A Randomized, Observer-Blinded, Phase 3 Study to Compare the Immunogenicity and Safety of 3 Lots of NVX-CoV2373 in Adults
Phase: PHASE3
Conditions: COVID-19, SARS-CoV-2 Infection
Sponsor: Novavax

Clinical Study Protocol 
2019nCoV-307 
Version 5.0/Amendment 4 
SARS-CoV-2 rS Vaccine 
COVID-19 
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A Randomized, Observer-Blinded, Phase 3 Study to 
Compare the Immunogenicity and Safety of 3 Lots of 
NVX-CoV2373 in Adults 
 
Investigational Product 
NVX-CoV2373 
Protocol Number 
2019nCoV-307 
Clinical Trial Registry Identifiers 
NCT05463068 
Version Number 
5.0 
Version Date 
July 20, 2022 
Amendment 
Amendment 4 
Indication Studied 
Prevention of COVID-19 caused by SARS-CoV-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. 

Clinical Study Protocol 
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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 of Technical 
Requirements for Pharmaceuticals for Human Use (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. 

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SPONSOR’S APPROVAL 
 
Title 
A Randomized, Observer-Blinded, Phase 3 Study to Compare the Safety, and 
Immunogenicity of 3 Lots of NVX-CoV2373 in Adults 
Protocol Number 
2019nCoV- 307 
Version Number 
5.0 
Version Date 
July 20, 2022 
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: 
 
 
 
Clinical Operations Representative 
Name: 
Title: 
 
 
 

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INVESTIGATOR’S AGREEMENT 
I have read the protocol, appendices, and accessory materials related to Study 2019nCoV-307 
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 

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TABLE OF CONTENTS 
STATEMENT OF COMPLIANCE ............................................................................................... 2 
SPONSOR’S APPROVAL ............................................................................................................ 3 
INVESTIGATOR’S AGREEMENT ............................................................................................. 4 
TABLE OF CONTENTS ............................................................................................................... 5 
LIST OF TABLES ......................................................................................................................... 8 
LIST OF FIGURES ........................................................................................................................ 8 
LIST OF APPENDICES ................................................................................................................ 9 
LIST OF ABBREVIATIONS ...................................................................................................... 10 
1 
SYNOPSIS ....................................................................................................................... 12 
1.1 
Schedule of Events ........................................................................................................ 14 
2 
INTRODUCTION ............................................................................................................ 16 
2.1 
Background ................................................................................................................... 16 
2.1.1 
Description of NVX-CoV2373 .................................................................................. 16 
2.1.2 
Supportive Nonclinical Data ...................................................................................... 17 
2.1.3 
Supportive Clinical Data ............................................................................................ 19 
3 
OBJECTIVES AND ENDPOINTS .................................................................................. 24 
4 
STUDY PLAN ................................................................................................................. 26 
4.1 
Study Schematic ............................................................................................................ 26 
4.2 
Study Design ................................................................................................................. 26 
4.3 
Design Rationale ........................................................................................................... 26 
5 
POPULATION ................................................................................................................. 27 
5.1 
Recruitment ................................................................................................................... 27 
5.2 
Definitions ..................................................................................................................... 27 
5.3 
Inclusion Criteria ........................................................................................................... 27 
5.4 
Exclusion Criteria .......................................................................................................... 28 
6 
STUDY CONDUCT ........................................................................................................ 29 
6.1 
Study Procedures by Visit ............................................................................................. 29 
6.1.1 
Screening Period ........................................................................................................ 29 
6.1.2 
Vaccine Administration Period (Day 1) ..................................................................... 29 
6.1.3 
Unscheduled Visit ...................................................................................................... 30 

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6.1.4 
EOS (Day 29) ............................................................................................................. 30 
6.2 
Discontinuation or Withdrawal ..................................................................................... 31 
6.2.1 
Withdrawal from Study .............................................................................................. 31 
6.2.1.1 
Replacement of Participants .................................................................................... 31 
6.2.1.2 
Participants Lost to Follow-up ................................................................................ 31 
6.3 
Study Termination by Sponsor ...................................................................................... 31 
7 
STUDY INTERVENTIONS ............................................................................................ 32 
7.1 
Description of Products ................................................................................................. 32 
7.1.1 
NVX-CoV2373 .......................................................................................................... 32 
7.1.1.1 
Formulation, Storage, Preparation, and Handling ................................................... 32 
7.1.1.2 
Packaging and Labeling .......................................................................................... 32 
7.1.1.3 
Dosing and Administration ..................................................................................... 32 
7.1.2 
Treatment Assignment and Bias Minimization .......................................................... 33 
7.1.2.1 
Treatment Allocation ............................................................................................... 33 
7.1.2.2 
Assessment and Verification of Compliance .......................................................... 33 
7.1.2.3 
Blinding ................................................................................................................... 33 
7.2 
Prior and Concomitant Therapies .................................................................................. 34 
7.2.1 
Prohibited Therapies .................................................................................................. 34 
8 
SAFETY ASSESSMENTS .............................................................................................. 35 
8.1 
Definitions ..................................................................................................................... 35 
8.2 
Documenting Adverse Events ....................................................................................... 36 
8.2.1.1 
Assessment of Causality .......................................................................................... 37 
8.2.2 
Time Frame for Collection ......................................................................................... 38 
8.2.3 
Classification of Events .............................................................................................. 38 
8.2.3.1 
Treatment-Emergent Adverse Event ....................................................................... 38 
8.2.3.2 
Adverse Events of Special Interest .......................................................................... 38 
8.2.3.3 
Medically Attended Adverse Events ....................................................................... 40 
8.2.3.4 
Pregnancy ................................................................................................................ 40 
8.2.3.5 
Overdose or Misuse ................................................................................................. 41 
8.3 
Reporting Adverse Events ............................................................................................. 41 
8.3.1.1 
Safety Reporting to Sponsor ................................................................................... 42 

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8.3.1.2 
Safety Reporting to Health Authorities, Independent Ethics Committees/ 
Institutional Review Boards, and Investigators ...................................................... 42 
8.3.1.3 
24/7 Medical Emergency Coverage for Urgent Protocol-related Medical 
Questions ................................................................................................................. 43 
9 
ANALYSIS ...................................................................................................................... 44 
9.1 
Sample Size Rationale ................................................................................................... 44 
9.2 
Analysis Sets ................................................................................................................. 44 
9.2.1 
Randomized Participants Analysis Set ....................................................................... 44 
9.2.2 
Full Analysis Set ........................................................................................................ 44 
9.2.3 
Safety Analysis Set..................................................................................................... 44 
9.2.4 
Per-Protocol Analysis Set ........................................................................................... 45 
9.2.4.1 
Anti-S Protein IgG Serology Subset ....................................................................... 45 
9.2.4.2 
Neutralization Assay Subset.................................................................................... 45 
9.2.4.3 
hACE2 Receptor-Binding Inhibition Assay Subset ................................................ 45 
9.3 
Statistical Analyses ....................................................................................................... 45 
9.3.1 
Background Analyses ................................................................................................. 45 
9.3.1.1 
Disposition and Protocol Compliance ..................................................................... 45 
9.3.1.2 
Demographics and Baseline Characteristics ........................................................... 46 
9.3.2 
Immunogenicity Analyses .......................................................................................... 46 
9.3.3 
Safety Analyses .......................................................................................................... 47 
9.3.3.1 
-Prior and Concomitant Medications and Vaccinations .......................................... 48 
9.3.3.2 
Vital Sign Measurements ........................................................................................ 48 
9.3.3.3 
Physical Examinations ............................................................................................ 48 
9.4 
Interim Analyses ........................................................................................................... 48 
9.5 
Final Analysis ................................................................................................................ 48 
10 
ETHICAL CONSIDERATIONS ..................................................................................... 49 
10.1 
Good Clinical Practice .................................................................................................. 49 
10.2 
Ethics Review ................................................................................................................ 49 
10.3 
Informed Consent .......................................................................................................... 49 
10.4 
Data Privacy .................................................................................................................. 50 
11 
OVERSIGHT ................................................................................................................... 51 
11.1 
Quality Control and Assurance ..................................................................................... 51 

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11.1.1 
Monitoring .................................................................................................................. 51 
11.1.2 
Audits ......................................................................................................................... 51 
11.1.3 
Protocol Deviations .................................................................................................... 52 
11.1.4 
Records ....................................................................................................................... 52 
11.1.4.1 
Data Capture and Management ............................................................................... 52 
11.1.4.2 
Source Documentation ............................................................................................ 52 
11.1.4.3 
Records Retention ................................................................................................... 53 
11.2 
Study Termination or Study Site Closure ..................................................................... 53 
12 
PUBLICATION POLICY ................................................................................................ 53 
13 
FINANCING AND INSURANCE .................................................................................. 54 
14 
REFERENCES ................................................................................................................. 55 
15 
APPENDICES .................................................................................................................. 57 
 
LIST OF TABLES 
Table 1 
Schedule of Events ............................................................................................... 15 
Table 2 
Study 2019nCoV-307 Objectives and Endpoints ................................................. 24 
Table 3 
Study Vaccinations ............................................................................................... 32 
Table 4 
Case Definitions of Probable and Confirmed Myocarditis, Pericarditis, and 
Myopericarditis .................................................................................................... 39 
Table 5 
Management of Suspected Myocarditis, Pericarditis, and Myopericarditis 
Cases..................................................................................................................... 40 
Table 6 
Potential Immune-Mediated Medical Conditions ................................................ 61 
Table 7 
Adverse Events Representing Complications Specific to COVID-191 ........................ 62 
LIST OF FIGURES 
Figure 1 
Flow Diagram for 2019nCoV-307 ....................................................................... 26 

