A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Mono and Combination Therapy With Monoclonal Antibodies in Participants With Mild to Moderate COVID-19 Illness (BLAZE-4)
Phase: PHASE2
Conditions: COVID-19
Sponsor: Eli Lilly and Company

Protocol: J2X-MC-PYAH 
 
A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and 
Safety of Mono and Combination Therapy with Monoclonal Antibodies in Participants with Mild 
to Moderate COVID-19 Illness (BLAZE-4) 
NCT04634409 
Approval Date: 18-May-2021 

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Protocol J2X-MC-PYAH(g)
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Title Page
Confidential Information
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of LY3819253, LY3832479, LY3853113, and VIR-7831 unless such persons are bound by a confidentiality agreement 
with Eli Lilly and Company or its subsidiaries. 
Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential information 
exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any public release. 
In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be reproduced or 
otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries.
Protocol Title:
A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and
Safety of Mono and Combination Therapy with Monoclonal Antibodies in Participants with Mild 
to Moderate COVID-19 Illness (BLAZE-4)
Protocol Number: J2X-MC-PYAH
Amendment Number: g
Compound(s): LY3819253, LY3832479, LY3853113, VIR-7831
Study Phase: 2
Short Title: A randomized, double-blind, placebo-controlled, Phase 2 study to evaluate 
combinations of monoclonal antibodies in participants with mild to moderate 
COVID-19 illness
Sponsor Name: Eli Lilly and Company
Legal Registered Address: Indianapolis, Indiana, USA 46285
Regulatory Agency Identifier Number(s)
IND: 150440
Approval Date: Protocol Amendment (g) Electronically Signed and Approved by Lilly on date 
provided below.
Approval Date: 18-May-2021 GMT

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Protocol J2X-MC-PYAH(g)
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Medical Monitor Name and Contact Information will be provided separately 

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Protocol J2X-MC-PYAH(g)
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Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Amendment f
16 Mar 2021
Amendment e
25 Jan 2021
Amendment d
15 Jan 2021
Amendment c
06 Jan 2021
Amendment b
03 Dec 2020
Amendment a
16 Oct 2020
Original Protocol
5 Oct 2020
Amendment g
Overall Rationale for the Amendment:
The purpose of this amendment is to incorporate a new treatment arm into the study design. 
Additionally, minor clarifications and edits were made for operational efficiency and 
consistency.
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis; 1.2 Schema; 1.3 Schedule of 
Activities; 3.4 Treatment Arms 12-14; 4.1 
Overall Design; 4.2 Scientific Rationale for 
Study Design; 4.3 Justification for Dose;
6.1 Study Intervention(s) Administered; 6.3 
Measure to Minimize Bias: Randomization 
and Blinding; 9.2 Sample Size 
Determination; 9.4 Statistical Analyses; 
9.4.2 Primary Endpoints
Added treatment arm 14 to 
study design
Allowance of additional high-
risk participants in triplet 
combination cohort
2.2 Background
Updated LY3853113 
pseudovirus assay information
Alignment with Investigator’s 
Brochure
5.1 Inclusion Criteria
Specified that criteria 27 and 28 
are applicable to treatment arms 
12 and 13 only
Differentiation of high-risk 
participants applicable for 
treatment arms 12 and 13 and 
treatment arm 14
5.1 Inclusion Criteria
Added new inclusion criterion 
30 for treatment arm 14
Differentiation of high-risk 
participants applicable for 
treatment arms 12 and 13 and 
treatment arm 14
5.2 Exclusion Criteria
Specified in exclusion criterion 
22 that participation in previous 
SARS-CoV-2 vaccine study is 
excluded if participant has 
received a SARS-CoV-2 
vaccine or is currently blinded 
to treatment allotment
Clarification

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Protocol J2X-MC-PYAH(g)
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Section # and Name
Description of Change
Brief Rationale
6.1 Study Intervention(s) Administered;
8.2.2 Vital Signs
Removed instructions for 
multiple administrations in 
treatment arms 9-14
Arms 9-14 will not utilize 
multiple administrations
Throughout
Minor editorial and formatting 
changes
Minor, therefore not detailed

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Protocol J2X-MC-PYAH(g)
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Table of Contents
1.
Protocol Summary......................................................................................................8
Synopsis.......................................................................................................................8
Schema.......................................................................................................................17
Schedule of Activities (SoA) ......................................................................................18
1.3.1.
Treatment Arms 1-6....................................................................................................18
1.3.2.
Treatment arms 7-8.....................................................................................................27
1.3.3.
Treatment Arms 9-14..................................................................................................37
2.
Introduction..............................................................................................................45
Study Rationale ..........................................................................................................45
Background ................................................................................................................45
Benefit/Risk Assessment ............................................................................................48
3.
Objectives and Endpoints.........................................................................................50
Treatment Arms 1-6....................................................................................................50
Treatment Arms 7-8....................................................................................................51
Treatment Arms 9-11..................................................................................................53
Treatment Arms 12-14................................................................................................54
4.
Study Design .............................................................................................................56
Overall Design............................................................................................................56
4.1.1.
Design Outline............................................................................................................56
Scientific Rationale for Study Design .........................................................................58
Justification for Dose..................................................................................................59
End of Study Definition..............................................................................................60
5.
Study Population ......................................................................................................61
Inclusion Criteria........................................................................................................61
Exclusion Criteria.......................................................................................................63
Lifestyle Considerations .............................................................................................64
Screen Failures ...........................................................................................................64
6.
Study Intervention....................................................................................................65
Study Intervention(s) Administered ............................................................................65
6.1.1.
Special Treatment Considerations...............................................................................67
6.1.2.
Temporary Stopping Criteria ......................................................................................68
Preparation/Handling/Storage/Accountability .............................................................69
Measures to Minimize Bias: Randomization and Blinding ..........................................69
Study Intervention Compliance...................................................................................71
Concomitant Therapy .................................................................................................71
Dose Modification......................................................................................................72
Intervention after the End of the Study........................................................................72
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................73
Discontinuation of Study Intervention ........................................................................73
Participant Discontinuation/Withdrawal from the Study .............................................73
7.2.1.
Discontinuation of Inadvertently Enrolled Participants ...............................................73

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Lost to Follow up .......................................................................................................74
8.
Study Assessments and Procedures .........................................................................75
Efficacy Assessments .................................................................................................75
8.1.1.
Symptoms and Overall Clinical Status Participant Questionnaire ................................75
Safety Assessments ....................................................................................................76
8.2.1.
Physical Examinations................................................................................................76
8.2.2.
Vital Signs..................................................................................................................76
8.2.3.
Clinical Laboratory Assessments ................................................................................77
8.2.4.
Hospitalization events.................................................................................................78
8.2.5.
Procedures of Special Interest.....................................................................................78
8.2.6.
Respiratory Support....................................................................................................79
Adverse Events and Serious Adverse Events ..............................................................79
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information.................................................................................................................79
8.3.2.
Method of Detecting AEs and SAEs ...........................................................................80
8.3.3.
Follow-up of AEs and SAEs.......................................................................................80
8.3.4.
Regulatory Reporting Requirements for SAEs ............................................................80
8.3.5.
Pregnancy...................................................................................................................80
8.3.6.
Hypersensitivity Reactions .........................................................................................80
8.3.7.
Infusion-related Reactions ..........................................................................................81
8.3.8.
Product Complaints ....................................................................................................81
Treatment of Overdose ...............................................................................................82
Pharmacokinetics........................................................................................................82
8.5.1.
Bioanalytical ..............................................................................................................83
Pharmacodynamics.....................................................................................................83
Genetics .....................................................................................................................83
Biomarkers.................................................................................................................83
Immunogenicity Assessments.....................................................................................84
Health Economics.......................................................................................................84
9.
Statistical Considerations.........................................................................................85
Statistical Hypotheses.................................................................................................85
Sample Size Determination.........................................................................................85
Populations for Analyses ............................................................................................87
Statistical Analyses.....................................................................................................87
9.4.1.
General Considerations...............................................................................................88
9.4.2.
Primary Endpoints......................................................................................................88
9.4.3.
Secondary Endpoints ..................................................................................................88
9.4.4.
Exploratory Analyses..................................................................................................90
9.4.5.
Immunogenicity Analyses...........................................................................................90
9.4.6.
Subgroup Analyses.....................................................................................................91
Interim Analyses.........................................................................................................91
Data Monitoring Committee (DMC)...........................................................................93
10.
Supporting Documentation and Operational Considerations ................................94
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................................94

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10.1.1.
Regulatory and Ethical Considerations........................................................................94
10.1.2.
Financial Disclosure ...................................................................................................94
10.1.3.
Informed Consent Process ..........................................................................................95
10.1.4.
Data Protection...........................................................................................................95
10.1.5.
Committees Structure .................................................................................................96
10.1.6.
Dissemination of Clinical Study Data .........................................................................96
10.1.7.
Data Quality Assurance ..............................................................................................96
10.1.8.
Source Documents......................................................................................................97
10.1.9.
Study and Site Start and Closure.................................................................................98
10.1.10. Publication Policy.......................................................................................................98
10.1.11. Investigator Information .............................................................................................98
10.1.12. Long-Term Sample Retention.....................................................................................99
Appendix 2: Clinical Laboratory Tests......................................................................100
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting.....................................................103
10.3.1.
Definition of AE.......................................................................................................103
10.3.2.
Definition of SAE.....................................................................................................104
10.3.3.
Recording and Follow-Up of AE and/or SAE ...........................................................105
10.3.4.
Reporting of SAEs....................................................................................................107
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information .............................................................................................108
Appendix 5: Genetics ...............................................................................................111
Appendix 6: Recommended Laboratory Testing for 
Hypersensitivity Events. ...........................................................................................112
Appendix 7: Liver Safety: Suggested Actions and Follow-up 
Assessments .............................................................................................................114
Appendix 8: Abbreviations .......................................................................................118
Appendix 9: Protocol Amendment History ...............................................................120
11.
References...............................................................................................................126

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Protocol J2X-MC-PYAH(g)
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1.
Protocol Summary
Synopsis
Protocol Title:
A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and 
Safety of Mono and Combination Therapy with Monoclonal Antibodies in Participants with Mild 
to Moderate COVID-19 Illness (BLAZE-4)
Rationale:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the 
pandemic spread of coronavirus disease 2019 (COVID-19), which in critical cases results in 
progressive pulmonary failure, complications with acute respiratory distress syndrome (ARDS), 
and death. There is an urgent need for effective therapeutics to modify disease outcomes.
LY3819253, LY3832479, and LY3853113 are neutralizing IgG1 monoclonal antibodies (mAb) 
to the spike protein of SARS-CoV-2. They are designed to block viral attachment and entry into 
human cells, and to neutralize the virus, potentially treating even established COVID-19 by 
providing a combination of specific, potent, neutralizing antibodies to SARS-CoV-2. 
VIR-7831 is a human IgG1 mAb that binds to the spike protein of SARS-CoV-2. It contains 
modifications to enhance both respiratory mucosal distribution and the half-life. An increased 
distribution to mucosal tissue is expected to result in higher and more sustained levels of VIR-
7831 in the respiratory mucosa, which is a potential advantage for treatment and prophylaxis.
The aim of the study is to evaluate the impact of LY3819253 alone, LY3853113 alone,
LY3819253 + LY3832479, LY3853113+ LY3819253 + LY3832479, and LY3819253 + VIR-
7831 on viral clearance and clinical outcomes in participants with COVID-19 illness. 
Additionally, the study aims to characterize the safety profile of LY3853113 alone and in 
combination with LY3819253 and LY3832479 in participants at high risk of developing severe 
COVID-19 illness. The data from this study will inform decisions for the clinical development of 
LY3819253, LY3832479, LY3853113, and VIR-7831. 
Objectives and Endpoints:
Treatment Arms 1-6:
Primary
Characterize the effect of LY3819253 alone and in 
combination with LY3832479, compared to placebo on 
SARS-CoV-2 viral load 

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7 (+2 days)
Secondary
The secondary objectives are to characterize the effect 
of LY3819253 alone and in combination with 
LY3832479, compared to placebo on…

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Protocol J2X-MC-PYAH(g)
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
overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 29
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

SARS-CoV-2 viral load and viral clearance

Change from baseline to 
o
Day 3 (+1 day)
o
Day 5 (±2 days)
o
Day 7 (±2 days)
o
Day 11 (±2 days)

Proportion of participants with viral load greater 
than 5.27 on Day 7 (+2 days) among participants 
enrolled with ≤8 days of symptoms prior to 
randomization 

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 3, 5, 7, 11, and 29)

Time to SARS-CoV-2 clearance 

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 11

symptom resolution

Time to symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days 
3, 5, 7, 11, 22, and 29

Change in symptom score (total of ratings) from 
baseline up to Days 7, 11, 22, and 29. 

AUC from baseline to Day 11

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 3, 5, 7, 11, 22, and 29

safety 

Safety assessments such as AEs and SAEs

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Days 22, 60, and 85
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

characterize clinical status for participants

Proportion (percentage) of participants who 
experience these events through Day 29: 
o
COVID-19 related hospitalization (defined as 
≥24 hours of acute care)
o
COVID-19 related emergency room visit, or
o
death 

characterize the pharmacokinetics of LY3819253 
and LY3832479

Mean concentration of LY3819253 and 
LY3832479 on Day 29
Abbreviations: AE = adverse event; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2. 

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Protocol J2X-MC-PYAH(g)
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Treatment Arms 7-8:
Primary
Characterize the effect of LY3819253 in combination 
with VIR-7831, compared to placebo on SARS-CoV-2 
viral load 

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7 (+2 days)
Secondary
The secondary objectives are to characterize the effect 
of LY3819253 in combination with VIR-7831, 
compared to placebo on…

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 29
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

SARS-CoV-2 viral load and viral clearance

Change from baseline to 
o
Day 3 (+1 day)
o
Day 5 (±2 days)
o
Day 7 (±2 days)
o
Day 11 (±2 days)

Proportion of participants with viral load greater 
than 5.27 on Day 7 (+2 days) among participants 
enrolled with ≤8 days of symptoms prior to 
randomization 

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 3, 5, 7, 11, and 29)

Time to SARS-CoV-2 clearance 

SARS-CoV-2 viral load AUC assessed through 
Day 11

symptom resolution

Time to symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days 
3, 5, 7, 11, 22, and 29

Change in symptom score (total of ratings) from 
baseline up to Days 7, 11, 22, and 29. 

AUC from baseline to Day 11

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 3, 5, 7, 11, 22, and 29

safety 

Safety assessments such as AEs and SAEs

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Days 22, 60, and 85
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

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Protocol J2X-MC-PYAH(g)
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
characterize clinical status for participants

Proportion (percentage) of participants who 
experience these events through Day 29: 
o
COVID-19 related hospitalization (defined as 
≥24 hours of acute care)
o
COVID-19 related emergency room visit, or
o
death 

characterize the pharmacokinetics of LY3819253 
and VIR-7831

Mean concentration of LY3819253 and VIR-7831
on Day 29
Abbreviations: AE = adverse event; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2. 
Treatment Arms 9-11:
Primary
Characterize the effect of LY3853113 alone and in 
combination with LY3819253 and LY3832479 after 
intravenous infusion compared to placebo on SARS-
CoV-2 viral load

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7
Secondary
The secondary objectives are to characterize the effect 
of LY3853113 alone and in combination with 
LY3819253 and LY3832479 after intravenous infusion 
compared to placebo on…

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 29
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

SARS-CoV-2 viral load and viral clearance

75th Percentile of SARS-CoV-2 viral load at Day 7

Change from baseline to 
o
Day 3
o
Day 5
o
Day 7
o
Day 11

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 3, 5, 7, 11, and 29)

Time to SARS-CoV-2 clearance 

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 11

symptom resolution

Time to symptom resolution 

Time to sustained symptom resolution

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days 
2-11, 22, and 29

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Protocol J2X-MC-PYAH(g)
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
symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 2-11, 22, and 29

safety 

Safety assessments such as AEs and SAEs

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 22
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

Characterize clinical status for participants

Proportion (percentage) of participants who 
experience these events through Day 29: 
o
COVID-19 related hospitalization (defined as 
≥24 hours of acute care),
o
COVID-19 related emergency room visit, or
o
death 

Characterize the pharmacokinetics of LY3853113, 
LY3819253, and LY3832479

Mean concentration of LY3853113, LY3819253, 
and LY3832479 on Day 29
Abbreviations: AE = adverse event; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2.
Treatment Arms 12-14:
Primary
Characterize the safety profile of LY3853113 alone 
and in combination with LY3819253 and LY3832479 
after intravenous infusion on SARS-CoV-2 viral load

Safety assessments such as AEs and SAEs
Secondary
The secondary objectives are to characterize the effect 
of LY3853113 alone and in combination with 
LY3819253 and LY3832479 after intravenous infusion 
on…

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 29
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

SARS-CoV-2 viral load and viral clearance

75th Percentile of SARS-CoV-2 viral load at Day 7

Change from baseline to 
o
Day 3
o
Day 5
o
Day 7
o
Day 11

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 3, 5, 7, 11, and 29)

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Protocol J2X-MC-PYAH(g)
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
Time to SARS-CoV-2 clearance 

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 11

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7

symptom resolution

Time to symptom resolution 

Time to sustained symptom resolution

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days 
2-11, 22, and 29

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 2-11, 22, and 29

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 22
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

Characterize clinical status for participants

Proportion (percentage) of participants who 
experience these events through Day 29: 
o
COVID-19 related hospitalization (defined as 
≥24 hours of acute care),
o
COVID-19 related emergency room visit, or
o
death 

Characterize the pharmacokinetics of LY3853113, 
LY3819253, and LY3832479

Mean concentration of LY3853113, LY3819253, 
and LY3832479 on Day 29
Abbreviations: AE = adverse event; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2.
Overall Design:
This is a Phase 2, randomized, single-dose study in participants with mild to moderate COVID-
19 illness. Treatment arms 1-11 are double-blind and placebo controlled, and treatment arms 12-
14 are open label.
Design Outline
Screening
Interested participants will sign the appropriate informed consent and child/adolescent assent 
document(s), as appropriate, prior to completion of any procedures. 
The investigator will review symptoms, risk factors and other non-invasive inclusion and 
exclusion criteria prior to any invasive procedures. If the participant is eligible after this review, 
then the site will perform the invasive procedures to confirm eligibility. 
Double-blind Treatment and Assessment Period
This is the general sequence of events during the treatment and assessment period:

Complete baseline procedures and sample collection

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Protocol J2X-MC-PYAH(g)
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
Participants are randomized to an intervention group 

Participants receive study intervention, and

Complete all safety monitoring and post-treatment sample collection. 
This table describes the visit and activity types for this study.
Study Day
Activity
Visit Type
1 
Follow SoA
Site 
2, 4, 6, and 22
Follow SoA
Telephone visit 
3, 5, 7, 11, 29, ED, 60, and 85
Follow SoA
May be conducted as outpatient 
clinic or home visit. Symptom 
assessments can be collected 
via telephone visit. 
8, 9, 10
Collection of symptom assessments
Telephone visit
Early discontinuation and follow-up
Follow SoA
May be conducted as outpatient 
clinic or home visit
169 (Arms 7 and 8 only)
AE/SAE collection, concomitant 
medications
Telephone visit
Abbreviations: SoA = schedule of activities
If a participant is hospitalized, procedures and assessments will continue per the SoA
(Section 1.3). 
This table describes discharge from hospital scenarios if an outpatient is subsequently 
hospitalized.
Discharge from hospital (Outpatients Subsequently Hospitalized)
If hospital discharge… 
Then…
Occurs prior to Day 29
participants will be asked to complete the remaining 
study assessments at the timepoints indicated in the 
SoA (Section 1.3). 
NOTE: Strategies to manage infection risks and reduce 
the burden of return visits should be used by sites, such 
as home visits.
Occurs on the same day as a study assessment visit
assessments do not need to be repeated if the study 
assessments occurred within 8 hours of discharge and 
there has been no change in clinical status and the 
information is available to the site.
Does not occur at or prior to Day 29
assessments will continue to occur weekly up to Day 
60 or until hospital discharge, whichever is sooner.
Abbreviations: SoA = schedule of activities
Post-treatment follow-up
Post-treatment follow-up assessments will be conducted at Day 60 and Day 85 to assess clinical 
status and for adverse events. Strategies to manage infection risks and reduce the burden of 
return visits may be used by sites, such as home visits. For Arms 7 and 8, an additional telephone 
visit will occur on Day 169 to assess for occurrence of any safety concerns.

