A Randomized, Double-blind, Placebo-Controlled, Phase 2/3 Study to Evaluate the Efficacy and Safety of LY3819253 and LY3832479 in Participants With Mild to Moderate COVID-19 Illness
Phase: PHASE2
Conditions: COVID-19
Sponsor: Eli Lilly and Company

Protocol J2W-MC-PYAB (m) 
 
A Randomized, Double-blind, Placebo-Controlled, Phase 2/3 Study to Evaluate the Efficacy and 
Safety of LY3819253 and LY3832479 in Participants with Mild to Moderate COVID-19 Illness 
 
NCT04427501 
 
Approval Date: 02-Mar-2021 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
1
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 and LY3832479, 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 2/3 Study to Evaluate the Efficacy and 
Safety of LY3819253 and LY3832479 in Participants with Mild to Moderate COVID-19 Illness
Protocol Number: J2W-MC-PYAB
Amendment Number: m
Compound(s): LY3819253, LY3832479
Study Phase: 2/3
Short Title: A randomized, double-blind, placebo-controlled, Phase 2/3 study to evaluate 
LY3819253 and LY3832479 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 (m) Electronically Signed and Approved by Lilly on date 
provided below.
Approval Date: 02-Mar-2021 GMT

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
2
Medical Monitor Name and Contact Information will be provided separately 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
3
Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Amendment (l)
03-February-2021
Amendment (k)
20-January-2021
Amendment (j)
07-January-2021
Amendment (i)
30-November-2020
Amendment (h)
Not applicable.  Not approved or submitted to 
regulatory agencies or independent review boards.
Amendment (g)
17-November-2020
Amendment (f)
20-October-2020
Amendment (e)
13-October-2020
Amendment (d)
18-September-2020
Amendment (c)
31-August-2020
Amendment (b)
31-July-2020
Amendment (a)
19-June-2020
Original Protocol
30-May-2020
Amendment m
Overall Rationale for the Amendment:
This amendment addresses the removal of treatment arms 16 and 17.  Treatment arms 16 and 17 
were planned to evaluate shorter administration times.  This evaluation will now take place in 
PYAB addendum 3.0 with treatment arms 20 and 21.  As a result, references to treatment arms 
16 and 17 in the main protocol were removed and the objectives and endpoints for treatment 
arms 13-14 and 18-19 were separated.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
4
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis
1.2 Schema 
1.3.2 Schedule of Activities (SoA)
3.0 Objectives and Endpoints
4.1.1 Design Outline
4.2 Scientific Rationale for Study 
Design
5.1 Inclusion Criteria 
6.1.2 Temporary Stopping Criteria 
8.2.2 Vital Signs
9.1 Statistical Hypotheses 
9.2 Sample Size Determination
9.4 Statistical Analyses
9.4.2 Primary Endpoints 
9.4.3.1 Key Secondary Endpoints
9.4.3.2 Safety
9.4.3.3 Additional Secondary 
Endpoints 
9.4.6 Subgroup Analyses 
9.5 Interim Analyses 
9.6 Data Monitoring Committee 
Treatment arms 16 and 17 
and related text were 
removed.
The evaluation of shorter administration 
times will now take place in the PYAB 3.0 
addendum with treatment arms 20 and 21.
1.1 Synopsis
3.0 Objectives and Endpoints
Treatment arms 13-14 and 
18-19 objectives and 
endpoints were separated
and updated.
The treatment arms 13-14 and 18-19 will be 
analyzed separately.  Endpoints updated for 
the removal of treatment arms 16-17 and 
also for clarity.
1.1 Synopsis 
1.2 Schema
4.1.1 Design Outline
Updated note to indicate 
that the protocol addenda 
include treatment arms for 
this study.
Generalized the statement to avoid future 
amendments if changes were made in the 
protocol addenda.
4.3 Justification for Dose
Added new subheadings and 
specify the subcutaneous 
dose
For clarification
5.1 Inclusion Criteria
Criterion #5 Replaced 
“agreements and guidance” 
with “requirements
Section 10.4 contains reproductive and 
contraceptive requirements.
9.1 Statistical Hypotheses
Updated hypothesis for 
treatment arms 13-14 and 
added hypothesis for 18-19.
Separated objectives and endpoints
9.2 Sample Size Determination
Updated text for treatment 
arms 13-14 and 18-19
New objectives and endpoints
9.4 Statistical Analyses
Key secondary endpoints of 
overall clinical status will 
use data from “multiple” 
treatment arms instead of 
“all”.
Updated analysis.
9.4.2 Primary Endpoints
Updated text for treatment 
arms 13-14 and 18-19
New objectives and endpoints

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
5
Section # and Name
Description of Change
Brief Rationale
9.4.3.1 Key Secondary Endpoints
Updated text for treatment 
arms 13-14 and 18-19
Updated objectives and endpoints
9.4.3.3 Additional Secondary 
Endpoints
Updated text for treatment 
arms 13-14 and 18-19
Updated objectives and endpoints
Throughout the protocol
Minor editorial and 
formatting changes
Minor, therefore not described

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
6
Table of Contents
1.
Protocol Summary......................................................................................................9
1.1.
Synopsis.......................................................................................................................9
1.2.
Schema.......................................................................................................................17
1.3.
Schedule of Activities (SoA) ......................................................................................18
1.3.1.
Treatment Arms 1-4 and 6 ..........................................................................................19
1.3.2.
Treatment Arms 7-9, 13-14, 18-19..............................................................................27
2.
Introduction..............................................................................................................35
2.1.
Study Rationale ..........................................................................................................35
2.2.
Background ................................................................................................................35
2.3.
Benefit/Risk Assessment ............................................................................................36
3.
Objectives and Endpoints.........................................................................................39
3.1.
Treatment arms 1-4 and 6 ...........................................................................................39
3.2.
Treatment arms 7-9.....................................................................................................41
3.3.
Treatment arms 13-14.................................................................................................43
3.4.
Treatment arms 18-19.................................................................................................45
4.
Study Design .............................................................................................................47
4.1.
Overall Design............................................................................................................47
4.1.1.
Design Outline............................................................................................................47
4.2.
Scientific Rationale for Study Design .........................................................................49
4.3.
Justification for Dose..................................................................................................51
4.4.
End of Study Definition..............................................................................................52
5.
Study Population ......................................................................................................53
5.1.
Inclusion Criteria........................................................................................................53
5.2.
Exclusion Criteria.......................................................................................................54
5.3.
Lifestyle Considerations .............................................................................................55
5.4.
Screen Failures...........................................................................................................55
6.
Study Intervention....................................................................................................56
6.1.
Study Intervention(s) Administered ............................................................................56
6.1.1.
Special Treatment Considerations...............................................................................57
6.1.2.
Temporary Stopping Criteria ......................................................................................58
6.2.
Preparation/Handling/Storage/Accountability.............................................................59
6.3.
Measures to Minimize Bias: Randomization and Blinding..........................................60
6.4.
Study Intervention Compliance...................................................................................60
6.5.
Concomitant Therapy .................................................................................................61
6.6.
Dose Modification......................................................................................................62
6.7.
Intervention after the End of the Study........................................................................62
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................63
7.1.
Discontinuation of Study Intervention ........................................................................63
7.2.
Participant Discontinuation/Withdrawal from the Study .............................................63
7.2.1.
Discontinuation of Inadvertently Enrolled Participants ...............................................63
7.3.
Lost to Follow up .......................................................................................................64

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
7
8.
Study Assessments and Procedures .........................................................................65
8.1.
Efficacy Assessments .................................................................................................65
8.1.1.
Symptoms and Overall Clinical Status Participant Questionnaire................................65
8.2.
Safety Assessments ....................................................................................................66
8.2.1.
Physical Examinations................................................................................................66
8.2.2.
Vital Signs..................................................................................................................66
8.2.3.
Clinical Laboratory Assessments ................................................................................67
8.2.4.
Hospitalization events.................................................................................................68
8.2.5.
Procedures of Special Interest.....................................................................................68
8.2.6.
Respiratory Support....................................................................................................69
8.3.
Adverse Events and Serious Adverse Events ..............................................................69
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information.................................................................................................................69
8.3.2.
Method of Detecting AEs and SAEs ...........................................................................69
8.3.3.
Follow-up of AEs and SAEs.......................................................................................70
8.3.4.
Regulatory Reporting Requirements for SAEs............................................................70
8.3.5.
Pregnancy...................................................................................................................70
8.3.6.
Hypersensitivity Reactions .........................................................................................70
8.3.7.
Infusion-related Reactions ..........................................................................................71
8.3.8.
Injection Site Reactions ..............................................................................................71
8.3.9.
Product Complaints ....................................................................................................71
8.4.
Treatment of Overdose ...............................................................................................72
8.5.
Pharmacokinetics........................................................................................................72
8.5.1.
Bioanalytical ..............................................................................................................73
8.6.
Pharmacodynamics.....................................................................................................73
8.7.
Genetics .....................................................................................................................73
8.8.
Biomarkers.................................................................................................................73
8.9.
Immunogenicity Assessments.....................................................................................74
8.10.
Health Economics.......................................................................................................74
9.
Statistical Considerations.........................................................................................75
9.1.
Statistical Hypotheses.................................................................................................75
9.2.
Sample Size Determination.........................................................................................75
9.3.
Populations for Analyses ............................................................................................77
9.4.
Statistical Analyses.....................................................................................................78
9.4.1.
General Considerations...............................................................................................78
9.4.2.
Primary Endpoints......................................................................................................79
9.4.3.
Secondary Endpoints ..................................................................................................79
9.4.4.
Exploratory Analyses..................................................................................................82
9.4.5.
Immunogenicity Analyses...........................................................................................82
9.4.6.
Subgroup Analyses.....................................................................................................83
9.5.
Interim Analyses.........................................................................................................83
9.6.
Data Monitoring Committee (DMC)...........................................................................85
10.
Supporting Documentation and Operational Considerations ................................86
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................................86
10.1.1.
Regulatory and Ethical Considerations........................................................................86

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
8
10.1.2.
Financial Disclosure ...................................................................................................86
10.1.3.
Informed Consent Process ..........................................................................................87
10.1.4.
Data Protection...........................................................................................................87
10.1.5.
Committees Structure .................................................................................................88
10.1.6.
Dissemination of Clinical Study Data .........................................................................88
10.1.7.
Data Quality Assurance ..............................................................................................88
10.1.8.
Source Documents......................................................................................................90
10.1.9.
Study and Site Start and Closure.................................................................................90
10.1.10. Publication Policy.......................................................................................................91
10.1.11. Investigator Information .............................................................................................91
10.1.12. Long-Term Sample Retention.....................................................................................91
10.2.
Appendix 2: Clinical Laboratory Tests........................................................................92
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting.......................................................95
10.3.1.
Definition of AE.........................................................................................................95
10.3.2.
Definition of SAE.......................................................................................................96
10.3.3.
Recording and Follow-Up of AE and/or SAE .............................................................97
10.3.4.
Reporting of SAEs......................................................................................................99
10.4.
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information .............................................................................................100
10.5.
Appendix 5: Genetics ...............................................................................................103
10.6.
Appendix 6: Recommended Laboratory Testing for 
Hypersensitivity Events............................................................................................104
10.7.
Appendix 7: Liver Safety: Suggested Actions and Follow-up 
Assessments .............................................................................................................106
10.8.
Appendix 8: Abbreviations .......................................................................................110
10.9.
Appendix 9: Protocol Amendment History ...............................................................112
11.
References...............................................................................................................137

