 
CCI
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CCI
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Abbreviation 
Definition 
GCP 
Good Clinical Practice 
GMF 
Geometric mean frequency 
GMI 
Geometric mean increase 
GMT 
Geometric mean titer 
GSK 
GlaxoSmithKline Biologicals S.A. 
HRT 
Hormonal replacement therapy 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation 
IDMC 
Independent data monitoring committee 
iDRC 
Internal data review committee 
IEC 
Independent ethics committee 
IgG 
Immunoglobulin G 
IMP 
Investigational medicinal product 
IRB 
Institutional review board 
LLOQ 
Lower limit of quantification 
LNP 
Lipid nanoparticle 
LPLV 
Last Participant Last Visit 
MAAE 
Medically attended adverse event 
modRNA 
Nucleoside-modified messenger RNA 
mRNA 
Messenger ribonucleic acid 
pIMD 
Potential immune-mediated disease 
CCI

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Abbreviation 
Definition 
PT 
Preferred term 
QTL 
Quality tolerance limit 
RT-PCR 
Reverse transcription polymerase chain reaction 
S 
Spike 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SoA 
Schedule of Activities 
SRT 
Safety Review Team 
ULN 
Upper limit of normal 
US 
United States 
VRBPAC 
Vaccines and Related Biological Products Advisory 
Committee 
WHO 
World Health Organization 
WOCBP 
Women of childbearing potential 
 
Term 
Definition 
Adverse Drug 
Reaction 
An adverse event where a causal relationship between a 
medicinal product and the adverse event is at least a reasonable 
possibility, i.e., the relationship cannot be ruled out. 
a. 
In the context of a clinical trial, an ADR can be serious or 
non-serious. Serious ADRs may be subject to expedited 
reporting if they are considered unexpected (see SUSAR 
definition). 
b. For marketed products, ADRs are subject to expedited 
reporting within the country where they are authorized 
CCI

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Term 
Definition 
Auxiliary 
Medicinal Product 
(AxMP) 
 
 
a. Authorised 
AxMP 
 
 
 
b. Unauthorized 
AxMP 
Medicinal products used in the context of a clinical trial but not 
as investigational medicinal products, such as medicinal 
products used for background treatment, challenge agents, 
rescue medication, or used to assess end-points in a clinical 
trial. Auxiliary medicinal products should not include 
concomitant medications, that is medications unrelated to the 
clinical trial and not relevant for the design of the clinical trial. 
Medicinal product authorized in accordance with Regulation 
(EC) No 726/2004, or in any Member State concerned in 
accordance with Directive 2001/83/EC, irrespective of changes 
to the labelling of the medicinal product. 
1. Safety reporting with regard to auxiliary medicinal 
products shall be made in accordance with Chapter 3 of 
Title IX of Directive 2001/83/EC. 
Medicinal product not authorized in accordance with 
Regulation (EC) No 726/2004 
1. Safety reporting for unauthorised auxiliary medicinal 
products will follow the same processes and procedures as 
SUSAR safety reporting 
Background 
treatment 
Type of medicinal product administered to each of the clinical 
trial participant, regardless of randomization group, to treat the 
indication that is the object of the study. Background treatment 
is generally considered to be the current standard care for the 
particular indication. In these trials, the IMP is given in 
addition to the background treatment and safety efficacy are 
assessed. The protocol may require that the IMP plus the 
background treatment is compared with an active comparator or 
with placebo plus background treatment 
Blinding 
A procedure in which 1 or more parties to the study are kept 
unaware of the intervention assignment in order to reduce the 
risk of biased study outcomes. The level of blinding is 
maintained throughout the conduct of the study, and only when 
the data are cleaned to an acceptable level of quality will 
appropriate personnel be unblinded or when required in case of 
an SAE. 
In an observer-blind study, the participant, the site, and sponsor 
personnel involved in the clinical evaluation of the participants 
are blinded while other study personnel may be aware of the 
treatment assignment. 

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Term 
Definition 
Certified copy 
A copy (irrespective of the type of media used) of the original 
record that has been verified (i.e., by a dated signature or by 
generation through a validated process) to have the same 
information, including data that describe the context, content, 
and structure, as the original. 
Challenge agents 
A product given to trial participants to produce a physiological 
response that is necessary before the pharmacological action of 
the IMP can be assessed. 
Co-administered 
(concomitant) 
products 
A product given to clinical trial participants as required in the 
protocol as part of their standard care for a condition which is 
not the indication for which the IMP is being tested and is 
therefore not part of the objective of the study. 
Comparator 
Any product used as a reference (including placebo, marketed 
product, GSK or non-GSK) for an investigational product being 
tested in a clinical trial. This is any product that is being used to 
assess the safety, efficacy, or other measurable value against 
the test product (IMP). 
eDiary 
Electronically registered participant data and automated data 
entries on, for example, a handheld mobile device, tablet, or 
computer. 
Eligible 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Essential 
documents 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of the data 
produced. 
Intervention 
number 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Investigational 
medicinal/vaccine 
product 
An IMP is a pharmaceutical form of an active substance or 
placebo being tested or used as a reference in a clinical study, 
including products already with a marketing authorization but 
used or assembled (formulated or packaged) in a way different 
from the authorized form, or when used for an unauthorized 
indication, or when used to gain further information about the 
authorized form. Medicinal products with a marketing 
authorization are IMPs when they are to be used as the test 
substance, reference substance, or comparator in a clinical 
study, provided the requirement(s) in the definition is/are met. 

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Term 
Definition 
Investigational 
Product 
A pharmaceutical form of an active substance or placebo being 
tested or used as a reference in a clinical trial, including 
products already with a marketing authorization but used or 
assembled (formulated or packaged) in a way different from the 
authorised form, or when used for an unauthorised indication, 
or when used to gain further information about the authorised 
form. 
Investigator 
A person responsible for the conduct of the clinical study at a 
study site. If a study is conducted by a team of individuals at a 
study site, the investigator is the responsible leader of the team 
and may be called the principal investigator. 
The investigator can delegate study-related duties and functions 
conducted at the study site to qualified individual or party to 
perform those study-related duties and functions. 
Medicinal products 
used to assess end-
points 
A product given to the participant in a Clinical Trial as a tool to 
assess a relevant clinical trial endpoint; it is not being tested or 
used as a reference in the clinical trial. 
Participant 
Term used throughout the protocol to denote an individual who 
has been contacted to participate or who participates in the 
clinical study as a recipient of the study intervention 
(vaccine(s)/product(s)/control). 
Synonym: subject. 
Participant number A unique identification number assigned to each participant 
who consents to participate in the study. 
Placebo 
An inactive substance or treatment that looks the same as, and 
is given in the same way as, an active drug or 
intervention/treatment being studied. 
Primary 
completion date 
The date on which the last participant in a clinical study was 
examined or received an intervention to collect final data for 
the primary outcome measure. 
Whether the clinical study ended according to the protocol or 
was terminated does not affect this date. For clinical studies 
with more than 1 primary outcome measure with different 
completion dates, this term refers to the date on which data 
collection is completed for all the primary outcome measures.  
Randomization 
Process of random attribution of intervention to participants to 
reduce selection bias. 

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Term 
Definition 
Rescue medication 
Medicines identified in the protocol as those that may be 
administered to the participants when the efficacy of the IMP is 
not satisfactory, or the effect of the IMP is too great and is 
likely to cause a hazard to the patient, or to manage an 
emergency situation. 
Source data 
All information in original records and certified copies of 
original records of clinical findings, observations, or other 
activities in a clinical study necessary for the reconstruction 
and evaluation of the study. Source data are contained in source 
documents (original records or certified copies). 
Standard of Care 
Medicine(s) for a specific indication, or a component of the 
standard care for a particular medical indication, based on 
national and/or international consensus; there is no regulatory 
significance to this term. 
1. Products/regimens considered standard of care may differ 
country to country, depending on consensus in individual 
countries 
Study completion 
date 
The date on which the last participant in a clinical study was 
examined or received an intervention/treatment to collect final 
data for the primary outcome measures, secondary outcome 
measures, and AEs (that is, the last participant's last visit or 
LPLV). 
Study intervention 
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or placebo 
intended to be administered to a participant. 
Note: “Study intervention” and “study treatment” are used 
interchangeably unless otherwise specified. 
Study monitor 
An individual assigned by the sponsor and responsible for 
assuring proper conduct of clinical studies at 1 or more 
investigational sites. 
SUSAR 
Suspected Unexpected Serious Adverse Reaction; in a clinical 
trial, a serious adverse reaction that is considered unexpected, 
i.e., the nature or severity of which is not consistent with the 
reference safety information (e.g., Investigator's Brochure for 
an unapproved investigational medicinal product). All adverse 
drug reactions (ADRs) that are both serious and unexpected are 
subject to expedited reporting. 
 

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1. 
PROTOCOL SUMMARY  
1.1. 
Synopsis  
Protocol Title: A Phase 2 randomized, active-controlled, observer-blind study to assess 
the safety, reactogenicity, and immunogenicity of a booster dose of investigational 
COVID-19 mRNA vaccines in healthy adults who previously received a complete 
primary vaccination series with or without booster dose(s). 
Brief Title: A study on the safety, reactogenicity, and immune response of a booster dose 
of investigational COVID-19 mRNA vaccines in healthy adults. 
Rationale: Refer to Section 2.2. 
Objectives, Endpoints, and Estimands: Refer to Section 3. 
Overall Design: Refer to Section 4.1. 
Number of Participants: Refer to Section 9.5. 
Data Monitoring/Other Committee: Refer to Section 8.5. 

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1.2. 
Schema  
Figure 1 
Part A: Study design overview  
 
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Figure 2 
Part B: Study design overview  
 
 
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1.3. 
Schedule of Activities   
Table 1 
Schedule of activities for Part A  
Day 1 
Day 8 
Phone Call/ 
Visitb 
Day 29 
Day 91 
Day 181 
(EoS) 
Unscheduled 
Visitc 
ET Visit 
Notes 
Window (days) 
0a 
±1 
±3 
±7 
±7 
Visit 
1 
2 
3 
4 
Informed consent 
X 
 
 
 
 
 
 
See Section 10.1.3 for details 
Distribution of participant card 
X 
 
 
 
 
 
 
See Section 8.4.8 for details 
Inclusion/exclusion assessment 
X 
 
 
 
 
 
 
See Sections 5.1 and 5.2 for inclusion 
and exclusion criteria 
Demographics 
X 
 
 
 
 
 
 
See Section 8.1.1 for more information 
Medical history (including vaccination history) 
X 
 
 
 
 
Xd 
 
See Section 8.1.2 for more information 
Concomitant medication/vaccination 
X 
X 
X 
X 
X 
X 
X 
See Section 6.9 for more information 
Vital sign measurementse 
X 
 
 
 
X 
 
See Section 8.3.2 for more information 
Physical examinationf 
X 
 
X 
X 
X 
X 
X 
See Section 8.3.1 for more information 
Pregnancy testg 
X 
 
 
 
 
 
 
See Section 8.3.3 for more information 
Blood sample for immunogenicity 
 
 and, if needed, for eligibility 
assessment (~56 mL)h 
X 
 
X 
X 
X 
 
 
See Section 8.2 for more information 
 
 
X 
Xb 
 
 
 
 
 
See Section 8.2 for more information 
SARS-CoV-2 anti-nucleocapsid antibody 
serology 
Xi 
 
X 
X 
X 
 
 
See Section 8.2 for more information 
SARS-CoV-2 RT-PCR (swab) 
Xj 
 
 
 
 
X 
 
See Section 8.4.4.2 for more information 
Randomization 
X 
 
 
 
 
 
 
See Section 6.3 for more information 
Study intervention administration (including 30-
minute post-vaccination observation) 
X 
 
 
 
 
 
 
See Section 6.1 for more informatio 
Initiate eDiary for solicited AEs 
X 
 
 
 
 
 
 
See Section 10.3.6 for more information 
Site staff review of eDiary 
 
X 
 
 
 
 
 
See Section 10.3.6 for more information 
Return of the eDiary device 
 
 
X 
 
 
 
 
See Section 10.3.6 for more information 
Recording of AESIs, MAAEs, and SAEs 
X 
X 
X 
X 
X 
X 
X 
See Section 10.3.6 for more information 
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Day 1 
Day 8 
Phone Call/ 
Visitb 
Day 29 
Day 91 
Day 181 
(EoS) 
Unscheduled 
Visitc 
ET Visit 
Notes 
Window (days) 
0a 
±1 
±3 
±7 
±7 
Visit 
1 
 
2 
3 
4 
Recording of SAEs related to study participation, 
or to a concurrent GSK medication/vaccinek 
X 
X 
X 
X 
X 
X 
X 
See Section 10.3.6 for more information 
Recording of unsolicited AEs 
X 
X 
X 
 
 
Xl 
 
See Section 10.3.6 for more information 
Participant study completion 
 
 
 
 
X 
 
 
See Section 4.4 for EoS definition 
AE: adverse event; AESI: adverse events of special interest; 
; EoS: end-of-study; ET: early termination; IgG: immunoglobulin G; MAAE: medically 
attended adverse event; RT-PCR: reverse transcriptase polymerase chain reaction; SAE: serious adverse event; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2 
Of note, safety follow-up may be completed via an unscheduled visit as permitted by country regulations. 
a. 
If a protocol-related procedure needs to be conducted to confirm eligibility or if the participant is likely to fulfill the eligibility criteria after a period of delay, the study intervention 
administration may be postponed up to a maximum of 14 days until the result is obtained and/or eligibility can be confirmed (refer to Section 5.5 for details). 
b. 
Additional planned visit only for participants in 
 
c. 
In case of acute COVID-19 assessment, the unscheduled visit may be used to collect a SARS-CoV-2 swab for RT-PCR testing. Participants will be asked to contact the site 
immediately should they experience any symptoms of COVID-19, myocarditis, or pericarditis, and an unscheduled visit may be performed. 
d. 
Evaluation and review of present COVID-19 illness history of the participants, including medical records to define the severity of COVID-19. 
e. 
Vital sign measurements (temperature, pulse rate, respiration rate, and blood pressure) should be collected before and after study intervention administration on Day 1. 
f. 
A complete physical examination including height and weight will be performed on Day 1 prior to study intervention administration. Only symptom-directed physical examinations 
will be performed if clinically indicated at subsequent visits. 
g. 
A urine pregnancy test will be performed on Day 1 for female participants of childbearing potential. Negative confirmation is required prior to study intervention administration. 
h. 
Other analyses, such as serum FSH to confirm postmenopausal status, may be performed if required. 
i. 
Randomization and study intervention administration may proceed before the anti-nucleocapsid antibody results are available. 
j. 
A SARS-CoV-2 swab for RT-PCR testing should be obtained at Day 1 to establish baseline characteristics. Randomization and study intervention administration may proceed 
before the results are available. 
k. 
SAEs related to study participation, or to a concurrent GSK medication/vaccine, should be collected from the time that informed consent is obtained (prior to study intervention 
administration) until the participant is discharged from the study. 
l. 
Unsolicited AEs will only be collected if the unscheduled visit occurs within Days 1 through 28 after vaccination. 
 