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Protocol J2X-MC-PYAH(g)
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Disclosure Statement: This is a treatment study that is participant and investigator blinded, 
unless noted otherwise. 
Number of Participants:
Treatment arms 1-6
The initial planned sample size is approximately 500 participants allocated across five treatment 
arms (treatment arms 1 through 5). The planned sample size is approximately 100 participants 
for treatment arm 6. Since treatment arm 6 begins enrollment after treatment arms 1-5, additional 
participants will be enrolled in treatment arm 1 to ensure at least a 50% increase in placebo 
participants and concurrent placebo control for the primary comparison of treatment arm 6. 
Additional participants will also be enrolled in treatment arm 3 to ensure at least a 50% increase 
in LY3819253 700 mg + LY3832479 1400 mg participants to provide concurrent enrollment of 
an additional treatment arm.
Up to 100 additional participants may be introduced either for each optional treatment arm or in
addition to an existing treatment arm (including placebo). See Section 9.5 for interim analysis 
details.
Treatment arms 7-8
The planned sample size is approximately 100 participants per treatment arm. 
Treatment arms 9-11
The planned sample size is approximately 122 participants per treatment arm.
Treatment arms 12-14
Approximately 100 participants will be enrolled into treatment arm 12 and approximately 50 
participants will be enrolled into treatment arm 13. Approximately 140 participants will be 
enrolled into treatment arm 14 once treatment arms 12 and 13 have completed enrollment.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
16
Intervention Groups and Duration: 
This table describes the planned treatment arms. 
Treatment 
arms
Dose
Intervention
Participant 
Population
1
---
Placebo
---
2
175 mg + 350 mg
LY3819253 + LY3832479
---
3
700 mg + 1400 mg
LY3819253 + LY3832479
---
4
2800 mg + 2800 mg
LY3819253 + LY3832479
---
5
700 mg
LY3819253
---
6
350 mg + 700 mg
LY3819253 + LY3832479
---
7
700 mg + 500 mg
LY3819253 + VIR-7831
---
8
---
Placebo
---
9
175 mg
LY3853113
Low risk
10
175 mg + 700 mg + 1400 mg
LY3853113 + LY3819253 + LY3832479
Low risk
11
---
Placebo
Low risk
12
175 mg
LY3853113
High riska
13
175 mg + 700 mg + 1400 mg
LY3853113 + LY3819253 + LY3832479
High riska
14
175 mg + 700 mg + 1400 mg
LY3853113 + LY3819253 + LY3832479
High riskb
a
See Section 5.1, Inclusion Criteria 27 and 28 for definition of high-risk participants applicable for treatment arms 
12 and 13
b See Section 5.1, Inclusion Criterion 30 for definition of high-risk participants applicable for treatment arm 14
Treatment arm 1 is the corresponding placebo control for treatment arms 2-4 and 6.
Treatment arm 8 is the corresponding placebo control for treatment arm 7.
Treatment arm 11 is the corresponding placebo control for treatment arms 9 and 10.
Optional treatment arms may be added based on interim analysis results and/or other emerging 
data. 
Participants will receive a single treatment on Day 1, assessments occur to Day 29 and follow-up 
to Day 85 for Arms 1-6, 9-14, and Day 169 for Arms 7-8.
Data Monitoring Committee: Yes, there will be an assessment committee.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
17
Schema
a
See Section 5.1, Inclusion Criteria 27 and 28 for definition of high-risk participants applicable for treatment arms 
12 and 13
b See Section 5.1, Inclusion Criterion 30 for definition of high-risk participants applicable for treatment arm 14
Note: Additional arms may be added based on interim analysis results and other emerging data.
Abbreviations: LY = Lilly study intervention.
Figure 1.
Study J2X-MC-PYAH schema

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
18
Schedule of Activities (SoA)
Assessments obtained previously as part of routine clinical care may be used as the baseline assessment if they were done no more 
than 48 hours before randomization. Visits may be conducted as a telephone call, outpatient clinic or home visit, as long as the 
protocol SoA is followed. Refer to the study day and visit type table in Section 4.1.1 for additional clarification.
1.3.1.
Treatment Arms 1-6
This SoA is for participants in Treatment Arms 1 through 6.
Schedule of Activities for Treatment Arms 1-6
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Procedures
Informed consent
X
Inclusion and 
exclusion criteria 
review
X
Demographics
X
Including age, gender, race, ethnicity 
Preexisting 
conditions and 
medical history
X
Obtained from interview or available 
information.
Includes: risk factors and comorbidities 
associated with severe COVID-19 illness, such 
as living in a nursing home or long-term care 
facility. 
Prespecified 
medical history: 
COVID-19
X
Includes COVID-19 diagnosis date and onset 
of COVID-19 symptoms.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
19
Schedule of Activities for Treatment Arms 1-6
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Height
X
Weight
X
Prior treatments 
of special interest 
within the last 30 
days
X
NSAIDs, antivirals, antibiotics, anti-malarials, 
corticosteroids, immunomodulators or other 
investigational treatments.
Substance use 
(tobacco)
X
Includes use of e-cigarettes, such as vaping
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events 
(AEs)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Any events that occur after signing the 
informed consent are considered AEs as 
defined in Section 10.3.
Additional details regarding reporting 
frequency and method of detecting AEs 
and SAEs can be found in Section 8.3.
Physical Evaluation or Clinical Assessments
Physical 
examination
X
Symptom-directed 
physical exam
X
X
X
As indicated based on participant status 
and standard of care. May be performed 
by qualified personnel per local 
regulations.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
20
Schedule of Activities for Treatment Arms 1-6
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Vital signs and 
oxygen support
X
X
X
X
X
X
X
X
X
X
X
Documentation of hospital-based exam is 
acceptable.
Includes: body temperature, pulse rate, 
BP, respiratory rate, SpO2, and 
supplemental oxygen flow rate, FiO2 if 
known, method of delivery, if applicable, 
and oxygen support procedures. 
Record SpO2 while participant is at rest.
Screening visit only: SpO2 while 
breathing room air. Data not collected on 
CRF.
Day 1 timing:

immediately before administration

every 15 minutes during the infusion, 
as possible and applicable, and

every 30 minutes for 1 hour after the 
administration. 
During infusion, only record pulse rate, 
BP and SpO2. Automation may be used. 
See Section 8.2.2 for data collected on 
CRF.
All other study days: once daily. 

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
21
Schedule of Activities for Treatment Arms 1-6
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Hospitalization 
events
Daily
X
X
X
X
X
X
Record if the following events occur or 
occurred since prior visit:

Emergency room visits

Hospitalized

ICU admittance

Extended care facility admittance, 
and

Discharge
Clinical status and 
concomitant 
procedures if 
participant is 
hospitalized
Daily if hospitalized
X
X
X
X
Documentation from hospital records is 
acceptable if hospitalized at any time.
Includes the following:

NEWS 2 Consciousness (ACVPU)

Limitation on activities due to 
COVID-19 (Patient Global 
Assessment for Daily Activities of 
Physical Function)

Concomitant procedures of interest 
for organ support (e.g., proning, renal 
support)
Additional organ support (e.g., pressors, 
renal replacement). Oxygen support and 
vital signs data should be collected while 
participant is hospitalized.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
22
Schedule of Activities for Treatment Arms 1-6
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Laboratory Tests and Sample Collection
Hematology
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any time 
during the day
No samples needed if participant is 
hospitalized
Lilly-designated central laboratory
Clinical chemistry
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any time 
during the day
No samples needed if participant is 
hospitalized 
Lilly-designated central laboratory
C-reactive protein 
(CRP); high -
sensitivity 
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any time 
during the day 
No sample needed if participant is hospitalized
Lilly-designated central laboratory
Ferritin
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any time 
during the day 
No sample needed if participant is hospitalized
Lilly-designated central laboratory

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
23
Schedule of Activities for Treatment Arms 1-6
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
D-dimer
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any time 
during the day 
No sample needed if participant is hospitalized
Lilly-designated central laboratory
Procalcitonin
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any time 
during the day 
No sample needed if participant is hospitalized
Lilly-designated central laboratory
Troponin I and 
Troponin T
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any time 
during the day 
No sample needed if participant is hospitalized
Lilly-designated central laboratory
Documentation of 
positive SARS-
CoV-2 viral 
infection 
X
Sample for first positive test must be collected 
within 3 days prior to start of infusion. 
Local laboratory and/or Point-of-Care testing.
Urine or serum 
pregnancy 
X
X
X
Only for WOCBP (Section 10.4, Appendix 4) 
Local laboratory

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
24
Schedule of Activities for Treatment Arms 1-6
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Pharmacokinetic 
(PK) sample
for
LY3819253
LY3832479
X
X
X
X
X
X
Day 1: no pre-dose sample needed; one post-
dose sample within 30 minutes after the end of 
infusion (may include the flush). 
All other scheduled samples may occur at any 
time during the day.
No samples needed if participant is 
hospitalized.
Lilly-designated central laboratory 
Immunogenicity 
(ADA) sample for
LY3819253
LY3832479
X
X
X
X
X
X
Day 1: collect before treatment administration. 
All other scheduled and unscheduled 
immunogenicity samples should be collected 
with a time-matched PK sample.
No samples needed if participant is 
hospitalized.
Lilly-designated central laboratory
Pharmacodynamic 
(PD) NP swab 
X
X
X
X
X
X
X
Swab is taken from both nostrils. 
Day 1: swab before treatment administration.
No samples needed if participant is 
hospitalized
Lilly-designated central laboratory
Exploratory 
biomarker 
samples
X
X
X
X
X
X
Day 1: before treatment administration.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
25
Schedule of Activities for Treatment Arms 1-6
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Exploratory 
serum sample
X
X
Pharmacogenetics 
sample
X
Lilly-designated central laboratory
Randomization and Dosing
Randomization
X
Administer study 
intervention
X
Study intervention must be administered 
within 3 days from the time of first positive 
SARS-CoV-2 test sample collection.
For participants that receive dialysis on the 
same day as administration of study 
intervention, complete dialysis first followed 
by the study treatment.
Participants will be monitored for at least 1 
hour after completion of treatment 
administration. 
Participant Questionnaire
Symptoms 
(patient symptom 
assessment) and 
overall clinical 
status
Daily on Days 1-11 for outpatients only 
X
X
X
X
X
Day 1: assess prior to dosing

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
26
Abbreviations: ACVPU = alert, consciousness, verbal, pain, unresponsive scale; ADA = anti-drug antibody; AEs = adverse events; BP = blood pressure; CRF = 
case report form; ED = early discontinuation visit; FiO2 = fraction of inspired oxygen in the air; ICU = intensive care unit; NP = nasopharyngeal; NSAIDs = 
non-steroidal anti-inflammatory drugs; SAEs = serious adverse events; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SpO2 = saturation 
of peripheral oxygen; WOCBP = women of child-bearing potential. 

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
27
1.3.2.
Treatment arms 7-8
This SoA is for participants in Treatment Arms 7 and 8. 
Schedule of Activities for Treatment Arms 7-8
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment follow-
up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
169
Screening and Day 1 procedures may 
occur on the same day.
* = telephone visit(s) for all treatment 
arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
±7
Visits may not be combined.
Procedures
Informed consent
X
Inclusion and 
exclusion criteria 
review
X
Demographics
X
Including age, gender, race, ethnicity 
Preexisting 
conditions and 
medical history
X
Obtained from interview or available 
information.
Includes: risk factors and comorbidities 
associated with severe COVID-19 
illness, such as living in a nursing home 
or long-term care facility. 
Prespecified 
medical history: 
COVID-19
X
Includes COVID-19 diagnosis date and 
onset of COVID-19 symptoms.
Height
X
Weight
X

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
28
Schedule of Activities for Treatment Arms 7-8
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment follow-
up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
169
Screening and Day 1 procedures may 
occur on the same day.
* = telephone visit(s) for all treatment 
arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
±7
Visits may not be combined.
Prior treatments 
of special interest 
within the last 30 
days
X
NSAIDs, antivirals, antibiotics, anti-
malarials, corticosteroids, 
immunomodulators or other 
investigational treatments.
Substance use 
(tobacco)
X
Includes use of e-cigarettes, such as 
vaping
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events 
(AEs)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Any events that occur after signing 
the informed consent are considered 
AEs as defined in Section 10.3.
Additional details regarding 
reporting frequency and method of 
detecting AEs and SAEs can be 
found in Section 8.3.
Physical Evaluation or Clinical Assessments
Physical 
examination
X
Symptom-directed 
physical exam
X
X
X
As indicated based on participant 
status and standard of care. May be 
performed by qualified personnel 
per local regulations.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
29
Vital signs and 
oxygen support
X
X
X
X
X
X
X
X
X
X
X
Documentation of hospital-based 
exam is acceptable.
Includes: body temperature, pulse 
rate, BP, respiratory rate, SpO2, and 
supplemental oxygen flow rate, 
FiO2 if known, method of delivery, 
if applicable, and oxygen support 
procedures. 
Record SpO2 while participant is at 
rest.
Screening visit only: SpO2 while 
breathing room air. Data not 
collected on CRF.
Day 1 timing (for each 
administration):

immediately before 
administration

every 15 minutes during the 
infusion, as possible and 
applicable

Approximately 30 minutes after 
the end of the first infusion

every 30 minutes for 1 hour 
after the last administration. 
During each infusion, only record 
pulse rate, BP and SpO2. 
Automation may be used. See 
Section 8.2.2 for data collected on 
CRF.
All other study days: once daily. 
Hospitalization 
events
Daily
X
X
X
X
X
X
Record if the following events occur 
or occurred since prior visit:

Emergency room visits

Hospitalized

ICU admittance

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
30
Schedule of Activities for Treatment Arms 7-8
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment follow-
up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
169
Screening and Day 1 procedures may 
occur on the same day.
* = telephone visit(s) for all treatment 
arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
±7
Visits may not be combined.

Extended care facility 
admittance, and

Discharge
Clinical status and 
concomitant 
procedures if 
participant is 
hospitalized
Daily if hospitalized
X
X
X
X
Documentation from hospital 
records is acceptable if hospitalized 
at any time.
Includes the following:

NEWS 2 Consciousness 
(ACVPU)

Limitation on activities due to 
COVID-19 (Patient Global 
Assessment for Daily Activities 
of Physical Function)

Concomitant procedures of 
interest for organ support (e.g., 
proning, renal support)
Additional organ support (e.g.,
pressors, renal replacement). 
Oxygen support and vital signs data 
should be collected while 
participant is hospitalized.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
31
Schedule of Activities for Treatment Arms 7-8
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment follow-
up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
169
Screening and Day 1 procedures may 
occur on the same day.
* = telephone visit(s) for all treatment 
arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
±7
Visits may not be combined.
Laboratory Tests and Sample Collection
Hematology
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any 
time during the day
No samples needed if participant is 
hospitalized
Lilly-designated central laboratory
Clinical chemistry
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any 
time during the day
No samples needed if participant is 
hospitalized 
Lilly-designated central laboratory
C-reactive protein 
(CRP); high -
sensitivity 
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any 
time during the day 
No sample needed if participant is 
hospitalized
Lilly-designated central laboratory

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
32
Schedule of Activities for Treatment Arms 7-8
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment follow-
up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
169
Screening and Day 1 procedures may 
occur on the same day.
* = telephone visit(s) for all treatment 
arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
±7
Visits may not be combined.
Ferritin
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any 
time during the day 
No sample needed if participant is 
hospitalized
Lilly-designated central laboratory
D-dimer
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any 
time during the day 
No sample needed if participant is 
hospitalized
Lilly-designated central laboratory
Procalcitonin
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any 
time during the day 
No sample needed if participant is 
hospitalized
Lilly-designated central laboratory

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
33
Schedule of Activities for Treatment Arms 7-8
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment follow-
up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
169
Screening and Day 1 procedures may 
occur on the same day.
* = telephone visit(s) for all treatment 
arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
±7
Visits may not be combined.
Troponin I and 
Troponin T
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any 
time during the day 
No sample needed if participant is 
hospitalized
Lilly-designated central laboratory
Documentation of 
positive SARS-
CoV-2 viral 
infection 
X
Sample for first positive test must be 
collected within 3 days prior to start of 
infusion. 
Local laboratory and/or Point-of-Care 
testing.
Urine or serum 
pregnancy 
X
X
X
Only for WOCBP (Section 10.4,
Appendix 4) 
Local laboratory

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
34
Schedule of Activities for Treatment Arms 7-8
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment follow-
up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
169
Screening and Day 1 procedures may 
occur on the same day.
* = telephone visit(s) for all treatment 
arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
±7
Visits may not be combined.
Pharmacokinetic 
(PK) sample
for
LY3819253
VIR-7831
X
X
X
X
X
X
Day 1: VIR-7831 PK will be tested pre-
dose. No LY3819253 pre-dose sample 
needed; one post-dose sample within 30 
minutes after the end of second infusion 
will be shared by LY3819253 and VIR-
7831 (may include the flush). 
All other scheduled samples may occur 
at any time during the day.
No samples needed if participant is 
hospitalized.
Lilly-designated central laboratory 
Immunogenicity 
(ADA) sample for
LY3819253
VIR-7831
X
X
X
X
X
X
Day 1: collect before treatment 
administration. 
All other scheduled and unscheduled 
immunogenicity samples should be 
collected with a time-matched PK 
sample.
No samples needed if participant is 
hospitalized.
Lilly-designated central laboratory

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
35
Schedule of Activities for Treatment Arms 7-8
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment follow-
up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
169
Screening and Day 1 procedures may 
occur on the same day.
* = telephone visit(s) for all treatment 
arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
±7
Visits may not be combined.
Pharmacodynamic 
(PD) NP swab 
X
X
X
X
X
X
X
Swab is taken from both nostrils. 
Day 1: swab before treatment 
administration.
No samples needed if participant is 
hospitalized
Lilly-designated central laboratory
Exploratory 
biomarker 
samples
X
X
X
X
X
X
Day 1: before treatment administration.
Exploratory 
serum sample
X
X
Pharmacogenetics 
sample
X
Lilly-designated central laboratory
Randomization and Dosing
Randomization
X

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
36
Schedule of Activities for Treatment Arms 7-8
Study 
J2X-MC-PYAH
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment follow-
up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
169
Screening and Day 1 procedures may 
occur on the same day.
* = telephone visit(s) for all treatment 
arms
Visit Window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
±7
Visits may not be combined.
Administer study 
intervention
X
Study intervention must be administered 
within 3 days from the time of first 
positive SARS-CoV-2 test sample 
collection.
For participants that receive dialysis on 
the same day as administration of study 
intervention, complete dialysis first 
followed by the study treatment.
Participants will be monitored at least 
30 minutes after the first infusion and at 
least 1 hour after the last infusion.
Participant Questionnaire
Symptoms 
(patient symptom 
assessment) and 
overall clinical 
status
Daily on Days 1-11 for outpatients only
X
X
X
X
X
Day 1: assess prior to dosing
Abbreviations: ACVPU = alert, consciousness, verbal, pain, unresponsive scale; ADA = anti-drug antibody; AEs = adverse events; BP = blood pressure; CRF = 
case report form; ED = early discontinuation visit; FiO2 = fraction of inspired oxygen in the air; ICU = intensive care unit; NP = nasopharyngeal; NSAIDs = 
non-steroidal anti-inflammatory drugs; SAEs = serious adverse events; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SpO2 = saturation 
of peripheral oxygen; WOCBP = women of child-bearing potential. 

