A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 Vaccines
Phase: PHASE3
Conditions: COVID-19
Sponsor: Novavax

SARS-CoV-2 rS Vaccines 
Novavax 
Study Protocol 2019nCoV-314 Amendment 2 v4.0 
Confidential 
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A Phase 3, Randomized, Double-Blinded Study to 
Evaluate the Safety and Immunogenicity of Omicron 
Subvariant and Bivalent SARS-CoV-2 rS Vaccines in 
Adolescents Previously Vaccinated with mRNA 
COVID-19 Vaccines 
Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines 
 
Investigational Products 
Monovalent SARS-CoV-2 Omicron XBB.1.5 subvariant vaccine 
(NVX-CoV2601). 
Bivalent prototype (Wuhan-Hu-1) and Omicron XBB.1.5 subvariant vaccine 
(site-mixed NVX-CoV2373 + NVX-CoV2601). 
Protocol Number 
2019nCoV-314 
Clinical Trial Registry 
Identifiers 
NCT05973006 
Version Number 
4.0 
Version Date 
21 August 2023 
Version 
Amendment 2 
Sponsor 
Novavax, Inc 
21 Firstfield Road 
Gaithersburg, MD 20878 
United States 
 
Confidentiality Statement 
 
The information in this document is considered privileged and confidential by Novavax, Inc., 
and may not be disclosed to others except to the extent necessary to obtain Institutional Review 
Board (IRB) approval and informed consent, or as required by national and local laws. Persons 
to whom this information is disclosed must be informed that this information is privileged and 
confidential and that it should not be further disclosed. 

SARS-CoV-2 rS Vaccines 
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STATEMENT OF COMPLIANCE 
The study will be conducted in compliance with this clinical study protocol, Good Clinical 
Practices (GCP) as outlined by International Council for Harmonisation (ICH) E6(R2), and all 
applicable local and national regulatory requirements. Enrollment at any clinical study site may 
not begin prior to that site receiving approval from the ethics committee of record for the 
protocol and all materials provided to potential participants. 
Any amendments to the protocol or changes to the consent document will be approved before 
implementation of that amendment. Reconsent of previously enrolled participants may be 
necessary depending on the nature of the amendment. 
The Principal Investigator will ensure that changes to the study plan as defined by this protocol 
will not be made without prior agreement from the Sponsor and documented approval from the 
ethics committee of record, unless such a change is necessary to eliminate an immediate hazard 
to the study participants. 
All personnel involved in the conduct of this study have completed Human Subjects Protection 
and GCP Training as outlined by their governing institution. 

SARS-CoV-2 rS Vaccines 
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Study Protocol 2019nCoV-314 Amendment 2 v4.0 
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SPONSOR’S APPROVAL 
 
Title 
A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and 
Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in 
Adolescents Previously Vaccinated with mRNA COVID-19 Vaccines 
Protocol Number 
2019nCoV-314 
Version Number 
4.0 
Version Date 
21 August 2023 
Amendment 
Amendment 2 
The design of this study as outlined by this protocol has been reviewed and approved by the 
Sponsor’s responsible personnel as indicated in the signature table below. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical Representative 
Name: 
Title: 
Signature/Date: 
 
 
 
 
Clinical Operations Representative 
Name: 
Title: 
Signature/Date: 
 
 
 

SARS-CoV-2 rS Vaccines 
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Study Protocol 2019nCoV-314 Amendment 2 v4.0 
Confidential 
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INVESTIGATOR’S AGREEMENT 
I have read the protocol, appendices, and accessory materials related to Study 2019nCoV-314 
and agree to the following: 
• To conduct this study as described by the protocol and any accessory materials. 
• To protect the rights, safety, and welfare of the participants under my care. 
• To provide oversight to all personnel to whom study activities have been delegated. 
• To control all investigational products provided by the Sponsor and maintain records of 
the disposition of those products. 
• To conduct the study in accordance with all applicable local and national regulations, the 
requirements of the ethics committee of record for my clinical site, and Good Clinical 
Practices as outlined by ICH E6(R2). 
• To obtain approval for the protocol and written materials provided to participants prior to 
initiating the study at my site. 
• To obtain informed consent – and updated consent in the event of new information or 
amendments – from all participants enrolled at my study site prior to initiating any 
study-specific procedures or administering investigational products to those participants 
• To maintain records of each participant’s participation and all data required by the 
protocol. 
 
 
 
Name 
Title 
Institution 
Signature 
Date 

SARS-CoV-2 rS Vaccines 
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Study Protocol 2019nCoV-314 Amendment 2 v4.0 
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SUMMARY OF CHANGES 
Version 1.0 and Version 2.0 of the protocol were signed and approved internally but were not 
released externally. The changes to Amendment 1.0 Version 3.0 incorporated in Amendment 2.0 
Version 4.0 of the protocol, dated 21 August 2023 are summarized in the table below. Editorial 
and formatting changes are not included in this summary. 
 
Section Number 
Summary of Change 
Rationale for Change 
Section 1.1 Table 1 Schedule of 
Events 
Section 6.1.2.2 Day 0 – On-site 
Study Vaccination 
Section 6.1.2.3 Day 28 – In- 
person/Home Health Care 
Follow-up Visit (-1 to + 7 Days) 
Section 1 Synopsis Exploratory 
Objectives and Corresponding 
Endpoints 
Section 3 Objectives and 
Endpoints Table 2 
Section 9.2.4.4 Mucosal hACE2 
Receptor Binding Inhibition 
Assay Subset 
9.3.2.3 Analysis of Exploratory 
Immunogenicity Endpoints 
Specify terminology: SARS-CoV-2 
mucosal IgA-mediated hACE2 
receptor binding inhibition and/or 
antibody responses in a mucosal 
IgA-mediated hACE2 receptor 
binding inhibition assay. 
Clarify that the hACE2 receptor 
binding inhibition assay is a 
mucosal IgA-mediated assay. 
Section 6.1.1.2 
Unscheduled Study Visits 
Section 6.1.2.8.2 
Unscheduled Visit due to 
Suspected COVID-19 
…must contact the site within 3 
days of symptom onset. If possible, 
the participant should be brought in 
for an in-person visit to help gather 
vital signs and do any necessary 
work up inclusive of physical 
examination.…Only in situations 
where the participant cannot come 
in, should a telehealth visit be 
planned. must contact sites within 3 
days of symptom onset for an 
unscheduled telehealth visit due to 
suspected COVID 19. 
To clarify that whenever possible 
an on-site rather than a telehealth 
visit will be conducted for 
participants with suspected 
COVID-19 illness. 
Section 7.4.1 
Prohibited Therapies 
Topical tacrolimus and ocular 
cyclosporine are permitted. Use of 
inhaled glucocorticoids is 
prohibited. Rabies immune globulin 
should be administered if medically 
indicated. 
Reference to prohibited use of 
inhaled glucocorticoids was 
removed. 
Abbreviations: COVID-19 = coronavirus disease 2019; hACE2 = human angiotensin-converting enzyme 2; 
IgA = Immunoglobulin A; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. 

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TABLE OF CONTENTS 
STATEMENT OF COMPLIANCE ............................................................................................... 2 
SPONSOR’S APPROVAL ............................................................................................................ 3 
INVESTIGATOR’S AGREEMENT ............................................................................................. 4 
SUMMARY OF CHANGES ......................................................................................................... 5 
LIST OF TABLES ....................................................................................................................... 10 
LIST OF FIGURES ...................................................................................................................... 10 
LIST OF APPENDICES .............................................................................................................. 10 
LIST OF ABBREVIATIONS ...................................................................................................... 11 
1 
SYNOPSIS .......................................................................................................................... 14 
1.1 
Schedule of Events ........................................................................................................... 17 
2 
INTRODUCTION ............................................................................................................... 21 
2.1 
Background ...................................................................................................................... 21 
2.1.1 
Description of SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccines ....... 22 
2.1.2 
Supportive Nonclinical Data ......................................................................................... 22 
2.1.3 
Supportive Clinical Data ............................................................................................... 23 
2.1.3.1 
Clinical Pharmacology and Safety ............................................................................. 23 
2.1.4 
Benefit: Risk Assessment .............................................................................................. 26 
2.2 
Study Rationale ................................................................................................................ 27 
3 
OBJECTIVES AND ENDPOINTS ..................................................................................... 28 
4 
STUDY PLAN .................................................................................................................... 30 
4.1.1 
Study Schematic ............................................................................................................ 30 
4.1.2 
Study Design ................................................................................................................. 30 
4.1.3 
Design Rationale ........................................................................................................... 31 
5 
POPULATION .................................................................................................................... 31 
5.1 
Recruitment ...................................................................................................................... 31 
5.1.1 
Definitions ..................................................................................................................... 31 
5.1.2 
Inclusion Criteria ........................................................................................................... 32 
5.1.3 
Exclusion Criteria .......................................................................................................... 33 
5.2 
Other Considerations for Eligibility Criteria .................................................................... 34 
6 
STUDY CONDUCT ........................................................................................................... 35 
6.1 
Study Summary ................................................................................................................ 35 
6.1.1 
Scheduled Study Visits ................................................................................................. 35 
6.1.1.1 
Scheduled Study Visits .............................................................................................. 35 

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6.1.1.2 
Unscheduled Study Visits .......................................................................................... 36 
6.1.1.3 
COVID-19 Monitoring and Assessment of Severity ................................................. 36 
6.1.2 
Study Procedures ........................................................................................................... 37 
6.1.2.1 
Screening Period ........................................................................................................ 37 
6.1.2.2 
Day 0 – On-site Study Vaccination ............................................................................ 38 
6.1.2.3 
Day 28 – In-person/Home Health Care Follow-up Visit (-1 to + 7 Days) ................. 39 
6.1.2.4 
Day 56 – Phone Follow-up Visit (± 7 Days) .............................................................. 39 
6.1.2.5 
Day 90 – In-person/Home Health Care Follow-up Visit (± 7 Days) ......................... 40 
6.1.2.6 
Day 118 – Phone Follow-up Visit (± 7 Days) ............................................................ 40 
6.1.2.7 
Day 146 – Phone Follow-up Visit (± 15 Days) .......................................................... 40 
6.1.2.8 
Unscheduled Visit ...................................................................................................... 41 
6.1.2.9 
Day 180 – End of Study In-person/Home Health Care Visit (± 15 Days) ................. 41 
6.2 
Immunogenicity Assessments .......................................................................................... 42 
6.3 
Discontinuation or Withdrawal ........................................................................................ 43 
6.3.1 
Individual Participants ................................................................................................... 43 
6.3.1.1 
Withdrawal from Study. ............................................................................................. 43 
6.3.1.2 
Replacement of Participants ....................................................................................... 43 
6.3.1.3 
Participants Lost to Follow-up ................................................................................... 43 
6.3.1.4 
Study Vaccination Pause Rules .................................................................................. 44 
6.4 
Study Termination ............................................................................................................ 44 
7 
STUDY INTERVENTIONS ............................................................................................... 45 
7.1 
Description of Products .................................................................................................... 45 
7.1.1 
NVX-CoV2601 (5 µg) .................................................................................................. 45 
7.1.1.1 
Formulation, Storage, Preparation, and Handling ...................................................... 45 
7.1.1.2 
Dosing and Administration ........................................................................................ 45 
7.1.2 
Prototype/XBB.1.5 Bivalent Vaccine (5 µg [Total]) .................................................... 45 
7.1.2.1 
Formulation, Storage, Preparation, and Handling ...................................................... 45 
7.1.2.2 
Dosing and Administration ........................................................................................ 46 
7.2 
Treatment Assignment and Bias Minimization ................................................................ 46 
7.2.1 
Treatment Allocation ..................................................................................................... 46 
7.2.2 
Randomization Strategy and Procedure ........................................................................ 46 
7.2.3 
Extent and Maintenance of Blinding ............................................................................. 47 
7.2.4 
Unblinding Procedures .................................................................................................. 47 
7.2.4.1 
Planned Unblinding .................................................................................................... 47 
7.2.4.2 
Unplanned or Unintentional Unblinding .................................................................... 47 
7.3 
Assessment and Verification of Compliance ................................................................... 48 
7.4 
Prior and Concomitant Therapies ..................................................................................... 48 
7.4.1 
Prohibited Therapies ..................................................................................................... 48 

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8 
SAFETY MONITORING ................................................................................................... 49 
8.1 
Definitions ........................................................................................................................ 49 
8.2 
Documenting Adverse Events .......................................................................................... 51 
8.2.1 
Details of the Adverse Event ......................................................................................... 52 
8.2.1.1 
Assessment of Causality ............................................................................................. 52 
8.2.1.2 
Action Taken with Study Vaccine Due to Adverse Event ......................................... 52 
8.2.1.3 
Other Action Taken .................................................................................................... 53 
8.2.1.4 
AE Outcome ............................................................................................................... 53 
8.2.2 
Time Frame for Collection ............................................................................................ 53 
8.2.3 
Classification of Events ................................................................................................. 54 
8.2.3.1 
Treatment-Emergent Adverse Events ........................................................................ 54 
8.2.3.2 
Adverse Events of Special Interest ............................................................................. 54 
8.2.3.3 
Medically Attended Adverse Events .......................................................................... 56 
8.2.3.4 
Reactogenicity Symptoms .......................................................................................... 56 
8.3 
Reporting Adverse Events ................................................................................................ 57 
8.3.1 
Safety Reporting to Health Authorities, Independent Ethics 
Committees/Institutional Review Boards, and Investigators ........................................ 58 
8.3.2 
24/7 Medical Emergency Coverage for Urgent Protocol-related Medical 
Questions ....................................................................................................................... 58 
8.4 
Pregnancy ......................................................................................................................... 58 
8.5 
Overdose or Misuse .......................................................................................................... 59 
9 
ANALYSIS ......................................................................................................................... 59 
9.1 
Sample Size Calculations ................................................................................................. 59 
9.2 
Analysis Sets .................................................................................................................... 59 
9.2.1 
All Randomized Participants Analysis Set .................................................................... 60 
9.2.2 
Full Analysis Set ........................................................................................................... 60 
9.2.3 
Safety Analysis Set........................................................................................................ 60 
9.2.4 
Per-Protocol Analysis Set .............................................................................................. 60 
9.2.4.1 
Anti-S Protein IgG Serology Subset .......................................................................... 60 
9.2.4.2 
Neutralization Assay Subset....................................................................................... 60 
9.2.4.3 
hACE2 Receptor-Binding Inhibition Assay Subset ................................................... 60 
9.2.4.4 
Mucosal hACE2 Receptor Binding Inhibition Assay Subset ..................................... 61 
9.3 
Analyses to be Performed ................................................................................................ 61 
9.3.1 
Safety Analysis .............................................................................................................. 61 
9.3.1.1 
Solicited Adverse Events ........................................................................................... 61 
9.3.1.2 
Unsolicited Adverse Events ....................................................................................... 61 
9.3.1.3 
Prior and Concomitant Medications and Vaccinations .............................................. 61 
9.3.1.4 
Extent of Exposure ..................................................................................................... 62 

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9.3.1.5 
Vital Sign Measurements and Physical Examination ................................................. 62 
9.3.2 
Immunogenicity Analysis ............................................................................................. 62 
9.3.2.1 
Analysis of Primary Immunogenicity Endpoints ....................................................... 62 
9.3.2.2 
Analysis of Secondary Immunogenicity Endpoints ................................................... 63 
9.3.2.3 
Analysis of Exploratory Immunogenicity Endpoints ................................................. 63 
9.3.3 
Other Exploratory Analyses .......................................................................................... 64 
9.4 
Other Statistical Considerations ....................................................................................... 64 
9.4.1 
Population Analysis ...................................................................................................... 64 
9.4.1.1 
Disposition and Protocol Compliance ........................................................................ 64 
9.4.1.2 
Demographics and Baseline Characteristics .............................................................. 64 
9.4.1.3 
Listings of Population Analysis data .......................................................................... 65 
9.5 
Planned Interim Analyses ................................................................................................. 65 
9.6 
Specified Analyses for Independent Data Monitoring Committee Review ..................... 65 
9.7 
Procedures for Reporting Changes to the Planned Analysis ............................................ 65 
10 
ETHICAL CONSIDERATIONS ........................................................................................ 65 
10.1 
Good Clinical Practice ..................................................................................................... 65 
10.2 
Ethics Review ................................................................................................................... 65 
10.3 
Informed Consent ............................................................................................................. 66 
10.4 
Data Privacy ..................................................................................................................... 66 
11 
OVERSIGHT ...................................................................................................................... 67 
11.1 
Quality Control and Assurance ........................................................................................ 67 
11.1.1 
Monitoring ..................................................................................................................... 67 
11.1.2 
Audits ............................................................................................................................ 68 
11.1.3 
Protocol Deviations ....................................................................................................... 68 
11.1.4 
Records .......................................................................................................................... 68 
11.1.4.1 
Data Capture and Management .................................................................................. 68 
11.1.4.2 
Source Documentation ............................................................................................... 69 
11.1.4.3 
Records Retention ...................................................................................................... 69 
11.2 
Study Termination or Study Site Closure ........................................................................ 69 
12 
PUBLICATION POLICY ................................................................................................... 69 
13 
FINANCING AND INSURANCE ..................................................................................... 70 
14 
REFERENCES .................................................................................................................... 71 
15 
APPENDICES ..................................................................................................................... 75 

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LIST OF TABLES 
Table 1: 
Schedule of Events for Study 2019nCoV-314 ..................................................... 18 
Table 2: 
Study 2019nCoV-314 Objectives and Endpoints ................................................. 28 
Table 3: 
Study Groups and Treatments .............................................................................. 31 
Table 4: 
Investigational Treatments Used in This Study ................................................... 45 
Table 5: 
Case Definitions of Probable and Confirmed Myocarditis, Pericarditis, and 
Myopericarditis .................................................................................................... 55 
Table 6: 
Management of Probable or Confirmed Myocarditis, Pericarditis, and 
Myopericarditis Cases .......................................................................................... 56 
Table 7: 
Potential Immune-Mediated Medical Conditions ................................................ 75 
Table 8: 
Adverse Events Representing Complications Specific to COVID-191 ........................ 76 
Table 9: 
Modified FDA Toxicity Grading Scale for Clinical Abnormalities (Local 
and General Systemic Reactogenicity) ................................................................. 77 
Table 10: 
FDA Toxicity Grading Scale for Clinical Abnormalities (Vital Signs) ............... 78 
Table 11: 
COVID-19 Severity Grading Criteria .................................................................. 79 
 
LIST OF FIGURES 
Figure 1: 
Flow Diagram for Study 2019nCoV-314 ............................................................. 30 
 
 
LIST OF APPENDICES 
Appendix 1: 
Listings of Adverse Events of Special Interest .................................................... 75 
Appendix 2: 
Toxicity Grading Scale for Clinical Abnormalities (Local and General 
Systemic Reactogenicity and Vital Signs) ........................................................... 77 
Appendix 3: 
Assessment of COVID-19 Severity ..................................................................... 79 

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LIST OF ABBREVIATIONS 
 
Abbreviation 
Definition 
24/7 
24 hours 7 days a week 
2019nCoV 
Novel coronavirus 
AE 
Adverse event 
AESI 
Adverse event of special interest 
AHA 
American Heart Association 
ANCA 
Anti-neutrophil cytoplasmic antibody 
AR 
Adverse reaction 
BMI 
Body mass index 
CDC 
Centers for Disease Control 
CI 
Confidence interval 
COVID-19 
Coronavirus disease 2019 
CRO 
Clinical research organization 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eDiary 
Electronic participant-reported outcome diary application 
ELISA 
Enzyme-linked immunosorbent assay 
EOS 
End of study 
ER 
Emergency room 
EU 
European Union 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMC 
Geometric mean concentration 
GMEU 
Geometric mean ELISA unit 
GMFR 
Geometric mean fold rise 
GMT 
Geometric mean titer 
GMTR 
Geometric mean titer ratio (between groups) 
GP 
Glycoprotein 
hACE2 
Human angiotensin-converting enzyme 2 
HBV 
Hepatitis B virus 
HEENT 
Head, eyes, ears, nose, and throat 
HIV 
Human immunodeficiency virus 
HPV 
Human papilloma virus 

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Abbreviation 
Definition 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
ID50 
Inhibitory dilution at a concentration of 50% 
IEC 
Independent Ethics Committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IM 
Intramuscular 
IMP 
Investigational medical product 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System 
LB 
Lower bound 
LBCI 
Lower bound confidence interval 
LLOQ 
Lower Limit of Quantitation 
MAAE 
Medically attended adverse event 
MedDRA 
Medical Dictionary for Regulatory Activities 
MERS 
Middle East Respiratory Syndrome 
MHC 
Major histocompatibility complex 
mRNA 
Messenger ribonucleic acid 
NAb 
Neutralizing Antibody 
NVX-CoV2373 
Prototype vaccine with Matrix-M adjuvant 
NVX-CoV2515 
Omicron BA.1 subvariant vaccine with Matrix-M adjuvant 
NVX-CoV2601 
Omicron XBB.1.5 subvariant vaccine with Matrix-M adjuvant 
OTC 
Over-the-counter 
PCR 
Polymerase chain reaction 
PIMMC 
Potential immune-mediated medical conditions 
PP 
Per-Protocol 
PT 
Preferred term 
r 
Recombinant 
RNA 
Ribonucleic acid 
S 
Spike (protein) 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SAR 
Suspected adverse reaction 
SARS-CoV 
Severe acute respiratory syndrome coronavirus 