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LIST OF APPENDICES 
APPENDIX 1 PROTOCOL CHANGE HISTORY ................................................................ 57 
APPENDIX 2 LISTINGS OF ADVERSE EVENTS OF SPECIAL INTEREST ................ 61 

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LIST OF ABBREVIATIONS 
 
Abbreviation 
Definition 
24/7 
24 hours 7 days a week 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ANCA 
Anti-neutrophil cytoplasmic antibody 
ANCOVA 
Analysis of covariance 
ARDS 
Acute respiratory distress syndrome 
ATC 
Anatomical therapeutic chemical 
BAL 
Bronchoalveolar lavage 
BMI 
Body mass index 
CI 
Confidence interval 
COVID-19 
Coronavirus disease 2019 
CRO 
Clinical research organization 
DAIDS 
Division of AIDS 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
ELISA 
Enzyme-linked immunosorbent assay 
EoS 
End of Study 
ER 
Emergency room 
FAS 
Full Analysis Set 
FDA 
United States Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMEU 
Geometric mean ELISA unit 
GMFR 
Geometric mean fold rise 
GMT 
Geometric mean titer 
GMTR 
Between-group ratio of MN50 GMTs 
hACE2 
Human angiotensin-converting enzyme 2 
HEENT 
head nose ears and throat 
HREC 
Human Research Ethics Committee 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IM 
Intramuscular 

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Abbreviation 
Definition 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System 
MAAE 
Medically attended adverse event 
MedDRA 
Medical Dictionary for Regulatory Activities 
MERS 
Middle East Respiratory Syndrome 
MHC 
Major histocompatibility complex 
MN50 
Microneutralization assay with an inhibitory concentration of 50% 
OTC 
Over the counter 
PCR 
Polymerase chain reaction 
PIMMC 
Potential immune-mediated medical conditions 
PP 
Per-Protocol 
PT 
Preferred term 
Rs 
Recombinant spike 
S 
Spike (protein) 
SAE 
Serious adverse event 
SAR 
Serious adverse reaction 
SARS-CoV 
Severe acute respiratory syndrome coronavirus 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SCR 
Seroconversion rate 
sgRNA 
Subgenomic RNA 
SII 
Serum Institute of India 
SOC 
System organ class 
SOE 
Schedule of Events 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected unexpected serious adverse reaction 
TEAE 
Treatment-emergent adverse event 
Th1 
Type 1 T helper 
US 
United States 

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1 
SYNOPSIS 
 
Title 
A Randomized, Observer-Blinded, Phase 3 Study to Compare the Immunogenicity 
and Safety of 3 lots of NVX-CoV2373 in Adults 
Short Title 
Phase 3 lot consistency study for NVX-CoV2373 
Phase 
Phase 3 
Study Design 
This is a randomized, Phase 3 study comparing the immunogenicity and safety of 
3 different lots of Novavax vaccine with Matrix-M™ adjuvant (NVX-CoV2373). 
The study will enroll approximately 900 previously vaccinated adults 18 to 
49 years of age, inclusive. 
Participants will be screened at baseline with the goal of enrolling approximately 
900 previously vaccinated participants. Participants will be randomized 1:1:1 to 
receive 1 dose of the vaccine from 1 of 3 different lots, given on Day 1, at a dose 
level of 5 µg of antigen with 50 µg of Matrix-M adjuvant. 
All participants will remain on study for immunogenicity and safety data collection 
through 28 days following the vaccination. 
Study Rationale 
Novavax, Inc. has developed a recombinant vaccine adjuvanted with the saponin- 
based Matrix-M adjuvant (NVX-CoV2373) for the prevention of disease caused by 
SARS-CoV-2. 
The purpose of this study is to compare the consistency of immunogenicity and 
safety of 3 different lots of NVX-CoV2373 in previously vaccinated adult 
participants 18 to 49 years of age. Data from the study are intended to support the 
overall manufacturing consistency data submitted as part of regulatory submissions 
in the United States (US) and elsewhere, as needed. 
Target Population 
Medically stable male and non-pregnant females 18 to 49 years of age, inclusive, 
who have been previously vaccinated against SARS-CoV-2. 
Treatment Groups 
Total number of participants planned: Approximately 900 
Total number per vaccine group: 
Vaccine 
Age 
(years) 
Baseline 
Serostatus 
Number 
of doses 
Number of 
participants 
Dose 
(antigen/ 
Matrix-M 
adjuvant) 
Lot 1 
(Group 1) 
18 to 
49 
Previously 
vaccinated 
1 
300 
5µg / 50 µg 
Lot 2 
(Group 2) 
1 
300 
5µg / 50 µg 
Lot 3 
(Group 3) 
1 
300 
5µg / 50 µg 
Length of Participation 
On study (including screening and follow-up): up to 2 months. 
Intervention 
NVX-CoV2373 (5 µg): Prototype SARS-CoV-2 rS. Vaccine supplied as a solution 
for preparation for injection, at a concentration of 10 µg antigen and 100 µg 
Matrix-M adjuvant per mL. The NVX-CoV2373 vaccination regimen will 
comprise 1 intramuscular (IM) injection (Day 1) of 0.5 mL injection volume at a 
dose of 5 µg antigen. Three different lots will be used in the study. 
Primary Objective and 
Endpoint 
Hypothesis: Immunoglobulin G (IgG) antibody responses following 1 dose of 
vaccine will be equivalent across the 3 lots evaluated. 

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Objective: To demonstrate the equivalence of 3 different vaccine lots based on IgG 
responses. 
Endpoint: 
• 
IgG geometric mean enzyme-linked immunoassay (ELISA) unit (GMEU) 
concentrations (ie, GMEU/mL) to the SARS-CoV-2 spike protein at Day 
29 in each treatment arm; equivalence will be demonstrated if the 95% 
confidence intervals [CIs] of GMEU concentrations for all pairs of lots are 
within the pre-specified equivalence range of 0.67 to 1.5 GMEU/mL . 
Secondary Objectives 
and Corresponding 
Endpoints 
Objective: To characterize the IgG antibody responses to 3 different lots of 
NVX-CoV2373. 
Endpoint: 
• 
Proportion of participants in each treatment arm who achieve seroconversion 
(≥ 4-fold increase from baseline) in IgG concentrations to the SARS-CoV-2 
spike protein at Day 29. 
Objective: To characterize the neutralizing antibody responses to 3 different lots of 
NVX-CoV2373. 
Endpoints: 
• 
Microneutralization (MN) assay with inhibitory concentrations of 50% (MN50) 
geometric mean titers to the SARS-CoV-2 spike protein at Day 29 in each 
treatment arm. 
• 
Proportion of participants in each treatment arm who achieve seroconversion 
(≥ 4-fold increase from baseline) in MN assay with MN50 titers to the SARS- 
CoV-2 spike protein at Day 29. 
Objective: To characterize antibody responses in a human angiotensin-converting 
enzyme 2 (hACE2) receptor binding inhibition assay to the SARS-CoV-2 spike 
protein in participants vaccinated with 3 different lots of NVX-CoV2373. 
Endpoints: 
• 
hACE2 inhibition assay titers (geometric mean titers [GMTs]) at Day 29in 
each treatment arm. 
• 
Proportion of participants in each treatment arm who achieve 
seroconversion (≥ 4-fold increase from baseline) in hACE2 titers to the 
SARS-CoV-2 spike protein at Day 29. 
Objective: To compare the overall safety of 3 different lots of NVX-CoV2373. 
Endpoints: 
• 
Incidence, duration, severity, and relationship of medically attended 
adverse events (MAAEs) and adverse events of special interest (AESIs) 
(including myocarditis and/or pericarditis) through Day 29 (ie, 28 days 
after the vaccine dose). 
• 
Incidence and relationship of serious adverse events (SAEs) throughout 
the study. 
Exploratory Objectives 
and Corresponding 
Endpoints 
Objective: To utilize additional assays (current or to be developed) to best 
characterize the immune response for future vaccine development needs. 
Endpoint: Additional endpoints to compare immune responses may be developed 
based on the assays used. 

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Number of Sites 
Approximately 30 sites in the US 
Study Duration 
Estimated duration: 1 Month (excluding screening) 
1.1 
Schedule of Events 
The Schedule of Events (SOE) is presented in Table 1. 