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
9
1.
Protocol Summary
1.1.
Synopsis
Protocol Title: A Randomized, Double-blind, Placebo-Controlled, Phase 2/3 Study to Evaluate 
the Efficacy and Safety of LY3819253 and LY3832479 in Participants with Mild to Moderate 
COVID-19 Illness
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 and LY3832479 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.
This study aims to evaluate the impact of LY3819253 and LY3832479 on viral clearance and 
clinical outcomes in participants with COVID-19 illness.  The data from this study will inform 
decisions for the clinical development of LY3819253 and LY3832479. 
Objectives and Endpoints:
Treatment arms 1-4 and 6
Objectives
Endpoints
Primary
Characterize the effect of LY3819253, and LY3819253 
in combination with LY3832479, compared to placebo 
on SARS-CoV-2 viral load and viral clearance
Change from baseline to Day 11 (± 4 days) in SARS-
CoV-2 viral load 
Secondary
The secondary objectives are to characterize the effect 
of LY3819253, and LY3819253 in combination with 
LY3832479, compared to placebo on…

safety 

Safety assessments such as AEs and SAEs

SARS-CoV-2 viral load among participants with 
≤8 days since symptom onset

Change from baseline to Day 11 (± 4 days) in 
SARS-CoV-2 viral load among participants 
enrolled with ≤ 8 days of symptoms prior to 
randomization 

symptom resolution

Time to symptom resolution 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
10

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days
7, 11, 15 and 22

Change in symptom score (total of ratings) from 
baseline to Days 7, 11, 15 and 22 

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 7, 11, 15 and 22

SARS-CoV-2 viral load and viral clearance

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 7, 11, 15 and 22)

Time to SARS-CoV-2 clearance 

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 29

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Days 29, 60 and 85
o
COVID-19 related hospitalization
(defined as ≥24 hours of acute care)
o
a COVID-19 related emergency room 
visit, or 
o
death
Additional Secondary
Characterize the pharmacokinetics of LY3819253 and 
LY3819253 in combination with LY3832479

Mean concentration of LY3819253 and 
LY3819253 in the presence of LY3832479 on
Day 29

Mean concentration of LY3832479 in the presence 
of LY3819253 on Day 29
Abbreviations:  AE = adverse event; SAE =serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
11
Treatment arms 7-9
Objectives
Endpoints
Primary
Characterize the effect of LY3819253 in combination 
with LY3832479 compared to placebo on overall 
participant clinical status
Proportion (percentage) of participants who experience 
COVID-19 related hospitalization (defined as ≥24 
hours of acute care) or death from any cause by Day 
29.
Key Secondary
The key secondary objectives are to characterize the 
effect of LY3819253 in combination with LY3832479, 
compared to placebo on…

the reduction of SARS-CoV-2 viral load

Change from baseline to Day 7 (±2 days)

Persistently high SARS-CoV-2 viral load

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7 (+2 days)

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), or
o
a COVID-19 related emergency room 
visit, or 
o
death from any cause

sustained symptom resolution

time to sustained symptom resolution
Additional Secondary

SARS-CoV-2 viral load reduction

Change from baseline to 
o
Day 3 (+1 day)
o
Day 5 (±2 days)

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 7

SARS-CoV-2 viral clearance

Time to SARS-CoV-2 clearance 

symptom resolution

Time to symptom resolution 

Time to complete symptom resolution

Time to sustained complete symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days
2-11

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 2-11

safety 

Safety assessments such as AEs and SAEs
Abbreviations:  AE = adverse event; SAE =serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
12
Treatment arms 13-14
Objectives
Endpoints
Primary
Persistently high SARS-CoV-2 viral load for treatment 
arm 14 compared to treatment arm 13.
Proportion of participants with SARS-CoV-2 viral load 
greater than 5.27 on Day 7 (+2 days)
Key Secondary
Reduction of SARS-CoV-2 viral load for treatment 
arm 14 compared to treatment arm 13.
Change from baseline to Day 7 (±2 days)
Clinical status for treatment arm 14 compared to all 
high-risk placebo participants in treatment arms 8 and 
13.
Proportion (percentage) of participants who experience 
COVID-19 related hospitalization (defined as ≥24 
hours of acute care) or death from any cause by Day 
29.
Additional Secondary
Clinical status for treatment arm 14 compared to all 
high-risk placebo participants in treatment arms 8 and 
13.
Proportion (percentage) of participants who experience 
these events by Day 29

COVID-19 related hospitalization (defined as ≥24 
hours of acute care), or

a COVID-19 related emergency room visit, or 

death from any cause
Treatment arm 13 compared to treatment arm 14 on…

sustained symptom resolution

time to sustained symptom resolution

SARS-CoV-2 viral load reduction

Change from baseline to 
o
Day 3 (+1 day)
o
Day 5 (±2 days)

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 7 

SARS-CoV-2 viral clearance

Time to SARS-CoV-2 clearance 

symptom resolution

Time to symptom resolution 

Time to complete symptom resolution

Time to sustained complete symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days
2-11

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 2-11

safety 

Safety assessments such as AEs and SAEs, 
including date and time of events
Abbreviations:  AE = adverse event; SAE =serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
13
Treatment arms 18-19 
Objectives
Endpoints
Primary
Persistently high SARS-CoV-2 viral load for treatment 
arm 19 compared to treatment arm 18
Proportion of participants with SARS-CoV-2 viral load 
greater than 5.27 on Day 7 (+2 days)
Key Secondary
Reduction of SARS-CoV-2 viral load for treatment 
arm 19 compared to treatment arm 18
Change from baseline to Day 7 (±2 days)
Overall participant clinical status for treatment arm 19 
compared to all high-risk placebo participants in 
treatment arms 8 and 13
Proportion (percentage) of participants who experience 
COVID-19 related hospitalization (defined as ≥24 
hours of acute care) or death from any cause by Day 
29.
Additional Secondary
Clinical status for treatment arm 19 compared to all 
high-risk placebo participants in treatment arms 8 and 
13
Proportion (percentage) of participants who experience 
these events by Day 29

COVID-19 related hospitalization (defined as ≥24 
hours of acute care), or

a COVID-19 related emergency room visit, or 

death from any cause
Treatment arm 19 compared to treatment arm 18 on…

sustained symptom resolution

time to sustained symptom resolution

SARS-CoV-2 viral load reduction

Change from baseline to 
o
Day 3 (+1 day)
o
Day 5 (±2 days)

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 7 

SARS-CoV-2 viral clearance

Time to SARS-CoV-2 clearance 

symptom resolution

Time to symptom resolution 

Time to complete symptom resolution

Time to sustained complete symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days
2-11

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 2-11

safety 

Safety assessments such as AEs and SAEs, 
including date and time of events
Abbreviations:  AE = adverse event; SAE =serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
14
Overall Design:
This is a Phase 2/3, randomized, double-blind, placebo-controlled, single-dose study in 
participants with mild to moderate COVID-19 illness. 
Design Outline
Screening
Interested participants or their legally authorized representative 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.
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-dose sample collection.
This table describes the visit types for treatment arms 1-4 and 6.
Study Day
Visit Type
1  
Site  
2, 4, 5 and 6
Telephone visits
3, 7, 11, 15, 18, 22, 25 and 29
May be conducted as outpatient clinic or home visits
Early discontinuation and follow-up
May be conducted as outpatient clinic or home visits
This table describes the visit types for treatment arms 7-9, 13-14, 18-19.
Study Day
Activity
Visit Type
1  
Follow SoA
Site  
2, 4, 6 and 22
Follow SoA
Telephone visits
3, 5, 7, 11, and 29
Follow SoA
May be conducted as outpatient 
clinic or home visits
8, 9, and 10
Collect participant questionnaire 
symptom and overall clinical 
status assessments
Telephone visits
Early discontinuation and follow-up
Follow SoA
May be conducted as outpatient 
clinic or home visits
If a participant is hospitalized, procedures and assessments will continue per the SoA. 
This table describes discharge from hospital scenarios if an outpatient is subsequently 
hospitalized.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
15
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.  
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.
Disclosure Statement: This is a treatment study.  Treatment arms 1-9 and 13-14 are participant 
and investigator blinded. Treatment arms 18-19 are open label.
Number of Participants:
Treatment arms 1-4 and 6
Approximately 500 participants allocated across five treatment arms (treatment arms 1-4 and 6).  
Additional placebo participants may be enrolled to ensure up to 50 concurrent placebo controls 
for treatment arm 6.  
Up to 100 additional participants may be introduced for optional treatment arm 5.  See Section 9.5
for interim analysis details.
Treatment arms 7-9, 13-14, and 18-19
Participants in treatment arms 7-9, 13-14, and 18-19 are adults and adolescents with at least 1 
risk factor for developing severe COVID-19 illness.  There is no set sample size for the 
adolescent participants. 
The planned sample size for the primary comparison of treatment arms 7 and 8 is approximately 
1000 participants equally randomized to placebo or the combination of LY3819253 and 
LY3832479.  
The planned sample size for treatment arm 9 is approximately 500 participants. Since treatment 
arm 9 begins enrollment after treatment arm 7, additional participants will be enrolled in 
treatment arm 8 to ensure at least a 33% increase in placebo participants and adequate placebo 
control for the primary comparison of treatment arms 8 and 9.
The planned sample size for treatment arms 13 and 14 is approximately 400 participants 
randomized 2:3, placebo:combination of LY3819253 and LY3832479.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
16
The planned sample size for treatment arms 18 and 19 is approximately 460 participants per 
treatment arm. 
Intervention Groups and Duration:
This table describes the planned treatment arms.  
Treatment arms
Dose
Intervention
Route of Administration
1
---
Placebo
Intravenous
2
700 mg
LY3819253
3
2800 mg
LY3819253
4
7000 mg
LY3819253
Optional 5
To Be Determined
LY3819253
6
2800 mg + 2800 mg
LY3819253+LY3832479
7
2800 mg + 2800 mg
LY3819253+LY3832479
8
---
Placebo
9
700 mg + 1400 mg
LY3819253+LY3832479
13
---
Placebo
14
350 mg + 700 mg
LY3819253+LY3832479
18
700 mg + 1400 mg
LY3819253+LY3832479
19
250 mg + 500 mg
LY3819253+LY3832479
Subcutaneous
NOTE: PYAB protocol addenda also include treatment arms for this study.
The optional LY3819253 treatment arm 5 may be added based on interim analysis results.  
Participants will receive intervention on Day 1, assessments occur to Day 29 and follow-up to 
Day 85.
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 arms 7 and 9.  
Treatment arm 13 is the concurrent placebo control for treatment arm 14.  
Treatment arms 18-19 are open-label.  
Data Monitoring Committee: Yes.
An assessment committee will analyze the interim study data for treatment arms 1-4 and 6.
An external data monitoring committee (DMC) will analyze unblinded safety data for treatment 
arms 7-9, 13-14, and 18-19.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
17
1.2.
Schema
Abbreviations:  LY = Lilly study intervention; PYAA = J2W-MC-PYAA; PYAB = J2W-MC-PYAB; TBD = to be 
determined.
NOTE:  Treatment arms 1-9, 13-14, and 18 are administered as an intravenous infusion.  
Treatment arm 19 is administered as subcutaneous injection. 
PYAB protocol addenda also include treatment arms for this study.
Figure 1.
Study J2W-MC-PYAB schema