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Abbreviation 
Definition 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SARS-CoV-2 rS 
Severe acute respiratory syndrome coronavirus 2 recombinant spike protein 
nanoparticle vaccine 
SCR 
Seroconversion rate 
Sf9 
Spodoptera frugiperda 
SII 
Serum Institute of India 
SMC 
Safety Monitoring Committee 
SOC 
System organ class 
SOE 
Schedule of Events 
SOP 
Standard operating procedure 
Td 
Tetanus diphtheria 
Tdap/Dtap 
Tetanus, diphtheria and pertussis 
TEAE 
Treatment-emergent adverse event 
UK 
United Kingdom 
US 
United States 
VOC 
Variants of concern 
VRBPAC 
Vaccines and Related Biological Products Advisory Committee 
WHO 
World Health Organization 

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1 
SYNOPSIS 
 
Study Title 
A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and 
Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in 
Adolescents Previously Vaccinated with mRNA COVID-19 Vaccines 
Short Title 
Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines 
Study Phase 
3 
Study Design 
This is a Phase 3, randomized, double-blinded study to evaluate the safety and 
immunogenicity of booster doses of Omicron subvariant severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2) recombinant rS spike (S) protein nanoparticle 
vaccines (SARS-CoV-2 rS) adjuvanted with Matrix-M™ adjuvant (NVX-CoV2601 
[Omicron XBB.1.5]) and bivalent (NVX-CoV2373 [prototype] + NVX-CoV2601) in 
previously vaccinated adolescent participants ≥ 12 to < 18 years of age. 
Approximately 400 adolescents who have received a regimen of ≥ 2 doses of the 
Moderna and/or Pfizer-BioNTech monovalent and/or bivalent COVID-19 vaccines 
≥ 90 days previously will be randomized 1:1 to Group A or Group B: 
• 
Group A: 1 dose of NVX-CoV2601 (1 on Day 0) 
• 
Group B: 1 dose of bivalent NVX-CoV2373 + NVX-CoV2601 (1 on Day 0) 
All participants will remain on study for immunogenicity and safety data collection 
through Day 180. 
Rationale 
Novavax, Inc., is developing recombinant vaccines adjuvanted with the saponin based 
Matrix-M adjuvant for the prevention of disease caused by SARS-CoV-2. 
Given the widespread circulation of Omicron subvariants, regulatory body discussions, 
and the associated decreased immunogenicity and efficacy of previously approved 
vaccines based on the prototype Wuhan strain, vaccines based on the Omicron 
subvariant XBB.1.5 (NVX-CoV2601) were developed and are being evaluated for 
safety and immunogenicity. The Omicron subvariant product in this study will also be 
used in combination with a prototype (Wuhan-Hu-1) NVX-CoV2373 in the form of a 
site-mixed bivalent vaccine to explore the safety and immunogenicity of vaccines 
containing antigen for both the ancestral (Wuhan) and XBB.1.5 subvariant strains of 
SARS-CoV-2. 
This study is designed to assess the safety and immunogenicity of the Novavax 
Omicron XBB.1.5 subvariant vaccine (NVX-CoV2601) alone or in combination with 
the prototype Novavax vaccine (NVX-CoV2373) as a bivalent product in adolescent 
participants ≥ 12 to < 18 years of age who previously received ≥ 2 doses of 
approved/authorized monovalent and/or bivalent mRNA vaccines. 
The safety profile of the booster dose will be assessed along with its ability to increase 
antibody titers against the Omicron XBB.1.5 subvariant. If favorable safety and 
immunogenicity profiles are observed following the booster dose of NVX-CoV2601 or 
the bivalent product, this would support the use of bivalent, variant based vaccines in 
adolescents in the global COVID-19 vaccination effort. 
Target Population 
Medically stable male and non-pregnant female adolescents ≥ 12 to < 18 years of age. 
All participants will have received a regimen of ≥ 2 doses of the Moderna and/or Pfizer- 
BioNTech COVID-19 monovalent and/or bivalent vaccines ≥ 90 days prior to study 
vaccination. 

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Number of 
Participants 
Approximately 400 participants 
Length of 
Participation 
On study (including screening and follow-up): 
Up to approximately 194 days (7 months) 
Interventions 
1. NVX-CoV2601 (5 µg): Coformulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine 
with Matrix-M adjuvant: supplied as a solution for preparation for injection, at a 
concentration of 10 µg antigen and 100 µg adjuvant per mL. All injections will be 
administered in a 0.5 mL injection volume at a dose of 5 µg antigen with 50 µg 
Matrix-M adjuvant. 
2. Prototype/XBB.1.5 Bivalent Vaccine (5 µg): A site-mixed bivalent vaccine 
prepared by combining 0.25 mL of NVX-CoV2373 and 0.25 mL NVX-CoV2601. 
All injections will be administered in a 0.5 mL injection volume at a dose of 5 µg 
total antigen (2.5 µg prototype antigen + 2.5 µg Omicron XBB.1.5 antigen) with 
50 µg Matrix-M adjuvant. 
Primary Safety 
Objective and 
Endpoints 
Objective: To assess the overall safety of 1 heterologous booster dose of 
NVX-CoV2601 and the bivalent vaccine (NVX-CoV2373 + NVX-CoV2601). 
Endpoints: 
• 
Incidence, duration, and severity of solicited local and systemic adverse events 
(AEs) for 7 days following vaccination. 
• 
Incidence, severity, and relationship of unsolicited AEs through 28 days after 
vaccination 
• 
Incidence and severity of medically attended adverse events (MAAEs) attributed to 
study vaccine, adverse events of special interest (AESIs) (predefined list including 
potential immune-mediated medical conditions (PIMMCs), myocarditis and/or 
pericarditis, and complications specific to COVID-19), and serious adverse events 
(SAEs) through day 180 or end of study (EOS). 
Primary 
Immunogenicity 
Objective and 
Endpoints 
Objective: To describe the neutralizing antibody (NAb) response induced by 
NVX-CoV2601 and the bivalent vaccine (NVX-CoV2373 + NVX-CoV2601) against 
the Omicron XBB.1.5 strain. 
• 
Neutralizing antibody (NAb) geometric mean titers (GMTs) to the Omicron 
XBB.1.5 strain, assessed at Day 28 following initial study vaccination. 
• 
NAb geometric mean fold rise (GMFR) at Day 28 from baseline (Day 0). 
Secondary 
Objectives and 
Corresponding 
Endpoints 
Objective: To describe the NAb response induced by NVX-CoV2601 and the bivalent 
vaccine (NVX-CoV2373 + NVX-CoV2601) against the Omicron XBB.1.5 strain over 
time. 
Endpoints: 
• 
NAb GMTs to the Omicron XBB.1.5 strain at relevant time points (Days 0, 90, and 
180). 
• 
NAb GMFR at relevant time points (Days 90, and 180) from baseline (Day 0). 
Group 
Previous 
Vaccine 
Novavax Vaccine Booster 
(antigen/adjuvant) 
n 
A 
≥ 2 doses 
Moderna 
and/or 
Pfizer- 
BioNTech 
NVX-CoV2601 (5 μg/50 μg) 
200 
B 
Bivalent NVX-CoV2373 + NVX-CoV2601 
(5 μg/50 μg [total]) 
200 

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Objective: To describe immunoglobulin G (IgG) antibody levels induced by 
NVX-CoV2601 and the bivalent vaccine (NVX-CoV2373 + NVX-CoV2601) against 
the Omicron XBB.1.5 strain over time. 
Endpoints: 
• 
IgG geometric mean ELISA (enzyme linked immunosorbent assay) units (GMEUs) 
to the Omicron XBB.1.5 S protein at relevant time points (Days 0, 28, 90, and 
180). Derived/calculated endpoints based on these data will include GMFR. 
Exploratory 
Objectives and 
Corresponding 
Endpoints 
Objective: To describe the NAb and IgG antibody responses induced by 
NVX-CoV2601 and the bivalent vaccine (NVX-CoV2373 + NVX-CoV2601) against 
the ancestral (Wuhan) strain over time. 
Endpoints: 
• 
NAb titers and IgG GMEUs to the ancestral (Wuhan) strain at relevant time points 
(Days 0, 28, 90, and 180). Derived/calculated endpoints based on these data will 
include GMFR. 
Objective: To describe antibody responses in a human angiotensin converting enzyme-2 
(hACE2) receptor binding inhibition assay induced by NVX-CoV2601 and the bivalent 
vaccine (NVX-CoV2373 + NVX-CoV2601) to the Omicron XBB.1.5 and ancestral 
(Wuhan) strains over time. 
Endpoints: 
• 
GMTs to the Omicron XBB.1.5 and ancestral (Wuhan) strains at relevant time 
points (Days 0, 28, 90, and 180). Derived/calculated endpoints based on these data 
will include GMFR. 
Objective: To describe antibody responses in a mucosal IgA-mediated hACE2 receptor 
binding inhibition assay induced by NVX-CoV2601 and the bivalent vaccine 
(NVX-CoV2373 + NVX-CoV2601) to the Omicron XBB.1.5 and ancestral (Wuhan) 
strains over time. 
Endpoints: 
• 
GMTs to the Omicron XBB.1.5 and ancestral (Wuhan) strains at relevant time 
points (Days 0 and 28). Derived/calculated endpoints based on these data will 
include GMFR. 
Objective: To utilize additional assays (current or to be developed) to better 
characterize the immune response for future vaccine development needs. 
Endpoint: Additional endpoints to evaluate immune responses may be developed based 
on the assays used. 
Objective: To characterize the severity of COVID-19 in participants who become 
infected during the course of the study. 
Endpoint: Detected case will be characterized as mild, moderate, or severe as assessed 
using the provided criteria. 
Number of Sites 
Up to 25 sites in the United States and Canada (Canadian sites contingent upon 
additional approval). 
Study Duration 
Estimated duration: Approximately 7 months 

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1.1 
Schedule of Events 
The schedule of events (SOE) is presented in Table 1. 

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Table 1: 
Schedule of Events for Study 2019nCoV-314 
 
Study Day 
–14 to 01 
01 
28 
56 
90 
118 
146 
180 
Unscheduled 
Visit2, 19 
Window (days)3 
-1 to + 7 
± 7 
± 7 
± 7 
± 15 
± 15 
Study Visit 
Screening 
1 
219 
3 (Phone) 
419 
5 (Phone) 
6 (Phone) 
EOS4, 19 
Gen 
Sp 
Informed consent 
X 
Medical history5 
X 
Inclusion/exclusion criteria6 
X 
X7 
Demographics8 
X 
Prior/concomitant medications9 
X 
X7 
X 
X 
X 
X 
X 
X 
X 
X 
Vital sign measurements10 
X 
X7 
X 
X 
Urine pregnancy test (POCBP)11 
X 
X7 
Physical examination12 
X 
X7 
X 
X 
X 
Baseline ECG 
X7 
Monitoring and Assessment of COVID-19 
Severity13 
X 
X 
X 
X 
X 
X 
Nasal swab for SARS-CoV-2 (PCR) – 
anterior nares 
X7 
X 
Oral swab for SARS-CoV-2 (mucosal 
IgA-mediated hACE2 receptor-binding 
inhibition assay) 
X 
X 
Blood sampling for SARS-CoV-2 
serostatus (anti N-protein serology) 
X7 
X 
X 
Blood sampling for SARS-CoV-2 (ELISA 
for anti S-protein serology) 
X7 
X 
X 
X 
X 
Blood sampling for SARS-CoV-2 NAb 
assay 
X7 
X 
X 
X 
X 
Blood sampling for hACE2 receptor- 
binding inhibition assay 
X7 
X 
X 
X 
X 
Vaccination14 
X 

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Table 1: 
Schedule of Events for Study 2019nCoV-314 
 
Study Day 
–14 to 01 
01 
28 
56 
90 
118 
146 
180 
Unscheduled 
Visit2, 19 
Window (days)3 
-1 to + 7 
± 7 
± 7 
± 7 
± 15 
± 15 
Study Visit 
Screening 
1 
219 
3 (Phone) 
419 
5 (Phone) 
6 (Phone) 
EOS4, 19 
Gen 
Sp 
Reactogenicity/participant eDiary 
completion14,15 
X 
All unsolicited AEs 
X 
X 
X 
X 
MAAEs16,17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SAEs17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AESI (including PIMMCs, myocarditis 
and/or pericarditis, and complications 
specific to COVID-19)17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
EOS form18 
X 
Abbreviations: AE = adverse event; AESI = adverse event(s) of special interest; BMI = body mass index; ECG = electrocardiogram; eDiary = electronic 
participant-reported outcome diary application; ELISA = enzyme-linked immunosorbent assay; EOS = end of study; Gen = Unscheduled Visit due to a 
general medical issue; hACE2 = human angiotensin-converting enzyme 2; HEENT = head, eye, ear, nose, and throat (examination); ID = identification; 
POCBP = participants of childbearing potential; MAAE = medically attended adverse event; N = nucleocapsid (protein); NAb = neutralizing antibody; 
OTC = over-the-counter; PCR = polymerase chain reaction; PIMMC = potential immune-mediated medical conditions; S = spike (protein); SAE = serious 
adverse event; SAP = statistical analysis plan; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; Sp = Unscheduled Visit due to suspected 
COVID-19 symptoms. 
1. The Screening visit and Day 0 visit may be combined if feasible at any given study site. 
2. An Unscheduled Visit will be conducted by study personnel for safety follow-up for any participant experiencing a medical issue while on study. For 
general Unscheduled Visits, the investigator may also perform any of the assessments listed in the SOE if needed for the clinical evaluation of an AE. For 
an Unscheduled Visit due to suspected COVID-19 symptoms, confirmed symptomatic cases of COVID-19 should be recorded as an AE, SAE, or 
COVID-19 relevant AESI as appropriate and the visit may be conducted as a telehealth visit if required by local health regulations. Positive PCR swab 
results in asymptomatic participants should also be entered as an AE. 
3. Should a study pause occur, visits/windows will be adjusted to allow participants to continue without protocol deviation. 
4. EOS assessments will be conducted in person. Should participants decide to terminate early, a telephone call will occur to collect the maximum safety data 
possible. 
5. Including prior and concomitant medical conditions, all COVID-19 vaccinations, all other recent vaccinations (≤ 90 days), and significant surgical 
procedures. 
6. Specific exclusions to study vaccination will be assessed before any vaccination. Waivers for enrolling participants with exclusions will not be given. 
7. Performed prior to study vaccination. 

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Table 1: 
Schedule of Events for Study 2019nCoV-314 
 
Study Day 
–14 to 01 
01 
28 
56 
90 
118 
146 
180 
Unscheduled 
Visit2, 19 
Window (days)3 
-1 to + 7 
± 7 
± 7 
± 7 
± 15 
± 15 
Study Visit 
Screening 
1 
219 
3 (Phone) 
419 
5 (Phone) 
6 (Phone) 
EOS4, 19 
Gen 
Sp 
8. Screening only. Including age, year of birth, sex, race, ethnicity, weight, height, and BMI (derived). 
9. Prior and concomitant medications, including recent and current medications at the time of screening to be reviewed to ensure eligibility criteria are 
fulfilled. Concomitant medications include prescription and OTC (including vaccines in the past 90 days and all COVID-19 vaccinations) taken by the 
participant. Do not record herbals, vitamins, and supplements. 
10. Including respiratory rate, blood pressure, pulse rate, pulse oximetry and temperature (oral or via forehead/ear reader). On study vaccination days, vital 
sign measurements will be collected once before study vaccination to ensure participant has no evidence of fever prior to study vaccination. 
11. Participants of childbearing potential only. A urine pregnancy test will be performed at Screening and prior to study vaccination. A positive urine 
pregnancy test at any time will result in the participant not receiving any further study vaccination. A positive urine pregnancy test at Screening will result 
in screen failure. 
12. Full physical examination at screening to include HEENT, neck, lungs, heart, cardiovascular, abdomen and musculoskeletal system/extremities to allow 
for study vaccination; symptom-directed (targeted) physical examination at all other scheduled time points. Full physical examinations will be performed 
at any unscheduled visit. 
13. Participants will be asked to report any PCR/rapid test confirmed cases of COVID-19 that occurred since last contact. For all medically attended cases of 
COVID-19, an attempt will be made to obtain all relevant medical records in order to assess case severity. 
14. Following vaccination, participants will remain in the clinic or under study staff observation for at least 15 minutes post-vaccination to be monitored for 
any immediate hypersensitivity and anaphylaxis reactions. 
15. Participants will utilize an eDiary to record reactogenicity following vaccination and for an additional 6 days after vaccination. All eDiary entries will be 
reviewed and assessed by the investigator. 
16. All MAAEs will be collected for 28 days following vaccination. Only treatment related MAAEs will be collected throughout the duration of the study. 
17. Details regarding the dates and nature of any health encounters associated with SAEs, AESIs, and/or MAAEs that required a visit with a healthcare 
provider will be collected in the eCRF. 
18. EOS form will be completed for all participants, including participants who are terminated early. 
19. These visits may take place at the homes of trial participants or another safe, alternative location by a professionally trained Home Health Care provider. 

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2 
INTRODUCTION 
2.1 
Background 
Coronaviruses are medium sized, enveloped, positive-stranded ribonucleic acid (RNA) viruses, 
with a characteristic crown-like appearance in electron micrographs due to circumferential 
studding of the viral envelope with projections comprising the spike (S) protein. There are 
4 different strains (229E, OC43, NL63, and HKU1), which are ubiquitous in humans and 
generally result in mild upper respiratory illnesses and other common cold symptoms, including 
malaise, headache, nasal discharge, sore throat, fever, and cough (Su 2016). In addition, other 
coronavirus strains are widespread in animals, where they typically cause enteric disease. These 
zoonotic coronaviruses have been known to evolve into strains that can infect humans with 
serious consequences, including severe acute respiratory syndrome coronavirus (SARS-CoV) 
from 2002 to 2003, Middle East Respiratory Syndrome (MERS)-CoV since 2012, and most 
recently, the novel SARS-CoV-2 since 2019 (Habibzadeh 2020). 
In late December of 2019, an outbreak of respiratory disease caused by a novel coronavirus 
(2019nCoV) was detected in Wuhan, Hubei province, China. The virus’ rapidly discerned 
genetic relationship with the 2002-2003 SARS-CoV has resulted in adoption of the name 
“SARS-CoV-2,” with the disease being referred to as Coronavirus disease 2019 (COVID-19). 
Thereafter, reports from the United Kingdom (UK), Brazil, India, and South Africa revealed the 
emergence of the B.1.1.7 (Alpha), P.1 (Gamma), B.1.617.2 (Delta), and B.1.351 (Beta) and 
B.1.1.529 (Omicron) variants of SARS-CoV-2, respectively, with confirmed acquisition of 
mutations in key antigenic sites in the receptor-binding domain and N-terminal domain of the 
spike (S) protein. Omicron subvariants have persisted in circulation, with the XBB.1.5 subvariant 
accounting for approximately 82% of circulation as of 28 Apr 2023 (CDC 2022, CDC 2023). 
Current evidence demonstrates that variant strain mutations such as those in the Omicron 
XBB.1.5 sublineage confer the ability to evade both natural and vaccine induced neutralizing 
antibodies (Qu 2023, Yue 2023, Zhang 2022). 
Initial actions to stay ahead of SARS-CoV-2 evolution included direction from the US Food and 
Drug Administration (FDA) to recommend the development vaccines containing an Omicron 
BA.4/5 component (Marks 2022). On 26 January 2023, the Vaccines and Related Biological 
Products Advisory Committee (VRBPAC) met to discuss further updates to the composition of 
COVID-19 vaccines. At the conclusion of this meeting, the VRBPAC voted to harmonize the 
vaccine strain composition of primary series and booster vaccinations into a single, updated 
composition for the fall 2023 vaccination campaign. 
The present study will assess the safety and immunogenicity of an Omicron XBB.1.5 subvariant 
vaccine (NVX-CoV2601) alone as a monovalent product or in combination with the prototype 
Novavax vaccine (NVX-CoV2373) as a bivalent product in an adolescent population. The study 
will enroll adolescent participants ≥ 12 to < 18 years of age who have previously received 

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≥ 2 doses of the Moderna and/or Pfizer-BioNTech monovalent and/or bivalent vaccines 
≥ 90 days prior to study vaccination. 
2.1.1 
Description of SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccines 
NVX-CoV2373 is the prototype SARS-CoV-2 rS nanoparticle vaccine construct adjuvanted with 
Matrix-M adjuvant that is intended to be used for the active immunization for the prevention of 
mild, moderate, and severe COVID-19 caused by SARS-CoV-2. NVX-CoV2373 is constructed 
from the full-length, wild-type SARS-CoV-2 S glycoprotein (GP) based on the GenBank gene 
sequence MN908947, nucleotides 21563-25384 from the 2019 SARS-CoV-2 genome (Wuhan- 
Hu-1 strain). In the wake of emerging SARS-CoV-2 variants, Novavax continues to produce and 
investigate rS nanoparticle vaccines using the sequenced genomes from several variant strains 
(multiple potential sequences being evaluated with one to be down-selected for final production). 
The S protein from each virus is a type 1 trimeric GP that is produced as an inactive 
S0 precursor. The S-gene is then codon-optimized for expression in Spodoptera frugiperda (Sf9) 
insect cells. 
All SARS-CoV-2 rS vaccines are adjuvanted with Matrix-M adjuvant. Adjuvants are compounds 
which, when combined with a specific vaccine antigen, serve to increase the immune response to 
the vaccine. In general, adjuvants work by engaging one or more components of the innate 
immune system. Matrix-M is a saponin-based adjuvant, derived from the bark of the Quillaja 
saponaria Molina tree, which can be co-administered with an antigen to induce a targeted and 
enhanced immune response. The proposed mode of action of Matrix-M adjuvant does not 
include a depot effect, but rather occurs through a combination of activities, including 
recruitment and activation of innate immune cells to the site of vaccine injection, rapid antigen 
delivery to antigen-presenting cells, and enhanced antigen presentation via both major 
histocompatibility complex (MHC) I and MHC II molecules in the draining lymph nodes. 
The investigational products used in this study are manufactured by Serum Institute of India (SII) 
through a partnership with Novavax. Production of NVX-CoV2601 was initiated based on 
master virus seeds produced and supplied to SII by Novavax. Aside from the differences in 
antigenic composition compared to NVX-CoV2373; the manufacturing process and final 
composition will be the same as for the authorized NVX-CoV2373 vaccine. 
Additional product information, including manufacturing details and supportive clinical and 
nonclinical study summaries, can be found in the SARS-CoV-2 rS Investigator’s Brochure (IB) 
(Novavax 2022). 
2.1.2 
Supportive Nonclinical Data 
Supportive nonclinical data are available through studies conducted for the Novavax 
manufactured prototype SARS-CoV-2 rS product (NVX-CoV2373). Pharmacological properties 
of the vaccines used in this study are expected to be equivalent to those produced by Novavax. 

