A Double-Blind, Randomized, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of VIR-2482 for the Prevention of Illness Due to Influenza A
Phase: PHASE2
Conditions: Influenza A
Sponsor: Vir Biotechnology, Inc.

AMENDMENT 4 CLINICAL STUDY PROTOCOL 
Study Title 
A Double-Blind, Randomized, Placebo-Controlled Phase 2 Study to 
Evaluate the Efficacy and Safety of VIR-2482 for the Prevention of 
Illness Due to Influenza A  
Brief Title 
A Phase 2 Study to Evaluate the Efficacy and Safety of VIR-2482 for 
the Prevention of Illness Due to Influenza A 
Study Number 
VIR-2482-4002 
Compound 
VIR-2482 
Indication 
Prevention of Illness due to Influenza A 
Study Phase 
2 
Study Sponsor 
Vir Biotechnology, Inc. 
499 Illinois Street, Suite 500 
San Francisco, CA 94158, USA 
Regulatory 
Agency 
Identifying 
Numbers 
IND: 141155 
EudraCT: TBD 
NCT:NCT05567783 
Protocol Date 
29 June 2023, Version 1.0 
This study will be conducted in compliance with International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP), including the archiving of essential documents 
CONFIDENTIALITY STATEMENT  
This document contains confidential information that is the property of Vir Biotechnology, Inc. This confidential 
information is being provided to you, your staff, the applicable Institutional Review Board/Independent Ethics 
Committee, and applicable regulatory authorities solely for the purpose of evaluating or conducting this clinical 
study. This confidential information will be protected by you and your staff against disclosure to or use by third 
parties, except as necessary for the evaluation or conduct of the study. 

VIR-2482 
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INVESTIGATOR SIGNATURE PAGE  
 
VIR BIOTECHNOLOGY, INC 
499 ILLINOIS STREET SUITE 500 
SAN FRANCISCO, CA 94158 
 
STUDY ACKNOWLEDGMENT 
 
A Double-Blind, Randomized, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy 
and Safety of VIR-2482 for the Prevention of Illness Due to Influenza A  
 
This protocol has been approved by Vir Biotechnology, Inc. The following signature documents 
this approval.  
 
 
 
[See Appended Electronic Signature Page] 
Printed Name 
 
Signature and Date 
 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated.  
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Vir Biotechnology, Inc. I will discuss this material with them to ensure 
they are fully informed about the drugs and the study.  
 
 
 
 
Principal Investigator Printed Name 
 
Signature 
 
 
 
 
 
Date 
 

VIR-2482 
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PROTOCOL AMENDMENT 4 (29 JUNE 2023) SUMMARY OF CHANGES TABLE  
Protocol Document History  
Document 
Date 
Amendment 3 
22 September 2022 
Amendment 2 
19 August 2022 
Amendment 1 
11 July 2022 
Original Protocol 
01 June 2022 
Protocol Amendment 4 Summary of Changes  
Major changes are defined as changes that affect the design of the study, the safety of participants, the scope of the investigation, or 
the scientific quality of the study. The major changes and rationale for the changes from protocol Amendment 3 (dated 
22 September 2022) to protocol Amendment 4 (dated 29 June 2023), are as follows: 
Section # and Name 
Description of Change 
Brief Rationale 
1.2 Study Schema 
1.3 Schedule of Activities 
4.1 Overall Study Design 
Clarification on follow up period for influenza 
season 2 
Active influenza-like illness (ILI) symptom 
surveillance for influenza season 2 will be from 
Start of Influenza Season 2 (SOIS2) visit to End of 
Influenza Season 2 (EOIS2) visit, since no ILI 
expected after end of influenza season 
1.3 Schedule of Activities 
8.5.1 Influenza-Like Illness 
Monitoring and Influenza 
Confirmation Visit 
Update of Influenza Illness Monitoring Schedule 
from Start of Influenza Season 2 [SOIS2] to End 
of Influenza Season 2 [EOIS2] from passive 
surveillance every 2 months to every 3 months 
Maximize participant engagement and study 
retention during Influenza Season 2  
Removal of point-of-care respiratory viral panel 
RT-PCR testing from the season 2 ILI 
confirmation visit 
Nasopharyngeal swabs will be tested centrally with 
an assay that detects circulating strains of influenza 
A in the second season  

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Section # and Name 
Description of Change 
Brief Rationale 
ILI confirmation visit  influenza season 2 will be 
scheduled when participant experience both a 
systemic and respiratory symptom 
Minimize unnecessary ILI visits that are not due to 
symptomatic influenza infection to maximize 
participant engagement and study retention during 
Influenza Season 2 
9.3 Analysis Sets 
Update of definitions of All Participant Set, Full 
Analysis Set, Safety Set, Pharmacokinetic 
Analysis Set, Immunogenicity Analysis Set and 
Virology Analysis Set  
Align with the Statistical Analysis Plan (SAP) 
9.4.2 Primary 
Endpoint(s)/Estimand(s) Analysis 
Update of supplemental analysis and sensitivity 
analyses for primary endpoint 
Align with SAP 
1.1 Synopsis  
10.1.5 Committee Structure 
Clarification on role of Data Monitoring 
Committee (DMC) 
Clarify that the DMC will not make 
recommendations on conclusion or further 
enrollment of the study as the study has been fully 
enrolled in the first hemispheric influenza season 
and that an independent statistician will monitor 
for antibody dependent enhancement through the 
incidence of protocol defined influenza A illness 
cases and inform the DMC of any statistically 
significant imbalance  
Summary of Other Changes  
Other changes not considered major include: 
• Updated text throughout the protocol where relevant to specify for clarity regarding the start and end of influenza seasons in the 
study, including End of Influenza Season 1 (EOIS1), Start of Influenza Season 2 (SOIS2), and End of Influenza Season 2 (EOIS2) 
• Updated text throughout the protocol where relevant to specify for clarity, influenza season 1 corresponding to 2022-2023 
Northern hemisphere influenza season, and influenza season 2 corresponding to 2023-2024 Northern hemisphere influenza season 
• Updated Section 9 to clarify that SAP will be finalized prior to treatment unblinding 
• Addition of summary of major changes for previous protocol amendments in Section 10.5 
Administrative changes are not listed and may have included formatting, syntax, and other minor edits. 

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TABLE OF CONTENTS 
INVESTIGATOR SIGNATURE PAGE .........................................................................................2 
PROTOCOL AMENDMENT 4 (29 JUNE 2023) SUMMARY OF CHANGES TABLE .............3 
Protocol Document History .............................................................................................................3 
Protocol Amendment 4 Summary of Changes.................................................................................3 
Summary of Other Changes .............................................................................................................4 
1. 
PROTOCOL SUMMARY ..........................................................................................10 
1.1. 
Synopsis ......................................................................................................................10 
1.2. 
Study Schema .............................................................................................................13 
1.3. 
Schedule of Activities .................................................................................................14 
2. 
INTRODUCTION ......................................................................................................21 
2.1. 
Background .................................................................................................................21 
2.2. 
Study Rationale ...........................................................................................................21 
2.3. 
Benefit/Risk Assessment ............................................................................................23 
2.3.1. 
Risk Assessment .........................................................................................................24 
2.3.2. 
Benefit Assessment .....................................................................................................25 
2.3.3. 
Overall Benefit/Risk Conclusion ................................................................................25 
3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS ..................................................26 
4. 
STUDY DESIGN .......................................................................................................28 
4.1. 
Overall Study Design ..................................................................................................28 
4.1.1. 
Number of Participants ...............................................................................................29 
4.1.2. 
Intervention Groups and Duration ..............................................................................30 
4.2. 
Scientific Rationale for Study Design ........................................................................30 
4.3. 
Justification for Dose ..................................................................................................30 
4.4. 
End of Study Definition ..............................................................................................31 
5. 
STUDY POPULATION .............................................................................................32 
5.1. 
Inclusion Criteria ........................................................................................................32 
5.2. 
Exclusion Criteria .......................................................................................................33 
5.3. 
Lifestyle Considerations .............................................................................................34 
5.4. 
Screen Failures ............................................................................................................34 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ........................35 
6.1. 
Study Intervention(s) Administered ...........................................................................35 

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6.2. 
Preparation, Handling, Storage, and Accountability ..................................................35 
6.3. 
Dosage and Administration of VIR-2482 ...................................................................35 
6.4. 
Measures to Minimize Bias: Randomization and Blinding ........................................36 
6.4.1. 
Randomization ............................................................................................................36 
6.4.2. 
Blinding ......................................................................................................................36 
6.4.3. 
Unblinding ..................................................................................................................36 
6.5. 
Study Intervention Compliance ..................................................................................37 
6.6. 
Dose Modification ......................................................................................................37 
6.7. 
Continued Access to Study Intervention After the End of the Study .........................37 
6.8. 
Treatment of Overdose ...............................................................................................37 
6.9. 
Concomitant Therapy .................................................................................................38 
6.9.1. 
Concomitant Therapy Not Permitted During the Study .............................................38 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL .......................................39 
7.1. 
Discontinuation of Study Intervention........................................................................39 
7.2. 
Participant Discontinuation/Withdrawal from the Study ...........................................39 
7.3. 
Lost to Follow-up .......................................................................................................39 
7.4. 
Participant Replacement .............................................................................................40 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................41 
8.1. 
Screening Period .........................................................................................................41 
8.2. 
Efficacy Assessments .................................................................................................41 
8.3. 
Safety Assessments .....................................................................................................41 
8.3.1. 
Physical Examinations ................................................................................................41 
8.3.2. 
Vital Signs ..................................................................................................................42 
8.3.3. 
Electrocardiograms .....................................................................................................42 
8.3.4. 
Clinical Safety Laboratory Tests ................................................................................42 
8.3.5. 
Local Tolerability .......................................................................................................42 
8.3.6. 
Study Intervention Diary Card ....................................................................................43 
8.3.7. 
Pregnancy Testing ......................................................................................................43 
8.4. 
Adverse Events (AEs) Serious Adverse Events (SAEs), and Other Safety 
Reporting ....................................................................................................................43 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................43 
8.4.2. 
Follow-up of AEs and SAEs .......................................................................................44 

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8.4.3. 
Regulatory Reporting Requirements for SAEs ...........................................................44 
8.4.4. 
Adverse Events of Special Interest .............................................................................45 
8.4.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as AEs 
or SAEs .......................................................................................................................45 
8.4.6. 
Unsolicited Adverse Events ........................................................................................45 
8.4.7. 
Solicited Events ..........................................................................................................45 
8.4.8. 
AE Reporting and Clinical Events ..............................................................................45 
8.4.9. 
Special Situation Reports ............................................................................................46 
8.4.9.1. 
Pregnancy ...................................................................................................................46 
8.5. 
Influenza-Like Illness (ILI) Surveillance ...................................................................47 
8.5.1. 
Influenza-Like Illness Monitoring and Influenza Confirmation Visit ........................47 
8.5.2. 
Influenza Intensity and Impact Questionnaire ............................................................48 
8.5.3. 
Work Productivity and Activity Impairment (WPAI) ................................................48 
8.5.4. 
Virology and Resistance Surveillance ........................................................................49 
8.6. 
Pharmacokinetics ........................................................................................................49 
8.7. 
Genetics ......................................................................................................................49 
8.8. 
Immunogenicity Assessments ....................................................................................50 
8.9. 
Biomarkers ..................................................................................................................50 
8.9.1. 
Optional Future Biomedical Research ........................................................................50 
8.9.2. 
Optional Genetics Research ........................................................................................50 
8.10. 
Medical Resource Utilization and Health Economics ................................................51 
9. 
STATISTICAL CONSIDERATIONS .......................................................................51 
9.1. 
Statistical Hypotheses .................................................................................................51 
9.1.1. 
Multiplicity Adjustment..............................................................................................52 
9.2. 
Sample Size Determination ........................................................................................52 
9.3. 
Analysis Sets ...............................................................................................................53 
9.4. 
Statistical Analysis ......................................................................................................53 
9.4.1. 
General Considerations ...............................................................................................53 
9.4.2. 
Primary Endpoint(s)/Estimand(s) Analysis ................................................................54 
9.4.3. 
Secondary Endpoint(s)/Estimand(s) Analysis ............................................................55 
9.4.4. 
Exploratory Endpoint(s) Analysis ..............................................................................55 
9.4.5. 
Other Analyses ............................................................................................................56 
9.5. 
Interim Analysis ..........................................................................................................56 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................57 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ....................57 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................57 
10.1.2. 
Financial Disclosure ...................................................................................................57 
10.1.3. 
Informed Consent Process ..........................................................................................58 
10.1.4. 
Data Protection ...........................................................................................................58 
10.1.5. 
Committees Structure .................................................................................................59 
10.1.6. 
Data Quality Assurance ..............................................................................................59 
10.1.7. 
Source Documents ......................................................................................................60 
10.1.8. 
Electronic Case Report Forms (eCRFs) .....................................................................60 
10.1.9. 
Study and Site Start and Closure ................................................................................60 
10.1.9.1. 
First Act of Recruitment .............................................................................................60 
10.1.9.2. 
Study/Site Termination ...............................................................................................61 
10.1.10. 
Dissemination of Clinical Study Data ........................................................................61 
10.1.11. 
Publication Policy .......................................................................................................61 
10.2. 
Appendix  Clinical Laboratory Tests ..........................................................................62 
10.3. 
Appendix 2: Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting AEs, SAEs, SSRs, AESIs .............................................................63 
10.3.1. 
Definition of AE .........................................................................................................63 
10.3.2. 
Definition of SAE .......................................................................................................64 
10.3.3. 
Definitions of Special Situations (SSR) .....................................................................65 
10.3.4. 
Definition of Adverse Event of Special Interest (AESI) ............................................66 
10.3.5. 
Definition of Unsolicited AE and Solicited events .....................................................66 
10.3.6. 
Recording and Follow-Up of AEs, SAEs, SSRs (including Pregnancies), 
and/or AESIs ...............................................................................................................66 
10.3.7. 
Reporting of SAEs and SSRs (Including Pregnancies) ..............................................69 
10.4. 
Appendix 3: List of Abbreviations and Definitions of Terms ....................................70 
10.5. 
Appendix 4: Summary of Changes for Previous Protocol Amendments ...................72 
10.6. 
Appendix 5: Contraceptive and Barrier Guidance ......................................................78 
10.6.1. 
Definitions ..................................................................................................................78 
10.6.1.1. 
Woman of Non-Childbearing Potential (WONCBP) .................................................78 
10.6.1.2. 
Woman of Childbearing Potential (WOCBP) ............................................................78 

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10.6.2. 
Contraception Guidance .............................................................................................79 
10.7. 
Appendix 6: Influenza A Illness Definitions ..............................................................81 
10.7.1. 
Protocol-Defined ILI with Confirmed Influenza A ....................................................81 
10.7.2. 
CDC-Defined ILI with Confirmed Influenza A .........................................................81 
10.7.3. 
WHO-Defined ILI with Confirmed Influenza A ........................................................81 
10.8. 
Appendix 7: Hemispheric Influenza Season Definitions ............................................82 
10.9. 
Appendix 8: Local Tolerability Assessment ...............................................................83 
10.10. 
Appendix 9: Management of Injection-Related Reactions Including 
Systemic Symptoms (Anaphylaxis) ............................................................................84 
11. 
REFERENCES ...........................................................................................................86 
 
LIST OF TABLES  
Table 1: 
Schedule of Activities .................................................................................................14 
Table 2: 
Influenza-Like Illness Monitoring Schedule (D1 to End of Influenza Season 
1 [EOIS1]) ..................................................................................................................18 
Table 3: 
Influenza Illness Monitoring Schedule (Start of Influenza Season 2 [SOIS2] 
to End of Influenza Season 2 [EOIS2]) ......................................................................20 
Table 4: 
Intervention Groups ....................................................................................................30 
Table 5: 
Study Intervention(s) Administered ...........................................................................35 
Table 6: 
Protocol-Required Safety Laboratory Tests ...............................................................62 
 
LIST OF FIGURES  
Figure 1: 
Preferred IM Injection Schematic in Thigh by Study Arm. .......................................28 
 
 