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
18
1.3.
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
19
1.3.1.
Treatment Arms 1-4 and 6
This SoA is for participants in treatment arms 1-4 and 6.
Schedule of Activities for Treatment Arms 1-4 and 6
Study 
J2W-MC-PYAB
Screen
Double-blind treatment and assessments
E
D
Follow-up 
if hospital 
inpatient 
on Day 29
Post-
treatment
follow-up
Comments
Study Day
1
2
*
3
4
*
5
*
6
*
7
11
15
18
22
25
29
E
D
Every 7 
days until 
discharge 
or Day 60
60
85
Screening and Day 1 procedures 
may occur on the same day.
* = telephone visit(s)
Visit window 
(± number of days)
--
--
+1
+1
2
2
2
2
2
2
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:  timing of exposure and 
onset of symptoms suggestive of 
SARS-CoV-2 infection, and risk 
factors and comorbidities 
associated with severe COVID-19 
illness, such as living in a nursing 
home or long-term care facility. 
Height
X
Weight
X

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
20
Schedule of Activities for Treatment Arms 1-4 and 6
Study 
J2W-MC-PYAB
Screen
Double-blind treatment and assessments
E
D
Follow-up 
if hospital 
inpatient 
on Day 29
Post-
treatment
follow-up
Comments
Study Day
1
2
*
3
4
*
5
*
6
*
7
11
15
18
22
25
29
E
D
Every 7 
days until 
discharge 
or Day 60
60
85
Screening and Day 1 procedures 
may occur on the same day.
* = telephone visit(s)
Visit window 
(± number of days)
--
--
+1
+1
2
2
2
2
2
2
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.
Tobacco use
X
Concomitant 
medications
X
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
X
X
Any events that occur after signing 
the informed consent are 
considered AEs as defined in 
Section 10.3.
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 number J2W-MC-PYAB(m)
21
Schedule of Activities for Treatment Arms 1-4 and 6
Study 
J2W-MC-PYAB
Screen
Double-blind treatment and assessments
E
D
Follow-up 
if hospital 
inpatient 
on Day 29
Post-
treatment
follow-up
Comments
Study Day
1
2
*
3
4
*
5
*
6
*
7
11
15
18
22
25
29
E
D
Every 7 
days until 
discharge 
or Day 60
60
85
Screening and Day 1 procedures 
may occur on the same day.
* = telephone visit(s)
Visit window 
(± number of days)
--
--
+1
+1
2
2
2
2
2
2
2
2
4
4
Visits may not be combined.
Vital signs
X
X
X
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, and method of 
delivery, if applicable. 
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 the 
infusion 

every 15 minutes during the 
infusion, as possible, and

every 30 minutes for 2 hours 
after the infusion.  
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 number J2W-MC-PYAB(m)
22
Schedule of Activities for Treatment Arms 1-4 and 6
Study 
J2W-MC-PYAB
Screen
Double-blind treatment and assessments
E
D
Follow-up 
if hospital 
inpatient 
on Day 29
Post-
treatment
follow-up
Comments
Study Day
1
2
*
3
4
*
5
*
6
*
7
11
15
18
22
25
29
E
D
Every 7 
days until 
discharge 
or Day 60
60
85
Screening and Day 1 procedures 
may occur on the same day.
* = telephone visit(s)
Visit window 
(± number of days)
--
--
+1
+1
2
2
2
2
2
2
2
2
4
4
Visits may not be combined.
Hospitalization 
events
Daily
X
X
X
X
Record if the following events 
occur:

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
Documentation from hospital 
records is acceptable.
Includes: 
consciousness status (ACVPU),
limitation on activities due to 
COVID-19, and requirements for

Ongoing hospital medical 
care

Supplemental oxygen

Non-invasive ventilation or 
high flow oxygen device

Mechanical ventilation

ECMO, or

Additional organ support (e.g. 
pressors, renal replacement). 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
23
Schedule of Activities for Treatment Arms 1-4 and 6
Study 
J2W-MC-PYAB
Screen
Double-blind treatment and assessments
E
D
Follow-up 
if hospital 
inpatient 
on Day 29
Post-
treatment
follow-up
Comments
Study Day
1
2
*
3
4
*
5
*
6
*
7
11
15
18
22
25
29
E
D
Every 7 
days until 
discharge 
or Day 60
60
85
Screening and Day 1 procedures 
may occur on the same day.
* = telephone visit(s)
Visit window 
(± number of days)
--
--
+1
+1
2
2
2
2
2
2
2
2
4
4
Visits may not be combined.
Laboratory Tests and Sample Collection
Hematology
X
X
X
X
X
Day 1: before IV infusion
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 IV infusion
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

Ferritin

D-dimer

Procalcitonin

Troponin
X
X
X
X
X
Day 1: before IV infusion
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 number J2W-MC-PYAB(m)
24
Schedule of Activities for Treatment Arms 1-4 and 6
Study 
J2W-MC-PYAB
Screen
Double-blind treatment and assessments
E
D
Follow-up 
if hospital 
inpatient 
on Day 29
Post-
treatment
follow-up
Comments
Study Day
1
2
*
3
4
*
5
*
6
*
7
11
15
18
22
25
29
E
D
Every 7 
days until 
discharge 
or Day 60
60
85
Screening and Day 1 procedures 
may occur on the same day.
* = telephone visit(s)
Visit window 
(± number of days)
--
--
+1
+1
2
2
2
2
2
2
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
X
X
X
X
X
X
Day 1: before IV infusion and 
anytime just prior to the end of 
infusion.
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
X
X
X
X
X
X
Day 1:  collect before IV infusion. 
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 number J2W-MC-PYAB(m)
25
Schedule of Activities for Treatment Arms 1-4 and 6
Study 
J2W-MC-PYAB
Screen
Double-blind treatment and assessments
E
D
Follow-up 
if hospital 
inpatient 
on Day 29
Post-
treatment
follow-up
Comments
Study Day
1
2
*
3
4
*
5
*
6
*
7
11
15
18
22
25
29
E
D
Every 7 
days until 
discharge 
or Day 60
60
85
Screening and Day 1 procedures 
may occur on the same day.
* = telephone visit(s)
Visit window 
(± number of days)
--
--
+1
+1
2
2
2
2
2
2
2
2
4
4
Visits may not be combined.
Pharmacodynamic 
(PD) NP swab 
X
X
X
X
X
X
X
X
X
X
Swab is taken from both nostrils. 
Day 1: swab before IV infusion.
No samples needed if participant is 
hospitalized
Lilly-designated central laboratory
Exploratory 
biomarker 
samples
X
X
X
X
X
Day 1: before IV infusion.
No samples needed if participant is 
hospitalized
Lilly-designated central laboratory
Pharmacogenetics 
sample
X
Lilly-designated central laboratory
Randomization and Dosing
Randomization
X

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
26
Schedule of Activities for Treatment Arms 1-4 and 6
Study 
J2W-MC-PYAB
Screen
Double-blind treatment and assessments
E
D
Follow-up 
if hospital 
inpatient 
on Day 29
Post-
treatment
follow-up
Comments
Study Day
1
2
*
3
4
*
5
*
6
*
7
11
15
18
22
25
29
E
D
Every 7 
days until 
discharge 
or Day 60
60
85
Screening and Day 1 procedures 
may occur on the same day.
* = telephone visit(s)
Visit window 
(± number of days)
--
--
+1
+1
2
2
2
2
2
2
2
2
4
4
Visits may not be combined.
Administer study 
intervention (IV 
infusion)
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 the IV 
infusion, complete dialysis first 
followed by the IV infusion.
Participants will be monitored for 
at least 2 hours after completion of 
the infusion.
Participant Questionnaire
Symptoms and 
overall clinical 
status
Daily on Days 1-29 for outpatients only
X
X
X
Day 1: assess prior to dosing
Abbreviations:  ACVPU = alert, consciousness, verbal, pain, unresponsive scale; ADA = anti-drug antibody; BP = blood pressure; ECMO = extracorporeal membrane 
oxygenation; ED = early discontinuation visit; FiO2 = fraction of inspired oxygen in the air; ICU = intensive care unit; IV = intravenous; NP = nasopharyngeal; NSAIDS = non-
steroidal anti-inflammatory drugs; SpO2 = saturation of peripheral oxygen; WOCBP = women of child-bearing potential.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
27
1.3.2.
Treatment Arms 7-9, 13-14, 18-19
This SoA is for participants in treatment arms 7 through 9, and 13 and 14, 18 and 19.  
Schedule of Activities for Treatment Arms 7-9, 13-14, 18-19
Study 
J2W-MC-PYAB
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) 
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:  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 for 
COVID-19
X
Includes COVID-19 diagnosis date and 
onset of COVID-19 symptoms.
Height
X
Weight
X

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
28
Schedule of Activities for Treatment Arms 7-9, 13-14, 18-19
Study 
J2W-MC-PYAB
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) 
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Procedures
Prior treatments of 
special interest 
X
Within the last 30 days:  NSAIDs, 
antivirals, antibiotics, anti-malarials, 
corticosteroids, immunomodulators or 
other investigational treatments.
At any time:  SARS-CoV-2 vaccine.
Prior non-SARS-
CoV-2 vaccine 
treatments within 
the last 90 days
X
For adolescents only
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

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
29
Schedule of Activities for Treatment Arms 7-9, 13-14, 18-19
Study 
J2W-MC-PYAB
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) 
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Procedures
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.
Vital Signs and 
Oxygen Support
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.
X
X
X
X
X
X
X
X
X
X
X
Documentation of hospital-based exam is 
acceptable.
Record SpO2 while participant is at rest.
Screening visit only: SpO2 while breathing 
room air. Data not collected on CRF.
IV dose Day 1 timing:

immediately before administration

every 15 minutes during the infusion, 
as possible and applicable

if infusion is <15 minutes, immediately 
following completion of infusion

every 30 minutes for 1 hour after the 
administration.  
During infusion, only record pulse rate, BP 
and SpO2. Automation may be used.  
SQ dose Day 1 timing:  

immediately before injection, and

every 30 minutes for 1 hour after the 
administration.  
All other study days: once daily. 
See Section 8.2.2 for data collected on CRF.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
30
Schedule of Activities for Treatment Arms 7-9, 13-14, 18-19
Study 
J2W-MC-PYAB
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) 
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Procedures
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:

NEWS 2 Consciousness (ACVPU)

Limitation on activities due to 
COVID-19 using the 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 number J2W-MC-PYAB(m)
31
Schedule of Activities for Treatment Arms 7-9, 13-14, 18-19
Study 
J2W-MC-PYAB
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) 
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Procedures
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

Ferritin

D-dimer

Procalcitonin

Troponin
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 number J2W-MC-PYAB(m)
32
Schedule of Activities for Treatment Arms 7-9, 13-14, 18-19
Study 
J2W-MC-PYAB
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) 
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Procedures
Documentation of 
positive SARS-
CoV-2 viral 
infection 
X
Sample for first positive test must be 
collected within 3 days prior to start of 
administration.
Local laboratory and/or Point-of-Care 
testing.
Urine or serum 
pregnancy 
X
X
X
Only for WOCBP (Section 10.4
Appendix 4).  Not applicable for 
females pregnant at screening.  
Local laboratory
Pharmacokinetic 
(PK) sample
X
X
X
X
X
X
X
Day 1
IV infusion: before IV infusion (adults 
only) and within 30 minutes after the 
end of infusion .
SQ injection: anytime after dosing, 
preferably as close to the end of the 
visit as possible.
Day 3 sample for SQ dose, treatment 
arm 19, only.
All other scheduled samples may occur 
at any time during the day.
No samples needed if participant is 
hospitalized.
Lilly-designated central laboratory