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
37
1.3.3.
Treatment Arms 9-14
Schedule of Activities for Treatment Arms 9-14
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on the 
same day.
* = telephone visit(s) for all treatment arms
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Procedures
Informed Consent
X
Informed assent for 
adolescent 
participants
X
Parent or legal guardian signs informed consent form 
and participant signs assent form, as appropriate per 
local requirements.
Inclusion and 
exclusion criteria 
review
X
Demographics
X
Including age, gender, race, ethnicity
Preexisting 
conditions and 
medical history
X
Obtained from interview or available information.
Includes:  vaccination history (including SARS-CoV-
2 vaccinations), risk factors and comorbidities 
associated with severe COVID-19 illness, such as 
living in a nursing home or long-term care facility. 
Prespecified 
medical history: 
COVID-19
X
Includes COVID-19 diagnosis date and onset of 
COVID-19 symptoms.
Height
X
Weight
X

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
38
Schedule of Activities for Treatment Arms 9-14
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on the 
same day.
* = telephone visit(s) for all treatment arms
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Prior treatments of 
special interest 
within the last 30 
days
X
NSAIDs, antivirals, antibiotics, anti-malarials, 
corticosteroids, immunomodulators or other 
investigational treatments.
Substance use 
(Tobacco)
X
Includes use of e-cigarettes, such as vaping
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events 
(AEs)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Any events that occur after signing the informed 
consent are considered AEs as defined in 
Section 10.3.
Additional details regarding reporting frequency 
and method of detecting AEs and SAEs can be 
found in Section 8.3.
Physical Evaluation or Clinical Assessments
Physical 
examination
X
Symptom-directed 
physical exam
X
X
X
As indicated based on participant status and 
standard of care.  May be performed by 
qualified personnel per local regulations.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
39
Schedule of Activities for Treatment Arms 9-14
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on the 
same day.
* = telephone visit(s) for all treatment arms
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Vital signs and 
Oxygen Support
X
X
X
X
X
X
X
X
X
X
X
Documentation of hospital-based exam is 
acceptable.
Includes: body temperature, pulse rate, BP, 
respiratory rate, SpO2, and supplemental oxygen 
flow rate, FiO2 if known, method of delivery, if 
applicable, and oxygen support procedures. 
Record SpO2 while participant is at rest.
Screening visit only: SpO2 while breathing 
room air. Data not collected on CRF.
Day 1 timing:

immediately before administration

immediately following completion of 
infusion if infusion is <15 minutes

every 15 minutes during the infusion, as 
possible and applicable

every 30 minutes for 1 hour after the end of 
infusion
See Section 8.2.2 for data collected on CRF.
All other study days: once daily. 

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
40
Schedule of Activities for Treatment Arms 9-14
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on the 
same day.
* = telephone visit(s) for all treatment arms
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Hospitalization 
events
Daily
X
X
X
X
X
X
Record if the following events occur or occurred since 
prior visit:

Emergency room visits

hospitalized

ICU admittance, 

Extended care facility admittance, and

Discharge
Laboratory Tests and Sample Collection
Hematology
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any time during 
the day
No samples needed if participant is hospitalized
Lilly-designated central laboratory
Clinical Chemistry
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at any time during 
the day
No samples needed if participant is hospitalized 
Lilly-designated central laboratory
C-reactive protein 
(CRP); high -
sensitivity 
X
X
X
X
X
For adults only
Day 1: before treatment administration
All other days: sample may occur at any time during 
the day 
No sample needed if participant is hospitalized
Lilly-designated central laboratory

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
41
Schedule of Activities for Treatment Arms 9-14
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on the 
same day.
* = telephone visit(s) for all treatment arms
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Ferritin
X
X
X
X
X
For adults only
Day 1: before treatment administration
All other days: sample may occur at any time during 
the day 
No sample needed if participant is hospitalized
Lilly-designated central laboratory
D-dimer
X
X
X
X
X
For adults only
Day 1: before treatment administration
All other days: sample may occur at any time during 
the day 
No sample needed if participant is hospitalized
Lilly-designated central laboratory
Procalcitonin
X
X
X
X
X
For adults only
Day 1: before treatment administration
All other days: sample may occur at any time during 
the day 
No sample needed if participant is hospitalized
Lilly-designated central laboratory
Troponin I and 
Troponin T
X
X
X
X
X
For adults only
Day 1: before treatment administration
All other days: sample may occur at any time during 
the day 
No sample needed if participant is hospitalized
Lilly-designated central laboratory

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
42
Schedule of Activities for Treatment Arms 9-14
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on the 
same day.
* = telephone visit(s) for all treatment arms
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Documentation of 
positive SARS-
CoV-2 viral 
infection 
X
Sample for first positive test must be collected within 
3 days prior to start of infusion.
Local laboratory and/or Point-of-Care testing.
Urine or serum 
pregnancy 
X
X
X
Only for WOCBP (Section 10.4 Appendix 4) 
Local laboratory
Pharmacokinetic 
(PK) sample for
LY3853113
LY3819253
LY3832479
X
X
X
X
X
X
X
X
Day 1: no pre-dose sample needed; one post-dose 
sample within 30 minutes after the end of IV infusion
(may include the flush). 
All other scheduled samples may occur at any time 
during the day.
No samples needed if participant is hospitalized.
Lilly-designated central laboratory
Immunogenicity 
(ADA) sample for
LY3853113
LY3819253
LY3832479
X
X
X
X
X
X
Day 1:  collect before treatment administration. 
All other scheduled and unscheduled immunogenicity 
samples should be collected with a time-matched PK 
sample.
No samples needed if participant is hospitalized
Lilly-designated central laboratory
Pharmacodynamic 
(PD) NP swab 
X
X
X
X
X
X
X
Swab is taken from both nostrils. 
Day 1: swab before treatment administration.
No samples needed if participant is hospitalized
Lilly-designated central laboratory

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
43
Schedule of Activities for Treatment Arms 9-14
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on the 
same day.
* = telephone visit(s) for all treatment arms
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Exploratory 
biomarker samples
X
X
X
X
X
X
Day 1: before treatment administration.
Exploratory serum 
sample
X
X
X
Pharmacogenetics 
sample
X
For adults only
Lilly-designated central laboratory
Randomization and Dosing
Randomization
X
Administer study 
intervention
X
Study intervention must be administered within 3 
days from the time of first positive SARS-CoV-2 test 
sample collection.
For participants that receive dialysis on the same day 
as administration of study intervention, complete 
dialysis first followed by the study treatment.
Participants will be monitored for at least 1 hour after 
completion of treatment administration.
Participant Questionnaire
Symptoms (Patient 
Symptom 
Assessment) and 
overall clinical 
status
Daily on Days 1-11 for outpatients only 
X
X
X
X
X
Day 1: assess prior to dosing

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
44
Abbreviations: ADA = anti-drug antibody; AEs = adverse events; BP = blood pressure; CRF = case report form; ED = early discontinuation visit; FiO2 = 
fraction of inspired oxygen in the air; ICU = intensive care unit; NP = nasopharyngeal; NSAIDS = non-steroidal anti-inflammatory drugs; PK = 
pharmacokinetics; SAEs = serious adverse events; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SpO2 = saturation of peripheral oxygen; 
WOCBP = women of child-bearing potential.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
45
2.
Introduction
The efficient community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-
2) has resulted in the current pandemic of coronavirus disease 2019 (COVID-19), which in severe 
and critical cases results in progressive pulmonary infection, complicated by respiratory failure, with 
a high prevalence of acute respiratory distress syndrome. Although several therapies have been 
explored in severe COVID-19, none have improved survival, including antivirals, glucocorticoids, 
and immunoglobulins (Liu et al 2020). 
LY3819253, LY3832479, and LY3853113 are neutralizing IgG1 monoclonal antibodies (mAb) 
to the spike protein of SARS-CoV-2. They are designed to block viral attachment and entry into 
human cells, and to neutralize the virus, potentially treating even established COVID-19 by 
providing a combination of specific, potent, neutralizing antibodies to SARS-CoV-2. The 
blocking of viral entry into respiratory cells and viral replication, and viral neutralization is 
expected to mitigate the severity of disease in patients in whom ongoing viral spread and 
replication is the primary driver of COVID-19 pathophysiology. The decrease in viral replication 
may also shorten a patient’s extent and duration of viral shedding and transmission, positively 
impacting public health. 
VIR-7831 is a human IgG1 mAb that binds to the spike protein of SARS-CoV-2. It contains 
modifications to enhance both respiratory mucosal distribution and the half-life. An increased 
distribution to mucosal tissue is expected to result in higher and more sustained levels of VIR-
7831 in the respiratory mucosa, which is a potential advantage for treatment and prophylaxis.
Study Rationale
This study aims to evaluate the impact of LY3819253 alone, LY3819253 + LY3832479, 
LY3853113 alone, LY3853113 + LY3819253 + LY3832479, and LY3819253 + VIR-7831 on 
viral clearance and clinical outcomes in participants with mild to moderate COVID-19 illness. 
Additionally, this study aims to characterize the safety profile of LY3853113 alone and in 
combination with LY3819253 and LY3832479 in participants at high risk of developing severe 
COVID-19 illness. The data from this study will inform decisions for the clinical development of 
these neutralizing IgG1 mAbs. 
Background
LY3819253 and LY3832479
Nonclinical information for LY3819253 and LY3832479 is described in each respective 
Investigator’s Brochure (IB).
Lilly is evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) 
of LY3819253 in participants hospitalized for COVID-19, in a randomized, placebo-controlled, 
double-blind, single ascending dose, Phase 1, first in human study (Study J2W-MC-PYAA
[PYAA]). This study has completed dosing.
Lilly is also evaluating the safety, tolerability, PK, and immunogenicity of LY3832479 in 
healthy participants, in a randomized, placebo-controlled, single dose, Phase 1 study (Study J2Z-
MC-PGAA [PGAA]) under IND 150707. Concurrent with Study PGAA, LY3832479 is also 

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
46
under development in China in an ongoing Phase 1 clinical study in healthy participants, Study 
JS016-001-I.
Lilly is evaluating the safety, tolerability, PK, immunogenicity and efficacy of LY3819253 
alone, or in combination with LY3832479, in a randomized, placebo-controlled, double-blind
Phase 2 study in participants with mild to moderate COVID-19 (Study J2W-MC-PYAB 
[PYAB]). Dose levels administered in Study PYAB were informed by PYAA and PGAA. 
Specific treatment arms in PYAB are evaluating the safety and efficacy of LY3819253 in 
combination with LY3832479 in participants with risk factors for severe COVID-19. As of 04
November 2020, 542 participants received blinded treatment with either placebo or 2800 mg 
LY3819253 + 2800 mg LY3832479 in combination. As of that date, there have been no 
discontinuations due to AEs. Serious adverse events were reported for 4 participants across 
monotherapy and combination arms.
The SAEs were as follows: 

a severe SAE of upper abdominal pain in a participant who received placebo

a mild SAE of urinary tract infection in a participant who received LY3819253 and 
LY3832479 combination therapy

acute myocardial infarction in a participant who received blinded study treatment with
either placebo or LY3819253 2800 mg in combination with LY3832479 2800 mg, and

a severe SAE of diabetic ketoacidosis in a participant who received LY3819253 700 mg 
monotherapy
No infusion-related reactions were reported. One event of facial swelling and 1 event of 
hypersensitivity was noted on the day of infusion, with pruritis as the most common immediate 
hypersensitivity event. Other non-immediate hypersensitivity events reported included rash, 
stomatitis, and urticaria. A total of 20 patients receiving LY3819253 in combination with 
LY3832479 developed treatment-emergent adverse events (TEAEs). Most TEAES were mild to 
moderate in severity, similar across all dose groups, and comparable to placebo. The most 
frequently reported TEAEs were nausea and pruritus.
As of 24 September 2020, one serious infusion-related reaction was reported in a blinded 
ongoing study (J2W-NS-I001; ACTIV-2/A5401) of LY3819253 administered at 7000 mg versus 
placebo.
In addition, there is an ongoing Lilly and NIAID collaborative Phase 3 randomized, double-
blind, placebo-controlled trial (Study J2X-MC-PYAD [PYAD]) evaluating the efficacy and 
safety of LY3819253 in preventing SARS-CoV-2 infection and COVID-19 in skilled nursing 
and assisted living facility residents and staff.
LY3853113
LY3853113 is a novel, highly potent IgG1 neutralizing mAb targeting the spike protein of 
SARS-CoV-2 that was created in partnership with AbCellera Biologics Inc. (AbCellera; 
Vancouver, Canada).  It binds an epitope within the receptor binding domain (RBD) that is 
distinct from those bound by LY3819253 and LY3832479.  LY3853113 can neutralize the 
Wuhan reference strain as well as individual residues present in recent variants of concern (i.e.
L452R, D614G, N501Y, N439K, K417N, and E484K).  Critically, pseudovirus assays 
demonstrate that LY3853113 can neutralize variants with the specific combination of RBD 

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
47
residues of the B.1.1.351 (South African origin), B.1.1.28 (P.1/Brazil origin), B.1.427/B.1.429 
(California origin), and B.1.526 (New York origin) strains.  These variants were recently 
reported in the United States (CDC 2021), thus it is imperative that new treatments for these 
emerging variants are developed and deployed quickly.
Refer to the LY3853113 IB for additional information.
VIR-7831
In vitro data show VIR-7831 as a highly potent human IgG neutralizing SARS-CoV-2 antibody,
which has the potential to be an effective therapeutic in mild to critically ill patients with 
COVID-19. Additional nonclinical information for VIR-7831 is described in the IB.
Vir Biotechnology is currently conducting a first-in-human Phase 2/3 clinical study (COMET-
ICE, NCT04545060) for the treatment of adult patients aged 18 years and older with mild-to-
moderate COVID-19 who are at risk for progression to hospitalization or death. This study is a 
randomized, double-blind, multi-center, placebo-controlled trial of VIR-7831 (500 mg IV) with 2
planned interim analyses to allow early stopping for futility, efficacy or safety. The study 
includes a lead-in phase to evaluate the safety and tolerability of VIR-7831, followed by an 
expansion phase. Following review of available safety and tolerability data through Day 15 from 
21 participants in the lead-in phase, the independent data monitoring committee triggered 
expansion of the study to enroll additional participants across both treatment groups 
(approximately 1340 participants). VIR-7831 is also being studied for treatment of hospitalized 
participants with COVID-19 (ACTIV-3-TICO). As of 21 January 2021, two serious infusion-
related reactions (anaphylaxis and bronchospasm) have been reported in a blinded ongoing
hospitalized patient study (study number GSK 215149; ACTIV 3 TICO) of VIR-7831 
administered at 500 mg versus placebo. Both reactions required treatment, one required 
epinephrine. Both events resolved.

CONFIDENTIAL
Protocol J2X-MC-PYAH(g)
48
Benefit/Risk Assessment
LY3819253, LY3832479, and LY3853113
Information on the safety and tolerability of LY3819253 in humans will come from Studies
PYAA and PYAB. Information on the safety and tolerability of LY3832479 will come from 
Studies PGAA and PYAB. Information on the safety and tolerability of LY3853113 will come 
from Study PYAH and PYAH Addendum (4).
Anticipated risk is considered low and is based on the known mechanism of action for human 
derived neutralizing antibodies in acute viral disease states. LY3819253, LY3832479, and 
LY3853113 consist of highly specific mAbs directed at foreign (non-human) epitope(s). The 
complementarity determining regions (CDRs) of the mAbs were derived from B lymphocytes of 
2 individually convalescent naturally SARS-CoV-2-infected patients and, thus, have undergone 
natural positive and negative selection pressures in vivo, unlike humanized antibodies generated 
in mice. No clinically relevant off-target binding has been observed in tissue cross reactivity 
studies of membrane targets in human tissues. Therefore, off-target binding and tissue cross-
reactivity are considered unlikely.
A theoretical risk is that these interventions may cause antibody-dependent enhancement (ADE) 
of viral replication. This is based on responses observed to some monoclonal antibody therapies 
used in other unrelated viral diseases. To address this risk, LY3819253 and LY3832479 have 
been assessed with in vitro cell culture models and, for LY3819253, an in vivo nonhuman 
primate model.
The risk of clinical ADE is considered low due to

the structural features of LY3832479, which is engineered to suppress its binding to Fc 
receptors and C1qm

the absence of ADE from in vitro studies, and

the absence of ADE from in vivo nonhuman primate studies for LY3819253. 
To date, there is no evidence of productive enhancement of ADE with SARS-CoV-2. 
Additional manageable risks associated with most therapeutic monoclonal antibodies are the 
potential for infusion-related hypersensitivity and cytokine release reactions. Infusion-related 
hypersensitivity reactions have been observed in clinical studies and under the EUA. 
The infusions in this study will be administered at a controlled rate, the study participants will be 
monitored closely, and adjustments in the infusion rate will be made and/or the infusion stopped, 
if indicated. Additional information regarding infusion reaction management options is in 
Section 6.1.1.
Clinical worsening of COVID-19 after administration of LY3819253 has been reported from 
post-authorization treatment within 24 hours of infusion. Signs and symptoms may include fever, 
hypoxia or increased respiratory difficulty, arrythmia (e.g., atrial fibrillation, sinus tachycardia, 
and bradycardia), fatigue, and altered mental status. Some of these events required 
hospitalization. It is not known if these events were related to LY3819253 use or were due to 
progression of COVID-19. Refer to the IB, and EUA Fact Sheet for additional information.

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Protocol J2X-MC-PYAH(g)
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Given the data on LY3819253, LY3832479, and LY3853113, the well described safety profile of 
other therapeutic mAbs, and the lack of disease directed therapeutic options for patients with 
COVID-19 illness, the overall benefit-risk assessment for this study is considered favorable. 
VIR-7831
VIR-7831 is a highly specific human mAb directed at a non-human epitope.  No clinically 
relevant off-target binding has been observed in tissue cross reactivity studies of membrane 
targets in human tissues, thus off-target binding and tissue cross-reactivity are considered 
unlikely.  Anticipated risk of VIR-7831 is considered low and is based on the known mechanism 
of action for human derived neutralizing antibodies in acute viral disease states.
Potential risks of clinical significance include infusion reactions, hypersensitivity reactions and 
immunogenicity.
Theoretical risks associated with mAb administration during viral infection are

The absence of ADE in a series of in vitro studies

The absence of effect on cytokine production based on in vitro studies

the absence of ADE from an in vivo study with VIR-7831 wild type (a non-LS version of 
VIR7831) in the Syrian hamster model 
There is prior clinical experience with VIR-7831 in the setting of early treatment of COVID-19 
(VIR-7831-5001). No specific safety concerns were identified in individuals actively infected 
with SARS-CoV-2. In addition, preclinical animal studies administering VIR-7831 in the 
prophylactic setting have also demonstrated reduction of viral load and less weight loss in VIR-
7831-treated animals.
Given there are currently limited available preventative measures for COVID-19, the potentially 
higher exposure and/or disease risk of some participants in this study, and strength of the 
preclinical and clinical data, the Sponsor believes the potential benefit of participation in this 
study outweigh the risks. The overall benefit-risk assessment takes into account the potential 
benefit of VIR-7831 treatment through the potential ability to suppress viral replication and clear 
infected cells.
Investigator’s Brochures
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of LY3819253, LY3832479, LY3853113, and VIR-7831 may be found 
in each respective IB.

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3.
Objectives and Endpoints
Treatment Arms 1-6
Primary
Characterize the effect of LY3819253 alone and in 
combination with LY3832479, compared to placebo on 
SARS-CoV-2 viral load

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7 (+2 days)
Secondary
The secondary objectives are to characterize the effect 
of LY3819253 alone and in combination with 
LY3832479, compared to placebo on…

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 29
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

SARS-CoV-2 viral load and viral clearance

Change from baseline to 
o
Day 3 (+1 day)
o
Day 5 (±2 days)
o
Day 7 (±2 days)
o
Day 11 (±2 days)

Proportion of participants with viral load greater 
than 5.27 on Day 7 (+2 days) among participants 
enrolled with ≤8 days of symptoms prior to 
randomization 

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 3, 5, 7, 11, and 29)

Time to SARS-CoV-2 clearance 

SARS-CoV-2 viral load AUC assessed through 
Day 11

symptom resolution

Time to symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days 
3, 5, 7, 11, 22, and 29

Change in symptom score (total of ratings) from 
baseline up to Days 7, 11, 22, and 29. 