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Table 1 
Schedule of Events 
 
Study Day 
–30 to 11 
11 
Unscheduled 
visit 
29 
Window (days) 
– 
– 
+ 4 
Study Visit 
Screening 
1 
EOS2 
Informed consent 
X 
Medical history3 
X 
Inclusion/exclusion criteria4 
X 
X4 
Demographics 
X 
Prior/concomitant medications 
X5 
X6 
X 
X 
Vital sign measurements 
X 
X6 
X 
X 
Urine pregnancy test (WOCBP) 
X 
X6 
Physical examination 
X 
X6 
X 
X 
Baseline ECG 
X6 
Nasal swab at clinic for SARS- 
CoV-2 (PCR) – anterior nares 
X6 
Blood sampling for SARS-CoV-2 
(ELISA for anti S-protein serology, 
MN50 assay, and hACE2 receptor- 
binding inhibition assay) 
X6 
X 
Randomization 
X6 
Vaccination 
X7 
SAEs 
X 
X 
X 
X 
All MAAEs and AESIs (including 
PIMMCs, myocarditis or 
pericarditis])8 
X 
X 
X 
EOS form9 
X 
Abbreviations: AESI = adverse event(s) of special interest; ELISA = enzyme-linked immunosorbent assay; EOS = end of study; 
hACE2 = human angiotensin-converting enzyme 2; MAAE = medically attended adverse event; MN50 = microneutralization 
assay with an inhibitory concentration of 50%; PCR = polymerase chain reaction; PIMMC = potential immune-mediated 
medical conditions; S = spike (protein); SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome 
coronavirus 2; WOCBP = women of childbearing potential. 
1. The Screening visit and Day 1 visit may be combined if feasible at any given study site. 
2. EOS assessments will be conducted via on-site visit. Should participants decide to terminate early, a telephone call may 
occur to collect the maximum safety data possible. 
3. 
Significant medical history should be recorded, including prior and ongoing medical conditions and significant surgical 
procedures. 
4. 
Specific exclusions to study vaccination will be assessed before any vaccination. Waivers to enrolling participants with 
exclusions will not be given. 
5. 
Recent (≤ 90 days) and current medications, including non-COVID-19 vaccines, should be recorded in the concomitant 
medication eCRF. All COVID-19 vaccines administered prior to screening should be recorded in the vaccine history eCRF. 
6. 
Performed prior to study vaccination. 
7. 
On vaccination day, 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 reactions. 
8. 
Recording of SAEs, MAAEs, and AESIs (including potential immune-mediated medical conditions [PIMMCs] and 
myocarditis or pericarditis). See Table 4 for symptoms of myocarditis or pericarditis and Section 8.2.3.6 for instructions for 
follow-up. 
9. 
EOS form will be completed for all participants, including participants who are terminated early. 

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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). 
Nearly two years later, SARS-CoV-2 transmission remains high, partly due to the emergence of 
multiple variant strains of the virus. The World Health Organization (WHO) situation report 
from 09 February 2022 identified 399,600,607 confirmed cases and 5,757,562 deaths globally 
(WHO 2022). 
The present study aims to compare the immunogenicity and safety of 3 lots of NVX-CoV2373 in 
adults. 
2.1.1 Description of NVX-CoV2373 
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 in adults 18 years of age and 
older. 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. The S protein from each virus is a type 1 trimeric GP that 
is produced as an inactive S0 precursor. The S-gene was codon-optimized for expression in 
Spodoptera frugiperda (Sf9) insect cells. 
All SARS-CoV-2 rS vaccines are adjuvanted with Matrix-M adjuvant. 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 (APCs), and 
enhanced antigen presentation via both major histocompatibility complex (MHC) I and MHC II 
molecules in the draining lymph nodes. 

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The investigational products used in this study are manufactured by Serum Institute of India (SII) 
through a partnership with Novavax. 
Additional product information including manufacturing details, supportive clinical and 
nonclinical study summaries can be found in the SARS-CoV-2 rS Investigator’s Brochure (IB) 
(Novavax 2021). 
2.1.2 Supportive Nonclinical Data 
Supportive nonclinical data are available through studies conducted using Novavax 
manufactured SARS-CoV-2 rS products. Pharmacological properties of the SII-produced 
vaccines used in this study are expected to be equivalent to those produced by Novavax. 
2.1.2.1 
Pharmacology 
2.1.2.1.1 
NVX-CoV2373 Nonclinical Overview 
Mouse immunogenicity studies were conducted to evaluate several SARS-CoV-2 S protein 
variants and select the vaccine candidate (Tian 2020). The selected vaccine candidate, BV2373 
(3Q-2P), was demonstrated to be immunogenic and elicited functional antibodies. For the tested 
constructs, shallow dose responses with Matrix-M adjuvant were observed, suggesting that the 
adjuvant may be significantly antigen-sparing in large animals and humans. 
The candidate SARS-CoV-2 rS vaccine, based on the BV2373 construct (NVX-CoV2373), has 
been evaluated in dose titration studies in hamsters, cynomolgus macaques, rhesus macaques, 
and baboons. In hamsters, two-dose regimens with 1 or 10 µg SARS-CoV-2 rS/15 µg Matrix-M 
adjuvant were highly immunogenic, resulting in high anti-S immunoglobulin G (IgG) titers and 
high hACE2 binding inhibition titers in a shallow dose-dependent manner, suggestive of dose- 
sparing. Of note, anti-S IgG levels and human angiotensin-converting enzyme (hACE2) binding 
inhibition titers were highly correlated. In cynomolgus macaques, two-dose regimens of 5 or 
25 µg SARS-CoV-2 rS/25 or 50 µg Matrix-M adjuvant were also highly immunogenic, resulting 
in high anti-S IgG levels, high hACE2 binding inhibition titers, and high neutralizing antibody 
responses. The 5 and 25 µg antigen doses gave generally similar responses when administered 
twice with 50 µg of Matrix-M adjuvant. 
In rhesus macaques, 5 or 25 µg doses of SARS-CoV-2 rS were administered with 50 µg of 
Matrix-M adjuvant in one-dose or two-dose regimens, the latter at a 21-day interval. All active 
regimens elicited anti-S IgG, hACE2 binding inhibition, and neutralizing antibody responses, but 
antibody titers were approximately 20-30-fold higher after completion of the two-dose regimens. 
Antigen dose had little impact on immunogenicity in either one- or two-dose regimens. 
Virus challenge studies were performed in mice, hamsters, and cynomolgus and rhesus 
macaques. In 2 mouse challenge models, immunization with 1 or 2 doses of SARS-CoV-2 rS/ 
Matrix-M adjuvant suppressed viral replication, reduced lung inflammation, and reduced 
systemic morbidity (weight loss) after SARS-CoV-2 live virus challenge and were not associated 
with any obvious exacerbation of the inflammatory response to the virus or worsening of clinical 
outcomes. The best responses were seen in animals receiving 2 doses of adjuvanted vaccine. 
Similar protection (weight loss and activity level) against live virus challenge was seen in 
hamsters, a SARS-CoV-2 permissive species due to the presence of an ACE2 receptor with close 

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homology to the human molecule. Protection has been demonstrated in hamsters challenged both 
by direct inoculation and also by cohabitation with unimmunized SARS-CoV-2-infected 
animals. 
2.1.2.1.2 
Baboon SARS-CoV-2 Recombinant Spike Protein Immunogenicity 
Study NVX 702-087 
In baboons, which may be more predictive of responses in humans, 5 and 25 µg SARS-CoV-2 
rS/50 µg Matrix-M adjuvant induced high levels of anti-S IgG, hACE2-binding inhibiting 
antibodies, and neutralizing antibodies. Matrix-M adjuvant provided antigen-sparing effects and 
supported induction of functional antibodies. Importantly, Matrix-M-adjuvanted SARS-CoV- 
2 rS also appeared to induce strong Th1 CD4+ T-cell responses to SARS-CoV-2 S protein that 
included polyfunctional effector phenotypes. Current data in this small baboon study confirms 
that doses of 5 µg and 25 µg with 50 µg Matrix-M adjuvant were the correct doses to test 
clinically, with Matrix-M adjuvant appearing critical for maximum responses. This finding was 
confirmed in a Phase 1 trial in humans (Keech 2020). 
2.1.2.1.3 
SARS-CoV-2 rS Challenge of Cynomolgus Macaques Immunized in Study 
NVX 702-094 
Cynomolgus macaques administered with human doses of 5 or 25 μg SARS-CoV-2 rS 
adjuvanted with 50 μg Matrix-M adjuvant had high and comparable levels of anti-S IgG titers 
and hACE2 receptor binding inhibition titers detected 21 days after the first immunization. All of 
the macaques immunized with any dose or regimen of SARS-CoV-2 rS/Matrix-M adjuvant were 
protected against live virus challenge, as evidenced by the reduction of total viral RNA and 
subgenomic RNA (sgRNA) to below the limit of quantitation in bronchoalveolar lavages (BALs) 
and nasal swabs. 
Combined nasal and intratracheal challenge of immunized rhesus macaques showed reduction of 
nasal wash total SARS-CoV-2 RNA in all immunized animals relative to placebo-treated 
macaques as early as Day 2 post-challenge, and clearance of total viral RNA to below detectable 
limits in 90% of two-dose animals by Day 7 or 8. In BAL fluid, similar reductions in total viral 
RNA were noted and all two-dose animals cleared viral RNA by Day 4 post-challenge, as did 
90% of single-dose animals by Day 7 or 8. Considering sgRNA, believed to be a better marker of 
active viral replication, a similar pattern was noted. Animals immunized with 2 doses of 
SARS-CoV-2 rS with Matrix-M adjuvant cleared sgRNA from their nasal wash by Day 4 and 
had no detectable sgRNA in BAL fluids at any time. sgRNA reductions were less in animals 
immunized with 1 dose only, but sgRNA load were still markedly less than in placebo animals. 
No challenged animal in any vaccine group, regardless of completeness of protection, had any 
Evidence of vaccine-enhanced disease. 
2.1.2.2 
Toxicology 
A Good Laboratory Practice (GLP)-compliant toxicity study in New Zealand White rabbits was 
performed to evaluate 50 µg of SARS-CoV-2 rS (BV2373 construct) with and without 50 µg 
Matrix-M adjuvant. Immunization of rabbits up to 4 times with full human doses of SARS- CoV- 
2 rS, with or without 50 µg Matrix-M adjuvant, was well tolerated and had no effects on 
mortality, cageside observations, body weight, food consumption, or physical examination 