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
33
Schedule of Activities for Treatment Arms 7-9, 13-14, 18-19
Study 
J2W-MC-PYAB
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) 
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Procedures
Immunogenicity 
(ADA) sample
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 sample needed for Day 3 SQ dose.
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
X
X
Day 1: before treatment administration.
Day 60 and 85: serum sample only
No samples needed if participant is 
hospitalized
Lilly-designated central laboratory
Pharmacogenetics 
sample
X
For adults only
Lilly-designated central laboratory

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
34
Schedule of Activities for Treatment Arms 7-9, 13-14, 18-19
Study 
J2W-MC-PYAB
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) 
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Procedures
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 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; IV = intravenous; 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; SQ = 
subcutaneous; WOCBP = women of child-bearing potential.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
35
2.
Introduction
The efficient community spread of SARS-CoV-2 has resulted in the current pandemic of 
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). 
The SARS-CoV-2 gains entry to cells through binding of the spike (S) protein to ACE2 receptors 
on cells (Hoffmann 2020).  Eli Lilly and Company has a partnership with AbCellera Biologics 
Inc. (AbCellera; Vancouver, Canada) to develop neutralizing IgG1 monoclonal antibodies 
(mAbs) to the Spike (S) protein of SARS-CoV-2 as a potential treatment for COVID-19.  
Candidate antibody gene sequences have been selected from a recently recovered COVID-19 
United States patient’s serum using AbCellera’s core platform screening technologies. 
LY3819253 and LY3832479 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. 
2.1.
Study Rationale
This study aims to evaluate the impact of LY3819253 and LY3819253 in combination with 
LY3832479 on viral clearance and clinical outcomes in participants with mild to moderate 
COVID-19 illness.  The data from this study will inform decisions for the clinical development 
of these neutralizing IgG1mAbs. 
2.2.
Background
Nonclinical information for LY3819253 and LY3832479 are 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]). Study PYAA started prior to this study and informed the dose levels administered in 
Study PYAB.
Lilly is 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 under 
development in China in an ongoing Phase 1 clinical study in healthy participants, Study JS016-
001-I.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
36
2.3.
Benefit/Risk Assessment
Information on the safety and tolerability of LY3819253 in humans will come from Study 
PYAA. All available study data will be reviewed before that dose is administered in Study 
PYAB. 
Risk of Neutralizing Antibodies
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 and LY3832479 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 a convalescent 
naturally SARS-CoV-2-infected patient 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 for either intervention or in combination 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.
LY3819253 will also be administered to participants at sufficiently high dose levels to neutralize 
SARS-CoV-2 and avoid sub-neutralizing concentrations in the presence of virus that are 
typically associated with ADE.  
Risk of Infusion-related Reactions and Injection Site Reactions
Additional manageable risks associated with most therapeutic monoclonal antibodies are 
infusion-related hypersensitivity and cytokine release reactions.  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. and 
Section 6.1.2.
There is also potential for injection site reactions (ISRs) with subcutaneous dosing.  
LY3819253
As of 2 October 2020, 727 participants received blinded treatment of LY3819253 700 mg, 
2800 mg, or 7000 mg, or placebo.  Serious infusion-related reactions, including events consistent 
with anaphylaxis, were reported in these ongoing studies with LY3819253 (FDA EUA fact sheet 
2020).  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
37
Clinical worsening of COVID-19 after administration of LY3819253 has been reported and may 
include symptoms of pyrexia, hypoxia or increased respiratory difficulty, rapid heart rate (e.g. 
atrial fibrillation, sinus tachycardia), fatigue, and altered mental status. Some of these events 
required hospitalization.  It is unknown if these events were related to LY3819253 use or were 
due to progression of COVID-19. 
Combination of LY3819253 and LY3832479
As of 04 November 2020, 542 participants in Study PYAB received blinded treatment of either 
placebo or the combination of 2800 mg LY3819253 and 2800 mg LY3832479. Three
participants reported single immediate non-serious events of pruritis (2 events) and dyspnea (1
event).   
Benefit/Risk in the Adolescent Population
With respect to adolescents, there are no approved vaccines for the prevention of COVID-19 or 
approved drugs to treat COVID-19.  The SARS-CoV-2 infections in the adolescent population 
generally are less severe than adults and may even be asymptomatic (Hoang et al. 2020).  
However, the risks of serious illness requiring hospitalization and sometimes resulting in death, 
is higher in pediatric patients with a number of risk factors that generally correspond to those in 
adults, such as obesity, diabetes, chronic lung disease, and immunocompromised status, as well 
as some conditions that are unique to pediatrics, such as congenital heart disease (Kim et al.
2020; Shekerdemian et al. 2020).  
Adolescents with risk factors for severe disease and hospitalization may benefit from early 
administration of experimental anti-viral therapies such as the combination of LY3819253 and 
LY3832479, especially given the current safety profile. Based on FDA guidance documents, the 
data from even a small number of adolescents is useful in making regulatory science decisions
(FDA May 2020 and FDA June 2020).
Benefit/Risk in the Pregnant Population
In vitro tissue cross-reactivity assays with LY3819253 and LY3832479 determined that there is 
no binding to human fetal tissues. 
Interim analysis from this study suggest treatment with LY3819253 may decrease the risk of
hospitalization in mild to moderate COVID-19 patients (Chen et al. 2020).  Pregnant females and 
pregnant females with additional risk factors for severe disease and hospitalization may benefit 
from early administration of experimental anti-viral therapies such as the combination of 
LY3819253 and LY3832479, especially given the current safety profile. Based on the FDA 
guidance document, the data from this population may be useful in making regulatory science 
decisions and enrollment is encouraged in clinical trials (FDA May 2020). 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
38
Overall Benefit/Risk Assessment
Given the data on LY3819253 and LY3832479, 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.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of LY3819253 and LY3832479 may be found in each respective IB. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
39
3.
Objectives and Endpoints
3.1.
Treatment arms 1-4 and 6
Objectives
Endpoints
Primary
Characterize the effect of LY3819253, and LY3819253
in combination with LY3832479, compared to placebo 
on SARS-CoV-2 viral load and viral clearance
Change from baseline to Day 11 (± 4 days) in SARS-
CoV-2 viral load 
Secondary
The secondary objectives are to characterize the effect 
of LY3819253, and LY3819253 in combination with 
LY3832479, compared to placebo on…

safety 

Safety assessments such as AEs and SAEs

SARS-CoV-2 viral load among participants with 
≤8 days since symptom onset

Change from baseline to Day 11 (± 4 days) in 
SARS-CoV-2 viral load among participants 
enrolled with ≤ 8 days of symptoms prior to 
randomization

symptom resolution

Time to symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days
7, 11, 15 and 22

Change in symptom score (total of ratings) from 
baseline to Days 7, 11, 15 and 22 

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 7, 11, 15 and 22

SARS-CoV-2 viral load and viral clearance

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 7, 11, 15 and 22)

Time to SARS-CoV-2 clearance 

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 29

overall participant clinical status

Proportion (percentage) of participants who 
experience these events by Days 29, 60 and 85
o
COVID-19 related hospitalization
(defined as ≥24 hours of acute care)
o
a COVID-19 related emergency room 
visit, or 
o
death

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
40
Objectives
Endpoints
Additional Secondary
Characterize the pharmacokinetics of LY3819253 and 
LY3819253 in combination with LY3832479

Mean concentration of LY3819253 and 
LY3819253 in the presence of LY3832479 on Day 
29

Mean concentration of LY3832479 in presence of 
LY3819253 on Day 29
Exploratory
The exploratory objectives are to characterize the 
effect of LY3819253 and LY3819253 in combination 
with LY3832479 compared to placebo on…

SpO2 over time

SpO2 AUC assessed through Day 29

symptom severity

Symptom severity as assessed by mean AUC 
through Day 29 of symptom questionnaire

overall improvement using the NIAID ordinal 
scale

Comparison of the mean worst daily NIAID 
ordinal eight-point scale values at Days 7, 11, 15
and 22
Additional 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; NIAID = National Institute of Allergy and Infectious Diseases; SAE =serious 
adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SpO2 = saturation of peripheral 
oxygen.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
41
3.2.
Treatment arms 7-9
Objectives
Endpoints
Primary
Characterize the effect of LY3819253 in combination 
with LY3832479 compared to placebo on overall 
participant clinical status
Proportion (percentage) of participants who experience 
COVID-19 related hospitalization (defined as ≥24 
hours of acute care) or death from any cause by Day 
29.
Key Secondary
The secondary objectives are to characterize the effect 
of LY3819253 in combination with LY3832479, 
compared to placebo on…

the reduction of SARS-CoV-2 viral load

Change from baseline to Day 7 (±2 days)

persistently high SARS-CoV-2 viral load

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7 (+2 days)

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), or
o
a COVID-19 related emergency room 
visit, or 
o
death from any cause

sustained symptom resolution

time to sustained symptom resolution
Additional Secondary

SARS-CoV-2 viral load reduction

Change from baseline to 
o
Day 3 (+1 day)
o
Day 5 (±2 days)

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 7

SARS-CoV-2 viral clearance

Time to SARS-CoV-2 clearance 

symptom resolution

Time to symptom resolution 

Time to complete symptom resolution

Time to sustained complete symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days
2-11

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 2-11

safety 

Safety assessments such as AEs and SAEs

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
42
Objectives
Endpoints
Exploratory

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), or
o
death from any cause
Characterize the pharmacokinetics of LY3819253 in 
combination with LY3832479
Mean concentration of LY3832479 in presence of 
LY3819253 on Day 29
Abbreviations:  AE = adverse event; SAE =serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
43
3.3.
Treatment arms 13-14
Objectives
Endpoints
Primary
Persistently high SARS-CoV-2 viral load for treatment 
arm 14 compared to treatment arm 13
Proportion of participants with SARS-CoV-2 viral load 
greater than 5.27 on Day 7 (+2 days)
Key Secondary
Reduction of SARS-CoV-2 viral load for treatment 
arm 14 compared to treatment arm 13
Change from baseline to Day 7 (±2 days)
Clinical status for treatment arm 14 compared to all 
high-risk placebo participants in treatment arms 8 and 
13
Proportion (percentage) of participants who experience 
COVID-19 related hospitalization (defined as ≥24 
hours of acute care) or death from any cause by Day 
29.
Additional Secondary
Clinical status for treatment arm 14 compared to all 
high-risk placebo participants in treatment arms 8 and 
13
Proportion (percentage) of participants who experience 
these events by Day 29

COVID-19 related hospitalization (defined as ≥24 
hours of acute care), or

a COVID-19 related emergency room visit, or 

death from any cause
Treatment arm 13 compared to treatment arm 14 on…

sustained symptom resolution

time to sustained symptom resolution

SARS-CoV-2 viral load reduction

Change from baseline to 
o
Day 3 (+1 day)
o
Day 5 (±2 days)

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 7 

SARS-CoV-2 viral clearance

Time to SARS-CoV-2 clearance 

symptom resolution

Time to symptom resolution 

Time to complete symptom resolution

Time to sustained complete symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days
2-11

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 2-11

safety 

Safety assessments such as AEs and SAEs, 
including date and time of events

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
44
Objectives
Endpoints
Exploratory
Treatment arm 14 compared to treatment arms 8 and 
13 on 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), or
o
death from any cause
Characterize the pharmacokinetics of LY3819253 in 
combination with LY3832479
Mean concentration of LY3832479 in presence of 
LY3819253 on Day 29
Abbreviations:  AE = adverse event; SAE =serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
45
3.4.
Treatment arms 18-19
Objectives
Endpoints
Primary
Persistently high SARS-CoV-2 viral load for treatment 
arm 19 compared to treatment arm 18
Proportion of participants with SARS-CoV-2 viral load 
greater than 5.27 on Day 7 (+2 days)
Key Secondary
Reduction of SARS-CoV-2 viral load for treatment 
arm 19 compared to treatment arm 18
Change from baseline to Day 7 (±2 days)
Overall participant clinical status for treatment arm 19 
compared to all high-risk placebo participants in 
treatment arms 8 and 13
Proportion (percentage) of participants who experience 
COVID-19 related hospitalization (defined as ≥24 
hours of acute care) or death from any cause by Day 
29.
Additional Secondary
Clinical status for treatment arm 19 compared to all 
high-risk placebo participants in treatment arms 8 and 
13
Proportion (percentage) of participants who experience 
these events by Day 29