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1. 
PROTOCOL SUMMARY  
1.1. 
Synopsis  
Study Title  
A Double-Blind, Randomized, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and 
Safety of VIR-2482 for the Prevention of Illness Due to Influenza A 
Brief Title  
A Phase 2 Study to Evaluate the Efficacy and Safety of VIR-2482 for the Prevention of Illness 
Due to Influenza A 
Background and Rationale  
VIR-2482 is a human monoclonal antibody (mAb) under development for the prevention of 
illness due to influenza A. VIR-2482 binds to a conserved epitope in the stem region of 
influenza A hemagglutinin (HA) protein that neutralizes influenza A virus and retains Fc effector 
functions in vitro. Additionally, VIR-2482 contains a 2-amino acid modification that is designed 
to increase half-life, potentially enabling therapeutic concentrations for an entire influenza 
season with a single dose.  
VIR-2482 is being evaluated in this dose ranging, proof-of-concept Phase 2 study for the 
prevention of illness due to influenza A in healthy adults at low risk of developing serious 
influenza-related complications.  
Primary and Secondary Objectives and Endpoints  
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of VIR-2482 compared to 
placebo in the prevention of protocol-defined ILI 
with confirmed influenza A 
• Proportion of participants with protocol-
defined ILI with confirmed influenza A (by 
reverse transcription-polymerase chain reaction 
[RT-PCR]) 
To evaluate the safety and tolerability of 
VIR-2482 compared to placebo 
• Occurrence of adverse events (AEs) 
• Occurrence of serious adverse events (SAEs) 
• Occurrence of adverse events of special interest 
(AESI) 
• Occurrence of solicited events 
• Vital signs and laboratory assessments 

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Objectives 
Endpoints 
Secondary 
To evaluate the efficacy of VIR-2482 compared to 
placebo in the prevention of CDC-defined or 
WHO-defined ILI with confirmed influenza A 
• 
Proportion of participants with CDC-defined 
ILI with confirmed influenza A (by RT-PCR) 
• 
Proportion of participants with WHO-defined 
ILI with confirmed influenza A (by RT-PCR) 
Overall Study Design  
This is a double-blind, randomized, placebo-controlled, Phase 2 study of VIR-2482. A single 
dose of VIR-2482 or placebo will be administered intramuscularly (IM) to healthy adult 
volunteers, aged 18 to < 65, without pre-existing risk factors for serious complications from 
influenza infection, who have not received an influenza vaccination for influenza season 1 
(2022-2023 Northern hemisphere influenza season). A single dose of 450 mg VIR-2482, 
1200 mg VIR-2482, or placebo will be administered to study participants. Saline placebo was 
chosen as the control for this study to allow for an unconfounded assessment of the efficacy and 
safety of VIR-2482. The use of a placebo control in otherwise healthy participants who have 
chosen to forgo seasonal influenza vaccine is considered acceptable due to the low risk of serious 
influenza-related complications and the availability of effective treatment options in the event of 
infection.  
Eligible participants will be randomized in a 1:1:1 ratio to receive 450 mg VIR-2482, 1200 mg 
VIR-2482, or volume-matched placebo. Randomization will be stratified by country, as 
applicable.  
This is an event driven study. Based on a 2-sided type 1 error rate of 5%, a total of 36 events 
pooled across treatment arms will be needed to provide approximately 80% power to detect a 
true relative risk reduction of 70% in one of the VIR-2482 arms in the proportion of 
protocol-defined ILI with confirmed influenza A compared to placebo. The sample size will be 
approximately 3000 participants assuming the proportion of protocol-defined ILI with confirmed 
influenza A in the placebo arm is at least 2.25%. The minimum detectable relative risk reduction 
is approximately 54.5%.  
An unblinded independent Data Monitoring Committee (DMC) will evaluate safety data. 
Participants will continue to be monitored during influenza season 2 (2023-2024 Northern 
hemisphere influenza season). 
Brief Summary  
The purpose of this study is to evaluate the efficacy, safety, and tolerability of VIR-2482 
compared to placebo in preventing influenza A illness in healthy adults 18 to <65 years of age 
without pre-existing risk factors for serious complications from influenza infection. 

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Number of Participants  
Approximately 3000 participants will be randomized in a 1:1:1 ratio to receive 450 mg 
VIR-2482, 1200 mg VIR-2482, or volume-matched placebo. Participants are planned to be 
enrolled in multiple study sites. Enrollment will be stopped when at least 36 participants (blinded 
and pooled across treatment arms) have met the primary endpoint of protocol-defined ILI with 
confirmed influenza A. 
Intervention Groups and Duration  
Intervention groups include: 
• 450 mg VIR-2482 
• 1200 mg VIR-2482 
• Volume-matched placebo  
The total study duration for each participant is planned to be up to approximately 88 weeks. This 
includes a screening period of up to 28 days, a 1-day intervention period, and a follow-up period 
of approximately up to 84 weeks. 
Study intervention will be administered only once as an IM injection of 450 mg VIR-2482, 
1200 mg VIR-2482, or volume-matched placebo on Day 1.  
Key Eligibility Criteria  
Eligible participants include healthy adult men and women aged 18 to < 65 years. Key inclusion 
criteria include body mass index (BMI) of 18.0 kg/m2 to 35.0 kg/m2, inclusive, as well as no 
clinically significant findings from physical examination, 12-lead electrocardiogram (ECG), vital 
signs, and laboratory values. Key exclusion criteria include prior or planned receipt of any 
influenza vaccine for influenza season 1, history or clinical evidence of conditions considered 
high risk for developing influenza-related complications, or any other clinically significant 
medical condition. 
Independent Data Monitoring /Other Committee  
An unblinded DMC will evaluate safety data throughout the study as appropriate.  

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1.2. 
Study Schema  
 
EOIS = end of influenza season; SOIS = start of influenza season 

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Table 2: 
Influenza-Like Illness Monitoring Schedule (D1 to End of Influenza Season 1 [EOIS1]) 
 
In Person 
Remote 
In 
Person 
Days After ILI Symptoms 
Onset 
ILI 
Confirmation 
Visit 
(D1 +3 days) 
ILI-
D1 
ILI-
D2 
ILI-
D3 
ILI-
D4 
ILI-
D5 
ILI-
D6 
ILI-
D7 
ILI-
D8 
ILI-
D9 
ILI-
D10 
ILI-D28 
±3 days 
Symptom-directed PE 
X 
 
 
 
 
 
 
 
 
 
 
X 
Vital signs 
X 
 
 
 
 
 
 
 
 
 
 
 
Anti-influenza A Antibody titer 
X 
 
 
 
 
 
 
 
 
 
 
X 
Nasopharyngeal swab for 
virology/PKa     
X 
 
 
 
 
 
 
 
 
 
 
 
Nasopharyngeal swab for Point 
of Care Respiratory Viral Panel 
X 
 
 
 
 
 
 
 
 
 
 
 
Blood sample for PK 
X 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity (serum)b     
X 
 
 
 
 
 
 
 
 
 
 
 
Laboratory assessmentc     
X 
 
 
 
 
 
 
 
 
 
 
 
Optional RNA expression 
biomarkers (Whole Blood) 
X 
 
 
 
 
 
 
 
 
 
 
 
Protein Biomarker profiling 
(serum) 
X 
 
 
 
 
 
 
 
 
 
 
X 
Optional Future Biomedical 
Research (serum) 
X 
 
 
 
 
 
 
 
 
 
 
X 
Self-measured oral temperatured     
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
WPAI Questionnairee     
 
X 
 
 
 
 
 
 
X 
 
 
 
Flu-iiQ™f     
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
ILI symptom monitoring 
X 

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In Person 
Remote 
In 
Person 
Days After ILI Symptoms 
Onset 
ILI 
Confirmation 
Visit 
(D1 +3 days) 
ILI-
D1 
ILI-
D2 
ILI-
D3 
ILI-
D4 
ILI-
D5 
ILI-
D6 
ILI-
D7 
ILI-
D8 
ILI-
D9 
ILI-
D10 
ILI-D28 
±3 days 
Participant contact follow-up 
(phone call from site)g     
 
Xh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Review/record AEsi     
X 
Concomitant medicationsj     
X 
AE = adverse event; D = day; ILI = influenza-like illness; PE = physical examination; PK = pharmacokinetic; PRO = patient reported outcome; 
RNA = ribonucleic acid; WPAI = Work Productivity and Activity Impairment. 
a Obtain nasopharyngeal swab for virology/PK before nasopharyngeal respiratory viral panel as feasible. 
b This collection includes both an ADA and neutralizing antibody sample. 
c Only hematology, chemistry, and liver function panels from laboratory tests listed in Section 10.2. 
d Temperature should be measured and recorded once daily at approximately the same time each day. 
e WPAI Questionnaire will be completed on ILI-D1 and ILI-D8. 
f Influenza intensity and impact questionnaire (Flu-iiQTM) will be completed twice daily up to and including ILI-D10. 
g Participants will be asked if they have received medically attended healthcare for the ILI outside of the clinical study site and followed up regarding any 
reported symptoms via phone and during in-clinic visits on ILI Confirmation and ILI-D28. 
h Study site will contact participant to schedule in-clinic ILI Confirmation Visit. 
i Refer to Section 10.3.6 for reporting instructions. AEs will be assessed during in-person visits and phone calls from site. 
j Includes any concomitant medications, including antibiotic courses, in the past 30 days prior to ILI-D1. Concomitant medications will be recorded during in 
person visits and phone calls from site. 

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Table 3: 
Influenza Illness Monitoring Schedule (Start of Influenza Season 2 [SOIS2] 
to End of Influenza Season 2 [EOIS2])  
 
In Person 
Days After ILI Symptoms Onset 
ILI Confirmation Visit 
 (D1 +3 days) 
Symptom-directed PE 
X  
Vital signs 
X  
Anti-influenza A Antibody titer 
X  
Nasopharyngeal swab for virology/PK  
X 
Blood sample for PK 
X  
Laboratory assessmenta     
X 
Review/record AEsb     
X 
Concomitant medicationsc     
X 
AE = adverse event; D = day; ILI = influenza-like illness; PE = physical examination; PK = pharmacokinetic; 
RNA = ribonucleic acid; WPAI = Work Productivity and Activity Impairment. 
a Only hematology, chemistry, and liver function panels from laboratory tests listed in Section 10.2. 
b Refer to Section 10.3.6 for reporting instructions  
c Includes any concomitant medications, including antibiotic courses, in the past 30 days prior to ILI-D1, any 
influenza vaccines received for influenza season 2, or anti-influenza antiviral therapeutics. 

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2. 
INTRODUCTION  
2.1. 
Background  
VIR-2482 is a human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) of the kappa 
class that targets a highly conserved epitope in the stem region of the influenza A hemagglutinin 
(HA) protein that is being developed for the prevention of illness due to influenza A. The parent 
molecule of VIR-2482, MEDI8852, was isolated from human memory B cells by the Vir 
Biotechnology, Inc. (VIR) subsidiary, Humabs, and was further optimized by in vitro affinity 
maturation by MedImmune (Kallewaard 2016). In vitro data demonstrates neutralization activity 
against a wide variety of seasonal and pandemic strains of influenza A virus and in vivo 
protection of otherwise lethal influenza A infection in animal models. In addition, the epitope 
recognized by VIR-2482 is highly conserved among circulating influenza A virus strains.  
Influenza viruses are single-stranded, negative-sense, segmented, ribonucleic acid (RNA) viruses 
in the Orthomyxoviridae family which cause highly contagious respiratory illness. Annual 
influenza epidemics result in substantial morbidity and mortality with an estimated 3 to 5 million 
cases of severe disease requiring hospitalization worldwide and 290,000 to 650,000 deaths 
globally per the World Health Organization (WHO 2018). Of the circulating types of influenza 
virus, type A is the most common and most virulent and drives both seasonal hemispheric 
epidemics and periodic global pandemics characterized by marked increases in morbidity and 
mortality (Rambaut 2008). 
Despite advances in vaccines and small molecule antivirals, there remains an unmet medical 
need for the prevention and treatment of influenza illness, especially in populations at high risk 
for morbidity and mortality from influenza A virus where severe complications can cause 
significant healthcare burden. The current cornerstone of influenza prevention and epidemic 
control is strain-specific seasonal vaccination, an approach that has varying degrees of efficacy 
ranging from 10 to 60% over the last 14 years (CDC 2022). Mismatches between strains used to 
prepare the vaccine and actual circulating strains result in reduced effectiveness. A mAb with 
activity against a broad range of influenza viruses that provides a season-long and a consistent 
year-to-year protection without the need to rely on baseline host immune status for efficacy and 
strain-specific matching would help to address the unmet needs associated with the current 
approach to influenza prevention and epidemic control.  
2.2. 
Study Rationale  
A mAb with activity against a broad range of influenza A viruses that provides a season-long and 
a consistent year-to-year protection without the need to rely on baseline host immune status for 
efficacy and strain-specific matching would help to address the unmet needs associated with the 
current approach to influenza prevention and epidemic control. Currently, there are no influenza 
mAbs that have been approved for the prevention or treatment of influenza. With activity against 
a broad range of influenza A strains and extended half-life, VIR-2482 has the potential to be an 
effective prevention agent against influenza A and fulfill an unmet need.  

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VIR-2482 has been evaluated in a Phase 1, randomized, placebo-controlled study to evaluate the 
safety, tolerability, pharmacokinetics, and immunogenicity of VIR-2482 administered 
intramuscularly (IM) to healthy adult volunteers aged 18 to <65 years of age who have not 
received the seasonal influenza vaccine. The study was conducted in 2 Parts (Part A and Part B). 
Part A was a double-blind, single ascending dose of VIR-2482 study with 4 cohorts of 
25 participants/cohort who received a single dose of VIR-2482 or placebo at 60, 300, 1200, or 
1800 mg administered intramuscularly in a 4 (active): 1 (placebo) ratio to evaluate the safety and 
tolerability of VIR-2482. Part B was an open-label, safety and PK study portion following a 
second dose of VIR-2482. Enrollment is complete, with final results pending. Preliminary results 
indicate that VIR-2482 has a favorable safety and tolerability profile at doses up to 1800 mg. No 
treatment-emergent drug-related SAEs were observed and no AEs leading to study 
discontinuation were observed. Six of 100 participants reported mild injection site reactions that 
resolved within 48 hours. The majority of AEs were mild or moderate. No clinically significant 
laboratory abnormalities were observed. VIR-2482 exposures (Cmax and AUC) were 
dose-proportional across the tested doses (60 to 1800 mg). Tmax following intramuscular 
injection was 7 to 14 days. Apparent volume of distribution was typical for a monoclonal 
antibody (11.1 to 14.1 L). Terminal elimination half-life was 58 to 60 days, consistent with the 
half-life extending modification. 
VIR-2482 is being evaluated in this study for the prevention of illness due to influenza A in 
healthy adults at low risk of developing serious influenza-related complications. This is a Phase 
2 dose ranging, proof-of-concept study that will enroll healthy adults aged 18 to < 65 years of 
age without risk factors for serious complications from influenza infection who have chosen to 
forgo the seasonal influenza vaccination for influenza season 1 (2022-2023 Northern hemisphere 
influenza season). Placebo was chosen as the control for this study to allow for an unconfounded 
assessment of the efficacy and safety of VIR-2482. The use of a placebo control in otherwise 
healthy participants who have chosen to forgo seasonal influenza vaccine is considered 
acceptable due to the low risk of serious influenza-related complications and the availability of 
effective treatment options in the event of infection.  
In this study, a single dose of either 450 mg or 1200 mg (divided equally between 
2 intramuscular [IM] injections) VIR-2482 or volume-matched placebo will be administered at 
the beginning of the influenza season.  

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2.3. 
Benefit/Risk Assessment  
Detailed information about the known, potential, and expected benefits and risks and reasonably 
expected adverse events (AEs) may be found in the VIR-2482 Investigator’s Brochure (IB). 
The potential clinical risks of VIR-2482 are based on theoretical and known concerns associated 
with the mAbs class of therapeutics in general. The risk monitoring and mitigation strategy for 
the administration of VIR-2482 is outlined in the table below. The parent molecule of VIR-2482, 
MEDI8852, was found to be well tolerated at doses up to 3000 mg IV in studies of healthy 
volunteers (N = 32) and for treatment of patients with confirmed, uncomplicated influenza 
infection (N = 94). In patients with acute influenza, the most commonly reported AEs in all 
cohorts were those expected in a population with acute influenza illness, with no clear evidence 
of antibody-dependent enhancement (ADE) observed (Ali 2018). Although the theoretical risk of 
ADE with anti-influenza mAbs in the presence of infection remains, nonclinical in vitro and in 
vivo data, and ongoing clinical data with VIR-2482 suggest no evidence of ADE with influenza 
virus to date. One participant with acute influenza who received 3000 mg of MEDI8852 via 
intravenous infusion along with oseltamivir had a severe (Grade 3) investigational product 
related event of infusion-related reaction requiring termination of administration. The event 
resolved following treatment with IM dexamethasone, inhaled albuterol and oxygen. 
VIR-2482 was well tolerated in the Phase 1 clinical study (VIR-2482-3001) at IM doses of up to 
1800 mg. Most AEs were Grade 1 or 2 in severity and the majority were considered not related 
to VIR-2482. Injection site reactions (ISRs) were reported in 7.5% participants (6 of 80) that 
received VIR-2482, were mild (Grade 1) in severity, and resolved without sequelae. No subjects 
had a treatment-related SAE, or discontinued the study or study drug due to AEs. 