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Nonclinical safety, immunogenicity, and protective efficacy have now been confirmed in Phase 3 
clinical trials. Nonclinical data can be found in the Investigator’s Brochure. 
A good laboratory practice (GLP)-compliant developmental and reproductive toxicity study was 
completed in Sprague-Dawley rats. Females were immunized with placebo, 5 µg of SARS-CoV- 
2 rS antigen with 10 µg of Matrix-M adjuvant, or 10 µg of Matrix-M adjuvant alone. These 
doses were approximately 40-fold in excess of the human dose, on a weight-adjusted basis, in a 
50 kg human female. Doses were given on pre-mating Days 1 and 15, and then, after mating, at 
gestational Days 7 and 15. Dams immunized with antigen plus adjuvant, but not adjuvant alone, 
had strong anti-S immunoglobulin G (IgG) responses, and vaccine-induced antibody was 
transferred transplacentally to the fetuses. Mating and fertility, as well as the number and 
viability of fetuses, were unaffected by adjuvant or complete vaccine. There was no treatment 
effect on fetal malformations or skeletal abnormalities. In dams allowed to deliver, receipt of 
adjuvant or complete vaccine did not affect the gestational duration at delivery or the number of 
live pups; and there was also no impact of the attainment of developmental milestones by pups 
through 21 days of life. 
2.1.3 
Supportive Clinical Data 
Supportive clinical data are available via studies conducted using Novavax manufactured 
SARS-CoV-2 rS products. 
As of this date, clinical data are available from studies performed using NVX-CoV2373 and an 
Omicron BA.1 variant vaccine (NVX-CoV2515). 
The clinical development program for Novavax’s SARS-CoV-2 rS with Matrix-M adjuvant 
primarily comprises 4 clinical studies: a Phase 1-2 study of SARS-CoV-2 rS with or without 
Matrix-M adjuvant in healthy adult participants 18 to 59 years of age (Study 2019nCoV-101– 
Part 1) and SARS-CoV-2 rS with Matrix-M adjuvant in healthy adult participants 18 to 84 years 
of age (Study 2019nCoV-101 – Part 2); a Phase 2a/b study of SARS-CoV-2 rS with Matrix-M 
adjuvant in healthy adult participants 18 to 84 years of age living without human 
immunodeficiency virus (HIV) and medically stable adult participants 18 to 64 years of age 
living with HIV (Study 2019nCoV-501); and 2 Phase 3 studies in healthy and medically stable 
adult participants ≥ 18 years of age and adolescent participants 12 to < 18 years of age 
(Study 2019nCoV-301) and 18 to 84 years of age (Study 2019nCoV-302). 
2.1.3.1 
Clinical Pharmacology and Safety 
Clinical data from Phase 1-2 trials and additional clinical data from Phase 3 trials can be found in 
the Investigator’s Brochure and their respective publications (Novavax 2022, Keech 2020, 
Mallory 2022, Dunkle 2021, Heath 2021, Shinde 2021). In total, over 30,000 participants have 
been immunized with NVX-CoV2373 in clinical trials and 2,266,287 NVX-CoV2373 doses have 
been administered in Australia, Canada, European Union (EU), Israel, Japan, New Zealand, 

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Singapore, South Korea, Switzerland, Taiwan, and the United States (US) cumulatively as of 17 
November 2022. 
Study 2019nCoV-302 was a Phase 3, randomized (1:1), observer-blinded, placebo-controlled 
trial evaluating the efficacy, safety, and immunogenicity of 5 µg SARS-CoV-2 rS with 
50 µg Matrix-M adjuvant, administered 21 days apart on Days 0 and 21 as a coformulation, in 
15,139 healthy and medically stable (with comorbidities) participants 18 to 84 years of age 
conducted in the United Kingdom (UK). After the initial vaccination period, participants 
remained blinded and crossed over to the opposite treatment arm. An analysis of the primary 
efficacy endpoint, which included both immunogenicity and safety data, was performed. A total 
of 106 cases of polymerase chain reaction (PCR) -confirmed symptomatic mild, moderate, or 
severe COVID-19 were accrued for the final prespecified analysis of the primary endpoint, with 
10 (0.1%) in the NVX-CoV2373 group and 96 (1.4%) in the placebo group. All but 5 cases were 
mild or moderate in severity, with all 5 severe cases occurring in the placebo group. The 
resultant vaccine efficacy of NVX-CoV2373 to prevent symptomatic mild, moderate, or severe 
COVID-19 in baseline seronegative (to SARS-CoV-2) adult participants was 89.7% (95% CI: 
80.2, 94.6; p < 0.001), with a lower bound confidence interval (LBCI) > 30% meeting the 
prespecified study success criterion. PCR results of the final analysis by SARS-CoV-2 strain 
showed vaccine efficacy of 86.3% (95% CI: 71.3, 93.5) for the B.1.1.7 (Alpha) variant and 
96.4% (95% CI: 73.8, 99.5) for the ancestral (Wuhan) strain. NVX-CoV2373 induced robust 
immune responses (anti-S IgG and neutralizing antibody [Nab]), which were 1.3-fold (anti-S 
IgG) and 1.4-fold (Nab) higher in the younger age cohort (18 to 64 years) than in the older age 
cohort (65 to 84 years), but seroconversion rates (SCRs) were at least 98% in both age cohorts. 
NVX-CoV2373 was well tolerated, with similar frequencies of serious adverse events (SAEs), 
medically attended adverse events (MAAEs), and adverse events of special interest (AESIs) 
compared to placebo. Solicited local and systemic reactogenicity in a subset of 2,714 participants 
were higher for NVX-CoV2373 than placebo, but the majority of reported events were classified 
as grade 1 following first vaccination and grade 1 or grade 2 following second vaccination. The 
most frequent local AEs following each vaccination were tenderness and pain, with relatively 
short median durations following first (≤ 2.0 days) and second (≤ 3.0 days) vaccination. The 
most frequent solicited systemic AEs following each vaccination were headache, fatigue, and 
muscle pain, with relatively short median durations following first (≤ 1.5 days) and second 
(≤ 2.0 days) vaccination. Across the 2 age strata, participants in the older age cohort (65 to 
84 years of age) reported a lower frequency and intensity of solicited local and systemic 
treatment emergent adverse events (TEAEs) than participants in the younger age cohort (18 to 64 
years of age). 
Study 2019nCoV-301 is a Phase 3, randomized (2:1), observer-blinded, placebo-controlled trial 
with a pediatric expansion evaluating the efficacy, safety, and immunogenicity of NVX- 
CoV2373, administered 21 days apart on Days 0 and 21 as a coformulation, in 29,582 healthy 
and medically stable (with comorbidities or at high risk for COVID-19) adult participants 
18 years of age and older conducted in the United States (US) and Mexico and the safety and 
immunogenicity of NVX-CoV2373 in 2,247 healthy adolescent participants 12 to < 18 years of 

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age conducted in the US. In adults, final analysis of the primary efficacy endpoint yielded a VE 
of 90.41% (95% CI: 83.81, 94.32) for all participants. In addition, NVX-CoV2373 induced 
robust immune responses and safety data reflected an acceptable safety profile. These data were 
submitted to the FDA in support of a request for Emergency Use Authorization. Subsequently, 
safety and immunogenicity data following a booster dose of NVX-CoV2373 from this study 
supported Emergency Use Authorization of the vaccine as a booster dose. 
The pediatric expansion of Study 2019nCoV-301 evaluated the efficacy, safety, and 
immunogenicity of NVX-CoV2373 in participants 12 to < 18 years of age. Out of the 1468 and 
730 participants in the NVX-CoV2373 and placebo groups, respectively, who received both 
vaccinations, 1277 (87.0%) and 618 (84.7%), respectively, had at least 60 days of follow-up after 
their second vaccination. NVX-CoV2373 was well tolerated and elicited significantly enhanced - 
immune responses, with similar frequencies of SAEs, MAAEs, and AESIs compared to placebo. 
As of the data cut-off date for the primary efficacy analysis among 1,197 participants receiving 
2 doses of NVX-CoV2373 and 590 participants receiving 2 doses of placebo, a two-dose 
regimen of NVX-CoV2373 administered at least 21 days apart demonstrated high efficacy for 
preventing PCR-confirmed symptomatic mild, moderate, or severe COVID-19 (VE = 79.56% 
[95% CI: 46.87,92.13]). Of note, efficacy data were collected during the time in which the Delta 
variant of concern (VOC) was the predominant circulating variant in the US. 
As a continuation of the pediatric expansion of Study 2019nCoV-301, a third (booster) dose of 
NVX-CoV2373 was administered in an open-label manner to participants who remained in study 
follow-up (either blinded or unblinded) and had received their full primary series of NVX- 
CoV2373 as planned. Booster doses were administered no less than 5 months after completion of 
active vaccination. Immunogenicity and safety data following the booster dose demonstrated 
non-inferiority of the booster dose of NVX-CoV2373 vs the primary series, with a GMFR of 
2.7 (95% CI: 2.0, 3.5) and an LB of the 95% CI > 1.0 (primary endpoint, NAb titers vs the 
ancestral strain), and found the dose was well tolerated with an acceptable safety profile 
comparable with the primary series and similar data in adults. 
Study 2019nCoV-311 is an ongoing Phase 3, multi-part, randomized, observer-blinded trial in 
healthy adult participants who previously received prototype mRNA COVID-19 vaccines, with 
their last dose of mRNA vaccine approximately 6 months prior to study vaccination. In Part 1 of 
the study, 831 participants were randomized 1:1:1 to receive a single booster dose of either 
NVX-CoV2515, NVX-CoV2373, or a bivalent vaccine (NVX-CoV2515 + NVX-CoV2373, 5 μg 
total antigen). An interim analysis performed 28 days after study vaccination found the primary 
objective of the study was met, achieving the endpoints needed to demonstrate that the Omicron 
5 specific vaccine (NVX-CoV2515) produced a superior antibody response to the Omicron BA.1 
subvariant when compared to the prototype vaccine (NVX-CoV2373) at Day 14. Safety analyses 
determined NVX-CoV2515, NVX-CoV2373, and the bivalent vaccine were all well-tolerated 
with comparable and acceptable safety profiles. 

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2.1.4 
Benefit: Risk Assessment 
The SARS-CoV-2 rS nanoparticle vaccines contain purified protein antigens. They cannot 
replicate, the protein is not produced using infectious SARS-CoV-2, nor can the vaccines cause 
COVID-19. However, in common with all vaccines produced in cell culture or other systems, the 
SARS-CoV-2 rS nanoparticle vaccines contain residual non-vaccine proteins derived from the 
production system, and sensitization to these, or the SARS-CoV-2 S protein itself, may 
theoretically occur. While the occurrence of anaphylaxis is possible with the administration of 
any vaccine, whether licensed or in development, no such reactions have been observed in any of 
the Sponsor’s clinical trials to date. As clinical data become available, with increased exposure it 
is possible that this profile may change. The risk of AEs related to hypersensitivity will be 
mitigated by observation of participants for at least 15 minutes after study vaccination. 
The risk for enhanced COVID-19 in immunized participants is a theoretical risk. There is 
currently no evidence for immunoenhancement in nonclinical testing of SARS-CoV-2 rS or other 
Novavax baculovirus-Sf9-based vaccines taken into nonclinical evaluation or clinical trials. 
No risks have been identified in nonclinical or early clinical testing of SARS-CoV-2 or other 
coronavirus vaccines (SARS-CoV and MERS-CoV) developed using the baculovirus-Sf9 system 
to date. In supportive toxicology studies with other viral GP nanoparticle vaccines developed 
using the baculovirus-Sf9 system with different antigens, findings were generally consistent with 
an immune response to the vaccine formulations. These toxicological investigations indicated 
that baculovirus-Sf9-produced antigens (up to 240 µg total nanoparticle dose) with Matrix-M 
adjuvant (up to 100 µg) were well tolerated in the animal and antigen system tested with no 
evidence of toxicity suggestive of any unusual risk or target organ for toxicity. Non-adverse 
findings, including local injection site inflammation and serum chemical markers of 
inflammation (such as C-reactive protein), were transient and considered consistent with immune 
system stimulation consequent to immunization. 
Myocarditis or pericarditis has been reported following vaccination with NVX-CoV2373 in 
clinical trials and following emergency use authorization, and it is possible that these reports 
represent vaccine-associated AEs similar to those associated with messenger ribonucleic acid 
(mRNA) COVID-19 vaccines. While available data may not be sufficient to definitively 
establish a causal relationship with NVX-CoV2373, neither can a causal relationship be 
excluded. 
Myocarditis or pericarditis associated with mRNA vaccines has been reported in greatest 
numbers in males under the age of 30 years following a second dose, but cases have been 
reported in older males and in females as well, and also following the first dose. While some 
cases required intensive care support, available data from short-term follow-up suggest that most 
individuals have had resolution of symptoms with conservative management. Information is not 
yet available about potential long-term-sequelae. 

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The Centers for Disease Control and Prevention (CDC) has published clinical considerations for 
myocarditis and pericarditis after receipt of mRNA COVID-19 vaccines among adolescents and 
young adults which makes specific recommendations for the management of myocarditis and 
pericarditis (CDC 2021). A surveillance and management plan for suspected myocarditis and/or 
pericarditis cases based on CDC and American Heart Association (AHA) recommendations has 
been implemented in the clinical development plan of NVX-CoV2373 (CDC 2021, Law 2021, 
Gargano 2021). 
Findings to date suggest that SARS-CoV-2 rS when administered with Matrix-M adjuvant 
(NVX-CoV2373) demonstrated an acceptable safety profile and robust immunogenicity profile 
in healthy and medically stable adult participants 18 to 84 years. Results of an interim 35-day 
reactogenicity analysis on 1,283 participants aged 18 to 84 years in Part 2 of 
Study 2019nCoV-101 and 2,714 participants 18 to 84 years in Study 2019nCoV-302 showed a 
similar reactogenicity profile between younger and older participants, with both local and 
systemic reactogenicity events occurring less frequently in older adults. In addition, nearly 
31,000 individuals have to date received at least 1 dose of NVX-CoV2373 and ongoing reviews 
of the accumulated safety data support continued development of the vaccine and vaccines based 
on the same platform. 
For the NVX-CoV2373 vaccine, clinical efficacy results are also available from studies run in 
the UK and South Africa. In the UK study (Study 2019nCoV-302), the overall efficacy of the 
vaccine was 89.7% (95% CI: 80.2, 94.6) and, in post hoc analyses, efficacy estimates for the 
B.1.1.7 (Alpha) variant and for the ancestral strain were 86.3% and 96.4%, respectively. In the 
South Africa study (Study 2019nCoV-501), the efficacy of the vaccine in all study participants 
was 48.6% (95% CI: 28.4, 63.1) and 55.4% (95% CI: 35.9, 68.9) in participants who were 
HIV-negative. The efficacy estimates in South Africa were generated in a period of > 90% 
B.1.351 (Beta) variant virus circulation. 
2.2 
Study Rationale 
In response to the emergence of the Omicron variant of SARS-CoV-2, Novavax, in conjunction 
with SII, has developed a Matrix-M-adjuvanted rS protein nanoparticle vaccine using the 
sequenced genome from the Omicron XBB.1.5 subvariant (NVX-CoV2601) for the prevention 
of disease caused by SARS-CoV-2 using the same recombinant baculovirus and insect cell 
vaccine platform technology employed previously to produce other SARS-CoV-2, influenza, and 
respiratory syncytial virus vaccines. NVX-CoV2601 will also be used in combination with 
NVX-CoV2373 in the form of a site-mixed bivalent vaccine (NVX-CoV2373 + NVX-CoV2601) 
to explore the safety and immunogenicity of vaccines containing antigen for both the ancestral 
(Wuhan) and Omicron subvariant strain of SARS-CoV-2. 
In sera tested from vaccinees who had received prior mRNA vaccines, Omicron neutralization 
was completely lost in > 50% of individuals accompanied by a 43-fold geometric mean titer 
(GMT) decrease for the Moderna vaccine and 122-fold decrease for the Pfizer-BioNTech 
vaccine. In subjects who had been recently boosted, Omicron neutralization for the Moderna 

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vaccine was only 6-fold lower than for the original wild-type neutralization, similarly for the 
Pfizer-BioNTech vaccine, the fold decrease was only 4 (Garcia-Beltran 2021). These tests show 
that 2-doses of mRNA vaccines are effective against the wild-type variant, but suboptimal for 
inducing equivalent neutralizing antibodies to the Omicron variant. In participants who had been 
boosted with an mRNA vaccine within the last 3-months showed correlation in 
cross-neutralization between the wild-type variant and the Omicron variant. 
Novavax, Inc. is developing recombinant vaccines adjuvanted with the saponin based Matrix-M 
adjuvant for the prevention of disease caused by SARS-CoV-2. Both nonclinical and clinical 
data to date support continued clinical development of SARS-CoV-2 rS vaccines combined with 
Matrix-M adjuvant as potential vaccines against SARS-CoV-2. 
This study is designed to assess the safety and immunogenicity of the Novavax Omicron 
XBB.1.5 subvariant vaccine (NVX-CoV2601) alone as a monovalent product or in combination 
with the prototype Novavax vaccine (NVX-CoV2373) as a bivalent product in adolescent 
participants ≥ 12 to < 18 years of age who previously received ≥ 2 doses of approved/authorized 
monovalent and/or bivalent mRNA vaccines. 
If favorable immunogenicity and safety profiles are observed following the booster doses of the 
bivalent product (NVX-CoV2373 + NVX-CoV2601), this would support the use of variant 
and/or bivalent vaccines in the global COVID-19 vaccination effort. 
3 
OBJECTIVES AND ENDPOINTS 
The primary objectives in this study are to assess the overall safety of 1 heterologous booster 
dose of NVX-CoV2601 and the bivalent vaccine (NVX-CoV2373 + NVX-CoV2601) and to 
describe the NAb responses induced against the Omicron XBB.1.5 strain. An overview of the 
study objectives and endpoints is provided in Table 2. 
 
Table 2: 
Study 2019nCoV-314 Objectives and Endpoints 
 
Tier 
Objectives 
Endpoints 
Primary Safety 
Objective and 
Endpoints 
To assess the overall safety of 1 
heterologous booster dose of 
NVX-CoV2601 and the bivalent vaccine 
(NVX-CoV2373 + NVX-CoV2601). 
• Incidence, duration, and severity of 
solicited local and systemic AEs for 7 
days following vaccination. 
• Incidence, severity, and relationship of 
unsolicited AEs through 28 days after 
vaccination 
• Incidence and severity of MAAEs 
attributed to study vaccine, AESIs 
(predefined list including PIMMCs, 
myocarditis and/or pericarditis, and 
complications specific to COVID-19), 
and SAEs through day 180 or EOS. 