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Table 2 
Schedule of activities for Part B  
Day 1 
Day 8 
Day 29 
Day 91 
Day 181 
(EoS) 
Unscheduled 
Visitb 
ET Visit 
Notes 
Window (days) 
0a 
±1 
±3 
±14 
±14 
Visit 
1 
Phone Call 
1 
2 
Phone Call 
2  
Phone Call 
3  
Informed consent 
X 
 
 
 
 
 
 
See Section 10.1.3 for details 
Distribution of participant card 
X 
 
 
 
 
 
 
See Section 8.4.8 for details 
Inclusion/exclusion assessment 
X 
 
 
 
 
 
 
See Sections 5.1 and 5.2 for inclusion 
and exclusion criteria 
Demographics 
X 
 
 
 
 
 
 
See Section 8.1.1 for more information 
Medical history (including vaccination history) 
X 
 
 
 
 
Xc 
 
See Section 8.1.2 for more information 
Concomitant medication/vaccination 
X 
X 
X 
X 
X 
X 
X 
See Section 6.9 for more information 
Vital sign measurementsd 
X 
 
 
 
 
X 
 
See Section 8.3.2 for more information 
Physical examinatione 
X 
 
X 
 
 
X 
X 
See Section 8.3.1 for more information 
Pregnancy testf 
X 
 
 
 
 
 
 
See Section 8.3.3 for more information 
Blood sample for immunogenicity (neutralizing 
titers) and, if needed, for eligibility assessment 
(~20 mL)g 
X 
 
X 
 
 
 
 
See Section 8.2 for more information 
SARS-CoV-2 anti-nucleocapsid antibody 
serology 
Xh 
 
X 
 
 
 
 
See Section 8.2 for more information 
SARS-CoV-2 RT-PCR (swab) 
Xi 
 
 
 
 
X 
 
See Section 8.4.4.2 for more 
information 
Randomization 
X 
 
 
 
 
 
 
See Section 6.3 for more information 
Study intervention administration (including 30-
minute post-vaccination observation) 
X 
 
 
 
 
 
 
See Section 6.1 for more informatio 
Initiate eDiary for solicited AEs 
X 
 
 
 
 
See Section 10.3.6 for more information 
Site staff review of eDiary 
 
X 
 
 
 
 
 
See Section 10.3.6 for more information 
Return of the eDiary device 
 
 
X 
 
 
 
 
See Section 10.3.6 for more information 
Recording of AESIs, MAAEs, and SAEs 
X 
X 
X 
X 
X 
X 
X 
See Section 10.3.6 for more information 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccinej 
X 
X 
X 
X 
X 
X 
X 
See Section 10.3.6 for more information 
Recording of unsolicited AEs 
X 
X 
X 
 
 
Xk 
 
See Section 10.3.6 for more information 
Participant study completion 
 
 
 
 
X 
 
 
See Section 4.4 for EoS definition 

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AE: adverse event; AESI: adverse events of special interest; EoS: end-of-study; ET: early termination; MAAE: medically attended adverse event; RT-PCR: reverse 
transcriptase polymerase chain reaction; SAE: serious adverse event; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2 
Of note, safety follow-up may be completed via an unscheduled visit as permitted by country regulations. 
a. 
If a protocol-related procedure needs to be conducted to confirm eligibility or if the participant is likely to fulfill the eligibility criteria after a period of delay, the study 
intervention administration may be postponed up to a maximum of 14 days until the result is obtained and/or eligibility can be confirmed. 
b. In case of acute COVID-19 assessment, the unscheduled visit may be used to collect a SARS-CoV-2 swab for RT-PCR testing. Participants will be asked to contact the 
site immediately should they experience any symptoms of COVID-19, myocarditis, or pericarditis, and an unscheduled visit may be performed. 
c. 
Evaluation and review of present COVID-19 illness history of the participants, including medical records to define the severity of COVID-19. 
d. Vital sign measurements (temperature, pulse rate, respiration rate, and blood pressure) should be collected before and after study intervention administration on Day 
1. 
e. 
A complete physical examination including height and weight will be performed on Day 1 prior to study intervention administration. Only symptom-directed physical 
examinations will be performed if clinically indicated at subsequent visits. 
f. 
A urine pregnancy test will be performed on Day 1 for female participants of childbearing potential. Negative confirmation is required prior to study intervention 
administration. 
g. Other analyses, such as serum FSH to confirm postmenopausal status, may be performed if required. 
h. Randomization and study intervention administration may proceed before the anti-nucleocapsid antibody results are available. 
i. 
A SARS-CoV-2 swab for RT-PCR testing should be obtained at Day 1 to establish baseline characteristics. Randomization and study intervention administration may 
proceed before the results are available. 
j. 
SAEs related to study participation, or to a concurrent GSK medication/vaccine, should be collected from the time that informed consent is obtained (prior to study 
intervention administration) until the participant is discharged from the study. 
k. 
Unsolicited AEs will only be collected if the unscheduled visit occurs within Days 1 through 28 after vaccination. 

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Table 3 
Intervals between study visits for Part A  
Interval 
Planned visit interval  
Allowed interval range 
Visit 1 (Day 1)→Phone call /
 
(Day 8) 
7 days 
7±1 day 
Visit 1 (Day 1)→Visit 2 (Day 29) 
28 days 
28±3 days 
Visit 1 (Day 1)→Visit 3 (Day 91) 
90 days 
90±7 days 
Visit 1 (Day 1)→Visit 4 (Day 181) 
180 days 
180±7 days 
If the study intervention date is different from the ICF signature date, the study intervention date needs to be taken as a 
reference for calculating intervals relative to subsequent visits. 
Interval is computed as the difference between 2 dates. 
Table 4 
Intervals between study visits for Part B  
Interval 
Planned visit interval  
Allowed interval range 
Visit 1 (Day 1)→Phone call 1 (Day 
8) 
7 days 
7±1 day 
Visit 1 (Day 1)→Visit 2 (Day 29) 
28 days 
28±3 days 
Visit 1 (Day 1)→Phone call 2 (Day 
91) 
90 days 
90±14 days 
Visit 1 (Day 1)→Phone call 3 (Day 
181) 
180 days 
180±14 days 
If the study intervention date is different from the ICF signature date, the study intervention date needs to be 
taken as a reference for calculating intervals relative to subsequent visits. 
Interval is computed as the difference between 2 dates. 
2. 
INTRODUCTION  
2.1. 
Background  
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) was declared a pandemic by the World Health 
Organization (WHO) on 11 March 2020 [WHO, 2020]. As of 9 February 2023, more 
than 755 million cases have been reported worldwide, leading to more than 6.8 million 
deaths [WHO, 2023], although this is likely to be substantial underestimate of the true 
burden of disease [WHO, 2021a]. On 30 January 2023, the WHO Director-General 
concurred that the ongoing COVID-19 pandemic continues to constitute a public health 
emergency of international concern [WHO, 2023]. 
By December 2020, the United States (US) Food and Drug Administration (FDA) and 
European Medicines Agency (EMA) authorized the first vaccines containing Ancestral 
strain spike proteins. Since then, the emergence of SARS-CoV-2 variants (e.g., Delta and 
Omicron) that have the potential to escape immunity conferred by the originally approved 
vaccines prompted the need for continued development of COVID-19 mRNA vaccines to 
provide protection against circulating variants of concern [Garcia-Beltran, 2021; Zhou, 
2021]. Accumulating real world data substantiate both the protective benefits of mRNA 
COVID-19 vaccines over non-mRNA vaccines [Self, 2021], and the need for additional 
doses beyond the primary series due to waning immunity. At least 126 countries 
worldwide have issued recommendations on booster or additional vaccinations [WHO, 
2021b]. 
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In partnership with CureVac AG, GlaxoSmithKline Biologicals S.A. (GSK) developed 
CV0501, a monovalent modified-nucleoside mRNA COVID-19 vaccine encoding the 
 spike protein, which was a circulating variant of concern [CDC, 2023]. 
The Phase 1 study for CV0501, study 218595 (CV2 SARS-COV2-012 BST), entitled “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” is 
currently ongoing and its interim analyses provided the basis for the design of this 
Phase 2 study. 
In June 2022, the Vaccines and Related Biological Products Advisory Committee 
(VRBPAC) recommended that COVID-19 vaccine strain composition be updated to 
include the dominant circulating variant of concern, Omicron BA.4-5 [Marks, 2022]. 
Subsequently, Moderna and Pfizer-BioNTech obtained authorization for their bivalent 
formulations to be used as a single booster dose in select populations [FDA, 2022]. 
Due to the June 2022 VRBPAC recommendation to change from monovalent to bivalent 
COVID-19 booster vaccination, CureVac and GSK have developed CV0701, a bivalent 
modified-nucleoside mRNA COVID-19 vaccine encoding the 
 and 
. It is an admix of 2 monovalent modified-nucleoside mRNA 
COVID-19 vaccines; CV0601 
) and CV0801 
 
. 
 
 The vaccines are intended to be administered 
intramuscularly as a single booster dose for prevention of COVID-19 caused by SARS-
CoV-2. 
2.2. 
Study rationale   
2.2.1. 
Study rationale for Part A  
Within this Phase 2 study, the purpose of Part A is to evaluate the safety, reactogenicity 
and immunogenicity of CV0701 and CV0601 in healthy adults who have previously 
received a complete primary vaccination series with or without booster dose(s). By 
including both bivalent and monovalent vaccine candidates, the study will also provide 
information on possible immune interference between the 
 and 
 
spike protein antigens encoded in the bivalent vaccine (CV0701), compared with the 
 spike protein antigen solely encoded in the monovalent vaccine (CV0601).Within 
the study, CV0701 and CV0601 will be compared to 
 
 in a randomized observer-blinded fashion.  
2.2.2. 
Study rationale for Part B  
The purpose of Part B is to evaluate the safety and Day 29 immunogenicity of CV0801 
under 3 different storage conditions.  
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2.3. 
Benefit/risk assessment  
2.3.1. 
Risk assessment  
Detailed information about the known and expected risks of the CV0601, CV0701, and 
CV0801 vaccines is provided in the Investigator’s Brochure (IB). Important potential 
risks are the following: 
• 
Hypersensitivity reactions, including anaphylaxis 
• 
Myocarditis 
• 
Pericarditis 
To mitigate these important potential risks, the following risk mitigation strategies have 
been included in the protocol: 
• 
All participants will remain under observation at the vaccination center for at least 
30 minutes after vaccination. 
• 
Individuals with history of hypersensitivity or severe allergic reaction to any 
previous mRNA vaccine or any component of the study intervention(s) are excluded 
from the study enrollment, and participants will be instructed to contact the study site 
immediately for occurrence of any possible hypersensitivity reaction within 1 day of 
vaccination. 
• 
Individuals at increased risk of myocarditis or pericarditis and individuals with a 
history of myocarditis or pericarditis are excluded from the study enrollment. All 
participants will be educated on the symptoms of myocarditis and pericarditis and 
will receive guidance on contacting study personnel and seeking medical care if any 
of these symptoms occur. Any participants with suspected myocarditis or pericarditis 
within 6 weeks after study intervention administration will be referred to a 
cardiologist by the investigator for diagnosis and management. A safety follow-up 
will be ensured until resolution of symtpoms and/or abnormal test findings. 
• 
Anaphylaxis or severe hypersensitivity within 24 hours after study intervention 
administration, myocarditis and pericarditis will be collected as adverse events of 
special interest (AESIs). 
• 
Participants will receive close medical monitoring and medical assessments during 
the study per the Schedule of Activities (SoA) (Table 1 and Table 2). 
In addition, vasovagal syncope and other anxiety related reactions as a psychogenic 
response to the needle injection can occur following or even before any vaccination. 
Therefore, all participants will remain under observation at the vaccination center for at 
least 30 minutes after the vaccination. 
The potential risks associated with the investigational vaccines are considered acceptable, 
considering the measures planned to minimize risk to participants in this study and 
experience from the Phase 1 study with CV0501, the monovalent modified-nucleoside 
mRNA vaccine encoding an 
 spike protein using the 
 as 
CV0601, CV0701, and CV0801 (see Section 4.3). 
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Whilst the June 2022 VRBPAC recommended a bivalent vaccine encoding the Original 
and 
, a monovalent vaccine encoding the 
 