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2.3.1. 
Risk Assessment  
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Anaphylaxis and other 
serious allergic reactions 
and injection-related 
reactions 
Expected local discomfort following IM 
injection of VIR-2482 has been observed in 
prior studies, although no cases of systemic 
allergic reactions or anaphylaxis have been 
observed to date with IM VIR-2482. 
• All participants will be monitored for at least 2 hours following 
the IM administration of VIR-2482 and specific guidance for the 
management of systemic reactions such as anaphylaxis is 
provided in Section 10.10. 
• Study personnel will be trained to recognize and treat 
anaphylaxis appropriately. 
• Trial participants will be educated to contact the clinical site at 
any point in time if there are any worsening, new, or unresolving 
symptoms at the injection site(s). 
Development of Anti-
Drug Antibodies (ADA) 
The mAb class of therapeutics is recognized 
to have the potential to elicit ADA responses 
in recipients with repeated dosing that may 
impact the pharmacokinetics, 
pharmacodynamics, safety, and/or efficacy, 
of the drug. 
• Participants in this study will be monitored for the development 
of ADA at regular intervals as outlined in the SoA in accordance 
with established guidance. 
Antibody-Dependent 
Enhancement (ADE)  
Although there is a theoretical risk of ADE 
with anti-influenza mAbs in the presence of 
infection, nonclinical in vitro and in vivo 
data, and ongoing clinical data with 
VIR-2482, suggest no evidence of ADE with 
influenza virus. 
• Participants in this study will be monitored for important 
potential risks, including anaphylaxis, assessment of safety in 
the presence of influenza A infection and routine 
pharmacovigilance and risk minimization activities will be 
performed. 
• The DMC will be able to monitor cases of influenza A in an 
unblinded manner and recognize any imbalances in the 
treatment arms of the study and make recommendations 
accordingly 
• This study will enroll healthy adults aged 18 to <65 years of age. 
This approach is supported by the safety profile of the parent 
molecule (MEDI8852), the low risk of influenza-related 
complications in this otherwise healthy population, and low 
potential for antibodies to enhance viral disease (ie, ADE). 

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2.3.2. 
Benefit Assessment  
This is a Phase 2 study being conducted in healthy participants. Clinical benefit of VIR-2482 has 
not been established. Participation in this study will contribute to the clinical development of 
VIR-2482 as a potential therapy for the prevention of illness due to influenza A.  
2.3.3. 
Overall Benefit/Risk Conclusion  
VIR-2482 is a mAb with activity against a broad range of influenza viruses that may provide 
safe, well tolerated, and highly effective season-long protection, and that does not rely on 
baseline host immune competency for efficacy. Therefore, VIR-2482 has the potential to address 
the unmet needs associated with the current approach to influenza prevention and epidemic 
control. Taking into account the measures taken to minimize risk described in the Risk 
Assessment Table to participants enrolling in this study, the potential risks identified in 
association with VIR-2482 are reasonable given the current unmet need for the prevention of 
serious illness due to influenza A. In addition, this study is being conducted in participants at low 
risk of complications to minimize the risk of severe influenza A disease in case of limited 
activity of VIR-2482. Safety of the participants will be monitored in this study through routine 
pharmacovigilance activities.  

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3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS  
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of VIR-2482 compared to 
placebo in the prevention of protocol-defined ILI 
with confirmed influenza A 
• Proportion of participants with protocol-
defined ILI with confirmed influenza A (by 
reverse transcription-polymerase chain reaction 
[RT-PCR]) 
To evaluate the safety and tolerability of VIR-
2482 compared to placebo 
• Occurrence of adverse events (AEs) 
• Occurrence of serious adverse events (SAEs) 
• Occurrence of adverse events of special interest 
(AESI) 
• Occurrence of solicited events 
• Vital signs and laboratory assessments 
Secondary 
To evaluate the efficacy of VIR-2482 compared to 
placebo in the prevention of CDC-defined or 
WHO-defined ILI with confirmed influenza A 
• Proportion of participants with CDC-defined 
ILI with confirmed influenza A (by RT-PCR)  
• Proportion of participants with WHO-defined 
ILI with confirmed influenza A (by RT-PCR)  
Exploratory/Other  
To evaluate the effect of VIR-2482 compared to 
placebo on the severity and duration of illness in 
participants with confirmed influenza A 
• Severity and duration of participant-reported 
signs and symptoms of influenza-like illness 
(ILI) due to influenza A, as measured by Flu-
iiQTM  
To characterize the serum PK of VIR-2482 
following a single dose 
• Single-dose VIR-2482 serum PK parameters 
including but not limited to: Cmax, Clast, Tmax, 
Tlast, AUCinf, AUClast, % AUCexp, t1/2, λz, Vz/F, 
CL/F. 
To characterize the nasopharyngeal sample (NPS) 
PK of VIR-2482 following a single dose 
• Single-dose VIR-2482 NPS PK parameters 
including but not limited to: Cmax, Clast, Tmax, 
Tlast, AUCinf, AUClast, % AUCexp, t1/2, λz. 
To evaluate the relationship between VIR-2482 
exposure and the incidence of influenza A 
infection 
• Exposure-response for VIR-2482 
To evaluate the immunogenicity (induction of 
ADA) response to VIR-2482 
• Incidence and titers (if applicable) of ADA to 
VIR-2482  
Evaluate the effect of VIR-2482 versus placebo 
on potential biomarkers of host response in 
participants with confirmed influenza A 
• Evaluation of host immune responses and 
exploratory biomarkers related to influenza A, 
and/or VIR-2482, including antibody, genetic, 
transcriptomic, virologic, and proteomic 
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Objectives 
Endpoints 
To evaluate seroconversion to circulating strains 
of influenza A virus 
• Proportion of subjects with symptomatic and 
asymptomatic seroconversion to circulating 
strains of influenza A as measured by serotype-
specific HAI titers. 
The occurrence of influenza infection by virus 
subtype 
• Number and proportion of participants with 
laboratory-confirmed influenza subtype by 
treatment group 
To evaluate the effect of VIR-2482 compared to 
placebo on the magnitude of viral load in 
nasopharyngeal samples at time of ILI 
• Quantification of the influenza A viral load 
present in nasopharyngeal sample at the time of 
ILI visit by RT-qPCR  
Monitor the emergence of influenza A resistance 
to VIR-2482  
• Emergence of viral resistance to VIR-2482 in 
influenza A 
Monitor the occurrence non-influenza A 
respiratory viral infections 
• Occurrence of laboratory-confirmed (by RT-
PCR) non-influenza A respiratory viral 
infections, including influenza B 
Measure of Work Productivity and Activity 
Impairment (WPAI) due to influenza A illness 
• Work time missed, work productivity loss, and 
activity impairment due to influenza A using 
the validated WPAI questionnaire 
Primary Estimand/Coprimary Estimands  
The primary clinical question of interest is:  
What is the relative risk between VIR-2482 (450 mg or 1200 mg) versus placebo of 
protocol-defined ILI with confirmed influenza A after administration of study intervention, 
regardless of the receipt of any non-study influenza antiviral for treatment or prophylaxis or of 
an authorized influenza vaccine? 
Refer to Section 9.4.2 for details regarding the primary estimand.  
Secondary Estimand(s)  
The clinical questions of interest for the secondary objectives are:  
• What is the relative risk between VIR-2482 (450 mg or 1200 mg) versus placebo of 
CDC-defined ILI with Confirmed Influenza A after administration of study intervention, 
regardless of the receipt of any non-study influenza antiviral for treatment or prophylaxis or 
of an authorized influenza vaccine?  
• What is the relative risk between VIR-2482 (450 mg or 1200 mg) versus placebo of 
WHO-Defined ILI with Confirmed Influenza A after administration of study intervention, 
regardless of the receipt of any non-study influenza antiviral for treatment or prophylaxis or 
of an authorized influenza vaccine? 
Refer to Section 9.4.3 for details regarding the secondary estimand.  

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4. 
STUDY DESIGN  
4.1. 
Overall Study Design  
This is a double-blind, randomized, placebo-controlled, Phase 2 study of VIR-2482 administered 
intramuscularly (IM) to healthy adult volunteers aged 18 to < 65 years of age, who have not 
received an influenza vaccination for season 1 (2022-2023 Northern hemisphere influenza 
season). The study is designed to evaluate the safety, tolerability, and efficacy of VIR-2482 in 
preventing influenza A illness. An independent Data Monitoring Committee (DMC) will ensure 
thorough evaluation of safety data and early detection of potential safety signals. 
Randomization will be stratified by country as applicable. Efforts will be made to enroll all study 
participants during the first 12 weeks of influenza season 1. Eligible participants will be 
randomized 1:1:1 to receive 450 mg VIR-2482, 1200 mg VIR-2482, or placebo on Day 1. 
The preferred injection site is the vastus lateralis (thigh), with the dorsogluteal (buttock) site as 
an alternative. All participants will be administered 2 IM injections of blinded study intervention 
using identical administration procedures irrespective of study arm. Participants will be 
administered 2 doses of placebo (placebo arm), or 1 dose of VIR-2482 and 1 dose of placebo 
(450 mg arm), or 2 doses of VIR-2482 (1200 mg arm) under double blinded conditions as 
outlined in Figure 1. Each injection will be 4 mL in volume. Refer to Section 6.3 and the 
Pharmacy Manual for detailed study intervention preparation and administration instructions. 
Participants will remain at the clinical investigative site for a minimum of 2 hours post-dose to 
assess safety and local tolerability of VIR-2482 at injection site(s) and complete assessments per 
the Schedule of Activities. 
Figure 1: 
Preferred IM Injection Schematic in Thigh by Study Arm.  
 
Following study intervention, participants will also complete a daily Study Intervention Diary 
Card on Days 1 to 7 (Section 8.3.6). A thermometer and ruler will be provided to all participants 
to aid in recording the required information (Section 8.3.6) in the Study Intervention Diary Card.  

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Participants will be actively monitored for ILI throughout the study. Participants will complete 
ILI symptom surveillance questions twice a week from Day 1 through the EOIS1 visit via 
electronic instrument, see Section 10.8 for further details of EOIS1. Participants experiencing ILI 
will complete in-clinic evaluations, phone evaluations, self-reported symptoms, influenza 
symptom severity, and WPAI questionnaires, and be followed per the Influenza-Like Illness 
Monitoring Schedule (Section 8.5.1).  
All participants will have a follow-up visit approximately 1, 4, and 12 weeks after receiving 
study intervention, an EOIS1 visit (approximately 2 weeks after the EOIS1), and a visit at 
approximately the Start of Influenza Season 2 (SOIS2) for the assessment of safety, PK, and 
ADA. In addition to the scheduled PK sampling for all trial participants as outlined in the SoA, 
PK sampling will also occur during any ILI confirmation visits as applicable.  
Following the EOIS1 visit, participants will be contacted every 3 months by the study site to 
determine if the participant experienced an ILI during the previous months. During these phone 
visits, the clinical site must document any ILI with confirmed influenza A, AEs, and visits to 
medical professionals per the Schedule of Activities. From SOIS2 to the End of Influenza Season 
2 (EOIS2), participants will also receive weekly reminders to complete ILI symptom 
surveillance questions via electronic instrument. Participants experiencing symptoms consistent 
with ILI will complete the in-clinic evaluation per Table 3 Influenza-Like Illness Monitoring 
Schedule (SOIS2 to EOIS2) (Section 8.5.1). 
In the event participants experience influenza illness, participants should be offered standard of 
care therapy per local treatment guidelines, which may include antiviral therapy. Consistent with 
the different mechanisms of action of the current licensed influenza antivirals and stem-directed 
mAbs, available data suggests that VIR-2482 will not interfere with their mechanism of action. 
Study enrollment will conclude following EOIS1 if there are at least 36 participants across all 3 
treatment arms who meet the primary endpoint. Details will be described in the Statistical 
Analysis Plan (SAP). 
4.1.1. 
Number of Participants  
Assuming the attack rate of 2.25% for influenza A in the placebo arm, approximately 
3000 participants will be randomized at a 1:1:1 ratio to receive 450 mg VIR-2482, 1200 mg 
VIR-2482, or volume-matched placebo: 
• 1000 participants to receive 450 mg VIR-2482 
• 1000 participants to receive 1200 mg VIR-2482 
• 1000 participants to receive volume-matched placebo 
A total of 36 events will be needed to provide approximately 80% power with alpha=0.05, to 
detect a true relative risk reduction of 70% in one VIR-2482 arm in the primary endpoint. No 
further enrollment will be required once 36 events (protocol-defined ILI with confirmed 
influenza A) are observed (blinded and pooled across treatment arms). The study has selected a 
conservative attack rate of 2.25% for influenza A in unvaccinated individuals based on observed 
historical attack rates from multiple placebo-controlled influenza vaccine studies 
(Jayasundara 2014; Osterholm 2012). 

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4.1.2. 
Intervention Groups and Duration  
Table 4: 
Intervention Groups 
Intervention 
Dose 
Route 
Number of Doses 
Schedule 
VIR-2482 
450 mg 
IM 
1 (2 injections) 
Single dose on Day 1 
VIR-2482 
1200 mg 
IM 
1 (2 injections) 
Single dose on Day 1 
Placebo 
NA 
IM 
1 (2 injections) 
Single dose on Day 1 
The total study duration for each participant is planned to be up to approximately 88 weeks. This 
includes an up to 28-day screening period, 1-day intervention period, and approximately up to 
84-week follow-up period. 
4.2. 
Scientific Rationale for Study Design  
VIR-2482 is being evaluated for the prevention of illness due to influenza A in healthy adults at 
low risk of developing serious influenza-related complications. VIR-2482 has high in vitro 
potency against a wide variety of seasonal and pandemic strains of influenza A virus and is 
effective in the prevention of otherwise lethal influenza A infection in animal models. In 
addition, the epitope recognized by VIR-2482 is highly conserved among influenza A virus and 
has a high barrier to the development of resistance in vitro.  
This randomized, placebo-controlled, Phase 2 study is designed to evaluate the safety, 
tolerability, and efficacy of VIR-2482 for the prevention of influenza A illness in healthy adults 
without risk factors for serious complications from influenza infection. To adequately assess the 
ability of VIR-2482 to prevent influenza A illness, the study will commence prior to influenza 
season 1. 
The study is designed to assess the efficacy of VIR-2482 in the prevention of influenza A illness 
and to collect additional safety, tolerability, and PK data. VIR-2482 was previously studied in an 
ascending dose Phase 1 study in which doses of up to 1800 mg were generally well tolerated.  
This study will enroll healthy adults aged 18 to <65 years of age, without risk factors for serious 
complications from influenza infection who have chosen to forgo the seasonal influenza 
vaccination for season 1. This approach is supported by the safety profile of VIR-2482 in the 
completed Phase 1 study and the safety profile of the parent molecule (MEDI8852), the low risk 
of influenza-related complications in this otherwise healthy population, and low potential for 
antibodies to enhance viral disease (ADE).  
Placebo was chosen as the control for this study to allow for an unconfounded assessment of the 
efficacy and safety of VIR-2482. The use of a placebo control in otherwise healthy participants 
who have chosen to forgo seasonal influenza vaccine is considered acceptable due to the low risk 
of serious influenza-related complications and the availability of effective antiviral treatment 
options in the event of infection.  
4.3. 
Justification for Dose  
In this study, a single dose of either 450 mg or 1200 mg VIR-2482 will be administered at the 
beginning of influenza season 1. These doses were selected based on the acceptable safety and 

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tolerability of doses up to 1800 mg in the earlier Phase 1 study (VIR-2482-3001), in vitro 
neutralization data, a range of lung tissue distribution assumptions, and serum PK simulations 
based on data collected in VIR-2482-3001.  The doses of 450 mg and 1200 mg were selected to 
generate data to characterize the PK/PD relationship and optimize the dose for Phase 3 clinical 
development. 
The in vitro neutralization activity of VIR-2482 has been characterized through multiple 
microneutralization studies, which collectively have determined neutralizing activity against 
26 H1N1 and 37 H3N2 wild-type live viruses (details in the VIR-2482 Investigator’s Brochure 
Edition 3). 
 