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findings. There were no test article-related gross or histopathologic findings based on an 
examination of all body systems, including the myocardium and pericardium, aside from 
subacute inflammation at the injection sites, which was deemed a typical response to 
immunization. Findings from this study are considered relevant to the new vaccine constructs as 
the only significant changes are to the antigen and the rest of the vaccine constructs are produced 
using consistent manufacturing processes (MHRA 2021). 
A GLP-compliant developmental and reproductive toxicity (DART) 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 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. The clinical development program for Novavax’s SARS-CoV-2 rS 
with Matrix-M adjuvant comprises 4 ongoing clinical studies: a Phase ½ 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 subjects 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 
Study 2019nCoV-101 was the first clinical study initiated with SARS-CoV-2 rS nanoparticle 
vaccine. This 2-part, randomized, observer-blinded, placebo-controlled, Phase ½ trial now has 
final results for study Part 1 and through Day 217 for study Part 2. 
Study 2019nCoV-101 – Part 1 (Phase 1) was designed to evaluate the immunogenicity and safety 
of 5 and 25 µg SARSCoV-2 rS nanoparticle -vaccine with or without 50 µg Matrix-M adjuvant 
in 134 healthy participants ≥ 18 to ≤ 59 years of age. Results for the Phase 1 portion of the trial 
showed that SARS-CoV-2 rS with Matrix-M adjuvant was well tolerated and elicited robust 
immune responses. There were no serious adverse events (SAEs) or adverse events of special 
interest (AESIs) reported. Reactogenicity was mainly mild in severity and of short duration 
(mean ≤ 2 days), with second vaccinations inducing greater local and systemic reactogenicity. 
The adjuvant significantly enhanced immune responses (anti-S IgG, hACE2 receptor binding 

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inhibition antibody, and neutralizing antibody) and was antigen dose-sparing. The vaccine also 
induced antigen specific-T cells with a largely type 1 T helper (Th1) phenotype. An interim 
analysis performed at Day 35 using COVID-19 convalescent sera found the 2-dose 5 µg 
SARS-CoV-2 rS/Matrix-M adjuvant induced mean anti-S IgG and neutralizing antibody 
responses that exceeded the mean responses in convalescent sera from COVID-19 patients with 
clinically significant illnesses. 
Study 2019nCoV-101 – Part 2 (Phase 2) was designed to evaluate the immunogenicity, safety, 
and preliminary efficacy of 5 and 25 µg SARS-CoV-2 rS nanoparticle vaccine with 50 µg 
Matrix-M adjuvant in up to 1,500 healthy adults ≥ 18 to ≤ 84 years of age with more 
comorbidities than the participant population in Part 1 of the study. Study vaccinations 
comprised up to 3 intramuscular (IM) injections (Day 1 and Day 21 [priming doses] and Day 189 
[booster – active or placebo]). A subset of participants received a fourth injection at Day 357. A 
217-day safety and immunogenicity analysis was conducted on 1,283 participants. This analysis 
comprised 700 participants aged 18 to 59 years (the same age range of Part 1 of the study) and 
583 participants aged 60 to 84 years. Overall, local and systemic reactogenicity data from this 
analysis were consistent with the reactogenicity data in Part 1 of the study, with no safety 
concerns between the younger and older age cohorts. Both the 5 and 25 µg doses of 
SARS-CoV-2 rS with Matrix-M adjuvant were well tolerated with few participants (9; 0.7%) 
having SAEs. Regarding immunogenicity, robust responses were observed in both younger and 
older adults in the 2-dose 5 µg SARS-CoV-2 rS/Matrix-M adjuvant arm. While an attenuation of 
immune responses (approximately 2-fold lower SARS-CoV-2 wild-type neutralizing antibody 
activity in older participants) was observed when stratified by age group (18 to 59 years, 
inclusive and 60 to 84 years, inclusive), geometric mean fold increases in neutralizing antibodies 
were still increased > 95-fold compared to baseline. 
Study 2019nCoV-501 is a Phase 2a/b, 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 (NVX-CoV2373), administered 21 days apart on Days 0 and 21 as a 
coformulation, in 4,164 healthy HIV-negative participants 18 to 84 years of age and 
244 medically stable HIV-positive participants 18 to 64 years of age conducted in South Africa. 
Participants were randomized equally between vaccine and placebo for the initial vaccination 
period. Following the initial vaccination period, participants in the active treatment arm received 
one booster injection and one placebo injection 21 days apart, and the placebo group crossed 
over to receive active vaccine (2 injections 21 days apart). An analysis of the primary efficacy 
endpoint, which included both immunogenicity and safety data, was performed. A total of 
147 polymerase chain reaction (PCR)-confirmed symptomatic mild, moderate, or severe 
COVID-19 cases were accrued for the complete analysis of the primary efficacy endpoint, with 
51 (3.62%) cases for NVX-CoV2373 vs 96 (7.05%) cases for placebo. The resultant vaccine 
efficacy of NVX-CoV2373 in prevention of symptomatic mild, moderate, or severe COVID-19 
in adult participants, seronegative (to SARS-CoV-2) at baseline, was 48.6% (95% confidence 
interval [CI]: 28.4, 63.1), meeting the success criterion of a lower bound CI > 0. In HIV-negative 
and HIV-positive participants, the resultant vaccine efficacy was 55.4% (95% CI: 35.9, 68.9) and 
-35.4% (95% CI: -236.9, 45.6). Forty-one (93.2%) of 44 participants with a primary endpoint 
had whole genome sequence data available (samples from 3 cases in the placebo group could not 
be sequenced), and 38 (92.7%) of 41 were identified as the B.1.351 (Beta) variant, resulting in a 

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post-hoc vaccine efficacy of NVX-CoV2373 in prevention of symptomatic mild, moderate, or 
severe COVID-19 in all and HIV-negative adult participants, seronegative (to SARS-CoV-2) at 
baseline, of 43.0% (95% CI: -9.8, 70.4) and 51.0% (95% CI: -0.6, 76.1), respectively, for the 
B.1.351 (Beta) variant. NVX-CoV2373 induced robust immune responses (anti-S IgG and 
neutralizing antibody) in both HIV-negative and HIV-positive participants vs placebo. In 
baseline seronegative participants, immune responses were approximately 2-fold lower in 
HIV-positive participants vs HIV-negative participants. NVX-CoV2373 was well tolerated in 
both HIV-negative and HIV-positive participants, with similar frequencies of severe adverse 
events (AEs), SAEs, medically attended adverse events (MAAEs), and AESIs compared to 
placebo. Solicited local and systemic reactogenicity in all participants were higher for NVX- 
CoV2373 than placebo, but the majority of events were classified as grade 1. Pain and tenderness 
were the most frequently reported local AEs after each vaccination, with relatively short median 
durations (2.0 days for NVX-CoV2373 and 1.0 day for placebo). Headache, fatigue, and muscle 
pain were the most frequently reported systemic AEs after each vaccination, with relatively short 
median durations (2.0 days for NVX-CoV2373 and placebo). 
Study 2019nCoV-302 is 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 MatrixM- 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 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 
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), 
which were 1.3-fold (anti-S IgG) and 1.4-fold (neutralizing antibody) 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 SAEs, MAAEs, and 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 

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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 subjects 12 to < 18 years of 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. 
2.1.4 
Benefit:Risk Assessment 
Novavax has collected safety, efficacy, and immunogenicity data from approximately 
50,000 participants across 5 clinical trials, including 2 independent Phase 3 trials in the 
US/Mexico (Study 2019nCoV-301) and the UK (Study 2019nCoV-302). The data from these 
trials, along with supporting preclinical studies, indicate that the known and potential benefits of 
the vaccine outweigh its known and potential risks. 
Myocarditis or pericarditis has been reported following vaccination with NVX-CoV2373 in 
clinical trials, and it is possible that these reports represent vaccine-associated adverse events 
similar to those associated with 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 require 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. 
The CDC has published clinical considerations for myocarditis and pericarditis after receipt of 
mRNA COVID-19 vaccines among adolescents and young adults [CDC 2021] which makes 
specific recommendations for the management of such cases. A surveillance and management 
plan for suspected myocarditis and/or pericarditis cases based on CDC and AHA 
recommendations [CDC 2021, Law 2021, Gargano 2021] has been implemented in the clinical 
development plan of NVX-CoV2373. 
 
Study Rationale 
Novavax, Inc. has developed a recombinant vaccine adjuvanted with the saponin-based 
Matrix-M adjuvant for the prevention of disease caused by SARS-CoV-2 (NVX-CoV2373). 
Both nonclinical and clinical data to date support continued clinical development of SARS-CoV- 

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2 recombinant spike protein nanoparticle vaccines (SARS-CoV-2 rS) combined with Matrix-M 
adjuvant as potential vaccines against SARS-CoV-2. 
The purpose of this study is to compare the immunogenicity and safety of 3 different lots of 
NVX-CoV2373 in previously vaccinated adult participants 18 to 49 years of age, inclusive. Data 
from the study are intended to support the overall manufacturing data submitted as part of the 
Biological License Application in the United States and as part of other Regulatory submissions 
in other countries. 