 is also included in the original study (Part A) to evaluate specific scientific 
objectives that cannot be met with bivalent vaccines alone. It is not anticipated that the 
participants randomized to the monovalent vaccine cohort will be disadvantaged 
compared to their bivalent counterparts, and there is scientific equipoise between all 
groups. 
Refer to the Prescribing Information or Summary of Product Characteristics for expected 
adverse reactions associated with 
 [Summary 
of product characteristics; Prescribing information]. 
2.3.2. 
Benefit assessment  
Participants are not expected to directly benefit from study participation. However, their 
participation in this study will contribute to generating information regarding the safety 
and immunogenicity of the vaccine.  
Additionally, study participants may benefit from gaining information about their general 
health status through the medical evaluations/assessments associated with this study (i.e., 
physical examination). 
2.3.3. 
Overall benefit/risk conclusion  
Considering the measures taken to minimize risk to participants in this study and given 
the accumulation of favorable safety/immunogenicity data from the Phase 1 study of 
CV0501 (see Section 4.3), the potential risks are justified by the anticipated benefits 
linked to the development of the investigational vaccines CV0601, CV0701, and 
CV0801. 
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3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS  
Table 5 
Objectives and endpointsfor Part A  
Primary Objectives 
Primary Endpoints (population summary) 
To compare the immunogenicity of CV0701 and 
CV0601 booster vaccines with 
 
 at Day 29  
• 
Serum neutralization titers against pseudovirus bearing 
specific 
 spike protein at Day 29 (GMT) 
• 
Serum neutralization titers against pseudovirus bearing 
specific 
spike protein at Day 29 (GMT) 
To evaluate the safety and reactogenicity of 
CV0701 and CV0601 booster vaccines  
• 
Occurrence of solicited administration site and systemic 
AEs within 7 days (i.e., from Day 1 to Day 7 included) of 
study intervention administration (percentage of 
participants) 
• 
Occurrence of unsolicited AEs within 28 days (i.e., from 
Day 1 to Day 28 included) of study intervention 
administration (percentage of participants) 
• 
Occurrence of MAAEs, SAEs and AESIs from Day 1 
through the end of the study (approximately 180 days 
after the study intervention administration), each 
summarized separately (percentage of participants) 
Secondary Objective 
Secondary Endpoints (population summary) 
To compare the immunogenicity of CV0701 and 
CV0601 booster vaccines with 
 
  
• 
Serum neutralization titers against pseudovirus bearing 
specific 
 spike protein at Day 91 and Day 181 
(GMT) 
• 
Serum neutralization titers against pseudovirus bearing 
specific 
spike protein at Day 91 and 
Day 181 (GMT) 
• 
Serum neutralization titers against pseudovirus bearing 
specific 
spike protein at Day 29, 91 and 
Day 181 (GMT) 
• 
Seroresponse* from baseline of serum neutralization 
titers against pseudovirus bearing specific 
 spike 
protein at Day 29 (percentage of participants) 
• 
Seroresponse* from baseline of serum neutralization 
titers against pseudovirus bearing specific 
 
spike protein at Day 29 (percentage of 
participants) 
• 
Seroresponse* from baseline of serum neutralization 
titers against pseudovirus bearing specific 
 
spike protein at Day 29 (percentage of participants) 
• 
Fold increase from baseline of serum neutralization 
titers against pseudovirus bearing specific 
 spike 
protein at Day 29, Day 91, and Day 181 (GMI) 
• 
Fold increase from baseline of serum neutralization 
titers against pseudovirus bearing specific 
 
spike protein at Day 29, Day 91, and Day 181 
(GMI) 
• 
Fold increase from baseline of serum neutralization 
titers against pseudovirus bearing specific 
 
spike protein at Day 29, Day 91, and Day 181 (GMI) 
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AE: adverse event; AESI: adverse events of special interest; GMI: geometric mean increase; GMT: geometric mean 
titer; IgG Ab: immunoglobulin G antibody; MAAE: medically attended adverse event; mRNA: messenger ribonucleic 
acid; RT-PCR: reverse transcriptase polymerase chain reaction; SAE: serious adverse event; SARS-CoV-2: severe 
acute respiratory syndrome coronavirus 2 
*
 
 
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Table 6 
Objectives and endpointsfor Part B  
Primary Safety Objective 
Primary Safety Endpoints (population summary) 
To evaluate the safety and reactogenicity 
of three CV0801 booster vaccine 
manufacturing specifications 
Solicited events: 
• 
Occurrence of solicited administration site and 
systemic AEs within 7 days (i.e., from Day 1 to Day 7 
included) of study intervention administration 
(percentage of participants) 
Unsolicited events: 
• 
Occurrence of unsolicited AEs within 28 days (i.e., from 
Day 1 to Day 28 included) of study intervention 
administration (percentage of participants) 
SAEs, AESIs and MAAEs: 
• 
Occurrence of MAAEs, SAEs and AESIs from Day 1 
through the end of the study (approximately 180 days 
after the study intervention administration), each 
summarized separately (percentage of participants) 
Primary Immunogenicity Objective 
Primary Immunogenicity Endpoint 
To evaluate the immunogenicity of three 
CV0801 booster vaccine manufacturing 
specifications 
• 
Serum neutralization titers against pseudovirus bearing 
specific 
 spike protein at Day 29 (GMT) 
AE: adverse event; AESI: adverse events of special interest; GMT: geometric mean titer; MAAE: medically 
attended adverse event; SAE: serious adverse event 
Complementary details on estimands such as impact of intercurrent events is provided in 
Section 9. 
4. 
STUDY DESIGN  
4.1. 
Overall design   
4.1.1. 
Overall study design of Part A  
Part A of the randomized, observer-blind Phase 2 study will evaluate the safety, 
reactogenicity and immunogenicity of a single booster dose of CV0701 and CV0601 
compared to
 
 in healthy adults who have 
previously received a complete primary vaccination series with or without booster 
dose(s). Multiple dose strengths of CV0701 will be evaluated. Participants will be 
randomized equally across 5 arms, which will include 
 
 
 to serve as a standard of care control). An overview of the study design is 
provided in Section 1.2, Figure 1. 
There are 2 investigational products in Part A (see also Section 6.1, Table 7): 
1. CV0601, a monovalent modified-nucleoside mRNA COVID-19 vaccine encoding 
 spike protein. 
2. CV0701, a bivalent modified-nucleoside mRNA COVID-19 vaccine encoding spike 
proteins: 1)
 (CV0801) and 2) 
 (CV0601). 
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. The mRNA is encapsulated in LNPs 
 
 which enhance mRNA uptake into the cells where the mRNA is 
translated into antigen.
. The bivalent vaccine CV0701 will be presented as 
2 separate components in glass vials. These components will be mixed in a separate 
10 mL vial prior to administration according to directions provided in the Pharmacy 
Manual. 
Comparator: 
  
4.1.2. 
Overall design of Part B  
Part B of the randomized and observer-blind Phase 2 study will evaluate the safety, 
reactogenicity and immunogenicity of CV0801 (a monovalent modified-nucleoside 
mRNA COVID-19 vaccine encoding 
spike protein) under 3 different 
storage conditions in healthy adults who have previously received a complete primary 
vaccination series with or without booster dose(s). Participants will be randomized 
equally across 3 arms:  
• 
Condition 1: CV0801 
 baseline-control 
• 
Condition 2: CV0801 
 intermediate storage conditions 
• 
Condition 3: CV0801 
 maximum storage conditions 
Condition 1 clinical trial material will serve as the baseline-control from which safety, 
reactogenicity and immunogenicity of Condition 2 and 3 (intermediate and maximum 
storage conditions) materials will be compared. 
An overview of the study design is provided in Section 1.2, Figure 2. 
Details on safety monitoring by the Independent Data Monitoring Committee (IDMC) 
and internal Data Review Committee (iDRC) are provided in Section 8.5 for both parts of 
the study. 
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This study will be conducted by a contract research organization (CRO; PPD, part of 
Thermo Fisher Scientific). 
4.2. 
Scientific rationale for study design  
4.2.1. 
Scientific rationale for study design for Part A  
Interim data from the CV0501 Phase 1 study informs the study design of Part A (CV0701 
and CV0601 Phase 2 study). This is founded on the basis that a similar safety profile can 
be expected as these investigational vaccines
 
 
 
 
 
 
 
 
 
 
 These 2 vaccine candidates will be 
compared against 
 
 which represents current 
standard of care, in a randomized, observer-blinded, and contemporaneously enrolled 
study. Part A of the Phase 2 study measures post-vaccination serum neutralization titers 
for its main immunologic endpoints. Post-vaccination neutralizing titers have been 
associated with COVID-19 vaccine efficacy in several analyses of 
 studies 
leading to vaccine authorization or licensure [Feng, 2021; Fong, 2022; Fong, 2023; 
Gilbert, 2022]. Vaccine efficacy increased with the neutralizing titer in each of these 
analyses of mRNA vaccines. These associations within a clinical study setting are 
additionally supported by meta-analyses of vaccine effectiveness within large 
populations, mechanistic biologic studies of nonhuman primates and therapeutic 
intravenous administration of virus neutralizing monoclonal antibodies. 
4.2.2. 
Scientific rationale for study design for Part B  
mRNA vaccine stability is affected by product-specific characteristics (such as 
molecular weight, buffer, lipid nanoparticle [LNP] encapsulation, etc), manufacturing 
processes-specific characteristics such as the length of time the vaccine is in liquid 
form (either during manufacturing, fill and finish, or during preparation and handling 
of the vaccine at different temperatures), and storage conditions of the finished 
product.  
The effect of these manufacturing and storage conditions on the final attributes of the 
vaccine is mainly derived from product and process knowledge and from clinical 
experience collected throughout all phases of product development. 
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Through this Part B of the Phase 2 study, the Companies (GSK and CureVac) aim to 
develop data on products stored at different conditions within a clinical trial setting. In 
doing so, this amendment will compare the safety, reactogenicity, and Day 29 
immunogenicity of 2 specifications of booster dose investigational COVID-19 mRNA 
vaccines exposed to storage conditions.  
4.3. 
Justification for dose  
The doses to be evaluated in this Phase 2 study are: 
• 
CV0701 Bivalent 
: 
 
• 
CV0701 Bivalent 
: 
 
• 
CV0701 Bivalent 
: 
 
• 
CV0601 Monovalent 
: 
 
• 
CV0801 Monovalent 
:
 at 3 different storage conditions. 
The bivalent and monovalent doses selected in this study are based on interim safety and 
immunogenicity data from the CV0501 Phase 1 study.  
The CV0501 Phase 1 is an open-label study enrolling healthy adults 18 years of age and 
older who have previously completed at least a 2-dose priming series of the original 
monovalent mRNA COVID-19 vaccines. Booster doses were allowed if the 6-month 
timeframe since vaccination was maintained. The 2-part study of 180 participants 
includes a Part A dose-escalation phase in which 5 sequential cohorts (n=30 per dose 
group) were enrolled to receive doses ranging from 
 to 
. Participants aged 18 
to 64 years formed the Younger Adults age-dose cohorts; the Older Adults age-dose 
cohorts comprised participants aged 65 or older. Part B is a prospectively designed dose-
down portion of the study evaluating 
 and 
 dose levels (n=15 participants per 
dose) in an 18 to <65-year age group. CV0501 safety is assessed by evaluating solicited 
and unsolicited adverse events (AEs), medically attended AEs (MAAEs), serious AEs 
(SAEs), and AESIs. Immunogenicity is evaluated through SARS-CoV-2 neutralizing 
levels against 
 (strain matched to the variant encoded in CV0501) and 
 (strain for scientific comparative purposes), in addition to other planned 
assessments of the immune response including binding immunoglobulin G (IgG) and 
cell-mediated immunity.  
 