 
 
 However, the potential contribution of mAb effector function to clinical 
efficacy has not been characterized. Additionally, the extent of mAb distribution to human lung 
tissue is also not precisely defined, with conflicting estimates ranging from 5% to 31% reported 
in the literature (Aweda 2022, Magyarics 2019; Shah 2013; Chigutsa 2022; Chigutsa 2021; 
Jones 2021; Eigenmann 2017; Baxter 1994; Covell 1986). Furthermore, it is not known whether 
mAb distribution to lung tissue is dose-proportional, or if mAb elimination half-life in the lung 
differs from mAb serum elimination half-life.  Therefore, it is unclear if a simple plasma:tissue 
partitioning coefficient is an accurate metric for estimating VIR-2482 levels at the site of drug 
action. 
VIR-2482-4002 is designed as a proof-of-concept dose ranging study, intended to generate PK 
and clinical data that will help address these uncertainties surrounding lung tissue distribution 
and whether mechanisms other than neutralizing activity may contribute to clinical effect. 
 
 (not 
considering the potential contribution of effector functions that are intact in VIR-2482), 1200 mg 
is anticipated to maintain efficacious exposures for 6 months, while 450 mg is anticipated to 
maintain efficacious exposures for 4 months. The dose of 450 mg was selected to generate data 
to inform on the lower threshold of VIR-2482 exposure required for efficacy, and to assess 
whether clinical effect may be superior to that predicted by neutralization data alone. 
4.4. 
End of Study Definition  
The end of study is defined as the last scheduled visit (or completed contact) of the last 
participant. 

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5. 
STUDY POPULATION  
Healthy adult male and nonpregnant, nonlactating females aged 18 to < 65 years. 
5.1. 
Inclusion Criteria  
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be 18 to < 65 years of age, at time of randomization. 
Type of Participant and Disease Characteristics 
2. Participants must be in good health, determined from medical history (eg, chronic 
conditions such as hypertension, hyperlipidemia, gastroesophageal reflux disease, 
anxiety and depression must be controlled with a stable dose of medication, defined as 
no change to dose or frequency within the previous 30 days), and no clinically 
significant findings from physical examination, 12-lead electrocardiogram (ECG), vital 
signs, and laboratory values. 
Weight 
3. Body mass index (BMI) 18.0 kg/m2 to 35.0 kg/m2, inclusive. 
Sex and Contraceptive/Barrier Requirements 
4. Female participants must have either negative pregnancy testing, documented 
permanent infertility, or confirmation of post-menopausal status.  
Female participants who are Women of childbearing potential (WOCBP) must have a 
negative blood pregnancy test at screening, a negative urine pregnancy test on Day 1, 
and cannot be breastfeeding. WOCBP will agree to use effective or highly effective 
methods of contraception 14 days before the first dose of study intervention through 
last scheduled follow-up visit, and will also agree to refrain from egg donation and in 
vitro fertilization from the time of study intervention administration through last 
scheduled follow-up visit . 
Informed Consent 
5. Capable of giving signed informed consent as described in Section 10.1.3, which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 

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5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. History or clinical evidence of conditions considered high risk for developing 
influenza-related complications listed below: 
 
Established diagnosis of:  
− Asthma  
− Neurological and neurodevelopmental conditions (such as cerebral palsy, epilepsy 
[seizure disorders], stroke, intellectual disability, moderate to severe developmental 
delay, muscular dystrophy, or spinal cord injury)  
− Chronic lung disease (such as chronic obstructive pulmonary disease [COPD], 
emphysema, and cystic fibrosis)  
− Heart disease (such as congenital heart disease, congestive heart failure and 
coronary artery disease)  
− Blood disorders (such as sickle cell disease and Thalassemia)  
− Endocrine disorders (such as diabetes and adrenal insufficiency)  
− Chronic kidney disease  
− Chronic liver disease  
− Metabolic disorders (such as inherited metabolic disorders and mitochondrial 
disorders)  
− Weakened immune system due to disease or medication (such as individuals with 
HIV or AIDS, or cancer, or those on chronic steroids)  
− People younger than 19 years of age who are receiving long-term aspirin therapy 
2. History of confirmed influenza infection within 3 months prior to randomization. 
3. Febrile illness with or without respiratory symptoms (eg, cough, nasal congestion) 
within 5 days prior to randomization. 
4. History of malignancy within 5 years (treated squamous or non-invasive basal cell skin 
cancers are permitted) or participant is under evaluation for malignancy. 
5. Any condition or receipt of any medication contraindicating IM injection, as judged by 
the investigator. 
6. History of a severe allergic reaction with generalized urticaria, angioedema or 
anaphylaxis within the 2 years prior to randomization.  
7. Participant has a clinically significant medical condition, physical exam finding, or 
abnormal laboratory result at screening that in the clinical judgment of the investigator 
make the participant at undue risk to forgo seasonal influenza vaccination or safely 
participate in the study. 

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Prior/Concomitant Therapy 
8. Prior or planned receipt of any influenza vaccine for the upcoming season (relative to 
Day 1 dosing). Influenza vaccination is permitted following completion of the EOIS 
visit. 
9. Received any investigational agent within 90 days or within 5 half-lives of the 
investigational agent, whichever is longer, before study intervention administration. 
5.3. 
Lifestyle Considerations  
Lifestyle considerations are not applicable to this study. 
5.4. 
Screen Failures  
A screen failure occurs when a participant who consents to participate in the clinical study 
subsequently does not enter the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities.  
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once. Rescreened participants should be assigned a new participant number for every 
screening/rescreening event. 

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6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY  
Study intervention is defined as any investigational intervention, marketed product, or placebo 
intended to be administered to a study participant according to the study protocol. 
6.1. 
Study Intervention(s) Administered  
Table 5: 
Study Intervention(s) Administered 
Intervention Label 
450 mg VIR-2482 
1200 mg VIR-2482 
Placebo 
Intervention Name 
VIR-2482 
VIR-2482 
Placebo 
Type  
Biologic 
Biologic 
Placebo to biologic  
Dose Formulation 
Solution of lyophilized 
solid, reconstituted 
with sterile water for 
injection, USP 
Solution of lyophilized 
solid, reconstituted 
with sterile water for 
injection, USP 
Sterile 0.9% (w/v) 
sodium chloride 
solution 
Unit Dose Strength(s) 
300 mg  
300 mg 
0 mg 
Dosage Level(s) 
450 mg once 
1200 mg once 
Once 
Route of 
Administration 
IM  
IM  
IM  
Use 
Experimental 
Experimental 
Experimental 
IMP and NIMP/AxMP 
IMP  
IMP  
IMP  
Sourcing 
Provided by the 
sponsor.  
Provided by the 
sponsor.  
Provided locally by the 
study site, subsidiary, 
or Sponsor. 
Packaging and 
Labeling 
Study intervention will 
be provided in vial. 
Each vial will be 
labeled as required per 
country requirement. 
Study intervention will 
be provided in vial. 
Each vial will be 
labeled as required per 
country requirement. 
Provided by site or 
may be provided by the 
sponsor in its 
commercially available 
packaging. 
6.2. 
Preparation, Handling, Storage, and Accountability  
Detailed instructions for study interventions will be provided in the Pharmacy Manual. 
6.3. 
Dosage and Administration of VIR-2482  
On the day of dosing, the pharmacist or designee will prepare the drug per Pharmacy Manual 
instructions. A qualified clinical investigative site staff member under the general supervision of 
the investigator or designee will administer study intervention to study participants via IM 
injections. 
Study intervention administration should be performed in a setting where personnel and 
equipment are available for the management of severe systemic reactogenicity including 
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Management guidelines for these potential symptoms are provided in Section 10.10. 
Refer to the Pharmacy Manual for detailed study intervention preparation and administration 
instructions. 
6.4. 
Measures to Minimize Bias: Randomization and Blinding  
6.4.1. 
Randomization  
Randomization will be used to minimize participant selection bias. All participants will be 
centrally randomized to receive study intervention (VIR-2482 1200 mg or VIR-2482 450 mg or 
placebo) using an Interactive Response Technology (IRT) system. Before the study is initiated, 
training on the IRT system will be provided to each site. 
6.4.2. 
Blinding  
This study will be double-blind: the sponsor, investigators, study staff participating in participant 
care or clinical evaluations, and participants will remain blinded to each participant’s assigned 
study intervention throughout the course of the study. To help maintain this blind, designated 
unblinded study staff will be responsible for the reconstitution and dispensation of all study 
intervention and will endeavor to ensure that there are no differences in time taken to dispense 
following randomization. In addition, only unblinded staff may receive, store, and handle study 
intervention. The study intervention should be prepared away from view of the blinded staff and 
the participant. Every IM injection must be labeled to maintain the blind.  
6.4.3. 
Unblinding  
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the participant, the investigator may obtain treatment assignment for that participant. If the 
event requires that an expedited regulatory report be sent to one or more regulatory agencies, a 
copy of the report, identifying the participant’s intervention assignment, may be sent to 
investigators in accordance with local regulations and/or sponsor policy. 
At the initiation of the study, study site personnel will be instructed on the method for breaking 
the blind. The unblinding method will be either manual or electronic. A participant should 
continue in the study if that participant’s intervention assignment is unblinded. 
Unblinding of Individual Participant Treatment Assignments by Investigator for Medical 
Emergencies or Urgent Clinical Situations 
Unblinding of the individual participant’s treatment by the investigator will be limited to medical 
emergencies or urgent clinical situations in which knowledge of the participant’s study treatment 
is necessary for clinical management. In such cases, investigators will use their best judgment as 
to whether to unblind without first attempting to contact the medical monitor to discuss 
unblinding. If investigators deem it unnecessary to unblind immediately, they will first attempt to 
contact the medical monitor to discuss unblinding. If investigators have tried but are unable to 
reach the medical monitor, they will use their best judgment, based on the nature and urgency of 
the clinical situation, and may proceed with unblinding.  
Contact information for the medical monitor (or appropriate backup) will be in a separate 
document. 

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If a participant’s treatment assignment has been unblinded for a medical emergency or urgent 
clinical situation, the medical monitor will be notified within 24 hours of the unblinding event. 
The reason and the date of the unblinding will be documented clearly in the participant’s study 
file. Information about the treatment assignment obtained from the unblinding will be maintained 
in a secure location with controlled access and will not be shared with sponsor, the contract 
research organization (CRO), or any site personnel (other than the physician treating the 
participant). In addition, the investigator will consider whether the clinical event that prompted 
unblinding will be considered an SAE, according to the regulatory definitions or criteria for 
SAEs, and if so, submit an SAE report to sponsor or designee, per Section 10.3.2. 
Unblinding of Individual Participant Treatment Assignments by Sponsor or Designee for 
SAEs or Safety Concerns 
Sponsor or designee will also unblind any SAE reports in compliance with regulatory reporting 
requirements. In addition, the sponsor may, for matters relating to safety, unblind individual 
participants at any time. 
6.5. 
Study Intervention Compliance  
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose administered 
in the clinic will be recorded in the source documents. Refer to Pharmacy Manual for further 
details. 
6.6. 
Dose Modification  
This is a single-dose study and dose modifications are not applicable. 
6.7. 
Continued Access to Study Intervention After the End of the Study  
No access to study intervention will be available to participants after the end of the study. 
6.8. 
Treatment of Overdose  
No specific treatment is recommended for an overdose. The treating physician may provide 
supportive measures depending on the symptoms. 
In the event of an overdose, the treating physician should: 
• Contact the medical monitor immediately. 
• Closely monitor the participant for any AE/SAE and laboratory abnormalities until the 
overdose is considered to be resolved. 
• Refer to Section 10.3.5 for reporting of Overdose to sponsor. 

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6.9. 
Concomitant Therapy  
Any medication or vaccine (including over-the-counter or prescription medicines, recreational 
drugs, vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrollment or receives during the study must be recorded in the electronic case report forms 
(eCRFs). 
Participants will be counseled to make efforts to proactively inform the site about starting new 
over-the-counter or prescription medicines, recreational drugs, vitamins, and/or herbal 
supplements over the course of the study. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
6.9.1. 
Concomitant Therapy Not Permitted During the Study  
Any other experimental or authorized influenza vaccine or anti-influenza antiviral therapeutic is 
not permitted during influenza season 1 with the exception of participants who acquire 
laboratory diagnosed, symptomatic influenza illness. 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL  
Discontinuation of specific sites or of the study as a whole are detailed in Section 10.1.9. 
7.1. 
Discontinuation of Study Intervention  
A participant will be permanently discontinued from completion of the injection or injections if 
they experience life-threatening, injection related reactions (IRRs) including severe allergic or 
hypersensitivity reactions or severe cytokine release syndrome. 
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention. If study intervention is permanently discontinued, the participant will remain in the 
study to be evaluated for follow-up assessments. See the SoA in Section 1.3 for data to be 
collected at the time of discontinuation of study intervention and follow-up and for any further 
evaluations that need to be completed.  
7.2. 
Participant Discontinuation/Withdrawal from the Study  
• A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, or 
compliance reasons.  
• At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted, as shown in the SoA. See SoA for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
• If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must document this in the site study records. 
7.3. 
Lost to Follow-up  
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible, counsel the participant on the importance of maintaining the assigned visit schedule 
and ascertain whether the participant wishes to and/or should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, [3] telephone calls, and if 
necessary, a certified letter to the participant’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to be lost to 
follow-up from the study. 

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Site personnel will attempt to collect the vital status of the participant within legal and ethical 
boundaries for all participants randomized, including those who did not get study intervention. 
Public sources may be searched for vital status information. If vital status is determined as 
deceased, this will be documented and the participant will not be considered lost to follow-up. 
Sponsor personnel will not be involved in any attempts to collect vital status information. 
7.4. 
Participant Replacement  
Participants who withdraw or are withdrawn before the first study intervention administration 
may be replaced.  

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8. 
STUDY ASSESSMENTS AND PROCEDURES  
• Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol waivers 
or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention. 
• Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICF may be utilized for screening or baseline 
purposes provided the procedures met the protocol-specified criteria, were performed within 
the timeframe defined in the SoA and the participant’s consent for use in the study was 
obtained. 
• Safety/laboratory/analyte results that could unblind the study will not be reported to 
investigative sites or other blinded personnel until the study has been unblinded. 
8.1. 
Screening Period  
Informed consent must be obtained before conducting any study-related procedures. Participant 
eligibility will be evaluated during the screening period and includes the assessments outlined in 
the SoA. The screening period duration is up to 28 days before a participant’s first dose of study 
intervention. 
8.2. 
Efficacy Assessments  
Planned timepoints for all efficacy assessments are provided in the SoA. 
8.3. 
Safety Assessments  
Planned timepoints for all safety assessments are provided in the SoA. 
8.3.1. 
Physical Examinations  
• A complete physical examination will be conducted to determine study eligibility at 
screening. Height and weight will also be measured and recorded. 
• A symptom-directed physical examination will be performed at subsequent visits as defined 
in the SoA. The symptom-directed physical examinations will be performed based on signs 
and symptom the participant has reported and/or in the opinion of the investigator. 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 

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8.3.2. 
Vital Signs  
• Vital signs will be measured in a supine position after 5 minutes of rest and will include 
temperature, systolic and diastolic blood pressure, and pulse and respiratory rate.  
8.3.3. 
Electrocardiograms  
• Single 12-lead ECG(s) will be obtained as outlined in the SoA (see Section 1.3) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and 
[QTc] intervals.  
8.3.4. 
Clinical Safety Laboratory Tests  
• See Section 10.2 for the list of clinical laboratory tests to be performed and the SoA for the 
timing and frequency. 
• The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study as an AE or SAE, if applicable 
(Section 10.3). The laboratory reports must be filed with the source documents.  
• All laboratory tests with values considered clinically significantly abnormal through the 
EOIS2 visit should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor. 
− If clinically significant values do not resolve within a period of time judged reasonable by 
the investigator, an evaluation to identify the etiology should be undertaken, and the 
sponsor notified. 
− All protocol-required laboratory tests, as defined in Section 10.2, must be conducted in 
accordance with the Laboratory Manual and the SoA. 
− If laboratory values from non-protocol-specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (eg, SAE or AE or dose 
modification), then the results must be recorded. 
8.3.5. 
Local Tolerability  
VIR-2482 has been well tolerated when administered by IM injection to date. In the prior VIR-
2482-3001 study in which doses up to 1800 mg were administered as up to 3 separate IM 
injections, there were no cases of treatment-emergent immune reactions, no drug related Grade 3 
or 4 AEs, and only Grade 1 (mild) injection site reactions were reported in 7.5% participants 
(6 of 80) that received VIR-2482. As IM VIR-2482 has generally been well tolerated to date, 
VIR-2482-4002 study participants will be monitored for at least 2 hours following the IM 
administration of study intervention and the local tolerability assessment to be conducted for each 
injection site will be performed approximately 1 hour post-dose per the SoA using the assessment 
tool in Section 10.9. 
At the discretion of the investigator, unscheduled visits are permitted as needed for follow up of 
any unresolved local tolerability symptoms. Management guidelines for these symptoms are 
provided in Section 10.10. 