AUC from baseline to Day 11

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 3, 5, 7, 11, 22, and 29

safety 

Safety assessments such as AEs and SAEs

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Days 22, 60, and 85

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o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

characterize clinical status for participants

Proportion (percentage) of participants who 
experience these events through Day 29: 
o
COVID-19 related hospitalization (defined as 
≥24 hours of acute care)
o
COVID-19 related emergency room visit, or
o
death 

characterize the pharmacokinetics of LY3819253
and LY3832479

Mean concentration of LY3819253 and 
LY3832479 on Day 29
Exploratory

Characterize emergence of viral resistance to 
LY3819253 and LY3819253 in combination with 
LY3832479

Comparison from baseline to the last evaluable 
time point up to Day 29
Abbreviations: AE = adverse event; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2. 
Treatment Arms 7-8
Primary
Characterize the effect of LY3819253 in combination 
with VIR-7831, compared to placebo on SARS-CoV-2 
viral load

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7 (+2 days)
Secondary
The secondary objectives are to characterize the effect 
of LY3819253 in combination with VIR-7831, 
compared to placebo on…

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 29
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

SARS-CoV-2 viral load and viral clearance

Change from baseline to 
o
Day 3 (+1 day)
o
Day 5 (±2 days)
o
Day 7 (±2 days)
o
Day 11 (±2 days)

Proportion of participants with viral load greater 
than 5.27 on Day 7 (+2 days) among participants 
enrolled with ≤8 days of symptoms prior to 
randomization 

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 3, 5, 7, 11, and 29)

Time to SARS-CoV-2 clearance 

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Protocol J2X-MC-PYAH(g)
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
SARS-CoV-2 viral load AUC assessed through 
Day 11

symptom resolution

Time to symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days 
3, 5, 7, 11, 22, and 29

Change in symptom score (total of ratings) from 
baseline up to Days 7, 11, 22, and 29.

AUC from baseline to Day 11

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 3, 5, 7, 11, 22, and 29

safety 

Safety assessments such as AEs and SAEs

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Days 22, 60, and 85
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

characterize clinical status for participants 

Proportion (percentage) of participants who 
experience these events through Day 29: 
o
COVID-19 related hospitalization (defined as 
≥24 hours of acute care)
o
COVID-19 related emergency room visit, or
o
death 

characterize the pharmacokinetics of LY3819253
and VIR-7831

Mean concentration of LY3819253 and VIR-7831
on Day 29
Exploratory

characterize emergence of viral resistance to 
LY3819253 in combination with VIR-7831

Comparison from baseline to the last evaluable 
time point up to Day 29
Abbreviations: AE = adverse event; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2.

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Treatment Arms 9-11
Primary
Characterize the effect of LY3853113 alone and in 
combination with LY3819253 and LY3832479 after 
intravenous infusion compared to placebo on SARS-
CoV-2 viral load

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7
Secondary
The secondary objectives are to characterize the effect 
of LY3853113 alone and in combination with 
LY3819253 and LY3832479 after intravenous infusion 
compared to placebo on…

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 29
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

SARS-CoV-2 viral load and viral clearance

75th Percentile of SARS-CoV-2 viral load at Day 7

Change from baseline to 
o
Day 3
o
Day 5
o
Day 7
o
Day 11

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 3, 5, 7, 11, and 29)

Time to SARS-CoV-2 clearance 

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 11

symptom resolution

Time to symptom resolution 

Time to sustained symptom resolution

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days 
2-11, 22, and 29

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 2-11, 22, and 29

safety 

Safety assessments such as AEs and SAEs

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 22
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

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
Characterize clinical status for participants

Proportion (percentage) of participants who 
experience these events through Day 29: 
o
COVID-19 related hospitalization (defined as 
≥24 hours of acute care),
o
COVID-19 related emergency room visit, or
o
death 

Characterize the pharmacokinetics of LY3853113, 
LY3819253, and LY3832479

Mean concentration of LY3853113, LY3819253, 
and LY3832479 on Day 29
Exploratory

Characterize emergence of viral resistance to
LY3853113

Comparison from baseline to the last evaluable
time point up to Day 29
Abbreviations: AE = adverse event; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2.
Treatment Arms 12-14
Primary
Characterize the safety profile of LY3853113 alone 
and in combination with LY3819253 and LY3832479
after intravenous infusion on SARS-CoV-2 viral load

Safety assessments such as AEs and SAEs
Secondary
The secondary objectives are to characterize the effect 
of LY3853113 alone and in combination with 
LY3819253 and LY3832479 after intravenous infusion 
on…

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 29
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

SARS-CoV-2 viral load and viral clearance

75th Percentile of SARS-CoV-2 viral load at Day 7

Change from baseline to 
o
Day 3
o
Day 5
o
Day 7
o
Day 11

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 3, 5, 7, 11, and 29)

Time to SARS-CoV-2 clearance 

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 11

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7

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
symptom resolution

Time to symptom resolution 

Time to sustained symptom resolution

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days 
2-11, 22, and 29

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 2-11, 22, and 29

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Day 22
o
COVID-19 related hospitalization 
(defined as ≥24 hours of acute care)
o
Death

Characterize clinical status for participants

Proportion (percentage) of participants who 
experience these events through Day 29: 
o
COVID-19 related hospitalization (defined as 
≥24 hours of acute care),
o
COVID-19 related emergency room visit, or
o
death 

Characterize the pharmacokinetics of LY3853113, 
LY3819253, and LY3832479

Mean concentration of LY3853113, LY3819253, 
and LY3832479 on Day 29
Exploratory

Characterize emergence of viral resistance to
LY3853113

Comparison from baseline to the last evaluable
time point up to Day 29
Abbreviations: AE = adverse event; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2.

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4.
Study Design
Overall Design
This is a Phase 2, randomized, single-dose study in participants with mild to moderate COVID-
19 illness. Treatment arms 1-11 are double-blind and placebo controlled, and treatment arms 12-
14 are open label.
4.1.1.
Design Outline
Abbreviations: PD = pharmacodynamic; PYAH = Study J2X-MC-PYAH.
Figure 2.
Overview of participant flow from time of SARS-CoV-2 symptoms to 
treatment administration. 
Screening
Interested participants will sign the appropriate informed consent and child/adolescent assent 
document(s), as appropriate, prior to completion of any procedures. The participant may enter 
the study with a previous positive SARS-CoV-2 viral test result from an external testing facility. 
This test result must be the first time the participant has tested positive for SARS-CoV-2.
The investigator will review symptoms, risk factors and other non-invasive inclusion and 
exclusion criteria prior to any invasive procedures. If the participant is eligible after this review, 
then the site will perform the invasive procedures to confirm eligibility.
Double-blind Treatment and Assessment Period
This is the general sequence of events during the treatment and assessment period:

Complete baseline procedures and sample collection

Participants are randomized to an intervention group

Participants receive study intervention, and

Complete all safety monitoring and post-treatment sample collection.

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This table describes the planned treatment arms.
Treatment 
arms
Dose
Intervention
Participant 
Population
1
---
Placebo
---
2
175 mg + 350 mg
LY3819253 + LY3832479
---
3
700 mg + 1400 mg
LY3819253 + LY3832479
---
4
2800 mg + 2800 mg
LY3819253 + LY3832479
---
5
700 mg
LY3819253
---
6
350 mg + 700 mg
LY3819253 + LY3832479
---
7
700 mg + 500 mg
LY3819253 + VIR-7831
---
8
---
Placebo
---
9
175 mg
LY3853113
Low risk
10
175 mg + 700 mg + 1400 mg
LY3853113 + LY3819253 + LY3832479
Low risk
11
---
Placebo
Low risk
12
175 mg
LY3853113
High riska
13
175 mg + 700 mg + 1400 mg
LY3853113 + LY3819253 + LY3832479
High riska
14
175 mg + 700 mg + 1400 mg
LY3853113 + LY3819253 + LY3832479
High riskb
a
See Section 5.1, Inclusion Criteria 27 and 28 for definition of high-risk participants applicable for treatment arms 
12 and 13
b See Section 5.1, Inclusion Criterion 30 for definition of high-risk participants applicable for treatment arm 14
Treatment arm 1 is the corresponding placebo control for treatment arms 2-4 and 6. 
Treatment arm 8 is the corresponding placebo control for treatment arm 7. 
Treatment arm 11 is the corresponding placebo control for treatment arms 9 and 10.
This table describes the visit and activity types for this study.
Study Day
Activity
Visit Type
1 
Follow SoA
Site 
2, 4, 6, and 22
Follow SoA
Telephone visit 
3, 5, 7, 11, 29, ED, 60, and 85
Follow SoA
May be conducted as outpatient clinic 
or home visit. Symptom assessments 
can be collected via telephone visit.
8, 9, 10
Collection of symptom assessments
Telephone visit
Early discontinuation and follow-up
Follow SoA
May be conducted as outpatient clinic 
or home visit
169 (Arms 7 and 8 only)
AE/SAE collection, concomitant 
medications
Telephone visit
Abbreviations: SoA = schedule of activities
If a participant is hospitalized, procedures and assessments will continue per the SoA
(Section 1.3). 

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This table describes discharge from hospital scenarios if an outpatient is subsequently 
hospitalized.
If hospital discharge… 
Then…
Occurs prior to Day 29
participants will be asked to complete the remaining 
study assessments at the timepoints indicated in the 
SoA (Section 1.3).
NOTE: Strategies to manage infection risks and reduce 
the burden of return visits should be used by sites, such 
as home visits.
Occurs on the same day as a study assessment visit
assessments do not need to be repeated if the study 
assessments occurred within 8 hours of discharge and 
there has been no change in clinical status and the 
information is available to the site.
Does not occur at or prior to Day 29
assessments will continue to occur weekly up to Day 
60 or until hospital discharge, whichever is sooner.
Post-treatment follow-up
Post-treatment follow-up assessments will be conducted at Day 60 and Day 85 to assess clinical 
status and for adverse events. Strategies to manage infection risks and reduce the burden of 
return visits may be used by sites, such as home visits. For Arms 7 and 8, an additional telephone 
visit will occur on Day 169 to assess for occurrence of any safety concerns.
Scientific Rationale for Study Design
Overall Design
This study is designed to evaluate the efficacy of LY3819253 alone, LY3853113 alone,
LY3819253 in combination with LY3832479 in a dose-ranging design, LY3853113 in 
combination with LY3819253 and LY3832479, and LY3819253 in combination with VIR-7831 
at a single dose in order to inform the clinical drug development plan for these interventions.
Alternative doses, routes of administration (IV or SQ), and/or treatment combinations may also 
be assessed via the addition of treatment arms. Up to 100 additional participants may be 
introduced either for each optional treatment arm or in addition to an existing treatment arm 
(including placebo).
The follow-up at Day 85 adequately covers the duration for immune response for Arms 1-6 and 
Arms 9-14. Likewise, the follow-up at Day 169 adequately covers the duration for immune 
response for Arms 7 and 8.
Participant Characteristics
The participant population are those infected with SARS-CoV-2 that have developed symptoms 
consistent with COVID-19. There is historical evidence that patients infected with upper 
respiratory viruses who are treated early in their disease course have better responses to anti-viral 
therapies (Aoki et al. 2003). This hypothesis will be tested with a focused subgroup analysis on 
participants who received intervention within 8 days of symptom onset and using a virology 
endpoint (see Section 3).

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Low Risk Participants
The population of participants with mild to moderate COVID-19 illness was chosen to evaluate 
if effective antiviral antibody therapy may prevent progression to the severe form of COVID-19 
illness by treating this population early in their disease course and prior to respiratory 
compromise and failure. 
High Risk Participants
The population of participants in treatment arms 12-14 are required to have at least 1 risk factor 
for developing severe COVID-19 illness (see Section 5.1, Inclusion Criteria 27 and 28 for 
treatment arms 12 and 13, and Inclusion Criterion 30 for treatment arm 14).  The risk factors 
were based on the Centers for Disease Control guidance (CDC 2021).  Participants with these 
risk factors are at higher risk for more severe disease and hospitalization.
Adolescent Participants
There are no approved treatments for adolescents infected with SARS-CoV-2 or to prevent 
infection in adolescents with comorbidities that place them at increased risk should they become 
exposed to SARS-CoV-2.  Adolescents with mild or moderate COVID-19 at higher risk for 
severe disease and hospitalization are included in this study.
To minimize invasive procedures and blood volume collection concerns in adolescents, certain 
laboratory tests and sample collections are excluded for this population.
Interim Reviews
The interim safety and efficacy reviews will inform the clinical drug development plans for 
LY3819253 alone, LY3853113 alone, LY3819253 in combination with LY3832479,
LY3853113 in combination with LY3819253 and LY3832479, and LY3819253 in combination 
with VIR-7831. 
Justification for Dose
LY3819253
LY3819253 700 mg was estimated as the maximum therapeutic dose based on PK/PD viral 
dynamics modeling and has a sustained concentration above the in vitro IC90 of viral cell-entry 
neutralization in the lung tissue for at least 28 days in 90% of the participant population. The 
maximum dose of 2800 mg was selected to encompass the maximum therapeutic dose range and 
was selected to explore a wide exposure-response range to mitigate uncertainty and variability in 
the PK and PD and to establish safety and tolerability of LY3819253. The lowest LY3819253 
dose of 175 mg was selected to be approximately 50% of maximum response (Emax) to increase
the probability of demonstrating a dose or exposure-response relationship.
LY3832479
LY3832479 1400 mg dose was selected as the maximum therapeutic dose based on PK/PD viral 
dynamics modeling and has a sustained concentration above the in vitro IC90 of viral cell-entry 
neutralization in the lung tissue for at least 28 days in 90% of the participant population. The 
maximum 2800 mg dose of LY3832479 was selected to optimize the evaluation of dose-

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60
response. The lowest dose of 350 mg was selected to achieve at least 50% of the maximum 
response to increase the probability of demonstrating a dose or exposure-response relationship. 
VIR-7831
The 500 mg dose of VIR-7831 is currently being evaluated in two clinical trials (NCT04545060 
and NCT04501978), with approximately 250 participants dosed to date.
This dose was selected based on extensive nonclinical data and expected human PK extrapolated 
from cynomolgus monkeys.
LY3853113 alone or in combination with LY3819253 and LY3832479
The intravenous target therapeutic doses of LY3853113 (175 mg), LY3819253 (700 mg) and
LY3832479 (1400 mg) were selected individually using PK/PD modeling. The PK/PD modeling 
approach includes in vitro potency data (i.e. IC90), predicted human PK, and the expected 
response in terms of maximal reduction in viral load. For each drug separately, the intention was
to identify a dose that results in drug concentration above IC90 in at least 90% of patients for at 
least 28 days, and that also results in maximum viral load reduction based on a PK-viral dynamic 
model. Also, 700 mg of LY3819253 and 1400 mg of LY3832479 are the currently authorized
doses.
LY3819253 + LY3832479 Combination, LY3853113 + LY3819253 + LY3832479 
Combination, and LY3819253 + VIR-7831 Combination
Arms 2-4, 6-7, 9-10, 12-14: To provide coverage of the different epitopes on SARS-CoV-2 
receptor binding domain sites, the dose selection rationale for each single mAb intervention in 
the combination is the same as for the individual dose rationale for a single mAb intervention. 
Optional Arm(s): The dose levels for optional arms and any additional arms will be determined 
based on interim analysis results in the study and/or other emerging data. 
End of Study Definition
A participant is considered to have completed the study if they have completed all required 
phases of the study including the last scheduled procedure shown in the SoA (Section 1.3).
The end of the study is defined as the date of last scheduled procedure shown in the SoA 
(Section 1.3) for the last participant in the trial globally. 

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5.
Study Population 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
Due to the criticality of participant health, verbal interview of the potential participant, or their 
legal representative or family member, may be the source for disease characteristics and medical 
history, unless otherwise specified within the eligibility criteria.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. For low-risk participant arms only: Are ≥18 and <65 years of age at the time of 
randomization and do not have the risk factors defined in Criterion 27
27. For high-risk participant arms 12 and 13 only:
a.
Are ≥18 years of age and satisfy at least one of the following risk factors at the 
time of screening
i. Are ≥65 years of age
ii. Have a BMI ≥35
iii. Have chronic kidney disease
iv. Have type 1 or type 2 diabetes 
v. Have immunosuppressive disease
vi. Are currently receiving immunosuppressive treatment, or
vii. Are ≥ 55 years of age AND have
1. cardiovascular disease, OR
2. hypertension, OR 
3. chronic obstructive pulmonary disease or other chronic respiratory 
disease
28. For high-risk participant arms 12 and 13 only:
a.
Are 12-17 years of age (inclusive) AND satisfy at least one of the following risk 
factors at the time of screening
i. Have a BMI ≥85th percentile for their age and gender based on CDC 
growth charts (CDC 2017)
ii. Have sickle cell disease 
iii. Have congenital or acquired heart disease 
iv. Have neurodevelopmental disorders, for example, cerebral palsy 
v. Have a medical-related technological dependence, for example, 
tracheostomy, gastrostomy, or positive pressure ventilation (not related to 
COVID-19)
vi. Have asthma or reactive airway or other chronic respiratory disease that 
requires daily medication for control
vii. Have type 1 or type 2 diabetes
viii. Have chronic kidney disease

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ix. Have immunosuppressive disease, or
x. Are currently receiving immunosuppressive treatment.
30. For high-risk participant arm 14 only:
a.
Are ≥12 years of age and satisfy at least one of the following risk factors at the 
time of screening
i. Are ≥65 years of age
ii. Are adults (≥18 years of age) with BMI >25 kg/m2, or if age 12-17, have 
BMI ≥85th percentile for their age and gender based on CDC growth 
charts (CDC 2017)
iii. Have chronic kidney disease
iv. Have type 1 or type 2 diabetes
v. Have immunosuppressive disease
vi. Are currently receiving immunosuppressive treatment
vii. Have cardiovascular disease (including congenital heart disease) or 
hypertension
viii. Have chronic lung diseases (for example, chronic obstructive pulmonary 
disease, asthma [moderate-to-severe], interstitial lung disease, cystic 
fibrosis and pulmonary hypertension)
ix. Have sickle cell disease
x. Have a neurodevelopmental disorder (for example, cerebral palsy) or other 
conditions that confer medical complexity (for example, genetic or 
metabolic syndromes and severe congenital anomalies), or
xi. Have a medical-related technological dependence (for example, 
tracheostomy, gastrostomy, or positive pressure ventilation [not related to 
COVID-19])
Disease Characteristics
2. Are currently not hospitalized
3. Have one or more mild or moderate COVID-19 symptoms (CDC 2020; FDA 2021 ) 
i. Fever
ii. Cough
iii. Sore throat
iv. Malaise
v. Headache
vi. Muscle pain 
vii. Gastrointestinal symptoms, or
viii. Shortness of breath with exertion
ix. Nasal congestion or runny nose
x. New loss of smell
xi. Chills
4. Must have sample collection for first positive SARS-CoV-2 viral infection determination 
≤3 days prior to start of the infusion

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Sex
5. Are men or non-pregnant women
Reproductive and Contraceptive agreements and requirements are provided in 
Section 10.4, Appendix 4. Contraceptive use by men or women should be consistent with 
local regulations for those participating in clinical studies. 
Study Procedures
6. Understand and agree to comply with planned study procedures
7. Agree to the collection of nasopharyngeal swabs and venous blood
Informed Consent
8. The participant or legally authorized representative gives signed informed consent and/or 
assent 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 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
9. For low-risk participants only: Have a BMI ≥35
Note: BMI is rounded to the nearest whole number, for example, 34.5 is rounded to 35.
10. Have SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 <300, respiratory rate ≥30 per 
minute, heart rate ≥125 per minute (FDA resource page, WWW) 
11. Require mechanical ventilation or anticipated impending need for mechanical ventilation 
12. Have known allergies to any of the components used in the formulation of the 
interventions
13. Have hemodynamic instability requiring use of pressors within 24 hours of 
randomization 
14. Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides 
COVID-19) that in the opinion of the investigator could constitute a risk when taking 
intervention
15. Have any co-morbidity requiring surgery within <7 days, or that is considered life-
threatening within 29 days
16. Have any serious concomitant systemic disease, condition or disorder that, in the opinion 
of the investigator, should preclude participation in this study
Other Exclusions
17. Have a history of a positive SARS-CoV-2 serology test
18. Have a history of a positive SARS-CoV-2 test prior to the one serving as eligibility for 
this study
19. Have received an investigational intervention for SARS-CoV-2 prophylaxis within 30 
days before dosing
20. Have received treatment with a SARS-CoV-2 specific monoclonal antibody

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21. Have received convalescent COVID-19 plasma treatment 
22. For low-risk arms only: Have received a SARS-CoV-2 vaccine OR have participated in a 
previous SARS-CoV-2 vaccine study and are currently blinded to treatment allotment
23. Have participated, within the last 30 days, in a clinical study involving an investigational 
intervention. If the previous investigational intervention has a long half-life, 5 half-lives 
or 30 days, whichever is longer, should have passed.
24. Are concurrently enrolled in any other type of medical research judged not to be 
scientifically or medically compatible with this study
25. Are pregnant or breast feeding
26. Are investigator site personnel directly affiliated with this study
29. Have body weight <40 kg.
Lifestyle Considerations
Reproductive and Contraceptive guidance is provided in Section 10.4, Appendix 4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently enrolled in 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. Minimal information includes demography, screen failure details, eligibility criteria, 
and any serious adverse event (SAE).
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
rescreened. 