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3 
OBJECTIVES AND ENDPOINTS 
The purpose of this study is to compare the immunogenicity and safety of 3 different lots of 
NVX-CoV2373 in previously vaccinated adult participants 18 to 49 years of age, inclusive. 
An overview of all study objectives and endpoints is provided in Table 2. 
Table 2 
Study 2019nCoV-307 Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
To demonstrate the equivalence of 
3 different vaccine lots based on 
IgG responses. 
IgG geometric mean ELISA unit 
(GMEU) concentrations (ie, 
GMEU/mL) to the SARS-CoV-2 
spike protein at Day 29 in each 
treatment arm; equivalence will be 
demonstrated if the 95% confidence 
intervals [CIs] of GMEU 
concentrations for all pairs of lots 
are within the pre-specified 
equivalence range of 0.67 to 1.5 
GMEU/mL. 
Secondary 
To characterize the IgG antibody 
responses to 3 different lots of 
NVX-CoV2373. 
Proportion of participants in each 
treatment arm who achieve 
seroconversion (≥ 4-fold increase 
from baseline) in IgG 
concentrations to the SARS-CoV-2 
spike protein at Day 29. 
To characterize the neutralizing 
antibody responses to 3 different 
lots of NVX-CoV2373. 
• 
MN50 geometric mean titers to 
the SARS-CoV-2 spike protein 
at Day 29 in each treatment 
arm. 
• 
Proportion of participants in 
each treatment arm who 
achieve seroconversion 
(≥ 4-fold increase from 
baseline) in MN50 titers to the 
SARS-CoV-2 spike protein at 
Day 29. 
To characterize antibody responses 
in a human angiotensin-converting 
enzyme 2 (hACE2) receptor 
binding inhibition assay to the 
SARS-CoV-2 spike protein in 
participants vaccinated with 
3 different lots of NVX-CoV2373. 
• hACE2 inhibition assay titers 
(geometric mean titer [GMTs]) 
at Day 29 in each treatment arm 
• Proportion of participants in 
each treatment arm who 
achieve seroconversion 
(≥ 4-fold increase from 
baseline) in hACE2 titers 
concentrations to the 
SARS-CoV-2 spike protein at 
Day 29. 

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Table 2 
Study 2019nCoV-307 Objectives and Endpoints 
 
Objectives 
Endpoints 
To compare the overall safety of 
3 different lots of NVX-CoV2373. 
• Incidence, duration, severity, 
and relationship of MAAEs and 
AESIs (including myocarditis 
and/or pericarditis) through 
Day 29 (ie, 28 days after 
vaccine dose). 
• 
Incidence and relationship of 
SAEs throughout the study. 
Exploratory 
To utilize additional assays (current 
or to be developed) to best 
characterize the immune response 
for future vaccine development 
needs. 
Additional endpoints to compare 
immune responses may be 
developed based on the assays used. 

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4 
STUDY PLAN 
4.1 
Study Schematic 
Figure 1 
Flow Diagram for 2019nCoV-307 
Participants 
 
N= 900 participants 
Randomized 1:1:1 
Screening 
Day -30 to 1 
Screening and Day 0 
procedures may be 
combined if feasible 
IM Injection 
Day 1 
Unscheduled 
Vac
S
c
t
i
u
n
d
a
y
t on 
Visit 
Up to 2 months (total duration 
Vaccine Dose 5 µg antigen + 50 µg 
Matrix-M adjuvant 
From 3 different lots 
EOS Visit 
Day 29 
Lot 1 NVX-CoV2373: n = 300 
Lot 2 NVX-CoV2373: n = 300 
Lot 3 NVX-CoV2373: n = 300 
Abbreviations: EOS = end of study 
 
4.2 
Study Design 
This is a randomized, Phase 3 study comparing the immunogenicity and safety of 3 different lots 
of NVX-CoV2373. The study will enroll approximately 900 previously vaccinated adults 18 to 
49 years of age, inclusive. 
Participants will be screened at baseline with the goal of enrolling approximately 900 previously 
vaccinated participants. Participants will be randomized 1:1:1 to receive 1 dose of the vaccine 
from 1 of 3 different lots, given on Day 1, at a dose level of 5 µg of antigen with 50 µg of 
Matrix-M adjuvant. 
All participants will remain on study for immunogenicity and safety data collection through 
28 days following the vaccination. 
4.3 
Design Rationale 
Novavax, Inc. has developed a recombinant vaccine adjuvanted with the saponin-based 
Matrix-M adjuvant for the prevention of disease caused by SARS-CoV-2 (NVX-CoV2373). 
The purpose of this study is to compare the consistency of immunogenicity and safety of the 
3 different lots of NVX-CoV2373 in previously vaccinated adult participants 18 to 49 years of 
age. Data from the study are intended to support the overall manufacturing consistency data 
submitted as part of regulatory submissions in the US and elsewhere, as needed. 

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5 
POPULATION 
5.1 
Recruitment 
Approximately 1200 potential participants will be screened in order to meet the goal of 900 
randomly assigned participants, who will be further divided into 3 groups of 300 participants 
each. 
5.2 
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 one or 
more eligibility criteria or who has withdrawn consent prior to treatment assignment. Screen 
failures may not be rescreened. 
An enrolled participant is one who has been deemed eligible and has been assigned to a 
treatment group. 
5.3 
Inclusion Criteria 
To be included in this study, each individual must satisfy all of the following criteria: 
1. Adults 18 to 49 years of age, inclusive, at screening. 
2. Willing and able to give informed consent 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 at least 12 consecutive 
months]) must agree to be heterosexually inactive from at least 28 days prior to enrollment 
and through the end of study (EOS) visit OR agree to consistently use a medically acceptable 
method of contraception from at least 28 days prior to enrollment and through the EOS visit. 
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 
study vaccination. 
5. Agree 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. 
6. Documented receipt of either 2 or 3 doses of the investigational Novavax vaccine with 
Matrix-M adjuvant (NVX-CoV2373); OR documented receipt of a full course of an FDA- 
authorized/approved COVID-19 vaccine with or without a booster vaccine injection after 
primary series; OR documented receipt of a full course of heterologous COVID-19 vaccines 
mentioned above. The most recent dose must have been administered at least 6 months prior 
to study vaccination. 

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5.4 
Exclusion Criteria 
Participants meeting any of the following criteria will be excluded from the study. 
1. History of laboratory-confirmed (by polymerase chain reaction [PCR] or rapid antigen test) 
COVID-19 infection ≤ 4 months prior to randomization. 
2. Current participation in research involving receipt of an investigational product 
(drug/biologic/device). 
3. Any known allergies or history of anaphylaxis to the active substance or any of the other 
ingredients contained in the investigational product. 
4. Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) or 
therapy that causes clinically significant immunosuppression. 
5. Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccine 
which may be received > 4 days prior to study vaccine, or rabies vaccine which may be 
received at any time if medically indicated. 
6. 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. 
7. Active cancer (malignancy) on chemotherapy that is judged to cause significant 
immunocompromise within 1 year prior to first study vaccination (with the exception of 
malignancy cured via excision, at the discretion of the investigator). 
8. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the 
EOS visit. 
9. Suspected or known history of alcohol abuse or drug addiction within 3 months prior to the 
study vaccine dose that, in the opinion of the investigator, might interfere with protocol 
compliance. 
10. 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 trial vaccine or interpretation 
of study results (including neurologic or psychiatric conditions likely to impair the quality of 
safety reporting). 
11. 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). 
12. Participants with a history of myocarditis or pericarditis. 

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6 
STUDY CONDUCT 
This is a Phase 3, randomized, study comparing the immunogenicity and safety of different lots 
of NVX-CoV2373. In this study, approximately 900 previously vaccinated adults 18 to 49 years 
of age will receive 1 dose of NVX-CoV2373 from 3 different lots, given on Day 1. 
Following vaccination, all participants will remain on study for immunogenicity and safety data 
collection through Day 29 (EoS). Scheduled study visits will occur for Screening, Day 1, and 
Day 29. 
6.1 
Study Procedures by Visit 
6.1.1 Screening Period 
The following activities will occur at the Screening Visit. The Screening Visit can be and is 
expected to be combined with the Day 1 Visit. 
• 
Informed consent 
• 
Medical history, including prior and concurrent medical conditions and significant 
surgical procedures. 
• 
Inclusion and exclusion criteria 
• 
Demographics including age, sex, race, and ethnicity. 
• 
Prior and concomitant medications, including recent (≤ 90 days) and current 
medications and vaccinations, are to be reviewed to ensure eligibility criteria are 
fulfilled. Concomitant medications include prescription and OTC (including 
vaccines) medications taken by the participant during the study. Do not record 
herbals, vitamins, and supplements. 
• 
Vital sign measurements including respiratory rate, blood pressure, pulse rate, and 
temperature (oral or via forehead/ear reader). Urine pregnancy test in women of 
childbearing potential. A positive test will result in screen failure. 
• 
Physical examination at screening to include height and weight, head nose ears and 
throat (HEENT), neck, lungs, heart, cardiovascular, abdomen, and musculoskeletal 
system/extremities to allow for study vaccination. 
• 
Recording of SAEs. 
6.1.2 Vaccine Administration Period (Day 1) 
The following activities will occur at the Day 1 visit. 
• 
Inclusion and exclusion criteria 
• 
Prior/concomitant medications 
• 
Vital sign measurements, including respiratory rate, blood pressure, pulse rate, and 
temperature (oral or via forehead/ear reader). Temperature will be taken prior to 
vaccination to ensure participant has no evidence of fever. 
• 
Urine pregnancy test in women of childbearing potential. A positive test will result in 
disqualification. 
• 
Baseline ECG 
• 
Physical examination – symptom directed (targeted) if Screening and Day 1 are not 
combined into a single visit 