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8.3.6. 
Study Intervention Diary Card  
After receipt of study intervention, study participants will record temperature at least daily (twice 
daily as able) from Days 1 to 7 in an electronic diary card. In addition, participants will record 
daily measurement and intensity grade of solicited injection site and systemic reactions in the 
electronic diary card from Days 1 to 7. Participants will be instructed on how to record 
temperature and solicited injection site and systemic reactions. 
8.3.7. 
Pregnancy Testing  
A pregnancy test or confirmation of post-menopausal status must be confirmed for all female 
participants. Post-menopausal status is defined as no menses for 12 months without an 
alternative medical cause. Confirmation of negative FSH is required to confirm post-menopausal 
status. Pregnancy tests will be performed for WOCBP only. Pregnancy testing will be performed 
per the SoA and any time pregnancy is suspected. A WOCBP who is known to be pregnant or 
who does not have a negative pregnancy test at screening is not eligible for study participation. A 
blood pregnancy test will be performed at screening and urine pregnancy tests will be performed 
thereafter. During the study, the results of these pregnancy tests must be known prior to study 
intervention administration. A WOCBP determined to be pregnant while on study will be 
followed until the pregnancy outcome is known, as described in Section 8.4.9.1. 
8.4. 
Adverse Events (AEs) Serious Adverse Events (SAEs), and Other 
Safety Reporting  
The definitions of AEs, SAEs, and other safety events are provided in Section 10.3. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up all AEs (Section 10.3.5). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information  
After signing of the ICF, but prior to initiation of study medication, AEs/SAEs related to 
protocol-mandated procedures should be reported. Following initiation of study intervention, all 
AEs/SAEs, regardless of cause or relationship, will be recorded for the entire duration of the 
study. 
Medical occurrences that begin before the start of study intervention but after obtaining informed 
consent will be recorded as medical history/current medical conditions, not as AEs. 
All SAEs, regardless of causal relationship, will be collected from signing of the ICF until the 
end of the study. 
All SAEs must be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, from the investigator or designee awareness of the 

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event, as indicated in Section 10.3. The investigator will submit any updated SAE data to the 
sponsor or designee within 24 hours of it being available. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the investigator must promptly 
notify the sponsor. 
8.4.2. 
Follow-up of AEs and SAEs  
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All AEs, SAEs, and AEs of special interest, pregnancy, and special 
situation reports (as defined in Section 10.3) will be followed until resolution, stabilization, the 
event is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Further information on follow-up procedures is provided in Section 10.3.5. 
8.4.3. 
Regulatory Reporting Requirements for SAEs  
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met. The investigator will record the SAE 
information on the appropriate form and submit it to sponsor or designee within 24 hours of 
awareness of the event. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, institutional review boards (IRBs)/independent ethics committees 
(IECs), and investigators. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review the 
information, document the review, file the safety report along with the relevant study documents 
and will notify the IRB/IEC, if appropriate according to local requirements. 
Assessment of expectedness for SAEs will be determined by the sponsor using the reference 
safety information (RSI) as specified in the IB. Assessment of expectedness for marketed 
products will be determined by the sponsor using the product label. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary. 

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8.4.4. 
Adverse Events of Special Interest  
Adverse events of special interest are defined as relevant known toxicities of other therapeutic 
mAbs or as a result of signals observed from previous studies in the nonclinical programs, or in 
the clinical program with VIR-2482 that the sponsor will monitor throughout the study. AESIs 
may be updated during the course of the study based on accumulating safety data. 
Adverse events of special interest include: 
• Hypersensitivity reactions 
• Adverse events potentially related to ADA 
• Adverse events potentially related to ADE 
8.4.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as AEs or 
SAEs  
Laboratory abnormalities without an associated AE (signs or symptoms) and/or which do not 
require medical intervention, are not themselves recorded as AEs or SAEs. However, laboratory 
abnormalities (eg, clinical chemistry, hematology, and urinalysis) that require medical or surgical 
intervention or lead to study intervention interruption, modification, or discontinuation must be 
recorded as an AE, as well as an SAE, if applicable. In addition, laboratory or other abnormal 
assessments (eg, vital signs) that are associated with signs and/or symptoms must be recorded as 
an AE or SAE if they meet the definition of an AE or SAE as described in Section 10.3. If the 
laboratory abnormality is part of a clinical syndrome, record the syndrome or diagnosis (eg, 
anemia), not the laboratory result (ie, decreased hemoglobin). 
Severity should be recorded and graded according to the Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (presented in 
Section 10.3). 
8.4.6. 
Unsolicited Adverse Events  
An unsolicited AE is an AE that was not solicited during the Local Tolerability Assessment 
(Section 10.9) or the Study Intervention Diary Card (Section 8.3.6) and that is reported by a 
participant who has provided documented informed consent. 
8.4.7. 
Solicited Events  
Solicited events are predefined local and systemic reactions for which the participant is 
specifically questioned, and which are reported by the participant during the Local Tolerability 
Assessment (Section 10.9) and on the Study Intervention Diary Card (Section 8.3.6).  
Solicited events that qualify as SAEs should be reported as SAEs, as applicable.  
8.4.8. 
AE Reporting and Clinical Events  
Cases of ILI with confirmed influenza A (Section 10.7), will be reported as Clinical Events, and 
should not be reported as adverse events unless the signs or symptoms of influenza A, are more 
severe than expected given the participant's clinical status and medical history or if the 
investigator considers that there is a causal relationship between the study treatment or protocol 
design/procedures and the disease progression. 

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Clinical Events that qualify as an SAE should be reported as SAEs as applicable. 
8.4.9. 
Special Situation Reports  
All special situation reports (SSR) will be collected from the start of intervention until the end of 
follow-up period and include all reports of medication error, abuse, misuse, overdose, pregnancy, 
drug interactions, exposure via breastfeeding, unexpected benefit, occupational exposure, 
transmission of infectious agents via the product, counterfeit or falsified medicine, and product 
complaints. 
The investigator will record the special situation information on the appropriate form and submit 
it to the sponsor or designee within 24 hours of learning of the situation. These reports must 
consist of situations that involve study intervention and/or protocol-required concomitant 
medications but do not apply to non-required concomitant medications. 
Special situations involving non-required concomitant medications do not need to be reported; 
however, for special situations that result in AEs due to a non-required concomitant medication, 
the AE should be reported. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse” but may be more appropriately documented as a protocol deviation. 
All clinical sequelae in relation to these SSRs (from required and non-required medication) will 
be reported as AEs or SAEs. Details of the symptoms and signs, clinical management, and 
outcome will be reported, when available. 
8.4.9.1. 
Pregnancy  
• Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study intervention and until the end of study. 
• If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor or designee within 24 hours of learning of the 
female participant or female partner of male participant pregnancy. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
• Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such. 
• The participant/pregnant female partner (after obtaining the necessary signed informed 
consent from the female partner) will be followed to determine the outcome of the 
pregnancy. The investigator will collect follow-up information on the participant/pregnant 
female partner and the neonate and the information will be forwarded to the sponsor. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in Section 8.4.3. 
While the investigator is not obligated to actively seek this information in former study 
participants/pregnant female partner, if he/she learns of any SAE and considers the event to 
be reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor. 

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Any female participant who becomes pregnant while participating in the study may continue 
study participation and continue safety follow-up visits as per SoA 
Prior to continuation of study intervention following pregnancy, the following must occur: 
• The sponsor and the relevant IRB/IEC give written approval. 
• The participant gives signed informed consent. 
• The investigator agrees to monitor the outcome of the pregnancy and the status of the 
participant and her offspring. 
The study participant and/or pregnant female partner, as applicable, should receive any necessary 
counseling regarding the risk of continuing the pregnancy and the possible effects on the fetus. 
8.5. 
Influenza-Like Illness (ILI) Surveillance  
8.5.1. 
Influenza-Like Illness Monitoring and Influenza Confirmation Visit  
For influenza season 1, participants will be actively monitored for ILI from Day 1 to the EOIS1 
visit. See the SoA for details. 
Participants experiencing symptoms consistent with ILI, such as those defined in Section 10.7, 
will report the symptoms of ILI by answering provided PRO questions in the affirmative. 
Electronic instrument will be used. Reporting should occur on the same day as symptom onset 
and an in-clinic evaluation per the Influenza-Like Illness Monitoring Schedule (Section 1.3) 
should be scheduled. 
Efforts will be made to have first in-clinic evaluation within one day and preferably no longer 
than 3 days from symptom onset. An additional in-clinic evaluation should be scheduled 
approximately 28 days after symptom onset. Study participants will be educated on the 
symptoms of ILI and how to reach the study site. The participants will also be provided with 
contact information for the study site. 
In-clinic evaluation to confirm ILI symptoms and influenza A will include, but not be limited to, 
physical examination (including vital signs), laboratory testing (including safety), 
nasopharyngeal swab for point of care respiratory viral panel for influenza A RT-PCR, blood 
collection for PK and ADA, and review of AEs and concomitant medications as appropriate. A 
nasopharyngeal swab for virology/PK testing will also be sent to a central laboratory for viral 
confirmation, quantitation, and/or sequencing; aliquots from this nasopharyngeal swab will also 
be used for PK analysis. 
Each participant presenting with symptoms consistent with ILI will be followed via daily site 
outreach by telephone call through Day 10 following initial presentation. During the in-clinic 
visits and via phone calls, participants will be asked if they have received medically attended 
healthcare for ILI outside of the clinical study site and followed up with regarding any reported 
symptoms. During the in-clinic visits and via phone calls, AEs and concomitant medications 
should also be reported. At the discretion of the investigator, unscheduled in-clinic visits are 
permitted during the ILI monitoring period. 

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Participants will report ILI symptoms on the electronic device from ILI-D1 to ILI-D10. Oral 
body temperature will be measured daily from ILI-D1 to ILI-D10 (10 days inclusive) from 
symptom onset and recorded, by the participant. A thermometer will be proactively provided to 
participants prior to the ILI-D1 visit. Participants will complete self-reported influenza symptom 
severity assessments on the electronic device from ILI-D1 to ILI-D10 (10 days inclusive) after 
symptom onset as part of the Flu-iiQTM.  Participants will also complete the WPAI questionnaire 
on ILI-D1 and ILI-D8 after symptom onset. 
For participants who test negative for Influenza A at the ILI Confirmation Visit and have 
continued symptoms without an alternative diagnosis, investigators may bring them back for 
another ILI Confirmation Visit to retest for Influenza A infection if clinically indicated. For 
participants who are determined to not be positive for influenza A at the ILI confirmation visit, 
symptoms should be recorded and followed as AEs. 
For influenza season 2, participants will also receive weekly reminders to complete ILI symptom 
surveillance questions via electronic instrument. Participants experiencing symptoms consistent 
with ILI will report the symptoms of ILI by answering provided PRO questions in the 
affirmative. An in-clinic evaluation per the Influenza-Like Illness Monitoring Schedule (SOIS2 
to EOIS2) should be scheduled (Table 3); reported symptoms triggering in-clinic evaluations 
may be assessed by the investigators prior to scheduling the in-clinic visit to confirm they are 
consistent with ILI and that the visit is warranted. Efforts will be made to have the in-clinic 
evaluation within one day and preferably no longer than 3 days from symptom onset. In-clinic 
evaluation will be completed per Table 3.To minimize the attrition of trial participants in the 
second influenza season, the threshold to trigger an ILI visit has been optimized to enrich for 
scheduled ILI visits more likely to be associated with PCR confirmed Influenza A and will 
require both a systemic and a respiratory symptom as described in Section 10.7. To ensure that 
the confirmatory RT-PCR assay used in the second influenza season has acceptable sensitivity, 
confirmatory RT-PCR on NPS swabs collected at ILI visits will be run at the virology central lab 
using an assay that detects circulating influenza A strains. 
8.5.2. 
Influenza Intensity and Impact Questionnaire  
For influenza season 1, participants will complete the Flu-iiQTM, a self-assessment of systemic 
and respiratory symptoms associated with influenza (ie, cough, sore throat, headache, nasal 
congestion, feverishness or chills, muscle or joint pain, and fatigue). They will score the severity 
of their symptoms using a 4-point rating scale (0, None; 1, Mild; 2, Moderate; 3, Severe). 
Additional items related to physical, social and emotional well-being will also be collected. This 
information will be captured per the Influenza-Like Illness Monitoring Schedule (Table 2). The 
4-point rating scale will only be used in the exploratory endpoints to determine severity and 
duration of participant-reported signs and symptoms during an ILI due to influenza A through 
EOIS1. 
8.5.3. 
Work Productivity and Activity Impairment (WPAI)  
The WPAI is a validated, patient-reported, quantitative assessment of absenteeism (work time 
missed), presenteeism (reduced on-the-job effectiveness), work productivity loss and activity 
impairment due to a specific health problem. Participants who present with ILI through EOIS1 
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8.5.4. 
Virology and Resistance Surveillance  
Viral parameters including the virus type, subtype and viral load by qRT-PCR will be evaluated 
at the ILI visit for participants who present with laboratory-confirmed influenza A infection. 
Resistance surveillance for potential emergence of resistance to VIR-2482 will be conducted for 
all participants who received study intervention and present with laboratory-confirmed influenza 
A infection, as per the Influenza-Like Illness Monitoring Schedule (Table 2 and Table 3). Deep 
sequencing analysis of influenza A virus may be attempted on samples from nasopharyngeal 
swabs from participants with confirmed influenza A virus infection with viral load above the 
limit of the sequence assay. To evaluate the emergence of antiviral resistance, recombinant virus 
containing the HA gene from participants with confirmed influenza A virus infection will be 
generated using established reverse genetic procedures, and recombinant viruses will be 
subjected to in vitro phenotypic analysis to determine the neutralization activity of VIR-2482.  
8.6. 
Pharmacokinetics  
Blood samples will be collected and processed to serum for measurement of VIR-2482 
concentrations using a validated assay. An aliquot of serum from PK samples will be used for 
blood urea nitrogen (BUN) analysis to normalize nasopharyngeal drug concentration values.  
Instructions for the collection and handling of blood samples will be provided by the sponsor in 
the Laboratory Manual. The actual date and time (24-hour clock time) of each sample collection 
will be recorded. 
Nasopharyngeal samples (NPS) will be collected to assess the concentration of VIR-2482 in 
nasal secretions using a qualified assay. NPS will be collected from all participants at the EOIS1 
visit and the ILI confirmation visit. An optional NPS sub-study may be initiated at Sponsor 
discretion, and will include collection of additional NPS from a subset of approximately 
300 participants pooled across all treatment groups, at timepoints specified in the SoA. The 
Sponsor will notify study sites of any decision to trigger initiation of the sub-study by Protocol 
Clarification Letter (PCL) and will also notify sites when sub-study enrollment is completed by a 
subsequent PCL. Instructions for the collection and handling of nasopharyngeal samples will be 
provided by the sponsor in the Laboratory Manual. The actual date and time (24-hour clock time) 
of each sample collection will be recorded. 
Sample collection timepoints for all trial participants are specified in the SoA (Section 1.3). 
VIR-2482 concentration information that may unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded. 
8.7. 
Genetics  
See Section 8.9.2. 