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6.
Study Intervention
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol.
Study Intervention(s) Administered
Each participant will receive a single administration of either placebo, LY3819253, LY3853113,
LY3819253 in combination with LY3832479, LY3853113 in combination with LY3819253 and 
LY3832479, or LY3819253 in combination with VIR-7831. Study intervention must be 
administered within 3 days of the first positive SARS-CoV-2 test sample collection.
Treatment Arms 1-6
Intervention 
Name
Placebo
LY3819253 + 
LY3832479
LY3819253 + 
LY3832479
LY3819253 + 
LY3832479
LY3819253
LY3819253 + 
LY3832479
Dose 
Formulation
0.9% sodium 
chloride 
solution
Solution
Dosage Level(s) 
(mg)
Not applicable
175 mg + 
350 mg
700 mg + 
1400 mg
2800 mg + 
2800 mg
700 mg
350 mg + 
700 mg
Use
Placebo
Experimental
IMP and NIMP
IMP
IMP
Sourcing
Commercially 
available 0.9% 
sodium 
chloride 
solution
From Lilly
Packaging and 
Labeling
Commercially 
available 0.9% 
sodium 
chloride 
solution
Study Intervention will be provided in glass vials and will be labeled 
appropriately
Abbreviations: IMP = investigational medicinal product.

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Treatment Arms 7-8
Intervention Name
Placebo
LY3819253 + VIR-7831
TBD
Dose Formulation
0.9% sodium 
chloride solution
Solution
Solution
Dosage Level(s) 
(mg)
Not applicable
700 mg + 500 mg
TBD
Use
placebo
Experimental
Experimental
IMP and NIMP
IMP
IMP
IMP
Sourcing
Commercially 
available 0.9% 
sodium chloride 
solution
From Lilly
From Lilly
Packaging and 
Labeling
Commercially 
available 0.9% 
sodium chloride 
solution
Provided in glass vials and 
labeled appropriately
Provided in glass vials and 
labeled appropriately
Abbreviations: IMP = investigational medicinal product.
Treatment Arms 9-14
Intervention Name
Placebo
LY3853113
LY3853113 + LY3819253 + 
LY3832479
Dose Formulation
0.9% sodium 
chloride solution
Solution
Solution
Dosage Level(s) 
(mg)
Not applicable
175 mg
175 mg + 700 mg + 1400 mg
Use
Placebo
Experimental
Experimental
IMP and NIMP
IMP
IMP
IMP
Sourcing
Commercially 
available 0.9% 
sodium chloride 
solution
From Lilly
From Lilly
Packaging and 
Labeling
Commercially 
available 0.9% 
sodium chloride 
solution
Study Intervention will be 
provided in glass vials and 
will be labeled 
appropriately.
Study Intervention will be 
provided in glass vials and will 
be labeled appropriately.
Abbreviations: IMP = investigational medicinal product.
Infusion information may be found in the pharmacy preparation instructions.
Arms 1-6
Participants should be monitored for at least 1 hour after completion of infusion. The infusion 
rate may be reduced as deemed necessary if an infusion reaction is observed (Section 6.1.1.2).
Arms 7-8
Participants should receive LY3819253 or placebo first and should be monitored for at least 30 
minutes after completion of the LY3819253 or placebo infusion and before infusion of VIR-
7831 or placebo. Participants should be monitored for at least 1 hour after VIR-7831 infusion or 

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placebo. The infusion rate may be reduced as deemed necessary if an infusion reaction is 
observed (Section 6.1.1.2).
This protocol allows some alteration from the currently outlined dosing schedule, but the 
maximum doses will not exceed 2800 mg for LY3819253 or LY3832479, and 500 mg for VIR-
7831.
Arms 9-14
Participants should be monitored for at least 1 hour after completion of infusion. The infusion 
rate may be reduced as deemed necessary if an infusion reaction is observed (Section 6.1.1.2).
Further details will be included in the pharmacy preparation instructions (PPI). The site must 
have resuscitation equipment, emergency drugs and appropriately training staff available during 
the infusion and for at least 1 hour after the completion of the infusion. 
6.1.1.
Special Treatment Considerations
6.1.1.1.
Premedication for Infusions
Premedication for infusions is not planned. However, if an infusion reaction occurs during 
administration or if the participant has a medical history suggesting a potential benefit from 
premedication, the study investigator(s) should determine the appropriate premedication.
The investigators and sponsor may decide to use premedication if the frequency of infusion 
reactions among participants warrants it.
If minor infusion reactions are observed, administration of acetaminophen, 500 mg to 1000 mg, 
antihistamines and/or other appropriately indicated medications may be given prior to the start of 
infusions for subsequent participants. 
The decision to implement premedication for infusions in subsequent participants will be made 
by the investigator and sponsor and recorded in the study documentation. 
Any premedications given will be documented as a concomitant therapy. 
6.1.1.2.
Management of Infusion Reactions
All participants should be monitored closely, as there is a risk of infusion reaction and 
hypersensitivity (including anaphylaxis) with any biological agent. 
Symptoms and Signs
Symptoms and signs that may occur as part of an infusion reaction include, but are not limited to 
fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash 
including urticaria, pruritus, myalgia, hypoxia, rapid heart rate, fatigue, altered mental status, and 
dizziness. 
Infusion-related reactions severity will be assessed and reported using the Division of AIDS
(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, version 2.1 
(July 2017). 

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This table describes the severity of reactions according to DAIDS. 
Parameter
Mild
Moderate
Severe
Severe and 
Potentially 
Life-threatening
Acute Allergic 
Reaction
Localized urticaria 
(wheals) with no 
medical intervention 
indicated
Localized urticaria 
with intervention 
indicated 
OR 
Mild angioedema 
with no intervention 
indicated
Generalized Urticaria 
OR
Angioedema with 
intervention indicated 
OR
Symptoms of mild 
bronchospasm
Acute anaphylaxis 
OR 
Life-threatening 
bronchospasm 
OR
Laryngeal edema
Cytokine 
Release 
Syndromea
Mild signs and 
symptoms 
AND
Therapy, that is, 
antibody infusion 
interruption not 
indicated
Therapy (that is, 
antibody infusion) 
interruption 
indicated
AND
Responds promptly 
to symptomatic 
treatment
OR
Prophylactic 
medications 
indicated for ≤24 
hours
Prolonged severe 
signs and symptoms 
OR
Recurrence of 
symptoms following 
initial improvement
Life-threatening 
consequences 
(for example, 
requiring pressor or 
ventilator support)
a
A disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath.
Source: Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 
2.1 (July 2017).
Site Needs
The clinical site should have necessary equipment and medications for the management of any 
infusion reaction, which may include but is not limited to oxygen, IV fluid, epinephrine, 
acetaminophen and antihistamine.
Management of Infusion Reactions
Investigators should determine the severity of the infusion reaction and manage infusion 
reactions based on standard of care and their clinical judgment. If an infusion reaction occurs, 
then supportive care should be used in accordance with the signs and symptoms.
If a participant permanently discontinues from study intervention, they should complete AE 
monitoring and other procedures as stated in the SoA (Section 1.3). 
6.1.2.
Temporary Stopping Criteria
The Assessment Committee (AC) members individually will review unblinded safety data and 
meet as described in the AC Charter. The AC will conduct a full safety review before 
determining if enrollment should be stopped and/or other study parameters should be modified. 
(see Section 9.6).

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This table describes the location of AE-related information in this protocol.
Topic
Location
DAIDS table describing severity of reactions
Section 6.1.1.2
Definition of AEs 
Section 10.3.1
Assessment of Intensity/Severity 
Section 10.3.3
Abbreviations: DAIDS = Division of AIDS. 
Changes to the planned dosing schedule must be appropriately documented and communicated 
with the study personnel and the IRB/IEC before dosing continues. 
Preparation/Handling/Storage/Accountability
The investigator or designee must confirm appropriate storage conditions have been maintained 
during transit for all study intervention received and any discrepancies are reported and resolved 
before use of the study intervention.
To protect blinding, the interventions must be prepared by an unblinded site personnel qualified 
to prepare study intervention who are not involved in any other study-related procedures. 
Instructions for preparation will be provided by the sponsor.
Only participants enrolled in the study may receive study intervention and only authorized site 
staff may supply or administer study intervention. 
All study intervention must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access limited 
to the investigator and authorized site staff.
The investigator or designee is responsible for study intervention accountability, reconciliation, 
and record maintenance (i.e., receipt, reconciliation, and final disposition records).
Further guidance and information for the final disposition of unused study interventions are 
provided in the pharmacy manual.
Measures to Minimize Bias: Randomization and Blinding
Randomization
All participants will be centrally randomized to study intervention using an Interactive Web 
Response System (IWRS). Before the study is initiated, the log in information and directions for 
the IWRS will be provided to each site.
Participants will be stratified by duration since symptom onset to randomization (≤8 days versus 
>8 days). For treatment arms 12-13, participants will also be stratified by whether they received 
a SARS-CoV-2 vaccine or not prior to screening.
For arms 1-11, all eligible participants will be randomized, initially following an equal allocation 
to treatment arms. For arms 12-13, eligible participants will be randomized following a 2:1 
allocation to treatment arms. Periodic adjustments to the allocation ratio, informed by planned 
interim analyses, may be made in an effort to achieve an equal allocation across the treatment 
arms at the end of enrollment. Given the staggered start of treatment arms, additional participants 

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may be enrolled in existing treatment arms and the allocation ratio may change accordingly. See 
Section 9.5 for details. 
Participants will be assigned to treatment arm 14 after treatment arms 12 and 13 have completed 
enrollment.

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Blinding
Treatment arms 1-11 will be blinded. Neither participants, nor investigators, nor the sponsor 
study team will be aware of treatment assignments prior to the final data base locks at the 
conclusion of the study. Treatment arms 12-14 will be open label.
This table describes general procedures for unblinding.
Unblinding (IWRS)

Emergency unblinding for adverse events may be performed through the 
IWRS. All actions resulting in an unblinding event are recorded and 
reported by the IWRS

In case of an emergency, the investigator has the sole responsibility for 
determining if unblinding of a participants’ intervention assignment 
is warranted

Participant safety must always be the first consideration in making such a 
determination. However, the investigator should make all attempts to 
contact the Medical Monitor in advance of unblinding

If a participant’s intervention assignment is unblinded, the sponsor must be 
notified immediately after breaking the blind even if consultation occurred 
in advance

The date and reason that the blind was broken must be recorded in the 
source documentation and case report form. 
Abbreviations: IWRS = interactive web-response system.
If an investigator, site personnel performing assessments, or participant is unblinded while the 
infusion is ongoing, the participant must be discontinued from the study intervention and the 
infusion stopped. If any amount of study intervention was administered, follow procedures 
according to the SoA (Section 1.3). 
Study Intervention Compliance
Participants will receive study intervention directly from the investigator or designee, under 
medical supervision. The date and time of dosing will be recorded in the source documents and 
recorded in the CRF. The dose of study intervention and study participant identification will be 
confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study intervention. 
Concomitant Therapy
Prior Treatment 
Any prior therapy, such as antivirals, antibiotics, or anti-malarials used in the prior 30 days to 
signing informed consent should be recorded.
Any SARS-CoV-2 vaccine should be recorded.  Any non-SARS-CoV-2 vaccine received in the 
prior 90 days to signing informed consent should be recorded.
Therapy prior to enrollment with antivirals including lopinavir/ritonavir, remdesivir, or other 
therapeutic agents (e.g., corticosteroids) are permitted. 
Convalescent COVID-19 plasma treatment is not allowed prior to enrollment.

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Concomitant Therapy
Participants should be treated according to standard of care, even as it evolves, and medications 
may be part of the treatment paradigm. Therefore, remdesivir may be initiated as standard of care 
for hospitalized participants (if available through the FDA Emergency Use Authorizations) 
outside of local standard of care per written policies or guidelines. 
If the local standard of care per written policies or guidelines (that is, not just an individual 
clinician decision) includes lopinavir/ritonavir, chloroquine, hydroxychloroquine or other 
investigational agents, then initiating these during the study is permitted, but may require 
additional safety monitoring by the site. 
Convalescent COVID-19 plasma treatment is not allowed. 
Any medication, investigational agent, or vaccine, including over the counter or prescription 
medicines, vitamins, and/or herbal supplements, or other specific categories of interest that the 
participant is receiving at the time of enrollment or receives during the study must be recorded 
along with

Reason for use

Dates of administration including start and end dates, and

Dosage information including dose and frequency for concomitant therapy of special
interest.
Acetaminophen and corticosteroid use are permitted at any time during the study. 
Other concomitant medication may be considered on a case-by-case basis by the investigator in 
consultation with the sponsor if required.
The sponsor should be contacted if there are any questions regarding concomitant or prior 
therapy.
Dose Modification
No dose modifications are planned for this study.
Intervention after the End of the Study
No continued access is planned after completion of this study, as additional efficacy would be 
needed to demonstrate continued access criteria.

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7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
Discontinuation of specific sites or of the trial as a whole are handled as part of regulatory, 
ethical, and trial oversight considerations in Section 10.1.9, Appendix 1.
Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) study intervention. If the study treatment is definitively discontinued, the 
participant will remain in the study for the remainder of the assessment visits through Day 29 
and also for the post-treatment follow-up visits on Days 60 and 85 for all treatment arms and 
Day 169 for treatment arms 7 and 8 as described in the SoA (Section 1.3).
Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study 

at any time at his/her own request 

at the request of his/her designee (for example, parents or legal guardian)

at the discretion of the investigator for safety, behavioral, compliance, or administrative 
reasons

if the participant becomes pregnant during the study, or

if enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be scientifically or 
medically compatible with this study.
If the participant, for any reason, requires treatment with another therapeutic agent that has been 
demonstrated to be effective for treatment of the study indication, discontinuation from the study 
occurs prior to introduction of the new agent.
Discontinuation is expected to be uncommon.
At the time of discontinuation, if possible, an early discontinuation visit should be conducted as 
described in the SoA (Section 1.3). The participant should also return for the post-treatment 
follow-up visits. 
If the participant discontinues on the same day as a normally scheduled visit, only one set of 
laboratory tests, sample collection and assessments are collected.
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, they may request destruction of any samples taken and not tested, and 
the investigator must document this in the site study records.
7.2.1.
Discontinuation of Inadvertently Enrolled Participants
If the sponsor or investigator identify a participant who did not meet enrollment criteria and was 
inadvertently enrolled, then the participant should be discontinued from study intervention unless 

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there are extenuating circumstances that make it medically necessary for the participant to 
continue study intervention. 
If the investigator and the sponsor CRP agree it is medically appropriate to continue, the 
investigator must obtain documented approval from the sponsor CRP to allow the inadvertently 
enrolled participant to continue in the study with or without treatment with investigational 
product. 
Safety follow-up is as outlined in 

Section 1.3 (Schedule of Activities) 

Section 8.2 (Safety Assessments), and 

Section 8.3 (Adverse Events and Serious Adverse Events).
Lost to Follow up
A participant will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and is unable to be contacted by the study site. Site personnel are expected to make diligent 
attempts to contact participants who fail to return for a scheduled visit or were otherwise unable 
to be followed up by the site.
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants that received study 
intervention. Public sources may be searched for vital status information. If vital status is 
determined to be 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.

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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.
Monitoring of blinded safety data will continue throughout the study and will be conducted by 
blinded study team members. Details of the blinded safety reviews, including the frequency and 
approximate timing, are specified in the trial level safety review plan.
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.
Efficacy Assessments
Hospitalization events (Section 8.2.4), procedures of special interest (Section 8.2.5), vital signs 
(Section 8.2.2) and symptomology (Section 8.1.1) will be used to characterize the effect of 
LY3819253 alone, LY3853113 alone, LY3819253 in combination with LY3832479, 
LY8353113 in combination with LY3819253 and LY3832479, or LY3819253 in combination 
with VIR-7831 compared to placebo on clinical status from baseline to Days 3, 5, 7, 11, 22 and 
29.
8.1.1.
Symptoms and Overall Clinical Status Participant Questionnaire
Participants will rate their overall clinical status and severity of symptoms associated with 
COVID-19 by a daily questionnaire. This questionnaire is for outpatients only.
Participants will complete three questions about their overall clinical status daily, including 

severity of symptoms 

general physical health, and 

change in overall health.
The questionnaire contains these symptoms 

cough 

shortness of breath 

feeling feverish 

fatigue 

body aches and pain 

sore throat 

chills 

headache

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
loss of appetite, and

changes in taste and smell. 
Each symptom will be scored daily by the participant as experienced during the past 24 hours. 
Rating
Score
None or absent
0
Mild
1
Moderate
2
Severe
3
Participants will rate changes in taste and smell with a yes/no response.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA (Section 1.3).
8.2.1.
Physical Examinations
A complete physical examination will be performed at the screening visit. This examination 
excludes pelvic, rectal, and breast examinations unless clinically indicated.
A symptom-directed physical examination will be performed at other visits, as specified in the 
SoA and as clinically indicated.
Investigators should pay special attention to clinical signs related to COVID-19, to ongoing 
medical conditions and to previous serious illnesses.
8.2.2.
Vital Signs
Vital signs will be measured as specified in the SoA (Section 1.3) and as clinically indicated. 
Vital signs include

Body temperature

Blood pressure

Pulse rate

Respiration rate

Saturation of peripheral oxygen, and

Supplemental oxygen flow rate, FiO2 if known, and method of delivery, if applicable.