 
 
 
 
 
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 Additionally, all 
Phase 2 doses will be compared to the 
 
 This 
will enable comparisons to be made between monovalent and bivalent 
 containing 
vaccines contemporaneously, in a randomized design, within a single study population.  
In Part B of the Phase 2 study, the 
 dose will provide exploratory data on any 
changes in reactogenicity, safety and immunogenicity due to reduced vaccine stabiltiy 
under different storage conditions, at doses levels consistent with Part A, which allow for 
comparative assessment. 
4.4. 
End-of-study definition  
A participant is considered to have completed the study if the participant has completed 
all periods of the study including the last visit. 
The end-of-study (EoS) is defined as the date of last participant last visit (LLV; Visit 
4/Phone call 3, Day 181) or the date of the last testing released of the Human Biological 
Samples, related to primary and secondary endpoints, whichever occurs later. The EoS 
must be achieved no later than 8 months after LPLV. The EoS cannot be before LPLV. 
5. 
STUDY POPULATION  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion criteria  
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
1. Is at least 18 years old and has achieved legal age according to local regulations in 
each participating country. 
2. Must provide documented informed consent prior to any study procedures being 
performed. 
3. Can and will comply with the requirements of the protocol (e.g., completion of the 
diary cards, return for follow-up visits), in the opinion of the investigator. 
4. Is healthy or medically stable as determined by the investigator’s judgment based on 
medical history, vital sign measurements, and physical examination findings. 
Participants with pre-existing stable disease, defined as disease not requiring 
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significant change in therapy or hospitalization for worsening disease during the 
6 weeks before enrollment, can be included. 
5. Prior receipt of an mRNA COVID-19 vaccine. This may be from a completed 
primary vaccination series or booster dose(s) of an approved or authorized mRNA 
COVID-19 vaccine. The last vaccination must be an mRNA COVID-19 vaccination 
received at least 3 months prior to randomization. 
6. If the participant is a woman of childbearing potential, the participant may be 
enrolled in the study, if she has: 
− 
practiced adequate contraception for 30 days prior to study intervention 
administration; and 
− 
has a negative pregnancy test result on the day of study intervention 
administration; and 
− 
has agreed to continue adequate contraception for 2 months after study 
intervention administration. 
Refer to Section 10.4.1 for definitions of woman of childbearing potential and 
adequate contraception. 
Female participants of non-childbearing potential may be enrolled in the study. Non-
childbearing potential is defined as current salpingectomy , hysterectomy, 
ovariectomy, or postmenopause. Refer to Section 10.4.1 for definitions of women of 
childbearing potential, menarche and menopause. 
5.2. 
Exclusion criteria  
Participants are excluded from the study if any of the following criteria apply: 
1. Is pregnant or has a positive pregnancy test result at Visit 1. 
2. Is breastfeeding or will (re)start breastfeeding from the study intervention 
administration to 3 months after study intervention administration. 
3. Has any medical disease or psychiatric condition that, in the opinion of the 
investigator, precludes study participation because it would place the participant at 
an unacceptable risk of injury, would render them unable to meet the requirements of 
the protocol, or may interfere with successful completion of the study. 
4. Has any history of an immunosuppressive or immunodeficient condition resulting 
from disease (e.g., HIV infection or congenital immunodeficiency). 
5. Has used immunosuppressants or other immune-modifying drugs for 14 consecutive 
days or more within 3 months prior to the study intervention administration (for 
corticosteroids, this will mean prednisone ≥20 mg/day or equivalent). Non-systemic 
(e.g., inhaled, topical, or intra-articular) corticosteroids are allowed. If systemic 
corticosteroids have been administered short term (<14 days) for treatment of an 
acute illness, participants should not be enrolled into the study until corticosteroid 
therapy has been discontinued for at least 28 days before study intervention 
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6. Has an acute medical illness or acute febrile illness with oral temperature ≥38.0°C or 
≥100.4°F within 72 hours prior to study intervention administration. 
7. Has participated in another study involving any investigational product, vaccine, or 
device within 28 days before the study intervention administration and/or planned 
participation through EoS. 
8. Has participated in Part A of this study. 
9. Has a history of hypersensitivity or severe allergic reaction including anaphylaxis, 
generalized urticaria, angioedema, and other significant reactions to any previous 
mRNA vaccine or any component of the study intervention(s). 
10. Has received or plans to receive immunoglobulins or any blood or blood products 
within 3 months before study intervention administration through EoS. 
11. Has a bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), 
or prior history of significant bleeding or bruising following intramuscular injections. 
12. Has a history of chronic alcohol consumption and/or drug abuse as deemed by the 
investigator to render the potential participant unable/unlikely to provide accurate 
safety reports or comply with study procedures. 
13. Has a 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 and persistent myocardial infection. 
14. Has received a live vaccine 30 days before the study intervention administration or 
has a planned administration within 30 days after the study intervention 
administration. 
15. Has received a non-replicating vaccine (e.g., inactivated and subunit influenza 
vaccine or pneumococcal conjugate vaccine) 8 days before the study intervention 
administration or has a planned administration within 14 days after the study 
intervention administration. 
16. Has a history of SARS-CoV-2 infection within 3 months before study intervention 
administration. 
17. Has had known close contact with anyone who had a confirmed SARS-CoV-2 
infection within 2 weeks before study intervention administration. 
18. Is an employee or family member of the investigator or study site staff. 
5.3. 
Lifestyle considerations  
Not applicable for this study. 

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5.4. 
Screen failures  
A screen failure occurs when a participant who has consented to participate in the clinical 
study is not subsequently randomized to study intervention/entered into the study. A 
minimal set of screen failure information is required to ensure transparent reporting of 
screen failure participants to meet the CONSORT publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria and any SAE. 
Participants who do not meet the criteria for study entry may be rescreened if the reason 
for exclusion may have changed. A new participant number will be assigned when a 
participant is rescreened. Previously assigned participant numbers are to be recorded in 
the participants’ electronic case report form (eCRF). 
5.5. 
Criteria for temporarily delaying administration of study 
intervention  
If a protocol-related procedure needs to be conducted to confirm eligibility or if the 
participant is likely to fulfill the eligibility criteria after a period of delay, the study 
intervention administration may be postponed up to a maximum of 14 days until the 
result is obtained and/or eligibility can be confirmed. The participant can only be 
vaccinated once the investigator receives the results and/or confirms the eligibility 
criteria. The investigator should repeat the following screening evaluations (see also 
Table 1 and Table 2) to confirm eligibility: inclusion/exclusion assessment, medical 
history, concomitant medication/vaccination recording, vital signs measurements, 
physical examination, and pregnancy test (for women of childbearing potential 
[WOCBP]). 
6. 
STUDY INTERVENTIONS AND CONCOMITANT 
THERAPY  
The definition of study intervention is provided in the table of definitions. 
6.1. 
Study interventions administered  
The study interventions administered in Part A include the CV0701 bivalent vaccine, 
CV0601 monovalent vaccine and comparator vaccine
 
. The information on the study interventions is presented in Table 7. 
The study interventions administered in Part B include the CV0801 monovalent 
vaccine under 3 different storage conditions: baseline-control, intermediate and 
maximum storage condition. The information on the study interventions is presented in 
Table 8. 
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Table 7 
Study intervention administered for Part A  
 
Group A 
Group B 
Group C 
Group D 
Group E 
Study 
intervention 
name 
CV0701 Bivalent 
 
 
 
CV0701 Bivalent 
  
 
CV0701 Bivalent 
  
  
CV0601 
Monovalent 
  
 
 
 
  
Study 
intervention 
formulation 
Modified mRNA 
Modified mRNA 
Modified mRNA 
Modified mRNA 
Modified mRNA 
Presentation 
Glass vial as a 
sterile colloidal 
dispersion in a 
frozen liquid 
formulation* 
Glass vial as a 
sterile colloidal 
dispersion in a 
frozen liquid 
formulation* 
Glass vial as a 
sterile colloidal 
dispersion in a 
frozen liquid 
formulation* 
Glass vial as a 
sterile colloidal 
dispersion in a 
frozen liquid 
formulation* 
 
 
 
Route of 
administration 
Intramuscular 
injection 
Intramuscular 
injection 
Intramuscular 
injection 
Intramuscular 
injection 
Intramuscular 
injection 
Administration 
site location 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
No of doses 
1 
1 
1 
1 
1 
Unit dose 
strength(s)**  
 
 
 
 
 
 
 
  
  
 
 
Dose volume  
Type (study 
intervention/ 
control) 
Study 
intervention 
Study 
intervention 
Study 
intervention 
Study 
intervention 
Comparator 
*The vaccines are vialed at a single concentration, and the final doses will be obtained with or without diluent prior to 
study intervention administration. CV0701 will be obtained by admixing the separate components (CV0601 and 
CV0801). 
**This table references target clinical doses. The calculated mRNA dose level by dilution is referenced in the Pharmacy 
Manual. 
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Table 8 
Study intervention for Part B  
 
Condition 1,  
baseline-control 
Condition 2, 
intermediate storage 
conditions 
Condition 3,  
maximum storage 
conditions 
Study intervention name 
CV0801 Monovalent 
 
µg 
CV0801 Monovalent 
µg 
CV0801 Monovalent 
µg 
Study intervention 
formulation 
Modified mRNA 
Modified mRNA 
Modified mRNA 
Presentation 
Glass vial as a sterile 
colloidal dispersion in a 
frozen liquid 
formulation* 
Glass vial as a sterile 
colloidal dispersion in a 
frozen liquid 
formulation* 
Glass vial as a sterile 
colloidal dispersion in a 
frozen liquid 
formulation* 
Route of administration 
Intramuscular injection 
Intramuscular injection 
Intramuscular injection 
Administration site 
location 
Deltoid 
Deltoid 
Deltoid 
No of doses 
1 
1 
1 
Unit dose strength**  
µg 
µg 
µg 
Dose volume  
Type (study intervention/ 
control) 
Study intervention 
Study intervention 
Study intervention 
*The vaccines are vialed at a single concentration, and the final doses will be obtained with diluent prior to 
study intervention administration.  
**This table references target clinical doses. 
Study participants must be observed closely for at least 30 minutes after the 
administration of the study intervention. Appropriate medical treatment must be readily 
available during the observation period in case of anaphylaxis, syncope or any other AEs 
following vaccination. 
6.2. 
Preparation, handling, storage, and accountability  
Refer to the Pharmacy Manual for instructions on how to prepare and dispense the study 
interventions. Appropriately qualified and experienced study staff (e.g., physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist), as 
allowed by local, state, and institutional guidance, should prepare and dispense the study 
interventions. A second staff member will verify the dispensing. The following activities 
must be performed: 
• 
The investigator or designee must confirm appropriate conditions (e.g., temperature) 
have been maintained during transit for all study interventions received, and any 
discrepancies are reported and resolved before use of the study intervention. 
• 
Only participants enrolled in the study may receive study intervention, and only 
authorized site staff may supply, prepare, or administer study intervention. 
• 
All study interventions must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. 
• 
The investigator is responsible for study intervention accountability, reconciliation, 
and record maintenance (i.e., receipt, reconciliation, and final disposition records). 
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• 
Further guidance and information for the final disposition of unused study 
interventions are provided in the Pharmacy Manual or other specified location. 
6.3. 
Assignment to study intervention  
Participants will be randomly assigned (1:1:1:1:1 in Part A and 1:1:1 in Part B) to the 
study groups using a central randomization system. The randomization will be based on 
permutation blocking scheme using country, previous known COVID-19 (yes, no), and 
age (< 65 years, ≥65 years) as stratification factors. 
6.4. 
Blinding  
The study will be conducted in an observer-blind manner, meaning that participants, the 
site, and sponsor personnel involved in the clinical evaluation of the participants will be 
blinded to treatment allocation. Other study personnel, such as the study pharmacist, may 
be aware of the treatment assignment. To maintain the observer-blind, the vaccines will 
be prepared and administered by unblinded qualified study personnel who will not 
participate in data collection, evaluation, review or entry of any study endpoint (i.e., 
safety or immunogenicity). 
In the event of a quality assurance audit, the auditor(s) will be allowed access to 
unblinded study intervention records at the site(s) to verify that randomization has been 
conducted accurately. 
A participant may continue in the study if that participant’s intervention assignment is 
unblinded. The primary reason for discontinuation (the event or condition which led to 
the unblinding) will be recorded in the eCRF. 
GSK’s Global Safety staff may unblind the intervention assignment for any participant 
with an SAE. If the SAE requires that an expedited regulatory report be sent to one or 
more regulatory agencies, a copy of the report, identifying the participant’s intervention 
assignment, may be sent to the investigators in accordance with local regulations and/or 
GSK policy. 
Blinding of laboratory testing 
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and the study to each sample. 
There will be no link between the study intervention groups and the identity of the 
participant. 
Emergency unblinding 
The central randomization system will be programmed with blind-breaking instructions. 
In case of an emergency, the investigator has the sole responsibility for determining if 
unblinding of a participant’s intervention assignment is warranted. Participant’s safety 
must always be the first consideration in making such a determination. If the investigator 
decides that unblinding is warranted, the investigator may, at the investigator’s discretion, 

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contact GSK to discuss the situation prior to unblinding a participant’s intervention 
assignment unless this could delay emergency treatment for the participant. If a 
participant’s intervention assignment is unblinded, GSK must be notified within 24 hours 
of this occurrence. The date and reason for the unblinding must be recorded. 
If the investigator is unable to access the central randomization system, they can contact 
the IRT helpdesk based on the information provided in the Pharmacy Manual.  
A physician other than the investigator (e.g., an emergency room physician) or 
participant/participant’s caregiver or family member may also request emergency access 
to the participant’s study intervention information as per participant card. 
6.5. 
Study intervention compliance  
The study intervention will be administered at the site, and participants will receive it 
directly from the investigator or designee, under medical supervision. The date of 
administration of each study intervention and dose will be recorded in the source 
documents. 
6.6. 
Dose modification  
Not applicable. 
6.7. 
Continued access to study intervention after the end of the 
study  
No long-term evaluation study is planned. 
6.8. 
Treatment of overdose  
There is no specific treatment or monitoring plan recommended for a vaccine overdose. 
The investigator should use medical judgment and consult the sponsor if a participant 
receives a greater vaccine dose than allowed per protocol. 
6.9. 
Prior and concomitant therapy  
Any concomitant medication/vaccination 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/vaccination are recorded fully in the eCRF. No concomitant medications will 
be provided by the sponsor or PPD. 
Please refer to the exclusion criteria (Section 5.2) for time permitted between receiving 
the study intervention and a concomitant vaccination. 