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8.8. 
Immunogenicity Assessments  
Blood samples will be collected for the measurement of immunogenicity (anti-drug antibody 
[ADA] and/ or neutralizing antibodies [Nab] as applicable) responses to VIR-2482. Specific 
blood collection timepoints are defined in the SoA. Analysis of ADA samples will be performed 
using a validated assay in a 3-tier format (screen, confirm, titer). Additional testing may be 
performed to detect the presence of NAb and/or characterize the immunogenicity response. 
Further details regarding the collection, processing, and analysis of immunogenicity samples are 
provided in the Laboratory Manual. 
8.9. 
Biomarkers  
Through EOIS1 biomarker samples will be collected from participants at baseline and after study 
intervention to evaluate host immune responses and exploratory biomarkers related to influenza 
A, non-influenza A respiratory viruses, and/or VIR-2482, including serology (anti-influenza 
antibody), transcriptomic, virologic, and proteomic parameters. To evaluate seroconversion, the 
proportion of subjects with seroconversion to circulating strains of influenza A as measured by 
serotype-specific HAI titers will be evaluated. To evaluate the effect of endogenous anti-
influenza A antibodies, additional serum testing of anti-influenza A antibodies may be 
performed. 
Serum samples will be collected to evaluate changes in serum biomarkers and proteins 
(including but not limited to inflammatory cytokines and chemokines, such as IL-6, IFN-alpha, 
IL-1, IL-3, TNF-alpha). Samples will be collected in accordance with the Laboratory Manual and 
SoA. 
Sponsor may store samples for up to 15 years after the end of the study to achieve study 
objectives. 
8.9.1. 
Optional Future Biomedical Research  
An optional serum sample may be collected for future biomedical research studies from 
participants who have consented to participate in the Optional Future Biomedical Research 
component of the study. The specimens collected will be used to increase our knowledge of 
influenza A infection and identify biomarkers that inform the scientific understanding of 
influenza A infection and/or its treatments. Participation is optional. Participants who do not 
wish to provide samples for future biomedical research may still participate in the study. 
8.9.2. 
Optional Genetics Research  
Optional blood samples for DNA and RNA isolation will be collected from participants who 
have consented to participate in the genetics analysis component of the study. The specimens 
collected will be used to evaluate associations between FcγR allelic expression, IgG1 allotype, 
and clinical outcomes. Sequencing of genomic polymorphisms, including but not limited to 
FCGR2A, FCGR2B, FCGR3A, and IGHG1 loci, will be performed on whole blood samples 
collected pre-dosing in participants who opt-in for the genetic research component of this study. 
Whole blood samples for RNA expression will be collected to evaluate cellular populations and 
transcriptomes. Participation is optional. Participants who do not wish to participate in the 
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If a DNA sample is not obtained at the Day 1 visit, it may be drawn at any time in the study. In 
the event of DNA extraction failure, a replacement genetic blood sample may be requested from 
the participant. Signed informed consent will be required to obtain a replacement sample unless 
it was included in the original consent. 
Samples will be collected in accordance with the Laboratory Manual and SoA. 
8.10. 
Medical Resource Utilization and Health Economics  
For all participants throughout the study, the investigator and study-site personnel will collect 
data about health care resource utilization associated with medical encounters. 
The data collected will: 
• Include the reasons and duration of hospitalizations and emergency room visits and  
• Exclude procedures, tests, and encounters mandated by the protocol. 
The sponsor may use the collected data to conduct economic analyses.  
9. 
STATISTICAL CONSIDERATIONS  
This section provides a high-level summary of the planned statistical analyses. Details of the 
statistical analyses will be provided in the SAP, which will be finalized prior to treatment 
unblinding. Further details regarding timing of analyses will be provided in the SAP. 
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol and the justification for making the change will be described 
in the SAP and/or the clinical study report. Additional exploratory analyses of the data will be 
conducted as deemed appropriate. 
9.1. 
Statistical Hypotheses  
The primary objective is to evaluate the efficacy of VIR-2482 1200 mg and VIR-2482 450 mg as 
compared to placebo in preventing protocol-defined ILI with confirmed influenza A. The null 
hypotheses to be tested corresponding to the primary estimand are as follows: 
• Null hypothesis: VIR-2482 1200 mg is not different from placebo with respect to the 
proportion of participants with protocol-defined ILI with confirmed influenza A. 
• Null hypothesis: VIR-2482 450 mg is not different from placebo with respect to the 
proportion of participants with protocol-defined ILI with confirmed influenza A. 
The null hypotheses corresponding to the key secondary estimands are as follows: 
• Null hypothesis: VIR-2482 1200 mg is not different from placebo with respect to the 
proportion of participants with CDC-Defined ILI with Confirmed Influenza A. 
• Null hypothesis: VIR-2482 1200 mg is not different from placebo with respect to the 
proportion of participants with WHO-Defined ILI with Confirmed Influenza A.  

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• Null hypothesis: Null hypothesis: VIR-2482 450 mg is not different from placebo with 
respect to the proportion of participants with CDC-Defined ILI with Confirmed Influenza A . 
• Null hypothesis: VIR-2482 450 mg is not different from placebo with respect to the 
proportion of participants with WHO-Defined ILI with Confirmed Influenza A. 
9.1.1. 
Multiplicity Adjustment  
A hierarchical fixed sequence testing procedure will be used to control the type I error at 
α = 0.05 for testing VIR-2482 1200 mg versus placebo and VIR-2482 450 mg versus placebo for 
the multiple endpoints. For the primary endpoint, first we will test VIR-2482 1200 mg versus 
placebo at α=0.05. If the test is statistically significant with VIR-2482 1200 mg superior to 
placebo, then we will proceed to test VIR-2482 450 mg versus placebo for the same endpoint 
α=0.05. For a test at any step to be considered statistically significant within the testing 
hierarchy, it must be statistically significant, and all previous tests (if any) within the hierarchy 
must be statistically significant at the 0.05 level. The complete testing hierarchy will be further 
defined in the SAP. 
Note that the formal comparisons precluded by the hierarchical testing strategy will be 
performed and the resulting p values considered as descriptive. 
9.2. 
Sample Size Determination  
This is an event driven study. Based on a 2-sided type 1 error rate of 5%, a total of 36 events will 
be needed to provide approximately 80% power, to detect a true relative risk reduction of 70% in 
one VIR-2482 arm in the proportion of protocol-defined ILI with confirmed influenza A over the 
entire influenza season 1 after the administration of study interventions. The sample size will be 
approximately 3000 participants (1000 per arm), if the proportion of protocol-defined ILI with 
confirmed influenza A in the placebo arm is 2.25%. The minimum detectable relative risk 
reduction is approximately 54.5%. The study has selected a conservative attack rate of 2.25% for 
influenza A in unvaccinated individuals based on observed historical attack rates from multiple 
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9.3. 
Analysis Sets  
For the purposes of analysis, the following analysis sets are defined: 
Participant Analysis Set 
Description 
All Participants Set  
The All Participants Set will include all participants who are 
randomized or receive any amount of study intervention. This 
analysis set will be used for all individual participant data listings and 
disposition summary tables, unless otherwise specified. 
Full Analysis Set (FAS) 
The FAS will include all randomized participants who 1) have not 
had confirmed influenza infection within 3 months prior to 
randomization [protocol exclusion criterion 2], 2) have not received 
an influenza vaccination for influenza season 1 [protocol exclusion 
criterion 8], and 3) receive any amount of study intervention. The 
FAS will be used for summaries of demographics and baseline 
characteristics and all efficacy analyses, in which participants will be 
analyzed according to the randomized study intervention. 
Safety Set 
The Safety Set will include all participants who receive any amount 
of study intervention. This Safety Set will be used for all safety 
analyses in which participants will be analyzed according to study 
intervention received.  
Pharmacokinetic Analysis Set 
The Pharmacokinetic Analysis Set will include all participants in the 
Safety Set who have receive 1 full dose of study intervention and 
have at least 1 measurable post-dose VIR-2482 concentration. 
Immunogenicity Analysis Set 
All participants in the Safety set who have at least 1 sample that has 
undergone testing for immunogenicity including screening, titers, or 
neutralizing characterization, as applicable. The Immunogenicity 
Analysis Set will be used for analyses of ADA. Participants will be 
analyzed according to the study intervention received. 
Virology Analysis Set 
All participants in the FAS with a nasopharyngeal swab obtained at 
the ILI confirmation visit. The Virology Analysis Set will be used for 
analyses of all virology parameters. Participants will be analyzed 
according to the randomized study intervention. 
Additional analysis sets related to the primary efficacy endpoint may be defined in the SAP, as 
appropriate. 
9.4. 
Statistical Analysis  
9.4.1. 
General Considerations  
All individual participant data for the All Participants Set will be presented in data listings. 
Continuous variables will be summarized using the following descriptive summary statistics: 
the number of participants (n), mean, SD, median, minimum value (min), and maximum value 
(max). The precision of the measurement for each continuous variable will be specified in the 
SAP. 

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Categorical variables will be summarized using counts and percentages. Percentages will be 
presented to 1 decimal place. 
Baseline value, unless otherwise specified, will be defined as the most recent non-missing 
measurement (scheduled or unscheduled) collected before the initial administration of study 
intervention. 
Change (absolute change) from baseline will be calculated as post-baseline value - baseline 
value. 
Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs reported with an onset 
date on or after the start of study drug through the end of the Treatment-Emergent (TE) period. 
The TE Period will include the time period starting from the date of the first dose of study drug 
to the completion of study participation. 
Completion of study participation for each individual participant is defined as one of the 
following: 
• For participants who complete the Follow-up Period: the EOIS2 visit 
• For participants who prematurely discontinue the study and do not withdraw consent: the 
Early Termination (ET) visit 
• For participants who withdraw consent: the date of withdrawal of consent 
• For participants are lost to follow-up: the date of the last contact. 
9.4.2. 
Primary Endpoint(s)/Estimand(s) Analysis  
The primary clinical question of interest is: What is the relative risk between VIR-2482 (450 mg 
or 1200 mg) versus placebo of protocol-defined ILI with confirmed influenza A after 
administration of study intervention, regardless of the receipt of any non-study influenza 
antiviral for treatment or prophylaxis or of an authorized influenza vaccine? 
The primary estimand is defined as follows: 
• Population: healthy adults 18 to <65 years of age, who have not received an influenza 
vaccination for the upcoming  season.  
• Primary Endpoint: proportion of participants in the FAS with protocol-defined ILI with 
confirmed influenza A 
• Treatment comparison: VIR-2482 (1200 mg or 450 mg) vs placebo 
• Potential intercurrent events:  
− Receipt of any non-study influenza antiviral for treatment or prophylaxis  
− Receipt of an authorized influenza vaccine 
− Death for reason(s) other than influenza illness 
− Participants who become unblinded to treatment assignment due to any reasons 
• Population-level summary: Relative risk  

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The primary efficacy analysis will be the comparison of the proportion of participants in the FAS 
with protocol-defined ILI with confirmed influenza A after administration of study intervention  
using a Poisson regression model with robust sandwich estimators adjusted for treatment group. 
Multiple occurrences of protocol-defined ILI with confirmed influenza A within one study 
participant will be counted once at the earliest occurrence. The adjusted relative risk reduction, 
calculated as 100% × (1 - adjusted relative risk) of protocol-defined ILI with confirmed 
influenza A for VIR-2482 1200 mg vs placebo will be estimated, along with the corresponding 
95% CI. Similarly, the adjusted relative risk reductions and the corresponding 95% CIs will be 
calculated for the treatment comparisons of VIR-2482 450 mg vs placebo.  
The primary analyses for the primary endpoint will be conducted using treatment policy strategy 
for intercurrent events other than death. All observed data collected after the intercurrent events 
other than death will be used in the analyses.  
A supplemental analysis of the primary endpoint will be based on responses prior to the 
intercurrent events by handling intercurrent events using ‘while on treatment’ strategy. 
Sensitivity analyses will be conducted as appropriate. Details will be specified in the SAP. 
Different approaches to handling missing data may be conducted. Details will be specified in 
SAP. 
9.4.3. 
Secondary Endpoint(s)/Estimand(s) Analysis  
The first key secondary endpoint is the proportion of participants with CDC-defined ILI with 
Confirmed Influenza A. The second key secondary endpoint is the proportion of participants 
with WHO-defined ILI with Confirmed Influenza A. The key secondary estimands are defined 
similarly to the primary estimand. The analyses of the first and second key secondary endpoints 
will be similar to the analysis of the primary endpoint. The adjusted relative risk reductions and 
the corresponding 95% CIs will be calculated for the treatment comparisons of VIR-2482 
1200 mg vs placebo and VIR-2482 450 mg vs placebo.  
The primary analyses for the key secondary endpoints will also be conducted using treatment 
policy strategy for intercurrent events other than death. All observed data collected after the 
intercurrent events other than death will be used in the analyses. Supplemental analyses for the 
key secondary endpoints will also be based on responses prior to the intercurrent events by 
handling intercurrent events using ‘while on treatment’ strategy. 
9.4.4. 
Exploratory Endpoint(s) Analysis  
Serum and NPS PK parameters of VIR-2482 will be computed using standard noncompartmental 
methods. Parameters include, but are not limited to: Cmax, Clast, Tmax, Tlast, AUCinf, AUClast, 
%AUCexp, t1/2, λz, Vz/F, and CL/F. PK parameters will be listed by participant and summarized 
using descriptive statistics. 
VIR-2482 serum and NPS concentration data may be pooled with data from other studies and 
used for estimation of population PK parameters. 
PK/PD analyses will be conducted to explore the relationship between VIR-2482 exposure and 
response variables including incidence of Influenza A. These analyses may include graphical 
plots, tabular summaries, and linear and/or nonlinear analyses. These analyses will be 
exploratory in nature and will be described further in the PK/PD SAP. 

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The analysis set for immunogenicity will be the Immunogenicity Analysis Set. Immunogenicity 
testing results will be listed for each study participant. Immunogenicity data summaries will 
include the incidence of samples screened positive for ADA, incidence of samples confirmed 
positive for ADA, and summaries of ADA titers and NAb, if applicable.  
Exploratory analyses may be conducted to establish correlations between immunogenicity results 
and safety, efficacy, or PK. These analyses may include graphical plots, tabular summaries, and 
linear or nonlinear analyses. Details of immunogenicity analyses will be provided in the SAP 
9.4.5. 
Other Analyses  
Other analyses, if any, will be provided in the SAP as appropriate. 
9.5. 
Interim Analysis  
No Interim Analysis (IA) will be conducted. Participants will be enrolled until a prespecified 
number is reached. 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS  
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
10.1.1. 
Regulatory and Ethical Considerations  
• This study will be conducted in accordance with the protocol and with the following: 
− Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
− Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
guidelines 
− Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.  
• Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
− Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical 
studies (if applicable), and all other applicable local regulations 
10.1.2. 
Financial Disclosure  
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 

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10.1.3. 
Informed Consent Process  
• The investigator or his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant [or their legally authorized representative] and answer all 
questions regarding the study. 
• Participants must be informed that their participation is voluntary. Participants [or their 
legally authorized representatives] will be required to sign a statement of informed consent 
that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and 
data protection requirements, where applicable, and the IRB/IEC or study center. 
• The participant’s medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
When applicable, participants must be reconsented to the most current version of the ICF(s) 
during their participation in the study. 
• A copy of the ICF(s) must be provided to the participant [or their legally authorized 
representative]. 
A participant who is rescreened is not required to sign another ICF if the rescreening occurs 
within the current 28 days screening period. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples 
for optional exploratory research. The investigator or authorized designee will explain to each 
participant the objectives of the exploratory research. Participants will be told that they are free 
to refuse to participate and may withdraw their consent at any time and for any reason during the 
storage period. A separate signature will be required to document a participant’s agreement to 
allow any remaining specimens to be used for exploratory research. Participants who decline to 
participate in this optional research will not provide this separate signature. 
10.1.4. 
Data Protection  
• Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are transferred to the sponsor will be anonymized except for the identifier; 
participant names or any information which would make the participant identifiable will not 
be transferred. 
• All participants must provide informed consent to the use and disclosure of their information 
obtained during the study. This includes informing the participant how his/her personal 
study-related data will be used by the sponsor, and the level of disclosure.  
• The participant must also be informed and consent to the possible examination of his/her 
medical records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/IEC members, and by inspectors 
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10.1.5. 
Committees Structure  
Independent Data Monitoring Committee 
An unblinded DMC will review safety data including cumulative safety data from on an ongoing 
basis throughout the study as appropriate. The roles and responsibilities of the DMC, including 
membership, scope, frequency of meetings and communication plan are defined in the DMC 
charter. 
The first formal DMC meeting to review safety data will occur after the first 10 participants 
present with protocol-defined ILI with confirmed influenza A or approximately 2 weeks after the 
last seasonal study participant is enrolled, whichever occurs first. 
An independent statistician will monitor the incidence of protocol defined influenza A illness 
cases and inform the DMC of any statistically significant imbalance. Enrollment will be 
concluded after EOIS1 if there are at least 36 participants across all 3 treatment arms who meet 
the primary endpoint definition for protocol-defined ILI with confirmed influenza A. Details will 
be described in the DMC charter. 
10.1.6. 
Data Quality Assurance  
• All participant data relating to the study will be recorded on printed or eCRFs unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
• Guidance on completion of CRFs will be provided in the data entry guidelines. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
• Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, remote, or on-site monitoring) are provided in the monitoring plan. 
• The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data. 
• The sponsor assumes accountability for actions delegated to other individuals (eg, CROs). 
• Records and documents, including signed ICFs, pertaining to the conduct of this study must 
be retained by the investigator for 25 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. 