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• 
Nasal swab at clinic for SARS-CoV-2 (PCR)—anterior nares 
• 
Blood sampling for SARS-CoV-2 (ELISA for anti-S protein serology, MN50 assay, 
and hACE2 receptor-binding inhibition assay) 
• 
Randomization 
• 
Vaccination 
• 
Recording of SAEs, MAAEs, and AESIs (including potential immune-mediated 
medical conditions [PIMMCs] and myocarditis or pericarditis). See Table 4 for 
symptoms of myocarditis or pericarditis and Section 8.2.3.6 for instructions for 
follow-up. 
• 
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 
reactions. 
6.1.3 Unscheduled Visit 
An Unscheduled Visit may be conducted by study personnel for safety follow-up for any 
participant experiencing a general medical issue while on study. During this visit, the following 
procedures will be performed: 
• 
Prior/concomitant medications 
• Vital sign measurements including respiratory rate, blood pressure, pulse rate, and 
temperature (oral or via forehead/ear reader). 
• 
Physical examination – symptom directed (targeted) 
• 
Recording of SAEs, MAAEs, and AESIs (including PIMMCs, myocarditis or 
pericarditis). See Table 4 for symptoms of myocarditis or pericarditis and Section 
8.2.3.6 for instructions for follow-up. 
NOTE: 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. 
6.1.4 EOS (Day 29) 
The following activities will be performed at the EOS Visit. EOS assessments will be conducted 
via an on-site visit. 
• Prior/concomitant medications 
• Vital sign measurements including respiratory rate, blood pressure, pulse rate, and 
temperature (oral or via forehead/ear reader). 
• Physical examination – symptom directed (targeted) 
• Blood sampling for SARS-CoV-2 (ELISA for anti-S protein serology, MN50 assay, 
and hACE2 receptor-binding inhibition assay) 
• Recording of SAEs, MAAEs, and AESIs (including PIMMCs, myocarditis or 
pericarditis). See Table 4 for symptoms of myocarditis or pericarditis and Section 
8.2.3.6 for instructions for follow-up. 

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6.2 
Discontinuation or Withdrawal 
6.2.1 Withdrawal from Study 
Participants are free to withdraw from the study at any time upon request. Participant 
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 but are encouraged to remain in the study for safety 
follow-up. In such cases, where only safety is being evaluated, participant contact may be 
managed via telemedicine contact (eg, telephone, web chat, video, FaceTime). 
6.2.1.1 
Replacement of Participants 
Participants who withdraw, are withdrawn or terminated from this study, or are lost to follow up 
after signing the informed consent form (ICF) but prior to study vaccination may be replaced. 
Participants who receive study vaccine and subsequently withdraw, discontinue, are terminated 
from the study, or are lost to follow-up will not be replaced. 
6.2.1.2 
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. 
The status of participants who fail to complete final assessments will be documented in the 
electronic case report form (eCRF). Data that would have been collected at subsequent visits will 
be considered missing. 
6.3 
Study Termination by Sponsor 
Although the Sponsor has every intention of completing the study, it reserves 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). 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 (CSR). 

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7 
STUDY INTERVENTIONS 
Study vaccinations will comprise 1 IM injection of NVX-CoV2373 of 0.5 mL injection volume 
at a dose of 5 µg antigen (Table 3). 
Table 3 
Study Vaccinations 
 
Vaccine 
Age (years) 
Baseline 
Serostatus 
Number of 
doses 
Number of 
participants 
Dose (antigen/ 
Matrix-M 
adjuvant) 
Lot 1 
(Group 1) 
18 to 49 
Previously 
vaccinated 
1 
300 
5 µg / 50 µg 
Lot 2 
(Group 2) 
18 to 49 
Previously 
vaccinated 
1 
300 
5 µg / 50 µg 
Lot 3 
(Group 3) 
18 to 49 
Previously 
vaccinated 
1 
300 
5 µg / 50 µg 
 
7.1 
Description of Products 
7.1.1 NVX-CoV2373 
7.1.1.1 
Formulation, Storage, Preparation, and Handling 
NVX-CoV2373 Prototype SARS-CoV-2 rS vaccine will be supplied as a solution for preparation 
for injection of SARS-CoV-2 rS at a concentration of 10 μg/mL and Matrix-M adjuvant at a 
concentration of 100 μg/mL. 
NVX-CoV2373 should be stored at 2 to 8°C in a secured location. DO NOT FREEZE. The study 
site will maintain a temperature log to establish a record of compliance with storage conditions. 
Further details on the trial vaccine can be found in the SARS-CoV-2 rS IB and a description of 
its preparation can be found in the Pharmacy Manual. 
7.1.1.2 
Packaging and Labeling 
The Sponsor will provide adequate quantities and appropriate labelling of SARS-CoV-2 rS with 
Matrix-M adjuvant and Syneos Health will ensure distribution to the study sites from a 
designated depot. The clinical unit pharmacy or equivalent will prepare the clinical trial 
materials. Detailed instructions for the handling of trial vaccine vials will be provided in a 
separate Pharmacy Manual. 
7.1.1.3 
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 the vaccine should be administered according to standard practice by 
qualified study site personnel in a way to maintain overall blinding, as described in the Pharmacy 
Manual. 

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All participants will be administered 1 single IM injection of NVX-CoV2373 of 0.5 mL injection 
volume on Day 1. 
7.1.1.3.1 
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 4), pending review of cases by the Central Cardiac 
Adjudication Committee that will report the results of their adjudication to the Sponsor to 
recommend whether enrollment may be resumed. 
7.1.2 Treatment Assignment and Bias Minimization 
7.1.2.1 
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 code with true 
treatment allocations will be held by Syneos Health during the study. Another randomization list 
(containing treatment) will be provided to clinical supplies. 
7.1.2.2 
Assessment and Verification of Compliance 
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), if the full dose was administered, 
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. 
7.1.2.3 
Blinding 
This is an observer-blinded study. To maintain the blind, unblinded study site personnel will 
manage vaccine logistics, preparation, and 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 trial vaccine. 
Within each study site, participants will be assigned to study treatment according to a list 
produced by Syneos Health. Prior to production, the randomization specification will be 
reviewed and agreed by the study team. 
An IWRS will be responsible for the allocation of randomization numbers to individual 
participants. Randomization will take place at baseline after confirmation that the participant 
meets the inclusion/exclusion criteria. A copy of the randomization code with true treatment 
allocations will be held by Syneos Health during the study. Another randomization list 
(containing treatment) will be provided to clinical supplies. 

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7.2 
Prior and Concomitant Therapies 
Administration of medications, therapies, or vaccines will be recorded in the concomitant 
medication 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 from the time of signing the ICF 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 all COVID-19 vaccines prior to screening should be recorded in the Vaccine History 
eCRF. Site staff will record the date(s) and brand of the SARS-CoV-2 vaccine received. 
7.2.1 Prohibited Therapies 
The following therapies are prohibited within the specified timeframes of study conduct: 
• 
Seasonal influenza vaccine may not be administered < 4 days before or < 7 days after 
the study vaccine. 
• 
No other vaccine except rabies vaccine (if medically indicated) ≤ 90 days before 
randomization until EOS. 
• 
No investigational product (drug/biologic/device) from time of randomization until 
after the last study visit. 
• 
No immunoglobulins, monoclonal antibodies, blood products, or any therapy that 
causes clinically significant immunosuppression within 90 days of study vaccination 
until the EOS visit. Similarly, rabies immune globulin should be administered if 
medically indicated. 

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8 
SAFETY ASSESSMENTS 
The timing and frequency of all safety assessments are listed in the SOE (Table 1). Recording of 
unsolicited AEs will be conducted by electronic data capture (EDC). AESIs, including PIMMCs, 
myocarditis or pericarditis and AESIs specific to complications of potential disease enhancement 
for COVID-19 or those of specific interest potentially related to COVID-19 vaccines will also be 
monitored and are to be reported according to timelines specified for SAEs (see APPENDIX 2 
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 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 exam, vital 
signs measurements) that are clinically significant in the medical and scientific 
judgment of the Investigator 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 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 an elective treatment of a pre-existing 
condition that did not worsen from baseline is not considered an SAE. 
− 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 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 or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 

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• Causality or relatedness – For each AE/SAE, the Investigator must document in the 
medical notes that he/she has reviewed the AE/SAE and has 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 – An AR is any AE caused by the investigational product. 
• Suspected adverse reaction (SAR) – An SAR is any AE for which there is a 
reasonable possibility that the investigational product 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 drug 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. 
• 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. 
− Life-threatening: These events require an ER visit or hospitalization. 
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. 
8.2 
Documenting Adverse Events 
Reactogenicity reactions will be collected if they meet the criteria for a MAAE, SAE, or AESI. 

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At every study visit following Screening, participants will be asked a standard question to elicit 
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). 
Care will be taken not to introduce bias when detecting 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 disorders listed in 
APPENDIX 2. 
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. 
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. 
8.2.1.1 
Assessment of Causality 
There may be situations in which an SAE occurs 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. 
• 
Re-challenge following second vaccination, if applicable. 
• 
Medical history. 
• 
Study treatment. 
• 
Mechanism of action of study vaccine. 
• 
Class effect (adjuvanted protein vaccines). 
• 
Concomitant treatments in use. 
• 
Withdrawal of study treatment. 
• 
Lack of efficacy/worsening of existing condition. 
• 
Possible vaccine enhancement of COVID-19. 