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These tables outline Day 1 vital signs data collection on the CRF in relation to the infusion(s). 
Infusion times may vary depending on the participant. 
Arms 1-6
Timepoint (minutes)
Collect data on CRF
Immediately before infusion
Yes
During Infusion, as possible (if applicable)
--
   15
No
   30
Yes
   45
No
   60 
Yes
After Administration – every 30 minutes for 1 hour after the end of the infusion
--
Abbreviations: CRF = case report form. 
Arms 7-8
Timepoint (minutes)
Collect data on CRF
Immediately before first infusion
Yes
During first infusion, as possible (if applicable)
--
   15
No
   30
Yes
   45
No
   60 
Yes
After first infusion – 30 minutes
--
After last infusion – every 30 minutes for 1 hour
--
Arms 9-11, 13, 14
Timepoint (minutes)
Collect data on CRF
Immediately before infusion
Yes
If infusion is <15 minutes, immediately following completion of infusion
Yes
During Infusions > 15 minutes, as possible (if applicable)
--
   15
No
   30
Yes
   45
No
   60 
Yes
After infusion – every 30 minutes for 1 hour after the end of the infusion
--
   end of infusion +30 minutes
Yes
   end of infusion +60 minutes
No
Additional vital signs may be measured during the study if warranted, as determined by the 
investigator.
8.2.3.
Clinical Laboratory Assessments
See Section 10.2, Appendix 2 for the list of clinical laboratory tests to be performed and the SoA 
(Section 1.3) for the timing and frequency. All protocol-required laboratory assessments, as 

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defined in Appendix 2, must be conducted in accordance with the laboratory manual and the 
SoA.
Clinically significant abnormal laboratory findings are those which are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 
participant's condition.
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 28 days after the dose of study intervention should be repeated until the 
values return to normal or baseline or are no longer considered clinically significant by the 
investigator or sponsor.
If such values do not return to normal/baseline within a period of time judged reasonable by the 
investigator, the etiology should be identified and the sponsor notified.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
The laboratory reports must be filed with the source documents. 
All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted in 
accordance with the laboratory manual and the SoA (Section 1.3).
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (e.g., SAE or AE or dose modification), report in the AE 
section of the CRF.
Pregnancy Testing
Women of childbearing potential (WOCBP) must undergo pregnancy testing according to the 
SoA. Participants who are pregnant will be discontinued from the study.
8.2.4.
Hospitalization events
If a participant is admitted to the hospital, the participant will remain in the study and follow the 
procedures outlined in the SoA (Section 1.3). Hospitalization is defined as ≥24 hours of acute 
care.
The date of hospitalization events will be recorded in the CRF and includes

hospitalization 

emergency room visit 

ICU admittance

Extended care facility admittance, and 

Discharge.
8.2.5.
Procedures of Special Interest
The participants’ clinical status and concurrent procedures of special interest will be recorded in 
the CRF and include consciousness status using the alert, consciousness, verbal, pain, 
unresponsive scale (ACVPU), limitation on activities due to COVID-19 using the patient global 
assessment for daily activities of physical function, and requirements for 

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
ongoing hospital medical care

supplemental oxygen

non-invasive ventilation or a high flow oxygen device 

mechanical ventilation

ECMO, or

additional organ support (e.g., pressors, renal replacement).
8.2.6.
Respiratory Support
Once enrolled in the study, participants may be managed with high-flow nasal cannula, 
noninvasive positive pressure ventilation or any other form respiratory support as needed per 
investigator discretion. 
Adverse Events and Serious Adverse Events
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 AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study intervention or study.
8.3.1.
Time Period and Frequency for Collecting AE and SAE Information
All AEs and SAEs will be collected from the time of signing of the informed consent form (ICF)
until participation in study has ended.
Adverse events that begin before the start of study intervention but after signing of the ICF will 
be recorded on the Adverse Event CRF.
Although all AEs after signing the ICF are recorded by the site in the CRF/electronic data entry, 
SAE reporting to sponsor begins after the participant has signed the ICF and has received study 
intervention. However, if an SAE occurs after signing the ICF, but prior to receiving study 
intervention, it needs to be reported within the SAE reporting timeframe if it is considered 
reasonably possibly related to study procedures.
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.3, Appendix 3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
Investigators are not obligated to actively seek 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.

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8.3.2.
Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences.
8.3.3.
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 SAEs 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.
8.3.4.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of a 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 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 (IRB)/Independent Ethics Committees 
(IEC), and investigators.
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then file 
it with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
8.3.5.
Pregnancy
Details of all pregnancies in female participants will be collected.
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Section 10.4, Appendix 4.
Abnormal pregnancy outcomes, for example, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, and ectopic pregnancy, are considered SAEs. 
8.3.6.
Hypersensitivity Reactions
Many drugs, but particularly biologic agents, carry the risk of systemic hypersensitivity 
reactions. 
If such a reaction occurs, additional details describing each symptom should be provided to the 
sponsor in the infusion-related reaction/hypersensitivity CRF.  
If symptoms and/or signs occur during or within 6 hours after infusion and are believed to be 
hypersensitivity or due to cytokine release, then investigators are encouraged to report the event 

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as infusion-related immediate hypersensitivity reaction or cytokine release-associated infusion 
reaction, respectively.
Sites should have appropriately trained medical staff and appropriate medical equipment 
available when study participants are receiving intervention. It is recommended that participants 
who experience a systemic hypersensitivity reaction be treated per the local standard of care.  
In the case of generalized urticaria or anaphylaxis, additional blood and urine samples should be 
collected as described in Section 10.6, Appendix 6, “Recommended Laboratory Testing for 
Hypersensitivity Events”. Laboratory results are provided to the sponsor via the central 
laboratory. 
In case of skin lesions or rash consistent with vasculitis, efforts should be made to perform the 
following as soon as possible

dermatology consultation

skin biopsy, and

photographs of lesions of interest, including skin biopsy site.
8.3.7. Infusion-related Reactions
As with other mAbs, infusion-related reactions may occur during or following IV administration. 
If an infusion-related reaction occurs, additional data describing each symptom and sign should 
be provided to the sponsor in the CRF.
This table describes the location of infusion-related reaction information in this protocol.
Topic
Location
Special treatment considerations
Section 6.1.1
Premedication for infusions
Section 6.1.1.1
Management of infusion reactions
Section 6.1.1.2
DAIDS table describing severity
Section 6.1.1.2
Treatment guidelines for infusion-related reactions 
Section 6.1.1.2
Symptoms occurring during or after infusion of study intervention may also be defined according 
to AE categories such as acute allergic reaction or cytokine release syndrome (refer to DAIDS).  
8.3.8. Product Complaints
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness or performance of a 
trial intervention.
Sponsor collects product complaints on study intervention and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.

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Participants will be instructed to contact the investigator as soon as possible if they have a 
complaint or problem with the intervention so that the situation can be assessed.
NOTE: AEs/SAEs that are associated with a product complaint will also follow the processes 
outlined in Section 8.3.3 and Appendix 10.3 of the protocol.
Time Period for Detecting Product Complaints
Product complaints that result in an adverse event will be detected, documented, and reported to 
the sponsor during all periods of the study in which the intervention is used.
If the investigator learns of any product complaint at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to an intervention 
provided for the study, the investigator will promptly notify the sponsor.
Prompt Reporting of Product Complaints to Sponsor
Product complaints will be reported to the sponsor within 24 hours after the investigator becomes 
aware of the complaint.
The Product Complaint Form will be sent to the sponsor by a method designated by the sponsor.
Follow-up of Product Complaints
Follow-up applies to all participants, including those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the product complaint.
New or updated information will be recorded on the originally completed form with all changes 
signed and dated by the investigator and submitted to the sponsor.
Treatment of Overdose
There is no known antidote for an overdose of LY3819253 alone, LY3853113 alone, 
LY3819253 in combination with LY3832479, LY3853113 in combination with LY3819253 and 
LY3832479, or LY3819253 in combination with VIR-7831. 
In the event of an overdose, the investigator should
1. Contact the sponsor immediately.
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities 
3. Provide supportive care as necessary, and
4. Document the quantity of the excess dose in the CRF.
Decisions regarding infusion interruptions or modifications will be made by the investigator, in 
consultation with the sponsor, based on the clinical evaluation of the participant.
Pharmacokinetics
Venous blood samples will be collected as specified in the SoA (Section 1.3) for determination 
of concentrations of LY3819253, LY3832479, LY3853113, and VIR-7831 used to evaluate the 
PK for LY3819253, LY3832479, LY3853113, and VIR-7831.  

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A maximum of 3 samples may be collected at additional time points during the study if 
warranted and agreed upon between the investigator and the sponsor.
Instructions for the collection and handling of biological samples will be provided by Lilly. 
Site personnel will record

The date and time (24-hour clock time) of administration (start and end of infusion), and

The date and time (24-hour clock time) of each PK sample.
It is essential that the times are recorded accurately.  
8.5.1.
Bioanalytical
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor. Concentrations of LY3819253, LY3832479, LY3853113, and VIR-
7831 will be assayed using a validated bioanalytical method. Analyses of samples collected from 
placebo-treated participants are not planned.
Sample retention is described in Appendix 1, Section 10.1.12. Remaining samples used for PK 
may be pooled and used for exploratory metabolism or bioanalytical method experiments as 
deemed appropriate.
Pharmacodynamics
The SARS-CoV-2 viral RNA level and viral clearance will be evaluated by nasopharyngeal 
swabs. See Section 10.2 Clinical Laboratory Tests, and Section 1.3, the SoA for sample 
collection information.  
Sample retention is described in Appendix 1, Section 10.1.12. Remaining samples may be used 
for additional exploratory studies to better understand LY3819253, LY3832479, LY3853113, 
VIR-7831 and the disease, which may include sequencing and/or culture of the virus for future 
studies.
Genetics
A whole blood sample will be collected for pharmacogenetic analysis where local regulations 
allow.  
See Section 10.2, Clinical Laboratory Tests, and Section 1.3, the SoA for sample collection 
information.  
See Section 10.5 for genetic research, custody, and sample retention information.
Biomarkers
Blood samples will be collected from all participants for analysis of immune system-related 
markers. Serum, whole blood for cellular and/or epigenetic analysis, and whole blood RNA 
samples for exploratory biomarker research will be collected at the time specified in the SoA 
(Section 1.3) where local regulations allow.  
Samples will be stored and analysis may be performed on biomarkers thought to play a role in 
immune system related responses to viral infection including, but not limited to, immune 

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pathways, cellular composition, serum analytes, or epigenetic biomarkers, to evaluate their 
association with observed clinical responses to LY3819253, LY3832479, LY3853113, VIR-7831
and the disease state.
Samples may be used for research to develop methods, assays, prognostics and/or companion 
diagnostics related to the intervention target (S protein), the COVID-19 disease state, pathways 
associated with disease, and/or the mechanism of action of the study intervention.
Sample retention is described in Section 10.1.12. 
Immunogenicity Assessments
Visits and times
At the visits and times specified in the SoA (Section 1.3), venous blood samples will be collected 
to determine antibody production against LY3819253, LY3832479, LY3853113 and/or VIR-
7831. The actual date and time (24-hour clock time) of each sample collection will be recorded.  
Sample collection, handling, and use
Instructions for the collection and handling of blood samples will be provided by the sponsor.
Immunogenicity may be assessed by a validated assay designed to detect ADAs in the presence 
of LY3819253, LY3832479, LY3853113, and/or VIR-7831 at a laboratory approved by the 
sponsor. Antibodies may be further characterized for their ability to neutralize the activity of 
LY3819253, LY3832479, LY3853113, and/or VIR-7831.
Sample retention
Sample retention is described in Appendix 1, Section 10.1.12. 
Health Economics
This section is not applicable for this study.

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9.
Statistical Considerations
Statistical Hypotheses
For treatment arms 1-6, the null hypothesis for the primary endpoint is that there is no difference 
between any of the doses of LY3819253 alone or in combination with LY3832479, versus
placebo participants in the proportion of participants with SARS-CoV-2 viral load greater than 
5.27 on Day 7 (+2 days). 
For treatment arms 7-8, the null hypothesis for the primary endpoint is that there is no difference 
between LY3819253 in combination with VIR-7831 versus placebo participants in the 
proportion of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7 (+2 days).
For treatment arms 9-11, the null hypothesis for the primary endpoint is that there is no 
difference between LY3853113 alone or in combination with LY3819253 and LY3832479, 
versus placebo participants in the proportion of participants with SARS-CoV-2 viral load greater 
than 5.27 on Day 7.
Sample Size Determination
Sample Size
Treatment arms 1-6
The initial planned sample size is approximately 500 participants allocated across five treatment 
arms (treatment arms 1-5). The planned sample size is approximately 100 participants for 
treatment arm 6. Since treatment arm 6 begins enrollment after treatment arms 1-5, additional 
participants will be enrolled in treatment arm 1 to ensure at least a 50% increase in placebo 
participants and concurrent placebo control for the primary comparison of treatment arm 6.
Additional participants will also be enrolled in treatment arm 3 to ensure at least a 50% increase 
in LY3819253 700 mg + LY3832479 1400 mg participants to provide concurrent enrollment of 
an additional treatment arm.
Up to 100 additional participants may be introduced either for each optional treatment arm or in 
addition to an existing treatment arm (including placebo). See Section 9.5 for interim analysis 
details.
Sample size was determined based on pairwise comparisons of each dose compared to placebo. 
An assumed sample size of 100 participants in treatment arms 2, 4-6 and 150 participants in 
treatment arms 1 and 3 provides greater than 90% power to test the superiority of at least one 
dose of LY3819253 or the combination of LY3819253 and LY3832479 versus placebo at the 
two-sided 0.05 alpha level, adjusted for multiplicity, on the proportion of participants with 
SARS-CoV-2 viral load greater than 5.27 at Day 7 (+2 days). This assumes the true underlying 
proportion of participants meeting this endpoint is 5% in the LY3819253 arm of 700 mg, and 
LY3819253 + LY3832479 combination treatment arms for dose levels 2800 mg + 2800 mg, and 
700 mg + 1400 mg, 7% for dose level 350 mg + 700 mg and for dose level 175 mg + 350 mg,
and 19% in the placebo arm. 
Treatment arms 7-8
The planned sample size is approximately 100 participants per treatment arm.

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Sample size was determined based on a pairwise comparisons of LY3819253 in combination 
with VIR-7831 compared to placebo. An assumed sample size of 100 participants in treatment 
arms 7 and 8 provides greater than 87% power to test the superiority at the two-sided 0.05 alpha 
level, on the proportion of participants with SARS-CoV-2 viral load greater than 5.27 at Day 7 
(+2 days). This assumes the true underlying proportion of participants meeting this endpoint is 
5% in the LY3819253 700 mg + VIR-7831 500 mg treatment arm and 19% in the placebo arm.  
The sample size calculations were performed using simulations from the software EAST© v6.5.  
Periodic adjustments to the allocation ratio of participants may be made based on interim 
analyses. See Section 9.5 for details.
Treatment arms 9-11
The planned sample size is approximately 122 participants per treatment arm.
Sample size was determined based on pairwise comparisons of each dose compared to placebo. 
An assumed sample size of 122 participants per treatment arm provides about 84% power to test 
the superiority of either LY3853113 alone or the combination with LY3819253 and LY3832479 
versus placebo at the two-sided 0.05 alpha level on the proportion of participants with SARS-
CoV-2 viral load greater than 5.27 at Day 7. This assumes the true underlying proportion of 
participants meeting this endpoint is 12% in both the LY3853113 alone treatment arm and the 
LY3853113 + LY3819253 + LY3832479 combination treatment arm, and 28% in the placebo 
arm. 
Treatment arms 12-14
Approximately 100 participants will be enrolled into treatment arm 12 and approximately 50
participants will be enrolled into treatment arm 13.  Treatment arm 12 includes a greater number 
of participants to assess the tolerability of undiluted LY3853113 administration. Approximately 
140 participants will be enrolled into treatment arm 14 once treatment arms 12 and 13 have 
completed enrollment.
Stratification
Treatment arms 1-13
Participants will be stratified by duration since symptom onset category (≤8 days versus 
>8 days).
Treatment arms 12-13
Participants will be stratified by whether a participant received a SARS-CoV-2 vaccine or not 
prior to screening.

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Populations for Analyses
This table defines the populations for analysis. 
Population
Description
Entered
All participants who sign the informed consent form
Efficacy
All randomized participants who received study intervention and provided at 
least one post-baseline measure for the relevant endpoint. Participants will be 
analyzed according to the intervention to which they were randomized. 
(Intention to treat).
Safety
All participants randomly assigned and who received study intervention. 
Participants will be analyzed according to the intervention they actually 
received.
Pharmacokinetic 
All randomized participants who received study intervention and have 
evaluable PK sample. Participants will be analyzed according to the 
intervention they received.
Statistical Analyses
Statistical analysis of this study will be the responsibility of the Sponsor or its designee.
Unless otherwise specified, treatment effects will be conducted using 2-sided tests at an alpha 
level of 0.05. No adjustment for multiplicity will be performed in this study. 
Analyses will be performed separately for treatment arms 

1-6

7 and 8,

9-11,

12 and 13, and

14.
For treatment arms 12 and 13, participants who have received a SARS-CoV-2 vaccine prior to 
screening may be summarized separately from those who have not received a SARS-CoV-2 
vaccine prior to screening, for all efficacy outcomes.
Details of the handling of dropouts or missing data will be fully described in the statistical 
analysis plan (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. Additional exploratory analyses of the data will be conducted as deemed appropriate.
The SAP will be finalized prior to the first final database lock (i.e., first unblinding of the 
sponsor), and it will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses of the most 
important endpoints including primary and secondary endpoints.

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9.4.1. General Considerations
This table describes the general statistical methods that may be used in this study. 
Method
Analysis 
Descriptive Statistics
number of participants, mean, standard deviation, 
median, minimum, and maximum for continuous 
measures, and frequency counts and percentages for 
categorical measures
Kaplan-Meier curves and summary statistics
Treatment comparisons of time-to-event based 
endpoints
Logistic regression analysis
Treatment comparisons of binary variables with 
treatment and randomization stratification variables in 
the model.
Nonparametric 
(for example, Mann-Whitney or van Elteren tests)
Treatment comparison of ordinal, nominal and non-
normally distributed continuous variables.
Additional statistical methodology, sensitivity analyses accounting for missing data, and 
adjustments for covariates, if any, will be described in the SAP. 
9.4.2.
Primary Endpoints
Treatment Arms 1-11
The primary endpoint is the proportion of participants with SARS-CoV-2 viral load greater than 
5.27 on Day 7, corresponding to Ct value of 27.5 based on nasopharyngeal swab sampling for 
reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2.  
Statistical hypotheses testing for the primary endpoint will be conducted using a logistic 
regression model at the two-sided 0.05 level.
Full details will be provided in the SAP.
Treatment Arms 12-14
All investigational product and protocol procedure AEs will be listed, and if the frequency of 
events allows, safety data will be summarized using descriptive methodology.
The incidence of AEs and SAEs for each treatment will be presented by severity and by 
association with intervention as perceived by the investigator. Adverse events reported prior to 
randomization will be distinguished from those reported as new or increased in severity during 
the study post-randomization.
Safety parameters that will be assessed include, but are not limited to, safety laboratory 
parameters, and vital signs. The parameters will be listed and summarized using standard 
descriptive statistics. Additional analysis will be performed if warranted upon review of the data. 
9.4.3.
Secondary Endpoints
9.4.3.1.
Safety (Arms 1-11)
Safety analyses will be conducted using the safety population described above. 

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All investigational product and protocol procedure AEs will be listed, and if the frequency of 
events allows, safety data will be summarized using descriptive methodology.
The incidence of AEs and SAEs for each treatment will be presented by severity and by 
association with intervention as perceived by the investigator. Adverse events reported prior to 
randomization will be distinguished from those reported as new or increased in severity during 
the study post-randomization.
Safety parameters that will be assessed include, but are not limited to, safety laboratory 
parameters, and vital signs. The parameters will be listed and summarized using standard 
descriptive statistics. Additional analysis will be performed if warranted upon review of the data. 
9.4.3.2.
Additional Secondary Endpoints
Additional secondary endpoints include

Proportion (percentage) of participants who experience these events by Day 29
o
COVID-19 related hospitalization (defined as ≥ 24 hours of acute care), or
o
death.

SARS-CoV-2 viral load change from baseline to 
o
Day 3 
o
Day 5
o
Day 7
o
Day 11

Proportion of participants with viral load greater than 5.27 on Day 7 among participants 
enrolled with ≤ 8 days of symptoms prior to randomization

Proportion of participants that achieve SARS-CoV-2 clearance (Days 3, 5, 7, 11, and 29)

Time to SARS-CoV-2 clearance

SARS-CoV-2 viral load AUC assessed through Day 11.

75th percentile of SARS-CoV-2 viral load at Day 7

Time to symptom resolution 
o
symptoms are scored as absent

Proportion of participants demonstrating symptom resolution via the symptom questionnaire 
on Days 3, 5, 7, 11, 22, and 29

AUC from baseline to Day 11

Change in symptom score (total of ratings) from baseline up to Days 7, 11, 22, and 29

Time to symptom improvement
o
symptoms scored as moderate or severe at baseline are scored as mild or absent, AND 
o
symptoms scored as mild or absent at baseline are scored as absent.

Proportion of participants demonstrating symptom improvement via the symptom 
questionnaire on Days 3, 5, 7, 11, 22, and 29

Proportion (percentage) of participants who experience these events by Day 22
o
COVID-19 related hospitalization (defined as ≥ 24 hours of acute care) 
o
death.

Proportion (percentage) of participants who experience these events through Day 29: 
o
COVID-19 related hospitalization (defined as ≥24 hours of acute care),

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o
COVID-19 related emergency room visit, or
o
death.