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Use of all concomitant medications and vaccinations within 6 months prior to eligibility 
assessment to the end of the study will be recorded in the participant’s eCRF. 
All prior COVID-19 vaccines received (including those received more than 6 months 
before eligibility assessment) and all COVID-19 vaccines received during the study will 
be recorded. 
The minimum requirement is that the drug name and the dates of administration are 
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 intervention administration should also be recorded in the participant's 
eCRF. Any changes in concomitant medications should be recorded in the participant’s 
eCRF throughout the study. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL  
7.1. 
Discontinuation of study intervention  
As this is a single dose study, discontinuation from study intervention does not apply. 
7.2. 
Participant discontinuation/withdrawal from the study  
A participant may withdraw from the study at any time at the participant’s own request 
for any reason (or without providing any reason). 
A participant may be withdrawn at any time at the discretion of the investigator for 
safety, behavioral, or compliance reasons. 
All data and samples collected up to and including the date of withdrawal or of last 
contact with the participant will be included in the study analyses. If the participant 
withdraws consent for disclosure of future information, the sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, the participant may request destruction of any 
samples taken and not tested, and the investigator must document this in the site study 
records. 

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The primary reason for participant discontinuation/withdrawal from the study will be 
documented in the eCRF based on the list below: 
Reasons 
Additional items/Sub-reasons 
AE 
Unsolicited AE 
Solicited AE 
AESI 
SAEs 
Other 
Lost to follow-up 
Participant relocated  
Participant was incarcerated  
Other, specify 
Unknown 
Physician Decision 
Specify 
Withdrawal by Participant 
Burden of procedure  
Participant relocated  
Pursue alternative treatment  
COVID-19 pandemic  
Other 
Other 
Specify 
Participants who are withdrawn from the study because of AEs must be clearly 
distinguished from participants who are withdrawn for other reasons. The investigator 
will follow up participants who are withdrawn from the study due to an AE until the 
event is resolved (see Section 10.3.6.6). 
7.3. 
Lost to follow-up  
A participant will be considered lost to follow-up if the participant 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: 
1. The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, 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. 
2. 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, 3 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. 
3. Should the participant continue to be unreachable, the participant will be considered 
to have withdrawn from the study. 
8. 
STUDY ASSESSMENTS AND PROCEDURES  
• 
Study procedures and their timing are summarized in the SoA (Table 1 and Table 2). 
Protocol waivers or exemptions are not allowed.  

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• 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. Participants who have signed informed 
consent but are not eligible to proceed should be recorded in the eCRF with a status 
of ‘screen failure’. 
• 
Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of the ICF may be used for screening or 
baseline purposes, provided these procedures have met the protocol-specified criteria 
and were performed within the timeframe defined in the SoA. 
• 
In the event of a significant study-continuity issue (e.g., caused by a pandemic), 
alternate strategies for participant visits, assessments, study intervention distribution 
and monitoring may be implemented by the sponsor or the investigator, as per local 
health authority/ethics requirements. 
• 
Safety and laboratory results that could unblind the study will not be reported to the 
investigative sites or other blinded personnel until the study has been unblinded. 
In Part A, an overall volume of approximately 200 mL will be collected from each 
participant over the entire study period. Additional blood volume (~60 mL) may be 
required for the participants in the 
 
In Part B, an overall volume of approximately 40 mL will be collected from each 
participant over the entire study period. 
Repeat or unscheduled samples may be taken for safety reasons or due to technical issues 
with the samples. 
8.1. 
Administrative and general/baseline procedures  
8.1.1. 
Demographics  
Record demographic data such as age, year of birth, sex, race, and ethnicity in the 
participant’s eCRF. 
Collection of sex, race and ethnicity data is necessary to assess and monitor the diversity 
of the study participants, and to determine if the study participants are truly representative 
of the impacted population. 
8.1.2. 
Medical/vaccination history  
For establishment of participant’s eligibility, mRNA COVID-19 vaccination history 
should be achieved based on locally accepted documentation of vaccination. Other 
medical/vaccination history should be obtained by interviewing the participant and/or 
review of the participant’s medical records.  
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A record of any pre-existing conditions, signs, and/or symptoms present prior to the 
administration of the study intervention dose should be in the eCRF. 
8.2. 
Immunogenicity assessments  
Biological samples will be used for research planned in the protocol and for purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. 
Findings in this or future studies may make it desirable to use samples acquired in this 
study for research not planned in this protocol. In this case, all participants in countries 
where this is allowed will be asked to give consent to allow GSK, or a contracted partner, 
to use the samples for further research. The further research will be subject to prior 
institutional review board/independent ethics committee (IRB/IEC) approval, if required 
by local legislation. 
Information on further research and its rationale can be obtained from GSK. 
Sample testing will be done in accordance with the recorded consent of the individual 
participant. 
By default, collected samples will be stored for a maximum of 20 years. This storage 
period begins when the last participant performs the last study visit. This timeline can be 
adapted based on local laws, regulations or guidelines requiring different timeframes or 
procedures. In all cases, the storage period should be aligned with participant’s consent. 
These additional requirements must be formally communicated to, discussed and agreed 
with GSK. 
Planned timepoints for all immunogenicity assessments are provided in the SoA (Table 
1 and Table 2). Blood samples on Day 1 should be collected as last procedure following 
eligibility assessment prior to vaccination. 
8.2.1. 
Biological samples  
Blood samples for humoral immune response testing will be taken from all study 
participants. A subset of Part A participants (targeting 25% of the total enrollment in 
Part A) will undergo additional blood sampling for
 
 to evaluate 
. Immunogenicity assessments will be performed at 
sponsor-designated laboratories as detailed in the Laboratory Manual. 
A SARS-CoV-2 swab for reverse transcription polymerase chain reaction (RT-PCR) 
testing should be obtained on Day 1 to establish infection status at vaccination. In case of 
acute COVID-19 assessment, a SARS-CoV-2 swab for RT-PCR testing may also be 
collected at an unscheduled visit (see Section 8.4.4.2 for details). 
Refer to Table 9 and SoA (Table 1 and Table 2) for information on samples collected for 
different assessments. 
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Table 9 
Biological samples  
Sample type 
Quantity 
Unit 
Timepoint 
Subset name 
Part A 
Blood for humoral 
immunogenicity 
~56 
mL 
Days 1, 29, 91 and 181 
All participants 
Nasopharyngeal or mid-
turbinate swab specimen 
- 
- 
Day 1 and case-driven 
Participants with any 
symptoms of COVID-19 
Part B 
Blood for humoral 
immunogenicity 
~20 
mL 
Days 1 and 29  
All participants 
Nasopharyngeal or mid-
turbinate swab 
specimen 
- 
- 
Day 1 and case-driven 
Participants with any 
symptoms of COVID-19 
 
Additional exploratory testing to characterize the immune response of the 
vaccine/vaccine components (e.g., SARS-CoV-2 
 assays, assays to measure 
cross-reactive antibodies against other coronaviruses) or to characterize the disease may 
be performed on study samples if deemed necessary for accurate interpretation of the data 
and/or should such test(s) become available in the GSK’s laboratory or in a laboratory 
designated by GSK. These additional assays may not be represented in the 
objectives/endpoints of the study protocol. 
8.2.2. 
Laboratory assays  
Anti-spike neutralization activity in serum will be measured using pseudotyped virus 
neutralization assays with pseudotyped virus displaying spike proteins from 
SARS-CoV-2 
. Neutralization titers to 
other SARS-CoV-2 variants may also be tested. Binding IgG antibody (Ab) levels against 
SARS-CoV-2 
, and/or SARS-CoV-2 spike antigens 
from other variants will be measured. Serology testing for SARS-CoV-2 anti-
nucleocapsid antibody will be performed to assess for prior SARS-CoV-2 infections. 
 
 
 
 
 
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Table 10 
Laboratory assays  
Test Classification 
System 
Component 
Method 
Laboratory* 
Part A 
Serum 
neutralization titers 
Serum 
SARS-CoV-2 serum 
neutralization 
Pseudotyped virus 
neutralization assay 
Nexelis, a 
Q2 solutions 
company 
Humoral immunity 
Serum 
SARS-CoV-2 
binding IgG 
Multiplex electro-
chemiluminescence assay  
PPD BioA 
Lab 
 
Serum 
SARS-CoV-2 N 
protein serology (Ab) 
Electro-chemiluminescence 
immunoassay (ECL 
PPD GCL 
Cevac or 
GSK 
Molecular biology 
Nasopharyngeal or 
mid-turbinate swab 
SARS-CoV-2 
RT-PCR 
PPD GCL 
Molecular biology 
Nasopharyngeal or 
mid-turbinate swab 
SARS-CoV-2 
lineage/spike seq 
Sequencing (NGS) 
PPD GCL 
Part B 
Serum 
neutralization titers 
Serum 
SARS-CoV-2 serum 
neutralization 
Pseudotyped virus 
neutralization assay 
Nexelis, a 
Q2 
solutions 
company 
N protein serology 
(qualitative 
diagnostic assay) 
Serum 
SARS-CoV-2 N 
protein serology 
(Ab) 
Electro-
chemiluminescence 
immunoassay (ECL) 
PPD GCL 
Molecular biology 
Nasopharyngeal 
or mid-turbinate 
swab 
SARS-CoV-2 
RT-PCR 
PPD GCL 
Ab: antibody; 
; IgG: immunoglobulin G; NGS: next-generation sequencing; RT-PCR: 
reverse transcriptase polymerase chain reaction; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2 
*Refer to the list of clinical laboratories for details. 
All laboratory testing will be performed at GSK’s laboratory or in a laboratory designated 
by GSK. 
The addresses of clinical laboratories used for sample analysis are provided in a separate 
document accompanying this study protocol. 
GSK clinical laboratories have established a Quality System supported by procedures. 
The activities of GSK clinical laboratories are audited regularly for quality assessment by 
an internal (sponsor-dependent) but laboratory-independent Quality Department. 
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8.2.3. 
Immunological read-outs  
Table 11 
Immunological read-outs  
Blood sampling timepoint 
Subset name 
No. participants 
Component 
Type of contact and 
timepoint 
Sampling timepoint 
Part A 
Humoral immunity (on serum samples) 
Visit 1 (Day 1) 
Visit 2 (Day 29) 
Visit 3 (Day 91) 
Visit 4 (Day 181) 
Pre-vaccination 
1 month post-dose 
3 months post-dose 
6 months post-dose 
All participants 
~415 
SARS-CoV-2 serum 
neutralization 
SARS-CoV-2 binding IgG 
SARS-CoV-2 N protein 
serology (Ab) 
Part B 
Humoral immunity (on serum samples) 
Visit 1 (Day 1) 
Visit 2 (Day 29) 
Pre-vaccination 
1 month post-dose 
All participants 
~249 
SARS-CoV-2 serum 
neutralization 
SARS-CoV-2 N protein 
serology (Ab) 
 
8.3. 
Safety assessments  
Planned timepoints for all safety assessments are provided in the SoA (Table 1 and Table 
2). 
8.3.1. 
Physical examination  
A complete physical examination (including height and weight) will be performed on 
Day 1 prior to study intervention administration for each participant. 
Physical examination at each study visit after the study intervention administration visit 
will be performed only if the participant indicates during questioning that there might be 
some underlying pathology(ies) or if it is deemed necessary by the investigator or 
designee. 
8.3.2. 
Vital signs  
Vital signs will be measured in a sitting position after at least 5 minutes of rest and will 
include temperature (oral temperature is preferred), pulse rate, respiration rate, and 
systolic and diastolic blood pressure. 
Vital sign measurements should be collected before and after study intervention 
administration on Day 1 and at the unscheduled visit for participants with any symptoms 
of COVID-19, myocarditis or pericarditis. 
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Per standard clinical practice, vital sign measurements may be repeated per investigator’s 
discretion.  
8.3.3. 
Pregnancy testing  
WOCBP must perform a urine pregnancy test before the administration of any dose of 
study intervention. Pregnancy testing must be done even if the participant is menstruating 
at the time of the study visit. The study intervention may only be administered if the 
pregnancy test is negative. 
Refer to Section 8.4.6 for the information on study continuation for participants who 
become pregnant during the study. 
8.4. 
AEs, SAEs, and other safety reporting  
Safety will be assessed through the collection and evaluation of solicited AEs (Section 
10.3.3), unsolicited AEs (Section 10.3.4), MAAEs (Section 10.3.6), SAEs (Section 
10.3.6), and AESIs (Section 10.3.6). Solicited administration site AEs will include 
injection site pain, redness, swelling, and lymphadenopathy (localized axillary, cervical, 
or supraclavicular swelling or tenderness ipsilateral to the vaccination arm). Solicited 
systemic AEs will include fever, fatigue, headache, chills, myalgia, and arthralgia. 
AESIs will include the following: 
• 
Laboratory-confirmed moderate to severe case of COVID-19 
• 
Potential immune-mediated disorders (pIMDs) 
• 
Myocarditis and pericarditis 
• 
Anaphylaxis or severe hypersensitivity within 24 hours after study intervention 
administration 
All suspected cases of COVID-19, myocarditis, and pericarditis in study participants will 
be diagnosed and clinically evaluated, which may require unscheduled study site visits 
and additional SARS-CoV-2 laboratory testing. 
See Section 10.3 for definitions relating to safety information. 
The investigator and any qualified designees are responsible for detecting, documenting, 
and recording events that meet the definition of an AE or SAE and other safety 
information and remain responsible for following up all AEs (see Section 7). This 
includes events reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
Safety will also be assessed by physical examinations and vital sign measurements (as 
detailed in Sections 8.3.1 and 8.3.2, respectively). 