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8.2.2 Time Frame for Collection 
AEs reported or observed during the study will be recorded on the AE page of the eCRF. 
Medical occurrences that begin prior to administration of the study vaccine will be recorded on 
the Medical History/Current Medical Conditions section of the eCRF not the AE section. 
All AESIs and MAAEs 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, MAAEs, SAEs, cases of multisystem inflammatory syndrome, 
and hospitalized or fatal cases of COVID-19 following vaccination must be reported based on 
local regulatory reporting guidance for safety events. 
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, he/she should promptly notify the Sponsor. 
8.2.3 Classification of Events 
8.2.3.1 
Treatment-Emergent Adverse Event 
Treatment-emergent adverse events are defined as any AE occurring or worsening on or after the 
dose of study vaccine. 
8.2.3.2 
Adverse Events of Special Interest 
Participants will be assessed for diagnosis of an AESI at all study visits. AESIs include 
PIMMCs, myocarditis or pericarditis, AEs specific to COVID-19, or other potential AEs that 
may be determined at any time by regulatory authorities as additional information concerning 
COVID-19 is obtained. Listings of AESIs are presented in Appendix 2. 
8.2.3.2.1 
Myocarditis and/or Pericarditis (CDC Definition) 
Participants reporting signs or symptoms of myocarditis or pericarditis (fatigue, acute chest pain, 
shortness of breath, etc.[see Table 4]) within 4 weeks after vaccination should be evaluated as 
soon as possible by a physician who should initiate a 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 5). A Central 
Cardiac Adjudication Committee has been established to adjudicate probable 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 relevant eCRF pages. 
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 4 
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. 
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. 
3. 
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. 
4. 
Using either the original or the revised Lake Louise criteria [Ferreira 2018]. 
5. 
Based on the 2015 ESC Guidelines for the diagnosis and management of pericardial diseases [Adler 2015]. 
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. 

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Table 5 
Management of Suspected 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. 
 
 
8.2.3.2.2 
Electrocardiograms 
All participants will undergo a baseline ECG at Day 1 prior to study vaccine administration. 
Baseline ECGs will be read and interpreted by a Central Cardiac Adjudication Committee only 
as a comparison with new ECG(s) in the event that the participant experiences a cardiac event 
during the 28 days following vaccine administration that requires review by the Cardiac 
Adjudication Committee. 
8.2.3.3 
Medically Attended Adverse Events 
MAAEs are defined as AEs with medically attended visits, including hospital, emergency room, 
urgent care clinic, or other visits to or from medical personnel for any reason. Routine study 
visits will not be considered. MAAEs will be reported from the time of study vaccination until 
Day 29. 
8.2.3.4 
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 a clinical study pregnancy form. To 
ensure participant safety, each pregnancy must be reported to Syneos Health within 24 hours of 
learning of its occurrence. Each pregnancy must be followed up to determine outcome (including 

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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 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 Syneos Health using the pregnancy reporting forms 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: 
 
8.2.3.5 
Overdose or Misuse 
A drug overdose is defined as the accidental or intentional use of a drug or medicine or an 
administration error in an amount that is higher than is normally used. Every overdose must be 
reported to the CRO 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 eCRF AE page. Only overdoses associated with a clinical SAE 
needs to be reported as an SAE. The quantity and duration of 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 7.1.1.3). 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. 
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 the appropriate CRO 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 AESIs related to COVID-19 are to be reported within these timelines. 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 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. 

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If a non-serious AE becomes serious, this and other relevant follow-up information must also be 
provided to the CRO 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 AESIs will also be recorded in the eCRF. The investigator is responsible for 
informing the Institutional Review Board (IRB) of the SAE as per local requirements. 
Notification should be made within 24 hours using the dedicated fax line or email for the Syneos 
Health pharmacovigilance group: 
Syneos Health Safety and Pharmacovigilance fax number:
 
Syneos Health Safety and Pharmacovigilance email address: 
 
The report form should be attached to the email or fax; 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. 
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. 
8.3.1.1 
Safety Reporting to Sponsor 
Syneos Health will forward the SAE/AESI and pregnancy reports to the Sponsor’s safety 
representative(s) within 1 business day or 3 calendar days (whichever is earlier) of becoming 
aware of it. 
8.3.1.2 
Safety Reporting to Health Authorities, Independent Ethics Committees/ 
Institutional Review Boards, and Investigators 
Syneos Health will notify the Sponsor of any SAE and will perform follow-up activities with the 
concerned study site. Syneos Health will retain responsibility of expedited and periodic reporting 
according to national requirements. Procedure and timelines for safety reporting are provided in 
the Safety Management Plan as agreed by Syneos Health and the Sponsor. The Investigator must 
comply with any applicable study site-specific requirements related to the reporting of SAEs 
(particularly deaths and Suspected Unexpected Serious Adverse Reaction [SUSARs]) to the IRB 
that approved the study. Investigators should provide written documentation of IRB notification 
for each report to the CRO. In accordance with ICH GCP, Syneos Health will inform the 
investigators of findings that could adversely affect the safety of participant, impact the conduct 
of the study, or alter the IRB’s approval/favorable opinion to continue the study, as assessed by 
the Sponsor. In particular and in line with respective regulations, the CRO will inform the 
investigators of SUSARs. The investigator should place copies of Safety Reports in the 

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Investigator Site File. National regulations with respect to Safety Report notifications to 
investigators will be taken into account. When specifically required by regulations and 
guidelines, the CRO will provide appropriate Safety Reports directly to the concerned lead IRB 
and will maintain records of these notifications. When direct reporting is not clearly defined by 
national or study site-specific regulations, the investigator will be responsible for promptly 
notifying the concerned IRB of any Safety Reports provided by the CRO and of filing copies of 
all related correspondence in the Investigator Site File. 
8.3.1.3 
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 questions an on-call physician can be 
reached 24 hours 7 days a week (24/7): 
• 
Telephone: 
 

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9 
ANALYSIS 
This section includes a description of the statistical strategy and considerations for the study. 
Further detailed specifications for the analysis of data from the study will be presented in a 
Statistical Analysis Plan. 
9.1 
Sample Size Rationale 
The sample size and power are driven by the primary endpoint (ie, lot consistency in terms of 
immunogenicity measured by IgG response at Day 29). Based on IgG data from Novavax’s 
study 2019nCoV-101 Part 2, previously vaccinated participants in the 18-49-year-old age group 
who received the SARS-CoV-2 rS vaccine, exhibited an 80% confidence upper bound of Day 29 
IgG SD in log10 scale of 0.39. The immunogenic performance of the released lots should be 
approximately the same, ie, the lot-to-lot GMEU ratio should approximate 1.0. Under any 
manufacturing practices, between-lot variation exists and is considered normal. Assuming 10% 
variation (lot-to-lot GMEU ratio is 1.1), an evaluable sample size of 248 subjects for each lot in 
the per-protocol population will be required to achieve 97% power to demonstrate the lot-to-lot 
equivalence and provide the overall power of ~90% for all three lot-to-lot equivalence tests 
(Lot 1 vs. Lot 2, Lot 1 vs. Lot 3, and Lot 2 vs. Lot 3). Accounting for a ~5% dropout rate, a total 
enrollment sample size of 300 participants will provide 262 participants per lot. 
The statistical success criterion for demonstrating the equivalence of each lot (Lot 1, Lot 2, and 
Lot 3) is based on the IgG response at Day 29. Equivalence will be demonstrated if the 95% CIs 
of GMEUs for all pairs of lots are within the pre-specified equivalence range of 0.67 to 1.5. 
9.2 
Analysis Sets 
The following analysis sets are identified for analysis. 
9.2.1 Randomized Participants Analysis Set 
The Randomized Participants Analysis Set will include all participants who are 
randomized/enrolled, regardless of whether they actually received any study vaccine. The 
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 a dose of study vaccine, regardless of protocol violations or missing data. Participants in 
the FAS will be analyzed according to the vaccine group as randomized. Immunogenicity 
summaries and associated statistical analyses will be based primarily on the PP Analysis Set and 
may also be analyzed in the FAS. 
9.2.3 Safety Analysis Set 
The Safety Analysis Set will include all participants who provide consent, are 
randomized/enrolled, and receive 1 dose of study vaccine. Participants in the Safety Analysis Set 
will be analyzed as actually treated. The Safety Analysis set will be used for all safety analyses. 