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Table 2: 
Study 2019nCoV-314 Objectives and Endpoints 
 
Tier 
Objectives 
Endpoints 
Primary 
Immunogenicity 
Objective and 
Endpoints 
To describe the NAb response induced by 
NVX-CoV2601 and the bivalent vaccine 
(NVX-CoV2373 + NVX-CoV2601) 
against the Omicron XBB.1.5 strain. 
• NAb GMTs to the Omicron XBB.1.5 
strain, assessed at Day 28 following initial 
study vaccination. 
• NAb geometric mean fold rise (GMFR) at 
Day 28 from baseline (Day 0). 
Secondary 
Objectives 
To describe the NAb response induced by 
NVX-CoV2601 and the bivalent vaccine 
(NVX-CoV2373 + NVX-CoV2601) 
against the Omicron XBB.1.5 strain over 
time. 
• NAb GMTs to the Omicron XBB.1.5 
strain at relevant time points (Days 0, 90, 
and 180). 
• NAb GMFR at relevant time points (Days 
90 and 180) from baseline (Day 0) 
To describe immunoglobulin G (IgG) 
antibody levels induced by 
NVX-CoV2601 and the bivalent vaccine 
(NVX-CoV2373 + NVX-CoV2601) 
against the Omicron XBB.1.5 strain over 
time. 
• IgG GMEUs to the Omicron XBB.1.5 S 
protein at relevant time points (Days 0, 
90, and 180). Derived/calculated 
endpoints based on these data will include 
GMFR. 
Exploratory 
To describe the NAb and IgG antibody 
responses induced by NVX-CoV2601 and 
the bivalent vaccine (NVX-CoV2373 + 
NVX-CoV2601) against the ancestral 
(Wuhan) strain over time. 
• NAb titers and IgG GMEUs to the 
ancestral (Wuhan) strain at relevant time 
points (Days 0, 90, and 180). 
Derived/calculated endpoints based on 
these data will include GMFR. 
To describe antibody responses in a human 
angiotensin converting enzyme-2 (hACE2) 
receptor binding inhibition assay induced 
by NVX-CoV2601 and the bivalent 
vaccine (NVX-CoV2373 + 
NVX-CoV2601) to the Omicron XBB.1.5 
and ancestral (Wuhan) strains over time. 
• GMTs to the Omicron XBB.1.5 and 
ancestral (Wuhan) strains at relevant time 
points (Days 0, 90, and 180). 
Derived/calculated endpoints based on 
these data will include GMFR. 
To describe antibody responses in a 
mucosal IgA-mediated hACE2 receptor 
binding inhibition assay induced by 
NVX-CoV2601 and the bivalent vaccine 
(NVX-CoV2373 + NVX-CoV2601) to the 
Omicron XBB.1.5 and ancestral (Wuhan) 
strains over time. 
• GMTs to the Omicron XBB.1.5 and 
ancestral (Wuhan) strains at relevant time 
points (Days 0 and 28). 
Derived/calculated endpoints based on 
these data will include GMFR. 
To utilize additional assays (current or to 
be developed) to better characterize the 
immune response for future vaccine 
development needs. 
• Additional endpoints to evaluate immune 
responses may be developed based on the 
assays used. 
To characterize the severity of COVID-19 
in participants who become infected 
during the course of the study. 
• Detected case will be characterized as 
mild, moderate, or severe as assessed 
using the provided criteria. 
Abbreviations: AE = adverse event; AESI = adverse event(s) of special interest; ELISA = enzyme-linked 
immunosorbent assay; GMEU = geometric mean ELISA units; GMFR = geometric mean fold rise; GMT = 
geometric mean titer; hACE2 = human angiotensin-converting enzyme 2; IgG = immunoglobulin G; NAb = 

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neutralizing antibody; MAAE = medically attended adverse event; NAb = neutralizing antibody; PIMMC = 
potentially immune-mediated medical condition; S = spike; SAE = serious adverse event; SARS-CoV-2 = 
severe acute respiratory syndrome coronavirus 2. 
 
 
4 
STUDY PLAN 
4.1.1 
Study Schematic 
 
Figure 1: 
Flow Diagram for Study 2019nCoV-314 
 
Abbreviations: EOS = end of study; IM = intramuscular. 
Note: Group A = NVX-CoV2601 Day 0; Group B = Bivalent NVX-CoV2373 + NVX-CoV2601 Day 0. 
4.1.2 
Study Design 
This is a Phase 3, randomized, observer blinded study to evaluate the safety and immunogenicity 
of a booster dose of Omicron XBB.1.5 subvariant SARS-CoV-2 rS vaccines adjuvanted with 
Matrix-M adjuvant in previously vaccinated participants. 
Approximately 400 adolescents who have received a regimen of ≥ 2 doses of the Moderna and/or 
Pfizer-BioNTech monovalent and/or bivalent COVID-19 vaccines ≥ 90 days previously will be 
enrolled and randomized 1:1 to Group A or Group B. 
• Group A: 1 dose of NVX-CoV2601 (1 on Day 0) 
• Group B: 1 dose of bivalent NVX-CoV2373 + NVX-CoV2601 (1 on Day 0) 
Participants will remain on study for immunogenicity and safety data collection through 
Day 180. A tabular summary of the study design is provided below in Table 3, and a complete 
outline of study procedures is provided in Section 6.1.2. 

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Table 3: 
Study Groups and Treatments 
 
Group 
Previous Vaccine 
Novavax Vaccine Booster 
(antigen/adjuvant) 
n 
A 
≥ 2 doses Moderna 
and/or 
Pfizer-BioNTech 
NVX-CoV2601 (5 μg/50 μg) 
200 
B 
Bivalent NVX-CoV2373 + NVX-CoV2601 
(5 μg/50 μg [total]) 
200 
4.1.3 
Design Rationale 
This study is designed to assess the safety and immunogenicity of the Novavax Omicron 
XBB.1.5 subvariant vaccine (NVX-CoV2601) alone as a monovalent product or in combination 
with the prototype Novavax vaccine (NVX-CoV2373) as a bivalent product in adolescent 
participants ≥ 12 to < 18 years of age who previously received ≥ 2 doses of approved/authorized 
monovalent and/or bivalent mRNA vaccines. 
Enrolled participants are intended to match a representative US adolescent population, including 
participants with common vaccination histories and with no restrictions on prior COVID-19 
exposure. The sample size and study duration were selected to prioritize the collection of safety 
data. 
If favorable immunogenicity and safety profiles are observed following the booster doses of the 
bivalent product (NVX-CoV2373 + NVX-CoV2601), this would support the use of variant 
and/or bivalent vaccines in the global COVID-19 vaccination effort. 
5 
POPULATION 
5.1 
Recruitment 
Approximately 400 participants will be enrolled. Participants will be screened across 
approximately 25 different study sites located in the US and Canada (Canadian sites contingent 
upon additional approval). 
Participants will be medically stable male and nonpregnant females ≥ 12 to < 18 years of age 
who have previously received ≥ 2 doses of the Moderna and/or Pfizer-BioNTech monovalent 
and/or bivalent vaccines ≥ 90 days prior to study vaccination. 
5.1.1 
Definitions 
Participants officially enter the Screening Period following provision of informed consent. 
A screen failure is a consented participant who has been deemed ineligible on the basis of 1 or 
more eligibility criteria or who has withdrawn consent prior to treatment assignment. 

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An enrolled participant is one who has been deemed eligible and has been assigned to a 
treatment group. 
5.1.2 
Inclusion Criteria 
To be included in this study, each individual must satisfy all of the following criteria: 
1. Adolescents ≥ 12 to < 18 years of age at screening 
2. Participant and parent(s)/caregiver(s) or legally acceptable representative willing and able 
to give informed consent and assent, as required, prior to study enrollment and to comply 
with study procedures. 
3. Participants of childbearing potential (defined as any participant who has experienced 
menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or 
bilateral oophorectomy] or postmenopausal [defined as amenorrhea ≥ 12 consecutive 
months]) must agree to be heterosexually inactive from at least 28 days prior to 
enrollment and through the end of the study OR agree to consistently use a medically 
acceptable method of contraception listed below from ≥ 28 days prior to enrollment and 
through the end of the study. 
a. Condoms (male or female) with spermicide (if acceptable in country) 
b. Diaphragm with spermicide 
c. Cervical cap with spermicide 
d. Intrauterine device 
e. Oral or patch contraceptives 
f. Norplant®, Depo-Provera®, or other in country regulatory approved contraceptive 
method that is designed to protect against pregnancy 
g. Abstinence, as a form of contraception, is acceptable if in line with the participant's 
lifestyle 
NOTE: Periodic abstinence (eg, calendar, ovulation, sympto-thermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. 
4. Is medically stable, as determined by the investigator (based on review of health status, 
vital signs [to include body temperature], medical history, and targeted physical 
examination [to include body weight]). Vital signs must be within medically acceptable 
ranges prior to the vaccination. 
5. Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the 
duration of the study. 
NOTE: For participants who become hospitalized with COVID-19, participation in 
investigational treatment studies is permitted. 

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6. Have previously received ≥ 2 doses of the Moderna and/or Pfizer-BioNTech monovalent 
and/or bivalent COVID-19 vaccines with the last dose having been given ≥ 90 days 
previously prior to study vaccination. 
5.1.3 
Exclusion Criteria 
If an individual meets any of the following criteria, he or she is ineligible for this study: 
1. Received COVID-19 vaccines other than Moderna and/or Pfizer-BioNTech in the past, 
inclusive of clinical trial COVID-19 vaccines. 
2. Participation in research involving receipt of investigational products 
(drug/biologic/device) within 90 days prior to study vaccination. 
3. Received influenza vaccination within 14 days prior to study vaccination. 
4. Received any vaccine ≤ 45 days prior to study vaccination, except for rabies, human 
papilloma virus (HPV), tetanus-diphtheria (Td), tetanus, diphtheria, and pertussis 
(TDaP/DTap), hepatitis B virus (HBV), and meningococcal vaccines which may be given 
as medically indicated. 
5. Any known allergies to products contained in the investigational product. 
6. Any history of anaphylaxis to any prior vaccine. 
7. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring 
ongoing immunomodulatory therapy. 
NOTE: Stable endocrine disorders (eg, thyroiditis, pancreatitis), including stable diabetes 
mellitus with no history of diabetic ketoacidosis) are NOT excluded. 
8. Chronic administration (defined as > 14 continuous days) of immunosuppressant, 
systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to study 
vaccination. 
NOTE: An immunosuppressant dose of glucocorticoid is defined as a systemic dose 
≥ 10 mg of prednisone per day or equivalent. The use of topical or intranasal 
glucocorticoids is permitted. Topical tacrolimus and ocular cyclosporin are permitted. 
9. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 
90 days prior to study vaccination, except for rabies immunoglobulin which may be given 
if medically indicated. 
10. Active cancer (malignancy) on therapy within 3 years prior to study vaccination (with the 
exception of adequately treated non-melanomatous skin carcinoma or lentigo maligna 
and uterine cervical carcinoma in situ without evidence of disease, at the discretion of the 
investigator). 
11. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the 
end of study. 

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12. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the 
study vaccine dose that, in the opinion of the investigator, might interfere with protocol 
compliance. 
13. Any other condition that, in the opinion of the investigator, would pose a health risk to 
the participant if enrolled or could interfere with evaluation of the study vaccine or 
interpretation of study results (including neurologic or psychiatric conditions likely to 
impair the quality of safety reporting). 
14. Study team member or immediate family member of any study team member (inclusive 
of Sponsor, clinical research organization [CRO], and study site personnel involved in the 
conduct or planning of the study). 
15. Participants with a history of myocarditis or pericarditis. 
16. Respiratory symptoms in the past 3 days (ie, cough, sore throat, difficulty breathing). 
17. Temperature of > 38°C within 24 hours of planned study vaccination (site measured or 
participant measured). 
18. Blood pressure of ≥ 160/100 mmHg. 
5.2 
Other Considerations for Eligibility Criteria 
Participants meeting any of the following criteria may have planned study vaccination deferred 
for a later date, but these criteria are not exclusionary for study enrolment. 
• Respiratory symptoms in the past 3 days (ie, cough, sore throat, difficulty breathing). 
Participant may be vaccinated once all symptoms have been resolved for > 3 days. 
Out-of-window study vaccination is allowed for this reason (see NOTE). 
• Temperature of > 38°C within 24 hours of planned study vaccination (site measured or 
participant measured). Participant may be vaccinated once the fever has resolved and 
there has not been any temperature measured as being > 38°C for > 3 days without 
anti-pyrectics. Out-of-window study vaccination is allowed for this reason (see NOTE). 
NOTE: PCR testing for SARS-CoV-2 is likely to be indicated for either of the above 
reasons or if COVID-19 is suspected based on other symptoms or for potential 
exposure to SARS-CoV-2 infection through close contacts or based on local 
epidemiology. 
• Any participant who is otherwise eligible with a blood pressure of ≥ 160/100 mmHg may 
be retested onsite several times over a 3-hour interval to achieve a lower blood pressure. 
If the blood pressure remains ≥ 160/100 mmHg, study vaccination should be deferred for 
a later date if, at that time, the participant’s baseline blood pressure is found to be 
< 160/100 mmHg. 

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• Participants found to be SARS-CoV-2 positive during the study may be excluded from 
some analyses as per the statistical analysis plan (SAP) but will not be excluded from 
participation in the study. 
6 
STUDY CONDUCT 
A complete description of study procedures for participants is provided in Section 6.1.2 and a 
SOE is provided in Table 1. 
6.1 
Study Summary 
6.1.1 
Scheduled Study Visits 
All participants will follow the same treatment and assessment schedule and will remain on study 
for immunogenicity and safety data collection through Day 180, for a total study duration of up 
to 194 days (approximately 7 months). 
During the study, participants will have the option of remote (home) visits for Visits 2 (Day 28), 
4 (Day 90), Unscheduled (UNSCH) and EOS (Day 180). These home visits will be conducted by 
Illingworth Research Group who will act as an extension of the study trial sites. Illingworth Staff 
will be trained in the study and oversight will be provided by the PI they are assigned to support. 
Tasks conducted by the Illingworth Research team will include but not be limited to mobile 
research nursing, patient concierge, medical photography (if applicable) and any clinical research 
services/assessments as documented in the study protocol Schedule of Events and study plans for 
each visit conducted. 
6.1.1.1 
Scheduled Study Visits 
Scheduled study visits will occur for Screening and at Days 0, 28, 56, 90 118, 146, and 180: 
• Screening Period (Days -14 to 0). 
• Day 0: Randomization and booster administration. 
− Screening and Day 0 procedures can be conducted on the same day when feasible. 
• Day 28: Safety and immunogenicity follow-up for all participants. 
• Day 56: Phone Visit - Safety follow-up for all participants. 
• Day 90: Safety and immunogenicity follow-up for all participants. 
• Day 118: Phone Visit - Safety follow-up for all participants. 
• Day 146: Phone Visit - Safety follow-up for all participants. 
• Day 180: EOS visit for all participants. EOS procedures will be conducted via site visit 
when possible. These procedures should also be conducted for all participants upon early 
termination. 

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On vaccination Day 0, participants will remain in the clinic or under study staff observation for 
at least 15 minutes post-vaccination to be monitored for any immediate hypersensitivity and 
anaphylaxis reactions. Participants will utilize an electronic diary (eDiary) to record 
reactogenicity following vaccination. All participants will be asked to record reactogenicity on 
the day of vaccination and for an additional 6 days after vaccination. Should any reactogenicity 
event extend beyond 6 days after vaccination (toxicity grade ≥ 1), then it will be recorded using 
the Continuing Solicited AE form and followed to resolution per ICH guidelines for dataset 
capture. The toxicology grading scale implemented in the eDiary for the study is included in 
Appendix 2. 
Qualitative PCR tests will be performed on all participants on study Day 0. Confirmed 
symptomatic cases of COVID-19 should be recorded as an AE, SAE, or COVID-19 relevant 
AESI as appropriate. Positive PCR swab results in asymptomatic participants should also be 
entered as an AE. 
6.1.1.2 
Unscheduled Study Visits 
Unscheduled Visits may be conducted throughout the duration of the study either via in-person 
or by a Home Health Care provider as deemed necessary by the principal investigator. In many 
cases, they may be conducted by study personnel for safety follow-up for any participant 
experiencing a medical issue while on study. During an Unscheduled Visit, the principal 
investigator may elect to perform any of the assessments listed in the SOE (Table 1) including 
blood sample collection, physical assessments, or other optional testing for clinical evaluation of 
an AE. In situations where the unscheduled visit is not due to respiratory/non-respiratory 
symptoms consistent with suspected COVID-19, the visit may be done as an in-person clinical 
site visit or as a telehealth visit. If an in-person visit is done for non-COVID related symptoms, 
vital signs, physical examinations, and other procedures as needed may be done as requested by 
the Investigator. 
Participants and their guardians will be instructed to monitor for respiratory/non-respiratory 
symptoms of COVID-19 during the study. In cases of suspected COVID-19 illness where the 
participant has not been evaluated at an offsite medical facility, they must contact the site within 
3 days of symptom onset. If possible, the participant should have an in-person visit to help gather 
vital signs and do any necessary work up inclusive of physical examination. In cases where the 
participant has already been at an offsite facility, the site should endeavor to retrieve the visit 
notes. Only in situations where the participant cannot have an in-person visit should a telehealth 
visit be planned. Procedures for this visit are described in Section 6.1.2.8.2, and follow-up to 
confirm and assess the severity of the case of COVID-19 will be conducted at the next scheduled 
study visit. 
6.1.1.3 
COVID-19 Monitoring and Assessment of Severity 
At each scheduled study visit, participants will be asked to report any PCR/rapid test confirmed 
cases of COVID-19 that occurred since last contact. Additional follow-up for any prior reported 

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cases of COVID-19 (ie, an unscheduled telehealth visit due to suspected COVID-19) will be 
conducted as well. 
For all medically attended cases of COVID-19, an attempt will be made to obtain all medical 
records relevant to the COVID-19 healthcare visit and subsequent treatment in order to assess the 
severity of each case using the criteria provided in Appendix 3. Note, only the severity score 
should be recorded in the electronic case report form (eCRF). 
All PCR/rapid test confirmed symptomatic cases of COVID-19 should also be recorded as an 
AE, SAE, or COVID-19 relevant AESI as appropriate. 
Positive PCR swab results (performed in all participants at Day 0) in asymptomatic participants 
should also be entered as an AE. 
6.1.2 
Study Procedures 
6.1.2.1 
Screening Period 
The following procedures will be performed within 14 days of study vaccination. The Screening 
visit and Day 0 visit may be combined, if feasible, at any given study site. Screening information 
collected as part of a standard-of-care protocol prior to informed consent form (ICF) signing may 
be used if collected during the same healthcare visit. 
• Written informed consent will be obtained in conformance with Section 10.3 of this 
protocol. 
• Review of medical history, including prior and concomitant medical conditions, recent 
vaccinations (≤ 90 days), and significant surgical procedures. 
• Review of COVID-19 vaccination status, including number of prior vaccinations, 
vaccination type, and timing of most recent vaccination. 
• Inclusion and exclusion criteria review via participant discussion and medical history 
review consistent with Section 4.1.1. Specific exclusions to study vaccination will be 
assessed before any vaccination. Waivers for enrolling participants with exclusions will 
not be given. 
• Demographics, including age, year of birth, sex, race, ethnicity, weight, height, and body 
mass index (BMI; derived). 
• Prior and concomitant medications, including recent and current medications at the time 
of screening to be reviewed to ensure eligibility criteria are fulfilled (see details in 
Section 7.4). 
• Vital sign measurements, including respiratory rate, blood pressure, pulse rate, pulse 
oximetry, and temperature (oral or via forehead/ear reader). 
• Baseline electrocardiogram (ECG) 
• Urine pregnancy test for participants of childbearing potential only. A positive urine 
pregnancy test at Screening will result in screen failure. 