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8.4.1. 
Time period and frequency for collecting AE, SAE, and other 
safety information  
All solicited AEs will be collected for a 7-day follow-up period after study intervention 
administration (i.e., from Day 1 through Day 7).  
All unsolicited AEs will be collected for a 28-day follow-up period after study 
intervention administration (i.e., from Day 1 through Day 28). 
All SAEs, MAAEs and AESIs will be collected from the start of study intervention until 
study end. 
SAEs assessed as related to study participation (e.g., study intervention, 
protocol-mandated procedures, invasive tests, or change in existing therapy) or related to 
a GSK product (non-investigational medicinal product [IMP]) will be recorded from the 
time a participant consents to participate in the study until study end. 
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded as medical history/current medical conditions, not as 
AEs. 
Table 12 
Collection and reporting of safety information  
 
Pre- 
Dose* 
 
Study vaccine 
dose 
 
 
 
Study conclusion 
(Day 181) 
Day 1 
Day 7 
Day 28 
Solicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AESIs/MAAEs/SAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation or concurrent 
GSK medication/vaccine** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading to 
withdrawal from the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE: adverse event; AESI: adverse event of special interest; MAAE: medically-attended adverse event; SAE: serious 
adverse event 
* i.e., consent obtained on Day 1 (prior to vaccination). 
** Any SAEs assessed as related to study participation (e.g., protocol-mandated procedures, invasive tests, or change 
in existing therapy) or related to a GSK product will be recorded from the time a participant consents to participate in 
the study. 
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All SAEs and AESIs will be recorded and reported to the sponsor or designee 
immediately and under no circumstance should this exceed 24 hours, as indicated in 
Section 10.3. The investigator will submit any updated SAE data to the sponsor within 24 
hours of it being available. 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Section 10.3.6.2/Table 12. 
Investigators are not obligated to actively seek information on AEs or SAEs after the 
conclusion of the study participation. However, if the investigator learns of any SAE, 
including a death, after a participant has been discharged from the study, the investigator 
must record it in the medical records. If the investigator considers the event to be 
reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor. 
8.4.2. 
Method of detecting AEs and SAEs  
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
non-leading verbal questioning or the electronic diary (eDiary) of the participant is the 
preferred method to inquire about AE occurrences. 
8.4.3. 
Follow-up of AEs and SAEs  
After the initial AE/SAE/AESI, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and AESIs (as defined in Section 
8.4.4) will be followed until resolution, stabilization, the event is otherwise explained, or 
the participant is lost to follow-up (as defined in Section 7.3). Further information on 
follow-up procedures is provided in Section 10.3.6.6. 
8.4.4. 
AESIs  
The study will capture the following specific AESIs: 
• 
pIMDs 
• 
Any laboratory-confirmed moderate to severe case of COVID-19 
• 
Myocarditis and pericarditis 
• 
Anaphylaxis or severe hypersensitivity within 24 hours after study intervention 
administration 
All suspected cases of COVID-19, myocarditis, and pericarditis in study participants will 
be diagnosed and clinically evaluated, which may require unscheduled study site visits 
and additional testing based on the investigator’s judgment. 

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8.4.4.1. 
pIMDs  
pIMDs are a subset of AESIs that include autoimmune diseases and other inflammatory 
and/or neurologic disorders of interest which may or may not have an autoimmune 
etiology. AEs that need to be recorded and reported as pIMDs include those listed in the 
Table 13. Please refer to the Section 10.3.6.8 for reporting details. 
In order to facilitate the documentation of pIMDs in the eCRF, a pIMD standard 
questionnaire and a list of preferred terms (PTs) and PT codes corresponding to the above 
diagnoses will be available to investigators at study start. 
The investigator(s) must exercise their medical/scientific judgment to determine whether 
other diseases have an autoimmune origin (i.e., pathophysiology involving systemic or 
organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. In 
addition, the investigator should categorize each pIMD either as a new onset condition (if 
it started following study intervention administration) or as an exacerbation of a pre-
existing chronic condition (if it exacerbated following study intervention administration) 
in the eCRF. 
Table 13 
List of pIMDs  
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 
 
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” 

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Medical Concept 
Additional Notes 
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 
 
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 
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) 
 

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Medical Concept 
Additional Notes 
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 (e.g., Cutaneous lupus 
erythematosus, Lupus nephritis, etc.) 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 other inflammatory 
demyelinating variants  
Includes the following: 
• 
Acute necrotizing myelitis 
• 
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 (e.g., Optic neuritis) 
• 
Idiopathic nerve palsies/paresis (e.g., 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 

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Medical Concept 
Additional Notes 
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 (e.g., multifocal 
acquired 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 liquen planopilaris 
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  

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Medical Concept 
Additional Notes 
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” 
Goodpasture syndrome 
• 
Frequently used related terms include: “pulmonary renal 
syndrome” and “anti-Glomerular Basement Membrane disease 
(anti-GBM disease)” 
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 Loefgren syndrome 
Susac's syndrome 
 
8.4.4.2. 
SARS-CoV-2 infection, COVID-19 assessment and definitions  
Participants will be instructed to inform the investigator immediately in the event of a 
positive SARS-CoV-2 test or suspected SARS-CoV-2 infection. In the absence of a 
confirmed alternative diagnosis, symptoms of suspected SARS-CoV-2 infection are: 
• 
acute onset of fever and cough 
OR 
• 
acute onset of any 3 or more of the following signs or symptoms: fever, cough, 
general weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, 
nausea/diarrhea/anorexia. 
All participants with suspected COVID-19 may have an unscheduled visit, as per the 
investigator’s discretion, where they will undergo the assessments outlined in the SoA 
(Table 1 and Table 2): 
• 
Medical history 
• 
SARS-CoV-2 RT-PCR (swab) 

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• 
Physical examination including vital sign measurements 
• 
Review of AEs 
• 
Review of concomitant medication/vaccination 
When feasible, next generation sequencing will be performed on RT-PCR samples to 
determine the Pango lineage and WHO variants of concern. 
COVID-19 diagnosis and clinical evaluation may be performed by an external medical 
provider or the study site. Any available isolate genotyping results will also be requested. 
Participants with confirmed COVID-19 may also have an unscheduled convalescent 
visit(s) following recovery as per the investigator’s discretion. At this visit, participants 
may undergo the assessments listed in the SoA (Table 1 and Table 2). 
All laboratory-confirmed SARS-CoV-2 infections (regardless of symptoms or time from 
study intervention administration) should be documented as AEs, but only confirmed 
moderate to severe cases of COVID-19 should be reported as AESIs. Severity of 
COVID-19 should be assessed as below: 
• 
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. 
Separate from any clinical assessment of SARS-CoV-2 infection in the study, a SARS-
CoV-2 RT-PCR swab will be performed pre-vaccination and serology testing for SARS-
CoV-2 N protein will be performed pre-vaccination and post-vaccination to monitor for 
undetected SARS-CoV-2 infections at the timepoints specified in the SoA (Table 1 and 
Table 2). The results of these assessments do not affect participant enrollment. 
When there is enough evidence to make the diagnoses of confirmed moderate or severe 
COVID-19 infection, the AE must be reported as an AESI. Symptoms, signs, or 
conditions which might (or might not) lead to confirmed moderate or severe COVID-19 
infection, should be recorded and reported as AEs, but not as AESIs, until the final or 
definitive diagnosis has been made and alternative diagnoses eliminated or shown to be 
less likely. 
8.4.4.3. 
Myocarditis and pericarditis assessment and definitions  
All participants will be educated on the symptoms of myocarditis and pericarditis and 
will receive guidance on contacting study personnel and seeking medical care if any of 
these symptoms occur. All suspected or confirmed cases of myocarditis or pericarditis 
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Participants reporting acute chest pain, shortness of breath, palpitations, or other 
symptoms of myocarditis or pericarditis within 6 weeks after study intervention 
administration must be evaluated by a cardiologist with evaluation and management 
following current practice guidelines (e.g., American Heart Association or local standard 
of care). 
Suspected cases of myocarditis or pericarditis are defined as having at least 1 
sign/symptom of myocarditis or pericarditis and diagnostic findings including but not 
limited to the following: 
• 
ECG abnormality that a cardiologist judges consistent with probable or possible 
myocarditis or pericarditis, including the following: 
− 
Sustained atrial or ventricular arrhythmias 
− 
Second-degree Mobitz type II or worse atrioventricular block, new bundle 
branch block 
− 
Diffuse ST-segment elevation or PR-segment depression, compatible with 
pericarditis 
• 
An abnormal high sensitivity troponin I value that is confirmed abnormal on repeat 
testing. 
Confirmed cases of myocarditis/pericarditis are defined as follows: 
• 
Participants diagnosed by a cardiologist as a confirmed case of 
myocarditis/pericarditis based on international cardiac guidelines. 
Participants who have confirmed myocarditis or pericarditis will have safety follow-up 
until resolution of symptoms and/or of abnormal test findings.  
Functional cardiac evaluation (e.g., stress test echocardiogram) to detect potential late 
onset of cardiac function impairment must be performed in the event myocarditis or 
pericarditis is confirmed. 
Suspected cases of myocarditis and pericarditis will be assessed by unblinded committees 
(see Section 8.5). 
Symptoms or signs which might (or might not) lead to one of the diagnoses of 
myocarditis or pericarditis should be recorded and reported as AEs, but not as AESIs, 
until there is enough evidence supporting the diagnosis of myocarditis or pericarditis and 
alternative diagnoses eliminated or shown to be less likely. 
All confirmed and suspected cases of myocarditis or pericarditis will be reported by the 
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8.4.5. 
Regulatory reporting requirements for SAEs, AESI and other 
events  
• 
Prompt notification by the investigator to the sponsor of an SAE/AESI is essential so 
that legal obligations and ethical responsibilities toward the safety of participants and 
the safety of a study intervention under clinical investigation are met. See 
Section 10.3.6.2 for reporting timeframes. 
• 
For SAEs/AESIs, the investigator must always provide an assessment of causality at 
the time of the initial report, as defined in the Section 10.3.6.7. 
• 
An investigator who receives an investigator safety report describing an SAE or 
other specific safety information (e.g., summary or listing of SAEs) from the sponsor 
will review and then file it along with the IB and will notify the IRB/IEC, if 
appropriate according to local requirements. 
Table 14 
Timeframes for submitting SAE, pregnancy and other events reports 
to GSK  
Type of event 
Initial reports 
Follow-up of relevant information on a 
previous report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡ 
electronic AEs report 
24 hours* 
electronic AEs report 
Pregnancies 
24 hours* 
paper pregnancy notification 
report 
24 hours * 
paper pregnancy follow-up 
report 
AESIs 
24 hours** ‡ 
electronic AEs report 
24 hours* 
electronic AEs report 
*Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of an AESI. 
‡ For each SAE/AESI, the investigator must document in the medical notes that they have reviewed the SAE/AESI and 
have provided an assessment of causality. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
8.4.6. 
Pregnancy  
Female participants who become pregnant after administration of the study intervention 
may continue the study at the discretion of the investigator. 
• 
Details of all pregnancies in female participants will be collected after the start of 
study intervention and until the participant is discharged from the study. 
• 
If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor within 24 hours of learning of the 
female participant pregnancy. 
• 
Any pregnancy complication or elective termination of a pregnancy for medical 
reasons will be reported as an AE or SAE. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
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• 
The participant will be followed to determine the outcome of the pregnancy, 
considering local requirements. The investigator will collect follow-up information 
on the participant and the neonate, and the information will be forwarded to the 
sponsor. See Table 14 for reporting timeframes. 
• 
Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.4.5. While the investigator is not obligated to actively seek this information 
in former study participants, they may learn of an SAE through spontaneous 
reporting. 
8.4.7. 
Contact information for reporting SAEs, AESIs, and pregnancies  
Table 15 
Contact information for reporting SAEs, AESIs, and pregnancies  
Study contact for questions regarding SAEs, AESIs, and pregnancies 
Contact PPD pharmacovigilance  
Contacts for reporting SAEs, AESIs, and pregnancies 
Available 24/24 hours and 7/7 days 
SAE hotline: +1-800-201-8725 
Fax: +1-888-488-9697 
8.4.8. 
Participant card  
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
always keep the participant card in their possession for the duration of the study. In an 
emergency, this card serves to inform the responsible attending physician/family member 
that the participant is in a clinical study and that relevant information may be obtained by 
contacting the investigator(s) or their back-up. 
8.5. 
Committees structure  
8.5.1. 
IDMC  
An unblinded IDMC will meet to review all available safety data at scheduled timepoints. 
For the interim analysis, all available safety and immunogenicity data will be reviewed. 
At any time, the IDMC may provide a recommendation to the sponsor whether the study 
should be stopped, modified, or continue unchanged. The basis for any decision will be 
the review of all available immunogenicity and/or safety data. Ethical and regulatory 
authorities will be notified per local requirements in the event the study halts or 
terminates early. Additional details of the IDMC will be provided in a separate charter. 