COVID-19 related hospitalization (defined as ≥24 
hours of acute care), or

a COVID-19 related emergency room visit, or 

death from any cause
Treatment arm 19 compared to treatment arm 18 on…

sustained symptom resolution

time to sustained symptom resolution

SARS-CoV-2 viral load reduction

Change from baseline to 
o
Day 3 (+1 day)
o
Day 5 (±2 days)

SARS-CoV-2 viral load area under the response-
time curve (AUC) assessed through Day 7 

SARS-CoV-2 viral clearance

Time to SARS-CoV-2 clearance 

symptom resolution

Time to symptom resolution 

Time to complete symptom resolution

Time to sustained complete symptom resolution 

Proportion of participants demonstrating symptom 
resolution via the symptom questionnaire on Days
2-11

symptom improvement

Time to symptom improvement

Proportion of participants demonstrating symptom 
improvement via the symptom questionnaire on 
Days 2-11

safety 

Safety assessments such as AEs and SAEs, 
including date and time of events

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
46
Objectives
Endpoints
Exploratory
Treatment arm 19 compared to treatment arms 8 and 
13 on 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), or
o
death from any cause
Characterize the pharmacokinetics of LY3819253 in 
combination with LY3832479
Mean concentration of LY3832479 in presence of 
LY3819253 on Day 29
Abbreviations:  AE = adverse event; SAE =serious adverse event; SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
47
4.
Study Design
4.1.
Overall Design
This is a Phase 2/3, placebo-controlled, double-blind, randomized single-dose study in 
participants with mild to moderate COVID-19 illness.
4.1.1.
Design Outline
Abbreviations:  PD = pharmacodynamic; PYAB = Study J2W-MC-PYAB.
Figure 2.
Overview of participant flow from time of SARS-CoV-2 symptoms to IV 
infusion.
Screening
Interested participants or their legally authorized representative 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 patient 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.
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-dose sample collection.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
48
Treatment Arms
This table describes the planned treatment arms.  
Treatment arms
Dose
Intervention
Route of Administration
1
---
Placebo
Intravenous
2
700 mg
LY3819253
3
2800 mg
LY3819253
4
7000 mg
LY3819253
Optional 5
To Be Determined
LY3819253
6
2800 mg + 2800 mg
LY3819253+LY3832479
7
2800 mg + 2800 mg
LY3819253+LY3832479
8
---
Placebo
9
700 mg + 1400 mg
LY3819253+LY3832479
13
---
Placebo
14
350 mg + 700 mg
LY3819253+LY3832479
18
700 mg + 1400 mg
LY3819253+LY3832479
19
250 mg + 500 mg
LY3819253+LY3832479
Subcutaneous
NOTE: PYAB protocol addenda also include treatment arms for this study.    
As LY3819253 dose levels in Study J2W-MC-PYAA (PYAA) are determined to be safe, 
treatment arms 2-4 may be introduced in Study PYAB.    
An optional LY3819253-only treatment arm 5 may be added based on interim analysis results.  
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 arms 7 and 9.  
Treatment arm 13 is the concurrent placebo control for treatment arm 14.
Treatment arms 18-19 are open-label.  
For treatment arm 19, a safety review will occur after approximately 20 participants are dosed
and have at least 24 hours of safety data, before continuing dosing subsequent participants.  The 
investigator and the Lilly sponsor team are responsible for determining if safety is acceptable to 
continue dosing subsequent participants. 
Visit Types during the Treatment and Assessment Period
This table describes the visit types for treatment arms 1-4 and 6.
Study Day
Visit Type
1  
Site  
2, 4, 5 and 6
Telephone visits
3, 7, 11, 15, 18, 22, 25 and 29
May be conducted as outpatient clinic or home visits.
Early discontinuation and follow-up
May be conducted as outpatient clinic or home visits

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
49
This table describes the visit types for treatment arms 7-9, 13-14, 18-19.
Study Day
Activity
Visit Type
1  
Follow SoA
Site  
2, 4, 6 and 22
Follow SoA
Telephone visits
3, 5, 7, 11, and 29
Follow SoA
May be conducted as outpatient 
clinic or home visits
8, 9, and 10
Collect participant questionnaire 
symptom and overall clinical
status assessments
Telephone visits
Early discontinuation and follow-up
Follow SoA
May be conducted as outpatient 
clinic or home visits
Guidelines if a Participant is Hospitalized
If a participant is hospitalized, procedures and assessments will continue per the SoA. 
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.  
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.
4.2.
Scientific Rationale for Study Design
Overall Design
This study is designed to evaluate the efficacy of LY3819253 in a range of doses that will inform 
the clinical drug development plan for LY3819253, and to evaluate the efficacy of the 
combination of LY3819253 and LY3832479.
The follow-up at Day 85 adequately covers the duration for immune response.
Due to emerging data, participants will no longer receive placebo and new potential participants 
will have the opportunity to receive active intervention.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
50
Treatment arms 18-19 are open-label because of the change in primary endpoint to a more 
objective evaluation of change in viral load.  This also removes the need for a double-dummy 
design requiring every participant to receive an infusion and subcutaneous injections.  
Safety reviews are included for treatment arm 19 to minimize the risk of any unanticipated safety 
concerns in participants before fully enrolling the treatment arm. 
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 a virology endpoint 
(see Section 3).
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.  
The population of participants in treatment arms 7-9 are required to have at least 1 risk factor for 
developing severe COVID-19 illness. The risk factors were based on the Centers for Disease 
Control guidance (CDC resource page, available at: https://www.cdc.gov/coronavirus/2019-
ncov/need-extra-precautions/people-at-increased-
risk.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-
ncov%2Fneed-extra-precautions%2Fpeople-at-higher-risk.html).  Participants with these risk 
factors are at higher risk for more severe disease and hospitalization. This population was 
chosen to evaluate if effective antiviral antibody therapy may prevent hospitalization or death.
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.  Per FDA request, adolescents 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.
Pregnant Participants
Interim analysis from this study suggest treatment with LY3819253 may decrease the risk of 
hospitalization in mild to moderate COVID-19 patients (Chen et al. 2020).  Pregnant females and 
pregnant females with additional risk factors for severe disease and hospitalization may benefit 
from early administration of experimental anti-viral therapies such as the combination of 
LY3819253 and LY3832479, especially given the current safety profile. Per FDA guidance, 
pregnant individuals may be included in this study (FDA, May 2020).

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
51
Participants who have received a SARS-CoV-2 vaccination
SARS-CoV-2 vaccines are now available to the public.  Those who received a SARS-CoV-2
vaccine are now allowed in the study to assess the safety of LY3819253 and LY3832479 after a 
person received the vaccine.
Interim Reviews
The interim safety and efficacy reviews will inform the clinical drug development plan for
LY3819253 and the combination of LY3819253 and LY3832479.
4.3.
Justification for Dose
LY3819253
The dose levels of LY3819253 administered in this study are informed by Study PYAA. As dose
information from Study PYAA are determined to be safe, these dose levels may be added to the 
study. 
The starting dose of 700 mg LY3819253 in Study PYAA is selected based on PK and PK/PD of 
viral dynamics modeling to have 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 7000 mg is selected due to uncertainty in model predicted PK 
concentrations, viral load reduction and consideration of infusion volume in participants.  The 
dose will not exceed 7000 mg in this study. 
The projected human half-life is expected to be in the 2-4 weeks range.  
LY3819253 + LY3832479
To provide coverage of the different but overlapping 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 dose rationale for a single mAb intervention.  
2800 mg LY3819253 and 2800 mg LY3832479
The dose selection of 2800 mg LY3819253 and 2800 mg LY3832479 is based on PK and PK/PD 
modeling to have a sustained lung concentration above the in vitro IC90 of viral cell-entry 
neutralization (95th percentile of the estimates) in the lung tissue for at least 28 days in greater 
than 90% of the participant population.  The PK included additional variability to cover 
translational uncertainty.  The 95th percentile was chosen as a conservative measure.
The dose levels are fixed, not body weight based.  Given the planned dose levels, the predicted 
impact of body weight on therapeutic response will be minimal. 
Addition of adolescents
In treatment arms 7 and 8, adult participants are currently randomized 1:1 to receive placebo or a 
combination of 2800mg LY3819253 and 2800mg LY3832479. Based on PK extrapolation 
(exposure-matching), adolescents ≥ 40 kg dosed with 2800 mg are expected to reach the same 
exposure (Cmax and AUC) as adults for both LY3819253 and LY3832479.  Exclusion criterion 
#29 was added to ensure all participants have a body weight ≥ 40 kg.  Thus, adolescent 
participants will receive the same dose level as the adult participants.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
52
700 mg LY3819253 and 1400 mg LY3832479
In treatment arms 9 and 18, participants will receive a combination of 700 mg LY3819253 and
1400 mg LY3832479.  To provide coverage of the different but overlapping epitopes on SARS-
CoV-2 receptor binding domain sites for the combination of LY3819253 and LY3832479, the 
dose selection rationale for each single mAb in the combination is the same as for the dose 
rationale for a single mAb. 
The dose of 700 mg LY3819253 was confirmed as the maximum therapeutic dose in the PYAB 
interim analysis based on viral load, symptoms and clinical outcomes.  The dose of 1400 mg 
LY3832479 is selected as the maximum therapeutic dose based on an approximate 2-fold higher 
IC50 to LY3819253.  At these dose levels, the combination is expected to reduce viral load 
based on viral dynamic PK/PD modeling (updated with reduced translational uncertainty) and 
have a sustained concentration above the respective IC90 of viral neutralization for at least 28 
days in 90% of the participant population.
350 mg LY3819253 and 700 mg LY3832479
Treatment arm 14 participants will receive a combination of 350 mg LY3819253 and 700 mg 
LY3832479.  The doses were selected based on PK/PD modeling, in addition to interim PK, viral 
load, symptoms, clinical outcome and safety data from Study J2X-MC-PYAH (BLAZE-4).
250 mg LY3819253 and 500 mg LY3832479
Treatment arm 19 participants will receive a combination of 250 mg LY3819253 and 500 mg 
LY3832479.  The subcutaneous doses were selected based on PK/PD modeling as described 
above, in addition to interim PK, viral load, symptoms, clinical outcome and safety data from 
Study PYAH.   
4.4.
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.
The end of the study is defined as the date of last scheduled procedure shown in the SoA for the 
last participant in the trial globally.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
53
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.
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Are ≥12 years of age at the time of screening
Disease Characteristics
2. Are currently not hospitalized
3. Have one or more mild or moderate COVID-19 symptoms (FDA May 2020, Available at: 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/covid-19-
developing-drugs-and-biological-products-treatment-or-prevention)
i. Fever
ii. Cough
iii. Sore throat
iv. Malaise
v. Headache
vi. Muscle pain
vii. Gastrointestinal symptoms, or
viii. Shortness of breath with exertion
4. Must have sample collection for first positive SARS-CoV-2 viral infection determination
≤3 days prior to start of the infusion
Sex
5. Are males or females, including pregnant females
Reproductive and Contraceptive requirements are provided in Section 10.4, Appendix 4.  
Contraceptive use by males or females 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