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• Physical examination to include head, eyes, ears, nose, and throat (HEENT), neck, lungs, 
heart, cardiovascular, abdomen, and musculoskeletal system/extremities to allow for 
study vaccination. 
• Assessment of SAEs, starting from the time of informed consent. 
6.1.2.2 
Day 0 – On-site Study Vaccination 
The Screening and Day 0 Visits may be combined whenever feasible. If these visits are not 
combined, then the following procedures need to be performed and recorded for Day 0. 
Participant eligibility must be confirmed prior to vaccination. 
Prior to study vaccination, all participants with confirmed eligibility will have the following 
procedures performed: 
• Inclusion and exclusion criteria review via participant discussion and medical history 
review consistent with Section 4.1.1. Specific exclusions to study vaccination will be 
assessed before any study vaccination. 
• Prior and concomitant medications, including recent and current medications to be 
reviewed to ensure eligibility criteria are fulfilled (see details in Section 7.4). 
• Vital sign measurements, including respiratory rate, blood pressure, pulse rate, pulse 
oximetry, and temperature (oral or via forehead/ear reader). On study vaccination days, 
vital sign measurements will be collected once before study vaccination to ensure 
participant has no evidence of fever prior to study vaccination. 
• Urine pregnancy test for participants of childbearing potential only. A urine pregnancy 
test will be performed prior to study vaccination. A positive urine pregnancy test at any 
time will result in the participant not receiving any further study vaccination. 
• Symptom-directed (targeted) physical examination. Physical examination must be done 
prior to study vaccination. 
• Nasal swab (anterior nares) collection for SARS-CoV-2 PCR testing 
• Oral swab for SARS-CoV-2 mucosal IgA-mediated hACE2 receptor-binding inhibition 
assay 
• Blood sampling for immunogenicity tests: 
− SARS-CoV-2 (ELISA for anti-S-protein serology). 
− SARS-CoV-2 serostatus (anti-N-protein serology). 
− SARS-CoV-2 NAb assay. 
− Human angiotensin converting enzyme-2 (hACE2) receptor-binding inhibition assay. 
• Randomization/Enrollment 

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At the time of study vaccination, the following procedures will be conducted for all randomized 
participants: 
• Alcohol swab cleansing of the injection sites for study vaccine administration 
• Vaccination with study vaccine as an intramuscular (IM) injection. 
• Monitoring for any immediate hypersensitivity and anaphylaxis reactions. Participants 
will remain in clinic for at least 15 minutes post-vaccination for safety monitoring. 
• Assessment of unsolicited AEs, MAAEs (all and related to study vaccination), any SAEs, 
and AESIs (including PIMMCs, myocarditis and/or pericarditis, and complications 
specific to COVID-19). 
Following vaccination, participants will be trained to utilize an eDiary to record reactogenicity. 
All participants will be asked to record reactogenicity on the day of vaccination and for an 
additional 6 days after vaccination. Study site personnel should regularly review the eDiary for 
completeness. Should any reactogenicity event extend beyond 6 days after vaccination (toxicity 
grade ≥ 1), then it will be recorded using the Continuing Solicited AE form and followed to 
resolution per ICH guidelines for dataset capture. The toxicology grading scale implemented in 
the eDiary for the study is included in Appendix 2. 
6.1.2.3 
Day 28 – In-person/Home Health Care Follow-up Visit (-1 to + 7 Days) 
All participants will have the following procedures performed on Day 28: 
• Prior and concomitant medications (see details in Section 7.4). 
• Oral swab for SARS-CoV-2 mucosal IgA-mediated hACE2 receptor-binding inhibition 
assay. 
• Blood sampling for immunogenicity tests: 
− SARS-CoV-2 (ELISA for anti-S-protein serology). 
− SARS-CoV-2 serostatus (anti-N-protein serology). 
− SARS-CoV-2 NAb assay. 
− hACE2 receptor-binding inhibition assay. 
• COVID-19 monitoring and assessment of severity. 
• Assessment of unsolicited AEs, MAAEs (all and related to study vaccination), any SAEs, 
and AESIs (including PIMMCs, myocarditis and/or pericarditis, and complications 
specific to COVID-19). 
6.1.2.4 
Day 56 – Phone Follow-up Visit (± 7 Days) 
All participants will have the following safety information collected via a remote visit (eg, phone 
call) on Day 56: 
• Prior and concomitant medications (see details in Section 7.4). 

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• COVID-19 monitoring and assessment of severity 
• Assessment of any SAEs, AESIs (including PIMMCs, myocarditis and/or pericarditis, 
and complications specific to COVID-19), and related MAAEs. 
6.1.2.5 
Day 90 – In-person/Home Health Care Follow-up Visit (± 7 Days) 
All participants will have the following procedures performed on Day 90: 
• Prior and concomitant medications (see details in Section 7.4). 
• Symptom-directed (targeted) physical examination. 
• Blood sampling for immunogenicity tests: 
− SARS-CoV-2 (ELISA for anti-S-protein serology). 
− SARS-CoV-2 serostatus (anti-N-protein serology). 
− SARS-CoV-2 NAb assay. 
− hACE2 receptor-binding inhibition assay. 
• COVID-19 monitoring and assessment of severity 
• Assessment of any SAEs, AESIs (including PIMMCs, myocarditis and/or pericarditis, 
and complications specific to COVID-19), and related MAAEs. 
6.1.2.6 
Day 118 – Phone Follow-up Visit (± 7 Days) 
All participants will have the following safety information collected via a remote visit (eg, phone 
call) on Day 56: 
• Prior and concomitant medications (see details in Section 7.4). 
• COVID-19 monitoring and assessment of severity 
• Assessment of any SAEs, AESIs (including PIMMCs, myocarditis and/or pericarditis, 
and complications specific to COVID-19), and related MAAEs. 
6.1.2.7 
Day 146 – Phone Follow-up Visit (± 15 Days) 
All participants will have the following safety information collected via a remote visit (eg, phone 
call) on Day 146: 
• Prior and concomitant medications (see details in Section 7.4). 
• COVID-19 monitoring and assessment of severity 
• Assessment of any SAEs, AESIs (including PIMMCs, myocarditis and/or pericarditis, 
and complications specific to COVID-19), and related MAAEs. 

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6.1.2.8 
Unscheduled Visit 
6.1.2.8.1 
General Unscheduled Visit 
General Unscheduled Visits not due to respiratory/non-respiratory symptoms suspected to be 
COVID-19 will be conducted by study personnel for safety follow-up for any participant 
experiencing a general medical issue while on study. During this visit, the principal investigator 
may also perform any of the assessments listed in the SOE (Table 1) including blood sample 
collection, physical assessments, or other optional testing if needed for the clinical evaluation of 
an AE. 
• Prior and concomitant medications (see details in Section 7.4). 
• Vital sign measurements, including respiratory rate, blood pressure, pulse rate, pulse 
oximetry, and temperature (oral or via forehead/ear reader). 
• Full physical examination. 
• Assessment of unsolicited AEs (only for Unscheduled Visits occurring through 28 days 
after last study vaccination), MAAEs (only related MAAEs should be recorded if more 
than 28 days after last vaccination), SAEs, and AESIs (including PIMMCs, myocarditis 
and/or pericarditis, and complications specific to COVID-19). 
• Blood sample collection and other optional testing may be performed during an 
Unscheduled Visit if directed by the Investigator for clinical evaluation of an AE. 
6.1.2.8.2 
Unscheduled Visit Due to Suspected COVID-19 
In cases of suspected COVID-19 illness where the participant has not been evaluated at an offsite 
medical facility, they must contact the site within 3 days of symptom onset. If possible, the 
participant should have an in-person visit to help gather vital signs and do any necessary work up 
inclusive of physical examination. In cases where the participant has already been at an offsite 
facility, the site should endeavor to retrieve the visit notes. Only in situations where the 
participant cannot have an in-person visit should a telehealth visit be planned. 
For all telehealth visits: 
• Prior and concomitant medications (see details in Section 7.4). 
• Nasal swab (anterior nares) collection for SARS-CoV-2 PCR testing 
• Assessment of unsolicited AEs (only for Unscheduled Visits occurring through 28 days 
after last study vaccination), MAAEs (only related MAAEs should be recorded if more 
than 28 days after last vaccination), SAEs, and AESIs (including PIMMCs, myocarditis 
and/or pericarditis, and complications specific to COVID-19). 
6.1.2.9 
Day 180 – End of Study In-person/Home Health Care Visit (± 15 Days) 
All participants will have the following procedures performed on End of Study/In-Person Home 

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Health Care Visit. 
• Prior and concomitant medications (see definitions in Section 7.4). 
• Vital sign measurements, including respiratory rate, blood pressure, pulse rate, pulse 
oximetry, and temperature (oral or via forehead/ear reader). 
• Symptom-directed (targeted) physical examination. 
• Blood sampling for immunogenicity tests: 
− SARS-CoV-2 (ELISA for anti-S-protein serology). 
− SARS-CoV-2 serostatus (anti-N-protein serology). 
− SARS-CoV-2 NAb assay. 
− hACE2 receptor-binding inhibition assay. 
• COVID-19 monitoring and assessment of severity 
• Assessment of SAEs, AESIs (including PIMMCs, myocarditis and/or pericarditis, and 
complications specific to COVID-19), and related MAAEs. 
• Completion of the EOS form. 
6.2 
Immunogenicity Assessments 
Blood samples will be taken at the time points specified in the procedures above and in the SOEs 
(Section 1.1) to assess immune response (eg, IgG ELISA for anti-S protein serology, NAb assay, 
and hACE2 receptor-binding inhibition assay). 
Oral swabs will be taken at the time points specified in the procedures above and in the SOEs 
(Section 1.1) to assess IgA mediated hACE2 receptor-binding inhibition. 
hACE2 levels will be obtained at Day 0 and Day 28 from saliva biofluid samples to provide 
information about the mucosal IgA-mediated antibody response to SARS-CoV-2. The salivary 
gland epithelial cells express hACE2 and harbor a significant population of IgA-producing 
plasma cells. Secretory IgA in the saliva has been shown to have potent neutralizing activity 
against SARS-CoV-2 (Sheikh-Mohammed 2022). 
The details on the handling, processing, and shipping of immunogenicity samples will be 
provided separately in a laboratory manual. 
Participants will be asked to provide consent for the use of samples for future testing for assay 
development related to SARS-CoV-2 or other pathogens. Aliquots of all collected samples from 
this study may be retained for the stated purposes for a maximum of 25 years (starting from the 
date at which the last participant had the last study visit), unless local rules, regulations, or 
guidelines require different time frames or different procedures, in accordance with participant 
consent. 

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6.3 
Discontinuation or Withdrawal 
6.3.1 
Individual Participants 
6.3.1.1 
Withdrawal from Study 
Participants are free to withdraw from the study at any time upon request. Participation in the 
study may be stopped at any time at the discretion of the investigator or at the request of the 
Sponsor. 
Participants may refuse further procedures (including study vaccination) but are encouraged to 
remain in the study for safety follow-up. In such cases where only safety is being conducted, 
participant contact could be managed via telemedicine contact (eg, telephone, web chat, video, 
FaceTime). 
Any participant who withdraws from the study prematurely will undergo all EOS assessments at 
the time of withdrawal. The reason for the early EOS visit must be entered as withdrawal from 
study on the EOS form. 
Vaccination with a non-study, approved or deployed SARS-CoV-2 vaccine alone will not be 
considered a reason for withdrawal from the study. 
6.3.1.2 
Replacement of Participants 
Participants who sign the ICF but withdraw, are withdrawn or terminated from this study, or are 
lost to follow up prior to study vaccination may be replaced. Participants who receive study 
vaccine and subsequently withdraw, are discontinued from additional study visits, are terminated 
from the study, or are lost to follow-up will not be replaced. 
6.3.1.3 
Participants Lost to Follow-up 
Whenever possible, any participant who withdraws from the study prematurely will undergo all 
EOS assessments. Any participant who fails to return for final assessments will be contacted by 
the site in an attempt to have them comply with the protocol. 
All reasonable efforts, including contact of emergency contact, must be made to locate 
participants to determine and report their ongoing status. Lost to follow-up is defined by the 
inability to reach the participant after a minimum of 3 documented phone calls, text messages, 
faxes or emails (not performed on the same day), as well as a lack of response by the participant 
to one registered mail letter. All attempts should be documented in the participant’s source 
documents and/or medical records. If it is determined that the participant has died, the study site 
will use permissible local methods to obtain the date and cause of death and as much other 
information as can be obtained, including post-mortem reports. 

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The status of participants who fail to complete final assessments will be documented in the 
eCRF. Data that would have been collected at subsequent visits will be considered missing. 
6.3.1.4 
Study Vaccination Pause Rules 
Study vaccination will be paused in the event of reports of 2 or more events of probable or 
confirmed pericarditis or myocarditis (Table 5), pending review of cases by the Central Cardiac 
Adjudication Committee that will report the results of their adjudication to the Sponsor to 
determine whether enrollment may be resumed. 
Adverse events meeting any one of the following criteria will result in a hold being placed on 
subsequent vaccinations pending further review by the Sponsor’s Safety Monitoring Committee 
(SMC): 
• One or more participant with an SAE considered related to the investigational vaccine by 
the investigator and by the Sponsor. 
• Three or more participants with grade 3 (severe) single AE preferred term considered 
related to the investigational vaccine by the investigator and by the Sponsor. 
In addition, any SAE assessed as related to vaccine (by study investigator and/or the Sponsor) 
will be reported to the Sponsor’s SMC Chair as soon as possible, and within 24 hours of the 
Sponsor’s awareness of the event. If a pause rule is met, the SMC will conduct a safety review 
within 48 hours of the identification of AEs meeting the pause rule definition. In addition, the 
SMC Chair will advise the Clinical Team to advise all sites to immediately pause enrolment and 
further dosing the study participants. An ad hoc Sponsor’s SMC meeting will be convened to 
review the data and make alternative recommendations. The Sponsor’s SMC Charter defines 
processes for how this review will occur and how the Chair’s recommendations will be 
documented. 
The Sponsor, along with medical monitor (Syneos), may request an SMC review for any safety 
concerns deemed clinically significant that may arise in the trial and not associated with any 
specific pause rule. 
6.4 
Study Termination 
Although the Sponsor has every intention of completing the study, they reserve the right to 
discontinue it at any time for clinical or administrative reasons. 
The EOS is defined as the date on which the last participant completes the last study visit 
(including the EOS visit and any additional long-term follow-up). Any additional long-term 
follow-up that is required for monitoring of the resolution of an AE or finding may be appended 
to the clinical study report. 

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7 
STUDY INTERVENTIONS 
Study vaccinations will comprise 1 IM injection with the study treatment assigned (Table 4). 
 
Table 4: 
Investigational Treatments Used in This Study 
 
Product 
Section 
Antigen Dose 
Route 
Manufacturer 
NVX-CoV2601 coformulated Omicron XBB.1.5 
SARS-CoV-2 rS vaccine with Matrix-M adjuvant 
7.1.1 
5 μg 
IM 
Serum Institute 
of India 
Prototype/XBB.1.5 Bivalent Vaccine 
(Site-mixed NVX-CoV2373 + NVX-CoV2601) 
coformulated with Matrix-M adjuvant 
7.1.2 
5 μg (total) 
IM 
Serum Institute 
of India 
Abbreviations: IM = intramuscular 
7.1 
Description of Products 
7.1.1 
NVX-CoV2601 (5 µg) 
7.1.1.1 
Formulation, Storage, Preparation, and Handling 
NVX-CoV2601 (5 µg): Coformulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine with Matrix- 
M adjuvant: supplied as a solution for preparation for injection, at a concentration of 10 µg 
antigen and 100 µg adjuvant per mL. All study vaccines must be stored according to the labelled 
instructions in a secure cabinet or room with access restricted to necessary clinic personnel. The 
study site will be required to keep a temperature log to establish a record of compliance with 
storage conditions. 
The NVX-CoV2601 vaccine with Matrix-M adjuvant should be stored at 2°C to 8°C in a secured 
location. DO NOT FREEZE. 
7.1.1.2 
Dosing and Administration 
The vaccine should be drawn into a syringe on the day of administration by a qualified member 
of study site personnel and should be administered according to standard practice by qualified 
study site personnel as directed in the Pharmacy Manual. 
All injections will be administered in a 0.5 mL injection volume at a dose of 5 µg antigen with 
50 µg Matrix-M adjuvant at each injection. 
7.1.2 
Prototype/XBB.1.5 Bivalent Vaccine (5 µg [Total]) 
7.1.2.1 
Formulation, Storage, Preparation, and Handling 
The bivalent vaccine containing antigen for the ancestral (Wuhan) SARS-CoV-2 strain and 
Omicron XBB.1.5 subvariant, will be prepared from study supplies of NVX-CoV2373 and 
NVX-CoV2601. 

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All study vaccines must be stored according to the labelled instructions in a secure cabinet or 
room with access restricted to necessary clinic personnel. The study site will be required to keep 
a temperature log to establish a record of compliance with storage conditions. 
The vials for the preparation of the bivalent vaccine with Matrix-M adjuvant should be stored at 
2°C to 8°C in a secured location. DO NOT FREEZE. 
On the day of administration, the bivalent vaccine should be mixed according to the Pharmacy 
Manual in the clinic pharmacy or in an area designated for this function. All vaccines which are 
diluted or mixed in the study site clinic/investigational pharmacy should be used within 1 hour of 
being prepared and drawn into a syringe. For additional preparation, storage, and handling 
information for the bivalent vaccine, refer to the provided Pharmacy Manual. 
7.1.2.2 
Dosing and Administration 
The bivalent vaccine should be prepared and drawn into a syringe on the day of administration 
by a qualified member of study site personnel and should be administered according to standard 
practice by qualified study site personnel as directed in the Pharmacy Manual. 
All injections will be administered in a 0.5 mL injection volume at a dose of 5 µg total antigen 
(2.5 µg prototype antigen + 2.5 µg Omicron XBB.1.5 antigen) with 50 µg Matrix-M adjuvant at 
each injection. 
7.2 
Treatment Assignment and Bias Minimization 
7.2.1 
Treatment Allocation 
An Interactive Web Response System (IWRS) will be responsible for the allocation of 
randomization numbers to individual participants. A copy of the randomization/enrollment code 
with true treatment allocations will be held by Syneos during the study. A separate open-label 
serialized list (containing carton/vial treatments) will be provided to clinical supplies for 
investigational medical product (IMP) packaging and labeling. 
7.2.2 
Randomization Strategy and Procedure 
Randomization will take place on Day 0 after confirmation that the participant meets the 
inclusion/exclusion criteria. 
Eligible participants will be randomized 1:1 to Group A or Group B (approximately 200 
participants each). Randomization will be stratified by number of prior mRNA COVID-19 
vaccinations received and site. 
Within each study site, participants will be randomized to study treatment according to a list 
produced by Syneos. Prior to production, the randomization specification will be reviewed and 

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agreed to by the study team (the Sponsor and Syneos). Block size is considered potentially 
unblinding information and will only be known by unblinded study personnel. 
7.2.3 
Extent and Maintenance of Blinding 
This is a double-blind study. To maintain the blind, predetermined unblinded study site 
personnel will manage vaccine logistics, preparation, and potentially administration according to 
the Pharmacy Manual so as to maintain the blind from the remainder of the study site personnel 
and participants. The unblinded study site personnel may administer study vaccine if qualified to 
do so but will not be involved in study related assessments or have participant contact for data 
collection after administration of study vaccine. 
7.2.4 
Unblinding Procedures 
7.2.4.1 
Planned Unblinding 
A participant’s vaccine assignment will not be revealed to the site study team until the end of the 
study. Participants will be informed about which product they received as soon as feasible after 
the end of the study. 
7.2.4.2 
Unplanned or Unintentional Unblinding 
A participant’s vaccine assignment will not be revealed to the site study team until the end of the 
study unless medical treatment of the participant depends on knowing the study vaccine the 
participant received. Should a situation arise where unblinding is required, the investigator at that 
study site has the sole authority to obtain immediate unblinding via the IWRS. Prior to 
unblinding, or as soon thereafter as possible, the investigator should contact the Syneos Medical 
Monitor to discuss the medical emergency and the reason for revealing the actual vaccine 
combination received by that participant. Emergency code breaks performed using the IWRS 
must be clearly explained and justified in the eCRF. The date on which the code was broken 
must also be documented. 
When the investigator contacts the IWRS system to break a treatment code for a participant, they 
must provide the requested participant identifying information and confirm the necessity to break 
the treatment code for the participant. The investigator will then receive details of the study 
treatment for the specified participant and a blinded confirmation to document the unblinding 
will generate. The system will automatically inform the Sponsor and the Syneos Clinical Team 
via email that the code has been broken, but no treatment assignment will be communicated. 
It is the investigator’s responsibility to ensure that there is a procedure in place to allow access to 
the IWRS in case of emergency. The investigator will inform the participant how to contact their 
backup in cases of emergency when they are unavailable. The investigator will provide the 
protocol number, study vaccine name if available, participant number, and instructions for 
contacting the local entity which has responsibility for emergency code breaks to the participant 

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in case an emergency treatment code break is required at a time when the investigator and 
backup are unavailable. 
7.3 
Assessment and Verification of Compliance 
All doses of the study vaccine should be administered in the clinical unit under direct 
observation of clinic personnel and recorded in the eCRF. Clinic personnel will confirm that the 
participant has received the entire dose. 
The location (right or left arm, or other location if required), date, and timing of all doses of 
study vaccine will be recorded in the participants’ eCRF. If a participant is not administered 
study vaccine, the reason for the missed dose will be recorded. 
7.4 
Prior and Concomitant Therapies 
Administration of medications, therapies, or vaccines will be recorded in the eCRF. Prior 
medications include recent (≤ 90 days) and current medications and non-COVID-19 
vaccinations. Concomitant medications will include all medications (including vaccines) taken 
by the participant Day 0 through EOS (or through the early termination visit if prior to that time). 
Prescription and over-the-counter (OTC) drugs will be included. Do not record herbals, vitamins, 
and supplements. 
Receipt of any approved or authorized COVID-19 vaccine should also be recorded through EOS. 
Site staff will record the date(s) and brand of the approved or authorized SARS-CoV-2 vaccine 
combination received. 
7.4.1 
Prohibited Therapies 
The following therapies are prohibited within the specified timeframes of study conduct except 
to the extent that they are required to treat an ongoing illness or to maintain the participants’ 
health: 
• No COVID-19 vaccines during the course of the study. 
• No other vaccines (except for a licensed seasonal influenza vaccine as described in the 
next bullet or rabies, HPV, Td, TDaP, DTap, HBV, and meningococcal vaccines [if 
medically indicated]) will be allowed within 45 days prior to study vaccination or until 28 
days after study vaccination. 
• No influenza vaccine will be allowed within 14 days prior to study vaccination and 
within 14 days after study vaccination. 
• No investigational product (drug/biologic/device) within 90 days prior to study 
vaccination until after the last study visit. 