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10.1.7. 
Source Documents  
• Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
• Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.  
• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
• Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
10.1.8. 
Electronic Case Report Forms (eCRFs)  
• Data collected during the study will be recorded in each participant’s eCRF provided by the 
sponsor or designee.  
• The study site(s) will use an electronic data capture (EDC) system that is compliant with 
Food and Drug Administration (FDA) regulatory requirements per 21 CFR Part 11.  
• Data queries and data correction on the eCRF will be handled through EDC.  
• All transactions within the EDC system are fully documented within an electronic audit trail.  
• Data reported on the CRF must be transcribed from a source document with consistency and 
accuracy.  
• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.  
• Study monitors will perform ongoing source data verification to confirm the accuracy of data 
entered into the eCRF. Each set of completed eCRFs must be reviewed after being source 
verified by the monitor and electronically signed and dated by the investigator. 
10.1.9. 
Study and Site Start and Closure  
10.1.9.1. First Act of Recruitment  
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the date of first site open and will be the study start date. 

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10.1.9.2. Study/Site Termination  
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
For study termination: 
• Discontinuation of further study intervention development 
For site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the sponsor’s procedures, or GCP guidelines 
• Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants by 
the investigator 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
10.1.10. 
Dissemination of Clinical Study Data  
• Where required by applicable law, an investigator signatory will be identified for the 
approval of the CSR. The investigator will be provided reasonable access to appropriate 
study information and results. 
• Sponsor or designee will provide all investigators who enrolled participants into the study 
with a summary of the study results  
• Sponsor or its designee will provide the investigator with the randomization codes for their 
site only after completion of the full statistical analysis 
• The procedures and timing for public disclosure of study results summary will be in 
accordance with applicable laws.  
10.1.11. 
Publication Policy  
• Site-specific results of this study may be published or presented at scientific meetings subject 
to the terms and requirements of the clinical study agreement 

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10.2. 
Appendix  Clinical Laboratory Tests  
• The tests detailed in Table 6 will be performed by the central laboratory. 
Local laboratory results are only required in the event that the central laboratory results are not 
available in time for either study intervention administration and/or response evaluation. If a 
local sample is required, it is important that the sample for central analysis is obtained at the 
same time. Additionally, if the local laboratory results are used to make either a study 
intervention decision or response evaluation, the results must be recorded. 
• Additional tests may be performed at any time during the study as determined necessary by 
the investigator or required by local regulations. 
Table 6: 
Protocol-Required Safety Laboratory Tests 
Chemistry 
Hematology 
Albumin 
Blood urea nitrogen (BUN) 
Calcium 
Bicarbonate 
Chloride 
Creatinine 
Gammaglutamyltransferase 
Glucose (non-fasting) 
Lactate dehydrogenase (LDH) 
Potassium 
Protein (total) 
Sodium 
Liver Function Tests: Alkaline phosphatase 
(ALP), alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), bilirubin (total and 
direct) 
Platelet count 
Red blood cell (RBC) count 
Hemoglobin 
Hematocrit 
White blood cell (WBC) count with 
differential: neutrophils, lymphocytes, monocytes, 
eosinophils, basophils 
RBC indices: mean corpuscular volume (MCV), 
mean corpuscular hemoglobin (MCH), 
%reticulocytes 
Coagulation Parameters 
Pregnancy Testing 
D-dimer  
International normalized ratio (INR) time 
Partial thromboplastin time (PTT)/activated PTT 
(aPTT) 
Prothrombin time (PT) 
Highly sensitive (serum/plasma or urine) human 
chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential) 
 
Urinalysis 
Other Tests 
Specific gravity 
Glucose, pH, protein, blood, ketones, [bilirubin, 
urobilinogen, nitrite, leukocyte esterase] by 
dipstick 
Microscopic examination (if blood or protein is 
abnormal) 
All scheduled laboratory tests should be 
performed by a central laboratory, with the 
exception of those outlined in the protocol: 
Respiratory Viral Panel RT-PCR  
Highly sensitive urine human chorionic 
gonadotropin (hCG) pregnancy test may be 
performed locally  
Investigators must document their review of each laboratory safety report. 

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10.3. 
Appendix 2: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting AEs, SAEs, SSRs, AESIs  
10.3.1. 
Definition of AE  
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, temporally associated 
with the use of study intervention, whether or not considered related to the study intervention. 
• 
AEs may also include pre- or post-treatment complications that occur as a result of 
protocol-specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of study intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results or other safety assessments (eg, ECG, radiological scans, vital 
signs measurements) that require medical or surgical intervention or lead to study intervention 
interruption, modification, discontinuation, or are considered clinically significant in the medical 
and scientific judgment of the investigator 
• 
Laboratory or other abnormal assessments (eg, vital signs) that are associated with signs and/or 
symptoms must be recorded as an AE or SAE if they meet the definition of an AE or SAE. If the 
laboratory abnormality is part of a clinical syndrome, record the syndrome or diagnosis 
(eg, anemia), not the laboratory result (ie, decreased hemoglobin). 
• 
Exacerbation of a chronic or intermittent pre-existing condition (recorded as medical history) 
including either an increase in frequency and/or intensity of the condition 
• 
New condition detected or diagnosed after study intervention administration even though it may 
have been present before the start of the study 
• 
Signs, symptoms, or the clinical sequelae of a suspected study intervention interaction, including 
drug/drug, drug/food, drug/device and drug/alcohol interactions 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported as an 
AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if 
they fulfill the definition of an AE or SAE. 
 

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Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments that 
are associated with underlying disease, unless judged by the investigator to be more severe than 
expected for the participant’s condition 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy, transfusion, tooth extraction): the 
condition that leads to the procedure is the AE 
• 
Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital, hospitalization for elective surgery) 
• 
Overdose of study intervention without clinical sequelae 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the screening visit that do not worsen 
10.3.2. 
Definition of SAE  
An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or more of the 
criteria listed: 
Results in death 
Is life threatening 
The term “life threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether hospitalization occurred or was necessary, the AE 
should be considered serious. 
 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
Results in persistent or significant disability/incapacity 
 
The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions 
 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) that may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption 

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An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or more of the 
criteria listed: 
Is a congenital anomaly/birth defect 
Other medically important events 
• 
Medical or scientific judgment should be exercised by the investigator in deciding whether 
SAE reporting is appropriate in other situations such as significant medical events that may 
jeopardize the participant or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition. These events should usually be considered 
serious. 
− 
Examples of such events include invasive or malignant cancers, intensive treatment for 
allergic bronchospasm, blood dyscrasias, convulsions or development of intervention 
dependency or intervention abuse, suspected transmission of any infectious agent via an 
authorized medicinal product 
10.3.3. 
Definitions of Special Situations (SSR)  
Special Situation Report (SSR) Definitions 
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, participant, or consumer. 
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
participant. 
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information. 
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended dose 
as per protocol (as it applies to the daily dose of the participant in question). In cases of a 
discrepancy in drug accountability, overdose will be established only when it is clear that the 
participant has taken the excess dose(s). Overdose cannot be established when the pharmacist 
cannot account for the discrepancy except in cases in which the investigator has reason to suspect 
that the additional dose(s) were administered to the participant. 
Occupational exposure is defined as exposure to a study intervention as a result of one’s 
professional or nonprofessional occupation. 
Drug interaction is defined as any drug/drug, drug/food, or drug/device interaction. 
Unexpected benefit is defined as an unintended therapeutic effect where the results are judged to be 
desirable and beneficial. 
Transmission of infectious agents is defined as any suspected transmission of an infected agent 
through a Vir study intervention. 
Counterfeit or falsified medicine: Any study intervention with a false representation of (a) its 
identity, (b) its source, or (c) its history. 
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product. 
The signs, symptoms, and/or clinical sequelae resulting from a special situation will be reported as 
AE or SAE if they fulfill the definition of an AE or SAE. 

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10.3.4. 
Definition of Adverse Event of Special Interest (AESI)  
AESI Definition  
• 
An AESI is a noteworthy event for the particular product or class of products that the sponsor may 
wish to monitor carefully. It could be serious or non-serious (eg, hair loss, loss of taste, impotence), 
and could include events that might be potential precursors or prodromes for more serious medical 
conditions in susceptible individuals. 
10.3.5. 
Definition of Unsolicited AE and Solicited events   
Unsolicited AE and Solicited events 
• 
An unsolicited AE is an AE that was not solicited during the Local Tolerability Assessment or the 
Study Intervention Diary Card and that is communicated by a participant who has provided 
documented informed consent. 
• 
Solicited events are predefined events for which the participant is specifically questioned, and 
which are reported by the participant only during the Local Tolerability Assessment or the Study 
Intervention Diary Card. 
10.3.6. 
Recording and Follow-Up of AEs, SAEs, SSRs (including Pregnancies), and/or 
AESIs  
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE information into the section of the 
participant’s AE eCRF and the event description section of the SAE form. 
• 
All AEs/SAEs should be followed until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3). 
• 
It is not acceptable for the investigator to send photocopies of the participant’s medical records to 
sponsor in lieu of completion of the required forms. 
• 
There may be instances when copies of medical records for certain cases are requested by the 
Sponsor. In this case, all participant identifiers, with the exception of the participant’s unique study 
ID number, will be redacted on the copies of the medical records before submission to the Sponsor. 
• 
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. 
• 
For fatal or life-threatening events, copies of hospital case reports, discharge summaries, autopsy 
reports, and other documents should be submitted by email or fax when requested and applicable. 
Transmission of such documents should occur without personal participant identification, 
maintaining the traceability of a document to the participant identifiers. 
• 
Additional information may be requested to ensure the timely completion of accurate safety 
reports. 
• 
Any medications necessary for treatment of the AE/SAE must be recorded onto the concomitant 
medication section of the participant’s eCRF and the event description section of the SAE form. 

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AE and SAE Recording 
• 
Clinical endpoints that are specifically defined in the protocol, will be reported as Clinical Events 
and will not be collected as AEs in the CRF. The exception to this reporting requirement is when 
there is evidence suggesting a causal relationship between a drug and an event (eg, death from 
anaphylaxis). In this case, the investigator must immediately report the event to the sponsor. 
 
SSR (including Pregnancy) and AESI 
• 
When an SSR (including pregnancy)/AESI occurs, it is the responsibility of the investigator to 
review all documentation and record the relevant information on the corresponding case report 
form. 
• 
If the SSR/AESI is associated with an AE/SAE, the information will also be recorded as per 
AE/SAE recording procedures. 
 
Assessment of Severity 
The investigator will assess severity for each AE and SAE reported during the study according to the 
standard toxicity grading in the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventative Vaccine Clinical Trials  
Systemic 
Illness 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe (Grade 3)  
Potentially Life 
Threatening (Grade 4) 
Illness or 
clinical 
adverse event 
(as defined 
according to 
applicable 
regulations) 
No 
interference 
with activity 
Some 
interference 
with activity 
not requiring 
medical 
intervention 
Prevents daily 
activity and requires 
medical intervention 
ER visit or 
hospitalization 
Source: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative 
Vaccine Clinical Trials 
• 
For each event, the highest grade attained should be reported. 
 

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Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. The investigator will use clinical judgment to determine the 
relationship. 
• 
A reasonable possibility of a relationship conveys that there are facts, evidence, and/or arguments 
to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study intervention administration, will be 
considered and investigated. 
• 
An answer of Yes should be entered when, in the investigator’s opinion, there is a reasonable 
possibility that the AE is associated with study intervention. Otherwise, relationship to study 
intervention should be categorized as No.  
• 
The investigator will also consult the investigator’s brochure (IB) and/or product information, for 
marketed products, in his/her assessment. 
• 
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. 
• 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to sponsor. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial transmission 
of the SAE data to sponsor. 
• 
The investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AEs, SAEs, SSRs (including Pregnancies), AESIs 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested to elucidate the nature and/or causality of 
the AE or SAE as fully as possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. 
• 
New or updated information will be recorded in the originally submitted documents. 
• 
The investigator will submit any updated SAE data to sponsor within 24 hours of receipt of the 
information. 
 

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10.3.7. 
Reporting of SAEs and SSRs (Including Pregnancies)  
Safety (SAE, SSR, Pregnancy) Reporting via Paper Data Collection Tool 
• 
Email or Facsimile transmission of the SAE/SSR paper data collection tool is the preferred method 
to transmit this information to the sponsor pharmacovigilance vendor. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE/SSR data collection tool sent by overnight mail or courier 
services. 
• 
Initial notification via telephone does not replace the need for the investigator to complete and sign 
the SAE/SSR data collection tool within the designated reporting time frames.  
• 
The investigator is responsible for assessing SAE/SSR for causality and severity, and for final 
review and confirmation of accuracy of event information and assessments on the reporting forms. 
• 
Contacts for SAE/SSR reporting will be included in the Study Specific Reporting Guidelines. 
 