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9.2.4 Per-Protocol Analysis Set 
The PP Analysis Set will include all participants who receive the study vaccine according to the 
protocol, have serology results for Day 1 and Day 29 available after the vaccination, and have no 
major protocol violations that are considered clinically relevant to impact immunogenicity 
response as determined by Novavax prior to database lock. 
The analysis of the primary endpoint will be performed using the PP Analysis Set. 
Within the PP Analysis Set there are 3 subsets defined: Anti-S Protein IgG Serology Subset, 
Neutralization Assay Subset, and the hACE2 Receptor-binding Inhibition Assay Subset. 
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 prior to study vaccination will be included in this subset. 
9.2.4.2 
Neutralization Assay Subset 
All participants in the PP Analysis Set who are tested for neutralization prior to study 
vaccination 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 ACE2 receptor-binding inhibition prior 
to study vaccination will be included in this subset. 
9.3 
Statistical Analyses 
9.3.1 Background Analyses 
9.3.1.1 
Disposition and Protocol Compliance 
The number of participants consented, randomized/enrolled, and vaccinated will be presented by 
the study vaccine group for the Randomized Participants Analysis Set. 
The number (percentage) of participants in the Randomized Participants Analysis Set, FAS, 
Safety Analysis Set, and PP Analysis Set who have completed the study (from Day 1 through 
Day 29) will be summarized overall and by the study vaccine group. 
The number (percentage) of participants in the Safety Analysis Set who discontinue the study 
prior to EOS and the reason for discontinuation (eg, AE, investigator decision, lost to follow-up, 
non-compliance) will be presented overall and by the study vaccine group. A listing of all 
participants discontinued from the study will be presented, including the reason for 
discontinuation and day of last study contact. Day of last study contact will be calculated as 
follows: date of study discontinuation minus date of Day 1 vaccination +1. A listing of all 
screened participants who failed the inclusion/exclusion criteria will also be provided. 
The number (percentage) of participants in the Safety Analysis Set with major protocol 
deviations recorded throughout the study will be summarized by study vaccine group and 
protocol deviation category (Section 11.1.3). A listing of all participants with one or more major 
protocol deviations will also be provided and will include study vaccine group, study day 

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associated with the deviation relative to Day 1, protocol deviation category, and a description of 
the deviation as recorded by the site. 
9.3.1.2 
Demographics and Baseline Characteristics 
Baseline demographic and background characteristics (eg, age, sex, ethnicity, race, height, 
weight, body mass index [BMI, derived], and ECG) will be summarized overall and by the study 
vaccine group for the FAS, Safety Analysis Set, and PP Analysis Set. 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 Medical Dictionary for Regulatory Activities (MedDRA) 
terms. Baseline medical history recorded at Screening will be summarized by the study vaccine 
group and by MedDRA System Organ Class/Preferred Term (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. 
Participants will also be summarized by the study vaccine group and the name of previous 
COVID-19 vaccination. In addition, the time between first dose of previous COVID-19 
vaccination and Day 1 vaccination dose may be summarized by the study vaccine group using 
descriptive statistics. 
9.3.2 Immunogenicity Analyses 
The immunogenicity analysis will be performed using the PP Analysis Set. 
For the primary endpoint of IgG (GMEU/mL) to the SARS-CoV-2 spike protein in previously 
vaccinated participants 18 to 49 years of age, IgG GMEU, geometric mean fold rise 
(GMFRPost/Pre), and SCR will be summarized overall and by study vaccine group. 
IgG GMEU is calculated as the antilog of the mean of the log-transformed IgG GMEU at Days 1 
and 29. GMFRPost/Pre is calculated as the ratio of post-vaccination IgG GMEU at Day 29 to 
pre-vaccination IgG GMEU at the baseline (Day 1). 
Between-group ratio of IgG GMEUs (GMEUR) at Day 29 and the two-sided 95% CIs will be 
computed using analysis of covariance (ANCOVA), with the study vaccine group as the fixed 
effect and the ELISA unit at Day 1 (adjusted for intergroup variation in baseline 
[pre‑vaccination] ELISA unit) as the covariate under two-sided type I error rate of 0.05. No type 
I error rate adjustments will be made. The mean difference of all lots paired comparisons with 
their corresponding CI limits will then be exponentiated to obtain IgG GMEUR and the 
corresponding 95% CIs. 
As the 1st secondary endpoint of IgG GMEUs (EU/mL) to the SARS-CoV-2 spike protein, SCR 
(proportion of participants who achieve seroconversion ≥ 4-fold increase from baseline) in IgG 
GMEUs at Day 29 with corresponding two-sided exact binomial 95% CIs will be calculated 
using the Clopper-Pearson method. Two-sided 95% CIs of the difference in SCRs in IgG GMEU 
concentrations for all lots paired comparisons will be based on the Miettinen and Nurminen 
method. 

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For the 2nd secondary endpoints of neutralizing antibody response to 3 different lots of NVX- 
CoV2373 in previously vaccinated participants 18 to 49 years of age, MN50 GMT, GMFRPost/Pre, 
and SCR will be summarized overall and by the study vaccine group. 
MN50 GMT is calculated as the antilog of the mean of the log-transformed MN50 titers at Days 1 
and 29. GMFR is calculated as the ratio of post-vaccination MN50 GMTs at Day 29 to 
pre-vaccination MN50 GMTs at the baseline (Day 1). 
Between-group ratio of MN50 GMTs (GMTR) at Day 29 and the two-sided 95% CIs will be 
computed using ANCOVA, with the study vaccine group as the fixed effect and the titer at Day 1 
(adjusted for intergroup variation in baseline [pre‑vaccination] titers) as the covariate under 
two-sided type I error rate of 0.05. No type I error rate adjustments will be made. The mean 
difference of all lots paired comparisons and comparisons of combined 3 lots with each lot with 
their corresponding CI limits will then be exponentiated to obtain MN50 GMTRs and the 
corresponding 95% CIs. 
SCR (proportion of participants who achieve seroconversion ≥ 4-fold increase from baseline) in 
MN50 titers at Day 29 with corresponding 2-sided exact binomial 95% CIs will be calculated 
using the Clopper-Pearson method. Two-sided 95% CIs of the difference in SCRs in MN50 titers 
for all lots paired comparisons and comparisons of combined 3 lots with each lot will be based 
on the Miettinen and Nurminen method. 
For the 3rd secondary endpoints of antibody responses in a hACE2 receptor-binding inhibition 
assay, hACE2 GMTs, GMFRPost/Pre, and SCR will be summarized overall and by the study 
vaccine group (Lot 1, Lot 2, and Lot 3), and between-group hACE2 GMTR and difference in 
SCRs in hACE2 titers will be calculated using the same statistical methods applied for MN50 
titers. 
The same statistical methods applied for the analysis of MN50, IgG, and hACE2 may also be 
applied to characterize the immune response for future vaccine development needs as the 
exploratory endpoints. 
9.3.3 Safety Analyses 
The secondary endpoint, safety data include MAAEs and AESIs (predefined list) through Day 29 
(ie, 28 days after vaccine dose) and SAEs throughout the study. All safety analyses will be 
descriptive and conducted using the Safety Analysis Set. 
Unsolicited MAAEs through Day 29 including AESIs (predefined list), and SAEs throughout the 
study will be summarized overall and by the study vaccine group and by SOC and PT using 
MedDRA terms, as well as by severity and relationship to the study vaccine to present the 
number and percentage with its corresponding exact 95% CIs using Clopper-Pearson method. 
For multiple occurrences of an AE in the same participant, a participant will be counted only 
once within an SOC or a PT, using the most severe occurrence and closest reported relationship 
for the summarization by severity or relationship to the study vaccine, respectively. The duration 
of MAAEs and AESIs through Day 29 will also be summarized. 
A by-participant listing of MAAEs and AESIs through Day 29 and SAEs throughout the study 
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9.3.3.1 
-Prior and Concomitant Medications and Vaccinations 
Prior and concomitant medications and vaccinations will be summarized overall and by study 
vaccine group and preferred drug name as coded using the WHO drug dictionary for all 
participants in the Safety Analysis Set. Multiple occurrences of medication usage for a 
participant will be counted only once within an anatomical therapeutic chemical (ATC) term and 
standardized medication name. A by-participant listing of treatment-emergent concomitant 
medications (including vaccines) will be presented. 
9.3.3.2 
Vital Sign Measurements 
Vital sign measurements including temperature, respiratory rate, blood pressure, and pulse rate 
will be summarized as continuous variables. Descriptive statistics for vital signs will be 
presented by study vaccine group for all participants in the Safety Analysis Set, including means 
and SDs, median, minimum, and maximum. A by-participant listing of vital signs will be 
provided. 
9.3.3.3 
Physical Examinations 
Physical examination at screening will include height and weight, HEENT, neck, lungs, heart, 
cardiovascular, abdomen, and musculoskeletal system/extremities to allow for study vaccination. 
Symptom-directed (targeted) physical examination will be performed at all other scheduled time 
points. Abnormal results will also be summarized as clinically significant or not clinically 
significant. 
9.4 
Interim Analyses 
No interim analysis is planned. 
9.5 
Final Analysis 
The final analysis will be performed when the complete data for IgG GMEUs, MN50 titers, 
hACE2 titers, and safety data throughout the study (from Day 1 through Day 29) are available. 

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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 
HREC/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 
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 permission for the storage of serum samples for future research purposes. 
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. 

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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: 
1. 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. 
2. 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 Health 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 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. The monitor will be blinded to study vaccine assignment. A separate unblinded study 
monitor will be responsible for drug accountability. 
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 SOPs. 
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. 

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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, if 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 paper diary created for the study. These data collection tools are a validated 
EDC system that contains a system generated audit trail. Data required according to this protocol 
are recorded by study site personnel via data entry into the internet-based EDC software system 
or by study participant via the paper diary. 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 Syneos Health 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, and complete medical history and physical examination reports. 

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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. 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study vaccine or per local regulation, whichever is 
longer. These documents should be retained for a longer period, however, if required by 
applicable regulatory requirements or by an agreement with the Sponsor. 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 
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. 

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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 Syneos Health 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 Syneos Health nor 
the study site is financially responsible for further treatment of the disease under study. 

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14 
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