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• No chronic administration (defined as > 14 continuous days) of any immunosuppressant 
medication within 90 days prior to study vaccination until the last study visit (except 
topical or intranasal steroids, or short-term oral steroids with course lasting ≤ 14 days). 
Topical tacrolimus and ocular cyclosporine are permitted. Rabies immune globulin 
should be administered if medically indicated. 
8 
SAFETY MONITORING 
The timing and frequency of all safety assessments are listed in the SOE (Section 1.1). 
Solicited and unsolicited AEs will be graded for severity using the provided criteria 
(Appendix 2). Recording of solicited and unsolicited AEs will be conducted by electronic data 
capture (EDC). AESIs, including PIMMCs, myocarditis and/or pericarditis, and complications 
specific to COVID-19, will also be monitored (see Appendix 1 for details). 
A Central Cardiac Adjudication Committee has been established to adjudicate suspected 
myocarditis and/or pericarditis cases in the clinical development plan of NVX-CoV2373. 
Outcomes of the adjudications will be communicated to the Sponsor’s Safety Monitoring 
Committee (SMC). 
8.1 
Definitions 
• Adverse event – An AE is any untoward medical occurrence associated with the use of 
an intervention in humans whether or not it is considered intervention-related. Any 
abnormal laboratory test results or other safety assessments (eg, physical examination, 
vital signs measurements) that are clinically significant in the medical and scientific 
judgment of the investigator (ie, not related to progression of underlying disease) will be 
considered AEs. An exacerbation of a chronic or intermittent pre-existing condition, 
including either an increase in frequency and/or intensity, will be considered an AE. 
• Serious adverse event (SAE) – An event is considered “serious” if, in the view of either 
the Investigator or Sponsor, it results in any of the following outcomes: 
− Death 
− A life-threatening AE (an event is considered “life-threatening” if, in the view of 
either the investigator or Sponsor, its occurrence places the patient or participant at 
immediate risk of death. It does not include an AE or suspected adverse reaction (AR) 
that, had it occurred in a more severe form, might have caused death.) 
− Inpatient hospitalization or prolongation of existing hospitalization. In general, 
hospitalization signifies that the participant has been detained, usually involving 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. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an SAE. 

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− A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
− A congenital anomaly/birth defect 
− Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or participant and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room (ER) or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, or the development of drug dependency 
or drug abuse. 
• Causality or relatedness – For each AE/SAE, the investigator must document in the 
medical notes that they have reviewed the AE/SAE and have provided an assessment of 
causality as follows. 
− Not Related: There is no reasonable possibility of relationship to study vaccine. The 
AE does not follow a reasonable temporal sequence from administration of study 
vaccine or can be reasonably explained by the participant’s clinical state or other 
factors (eg, concurrent diseases, and concomitant medications). 
− Related: There is a reasonable possibility of relationship to study vaccine. The AE 
follows a reasonable temporal sequence from administration of study vaccine and 
cannot be reasonably explained by the participant’s clinical state or other factors (eg, 
concurrent diseases or concomitant medications), represents a known reaction to 
study vaccine or other vaccines in its class, is consistent with the known 
pharmacological properties of the study vaccine, and/or resolves with discontinuation 
of the study vaccine (and/or recurs with re-challenge, if applicable). 
• Adverse reaction (AR) – An AR is any AE caused by an IP. 
• Suspected adverse reaction (SAR) – An SAR is any AE for which there is a reasonable 
possibility that the IP caused the AE. For the purposes of investigational new drug (IND) 
safety reporting, “reasonable possibility” means there is evidence to suggest a causal 
relationship between the IP and the AE. SAR implies a lesser degree of certainty about 
causality than AR. 
• Unexpected – An event is considered unexpected if it is not listed in the IB, is not listed 
at the specificity or severity that has been observed, or, if an IB is not required or 
available, is not consistent with the risk information described in the General 
Investigational Plan or elsewhere in the IND. Unexpected also refers to events that are 
mentioned in the IB as occurring with a class of IPs or as anticipated from the 
pharmacological properties of the IP but are not specifically mentioned as occurring with 
the particular IP under investigation. 

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• Severity or intensity – The severity (or intensity) of an AE/SAE refers to the extent to 
which it affects the participant's daily activities and will be classified as mild, moderate, 
or severe using the following criteria: 
− Mild: These events require minimal or no treatment and do not interfere with the 
participant's daily activities. 
− Moderate: These events result in a low level of inconvenience or require minor 
therapeutic measures. Moderate events may cause some interference with normal 
functioning. 
− Severe: These events interrupt a participant's usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually incapacitating. 
If the severity of an AE/SAE changes, the most intense severity should be reported. An 
AE/SAE characterized as intermittent does not require documentation of the onset and 
duration of each episode. Grading criteria for specific AEs are provided in Appendix 2. 
8.2 
Documenting Adverse Events 
At every study visit, participants will be asked to report any medically related changes in their 
well-being. They will also be asked if they have been hospitalized, had any accidents, used any 
new medications, or changed concomitant medication regimens (both prescription and OTC 
medications). 
In addition to participant observations, AEs will be documented from any data collected on the 
AE page of the eCRF or other documents that are relevant to participant safety. 
Care will be taken not to introduce bias when detecting AEs, MAAEs, and SAEs. Open ended 
and non-leading verbal questioning of the participant is the preferred method to enquire about 
AE occurrences. AESIs will be inquired about according to the specific diseases listed in 
Appendix 1. 
When an AE/SAE occurs, it is the responsibility of the investigator to review all available 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) related to 
the event. The investigator will then record all relevant AE/SAE information in the eCRF. 
It is not acceptable for the investigator to send photocopies of the participant’s medical records 
in lieu of completion of the AE/SAE eCRF page. There may be instances when copies of 
medical records for certain cases are requested. 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. 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. 

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The following variables will be recorded for each AE: verbatim/AE description and date for AE 
start and stop, severity, seriousness, causality, any other action taken, and the outcome. A new 
AE must be recorded if the severity of the AE changes. 
Should an SAE have an outcome of death, the report should contain a comment regarding the 
co-involvement of progression of disease, if appropriate, and should assign main and 
contributory causes of death. 
8.2.1 
Details of the Adverse Event 
8.2.1.1 
Assessment of Causality 
There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report. However, it is very important that the investigator 
always makes an assessment of causality for every event before the initial transmission of the 
SAE data. The investigator may change their opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment. The 
causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
The investigator should consider the following before reaching a decision on causality 
assessment: 
• Time relationship between study vaccine injection and event’s onset. 
• Medical history. 
• Study treatment. 
• Mechanism of action of study vaccine. 
• Class effect. 
• Concomitant treatments in use. 
• Withdrawal of study treatment. 
• Lack of efficacy/worsening of existing condition. 
• Possible vaccine enhancement of COVID-19. 
• Erroneous treatment with study medication or concomitant medication. 
• Protocol-related process. 
8.2.1.2 
Action Taken with Study Vaccine Due to Adverse Event 
The action taken with study vaccine should be recorded using one of the following: 
• Permanently discontinued/withdrawn (with date). 
• Not applicable. 

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8.2.1.3 
Other Action Taken 
Details of any other actions taken should be specified: 
• Specific therapy/medication. 
• Surgical or medical procedure. 
8.2.1.4 
AE Outcome 
Each AE should be rated according to one of the following outcomes: 
• Recovered/resolved. 
• Recovering/resolving. 
• Not recovered/not resolved/ongoing. 
• Recovered with sequelae/resolved with sequelae. 
• Fatal. 
• Unknown. 
8.2.2 
Time Frame for Collection 
All AEs captured following the procedures listed in the SOE (Section 1.1) will be recorded on 
the AE page of the eCRF. 
Medical occurrences that begin prior to study vaccination will be recorded on the Medical 
History/Current Medical Conditions section of the eCRF and not in the AE section. 
All unsolicited AEs of any severity will be collected from the time of study vaccination through 
28 days after vaccination. 
All MAAEs will be collected through 28 days after vaccination and only treatment-related 
MAAEs will be collected after Day 28 until EOS. 
All AESIs will be collected from the time of study vaccination until EOS. 
All SAEs will be collected from signing of informed consent until completion of the EOS. 
All vaccine administration errors, AEs, SAEs, cases of multisystem inflammatory syndrome, and 
all cases of COVID19 following vaccination must be reported per applicable local regulatory 
reporting guidance for safety events that occur in participants during the study if they meet the 
regulatory reporting criteria. 
At any time after completion of the EOS visit, if an investigator learns of an SAE that could 
reasonably be considered related to study vaccine, they should promptly notify the Sponsor. 

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8.2.3 
Classification of Events 
8.2.3.1 
Treatment-Emergent Adverse Events 
Treatment-emergent adverse events are defined as any AE occurring or worsening on or after the 
study vaccination. 
8.2.3.2 
Adverse Events of Special Interest 
Participants will be assessed for diagnosis of an AESI at all study contacts. AESIs include 
myocarditis and/or pericarditis, other PIMMCs, and complications specific to COVID-19 (listed 
in Appendix 1), or other potential AEs that may be determined at any time by regulatory 
authorities as additional information concerning COVID-19 is obtained. Listings of AESI are 
presented in Appendix 1. 
An AESI must be reported as if it is an SAE (Section 8.3). 
8.2.3.2.1 
Myocarditis and/or Pericarditis (CDC Definition) 
Participants reporting signs or symptoms of myocarditis or pericarditis (eg, fatigue, acute chest 
pain, shortness of breath, etc., see Table 5) within 4 weeks after vaccination should be evaluated 
as soon as possible by a physician who should initiate diagnostic work up including but not 
limited to laboratory tests and initial cardiac evaluation. If probable or confirmed myocarditis 
and/or pericarditis is diagnosed after the initial evaluation, all efforts will be made to route the 
participants to be followed up preferentially by a cardiologist or pediatric cardiologist (as 
applicable) who should complete the initial evaluation and manage cases following current 
practice guidelines (eg, AHA or other national/local guidelines); this might include performing 
functional cardiac evaluation and follow up of the case until resolution (see Table 6). A Central 
Cardiac Adjudication Committee has been established to adjudicate suspected myocarditis and/or 
pericarditis cases in the clinical development plan of NVX-CoV2373. Outcomes of the 
adjudications will be communicated to the SMC (when applicable) and to the Sponsor. 
All myocarditis and/or pericarditis signs and symptoms, as well as all clinical evaluations, will 
be considered part of the study record and should be documented in the eCRF pages available to 
that end. Participants with confirmed myocarditis or pericarditis will be followed-up to document 
resolution of symptoms and/or abnormal test findings. 

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Table 5: 
Case Definitions of Probable and Confirmed Myocarditis, Pericarditis, and 
Myopericarditis 
 
Condition 
CDC Definition 
Acute 
myocarditis 
PROBABLE: 
Presence of ≥ 1 new or worsening of the following clinical symptoms:1 
• Chest pain, pressure, or discomfort 
• Dyspnea, shortness of breath, or pain with breathing 
• Palpitations 
• Syncope 
AND 
≥ 1 new finding of 
• Troponin level above upper limit of normal (any type of troponin) 
• Abnormal ECG or rhythm monitoring findings consistent with myocarditis2 
• Abnormal cardiac function or wall motion abnormalities on echocardiogram 
• cMRI findings consistent with myocarditis3 
AND 
• No other identifiable cause of the symptoms and findings 
CONFIRMED: 
Presence of ≥ 1 new or worsening of the following clinical symptoms:1 
• Chest pain, pressure, or discomfort 
• Dyspnea, shortness of breath, or pain with breathing 
• Palpitations 
• Syncope 
AND 
≥ 1 new finding of 
• Histopathologic confirmation of myocarditis4 
• cMRI findings consistent with myocarditis3 in the presence of troponin level above upper 
limit of normal (any type of troponin) 
AND 
• No other identifiable cause of the symptoms and findings 
Acute 
pericarditis5 
Presence of ≥ 2 new or worsening of the following clinical features: 
• Acute chest pain6 
• Pericardial rub on exam 
• New ST-elevation or PR-depression on ECG 
• New or worsening pericardial effusion on echocardiogram or MRI 
Myopericarditis 
This term may be used for patients who meet criteria for both myocarditis and pericarditis. 
Abbreviations: AV = atrioventricular; CDC = Centers for Disease Control and Prevention; cMRI = cardiac magnetic 
resonance imaging; ECG = electrocardiogram; ESC = European Society of Cardiology; MRI = magnetic 
resonance imaging. 
1. Persons who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis 
(probable or confirmed). 
2. To meet the ECG or rhythm monitoring criterion, a probable case must include at least one of 1) ST-segment or 
T-wave abnormalities; 2) Paroxysmal or sustained atrial, supraventricular, or ventricular arrhythmias; or 3) AV 
nodal conduction delays or intraventricular conduction defects. 

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3. Using either the original or the revised Lake Louise criteria (Ferreira 2018). 
4. Using the Dallas criteria (Aretz 1987). Autopsy cases may be classified as confirmed clinical myocarditis on the 
basis of meeting histopathologic criteria if no other identifiable cause. 
5. Based on the 2015 ESC Guidelines for the diagnosis and management of pericardial diseases (Adler 2015). 
https://academic.oup.com/eurheartj/article/36/42/2921/2293375 
6. Typically described as pain made worse by lying down, deep inspiration, or cough, and relieved by sitting up or 
leaning forward, although other types of chest pain might occur. 
Adapted from Gargano 2021. 
 
 
Table 6: 
Management of Probable or Confirmed Myocarditis, Pericarditis, and 
Myopericarditis Cases 
 
Clinical 
Presentation 
Procedures 
Probable or 
Confirmed 
Myocarditis, 
Pericarditis or 
Myopericarditis 
1) ER visit and evaluation by a physician (as per national/local guidelines): 
a. 
Diagnostic work up might include: 
i. CBC, Inflammatory markers: ESR, CRP 
ii. Cardiac markers: Troponin I, BNP, NT-proBNP 
iii. Chest radiograph 
iv. ECG 
2) Evaluation by a cardiologist/pediatric cardiologist (as applicable) 
a. 
Follow AHA or other national/local guidelines 
i. Diagnostic work might include: 
1. Stress test echocardiogram 
2. Cardiac biopsy 
3. cMRI 
4. Other laboratory or cardiac assessment tests as 
applicable 
b. Follow up until resolution 
Abbreviations: AHA = American Heart Association; BNP = brain natriuretic peptide; CBC = complete blood 
count; cMRI = cardiac magnetic resonance imaging; CRP = C-reactive protein; ECG = electrocardiogram; 
ER = emergency room; ESR = erythrocyte sedimentation rate; NT-proBNP = N-terminal pro b-type natriuretic 
peptide. 
 
8.2.3.3 
Medically Attended Adverse Events 
An MAAE is defined as an AE that leads to an unscheduled visit to a healthcare practitioner. 
8.2.3.4 
Reactogenicity Symptoms 
On the day of vaccination, participants will remain in clinic (or under observation) for at least 
15 minutes to be observed for any immediate hypersensitivity and anaphylaxis reactions. Site 
specific local and general systemic reactogenicity reactions including start and stop dates will be 
recorded following vaccination. 
Participants will utilize their eDiary to record reactogenicity following vaccination. All 
participants will be asked to record reactogenicity following vaccination on Day 0 and then daily 
for an additional 6 days after vaccination. Study site personnel should regularly review the 

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eDiary for completeness. Should any reactogenicity event extend beyond 6 days after 
vaccination, then it will be recorded using the Continuing Solicited AE form and followed to 
resolution per ICH guidelines for AE capture. Such AEs should be reported and managed as 
described in Section 8.3. The toxicology grading scale implemented in the eDiary for the study is 
included in Appendix 2. 
8.3 
Reporting Adverse Events 
All SAEs must be reported according to ICH Good Clinical Practice (GCP) or local regulations, 
applying the regulation with the stricter requirements. Investigators and other study site 
personnel must inform appropriate Novavax representatives of any SAE that occurs during the 
course of the study, from the time of informed consent until the EOS visit, regardless of whether 
it is judged to be causally related to study vaccine or procedures. Notification must occur within 
24 hours of when they become aware of it. AESIs, including PIMMC, myocarditis or pericarditis 
and complications specific to COVID-19 are to be reported within these timelines on the 
SAE/AESI Report form. The investigator should make every effort to obtain follow-up 
information on the outcome until the event is considered resolved, chronic and/or stable. 
SAE reports received that may be attributed to both the study vaccine and an 
approved/authorized vaccine from a different manufacturer will be reported to local regulatory 
authorities as applicable. SAE reporting forms allow for the notation of other factors that may 
have impacted the investigator’s assessment of causality. Investigators will be instructed to 
utilize this section of the reporting form to note the impact of an approved/authorized vaccine 
from a different manufacturer on the event, if applicable. Investigators will be required to report 
any SAEs in participants who received a different manufacturer’s approved/authorized vaccine 
to local health care and/or regulatory authorities as per the local regulatory guidelines. 
If a non-serious AE becomes serious, this and other relevant follow-up information must also be 
provided to Novavax Global Vaccine Safety within 24 hours as described above. The date when 
the AE becomes serious should be notated in the eCRF or on the SAE form. 
All SAEs and AESI will also be recorded in the eCRF. The investigator is responsible for 
informing the Independent Ethics Committee (IEC)/IRB of the SAE as per local requirements. 
Paper SAE forms should be completed at the study site and emailed within 24 hours of study site 
awareness of the event to the Novavax Global Vaccine Safety mailbox: 
 
The report form should be attached to the email; a notification email of the event describing it in 
the email text is not sufficient. There may be situations when an SAE has occurred, and the 
investigator has minimal information to include in the initial SAE report. However, it is very 
important that the investigator always makes an assessment of causality for every event prior to 
transmission of the SAE report form. 

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Minimum criteria for a reportable event are: 
• Identifiable patient (participant number) 
• A suspect product (ie, study vaccine) 
• An identifiable reporting source (investigator/study site identification), and 
• An event or outcome that can be identified as serious. 
Follow-up information on SAEs must also be reported by the investigator within the same time 
frames. 
8.3.1 
Safety Reporting to Health Authorities, Independent Ethics 
Committees/Institutional Review Boards, and Investigators 
Novavax or its designee will be responsible for notifications of SAEs and other qualifying events 
that are considered to be unexpected and related to study vaccine as expedited (eg, 7- or 15-Day 
reports to the relevant regulatory authorities and to participating investigators. In addition, 
Novavax or its designee will follow all applicable local and national regulatory requirements 
regarding safety reporting. Each investigator must comply with any applicable study local and 
national regulatory requirements related to the reporting of SAEs to the IRB/IECs responsible for 
reviewing the trial at their site, as well as the regulatory authority(ies) (where applicable). 
Timelines and responsibilities (Novavax and its designee) for expedited and periodic safety 
reporting to the Health Authorities, Independent Ethics Committees/ Institutional Review 
Boards, and Investigators are provided in the Safety Management Plan as agreed by the Syneos 
designee and Novavax. 
8.3.2 
24/7 Medical Emergency Coverage for Urgent Protocol-related Medical Questions 
In a study-related health emergency, when assigned medical monitors for a study cannot be 
reached by a caller, for discussion of urgent medical related questions an on-call physician can 
be reached 24 hours 7 days a week (24/7) via Syneos Call Center: 
• Telephone: 
 
8.4 
Pregnancy 
Pregnancy is not considered an AE unless there is a suspicion that an investigational vaccine 
may have interfered with the effectiveness of a contraceptive medication. Any pregnancy that 
occurs during study participation must be reported using the Pregnancy Assessment form. To 
ensure participant safety, each pregnancy must be reported to Novavax Global Vaccine Safety 
within 24 hours of learning of its occurrence. If pregnancy occurs, further vaccination will be 
discontinued. Pregnancy must be followed up to determine outcome (including spontaneous 
miscarriage, elective termination, normal birth, or congenital abnormality) and the status of both 
mother and child, even if the participant was discontinued from the study. Pregnancy 

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complications and elective terminations for medical reasons must be reported as an AE or SAE. 
Spontaneous miscarriages must be reported as an SAE. 
Any pregnancy brought to the investigator’s attention before the study is completed should be 
reported to Novavax Global Vaccine Safety using the Pregnancy Assessment form provided to 
sites. 
Any pregnancy brought to the investigator’s attention after the participant has completed the 
study but occurring while the participant was in the study must be promptly reported to: 
Novavax Global Vaccine Safety: 
 
8.5 
Overdose or Misuse 
A drug overdose is defined as the accidental or intentional use of an IP or an administration error 
in an amount that is higher than is normally used. Every overdose must be reported to Novavax 
Global Vaccine Safety within 24 hours of awareness, using the details provided in Section 8.3 if 
the overdose was associated with an SAE. Other overdoses and those associated with non-serious 
AEs should be reported in the AE eCRF. Only overdoses associated with a clinical SAE need to 
be reported as an SAE. The quantity and details regarding the excess dose should be documented 
in the eCRF. 
Overdose in this study is specifically defined as any dose greater than the intended protocol dose 
(Section 7). In case of overdose, it is recommended that the participant be monitored for any 
signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment be 
administered immediately. Note that administration of the “wrong” vaccine is a protocol 
deviation, but not, in the absence of associated AE, an SAE. 
9 
ANALYSIS 
9.1 
Sample Size Calculations 
The sample size for this study is based on clinical and practical considerations and not on a 
formal statistical power calculation. The sample size is considered sufficient to evaluate the 
objectives of the study. With 200 participants in each treatment group, there is a greater than 
99.9% probability to observe at least 1 subject with an AE if the true incidence of the AE is 5% 
and an 86.6% probability if the true incidence of the AE is 1%. 
9.2 
Analysis Sets 
The following analysis sets are identified for analysis. 