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The IDMC will meet at the following timepoints: 
• 
After 20% of participants have completed solicited reporting period (Day 7) (Part A 
only). 
• 
Interim analysis, which will be based on Day 29 data from Part A participants. 
• 
Every 3 months until the end of the study (Part A and Part B) 
• 
Ad hoc meetings, as needed, to review safety data. 
The composition of the IDMC will include a biostatistician and physicians with relevant 
clinical experience to the conduct of this study. This will include cardiologist(s) to 
provide expert input into cardiac-related AEs such as myocarditis and pericarditis, as well 
as physicians with prior experience serving on committees with a similar scope. 
8.5.2. 
iDRC  
An unblinded iDRC will review safety, reactogenicity, and immunogenicity data from the 
Part A Day 29 interim analysis to make recommendations on dose selection for a future 
 study. In addition, the iDRC will perform a review of the Part B Day 29 interim 
analysis. This committee will be limited to select senior experts from the sponsor. Details 
of this will be documented in an iDRC charter. 
8.5.3. 
Safety Review Team (SRT)  
An SRT is in place for each GSK product. It is comprised of a global cross-functional 
team responsible for the ongoing assessment of benefit-risk for a product. The SRT 
contributes to the continual assessment of incoming new efficacy and safety information. 
The SRT will remain blinded to study group allocation. 
8.6. 
Pharmacokinetics  
Not applicable. 
8.7. 
Pharmacodynamics  
Not applicable. 
8.8. 
Genetics  
Not applicable. 
8.9. 
Biomarkers  
Not applicable. 
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8.10. 
Immunogenicity assessments  
Immunogenicity is described in Section 8.2 
8.11. 
Health economics or medical resource utilization and health 
economics  
Not applicable. 
9. 
STATISTICAL CONSIDERATIONS  
The Statistical Analysis Plan (SAP) will be finalized prior to the first participant first visit 
and it will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses of 
the most important endpoints including primary and key secondary endpoints. Statistical 
analysis will be performed using SAS software Version 9.4 or later. Part A and Part B 
will be analyzed independently, the considerations outlined in this section apply 
separately to each part. 
9.1. 
Statistical hypothesis  
There is no hypothesis testing in this study; where statistical methods are applied, the 
emphasis will be on estimation with 95% confidence interval (CI). To provide 
preliminary evidence
 
 
 
 (see Section 9.3.2). 
9.2. 
Analysis sets  
The primary analysis of unsolicited AEs, MAAEs, SAEs, and AESIs will be based on the 
Exposed Set (ES), defined as data from all exposed participants. 
The primary analysis of solicited AEs will be based on the Diary Set, defined as data 
from all exposed participants for whom diary data are available. 
The primary analysis of immunogenicity will be based on the Per Protocol Set, defined as 
data from participants from the ES who were eligible, complied with vaccination as per 
protocol (e.g., vaccine not expired, with appropriate temperature storage), and had a pre-
dose and Day 29 anti-neutralizing titer against either the 
 
. Immunogenicity data at a post-vaccination visit will be censored in case 
of noncompliance for the blood sample visit. Likewise, immunogenicity data after the 
following intercurrent event will be censored: COVID-19, immunosuppressive or 
immunodeficient conditions, COVID-19 vaccination and prohibited 
medication/vaccination after study intervention.  
For all analyses, the study group will be defined by the vaccine administered at Visit 1. 
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9.3. 
Statistical analyses  
9.3.1. 
General considerations  
Analyses will be completed separately for part A and B, respectively. All descriptive 
analyses will be performed by vaccine group on data available, namely missing data will 
not be replaced. Subgroup analyses for safety and immunogenicity endpoints may be 
performed in selected groups and will be described in the SAP. For categorical variables, 
frequencies and percentages will be presented. Continuous variables will be summarized 
using descriptive statistics (number of participants, mean, standard deviation, median, 
and quartiles). 
9.3.2. 
Primary endpoints analysis  
The group GMT ratio associated 2-sided 95% CI and p-value for the null hypothesis that 
group GMT ratio is below 0.67 will be based on group contrast from an ANCOVA model 
on log10-transformed anti-neutralizing titer. The model will include the vaccine group, 
country, previous known COVID-19 infection (yes, defined by self-reporting or positive 
N protein at pre-vaccination, no), age (< 65 years, ≥ 65 years), and log10-transformed pre-
dose titer as fixed effects. For this model, a titer below a quantifiable threshold will be 
assigned half the threshold while a titer above a quantifiable threshold will be assigned 
the threshold. 
The primary safety endpoints as detailed in Table 5 for Part A and Table 6 for Part B 
will be analyzed as described in the SAP. For all reactogenicity and other safety 
endpoints, descriptive summary statistics will be provided for the Diary set and ES, 
respectively.  
9.3.3. 
Secondary endpoints analyses  
The secondary endpoints detailed in Table 5 for Part A 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, CIs and quartiles 
will also be provided for continuous immunogenicity variables. Seroresponse rate with 
95% CI, GMT of specific Ab with corresponding 95% CI and GMI from baseline of 
specific Ab with corresponding 95% CI will also be provided by group. The GMT, the 
GMI, and their 95% CI in each group will be analyzed using an ANCOVA on log10-
transformed tier with vaccine group, country, previous known COVID-19 infection (yes 
defined by self-reporting or positive N protein at pre-vaccination, no), age (< 65 years, ≥ 
65 years) and log10-transformed pre-dose titer as fixed effects. 
9.3.4. 
Tertiary endpoints analyses  
The tertiary endpoints for Part A detailed in Table 5 will be analyzed as described in the 
SAP. Graphical presentations will be considered as needed. 

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9.4. 
Interim analyses   
For each part, an interim analysis will be performed based on safety and immunogenicity 
data (neutralization titers matched to the variant encoded on the study vaccines) for all 
participants up to Day 29. This interim analysis will be performed on the ES. To maintain 
the study blinding, the unblinded analysis will be available to the IDMC, iDRC core 
members and study statisticians in charge of the analysis. In addition, aggregate 
summaries will be used for regulatory interaction before LSLV. However, all efforts 
will be made to ensure that participants, investigators and monitoring staff will 
continue to remain blinded.  
Analyses will be performed as follows: 
• 
Interim analysis: up to Day 29 safety and immunogenicity data (neutralization titers 
matched to the variant encoded on the candidate vaccines) for all participants (Part A 
and B separately). 
• 
Final analysis: up to Day 181 safety (Part A and Part B separately) and 
immunogenicity (Part A and Part B separately) data for all participants. 
9.5. 
Sample size determination  
9.5.1. 
Part A  
In Part A, approximately 415 participants will be enrolled and randomized in a 1:1:1:1:1 
ratio to receive 1 of the 3 CV0701 formulations, CV0601, or the comparator vaccine (i.e., 
83 participants will be enrolled in each of the 5 groups).  
The Part A study will provide preliminary evidence of 
 
 
 
 
 
 
 
9.5.2. 
Part B  
In Part B, a total of 249 participants will be enrolled and randomized in a 1:1:1 ratio to 
receive an injection of 1 of the 3 vaccine storage conditions (83 participants in each of 
the 3 groups). 
Part B study will provide preliminary evidence of 
 
 
 
 
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS  
10.1. 
Appendix 1: Regulatory, ethical, and study oversight 
considerations  
10.1.1. 
Regulatory and ethical considerations  
• 
This study will be conducted in accordance with the protocol and with the following: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) international ethical guidelines, 
− 
Applicable ICH GCP guidelines, 
− 
Applicable laws and regulations. 
• 
The protocol, protocol amendments, ICF, IB and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed 
and approved by the IRB/IEC before the study is initiated. 
• 
Substantial amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
• 
Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• 
The investigator will be responsible for the following, as applicable: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/IEC, 
− 
Notifying the IRB/IEC of SAEs or other significant safety findings as required 
by IRB/IEC procedures, 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of Title 21 Code of Federal Regulations, ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), and 
all other applicable local regulations. 
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10.1.2. 
Financial disclosure  
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. 
Informed consent process  
• 
The investigator or the investigator’s representative will explain the nature of the 
study, including the risks and benefits, to the participants and answer all questions 
regarding the study. 
• 
Potential participants must be informed that their participation is voluntary. They 
will be required to physically or digitally sign a statement of informed consent that 
meets the requirements of Title 21 Code of Federal Regulation Part 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
requirements, privacy and data protection requirements, where applicable, and the 
IRB/IEC or study center. 
• 
The medical record must include a statement that physical or digital informed 
consent was obtained before the participant was enrolled in the study and the date the 
physical or digital consent was obtained. The authorized person obtaining the 
informed consent must also sign the ICF. 
• 
Participants must be reconsented to the most current version of the ICF(s) during 
their participation in the study. 
• 
A physical, signed copy of the ICF(s) must be provided to the participant. 
• 
Participants who are rescreened are required to sign a new ICF. 
The ICF will contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research. The investigator or authorized designee will 
explain to each participant the objectives of the exploratory research. Participants will be 
told that they are free to refuse to participate and may withdraw their consent at any time 
and for any reason during the storage period. 
10.1.4. 
Recruitment strategy  
The study is planned to be conducted at sites in multiple countries. The recruitment plan 
will be defined by each participating site. 
The recruitment plan may be adapted based on the actual number of participants enrolled 
in each country. In case a site would fall behind in participant recruitment, a 
redistribution of the enrollment target per site in the participating countries may be made. 
This would allow the other participating sites to enroll additional participants to ensure 
full and timely enrollment of the overall targeted number of participants specified in this 
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The procedures for participants identification/recruitment must be approved by the 
IRB/IEC together with the material intended for participants identification/recruitment 
and participants use. Refer to the Study Procedures Manual for additional details. 
10.1.5. 
Data protection  
• 
Participants will be assigned a unique identifier by the investigator. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier only; 
participant names or any information which would make the participant identifiable 
will not be transferred. 
• 
GSK will ensure protection of the personal data of the investigator and site staff 
which is collected within the framework of and for the purpose of the study. 
• 
The participant must be informed that their personal study-related data will be used 
by the sponsor in accordance with local data protection law. The level of disclosure 
must also be explained to the participant, that their data will be used as described in 
the informed consent. 
• 
The participant must be informed that their medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• 
The contract between sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 
• 
Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect 
such data against accidental or unlawful loss, alteration, or unauthorized disclosure 
or access. GSK and/or trusted third parties working on behalf of GSK and/or 
institutions working with GSK for the purposes of this study are contractually bound 
to protect participant coded data. GSK will protect participant coded data and will 
only share it as described in the ICF. 
10.1.6. 
Dissemination of clinical study data  
• 
The key design elements of this protocol and results summaries will be posted on 
www.clinicaltrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocols summaries 
prior to study start and target results summaries submission within 12 months of 
primary/study completion date. Where external regulations require earlier disclosure, 
GSK will follow those timelines. 
• 
Where required by regulation, summaries will also be posted on applicable national 
or regional clinical study registers. 
• 
Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the study report and provided reasonable access to 
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with the full summary of the study results, including a summary of study results 
understandable to laypersons. The investigator is encouraged to share the plain 
language summary with the study participants, as appropriate. The full study report 
will be made available upon request, after decision on marketing authorization by 
regulatory authorities. 
• 
GSK will provide the investigator with the randomization codes and participant-level 
line listings for their site only after completion of the full statistical analysis. 
• 
GSK intends to make anonymized participant-level data from this study available to 
external researchers for scientific analyses or to conduct further research that can 
help advance medical science or improve patient care. This helps ensure that the data 
provided by study participants are used to maximum effect in the creation of 
knowledge and understanding. 
10.1.7. 
Data quality assurance  
• 
All participant data relating to the study will be recorded on printed or electronic 
CRFs unless transmitted to the sponsor or designee electronically (e.g., laboratory 
data). The investigator is responsible for verifying that data entries are accurate and 
correct by physically or electronically signing the CRF. 
• 
Guidance on completion of eCRFs will be provided in eCRF completion guidelines. 
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents. 
• 
Quality tolerance limits (QTLs) will be predefined in the Study Management Plan to 
identify systematic issues that can impact participant rights, safety and/or reliability 
of study results. These predefined parameters will be monitored during the study, 
and important deviations from the QTLs and remedial actions taken will be 
summarized in the clinical study report. 
• 
Monitoring details describing strategy, including definition of study critical data 
items and processes (e.g., risk-based initiatives in operations and quality such as risk 
management and mitigation strategies and analytical risk-based monitoring, 
involvement of central reading mechanism), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the monitoring 
plan. 
• 
The sponsor or designee is responsible for the data management of this study, 
including quality checking of the data. 
• 
The sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organizations). 
• 
Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for 25 years from the issue of the final clinical 
study report/equivalent summary unless local regulations or institutional policies 
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period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor. 
• 
When copies of source documents are shared externally for review by a central 
reader mechanism (e.g., endpoint adjudication committee, expert reader), documents 
are stored by the external body for 25 years. 
10.1.8. 
Source documents  
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data reported on the eCRF/eDiaries or entered in the eCRF/eDiaries that are 
transcribed from source documents must be consistent with the source documents or 
the discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records, depending on the study. Also, current medical 
records must be available. 
• 
Definition of what constitutes source data and its origin can be found in source data 
acknowledgment or monitoring guidelines. 
• 
The investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
• 
The sponsor or designee will perform monitoring to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and 
that the study is being conducted in accordance with the currently approved protocol 
and any other study agreements, ICH GCP, and all applicable regulatory 
requirements. 
10.1.9. 
Publication policy  
The results of this study may be published in peer reviewed scientific literature and/or 
presented at scientific meetings. The sponsor will comply with the requirements for 
publication of study results in accordance with standard editorial and ethical practice and 
as per the sponsor’s internal policy. Authorship will be determined by mutual agreement 
and in line with International Committee of Medical Journal Editors authorship 
requirements. 
10.2. 
Appendix 2: Clinical laboratory tests  
• 
The tests detailed in Table 10 will be performed at GSK’s laboratory or in a 
laboratory designated by GSK. 
• 
Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5. 
• 
Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 

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10.3. 
Appendix 3: AEs and SAEs: Definitions and procedures for 
recording, evaluating, follow-up, and reporting  
10.3.1. 
Definition of AE  
AE definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New condition detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
• 
Significant failure of an expected pharmacologic or biological action. 
• 
Events that occur as a result of protocol-mandated procedures (i.e., invasive 
procedures, modification of participant’s previous therapeutic regimen). 
Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 

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• 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital, admission for routine examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. Pre-existing 
diseases will be recorded in the medical history section of the eCRF. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from baseline. 
10.3.2. 
Definition of SAE  
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
a. 
Results in death. 
b. Is life threatening. 
The term 'life threatening' in the definition of 'serious' refers to an event in which 
the participant was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
− 
In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
− 
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity. 
− 
The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. 
− 
This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g., sprained ankle) that may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. 
Is a congenital anomaly/birth defect in the offspring of a study participant. 