Characterize the PK of LY3819253, LY3832479, LY3853113, and VIR-7831
o
Mean concentration of LY3819253 and LY3832479 on Day 29
o
Mean concentration of LY3819253 in combination with VIR-7831 on Day 29
o
Mean concentration of LY3853113 in combination with LY3819253 and LY3832479 
on Day 29
Full details of the analyses will be in the SAP.
9.4.3.3.
Pharmacokinetic Analyses 
Pharmacokinetic analyses will be conducted on data from all participants who receive 
intervention and have evaluable PK.
Concentration-time data for LY3819253, LY3832479, LY3853113, and VIR-7831 will be 
summarized descriptively. A population approach using a nonlinear mixed-effects modeling 
(NONMEM) program may also be performed. 
Study data may be pooled with the results of other studies for population PK and PK/PD analysis 
purposes.
9.4.4.
Exploratory Analyses
Full details of the planned exploratory analyses will be described in the SAP.
Additional exploratory analyses of the data will be conducted as deemed appropriate. Study 
results may be pooled with the results of other studies for safety, PD, or population PK and 
PK/PD analysis purposes.
9.4.5.
Immunogenicity Analyses
If data from validated immunogenicity assays are available, treatment-emergent anti-drug 
antibodies (TE-ADAs) may be assessed. 
Treatment-emergent ADAs are defined as participants

with a 2-fold (1 dilution) increase in titer than the minimum required dilution if no ADAs 
were detected at baseline (treatment-induced ADA) or 

with a 4-fold (2 dilutions) increase in titer compared with baseline if ADAs were detected 
at baseline (treatment-boosted ADA).
The frequency and percentage of participants with preexisting ADA and who are TE-ADA 
positive (TE-ADA+) to LY3819253, LY3832479, LY3853113, and/or VIR-7831 will be 
tabulated.  
The distribution of titers and frequency of neutralizing antibodies (if assessed) for the TE-ADA+ 
participants may also be tabulated.
The relationship between the presence of antibodies and PK parameters, efficacy response or 
safety to LY3819253, LY3832479, LY3853113 and/or VIR-7831 may also be assessed. 
Additional details may be provided in the SAP. 

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9.4.6.
Subgroup Analyses
This study is not powered for subgroup analyses; therefore, all subgroup analyses will be treated 
as exploratory.
Subgroup analyses will be conducted for the primary endpoint. Subgroups may include 

time of symptom onset to study randomization

baseline severity of COVID-19

age 

sex 

race 

ethnicity 

baseline weight

baseline body mass index, or

concomitant medication
Treatment group differences will be evaluated within each category of the subgroup regardless of 
whether the interaction is statistically significant. If any group within the subgroup is <10% of 
the total population, only summaries of the efficacy data will be provided, that is, no inferential 
testing.
Definitions for the levels of the subgroup variables, the analysis methodology, and any additional 
subgroup analyses will be defined in the SAP. 
Interim Analyses
The ongoing study may be modified based on planned interim analyses. Based on the observed 
data at the time of the interim analyses, the study may 

suspend enrollment to any treatment arm demonstrating lack of efficacy, and/or

initiate/expand enrollment to an additional/existing treatment arm (or arms).
The modifications proposed are done so to ensure participants are being exposed to treatment 
with an acceptable risk-benefit profile during the ongoing trial. Additionally, the potential 
modifications will provide information to more fully characterize the dose response profile. 
Monitoring of unblinded safety data (including AEs, SAEs, and selected laboratory 
measurements) will occur throughout the study and will be conducted by Assessment Committee 
(AC) members. Details of the unblinded safety reviews, including the frequency and
approximate timing, are specified in the AC charter. 
An interim analysis is planned when approximately 75 participants in each arm (treatment arms 
1-5) reach Day 7. Additional interim analyses may be conducted when at least 50% of
participants in treatment arm 6 reach Day 7 and also when at least 33% of participants in 
treatment arms 7 and 8 reach Day 7.
The approximate timing, decision criteria, and statistical methods associated with each possible 
modification to the ongoing trial will be fully described in the SAP and AC Charter and finalized 
prior to the first study unblinding.  

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Periodic adjustments to the allocation ratio may be made to achieve the planned allocation across 
treatment arms at the conclusion of enrollment. If additional placebo participants are enrolled, 
then the allocation ratio may change accordingly.
Prior to the primary endpoint, only the AC (and individuals as defined in the unblinding plan) is 
authorized to evaluate unblinded interim analyses and safety analyses. Study sites will receive 
information about interim results only if they need to know for the safety of their participants. 
Unblinding details are specified in the unblinding plan section of the SAP or in a separate 
unblinding plan document.  

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Data Monitoring Committee (DMC)
The sponsor will form an AC to analyze the interim study data. To minimize any bias introduced 
into the analysis of the study results, analysis plans will be finalized and approved prior to the 
interim analyses.
The primary goal of the AC is to review the interim results regarding the continuing safety of 
study participants and the continuing validity and scientific merit of the study. Information that 
may unblind the study during the analyses will not be reported to study sites or the blinded study 
team until the study has been unblinded. 
Overall committee structure information is in Section 10.1.5. Details of the AC will be provided 
in the AC charter.

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10.
Supporting Documentation and Operational Considerations
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 Harmonization (ICH) Good Clinical Practice (GCP) 
Guidelines, and

Applicable laws and regulations.
The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant documents 
(e.g., advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated.
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.
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, and

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.
Investigator sites are compensated for participation in the study as detailed in the clinical trial 
agreement.
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 study and for 1 year after 
completion of the study.

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10.1.3.
Informed Consent Process
The investigator or their 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 representative will be required to sign a statement of informed consent and 
child/adolescent assent, as appropriate, that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center.
Due to strict respiratory isolation policies, limited access to COVID-19 patient rooms, and 
SARS-CoV-2 transmissibility via droplet-contaminated paper, verbal consent and alternative 
methods of obtaining consent (for example, by phone) will be allowed if approved by the IRB. 
If a signed paper copy of the ICF or child/adolescent assent is allowed by site/institution policy, 
then the process of how it will be obtained and stored will need to be determined. 
Any variation from the standard consent process due to isolation and infection control should be 
sent to the IRB for approval prior to enrollment. The site will document the process in their 
regulatory files and demonstrate that the process has IRB concurrence or approval.
The medical record must include a statement that written informed consent or child/adolescent 
assent was obtained before the participant was entered in the study and the date the written 
consent or assent was obtained. The authorized person obtaining the informed consent or 
child/adolescent assent, and, if applicable, the individual designated to witness a verbal consent, 
must also sign the ICF.
Participants must be re-consented 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 the participant’s legally authorized 
representative and is kept on file.
10.1.4.
Data Protection
Participants will be assigned a unique identifier by the sponsor. Any participant records, datasets 
or tissue samples that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be transferred.
The participant must be informed that their personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent. 
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
The sponsor has processes in place to ensure data protection, information security and data 
integrity. These processes include appropriate contingency plan(s) for appropriate and timely 
response in the event of a data security breach.

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10.1.5.
Committees Structure
The AC will consist of members internal and external to the sponsor. The membership will 
include, at a minimum, a chair external to Lilly, a statistician and two physicians. The AC 
members will not have data entry/validation responsibilities or direct contact with the site(s) or 
testing facilities.  
10.1.6.
Dissemination of Clinical Study Data
A clinical study report will be provided for this study and a summary of study information 
provided on publicly available websites. 
10.1.7.
Data Quality Assurance
Investigator responsibilities
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.
Data monitoring and management
The Monitoring Plan includes

monitoring details describing strategy, for example, risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical Risk-
Based Monitoring 

methods 

responsibilities and requirements 

handling of noncompliance issues, and 

monitoring techniques.
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data. The sponsor assumes accountability for actions delegated to other 
individuals (e.g., Contract Research Organizations).
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. They will also ensure 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. 
If on-site monitoring activities cannot occur, alternative measures will be used. Examples of 
alternative measures are use of technology for off-site monitoring or providing pseudonymized 

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copies of source documents to the monitor electronically. The remote source data verification 
will be focused on critical efficacy data and important safety data. 
Records retention and audits
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for the time period outlined in the Clinical Trial Agreement (CTA) 
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.
The sponsor or its representatives will periodically check a sample of the participant data 
recorded against source documents at the study site. The study may be audited by the sponsor or 
its representatives, and by regulatory agencies at any time. Investigators will be given notice 
before an audit occurs.
Data Capture System
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor.
An electronic data capture system (EDC) will be used in this study for the collection of CRF 
data. The investigator maintains a separate source for the data entered by the investigator or 
designee into the sponsor-provided EDC system. 
Only symptom assessments might be directly recorded by the investigator site personnel or a 
delegate into the EDC. The directly entered data will serve as source documentation. The 
investigator will not maintain an original, separate, written or electronic record of these data. A 
certified copy of the respective data entry will be downloaded by the investigator for retention.
The investigator is responsible for the identification of any data to be considered source and for 
the confirmation that data reported are accurate and complete by signing the CRF.
Data collected via the sponsor-provided data capture systems will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture systems. Prior to decommissioning, the investigator will receive an archival 
copy of pertinent data for retention.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports will be provided to the investigator for review 
and retention. Data will subsequently be transferred from the central vendor to the Sponsor data 
warehouse.
Data from complaint forms submitted to Sponsor will be encoded and stored in the global 
product complaint management system.
10.1.8.
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.

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Data reported on the CRF 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. Current medical 
records must be available.
The definition of what constitutes source data can be found in Section 10.1.7.
10.1.9.
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
Site Closure
The sponsor 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 enough 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:

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 recruitment of participants by the investigator, or

Discontinuation of further study intervention development.
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 participants and 
assure appropriate participant therapy and/or follow-up.
10.1.10.
Publication Policy
In accordance with the sponsor’s publication policy, the results of this study will be submitted 
for publication by a peer-reviewed journal if the results are deemed to be of significant medical 
importance.
10.1.11.
Investigator Information
Physicians with specialties, including, but not limited to infectious disease, acute or critical care, 
pulmonary disease, immunology, or other appropriate specialties may participate as 
investigators.

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10.1.12.
Long-Term Sample Retention
Sample retention enables use of new technologies, response to regulatory questions, and 
investigation of variable response that may not be observed until later in the development of the 
intervention or after the intervention becomes commercially available.
This table describes the retention period for potential sample types.
Sample Type
Custodian
Retention Period After Last Participant 
Visit
Pharmacodynamic Samples
Sponsor or designee
up to 7 years
Pharmacogenetics sample
Sponsor or designee
up to 7 years
Exploratory Biomarker Samples
Sponsor or designee
up to 7 years
Immunogenicity (ADA) sample
Sponsor or designee
up to 7 years
Pharmacokinetic (PK) sample
Sponsor or designee
up to 2 years

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Appendix 2: Clinical Laboratory Tests
Clinical laboratory tests will be performed according to the SoA (Section 1.3). 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations.
Central and local laboratories will be used. The table below describes when the local or central 
laboratory will be used.
Laboratory results that could unblind the study will not be reported to investigative sites or other 
blinded personnel.
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5
of the protocol.
Pregnancy testing will be performed according to the SoA.
Investigators must document their review of each laboratory safety report.
Refer to Section 10.6 for recommended laboratory testing for hypersensitivity events.

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Clinical Laboratory Tests
Comments  
Hematology
Assayed by Lilly-designated laboratory. 
Hemoglobin
Hematocrit
Erythrocyte count (RBCs - Red Blood Cells)
Mean cell volume 
Mean cell hemoglobin
Leukocytes (WBCs - White Blood Cells) 
Differential
   Neutrophils, segmented
   Lymphocytes
   Monocytes
   Eosinophils
   Basophils
Platelets
Cell Morphology (RBC and WBC)
Clinical Chemistry
Assayed by Lilly-designated laboratory. 
Sodium
Potassium
Chloride
Bicarbonate
Total bilirubin
Direct bilirubin
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Gamma-glutamyl transferase (GGT)
Blood urea nitrogen (BUN)
Creatinine 
Creatine kinase (CK)
Uric acid
Total protein
Albumin
Calcium
Phosphorus
Glucose
Amylase
Lipase
Lactate dehydrogenase (LDH)
SARS-CoV-2 viral infection determination
Local laboratory and/or Point-of-Care testing
SARS-CoV-2 Test Panel
Assayed by Lilly-designated laboratory.

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Clinical Laboratory Tests
Comments  
C-reactive protein (CRP); high-sensitivity
For adults only
Ferritin
For adults only
D-dimer
For adults only
Procalcitonin 
For adults only
Troponin 
For adults only
Troponin I
For adults only
Troponin T
For adults only
Hormones (female)
Urine Pregnancy
Local laboratory
Serum Pregnancy
Local laboratory
Pharmacokinetic Samples  
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
   LY3819253
   LY3832479
   LY3853113
   VIR-7831
Pharmacodynamic sample
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
   SARS-CoV-2 nasopharyngeal swab
Pharmacogenetics sample
For adults only
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Exploratory Biomarker Samples 
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Serum
   RNA (PAXGene)
Whole Blood (EDTA) 
For adults only
   Whole Blood (EDTA) Epigenetics
For adults only
Exploratory Biomarker Serum
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Immunogenicity Samples
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
   Anti-LY3819253 antibodies 
   Anti-LY3832479 antibodies
   Anti-LY3853113 antibodies
   Anti-VIR-7831 antibodies

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Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
10.3.1.
Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions 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 drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdose 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. 
Events NOT Meeting the AE Definition

The following study-specific clinical events related to COVID-19 are exempt from 
adverse event reporting unless the investigator deems the event to be related to the 
administration of study drug:
o
Hypoxemia due to COVID-19 requiring supplemental oxygen;

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o
Hypoxemia due to COVID-19 requiring non-invasive ventilation or high flow 
oxygen devices;
o
Respiratory failure due to COVID-19 requiring invasive mechanical ventilation 
or ECMO

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.3.2.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization

In general, hospitalization signifies that the participant has been admitted to hospital 
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.

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d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but 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 in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.
10.3.3.
Recording and Follow-Up of AE and/or SAE
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Sponsor or designee in lieu of completion of the AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by Sponsor or designee. In this case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records before 
submission to Sponsor or designee.

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.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to one of the following categories, which together with serious (i.e., 

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SAE) criteria on the AE CRF (“results in death” and “life-threatening”), are aligned with the 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events, version 2.1 (July 2017).
Mild: Mild symptoms causing no or minimal interference with usual social and functional 
activities, with intervention not indicated.
Moderate: Moderate symptoms causing greater than minimal interference with usual 
social and functional activities, with intervention indicated.
Severe: Severe symptoms causing inability to perform usual social and functional 
activities, with intervention or hospitalization indicated.
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

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.

The investigator will use clinical judgment to determine the relationship.

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.

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 or designee. 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 or designee.

The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Sponsor or 

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designee 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.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Sponsor or designee with a copy of any 
post-mortem findings including histopathology. 

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to Sponsor or designee within 24 
hours of receipt of the information. 
10.3.4.
Reporting of SAEs
SAE Reporting via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE will be the electronic data collection 
tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as it becomes 
available.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see next 
section) or to the sponsor by telephone.

Contacts for SAE reporting can be found in site training documents.
SAE Reporting via Paper CRF

Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the sponsor.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames.

Contacts for SAE reporting can be found in site training documents.

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Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information
Women
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below).
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered.
Woman not of Childbearing Potential
Women in the following categories are not considered WOCBP
1. Premenarchal
2. Premenopausal female with either
a.
Documented hysterectomy
b. Documented bilateral salpingectomy, or
c.
Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than the above, 
(e.g., mullerian agenesis, androgen insensitivity), investigator discretion should be applied to 
determining study entry. 
Note: Determination can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female is defined as, women with:
a.
12 months of amenorrhea for women >55, with no need for FSH
b. 12 months of amenorrhea for women >40 years old with FSH ≥40 mIU/mL and 
no other medical condition such as anorexia nervosa and not taking medications 
during the amenorrhea (e.g., oral contraceptives, hormones, gonadotropin 
releasing hormone, anti-estrogens, selective estrogen receptor modulators 
(SERMs), or chemotherapy that induced amenorrhea)
Participation in the Study
Women of child-bearing potential may participate in this study.
Women of child-bearing potential must test negative for pregnancy prior to initiation of 
treatment as indicated by a negative urine pregnancy test at the screening visit.
Women of child-bearing potential who are completely abstinent or in a same sex relationship, as 
part of their preferred and usual lifestyle, must agree to either remain abstinent or stay in a same 
sex relationship without sexual relationships with males.
All other women of child-bearing potential must agree to use two forms of effective 
contraception, where at least one form is highly effective (less than 1% failure rate), for the 
entirety of the study.  

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Abstinence or contraception must continue for 90 days after the last dose of intervention.
Acceptable Methods of Contraception
Highly effective methods of contraception (less than 1% failure rate) comprise, but are not 
limited to

combination oral contraceptives 

implanted contraceptives, or 

intrauterine devices. 
Effective methods of contraception comprise but are not limited to diaphragms with spermicide 
or cervical sponges.  
Not Acceptable Methods of Contraception
Use of male and female condoms as a double barrier method is not considered acceptable due to 
the high failure rate when these barrier methods are combined. 
Barrier protection methods without concomitant use of a spermicide are not an effective or 
acceptable method of contraception.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), 
declaration of abstinence just for the duration of a trial, and withdrawal are not acceptable 
methods of contraception.
Men
Men, regardless of their fertility status, must agree to either remain abstinent (if this is their 
preferred and usual lifestyle) or use condoms as well as one additional highly effective method 
of contraception (less than 1% failure rate) or effective method of contraception with non-
pregnant women of child bearing potential partners for the duration of the study and until their 
plasma concentrations are below the level that could result in a relevant potential exposure to a 
possible fetus, predicted to be 90 days after the last dose.
Men with pregnant partners should use condoms during intercourse for the duration of the study 
and until the end of estimated relevant potential exposure to the fetus, predicted to be 90 days 
after the last dose.
Acceptable Methods of Contraception
Highly effective methods of contraception (less than 1% failure rate) comprise, but are not 
limited to

combination oral contraceptives 

implanted contraceptives, or 

intrauterine devices. 
Effective methods of contraception comprise but are not limited to diaphragms with spermicide 
or cervical sponges.  
Men and their partners may choose to use a double–barrier method of contraception that must 
include use of a spermicide.

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Other Guidance
Men should refrain from sperm donation for the duration of the study and until their plasma 
concentrations are below the level that could result in a relevant potential exposure to a possible 
fetus, predicted to be 90 days after the last dose. 
Collection of Pregnancy Information
Male participants with partners who become pregnant
The investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive study intervention.
After obtaining the necessary signed informed consent and assent (if applicable) from the 
pregnant female partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor within 24 hours of learning of the partner’s 
pregnancy. 
The female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the sponsor. Generally, the follow-up 
will be no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported including fetal status (presence or absence of anomalies) and 
indication for the procedure. 
Female Participants who become pregnant
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study.  The initial information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a participant's 
pregnancy. 
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate and the information will be 
forwarded to the sponsor. Generally, this information will include a follow-up of at least 5 half-
lives after last exposure or birth. Any termination of pregnancy will be reported, including fetal 
status (presence or absence of anomalies) or indication for the procedure.
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
A spontaneous abortion (occurring at <20 weeks gestational age) or still birth (occurring at >20 
weeks gestational age) is always considered to be an SAE and will be reported as such. 
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 8.3.4. While the 
investigator is not obligated to actively seek this information in former study participants, he or 
she may learn of an SAE through spontaneous reporting.
Any female participant who becomes pregnant while participating in the study will be withdrawn 
from the study and will follow the standard discontinuation process.

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Appendix 5: Genetics
Sample collection information is found in Appendix 2, Section 10.2 (Clinical Laboratory Tests).
Use/Analysis of DNA
Genetic variation may impact a participant’s response to study intervention, susceptibility to, and 
severity and progression of disease.  Variable response to study intervention may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease being 
treated.  Therefore, where local regulations and IRB/IEC allow, a blood sample will be collected 
for DNA analysis from consenting participants.
DNA samples may be used for research related to SARS-CoV-2 and related diseases. They may 
also be used to develop tests/assays including diagnostic tests related to LY3819253, 
LY3832479, LY3853113, VIR-7831 or SARS-CoV-2.  Genetic research may consist of the 
analysis of one or more candidate genes or the analysis of genetic markers throughout the 
genome as appropriate.
The samples may be analyzed as part of a multi-study assessment of genetic factors involved in 
the response to LY3819253, LY3832479, LY3853113, VIR-7831 or study interventions of this 
class to understand study disease or related conditions.
The results of genetic analyses may be reported in the clinical study report (CSR) or in a separate 
study summary.
The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality.
The samples will be retained at a facility selected by the sponsor or its designee while research 
on SARS-CoV-2 continues but no longer than 7 years or other period as per local requirements. 