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
54
Informed Consent
8. The participant or legally authorized representative give 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. 
Treatment arms 7-9, 13-14, 18-19
27. Are ≥18 years of age and satisfy at least one of the following at the time of screening

Are pregnant

Are ≥65 years of age

Have a BMI ≥35

Have chronic kidney disease

Have type 1 or type 2 diabetes

Have immunosuppressive disease

Are currently receiving immunosuppressive treatment, or

Are ≥ 55 years of age AND have
o
cardiovascular disease, OR
o
hypertension, OR 
o
chronic obstructive pulmonary disease or other chronic respiratory disease
Note: BMI is rounded to the nearest whole number, for example, 34.5 is rounded to 35.
28. Are 12-17 years of age (inclusive) AND satisfy at least one of the following at the time of 
screening

Are pregnant

Have a BMI ≥85th percentile for their age and gender based on CDC growth 
charts, https://www.cdc.gov/growthcharts/clinical_charts.htm

Have sickle cell disease 

Have congenital or acquired heart disease 

Have neurodevelopmental disorders, for example, cerebral palsy 

Have a medical-related technological dependence, for example, tracheostomy, 
gastrostomy, or positive pressure ventilation (not related to COVID-19)

Have asthma or reactive airway or other chronic respiratory disease that requires 
daily medication for control

Have type 1 or type 2 diabetes

Have chronic kidney disease

Have immunosuppressive disease, or

Are currently receiving immunosuppressive treatment.
5.2.
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
9. Have SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 < 300, respiratory rate ≥30 per 
minute, heart rate ≥125 per minute (FDA May 2020)

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
55
10. Require mechanical ventilation or anticipated impending need for mechanical ventilation 
11. Have known allergies to any of the components used in the formulation of the 
interventions
12. Have hemodynamic instability requiring use of pressors within 24 hours of 
randomization
13. 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
14. Have any co-morbidity requiring surgery within <7 days, or that is considered life-
threatening within 29 days
15. Have any serious concomitant systemic disease, condition or disorder that, in the opinion 
of the investigator, should preclude participation in this study.
Other Exclusions
16. Have a history of a positive SARS-CoV-2 serology test
17. Have a history of a positive SARS-CoV-2 test prior to the one serving as eligibility for 
this study
18. Have received an investigational intervention for SARS-CoV-2 prophylaxis within 30 
days before dosing
19. Have received treatment with a SARS-CoV-2 specific monoclonal antibody
20. Have received convalescent COVID-19 plasma treatment 
21. Exclusion criterion [21] removed in amendment (k)
22. 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.
23. Are concurrently enrolled in any other type of medical research judged not to be
scientifically or medically compatible with this study
24. Are breast feeding
25. Are investigator site personnel directly affiliated with this study, and  
29. Have body weight <40 kg.
5.3.
Lifestyle Considerations
Reproductive and Contraceptive guidance is provided in Section 10.4, Appendix 4.
5.4.
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. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
56
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.  
6.1.
Study Intervention(s) Administered
Each participant will receive either placebo, LY3819253, or a combination of LY3819253 and 
LY3832479.  
The optional treatment arm 5 LY3819253 dose level may be tested based on interim analysis 
results.  The dose levels for this optional treatment arm will not exceed 7000 mg and may 
include 175 mg.  
Study intervention must be administered within 3 days of the first positive SARS-CoV-2 test 
sample collection.
Intervention 
Name
Placebo
LY3819253
LY3832479
Dose 
Formulation
0.9% sodium chloride 
solution
Solution
Dosage Level(s) 
(mg)
Not applicable
250
350
700
2800
7000
500
700
1400
2800
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.
Infusion and subcutaneous dose preparation information may be found in the pharmacy 
preparation instructions.
The infusion rate may be reduced as deemed necessary if an infusion reaction is observed
(Section 6.1.1.2).  Participants will be monitored for at least 1 hour after completion of the 
infusion. 
Subcutaneous injections will be administered in the abdomen.  The dose will be administered as 
3 injections of 2-mL each.  Different quadrants of the abdomen should be used for each injection.  
Record the package number and location of administration.
The site must have age-appropriate resuscitation equipment, emergency drugs and appropriately 
training staff available during the infusion and for at least 1 hour after the completion of the 
infusion. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
57
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, and dizziness.  
Infusion-related reactions severity will be assessed and reported using the Division of Allergy 
and Infectious Diseases (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events, version 2.1 (July 2017). 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
58
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).
6.1.2.
Temporary Stopping Criteria
Changes to the planned dosing schedule must be appropriately documented and communicated 
with the study personnel and the IRB/IEC before dosing continues.  
Treatment arms 1-9, 13-14
The Assessment Committee (AC) members individually will review unblinded safety data for 
treatment arms 1-4 and 6, and meet as described in the AC Charter. The Assessment Committee 
(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).
The Data Monitoring Committee (DMC) may stop enrollment or change other study parameters
based on their review for treatment arms 7-9, 13-14, and 18.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
59
Treatment arm 19
For the first 20-30 participants administered intervention, dosing will be re-evaluated if these 
circumstances occur 

3 or more participants develop AEs that are considered to be related to study treatment
OR

1 or more participants develop AEs that are considered to be related to study treatment 
and are serious (SAEs) or graded as severe.
The investigator and the Lilly sponsor team are responsible for determining if safety is 
acceptable to continue dosing. 
Adverse Event-related Information
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
6.2.
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, where applicable, the interventions must be prepared by 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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
60
6.3.
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) and age at the time of screening (<18 years of age versus ≥18 years of age).  
All eligible participants will be randomized, initially following an equal allocation to treatment 
arms.  Given the staggered start of the 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. If additional placebo participants 
are enrolled, then the allocation ratio may change accordingly.  See Section 9.5 for details.
Blinding
For the blinded treatment arms, 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.  
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.
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.
6.4.
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 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
61
confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study intervention.  
6.5.
Concomitant Therapy
Prior Treatment 
Any prior therapy, such as antivirals, antibiotics, vaccines, or anti-malarials used as treatment 
prior 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.
For adolescent participants, record any non-SARS-CoV-2 vaccines received 90 days prior to 
signing informed consent.
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 participants hospitalized with severe disease (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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
62
6.6.
Dose Modification
This protocol allows some alteration from the currently outlined dosing schedule, but the 
maximum dose of LY3819253 will not exceed 7000 mg or the maximum tolerated dose from 
PYAA.  
6.7.
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
63
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.
7.1.
Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) study intervention. If the IV infusion 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 as described in the SoA.
7.2.
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, 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.  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 
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 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
64
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).
7.3.
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
65
8.
Study Assessments and Procedures
Study procedures and their timing are summarized in the SoA.
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.
8.1.
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 and LY3819253 in combination with LY3832479 compared to placebo on clinical 
status.
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

loss of appetite, and

changes in taste and smell.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
66
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.
8.2.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA.
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 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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
67
Treatments 1-4 and 6
This table outlines Day 1 vital signs data collection on the CRF in relation to the infusion for 
treatment arms 1-4 and 6.  Infusion times may vary depending on the participant.
Timepoint (minutes)
Collect data on CRF
Immediately before infusion
Yes
During Infusion, as possible
--
   15
No
   30
Yes
   45
No
   60 
Yes
After Infusion – every 30 minutes for 2 hours after the end of the infusion
--
   90
Yes
   120
No
   150
No
   180
No
Treatment arms 7-9, 13-14, 18
This table outlines Day 1 vital signs data collection on the CRF in relation to the infusion for 
treatment arms 7-9, 13-14, and 18.  Infusion times may vary depending on the participant. 
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
--
   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.
Treatment arm 19
Vital signs data collection on the CRF will occur immediately before the subcutaneous injection, 
and at 30 minutes after the injection.
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 
for the timing and frequency.  All protocol-required laboratory assessments, as 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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
68
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.
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.  
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.  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 

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).

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
69
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. 
8.3.
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.
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
70
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
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
If a hypersensitivity 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 
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. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
71
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.
Injection Site Reactions
For subcutaneous injections, manifestations of a local ISR may include erythema, induration, 
pain, pruritus, and edema. If an ISR is reported by a participant or site staff, the ISR CRF will be 
used to capture additional information about this reaction, for example, injection-site pain, 
degree and area of erythema, induration, pruritis and edema.
8.3.9. 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.
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
72
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.
8.4.
Treatment of Overdose
There is no known antidote for an overdose of LY3819253 or LY3819253 in combination with 
LY3832479. 
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.
8.5.
Pharmacokinetics
Venous blood samples will be collected as specified in the SoA for determination of 
concentrations of LY3819253 and LY3832479 used to evaluate the PK for LY3819253 and 
LY3832479.  
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.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
73
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 and LY3832479 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 used for exploratory analyses as deemed appropriate.
8.6.
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 and the disease, 
which may include sequencing and/or culture of the virus for future studies.
8.7.
Genetics
A whole blood sample will be collected in adult participants 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.
8.8.
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 
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 
pathways, cellular composition, serum analytes, or epigenetic biomarkers, to evaluate their 
association with observed clinical responses to LY3819253, LY3832479 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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
74
8.9.
Immunogenicity Assessments
Visits and times
At the visits and times specified in the SoA, venous blood samples will be collected to determine 
antibody production against LY3819253 or LY3832479.  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 or LY3832479 at a laboratory approved by the sponsor.  Antibodies may be 
further characterized for their ability to neutralize the activity of LY3819253 or LY3832479.
Samples used for immunogenicity may be used for exploratory analyses as deemed appropriate.
Sample retention
Sample retention is described in Appendix 1, Section 10.1.12.
8.10.
Health Economics
This section is not applicable for this study.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
75
9.
Statistical Considerations
9.1.
Statistical Hypotheses
For treatment arm 7, the hypothesis is whether there is a difference in the proportion of 
participants who experience a COVID-related hospitalization or death from any cause compared 
to concurrently enrolled placebo data from treatment arm 8.
For treatment arm 9, the hypothesis is whether there is a difference in the proportion of 
participants who experience a COVID-related hospitalization or death from any cause compared 
to all placebo data from treatment arm 8.  
For treatment arm 14, the hypothesis is whether there is a difference in the proportion of 
participants with persistently high SARS-CoV-2 viral load at Day 7 compared to treatment arm 
13.
For treatment arm 19, the hypothesis is non-inferiority in the proportion of participants with 
persistently high SARS-CoV-2 viral load at Day 7 compared to treatment arm 18. 
9.2.
Sample Size Determination
Sample Size
Treatment arms 1-4 and 6
The initial planned sample size is approximately 500 participants allocated across five treatment
arms (treatment arms 1-4 and 6). Additional placebo participants may be enrolled to ensure up to 
50 concurrent placebo controls for treatment arm 6.  
Up to 100 additional participants may be introduced for optional treatment arm 5. See Section 9.5
for interim analysis details.
Treatment arms 7-9
Participants in treatment arms 7-9 are adults and adolescents with at least 1 risk factor for 
developing severe COVID-19 illness. There is no set sample size for the adolescent participants.
The planned sample size for the primary comparison of treatment arms 7 and 8 is approximately 
1000 participants equally randomized to placebo or the combination of LY3819253 and
LY3832479.  
The planned sample size for treatment arm 9 is approximately 500 participants. Since treatment 
arm 9 begins enrollment after treatment arm 7, additional participants will be enrolled in 
treatment arm 8 to ensure at least a 33% increase in placebo participants and adequate placebo 
control for the primary comparison of treatment arms 8 and 9.
Treatment arms 13 and 14
Participants in treatment arms 13 and 14 are adults and adolescents with at least 1 risk factor for 
developing severe COVID-19 illness. There is no set sample size for the adolescent participants
or those with prior SARS-CoV-2 vaccine use.
The planned sample size for treatment arms 13 and 14 is approximately 400 participants 
randomized 2:3, placebo:combination of LY3819253 and LY3832479.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
76
Treatment arm 18
The planned sample size for treatment arm 18 is approximately 460 participants. 
Treatment arm 19
The planned sample size for treatment arm 19 is approximately 460 participants. 
Stratification
Participants will be stratified by