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f. 
Other situations: 
− 
Possible Hy’s Law case: alanine transaminase ≥ 3x upper limit of normal 
(ULN) AND total bilirubin ≥ 2x ULN (>35% direct bilirubin) or international 
normalized ratio >1.5 must be reported as an SAE. 
− 
Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive 
treatment for allergic bronchospasm, blood dyscrasias, convulsions, or 
development of intervention dependency or intervention abuse. 
10.3.3. 
Solicited AEs  
Definition of Solicited AEs 
• 
Solicited AEs are predefined administration site and systemic events for which the 
participant is specifically questioned and which are noted by the participant in 
their eDiary up to 6 days after study intervention administration, i.e., from Day 1 
through Day 7. 
Solicited administration site AEs will include pain, redness, and swelling at the 
administration site and lymphadenopathy (localized axillary, cervical, or supraclavicular 
swelling or tenderness ipsilateral to the vaccination arm). 
Solicited systemic AEs will include fever, fatigue, headache, chills, myalgia, and 
arthralgia. Note: Participants will be instructed to measure and record the temperature in 
the evening. Oral temperature measurement is preferred. If additional temperature 
measurements are taken at other times of the day, participants will be instructed to record 
the highest temperature in their eDiary. 
10.3.4. 
Unsolicited AEs  
Definition of Unsolicited AE 
• 
An unsolicited AE is an AE that was either not included in the list of solicited 
events or could be included in the list of solicited events but with an onset outside 
the specified period of follow-up for solicited events. Unsolicited AEs must have 
been communicated by participants who have signed the informed consent. 
Unsolicited AEs include both serious and nonserious AEs. 

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• 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, emergency room visit, or visit to/by a healthcare 
provider). The participants will be instructed to contact the site as soon as possible 
to report MAAE(s), as well as any events that, though not medically attended, are 
of participants’ concern. Detailed information about reported unsolicited AEs will 
be collected by qualified site personnel and documented in the participant’s 
records. 
• 
Unsolicited AEs that are not medically attended or perceived as a concern by the 
participant will be collected during an interview with the participant and by review 
of available medical records at the next visit. 
10.3.5. 
Definition of MAAE  
MAAE Definition 
• 
An MAAE is defined as an AE that results in a visit to a medical professional 
(e.g., televisit, physician’s office visit, urgent care visit, emergency room visit, or 
hospitalization). 
10.3.6. 
Recording, assessment, and follow-up of AEs, SAEs, MAAEs, 
AESIs, and pregnancies  
10.3.6.1. 
AE and SAE recording  
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE information. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the required form. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 
Recording of solicited AEs 
An eDiary will be used in this study to capture solicited administration site and systemic 
events. The participant should be trained on how and when to complete the eDiary. 

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Anyone who measures administration site or systemic events and who will record the 
event in the eDiary should be trained on using the eDiary. This training must be 
documented in the participant’s source record. 
If the collection of solicited AEs was not possible for any reasons via the eDiary and 
solicited AEs were reported to the investigator by the participant, then it would be 
possible for them to be reported directly to the site staff and submitted (e.g., via the 
eCRF). 
Any unreturned eDiary devices will be sought from the participant through telephone 
call(s) or any other convenient procedure. 
Recording of MAAEs 
For each solicited and unsolicited AE the participant experiences, the participant will be 
asked if they received medical attention (defined as an unscheduled visit to or from 
medical personnel for any reason, including emergency room visits). This information 
will be recorded in the participant’s eDiary (for solicited AEs) and in the participant’s 
eCRF as part of normal AE reporting (for unsolicited AEs). 
Medical attention received for SAEs/AESIs will have to be reported using the normal AE 
reporting process in the eCRF. 
10.3.6.2. 
Time period for collecting and recording AEs, SAEs, MAAEs, AESIs 
and pregnancies  
All solicited events that occur during the 7-day follow-up period after study intervention 
administration (Day 1 to Day 7) must be recorded into the eDiary, irrespective of 
intensity. An automatic reminder to complete the eDiary will be sent to the participants 
during this timeframe. All other AEs occurring within this timeframe should be recorded 
into the appropriate section of the eCRF, irrespective of their intensity or whether or not 
they are considered related to the study intervention. 
All unsolicited AEs that occur during the 28-day follow-up period after study 
intervention administration (Day 1 to Day 28) must be recorded into the appropriate 
section of the eCRF, irrespective of their intensity or whether or not they are considered 
related to the study intervention. 
The time period for collecting and recording SAEs, MAAEs and AESIs will begin at the 
first receipt of study interventions and will end approximately 6 months after the last 
administration of the study interventions (at study end). The SAEs related to study 
participation or to a concurrent GSK medication/vaccine will be collected from the time 
consent is obtained until the participant is discharged from the study. 
All AEs/SAEs leading to withdrawal from the study and pregnancies will be collected 
and recorded from the time of the first receipt of study intervention until the participant is 
discharged from the study (refer to Section 10.3.6.6 for details on follow-up of 
pregnancies). SAEs related to study participation or to a concurrent GSK 
medication/vaccine will be collected from the time informed consent is obtained until the 

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participant is discharged from the study. However, if the investigator learns of any SAE 
related to study participation after a participant has been discharged from the study, the 
investigator must promptly notify the sponsor. 
10.3.6.3. 
Assessment of intensity  
The intensity of the following solicited AEs will be assessed as described: 
Table 16 
Intensity scales for solicited events  
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 
 
2 
5.1 – 10 cm 
 
3 
>10 cm 
Lymphadenopathy* 
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 
Temperature** 
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 

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Event 
Intensity grade 
Parameter 
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 
* Defined as localized axillary, cervical or supraclavicular swelling or tenderness ipsilateral to the vaccination arm. 
** Refer to Section 10.3.3 for the preferred location for temperature measurement. 
The investigator will make an assessment of intensity for each AE/AESI/SAE reported 
during the study and assign it to one of the following categories: 
• 
Mild: 
A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities 
of daily living. 
• 
Moderate: 
A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant. 
• 
Severe: 
A type of AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. 
10.3.6.4. 
Assessment of causality  
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship. 
• 
A reasonable possibility of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 
• 
For causality assessment, the investigator will also consult the IB and/or product 
information for marketed products. 
• 
The investigator must review and provide an assessment of causality for each 
AE/SAE and document this in the medical notes There may be situations in which an 
SAE has occurred and the investigator has minimal information to include in the 
initial report to PPD pharmacovigilance. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to PPD pharmacovigilance. 
• 
The investigator may change their opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 

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• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
10.3.6.5. 
Assessment of outcomes  
The investigator will assess the outcome of all serious and nonserious unsolicited AEs 
recorded during the study as: 
• 
Recovered/resolved 
• 
Recovering/resolving 
• 
Not recovered/not resolved 
• 
Recovered with sequelae/resolved with sequelae 
• 
Fatal (SAEs only) 
10.3.6.6. 
Follow-up of AEs, SAEs, AESIs, pregnancies or any other events of 
interest  
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other health care professionals. 
• 
New or updated information will be recorded in the originally submitted documents. 
• 
The investigator will submit any updated SAE data to PPD pharmacovigilance 
within 24 hours of receipt of the information. 
After the initial AE/SAE/AESI/pregnancy or any other event of interest, the investigator 
is required to proactively follow each participant at subsequent visits/contacts. 
All SAEs, and nonserious AESIs (as defined in the Section 8.4.4), will be followed until 
the event is resolved, stabilized, otherwise explained, or the participant is lost to follow-
up. Other nonserious AEs must be followed until the end of the study or until the 
participant is lost to follow-up. 
Follow-up during the study 
All AEs/SAEs/AESIs documented at a previous visit/contact and defined as not 
recovered/not resolved or recovering/resolving will be reviewed at subsequent 
visits/contacts until study end. 
If a participant dies during their participation in the study or during a recognized follow-
up period, GSK will be provided with any available postmortem findings, including 
histopathology. 

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Follow-up of pregnancies 
Pregnant participants will be followed to determine the outcome of the pregnancy, 
considering local requirements. At the end of the pregnancy, whether full-term or 
premature, information on the status of the mother and child will be forwarded to PPD 
pharmacovigilance using the paper pregnancy follow-up report and the AE report if 
applicable. Generally, the follow-up period does not need to be longer than 6 to 8 weeks 
after the estimated date of delivery and should follow local requirements. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is an 
SAE, it should always be reported as such. 
Furthermore, the investigator must report any SAE occurring as a result of a post-study 
pregnancy that is considered by the investigator to be reasonably related to the study 
intervention to PPD pharmacovigilance as described in the Section 10.3.6.8. 
10.3.6.7. 
Updating of SAE, AESI, and pregnancy information after removal of 
write-access to the participant’s eCRF  
When additional SAE, AESI, or pregnancy information is received after write-access to 
the participant’s eCRF is removed, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be sent to the study contact for reporting SAEs (refer to Section 
8.4.3). 
10.3.6.8. 
Reporting of SAEs, AESIs and pregnancies  
Reporting SAEs to PPD pharmacovigilance via an electronic data collection tool as 
follows: 
• 
The primary mechanism for reporting an SAE will be the electronic data collection 
tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
After the study is completed at a given site, the electronic data collection tool will be 
taken offline to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken offline, then the site can report this information on a paper SAE form (see next 
section) or to the medical monitor by telephone. 
• 
If the site during the course of the study or after the study ends becomes aware of 
any serious or nonserious AEs, pregnancy exposure, related to any GSK non-IMP, 
they will report these events to PPD pharmacovigilance or to the concerned 

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competent authority via the national spontaneous reporting system. These will be 
classified as spontaneous individual case safety reports. 
• 
Contacts for SAE reporting can be found in Section 8.4.7. 
Reporting SAEs to PPD pharmacovigilance via paper data collection tool as follows: 
• 
Email/facsimile transmission of the SAE paper data collection tool is the preferred 
method to transmit this information to the medical monitor. 
• 
In rare circumstances and in the absence of email/facsimile equipment, notification 
by telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting 
timeframes. 
• 
Contacts for SAE reporting can be found in Section 8.4.7. 
10.3.7. 
Study and site start and closure  
Start of study and first act of recruitment 
The start of study and the first act of recruitment are defined as first participant first visit 
(first ICF signature date) at a country-level. 
Study/site termination 
GSK or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
For study termination: 
• 
Discontinuation of further study intervention development 
For site termination: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor’s procedures, or GCP guidelines 
• 
Inadequate or no recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
• 
Total number of participants included earlier than expected 

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If the study is prematurely terminated or temporarily suspended, the sponsor shall 
promptly inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
contract research organization(s) used in the study of the reason for termination or 
temporary 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. 
10.4. 
Appendix 4: Contraceptive and barrier guidance  
10.4.1. 
Definitions  
10.4.1.1. 
Women of childbearing potential  
Women from the time of menarche until becoming postmenopausal unless permanently 
sterile (see below) are considered WOCBP (fertile). 
10.4.1.2. 
Women of non-childbearing potential  
Women in the following categories are considered women of non-childbearing potential: 
1. Permanently sterile due to one of the following procedures: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
For permanently sterile individuals due to an alternate medical cause other than the 
above (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 
investigator discretion should be applied to determining study entry. If reproductive 
status is questionable, additional evaluation should be considered. 
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. 
− 
A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT). However, in the absence 
of 12 months of amenorrhea, confirmation with more than 1 FSH measurement 
is required. 
− 
Females on HRT and whose menopausal status is in doubt must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment. 

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10.4.2. 
Contraception guidance  
• 
WOCBP are eligible to participate if they agree to use a highly effective 
contraceptive method consistently and correctly according to the methods listed in 
GSK’s list of highly effective contraceptive methods (Table 17). 
Table 17 
Highly effective contraceptive methods  
Highly Effective Contraceptive Methods That Are User Dependent* 
Failure rate of <1% per year when used consistently and correctly 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Injectable 
• 
Oral 
Highly Effective Methods That Are User Independent  
• 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device 
• 
Intrauterine hormone-releasing system 
• 
Bilateral tubal occlusion/ligation 
Vasectomized partner 
(A vasectomized partner is a highly effective contraception method provided that the partner is the sole male 
sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly 
effective method of contraception should be used.)  
Male partner sterilization prior to the female participant’s entry into the study, and this male is the sole partner for that 
participant. 
(The information on the male sterility can come from the site personnel’s review of the participant’s medical 
records; medical examination and/or semen analysis, or medical history interview provided by her or her 
partner.) 
Sexual abstinence 
(Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the 
participant.)  
*Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with 
local regulations regarding the use of contraceptive methods for participants in clinical studies. 
10.5. 
Appendix 5: Protocol amendment history  
Not Applicable  

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11. 
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CONFIDENTIAL 
219075 (CV2 SARS-COV2-013 BST) 
Protocol Amendment 1 Final 
26 Sep 2023 
86 
 
 
 
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