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9.2.1 
All Randomized Participants Analysis Set 
The All Randomized Participants Analysis Set will include all participants who are 
randomized/enrolled, regardless of whether they actually received any study vaccine. The All 
Randomized Participants Analysis Set will be used for participant disposition summaries and 
will be analyzed according to the treatment as randomized/enrolled. 
9.2.2 
Full Analysis Set 
The Full Analysis Set (FAS) will include all participants who are randomized/enrolled and 
received at least 1 dose of study vaccine, regardless of protocol violations or missing data. The 
FAS may be the secondary analysis set used for any immunogenicity analyses and will be 
analyzed according to the treatment as randomized. 
9.2.3 
Safety Analysis Set 
The Safety Analysis Set will include all participants who provide consent, are randomized, and 
receive at least 1 dose of study vaccine. Participants in the Safety Analysis Set will be analyzed 
as actually treated. 
9.2.4 
Per-Protocol Analysis Set 
The Per-Protocol (PP) Analysis Set will be determined for each strain, serology assay and study 
visit. The PP Analysis set will include all participants who receive the full prescribed regimen of 
the study vaccine up to the visit according to protocol, have serology results for baseline and the 
time point analyzed, are PCR negative at baseline for SARS-CoV-2, and have no major protocol 
violations or an event (eg, COVID-19 infection) that are considered clinically relevant to impact 
immunogenicity response as determined prior to database lock. 
Within the PP Analysis Set there are 3 subsets defined: 
9.2.4.1 
Anti-S Protein IgG Serology Subset 
All participants in the PP Analysis Set who are tested for anti-S protein IgG serology using 
ELISA at each timepoint will be included in this subset. 
9.2.4.2 
Neutralization Assay Subset 
All participants in the PP Analysis Set who are tested using the neutralization assay at each 
timepoint will be included in this subset. 
9.2.4.3 
hACE2 Receptor-Binding Inhibition Assay Subset 
All participants in the PP Analysis Set who are tested for hACE2 receptor-binding inhibition 
titers at each timepoint will be included in this subset. 

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9.2.4.4 
Mucosal hACE2 Receptor Binding Inhibition Assay Subset 
All participants in the PP Analysis Set who are tested for mucosal IgA-mediated hACE2 receptor 
binding inhibition titers at each time point will be included in this subset. 
9.3 
Analyses to be Performed 
9.3.1 
Safety Analysis 
All safety analyses will be descriptive and conducted using the Safety Analysis Set. Listings will 
be provided for all safety parameters collected. 
9.3.1.1 
Solicited Adverse Events 
The number and percentage of participants with solicited injection site and systemic AEs through 
7 days after vaccination will be summarized overall and by vaccine group and by the worst 
maximum toxicity grade over 7 days. The durations of solicited local and systemic AEs after 
vaccination within the 7 Day diary period and entire safety follow-up period will also be 
summarized by vaccine group. 
9.3.1.2 
Unsolicited Adverse Events 
Unsolicited AEs will be coded by system organ class (SOC) and preferred term (PT) using 
Medical Dictionary for Regulatory Activities (MedDRA). 
Unsolicited AEs will be summarized according to the periods described in Section 8.2.2 both 
overall and by vaccine group and by SOC/PT, as well as by severity and relationship to the study 
vaccine to present the number and percentage with corresponding exact 95% CIs using the 
Clopper-Pearson method. For multiple occurrences of an adverse event in the same participant, a 
participant will be counted only once, using the most severe or most related occurrence for the 
summarization by severity or relationship to the study vaccine, respectively. 
All MAAEs (only related MAAEs beyond 28 days following vaccination), AESIs (predefined 
list), and SAEs throughout the study (up to the time of pre-planned analyses) will be summarized 
overall and by vaccine group as well as by severity. 
9.3.1.3 
Prior and Concomitant Medications and Vaccinations 
Prior and concomitant medications and vaccinations will be summarized overall and by vaccine 
group and preferred drug name as coded using the World Health Organization (WHO) drug 
dictionary for all participants on the Safety Analysis Set. 

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9.3.1.4 
Extent of Exposure 
The number of participants receiving study vaccine will be presented by vaccine group on the 
Safety Analysis Set. Below information will also be summarized by vaccine group: whether the 
vaccine is administered and the reason if not, whether the vaccine is administered per protocol 
and the reason if not, whether full dose is administered and the reason if not, anatomical location 
of the administration, follow-up time since the first vaccination. 
9.3.1.5 
Vital Sign Measurements and Physical Examination 
Listings will be provided for vital sign measurements and physical examinations data collected. 
9.3.2 
Immunogenicity Analysis 
All immunogenicity analyses will be descriptive. Listings will be provided for all 
immunogenicity data collected. 
9.3.2.1 
Analysis of Primary Immunogenicity Endpoints 
The analysis of the primary immunogenicity endpoints will be performed using the Per-Protocol 
(PP) Analysis Set and the Neutralization Assay Subset. 
The primary immunogenicity endpoints focus on NAb against the Omicron XBB1.5 strain at 
Day 28 following initial study vaccination. Neutralizing antibodies (NAb) GMT and GMFR 
(compared to Day 0) to the Omicron XBB.1.5 strain and corresponding 95% CIs, are 
summarized at Day 28 by vaccine group. GMT is calculated as the antilog of the mean of log- 
transformed titer values. GMFR is the antilog of the mean of log-transformed fold-rises. The 
95% CIs are calculated based on the t-distribution of the log transformed titer or fold-rise values, 
then back transformed to the original scale. The between-group ratio of GMT (GMTR) at Day 28 
and the two-sided 95% CIs are computed using the analysis of covariance with the vaccine group 
as the fixed effect and the titer at Day 0 (ie, adjusted for intergroup variation in baseline [pre- 
vaccination] titers) as the covariate. The mean difference between vaccine groups and the 
corresponding CI limits will then be exponentiated to obtain the ratio of NAb GMTs and the 
corresponding 95% CIs. There is no formal evaluation of statistical hypotheses. 
Seroresponse is defined as post-vaccination titer ≥4-fold increase from baseline value. 
Participants with a baseline value below the lower limit of quantitation (LLOQ) will be 
considered achieving seroresponse only if the post-baseline value is greater than or equal to 4 
times the LLOQ. The percentage of participants achieving seroresponse rate (SRR) is calculated 
at Day 28. 95% CIs of the SRR will be calculated based on the exact Clopper-Pearson method. 
Difference in SRR will be calculated at Day 28, with the 95% CI for the difference based on the 
method of Miettinen and Nurminen. 

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9.3.2.2 
Analysis of Secondary Immunogenicity Endpoints 
For the secondary immunogenicity endpoints of NAb response against the Omicron XBB.1.5 
strain over time, analyses will be performed using the Per-Protocol (PP) Analysis Set and the 
Neutralization Assay Subset. NAb GMTs to the Omicron XBB.1.5 strain and 95% CIs are 
summarized at Day 0, 90, and 180. NAb GMFR (compared to Day 0) and SRR to the Omicron 
XBB.1.5 strain and 95% CIs are summarized at Day 90 and 180. 
For the secondary immunogenicity endpoints of IgG antibody levels against the Omicron 
XBB.1.5 strain over time, analyses will be performed using the Per-Protocol (PP) Analysis Set 
and the Anti-S Protein IgG Serology Subset. IgG GMEUs to the Omicron XBB.1.5 strain and 
95% CIs are summarized at Day 0, 28, 90, and 180. IgG GMFR (compared to Day 0) and SRR to 
the Omicron XBB.1.5 strain and 95% CIs are summarized at Day 28, 90 and 180. 
Summary statistics used to evaluate secondary immunogenicity objectives are summarized by 
vaccine group. There is no formal evaluation of statistical hypotheses. 
9.3.2.3 
Analysis of Exploratory Immunogenicity Endpoints 
For the exploratory immunogenicity endpoints of NAb and IgG antibody responses against the 
ancestral (Wuhan) strain over time, analyses will be performed using the Per-Protocol (PP) 
Analysis Set, and within the Neutralization Assay Subset and the Anti-S Protein IgG Serology 
Subset respectively. NAb GMTs and IgG GMEUs to the ancestral (Wuhan) strain with 
corresponding 95% CIs are summarized at Day 0, 28, 90, and 180. NAb and IgG GMFR 
(compared to Day 0) and SRR with corresponding 95% CIs are summarized at Day 28, 90 and 
180. The endpoints will be analyzed by vaccine group. 
For the exploratory immunogenicity endpoints of antibody responses in a hACE2 receptor 
binding inhibition assay against the Omicron XBB.1.5 and ancestral (Wuhan) strains over time, 
analyses will be performed using the Per-Protocol (PP) Analysis Set and the hACE2 Receptor- 
Binding Inhibition Assay Subset. Serum hACE2 GMTs to the Omicron XBB.1.5 and ancestral 
(Wuhan) strains with corresponding 95% CIs are summarized at Day 0, 28, 90, and 180. hACE2 
GMFR (compared to Day 0) and SRR to the Omicron XBB.1.5 and ancestral (Wuhan) strains 
with corresponding 95% CIs are summarized at Day 28, 90 and 180. The endpoints will be 
analyzed by vaccine group. 
Mucosal IgA-mediated hACE2 receptor inhibition assay responses to the Omicron XBB.1.5 and 
ancestral (Wuhan) strains will be summarized using the PP Analysis Set and the Mucosal hACE2 
Receptor-Binding Inhibition Assay Subset. GMTs to the Omicron XBB.1.5 and ancestral 
(Wuhan) strains with corresponding 95% CIs will be summarized at Day 0 and Day 28. GMFR 
(compared to Day 0) and SRR with corresponding 95% CIs will be summarized at Day 28. 
The other exploratory Immunogenicity analyses will be defined in the SAP. 

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9.3.3 
Other Exploratory Analyses 
The other exploratory analyses will be defined in the SAP. 
9.4 
Other Statistical Considerations 
9.4.1 
Population Analysis 
9.4.1.1 
Disposition and Protocol Compliance 
The number of participants consented, randomized/enrolled, and vaccinated will be presented by 
vaccine group for the All Randomized Participants Analysis Set. 
The number (percentage) of participants in the All Randomized Participants Analysis Set, FAS, 
Safety Analysis Set, and PP Analysis Set for the primary endpoint only who have completed the 
study up to the time of pre-planned analyses (including EOS for the final analysis) will be 
summarized by vaccine group. 
The number (percentage) of participants who discontinue the study prior to EOS and the reason 
for discontinuation (eg, AE, investigator decision, lost to follow-up, non-compliance, etc.) will 
be presented by vaccine group. 
The number (percentage) of participants with major protocol deviation(s) recorded throughout 
the study will be summarized by vaccine group and protocol deviation category. 
9.4.1.2 
Demographics and Baseline Characteristics 
Baseline demographic and background characteristics (eg, age, gender, ethnicity, race, height, 
weight, and BMI [derived]) will be summarized by vaccine group for the FAS, Safety, and PP 
Analysis Sets. Frequencies and percentages will be presented for categorical variables. 
Continuous variables will be summarized using descriptive statistics (total number of 
participants, mean and standard deviation, median, minimum, and maximum). 
Medical history will be coded using MedDRA terms. Baseline medical history recorded at 
Screening will be summarized by the study vaccine group and by MedDRA SOC/PT for all 
participants in the Safety Analysis Set. Within each SOC and PT, the number and percentage of 
participants with at least one medical history event will be presented, respectively. Multiple 
events within a given SOC and PT for a participant will be counted once. 
The characterization of baseline immunity will be summarized, to include tabulation of PCR and 
anti-N results at Day 0, the brand(s) of mRNA vaccine previously received, the number of doses 
received, and the length of the interval between last mRNA vaccine and study investigational 
vaccine. 

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9.4.1.3 
Listings of Population Analysis data 
Listings of all data used for analysis of population parameters will be created. 
9.5 
Planned Interim Analyses 
A formal interim analysis will be carried out when the complete data is available to evaluate the 
primary endpoint. A set of secondary and exploratory endpoints will also be analyzed at this 
time, dependent on the availability of data. The database extract is expected to include 
immunogenicity data and safety data through Day 28. An independent statistics organization or 
the internal statistics team will perform the analysis and receive unblinded data at the time of 
analyses, following final determination of participant exclusions from analysis populations and 
database extract. At the time of Day 28 data extract with receipt of the randomization list, the 
Sponsor will be unblinded at the participant level to prepare for regulatory submissions. 
9.6 
Specified Analyses for Independent Data Monitoring Committee Review 
Data surrounding suspected cases of myocarditis/pericarditis will be provided to the appointed 
Central Cardiac Adjudication Committee as needed 
9.7 
Procedures for Reporting Changes to the Planned Analysis 
Changes to the analyses or analysis methods specified in the protocol will be documented in the 
SAP and in the clinical study report. 
10 
ETHICAL CONSIDERATIONS 
10.1 
Good Clinical Practice 
The investigator agrees that the study will be conducted according to the principles of ICH 
E6(R2). The investigator will conduct all aspects of this study in accordance with all national, 
state, and local laws or regulations. The study will be conducted in compliance with the protocol, 
current GCP guidelines – adopting the principles of the Declaration of Helsinki – and all 
applicable regulatory requirements. 
Prior to study initiation, the protocol and the informed consent documents will be reviewed and 
approved by the sponsor (or designee) and an appropriate ethics committee. Any amendment to 
the protocol or consent materials must also be approved by the study sponsor (or designee) and 
IRB and must be submitted/notified to the regulatory authority, as required, before they are 
implemented. 
10.2 
Ethics Review 
Prior to the start of the study, the investigator is responsible for ensuring that the protocol and 
consent form have been reviewed and approved by a relevant IRB. The IRB shall be 

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appropriately constituted and perform its functions in accordance with ICH GCP and local 
requirements as applicable. 
The IRB shall approve all protocol amendments (except for logistical or administrative changes), 
written informed consent documents and document updates, participant recruitment procedures 
(eg, advertisements), written information to be provided to the participants, IB, available safety 
information, information about payment and compensation available to participants, the 
investigator's curriculum vitae and/or other evidence of qualifications and any other documents 
requested by the IRB and Regulatory Authority (Competent Authority) as applicable. 
10.3 
Informed Consent 
The nature and purpose of the study shall be fully explained to each participant. They must be 
informed that participation is voluntary. 
Documentation of informed consent (either written or via eConsent) must be obtained from each 
participant prior to any study procedures being performed. The process of obtaining informed 
consent must be documented in the participant’s source documents. The authorized person 
obtaining the informed consent must also sign the ICF, and a copy of the ICF must be provided 
to the participant. Participants must be re-consented to the most current version of the ICF during 
their participation in the study. 
Participants will be requested to provide the name and contact information for an emergency 
contact and to provide consent for future testing to support establishment of correlates of 
protection against SARS-CoV-2 infection and disease (see Section 6.2 regarding sample 
retention). 
The consent documents to be used for the study shall include all the elements of informed 
consent as outlined in accordance with ICH GCP and local requirements as applicable and be 
reviewed and approved by the appropriate IRB prior to use. 
10.4 
Data Privacy 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain participant confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the written 
permission of the participant, except as necessary for monitoring and auditing by the sponsor, its 
designee, relevant regulatory authority(ies), or the IRB. 
The investigator and all employees and co-workers involved with this study may not disclose or 
use for any purpose other than performance of the study, any data, record, or other unpublished, 
confidential information disclosed to those individuals for the purpose of the study. Prior written 
agreement from the sponsor or its designee must be obtained for the disclosure of any said 
confidential information to other parties. 

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11 
OVERSIGHT 
11.1 
Quality Control and Assurance 
The Sponsor/designee shall implement and maintain quality control and quality assurance 
procedures with written standard operating procedures (SOPs) to ensure that the study is 
conducted and data are generated, documented, and reported in compliance with the protocol, 
ICH GCP, and applicable regulatory requirements. 
This study shall be conducted in accordance with the provisions of the Declaration of Helsinki 
(October 2013) and ICH GCP (CPMP/ICH/135/95 and updates). 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB. 
• Notifying the IRB of SAEs or other significant safety findings as required by IRB 
procedures. 
The investigator may not deviate from the protocol without a formal protocol amendment having 
been established and approved by an IRB, except when necessary to eliminate immediate 
hazards to the participant or when the change(s) involve(s) only logistical or administrative 
aspects of the study. Any deviations may result in the participant having to be withdrawn from 
the study and render that participant non-evaluable. 
The identification and reporting of serious breaches of ICH GCP or the protocol to the 
Regulatory Authorities and Ethics Committees will be conducted according to local SOPs and 
regulations. 
11.1.1 
Monitoring 
The Syneos clinical monitor, as a representative of the sponsor, is obligated to follow the study 
closely. In doing so, the monitor will visit the investigator and study site at periodic intervals as 
defined in the study monitoring and oversight plans in addition to maintaining necessary 
telephone and email contact. The monitor will maintain current personal knowledge of the study 
through observation, review of study records and source documentation, and discussion of the 
conduct of the study with the investigator and personnel. 
All aspects of the study will be carefully monitored by the sponsor or its designee for compliance 
with applicable government regulation with respect to current ICH E6(R2)guidelines and 
standard operating procedures. 

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11.1.2 
Audits 
The investigator and institution involved in the study will permit study-related monitoring, 
audits, IRB review, and regulatory inspections by providing direct access to all study records. In 
the event of an audit, the investigator agrees to allow the sponsor, their representatives, or the 
regulatory authority access to all study records. 
The investigator should promptly notify the sponsor of any audits scheduled by any regulatory 
authorities and promptly forward copies of any audit reports received to the sponsor. 
11.1.3 
Protocol Deviations 
The investigator or designee must document and explain in the participant’s source 
documentation any deviation from the approved protocol. The investigator may implement a 
deviation from, or a change to, the protocol to eliminate an immediate hazard to study 
participants without prior IRB approval. As soon as possible after such an occurrence, the 
implemented deviation or change, the reasons for it, and any proposed protocol amendments 
should be submitted to the IRB for review and approval, to the sponsor for agreement, and to the 
regulatory authorities, if required. 
A protocol deviation is any change, divergence, or departure from the study design or procedures 
defined in the protocol. An important deviation (sometimes referred to as a major or significant 
deviation) is a subset of protocol deviations that leads to a participant being discontinued from 
the study or significantly affects the participant’s rights, safety, or well-being and/or the 
completeness, accuracy, and reliability of the study data. An important deviation can include 
nonadherence to inclusion or exclusion criteria or nonadherence to regulatory authority including 
ICH E6(R2) guidelines. 
Protocol deviations will be documented by the clinical monitor throughout the course of 
monitoring visits. The investigator will be notified in writing by the monitor of deviations. The 
IRB should be notified of all protocol deviations, as appropriate, in a timely manner. 
Review and categorization of protocol deviations will occur prospectively during the study prior 
to database lock(s). 
11.1.4 
Records 
11.1.4.1 
Data Capture and Management 
All required study data will be entered by study site personnel in the eCRF or by study 
participants in the eDiary created for the study. Data required according to this protocol will be 
recorded by study site personnel via data entry into the internet-based EDC software system or 
by study participant via the eDiary. The investigator shall ensure that all data from participant 
visits are promptly entered into the eCRFs in accordance with the specific instructions given. 
The investigator must sign each eCRF to verify the integrity of the data recorded. All internal 

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Syneos and external study site personnel seeking access to the eCRF are supported by a Service 
Desk (if applicable). At the end of the study all data captured electronically will be provided to 
the investigator on CD ROM for archiving at the study site. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
11.1.4.2 
Source Documentation 
The investigator must maintain source documents, such as laboratory reports, consultation 
reports, reactogenicity diaries and complete medical history and physical examination reports. 
All information in the CRF must be traceable to the participant’s source documents. 
The investigator/institution shall provide direct access to source data/documents for study related 
monitoring, audits, IRB review, and regulatory inspection. 
11.1.4.3 
Records Retention 
The investigator/institution should maintain the study documents as specified in the ICH 
guidelines on GCP and as required by the applicable regulatory requirements. The 
investigator/institution should take measures to prevent accidental or premature destruction of 
these documents. 
It is the Sponsor’s responsibility to inform the investigator/institution as to when these 
documents no longer need to be retained. 
11.2 
Study Termination or Study Site Closure 
Although the sponsor has every intention of completing the study, they reserve the right to 
discontinue it at any time for clinical or administrative reasons. 
The end of the study is defined as the date on which the last participant completes the last study 
visit (including the EOS visit and any additional long-term follow-up). Any additional long-term 
follow-up that is required for monitoring of the resolution of an AE or finding may be appended 
to the clinical study report. 
12 
PUBLICATION POLICY 
The Sponsor shall retain the ownership of all data. When the study is complete the Sponsor shall 
arrange the analysis and tabulation of data. A clinical study report shall then be prepared, which 
may be used for publication, presentation at scientific meetings or submission to regulatory 
authorities. 
The Sponsor will generally support publication of multicenter studies only in their entirety and 
not as individual study site data. In this case, a coordinating investigator will be designated by 

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mutual agreement. Authorship will be determined by mutual agreement and in line with the 
International Committee of Medical Journal Editors authorship agreements. Authors will be 
provided reasonable access to all study data, statistical tables, figures, and relevant reports and 
will have the opportunity to review complete study results. All proposed publications based on 
this study must be participant to the Sponsor's approval requirements. 
The Sponsor assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and finalization 
of the study report, the results of this trial will be submitted for publication and/or posted in a 
publicly accessible database of clinical trial results. 
13 
FINANCING AND INSURANCE 
The investigator is required to provide financial disclosure information to allow the sponsor to 
submit the complete and accurate certification or disclosure statements required under US Title 
21 CFR Part 54 and local regulations. In addition, the investigator must provide to the sponsor a 
commitment to promptly update this information if any relevant changes occur during the course 
of the investigation and for 1 year following the completion of the study. 
Neither the sponsor nor the CRO nor the study site is financially responsible for further testing or 
treatment of any medical condition that may be detected during the screening process. In 
addition, in the absence of specific arrangements, neither the sponsor nor the CRO nor the study 
site is financially responsible for further treatment of the disease under study. 