duration since symptom onset category (≤8 days versus >8 days)

age at the time of screening (<18 years of age versus ≥18 years of age), and

and whether a participant received a SARS-CoV-2 vaccine or not prior to screening.
Treatment arms 1-4 and 6
Simulations
A viral dynamic model was used to simulate viral loads over time for participants treated with 
LY3819253 and placebo. This simulated population and Monte Carlo methods were used to 
estimate statistical power associated with the comparison of change from baseline to day of 
interest in SARS-CoV-2 viral load between LY3819253 and placebo.  
The mean log change from baseline to Day 11 (± 4 days) for LY3819253 and placebo in the 
simulated population were approximately -4.38 and -3.48 (standard deviation 1.9), respectively, 
representing an average of 87% viral load reduction. 
Given these assumptions, an assumed sample size of 100 participants per treatment arm provides 
approximately 91% power to test superiority of an investigational intervention vs placebo in 
effect on viral load, as measured by change from baseline to Day 11 (± 4 days), at the two-sided 
0.05 alpha level.
Periodic adjustments to the allocation ratio of participants will be informed by planned interim 
analyses. See Section 9.5 for details.
Treatment arms 7-9
Sample size justification is based on the endpoint of proportion of participants experiencing 
COVID-related hospitalization or death from any cause. A sample size of approximately 500 
adult participants per treatment arm provides greater than 90% power to demonstrate that 
LY3819253 in combination with LY3832479 is statistically significantly better than placebo, 
defined as odds ratio <1 in the proportion of participants experiencing a COVID-related 
hospitalization or death from any cause. This sample size calculation assumes a placebo event 
rate of 8.7% and a relative reduction of 60% for LY3819253 in combination with LY3832479, 
which were informed from available data on hospitalization or death events.

C O N FI D E N TI A L
Pr ot oc ol  n u m ber J 2 W-M C -P Y A B ( m)
7 7
Tre at me nt ar ms 1 3 - 1 4
S a m ple size j ust ificati o n f or t hese ar ms is base d o n t he e n d p oi nt of pr o p ortio n of  partici pa nts 
wi t h persiste ntl y hi g h S A R S -C o V -2 vi r al loa d at Da y  7. A sa m ple size of a p pr o xi matel y 4 0 0 
parti ci pa nts pr o vi des greater t ha n 9 0 % p o wer t o de m o nstrate t hat L Y 3 8 1 9 2 5 3 i n c o m bi nat i on 
wi t h L Y 3 8 3 2 4 7 9 is statisticall y si g nifica ntl y better t ha n place b o. T his sa mple size calc ulat i on 
ass u me d a place b o e ve nt rate of 3 0 % a n d a relat i ve re d ucti o n of  6 0 % for L Y 3 8 1 9 2 5 3 i n 
c o m bi nat i on wi t h L Y 3 8 3 2 4 7 9, w hic h were i nf or me d fr o m a vaila ble data o n rates of persiste ntl y 
hi g h S A R S -C o V -2 vi r al loa d.
Tre at me nt ar ms 1 8- 1 9
T he pri mar y  o bjecti ve f or t hese treat me nt ar ms is t o de m o nstrate n o n -i nferi ority ( NI) of  
treat me nt ar m 19 c o mpare d t o t he acti ve c o m parat or treat me nt a r m 1 8. 
A n NI b o u n dar y  of 1. 9 6 will be use d, w hic h is s maller t ha n t he i n verse of t he 9 7. 5t h perce nt ile of 
t he p osterior di stri b utio n of  t he o d ds ratio ( O R) f or treat me nt ar m 19 t o treat me nt ar m 18 f or t he 
D a y  7 persiste nt l y hi g h viral l oa d e n d p o i nt. T he p osteri or distri b ut i on of t he O R was deri ve d 
usi n g a Ba yesia n hierarc hical meta -a nal ysis of  PY A B data . 
T he NI mar gi n of 1. 9 6 e ns ures preser vat i on of at least 5 0 % of treat me nt ar m 1 9 efficac y,
esti mate d usi n g t he o bser ve d o d ds rati o . A d ditio nal  details re gar di n g t he just ificati on of t he NI 
b o u n dar y  of 1.9 6 will be pr o vi de d i n t he statist ical a nal ysis pla n ( S A P). 
T he ra n d omizat i on of  a p pr o xi matel y 9 2 0 parti ci pa nts acr oss treat me nt ar ms 1 8 a n d 1 9 pr o vi des 
8 5 % p o wer t o esta blis h NI of tr e at me nt ar m 1 9 c o m pare d t o treat me nt ar m 1 8 . If Da y  7 
persiste ntl y hi g h viral l o a d stat us has a n o d ds rati o of 1 f or t he c o mparis o n of ar m 1 9 , t he u p per 
b o u n d of t he 9 5 % CI of t he O R is ≤1. 9 6.
9. 3.
P o p ul ati o ns f or A n al yses
T h is ta ble defi nes t he p o p ulati o ns f or a nal ysis. 
P o p ul ati o n
Descri pti o n
E ntere d
All partici pa nts w h o si g n t he i nf or me d c o nse nt f or m
Efficac y
All ra n d o mize d partici pa nts w h o recei ve d st u d y i nter ve nti o n a n d pr o vi de d at 
least one p ost -baseli ne meas ure f or t he rele va nt e n d p oi nt. Partici pa nts will be 
a nal yze d acc or di n g t o t he i nter ve nti o n t o w hic h t he y were ra n d o mize d. 
(I nte nti on t o treat) .  
Safet y
All partici pa nts ra n d o ml y assi g ne d a n d w h o recei ve d st u d y i nter ve nti o n. 
Partici pa nts will be a nal yze d acc or di n g t o t he i nter ve nti o n t he y act uall y 
recei ve d.  
P har mac o ki netic 
All ra n d o mize d partici pa nts w h o recei ve d st u d y i nter ve nti o n a n d ha ve 
e va l ua ble P K sa m ple. Partici pa nts will be a nal yze d acc or di n g t o t he 
i nter ve nti on t he y recei ve d.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
78
9.4.
Statistical Analyses
Statistical analysis of this study will be the responsibility of the sponsor or its designee.
Unless otherwise specified, treatment effects using frequentist approaches will be conducted 
using 2-sided tests at an alpha level of 0.05. When Bayesian methods are used for analyses, and
posterior mean, posterior standard deviation, credible intervals, and posterior probability of the 
effect of interest will be summarized. For the Bayesian analyses, the prior distributions and 
success definitions will be fully described in the statistical analysis plan (SAP). No adjustment 
for multiplicity will be performed in this study. Details of the handling of dropouts or missing 
data will be fully described in the SAP. 
Analyses will be performed separately for treatment arms 

1-4 and 6

7 and concurrently enrolled 8

8 and 9, 

13 and 14, and

18 and 19.
Note, for the key secondary endpoints of overall clinical status the analysis will use data from 
multiple treatment arms.
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.
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
79
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 1-4 and 6
Primary endpoint for treatment arms 1-4 and 6 is the change from baseline to Day 11 (± 4 days) 
in SARS-CoV-2 viral load. Statistical hypothesis testing for the primary endpoint will be 
conducted using a mixed model repeated measure (MMRM) analysis method at the two-sided 
0.05 level.
Treatment Arms 7-9
The primary endpoint is the overall participant clinical status, measured by the proportion 
(percentage) of participants who experience COVID-19 related hospitalization (defined as ≥24
hours of acute care) or death from any cause by Day 29.
The primary analysis method will be a logistic regression with a primary success criterion of 
one-sided alpha level 0.025.
Treatment Arms 13-14
The primary endpoint is the difference in the proportion of participants with persistently high 
SARS-CoV-2 viral load at Day 7 between treatment arm 14 compared to treatment arm 13.
The primary analysis method will be a logistic regression with a primary success criterion of 
one-sided alpha level 0.025.
Treatment Arms 18-19
The primary endpoint is noninferiority in the proportion of participants with persistently high 
SARS-CoV-2 viral load at Day 7 between treatment arm 19 compared to treatment arm 18.
The primary analysis method will be a logistic regression with a primary success criterion of the 
upper bound of the 95% CI ≤1.96.
Full details will be provided in the SAP.
9.4.3.
Secondary Endpoints
9.4.3.1.
Key Secondary Endpoints 
Treatment arms 7-9
Key secondary endpoints for treatment arms 7-9 include

Reduction of SARS-CoV-2 viral load measured by change from baseline to Day 7 (±2 days)

The proportion of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7 
(+2 days)

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
a COVID-19 related emergency room visit, or 
o
death from any cause, and

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
80

Time to sustained symptom resolution 
o
symptoms are scored as absent. 
Treatment arms 13-14 and 18-19
Key secondary endpoints include

Reduction of SARS-CoV-2 viral load measured by change from baseline to Day 7 (±2 days), 
and

Proportion (percentage) of participants who experience COVID-19 related hospitalization 
(defined as ≥24 hours of acute care) or death from any cause by Day 29
9.4.3.2.
Safety
Safety analyses will be conducted using the safety population described above. 
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 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.
For treatment arms 13-14, 18-19 post-administration observations and AEs will be evaluated.
For treatment arm 19, reported injection site reactions will be further characterized. 
9.4.3.3.
Additional Secondary Endpoints
Treatment Arms 1-4 and 6
Additional secondary endpoints for treatment arms 1-4 and 6 include

Change from baseline to Day 11 (± 4 days) in SARS-CoV-2 viral load among participants 
enrolled with ≤8 days of symptoms prior to randomization

Time to symptom resolution 
o
symptoms are scored as absent

Proportion of participants demonstrating symptom improvement via the symptom 
questionnaire on Days 7, 11, 15 and 22

Proportion of participants demonstrating symptom resolution via the symptom questionnaire 
on Days 7, 11, 15 and 22

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.