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10.4. 
Appendix 3: List of Abbreviations and Definitions of Terms  
ADA 
anti-drug antibodies 
ADE 
antibody-dependent enhancement 
ADL 
activities of daily living 
AE 
adverse events 
AESI 
adverse event of special interest 
ANOVA 
analysis of variance 
BMI 
body mass index 
CIOMS 
Council for International Organizations of Medical Sciences 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
case report form 
CRO 
contract research organization 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DNA 
deoxyribonucleic acid 
DRE 
disease-related events 
DSUR 
Development Safety Update Report 
ECI 
event of clinical interest 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOIS 
End of Influenza Season 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FSH 
follicle stimulating hormone  
GCP 
Good Clinical Practice 
HA 
hemagglutinin 
IA 
interim analyses 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
DMC 
data monitoring committee 
IEC 
independent ethics committees 

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ILI 
influenza-like illness 
IM 
intramuscular 
INR 
international normalized ratio 
IRB 
institutional review boards 
IRR 
injection-related reactions 
IRT 
Interactive Response Technology 
HRT 
hormonal replacement therapy 
LSM 
least-square means 
MCV 
mean corpuscular volume 
NAb 
neutralizing antibody 
NPS 
nasopharyngeal sample 
PD 
pharmacodynamic 
PK 
pharmacokinetic 
PRO 
patient reported outcome 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QTL 
quality tolerance limits 
RBC 
red blood cell 
RNA 
ribonucleic acid 
RSI 
Reference Safety Information 
RT-PCR 
reverse transcription-polymerase chain reaction 
SAE 
serious adverse events 
SAP 
Statistical Analysis Plan 
SOIS 
Start of Influenza Season 
SSR 
Special Situation Report 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TE 
treatment-emergent 
TEAE 
treatment-emergent adverse event 
WBC 
white blood cell 
WOCBP 
women of childbearing potential 
WONCBP 
Women of non-childbearing potential 
WPAI 
Work Productivity and Activity Impairment 

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10.5. 
Appendix 4: Summary of Changes for Previous Protocol Amendments  
Protocol Amendment 3 (22 September 2022) Summary of Changes  
Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of Activities 
4.1 Overall Study Design 
8.5 Influenza-Like Illness 
Surveillance 
Addition of active ILI symptom surveillance from 
Week 52 to 84 
To enhance detection of ILI cases due to influenza, 
enable viral testing and PK sampling, and assess 
illness severity during the following influenza 
season   
1.3 Table 1. Schedule of Activities 
4.1 Overall Study Design 
8.3.6 Study Intervention Diary Card 
8.4.6 Unsolicited and Solicited 
Adverse Events 
10.3.5 Definition of Unsolicited and 
Solicited AEs 
Addition of Study Intervention Diary Card 
To incorporate collection of patient-reported local 
and systemic reactions from D1-D7 for added 
safety monitoring 
1.3 Table 2. Schedule of Activities 
ILI symptom surveillance in the ILI Monitoring 
Schedule 
To clarify that participants will report ILI 
symptoms on the electronic device from ILI-D1 to 
ILI-D10 
2.3 Benefit/Risk Assessment 
Addition of safety data summary from Phase 1 
VIR-2482-3001 study  
Additional safety data available for VIR-2482  

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Section # and Name 
Description of Change 
Brief Rationale 
3 Objectives, Endpoints, and 
Estimands 
Revised primary safety endpoint to include the 
occurrence of solicited events  
To clarify that solicited events will also be 
summarized in the summary of safety data 
Revised exploratory endpoint to include both 
symptomatic and asymptomatic seroconversion as 
part of the exploratory endpoint 
To clarify that asymptomatic seroconversion will 
be accounted for in exploratory analyses 
Revised exploratory endpoint to include influenza 
B in monitoring the occurrence of non-influenza A 
respiratory viral infections 
To clarify influenza B virus will be accounted for 
in exploratory analyses 
4.3 Justification of Dose 
Additional dose justification 
To provide additional detailed rationale for the 
dose selection 
8.4.4 Adverse Events of Special 
Interest 
Removal of Injection Site Reactions from AESI 
Injection site reactions will not need to be reported 
as AESIs based on tolerability data from 
VIR-2482-3001 study. 
8.4.5 Clinical Laboratory 
Abnormalities and Other Abnormal 
Assessments as AEs or SAEs 
10.3.6 Recording and Follow-Up of 
AEs, SAEs, SSRs (including 
Pregnancies), and/or AESIs 
Replaced Common Terminology Criteria for 
Adverse Events (CTCAE) grading scale with the 
Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventative 
Vaccine Trials. 
To use a grading scale that is appropriate for the 
trial population, as recommended by the FDA 
8.4.6 Unsolicited Adverse Events 
8.4.7 Solicited Events 
Definition of unsolicited and solicited events  
To provide additional clarity on the definition of 
unsolicited adverse events and solicited events  
8.5 Influenza-Like Illness 
Surveillance 
Participants will be educated on the ILI symptoms, 
how to reach the study site, and provided with 
contact information for the study site  
To clarify study participant education 
 

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Protocol Amendment 2 (19 August 2022) Summary of Changes  
Section # and Name 
Description of Change 
Brief Rationale 
1.3. Schedule of Activities, Table 1 
2.3.1. Risk Assessment 
4.1. Overall Study Design 
8.3.5. Local Tolerability 
Post-dose monitoring time 
Post-injection monitoring time has been extended to a minimum 
of 2 hours for thorough safety and tolerability monitoring. 
1.3. Schedule of Activities 
Table 2  
8.5.1. ILI monitoring and Influenza 
Confirmation Visit 
10.2. Appendix 2: Clinical 
Laboratory Tests, Table 5 
Influenza Confirmation Visit and 
Influenza A RT-PCR Confirmatory 
Testing 
Clarification of ILI evaluations, including using point-of-care as 
well as confirmatory central laboratory respiratory virus testing 
will be performed at the Influenza Confirmation Visit to 
facilitate rapid diagnosis and for endpoint determination. 
1.3. Schedule of Activities, Table 1 
8.6. Pharmacokinetics 
Addition of nasopharyngeal PK 
sampling 
Nasopharyngeal sampling at the EOIS visit, the ILI 
confirmation visit, and an optional sub-study for additional 
nasopharyngeal sampling are added to assess the concentration 
of VIR-2482 in nasal secretions. 
1.3. Schedule of Activities, Table 1 
Decrease frequency of ILI symptom 
monitoring, AE review, 
concomitant medication, physical 
examination, and vital signs  
To streamline SoA and minimize participant burden. 
3. Objectives, Endpoints, and 
Estimands 
8.5.3. Virology and Resistance 
Surveillance 
8.9. Biomarkers 
Addition of exploratory objectives 
Additional exploratory objectives added to further characterize 
asymptomatic infection, viral subtypes and dynamics, as well as 
nasopharyngeal PK to inform pharmacodynamics and 
pharmacokinetics. 
5.2. Exclusion Criteria 
Exclusion criteria # 9 update  
To specify that participants who received any investigational 
agent within 90 days or within 5 half-lives of the investigational 
agent, whichever is longer, before study intervention 
administration will not be eligible. 

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Section # and Name 
Description of Change 
Brief Rationale 
7.4. Participant Replacement 
Removal of participant replacement  Subjects will not be replaced if they withdraw during the study 
for non-safety reasons. 
9.4.2. Primary 
Endpoint(s)/Estimand(s) Analysis 
Primary efficacy analyses   
Treatment effect will be based on the treatment policy estimand, 
which considers the actual measurements of subjects regardless 
of adherence and rescue status. The “while on treatment” 
strategy will be considered for sensitivity analyses. 
9.5. Interim Analyses 
Interim analysis  
No formal interim analysis will be conducted. Participants will 
be enrolled until a prespecified number is reached. 
10.6. Appendix 6: Influenza A 
Illness Definitions 
Protocol-defined ILI with 
confirmed influenza A 
Updated criteria based on review of influenza case definitions 
and performance characteristics. 
 

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Protocol Amendment 1 (11 July 2022) Summary of Changes 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3 (Schedule of 
Activities, Table 1) 
Added monthly influenza-like illness (ILI) 
monitoring from post-end of influenza 
season (EOIS) to Week 48 
To align the schedule for ILI monitoring following the 
EIOS visit with Section 4.1 (Overall Study Design). 
Specified that Week 52 physical 
examinations will be symptom-directed 
To clarify the type of physical examination that will be 
performed at Week 52 
Section 1.3 (Schedule of 
Activities, Table 2) 
Section 8.5.1 (ILI Monitoring and 
Influenza Confirmation Visit) 
Section 10.2 (Appendix 2: Clinical 
Laboratory Tests, Table 5) 
Modified influenza A confirmation test to 
respiratory viral panel for influenza A 
reverse transcription-polymerase chain 
reaction (RT-PCR) confirmation 
To clarify the type of test that will be used for influenza 
confirmation 
Section 1.3 (Schedule of 
Activities, Table 2) 
Section 3 (Objectives, Endpoints, 
and Estimands) 
Section 8.5.1 (ILI Monitoring and 
Influenza Confirmation Visit) 
Section 8.5.2 (Influenza Intensity 
and Impact 
Questionnaire) - section retitled 
Modified influenza intensity and impact 
questionnaire to Flu-iiQTM (previously Flu-
PRO) 
Changed Flu-PRO to Flu-iiQTM which captures more 
frequent assessments, and is more compliant, shorter, and 
less burdensome for participants.  
Section 8.4.4 (Adverse Events of 
Special Interest) 
Modified injection-related reactions to 
injection site reactions and hypersensitivity 
reactions into separate bullets under the list 
of adverse events of special interest (AESI) 
To provide correct terminology and clarify injection site 
reactions and hypersensitivity reactions can be separate 
types of AESI 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3 (Schedule of 
Activities, Table 1) 
Section 5.2 (Exclusion Criteria) 
Section 10.2 (Appendix 2: Clinical 
Laboratory Tests, Table 5) 
Deleted the drug screen for cocaine, 
amphetamines, or opioids 
Sponsor decided not necessary for the target participant 
population 
Section 4.1.1 (Number of 
Participants) 
Corrected the study drug name to state VIR-
2482 in the bullet points (previously stated 
as 2218) 
To clarify the name of the study drug 
 

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10.6. 
Appendix 5: Contraceptive and Barrier Guidance  
10.6.1. 
Definitions  
10.6.1.1. Woman of Non-Childbearing Potential (WONCBP)  
Women in the following categories are considered WONCBP: 
1. Premenopausal female with permanent infertility due to one of the following (for the 
purpose of this study): 
a. Documented hysterectomy 
b. Documented bilateral salpingectomy 
c. Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
2. Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
• A high FSH level in the postmenopausal range may be used to confirm a postmenopausal 
state in women not using hormonal contraception or HRT. However, in the absence of 
12 months of amenorrhea, confirmation with more than one FSH measurement (> 40 IU/L or 
mIU/mL) is required.  
• Females on HRT and whose menopausal status is in doubt must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
10.6.1.2. Woman of Childbearing Potential (WOCBP)  
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
2. From the time of menarche until becoming postmenopausal unless with permanent 
infertility, as defined in Section 10.6.1.1  
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered. 

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10.6.2. 
Contraception Guidance  
Contraceptivesa Allowed During the Study Include: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per year when used 
consistently and correctly 
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationb 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)b 
• 
Bilateral tubal occlusion 
• 
Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole sexual 
partner of the woman of childbearing potential and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used. Spermatogenesis cycle 
is approximately 90 days. 
Note: documentation of azoospermia for a male participant can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history interview) 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
− 
oral 
− 
intravaginal 
− 
transdermal 
− 
injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
− 
oral 
− 
injectable 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the participant. 
Effective Methodsd That Are Not Considered Highly Effective Failure rate of ≥ 1% per year when 
used consistently and correctly 
• 
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary 
mode of action 
• 
Male or female condom with or without spermicidee 
• 
Cervical cap, diaphragm, or sponge with spermicide 
• 
A combination of male condom with either cervical cap, diaphragm, or sponge with spermicide 
(double-barrier methods)c 

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a Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive 
methods for those participating in clinical studies. 
b Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those when 
used consistently and correctly. 
c Male condoms must be used in addition to hormonal contraception. If locally required, in accordance with Clinical 
Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited to those which inhibit 
ovulation as the primary mode of action. 
d Considered effective, but not highly effective - failure rate of ≥1% per year. Periodic abstinence (calendar, 
sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational 
amenorrhea method (LAM) are not acceptable methods of contraception.  
e Male condom and female condom should not be used together (due to risk of failure from friction). 
 

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10.7. 
Appendix 6: Influenza A Illness Definitions  
Protocol definitions of influenza A illness for the primary and secondary study efficacy 
endpoints are as defined below. 
10.7.1. 
Protocol-Defined ILI with Confirmed Influenza A  
RT-PCR confirmed influenza A with: 
• At least one respiratory symptom: sore throat, cough, sputum production, wheezing, or 
difficulty breathing 
AND 
• At least one systemic symptom: temperature> 37.8°C, chills, weakness, or myalgias 
10.7.2. 
CDC-Defined ILI with Confirmed Influenza A  
• Temperature > 37.8°C with sore throat or cough with RT-PCR confirmed influenza A 
10.7.3. 
WHO-Defined ILI with Confirmed Influenza A  
• Temperature > 38°C with cough with RT-PCR confirmed influenza A 

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10.8. 
Appendix 7: Hemispheric Influenza Season Definitions  
End of Influenza Season 1, Start of Influenza Season 2, and End of Influenza Season 2 will be 
defined based on the approximate start and end of flu seasons in a given hemisphere. Given 
recent deviations in influenza seasons from established historical patterns, the hemispheric Start 
and End of Influenza Season dates will be defined by protocol clarification letter based on 
current hemispheric influenza epidemiology. EOIS1 was defined by protocol clarification letter 
as April 17, 2023.  

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10.9. 
Appendix 8: Local Tolerability Assessment  
Injection Time: 
 
 
Time Assessment Performed:  
 
Injection Site:  
Injection Location (check ONE): ☐LEFT 
☐RIGHT ☐N/A 
Local Reaction 
to Injectable 
Product 
Absent 
(Grade 0) 
Mild (Grade 1) Moderate (Grade 2) Severe (Grade 3) Potentially Life 
Threatening 
(Grade 4)* 
Pain  
Absent 
Does not 
interfere with 
activity 
Repeated use of non-
narcotic pain reliever 
> 24 hr or interferes 
with activity 
Any use of narcotic 
pain reliever or 
prevents daily 
activity 
ED visit or 
hospitalization 
Swelling 
Absent 
Mild discomfort 
to touch 
Discomfort with 
movement but 
minimal interference 
with daily activity 
Significant 
discomfort at rest 
OR prevents daily 
activity 
ED visit or 
hospitalization 
Erythema 
(Length) cm 
Absent 
2.5 to 5.0 cm 
 
cm 
5.1 to 10.0 cm 
 
cm 
☐ > 10.0 cm 
 
cm 
Necrosis or 
exfoliative 
dermatitis 
Bruising 
Absent 
2.5 to 5.0 cm 
 
cm 
5.1 to 10.0 cm 
 
cm 
> 10.0 cm 
 
cm 
ED visit or 
hospitalization 
Pruritis 
Absent 
Itching 
localized to 
injection 
site 
Itching beyond 
the injection site 
that is not 
generalized OR 
local itching 
>48hrs despite 
treatment 
Generalized 
itching that 
prevents daily 
activity 
ED visit or 
hospitalization 
 
First Initial & Surname (print) 
 
/ 
/ 
 
Signature 
Date 
* Grade 4 assessments must be documented as an AE or SAE. 

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10.10. 
Appendix 9: Management of Injection-Related Reactions Including 
Systemic Symptoms (Anaphylaxis)  
All participants should be monitored closely, as there is a risk of injection reaction and 
hypersensitivity with any biological agent. Pre-medications will be permitted at the investigator’s 
discretion and will be appropriately documented. 
Local Injection Site Reactions  
Signs and Symptoms 
Management 
Redness, soreness or swelling 
at the injection site 
Apply a cold compress to the injections site 
Consider giving an analgesic (eg, ibuprofen, acetaminophen 
paracetamol) 
Itching and redness 
Consider giving an antipruritic (eg, diphenhydramine) 
Observe patient closely for the development of generalized symptoms 
Slight bleeding 
Apply pressure and an adhesive compress 
Continuous bleeding 
Place gauze pads over the site and maintain direct and firm pressure 
Source: adapted from IAC 2019 
If a participant has evidence of necrosis/ulceration, the participant should be referred to a higher 
level of acute care (eg, hospital emergency room) for appropriate management. 
Systemic Reactions/Anaphylaxis  
As with any antibody, allergic reactions to study intervention are possible. Therefore, appropriate 
drugs and medical equipment to treat acute anaphylactic reactions must be immediately 
available, and study personnel must be trained to recognize and treat anaphylaxis (IAC 2019; 
ACIP 2022; Sampson 2006). 
Diagnosis of Anaphylaxis  
The most common signs and symptoms of anaphylaxis are cutaneous (eg, sudden onset of 
generalized urticaria, angioedema, flushing, pruritis). However, 10-20% of patients have no skin 
findings. 

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Danger Signs Include:  
• Rapid progression of symptoms 
• Evidence of respiratory distress (stridor, wheezing, dyspnea, increased work of breathing, 
persistent cough, cyanosis) 
• Vomiting 
• Abdominal pain 
• Hypotension 
• Dysrhythmia 
• Chest pain 
• Collapse 
Management of Anaphylaxis  
The following procedures should be followed in the event of a suspected anaphylactic reaction: 
1. Do not give additional doses of investigational product 
2. Call for additional medical assistance; activate emergency medical services 
3. Ensure appropriate monitoring is in place, such as continuous ECG and pulse oximetry 
4. First-line treatment: 
a. Administer epinephrine (1.0 mg/ml) aqueous solution (1:1000 dilution) – 0.5 mg 
(0.5ml) IM in the anterolateral thigh 
b. If using an epinephrine auto-injector – use 0.3 mg IM into the anterolateral thigh 
c. May be repeated every 5-15 minutes up to 3 times 
5. Optional treatment (antihistamine): 
a. Diphenhydramine 50 mg oral/IV/IM OR 
b. Hydroxyzine 25 mg oral/IM 
6. Give oxygen (8-10 L/minute) via facemask, as needed 
7. Normal saline rapid bolus – treat hypotension with rapid infusion of 1-2 liters IV 
8. Monitor patient until emergency medical services arrive. 

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11. 
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