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14 
REFERENCES 
Adler 2015 
Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of 
pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases 
of the European Society of Cardiology (ESC)Endorsed by: The European Association for 
Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2015 Nov 7;36(42):2921-2964 
Aretz 1987 
Aretz HT, Billingham ME, Edwards WD, et al. Myocarditis. A histopathologic definition and 
classification. Am J Cardiovasc Pathol. 1987 Jan; 1 (1):3-14. 
CDC 2022 
Centers for Disease Control and Prevention (CDC). SARS-CoV-2 Variant Classifications and 
Definitions. 26 Apr 2022. Available at: https://www.cdc.gov/coronavirus/2019- 
ncov/variants/variant-classifications.html 
CDC 2023 
Centers for Disease Control and Prevention. COVID Data Tracker. Atlanta, GA: US Department 
of Health and Human Services, CDC; 2023, April 28. Available at: https://covid.cdc.gov/covid- 
data-tracker/#variant-proportions 
CDC 2021 
Centers for Disease Control and Prevention. Clinical considerations: myocarditis and pericarditis 
after receipt of mRNA COVID-19 vaccines among adolescents and young adults. Available at: 
https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html. 
DAIDS 2017 
Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), 
National Institutes of Health (NIH), US Department of Health and Human Services. Division of 
AIDS (DAIDS) table for grading the severity of adult and pediatric adverse events. July 2017. 
Available at: https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf 
Dunkle 2021 
Dunkle LM, Kotloff KL, Gay MD, et al. Efficacy and safety of NVX-CoV2373 in adults in the 
United States and Mexico. New Engl J Med. 2022 Feb(386):531-543. 
doi10.1056/NEJMoa2116185. 

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FDA 2007 
U.S. Food and Drug Administration, Center for Biologics Evaluation and Research (US). 
Guidance for industry: Toxicity grading scale for healthy adult and adolescent volunteers 
enrolled in preventive vaccine clinical trials. September 2007. Available at: 
https://www.fda.gov/media/73679/download 
Ferreira 2018 
Ferreira VM, Schulz-Menger J, Holmvang G, et al. Cardiovascular Magnetic Resonance in 
Nonischemic Myocardial Inflammation: Expert Recommendations. Am Coll Cardiol. 2018 Dec 
18;72(24):3158-3176. 
Garcia-Beltran 2021 
Garcia-Beltran WF, St Denis KJ, Hoelzemer A, et al. mRNA-based COVID-19 vaccine boosters 
induce neutralizing immunity against SARS-CoV-2 Omicron variant. medRxiv [Preprint]. 2021 
Dec 14:2021.12.14.21267755. doi: 10.1101/2021.12.14.21267755 
Gargano 2021 
Gargano JW, Wallace M, Hadler SC, Langley G, Su JR, Oster ME, et al. Use of mRNA COVID- 
19 vaccine after reports of myocarditis among vaccine recipients: update from the advisory 
committee on immunization practices - United States, June 2021. MMWR Morb Mortal Wkly 
Rep. 2021 Jul 9;70(27):977-82. 
Habibzadeh 2020 
Habibzadeh P, Stoneman EK. The novel coronavirus: a bird’s eye view. Int J Occup Environ 
Med. 2020;11(2):65-71. 
Heath 2021 
Heath PT, Galiza EP, Baxter DN, et al. Safety and efficacy of the NVX-CoV2373 Covid-19 
vaccine. N Engl J Med 2021;385:1172-1183. 
Keech 2020 
Keech C, Albert G, Cho I, et al. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein 
nanoparticle vaccine. New Engl J Med. 2020;383:2320-2332. 
Lambert 2020 
Lambert P-H, Ambrosino DM, Andersen SR, et al. Consensus summary report for CEPI/BC 
March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 
vaccines. Vaccine. 2020;38(31):4783-4791. 

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Law 2021 
Law YM, Lal AK, Chen S, et al. Diagnosis and management of myocarditis in children: a 
scientific statement from the American Heart Association. Circulation. 2021;144:e123-e135. 
Mallory 2022 
Mallory RM, Formica N, Pfeiffer S, et al. Safety and immunogenicity following a homologous 
booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a 
secondary analysis of a randomised, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2022 
Nov;22(11):1565-1576. doi: 10.1016/S1473-3099(22)00420-0. 
Marks 2022 
Marks, P. (2022). "Coronavirus (COVID-19) update: FDA recommends inclusion of omicron 
BA.4/5 component for COVID-19 vaccine booster doses". Available at: 
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda- 
recommends-inclusion-omicron-ba45-component-covid-19-vaccine-booster." 
Novavax 2022 
Clinical Investigator’s Brochure for SARS-CoV-2 Recombinant Spike Protein Nanoparticle 
Vaccine (SARS-CoV-2 rS). Novavax, 2022. 
Qu 2023 
Qu P, Faraone JN, Evans JP, et al. Extraordinary Evasion of Neutralizing Antibody Response by 
Omicron XBB.1.5, CH.1.1 and CA.3.1 Variants. bioRxiv [Preprint]. 2023 Jan 
17:2023.01.16.524244. doi: 10.1101/2023.01.16.524244. 
Sheikh-Mohamed 2022 
Sheikh-Mohamed S, Isho B, Chao Y.C. et al. Systemic and mucosal IgA responses are variably 
induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection 
against subsequent infection. Mucosal Immunology (2022) 15:799–808. 
Shinde 2021 
Shinde V, Bhika S, Hoosain Z, Archary M, et al. Efficacy of NVX-CoV2373 Covid-19 Vaccine 
against the B.1.351 Variant. New Engl J Med. Preprint 2021 May 05 DOI: 
10.1056/NEJMoa2103055. 
Su 2016 
Su S, Wong G, Shi W, et al. Epidemiology, genetic recombination, and pathogenesis of 
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Tavares 2013 
Tavares F, Keyser F, Lambert P, et al. Optimal approaches to data collection and analysis of 
potential immune mediated disorders in clinical trials of new vaccines. Vaccine. 2013;31:1870- 
76. 
Yue 2023 
Yue C, Song W, Wang L, et al. ACE2 binding and antibody evasion in enhanced transmissibility 
of XBB.1.5. Lancet Infect Dis. 2023 Mar;23(3):278-280. doi: 10.1016/S1473-3099(23)00010-5. 
Zhang 2022 
Zhang X, Chen LL, Ip JD, et al. Omicron sublineage recombinant XBB evades neutralising 
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Mar;4(3):e131. doi: 10.1016/S2666-5247(22)00335-4. 

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15 
APPENDICES 
APPENDIX 1: 
LISTINGS OF ADVERSE EVENTS OF SPECIAL INTEREST 
Because it has been hypothesized that immunizations with or without adjuvant may be associated 
with autoimmunity, regulatory authorities have requested that Novavax instruct investigators to 
be especially vigilant regarding the PIMMCs listed in Table 7. Note that this regulatory request 
is not specific to Novavax’s SARS-CoV-2 rS or Matrix-M adjuvant; and there is no current 
evidence to suggest that the study vaccines in this protocol are, or are not, associated with these 
illnesses. The list is not intended to be exhaustive, nor does it exclude the possibility that other 
diagnoses may be AESI. 
 
Table 7: 
Potential Immune-Mediated Medical Conditions 
 
Categories 
Diagnoses (as MedDRA Preferred Terms) 
Neuroinflammatory 
Disorders: 
Acute disseminated encephalomyelitis (including site-specific variants: eg, non- 
infectious encephalitis, encephalomyelitis, myelitis, cranial nerve disorders 
including paralyses/paresis (eg, Bell’s palsy), ascending flaccid paralysis, 
generalized convulsion, Guillain-Barre syndrome (including Miller Fisher 
syndrome and other variants), immune-mediated peripheral neuropathies and 
plexopathies (including chronic inflammatory demyelinating polyneuropathy, 
multifocal motor neuropathy and polyneuropathies associated with monoclonal 
gammopathy), myasthenia gravis, multiple sclerosis, narcolepsy, optic neuritis, 
transverse myelitis, uveitis. 
Musculoskeletal and 
Connective Tissue 
Disorders: 
Antisynthetase syndrome, dermatomyositis, juvenile idiopathic arthritis (including 
Still’s disease), connective tissue disorder, polymyalgia rheumatic, polymyositis, 
psoriatic arthropathy, polychondritis, rheumatoid arthritis, scleroderma (including 
diffuse systemic form and CREST syndrome), spondyloarthritis (including 
ankylosing spondylitis, reactive arthritis [Reiter's Syndrome], axial 
spondyloarthritis, juvenile spondyloarthritis and undifferentiated spondyloarthritis), 
systemic lupus erythematosus, systemic sclerosis, Sjogren’s syndrome. 
Vasculitides: 
Large vessels vasculitis (including giant cell arteritis such as Takayasu's arteritis 
and temporal arteritis), medium sized and/or small vessels vasculitis (including 
polyarteritis nodosa, Kawasaki's disease, microscopic polyangiitis, Wegener's 
granulomatosis, Churg–Strauss syndrome [allergic granulomatous angiitis], 
Buerger’s disease [thromboangiitis obliterans], Eosinophilic granulomatosis with 
polyangiitis, necrotizing vasculitis and ANCA-positive vasculitis [type 
unspecified], Henoch-Schonlein purpura, Behcet's syndrome). 
Gastrointestinal Disorders: 
Crohn’s disease, celiac disease, ulcerative colitis, ulcerative proctitis. 
Hepatic Disorders: 
Autoimmune hepatitis, autoimmune cholangitis, cholangitis sclerosing primary 
biliary cirrhosis. 
Renal Disorders: 
Autoimmune glomerulonephritis (including IgA nephropathy, glomerulonephritis 
rapidly progressive, membranous glomerulonephritis, membranoproliferative 
glomerulonephritis, and mesangioproliferative glomerulonephritis). 

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Table 7: 
Potential Immune-Mediated Medical Conditions 
 
Categories 
Diagnoses (as MedDRA Preferred Terms) 
Cardiac Disorders: 
Autoimmune myocarditis/cardiomyopathy. 
Myocarditis and/or pericarditis. 
Skin Disorders: 
Alopecia areata, psoriasis, vitiligo, Raynaud’s phenomenon, erythema nodosum, 
autoimmune bullous skin diseases (including pemphigus, pemphigoid and 
dermatitis herpetiformis), cutaneous lupus erythematosus, morphoea, lichen planus, 
Stevens-Johnson syndrome. 
Hematologic Disorders: 
Autoimmune hemolytic anemia, immune thrombocytopenia, antiphospholipid 
syndrome, thrombocytopenia. 
Metabolic Disorders: 
Autoimmune thyroiditis, Basedow’s disease, Hashimoto thyroiditis, diabetes 
mellitus type 1, Addison’s disease. 
Other Disorders: 
Goodpasture syndrome, idiopathic pulmonary fibrosis, pernicious anemia, 
sarcoidosis. 
Abbreviations: ANCA = anti-neutrophil cytoplasmic antibody; IgA = immunoglobulin A; MedDRA = Medical 
Dictionary for Regulatory Activities. 
Source: Adapted from Tavares 2013. 
Complications specific to COVID-19 are listed in Table 8. The list is not intended to be 
exhaustive, nor does it exclude the possibility that other diagnoses may be AESIs. 
 
Table 8: 
Adverse Events Representing Complications Specific to COVID-191 
 
Categories 
Diagnoses (as MedDRA System Organ Class/Preferred Term) 
Respiratory/Infectious Disorders: 
ARDS, pneumonitis, septic shock-like syndrome. 
Cardiac Disorders: 
Acute cardiac injury, arrhythmia, myocarditis, pericarditis (including 
myopericarditis). 
Coagulopathy: 
Deep vein thrombosis, myocardial infarction, stroke. 
Renal Disorders: 
Acute kidney injury. 
Hematologic Disorders: 
Thrombocytopenia, septic shock-like syndrome. 
Inflammatory Disorders: 
Cytokine Release Syndrome2 related to COVID-19 infection, multisystem 
inflammatory syndrome in children (MIS-C). 
Neurologic Disorders: 
Generalized convulsions. 
Abbreviations: ARDS = acute respiratory distress syndrome; COVID-19 = coronavirus disease 2019; DAIDS = 
Division of AIDS; MedDRA = Medical Dictionary for Regulatory Activities. 
1. COVID-19 manifestations associated with more severe presentation and decompensation with consideration 
of enhanced disease potential. The current listing is based on Coalition for Epidemic Preparedness 
Innovations /Brighton Collaboration Consensus Meeting (12/13 March 2020) and expected to evolve as 
evidence accumulates (Lambert 2020). 
2. Cytokine release syndrome is a disorder characterized by nausea, headache, tachycardia, hypotension, rash, 
and/or shortness of breath (DAIDS 2017). 

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APPENDIX 2: 
TOXICITY GRADING SCALE FOR CLINICAL ABNORMALITIES 
(LOCAL AND GENERAL SYSTEMIC REACTOGENICITY AND 
VITAL SIGNS) 
 
Table 9: 
Modified FDA Toxicity Grading Scale for Clinical Abnormalities (Local and 
General Systemic Reactogenicity) 
 
Local Reaction to Injectable Product 
Mild 
(Grade 1) 
Moderate (Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Pain 
Does not interfere with 
activity 
Repeated use of non- 
prescription pain 
reliever >24 hours or 
interferes with 
activity 
Significant; any use 
of prescription pain 
reliever or prevents 
daily activity 
Requires ER visit or 
hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
Requires ER visit or 
hospitalization 
Erythema/rednessa 
2.5 − 5 cm 
5.1 − 10 cm 
>10 cm 
Necrosis or 
exfoliative 
dermatitisb 
Induration/swellinga 
2.5 − 5 cm 
5.1 − 10 cm 
>10 cm 
Necrosisb 
Systemic (General) 
Mild 
(Grade 1) 
Moderate (Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Feverc (°C) 
(°F) 
38.0 − 38.4 
100.4 − 101.1 
38.5 − 38.9 
101.2 − 102.0 
39.0 − 40 
102.1 − 104 
>40 
>104 
Nausea/vomiting 
Does not interfere with 
activity or 
1 − 2 episodes/24 hours 
Some interference 
with activity or 
>2 episodes/24 hours 
Prevents daily 
activity, or requires 
IV hydration outside 
of hospital 
Requires ER visit or 
hospitalization 
Headache 
Does not interfere with 
activity 
Repeated use of non- 
prescription pain 
reliever >24 hours or 
interferes with 
activity 
Significant; any use 
of prescription pain 
reliever or prevents 
daily activity 
Requires ER visit or 
hospitalization 
Fatigue/Malaise 
Does not interfere with 
activity 
Some interference 
with activity 
Significant, prevents 
daily activity 
Requires ER visit or 
hospitalization 
Myalgia 
Does not interfere with 
activity 
Some interference 
with activity 
Significant, prevents 
daily activity 
Requires ER visit or 
hospitalization 
Arthralgia 
Does not interfere with 
activity 
Some interference 
with activity 
Significant, prevents 
daily activity 
Requires ER visit or 
hospitalization 
a The measurements should be recorded as a continuous variable. 
b These events are not participant reported through the eDiary and will be monitored through the AE pages of the 
study database. 
c Oral temperature if participant collected, sites may collect temperature using local clinic practices/devices. 
Toxicity grade will be derived. 
Source: FDA 2007 

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Table 10: 
FDA Toxicity Grading Scale for Clinical Abnormalities (Vital Signs) 
 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life Threatening 
(Grade 4) 
Tachycardia (bpm) 
101 – 115 
116 – 130 
> 130 
ER visit or hospitalization for arrhythmia 
Bradycardia (bpm)a 
50 – 54 
45 – 49 
< 45 
ER visit or hospitalization for arrhythmia 
Hypertension (systolic) 
(mm Hg) 
141 – 150 
151 – 155 
> 155 
ER visit or hospitalization for malignant 
hypertension 
Hypertension (diastolic) 
(mm Hg) 
91 – 95 
96 – 100 
> 100 
ER visit or hospitalization for malignant 
hypertension 
Hypotension (systolic) 
(mm Hg) 
85 – 89 
80 – 84 
< 80 
ER visit or hospitalization for 
hypotensive shock 
Respiratory Rate 
(breaths per minute) 
17 – 20 
21 – 25 
> 25 
Intubation 
Note: Participant should be at rest for all vital sign measurements. 
a When resting heart rate is between 60 – 100 bpm. Use clinical judgement when characterizing bradycardia 
among some healthy participant populations (eg, conditioned athletes). 
Source: FDA 2007 

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APPENDIX 3: 
ASSESSMENT OF COVID-19 SEVERITY 
 
Table 11: 
COVID-19 Severity Grading Criteria 
Grade 
Criteria 
Mild 
≥ 1 of the following: 
• Fever (defined by subjective or objective measure, regardless of use of anti-pyretic 
medications) 
• New onset cough 
≥ 2 additional COVID-19 symptoms: 
• New onset or worsening of shortness of breath or difficulty breathing compared to baseline. 
• New onset fatigue. 
• New onset generalized muscle or body aches. 
• New onset headache. 
• New loss of taste or smell. 
• Acute onset of sore throat, congestion, or runny nose. 
• New onset nausea, vomiting or diarrhea. 
Moderate 
≥ 1 of the following: 
• High fever (≥ 38.4°C) for ≥ 3 days (regardless of use of anti-pyretic medications, need not be 
contiguous days). 
• Any evidence of significant lower respiratory tract infection (LRTI): 
• Shortness of breath (or breathlessness or difficulty breathing) with or without exertion 
(greater than baseline). 
• Tachypnea: 24 to 29 breaths per minute at rest. 
• SpO2: 94% to 95% on room air. 
• Abnormal chest X-ray or chest computerized tomography (CT) consistent with pneumonia or 
LRTI. 
• Adventitious sounds on lung auscultation (eg, crackles/rales, wheeze, rhonchi, pleural rub, 
stridor). 
Severe 
≥ 1 of the following: 
• Tachypnea: ≥ 30 breaths per minute at rest. 
• Resting heart rate ≥ 125 beats per minute. 
• SpO2: ≤ 93% on room air or PaO2/FiO2< 300 mmHg. 
• High flow oxygen (O2) therapy or non-invasive ventilation (NIV)/non-invasive positive 
pressure ventilation (NIPPV) (eg, continuous positive airway pressure [CPAP] or bilevel 
positive airway pressure [BiPAP]). 
• Mechanical ventilation or extracorporeal membrane oxygenation (ECMO). 
One or more major organ system dysfunction or failure to be defined by diagnostic testing/clinical 
syndrome/interventions, including any of the following: 
• Acute respiratory failure, including acute respiratory distress syndrome (ARDS). 
• Acute renal failure. 
• Acute hepatic failure. 
• Acute right or left heart failure. 

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Table 11: 
COVID-19 Severity Grading Criteria 
Grade 
Criteria 
• Septic or cardiogenic shock (with shock defined as systolic blood pressure [SBP] < 90 mm 
Hg OR diastolic blood pressure [DBP] < 60 mm Hg). 
• Acute stroke (ischemic or hemorrhagic). 
• Acute thrombotic event: acute myocardial infarction (AMI), deep vein thrombosis (DVT), 
pulmonary embolism (PE). 
• Requirement for: vasopressors, systemic corticosteroids, or hemodialysis. 
• Admission to an intensive care unit (ICU). 
• Death.