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Appendix 6: Recommended Laboratory Testing for 
Hypersensitivity Events.
Laboratory assessments should be performed if the participant experiences generalized urticaria 
or if anaphylaxis is suspected.

Collect sample after the participant has been stabilized, and within 1 to 2 hours of the 
event; however, samples may be obtained as late as 12 hours after the event as analytes 
can remain altered for an extended period of time.  Record the time at which the sample 
was collected.

Obtain a follow-up sample at the next regularly scheduled visit or after approximately 4 
weeks, whichever is later.

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Clinical Lab Tests for Hypersensitivity Events
Hypersensitivity Tests
Notes
Selected test may be obtained in the event of anaphylaxis or 
systemic allergic/hypersensitivity reactions.
LY3819253, LY3832479, 
LY3853113, and VIR-7831 
anti-drug antibodies 
(immunogenicity/ADA)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
LY3819253, LY3832479, 
LY3853113, and VIR-7831
concentrations (PK)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Tryptase
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Urine N-methylhistamine testing is performed in addition to 
tryptase testing.  Collect the first void urine following the event. 
Collect a follow-up urine sample after approximately 4 weeks.
Note: If a tryptase sample is obtained more than 2 hours after the 
event (that is, within 2 to 12 hours), or is not obtained because more 
than 12 hours have lapsed since the event, collect a urine sample for 
N-methylhistamine testing. 
N-methylhistamine
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Drug-specific IgE
Will be performed if a validated assay is available.
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Basophil activation test
Will be performed if a validated assay is available.
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
NOTE: The basophil activation test is an in vitro cell based assay 
that only requires a serum sample. It is a surrogate assay for drug 
specific IgE but is not specific for IgE.
Complement (C3, C3a and 
C5a)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Cytokine panel
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Abbreviations: ADA = anti-drug antibody; IgE = immunoglobulin E; PK = pharmacokinetic.

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Appendix 7: Liver Safety: Suggested Actions and Follow-up 
Assessments
Close Hepatic Monitoring
This table describes when close hepatic monitoring should occur.
If a participant with baseline results 
of ... 
develops the following elevations…
ALT or AST <1.5× ULN
ALT or AST ≥3× ULN
ALP <1.5× ULN
ALP ≥2× ULN
TBL <1.5× ULN
TBL ≥2× ULN (except for participants with Gilbert’s 
syndrome)
ALT or AST ≥1.5× ULN
ALT or AST ≥2× baseline
ALP ≥1.5× ULN
ALP ≥2× baseline
TBL ≥1.5× ULN
TBL ≥2× baseline (except for participants with Gilbert’s 
syndrome)
The laboratory tests listed in Appendix 2, including ALT, AST, ALP, TBL, direct bilirubin, 
gamma-glutamyl transferase, and creatine kinase, should be repeated within 48 to 72 hours to 
confirm the abnormality and to determine whether it is increasing or decreasing.
If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for the 
possible causes of the abnormal liver tests should be initiated by the investigator in consultation 
with the sponsor.
At a minimum, this evaluation should include a physical examination and a thorough medical 
history, including symptoms, recent illnesses (for example, heart failure, systemic infection, 
hypotension, seizures) recent travel, history of concomitant medications (including over-the-
counter), herbal and dietary supplements, history of alcohol use, and other substance abuse.
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests.  
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks if the 
participant’s clinical condition and laboratory results stabilize.  Monitoring of ALT, AST, ALP, 
and TBL should continue until levels normalize or return to approximate baseline levels. 

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Comprehensive Hepatic Evaluation  
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
one or more of these conditions occur:
If a participant with baseline 
results of... 
develops the following elevations…
ALT or AST <1.5× ULN
ALT or AST ≥3× ULN with hepatic signs/symptoms*, or
ALT or AST ≥5× ULN
ALP <1.5× ULN
ALP ≥3× ULN
TBL <1.5× ULN
TBL ≥2× ULN (except for participants with Gilbert’s syndrome)
ALT or AST ≥1.5× ULN
ALT or AST ≥2× baseline with hepatic signs/symptoms*, or
ALT or AST ≥3× baseline
ALP ≥1.5× ULN
ALP ≥2× baseline
TBL ≥1.5× ULN
TBL ≥1.5× baseline (except for participants with Gilbert’s syndrome) 
* Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, and/or 
eosinophilia >5%.
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for PT-INR; tests for viral hepatitis A, B, C, or E; tests 
for autoimmune hepatitis; and an abdominal imaging study (for example, ultrasound or CT scan). 
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the Lilly-designated medical monitor, including tests for hepatitis D virus 
(HDV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), acetaminophen levels, 
acetaminophen protein adducts, urine toxicology screen, Wilson’s disease, blood alcohol levels, 
urinary ethyl glucuronide, and serum phosphatidylethanol. 
Based on the circumstances and the investigator’s assessment of the participant’s clinical 
condition, the investigator should consider referring the participant for a hepatologist or 
gastroenterologist consultation, magnetic resonance cholangiopancreatography (MRCP), 
endoscopic retrograde cholangiopancreatography (ERCP), cardiac echocardiogram, or a liver 
biopsy.  

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Additional Hepatic Data Collection (Hepatic Safety CRF) 
Additional hepatic safety data collection in hepatic safety case report forms (CRF) should be performed in 
study participants who either have a hepatic event considered to be an SAE or meet 1 or more of these 
conditions:
If a participant with baseline...
has the following elevations…
ALT <1.5 ×ULN
ALT ≥5 × ULN on 2 or more consecutive blood tests 
ALP <1.5 × ULN
ALP ≥2 × ULN on 2 or more consecutive blood tests
TBL <1.5 × ULN
TBL ≥2 × ULN, except for cases of known Gilbert’s syndrome
ALT ≥1.5 × ULN
ALT ≥3 × baseline on 2 or more consecutive blood tests
ALP ≥1.5 × ULN
ALP ≥2 × baseline on 2 or more consecutive blood tests
TBL ≥1.5 × ULN
TBL ≥2 × baseline
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate
aminotransferase; TBL = total bilirubin; ULN = upper limit of normal.
Note:  The interval between the 2 consecutive blood tests should be at least 2 days.
Hepatic Evaluation Testing
The Lilly-designated central laboratory must complete the analysis of all selected testing except 
for microbiology testing.
Local testing may be performed in addition to central testing when necessary for immediate 
participant management.
Results will be reported if a validated test or calculation is available.
Hematology
Clinical Chemistry
Hemoglobin
Total bilirubin
Hematocrit
Direct bilirubin
Erythrocytes (RBCs - red blood cells)
Alkaline phosphatase (ALP)
Leukocytes (WBCs - white blood cells)
Alanine aminotransferase (ALT)
Differential:
Aspartate aminotransferase (AST)
    Neutrophils, segmented
Gamma-glutamyl transferase (GGT)
    Lymphocytes
Creatine kinase (CK)
    Monocytes
Other Chemistry
    Basophils
Acetaminophen
    Eosinophils
Acetaminophen protein adducts
Platelets
Alkaline phosphatase isoenzymes
Cell morphology (RBC and WBC)
Ceruloplasmin
Coagulation
Copper
Ethyl alcohol (EtOH)
Prothrombin time, INR (PT-INR)
Haptoglobin

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Serology
Immunoglobulin IgA (quantitative)
Hepatitis A virus (HAV) testing:
Immunoglobulin IgG (quantitative)
    HAV total antibody
Immunoglobulin IgM (quantitative)
    HAV IgM antibody
Phosphatidylethanol (PEth)
Hepatis B virus (HBV) testing:
Urine Chemistry
    Hepatitis B surface antigen (HBsAg)
Drug screen
    Hepatitis B surface antibody (anti-HBs)
Ethyl glucuronide (EtG)
    Hepatitis B core total antibody (anti-HBc)
Other Serology
    Hepatitis B core IgM antibody
Anti-nuclear antibody (ANA)
    Hepatitis B core IgG antibody
Anti-smooth muscle antibody (ASMA) a
    HBV DNA b
Anti-actin antibody c
Hepatis C virus (HCV) testing:
Epstein-Barr virus (EBV) testing:
    HCV antibody
    EBV antibody
    HCV RNA b
    EBV DNA b
Hepatitis D virus (HDV) testing:
Cytomegalovirus (CMV) testing:
    HDV antibody
    CMV antibody
Hepatitis E virus (HEV) testing:
    CMV DNA b
    HEV IgG antibody
Herpes simplex virus (HSV) testing:
    HEV IgM antibody
    HSV (Type 1 and 2) antibody 
    HEV RNA b
    HSV (Type 1 and 2) DNA b
Microbiology d
Liver kidney microsomal type 1 (LKM-1) antibody
Culture:
    Blood
    Urine
a
Not required if anti-actin antibody is tested.
b
Reflex/confirmation dependent on regulatory requirements, testing availability, or both.
c
Not required if anti-smooth muscle antibody (ASMA) is tested.
d
Assayed ONLY by investigator-designated local laboratory; no central testing available.

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Appendix 8: Abbreviations
Term
Definition
AC
assessment committee
ADA
anti-drug antibody
ADE 
antibody-dependent enhancement
assent
Agreement from a child or other individual who is not legally capable of providing 
consent, but who can understand the circumstances and potential risks involved in 
participating in a study.
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the participant is not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/his staff and the participant are not.
A double-blind study is one in which neither the participant nor any of the investigator 
or sponsor staff who are involved in the treatment or clinical evaluation of the 
participants are aware of the treatment received.
CIOMS
Council for International Organizations of Medical Sciences
Complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of an intervention.
Compliance
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements.
CRP
clinical research physician: Individual responsible for the medical conduct of the study.  
Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician or other medical officer.
DMC
data monitoring committee
ECG
Electrocardiogram
FiO2
fraction of inspired oxygen 
Enroll
The act of assigning a participant to a treatment.  Participants who are enrolled in the 
study are those who have been assigned to a treatment.
Enter
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives.
GCP
good clinical practice
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation

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IgG1
Immunoglobulin G1
IMP
Investigational Medicinal Product
Informed consent
A process by which a participant voluntarily confirms his or her willingness to 
participate in a particular study, after having been informed of all aspects of the study 
that are relevant to the participant’s decision to participate.  Informed consent is 
documented by means of a written, signed and dated informed consent form.
interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
Intervention
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IWRS
interactive web-response system
mAb
monoclonal antibody
NP
Nasopharyngeal
Participant
Equivalent to CDISC term “subject”: an individual who participates in a clinical trial, 
either as recipient of an investigational medicinal product or as a control
PK/PD
pharmacokinetics/pharmacodynamics
SAE
serious adverse event
SAP
statistical analysis plan
Screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SpO2
saturation of peripheral oxygen

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Appendix 9: Protocol Amendment History
Amendment f 16 March 2021
Overall Rationale for the Amendment:
The purpose of this amendment is to incorporate a new study intervention, LY3853113, into the 
study design.
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis; 1.2 Schema; 1.3 Schedule of 
Activities; 3 Objectives and Endpoints; 4.1 
Overall Design; 4.2 Scientific Rationale for 
Study Design; 6.1 Study Intervention(s) 
Administered; 8.1 Efficacy Assessments; 
8.4 Treatment of Overdose; 8.5 
Pharmacokinetics; 8.5.1 Bioanalytical; 8.6 
Pharmacodynamics; 8.8 Biomarkers; 8.9 
Immunogenicity Assessments; 10.2 
Appendix 2: Clinical Laboratory Tests; 10.5 
Appendix 5: Genetics; 10.6 Appendix 6: 
Recommended Laboratory Testing for 
Hypersensitivity Events
Added Arms 9-13 to study 
design; updated language 
throughout protocol to include 
LY3853113.
Arms added to incorporate new 
study intervention 
(LY3853113) into design; 
language updated throughout to 
align with the addition of 
LY3853113
1.1 Synopsis; 2 Introduction; 2.1 Study 
Rationale; 2.2 Background; 2.3 
Benefit/Risk Assessment
Provided background 
information for LY3853113
Updated section to include 
information about LY3853113
2.2 Background
Updated LY3819253+ 
LY3832479 safety information
Updated to provide more recent 
safety information
4.3 Justification for Dose
Added justification for 
LY3853113 + LY3819253 + 
LY3832479 combination
Updated to provide justification 
for LY3853113
5.1 Inclusion Criteria; 5.2 Exclusion 
Criteria; 10.1.3 Informed Consent Process
Added specifications for low or 
high-risk participants; 
expanded participant 
population to include 
adolescents
Alignment with updated study 
design
5.1 Inclusion Criteria
Criterion 3: Updated list of 
COVID-19 symptoms
Updated list to align with 
current guidance
5.1 Inclusion Criteria; Appendix 4: 
Contraceptive Guidance and Collection of 
Pregnancy Information
Criterion 5: Clarified provision 
of reproductive and 
contraceptive agreements and 
guidance in Appendix 4
Clarification
5.2 Exclusion Criteria
Added Criterion 29
Alignment with updated study 
design
6.3 Measures to Minimize Bias: 
Randomization and Blinding
Added stratification factors for 
arms 12-13; specified blinding 
for arms 1-11.
Alignment with updated study 
design
6.5 Concomitant Therapy
Added statement clarifying that 
prior SARS-CoV-2 vaccines 
should be recorded
Clarification

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Section # and Name
Description of Change
Brief Rationale
8.2.2 Vital Signs
Added new tables for Arms 9-
11, 13
Alignment with updated study 
design
9.1 Statistical Hypotheses; 9.2 Sample Size 
Determination; 9.4 Statistical Analyses; 
9.4.2 Primary Endpoints; 9.4.3.1 Safety 
(arms 1-11); 9.4.3.2 Additional Secondary 
Endpoints; 9.4.3.3 Pharmacokinetic 
Analyses; 9.4.5 Immunogenicity Analyses
Updated statistical 
considerations to incorporate 
LY3853113 into study design
Alignment with updated study 
design
Throughout
Minor editorial and formatting 
changes
Minor, therefore not detailed
Amendment e 25 January 2021
Overall Rationale for the Amendment:
The purpose of this amendment is to include a new follow-up phone visit for Arms 7 and 8 to 
assess for the occurrence of any safety concerns. Additionally, the amendment incorporates new 
background information for VIR-7831 and updates the benefit/risk language of LY3819253.
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis;
1.3.2. Treatment Arms 7-8;
4.1.1. Design Outline;
4.2. Scientific Rationale for Study Design
7.1. Discontinuation of Study Intervention
Added Day 169 timepoint with 
AE collection and concomitant 
medications
Added to assess for occurrence 
of any safety concerns for 
Arms 7 and 8
2.2. Background
Updated background 
information for VIR-7831
Included most up to date 
information on VIR-7831 from 
ongoing clinical trials
2.3. Benefit/Risk Assessment
Revised language regarding 
clinical worsening of COVID-
19 symptoms after LY3819253 
administration
Alignment with bamlanivimab 
EUA Fact Sheet
Throughout
Minor editorial and formatting 
changes
Minor, therefore not detailed
Amendment d 15 January 2021
Overall Rationale for the Amendment:
The purpose of this amendment is to remove pregnant women from the study population.

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Section # and Name
Description of Change
Brief Rationale
2.3 Benefit/Risk Assessment; 4.2 Scientific 
Rationale for Study Design; 5.1 Inclusion 
Criteria; 5.2 Exclusion Criteria; 7.2 
Participant Discontinuation/Withdrawal 
from the Study; 8.2.3 Clinical Laboratory 
Assessments; Appendix 4: Contraceptive 
Guidance and Collection of Pregnancy 
Information; 11 References
Removal of pregnant women 
from study population
Response to IRB feedback

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Amendment c 06 January 2021
Overall Rationale for the Amendment:
The purpose of this amendment is to incorporate a new study intervention, VIR-7831, into the 
study design.
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis; 1.2 Schema; 1.3 Schedule of 
Activities; 3 Objectives and Endpoints; 4.1 
Overall Design; 4.2 Scientific Rationale for 
Study Design; 6.1 Study Intervention(s) 
Administered; 8.1 Efficacy Assessments; 
8.4 Treatment of Overdose; 8.5 
Pharmacokinetics; 8.5.1 Bioanalytical; 8.6 
Pharmacodynamics; 8.8 Biomarkers; 8.9 
Immunogenicity Assessments; 10.2 
Appendix 2: Clinical Laboratory Tests; 10.6 
Appendix 6: Recommended Laboratory 
Testing for Hypersensitivity Events
Added Arms 7, 8, and 9 to 
study design; updated language 
throughout protocol to include 
VIR-7831
Arms added to incorporate new 
study intervention (VIR-7831) 
into design; language updated 
throughout to align with the 
addition of VIR-7831
1.3 Synopsis; 3 Objectives and Endpoints; 
9.4.3.2 Additional Secondary Endpoints
Removed Day 22 from 
proportion of participants that 
achieve SARS-CoV-2 
clearance
No NP swab collection on Day 
22
1.1 Synopsis; 2 Introduction; 2.1 Study 
Rationale; 2.2 Background; 2.3 
Benefit/Risk Assessment
Updated background 
information for VIR-7831
Updated to include information 
about VIR-7831
4.3 Justification for Dose
Added justification for 
LY3819253 + VIR-7831 
combination
Updated to provide justification 
for VIR-7831
5.1 Inclusion criteria; 5.2 Exclusion criteria; 
8.2.3 Clinical Laboratory Assessments;
8.3.5 Pregnancy; 10.4 Appendix 4: 
Contraceptive Guidance and Collection of 
Pregnancy Information
Updated study population to 
include pregnant women
Including due to potential 
favorable benefit/risk 
assessment for high-risk group
9.1 Statistical Hypotheses; 9.2 Sample Size 
Determination; 9.4.3.2 Additional 
Secondary Endpoints; 9.5 Interim Analyses
Updated statistical 
considerations to incorporate 
VIR-7831 into study design
Updated to align with amended 
study design
Throughout
Minor editorial and formatting 
changes
Minor, therefore not detailed

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Amendment b 03 December 2020
Overall Rationale for the Amendment:
The purpose of this amendment is to incorporate a new treatment arm (Arm 6) into the study 
design. Additionally, minor administrative changes and clarifications have been made to the 
Schedule of Activities and Secondary Objectives and Endpoints.
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis; 1.2 Schema; 
4.1.1 Design Outline; 6.1 
Study Intervention(s) 
Administered; 9.2 Sample Size 
Determination
Added treatment arm 6 to 
study; specified approximate 
number of participants to be 
enrolled into arms 3 and 6
Added to explore new 
dose level in study.
1.1 Synopsis; 3 Objectives and 
Endpoints; 6.1 Study 
Intervention(s) Administered; 
9.4.3.2 Additional Secondary 
Endpoints
Modified secondary endpoints 
for symptom resolution, 
symptom improvement, SARS-
CoV-2 viral load, and SARS-
CoV-2 clearance
Modified for consistency 
with other secondary 
endpoints
1.3 Schedule of Activities
Modified Day 11 visit window 
Administrative
6.1 Study Intervention(s) 
Administered
Changed ‘pharmacy manual’ to 
‘pharmacy preparation 
instructions’
Administrative
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding
Added language clarifying 
staggered enrollment of 
participants
Clarification
9.1 Statistical Hypotheses
Updated hypothesis to include 
arm 6
Modifications made to 
align with updated study 
design
9.5 Interim Analyses
Provided details of additional 
interim analysis
Added to align with 
updated study design
Throughout
Minor editorial changes
Minor, therefore not 
detailed

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Amendment a: 16 October 2020
Overall Rationale for the Amendment:
This amendment modifies the secondary endpoints that measure clinical events (deaths, hospitalizations, 
and ER visits) to include events through Day 29, in response to FDA feedback.
Section # and Name
Description of Change
Brief Rationale
Section 1.1 
Synopsis
Section 3 
Objectives and 
Endpoints
Section 9.4.3.2 
Additional
Secondary 
Endpoints
Added Day 29 to clinical 
events secondary endpoints 
FDA Feedback
Throughout the 
protocol
Minor editorial changes 
Minor, therefore not described

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11.
References
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