Change in symptom score (total of ratings) from baseline to Days 7, 11, 15 and 22 

SARS-CoV-2 viral load and viral clearance including: 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
81
o
Proportion of participants that achieve SARS-CoV-2 clearance (Days 7, 11, 15, and 
22)
o
Time to SARS-CoV-2 clearance 
o
SARS-CoV-2 viral load area under the concentration-time curve (AUC) assessed 
through Day 29

Proportion (percentage) of participants who experience these events by Days 29, 60 and 85
o
COVID-19 related hospitalization (defined as ≥ 24 hours of acute care)
o
a COVID-19 related emergency room visit, or 
o
death.
Treatment Arms 7–9
Additional secondary endpoints for treatment arms 7-9 include

SARS-CoV-2 viral load reduction change from baseline to 
o
Day 3 (+ 1 day) 
o
Day 5 (± 2 days)

SARS-CoV-2 viral load area under the response-time curve (AUC) assessed through Day 7

Time to SARS-CoV-2 clearance 

Time to symptom resolution 

Time to complete symptom resolution

Time to sustained complete symptom resolution  

Proportion of participants demonstrating symptom resolution via the symptom questionnaire 
on Days 2-11

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, and

Proportion of participants demonstrating symptom improvement via the symptom 
questionnaire on Days 2-11.
Treatment Arms 13–14, 18-19
Treatment arm 14 and treatment arm 19 will be compared to all high-risk placebo participants in 
pooled treatment arms 8 and 13, for proportion (percentage) of participants who experience these 
events by Day 29

COVID-19 related hospitalization (defined as ≥24 hours of acute care), or

a COVID-19 related emergency room visit, or 

death from any cause.
Additional secondary endpoints will compare

Treatment arm 13 to treatment arm 14, and

Treatment arm 19 to treatment arm 18.  
The endpoints are
o
time to sustained symptom resolution
o
SARS-CoV-2 viral load reduction change from baseline to 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
82

Day 3 (+ 1 day) 

Day 5 (± 2 days)
o
SARS-CoV-2 viral load area under the response-time curve (AUC) assessed through
Day 7
o
Time to SARS-CoV-2 clearance
o
Time to symptom resolution 
o
Time to complete symptom resolution
o
Time to sustained complete symptom resolution  
o
Proportion of participants demonstrating symptom resolution via the symptom 
questionnaire on Days 2-11
o
Time to symptom improvement

symptoms scored as moderate or severe at baseline are scored as mild or 
absent, AND 

symptoms scored as mild or absent at baseline are scored as absent, and
o
Proportion of participants demonstrating symptom improvement via the symptom 
questionnaire on Days 2-11.
Full details of the analyses will be in the SAP.
9.4.3.4.
Pharmacokinetic Analyses
Pharmacokinetic analyses will be conducted on data from all participants who receive 
intervention and have evaluable PK. LY3819253 and LY3832479 concentration data will be 
summarized descriptively by sample collection time (e.g., Day 29). Additional population
analysis approaches using non-linear mixed effects modeling may be used to evaluate exposure-
response of safety and efficacy.
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).

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
83
The frequency and percentage of participants with preexisting ADA and who are TE-ADA 
positive (TE-ADA+) to LY3819253 or LY3832479 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 or LY3832479 may also be assessed. Additional details may be provided in 
the SAP.
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

concomitant medication

high risk status for severe COVID-19 illness (treatment arms 1-4, 6), or

SARS-CoV-2 vaccine status (treatment arms 13-14, 18-19).  
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. 
9.5.
Interim Analyses 
Treatment Arms 1-4 and 6
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.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
84
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.
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. 
Periodic adjustments to the allocation ratio may be made to achieve an equal 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 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. 
Treatment Arms 7-9, 13-14, 18-19
Unblinded assessments of efficacy will be done separately for treatment arms 7 and 8, 8 and 9, 
13 and 14, and 18 and19. 
Treatment Arms 7 and 8
Assessments will begin when all participants for treatment arm 7 and concurrently enrolled 
treatment arm 8 complete the Day 29 visit. Equal allocation to treatment arms 7 and 8 is planned.  
Treatment Arms 8 and 9
Assessments will begin when all additional participants from treatment arm 8 and participants 
from treatment arm 9 complete the Day 29 visit. Additional participants will be enrolled in 
treatment arm 8 to ensure at least a 33% increase in placebo participants and adequate placebo
control for the primary comparison of treatment arms 8 and 9.
Safety Reviews
Safety reviews will occur as specified in the DMC charter.
PK/PD 
A limited number of pre-identified individuals may gain access to unblinded data, as specified in 
the unblinding plan prior to the primary lock, in order to initiate the population PK/PD model 
development processes. Following the database lock, the sponsor will be unblinded to analyze 
and report the data.
Unblinding  
Unblinding details are specified in the unblinding plan section of the SAP or in a separate 
unblinding plan document.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
85
9.6.
Data Monitoring Committee (DMC)
Treatment Arms 1-4 and 6
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.
Treatment Arms 7-9
An external DMC will analyze unblinded safety data as specified in a DMC charter.  
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 DMC will be 
provided in the DMC charter.
Treatment Arms 13-14, 18-19
An external DMC will analyze safety data as specified in a DMC charter.
Overall committee structure information is in Section 10.1.5. Details of the DMC will be 
provided in the DMC charter.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
86
10.
Supporting Documentation and Operational Considerations
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
10.1.1.
Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines

Applicable International Council for 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 (CTA).
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
87
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.  The medical record should also describe how the investigator 
determined that the person signing the ICF was the participant’s legally authorized representative 
(parent/guardian).  
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study, per the reconsenting guidelines as appropriate. Verbal reconsenting 
and alternative methods of obtaining consent may be utilized if approved by the IRB.
Minor participants must be re-consented if they reach the age of majority during the course of 
study, in order to continue participating.
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
88
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.
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.   
The DMC will consist of members external to the sponsor (Lilly).  The membership will include, 
at a minimum, a chair (physician), a statistician and another physician.  The DMC 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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
89
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 
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 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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
90
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.
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
91
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.  
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

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
92
10.2.
Appendix 2: Clinical Laboratory Tests
Clinical laboratory tests will be performed according to the SoA.  
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
93
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.
C-reactive protein (CRP); high-sensitivity
For adults only

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
94
Clinical Laboratory Tests
Comments  
Ferritin
For adults only
D-dimer
For adults only
Procalcitonin 
For adults only
Troponin 
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
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
Immunogenicity Samples
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
   Anti-LY3819253 antibodies 
   Anti-LY3832479 antibodies

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
95
10.3.
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;
o
Hypoxemia due to COVID-19 requiring non-invasive ventilation or high flow 
oxygen devices;

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
96
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.
d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
97

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., 
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).

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
98
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 
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
99

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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
100
10.4.
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 (WOCBP)
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:
d. 12 months of amenorrhea for women >55, with no need for FSH
e.
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 and not of child-bearing potential may participate in this 
study.
Women of child-bearing potential who are not pregnant at the time of study entry, and 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 who are not pregnant at the time of study entry, 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. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
101
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
102
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, 
this information will include a follow-up of at least 5 half-lives after last exposure or birth.  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 or are pregnant at the time of study entry
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study or is pregnant at the time of study entry. 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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
103
10.5.
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 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 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. 

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
104
10.6.
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
105
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 and LY3832479 
anti-drug antibodies 
(immunogenicity/ADA)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
LY3819253 and LY3832479 
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
106
10.7.
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 <1.5x ULN
ALT or AST ≥3x ULN
ALP <1.5x ULN
ALP ≥2x ULN
TBL <1.5x ULN
TBL ≥2x ULN (except for participants with Gilbert’s 
syndrome)
ALT or AST ≥1.5x ULN
ALT or AST ≥2x baseline
ALP ≥1.5x ULN
ALP ≥2x baseline
TBL ≥1.5x ULN
TBL ≥2x 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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
107
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 <1.5x ULN
ALT or AST ≥3x ULN with hepatic signs/symptoms*, or
ALT or AST ≥5x ULN
ALP <1.5x ULN
ALP ≥3x ULN
TBL <1.5x ULN
TBL ≥2x ULN (except for participants with Gilbert’s syndrome)
ALT or AST ≥1.5x ULN
ALT or AST ≥2x baseline with hepatic signs/symptoms*, or
ALT or AST ≥3x baseline
ALP ≥1.5x ULN
ALP ≥2x baseline
TBL ≥1.5x ULN
TBL ≥1.5x 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.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
108
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

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
109
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.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
110
10.8.
Appendix 8: Abbreviations
Term
Definition
AC
assessment committee
ADA
anti-drug antibody
ADE 
antibody-dependent enhancement
adolescent
Participant 12 to 17 years of age
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.
CTA
Clinical trial agreement
DMC
data monitoring committee
ECG
electrocardiogram
FiO2
fraction of inspired oxygen in the air
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

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
111
ICF
informed consent form
ICH
International Council for Harmonisation
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
Legal representative
An individual or judicial or other body authorized under applicable law to consent, on 
behalf of a prospective participant, to their participation in the clinical study.
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

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
112
10.9.
Appendix 9: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC).
Amendment l: 03 February 2021
Overall Rationale for the Amendment:
This amendment addresses changes in response to emerging data.  As a result, participants will no 
longer receive placebo, the sample size for treatment arms 13 and 14 is reduced, open-label 
treatment arms 16-19 are added and objectives and endpoints changed.  
Treatment arms 16 and 17 will evaluate faster infusion times using sentinel dosing.  
Treatment arm 18 will act as the active comparator for treatment arms 14, 16-17 and 19.  
Treatment arm 19 will evaluate the efficacy and safety of subcutaneous dosing.
Treatment arms 16-19 will not be blinded because of the change in primary endpoint to a more 
objective evaluation of change in viral load.  This also removes the need for a double-dummy 
design requiring every participant to receive an infusion and subcutaneous injections.
Section # and Name
Description of Change
Brief Rationale
Throughout the protocol
Removed treatment arms 13-14 
from most headers and sub-
headings where it was grouped 
with treatment arms 7-9.
Treatment arm 13-14 was added to new 
sections with new treatment arms 16-19.
1.1 Synopsis
New Objectives/Endpoints table 
for treatment arms 13-14, 16-19
Change in primary endpoint to viral load for 
treatment arms 14, 16-18.
Addition of new treatment arms and 
comparison analysis
1.1 Synopsis
Updated Treatment and 
Assessment Period
Addition of new treatment arms
1.1 Synopsis
Updated Disclosure Statement 
Addition of new open-label treatment arms.
1.1 Synopsis
Updated Number of Participants
Addition of new treatment arms and new 
objectives and endpoints
1.1 Synopsis
Updated Intervention Groups and 
Duration table.  Added text for 
new treatment arms.
Addition of new treatment arms
1.1 Synopsis
Updated Data Monitoring 
Committee treatment arms
Addition of new treatment arms
1.2 Schema
Updated the study schema
Added new treatment arms and associated 
note
1.3.2 Schedule of Activities
Added treatment arms 16-19 to 
this SoA
Treatment arms 16-19 will follow this SoA
1.3.2 Schedule of Activities
Vital Sign – updated text to 
include SQ dosing.
Addition of treatment arm 19

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
113
Section # and Name
Description of Change
Brief Rationale
1.3.2 Schedule of Activities
Pharmacokinetic (PK) sample –
clarified sample collection timing 
after the end of IV infusion
Site feedback that this needed clarification.
1.3.2 Schedule of Activities
Pharmacokinetic (PK) sample -
added Day 3 sample and sample 
times for SQ dose.
Needed to complete the PK profile for SQ 
dose.
Addition of SQ dose.
1.3.2 Schedule of Activities
Immunogenicity sample –
clarified that no sample is needed 
to match the Day 3 PK sample 
for SQ dose. 
Day 3 sample not needed to match the Day 
3 PK sample
2.3 Benefit/Risk Assessment
Added the risk of injection site 
reactions (ISRs).
Addition of SQ dose
3.3 Objectives and Endpoints
Added new objectives and 
endpoints table for treatment 
arms 13-14, 16-19
Change in primary endpoint to viral load for 
treatment arms 14, 16 and 17 compared to 
treatment arm 18.
Addition of new treatment arms and 
comparison analysis
4.1.1 Design Outline
Updated Figure 2 participant 
flow diagram
Included injections for SQ dosing
4.1.1 Design Outline
Treatment and Assessment 
Period – updated last bullet from 
post-infusion to post-dose
Addition of SQ dosing
4.1.1 Design Outline
Updated Treatment arm table
Addition of new treatment arms
4.1.1 Design Outline
Added treatment arms 16-19 will 
be open-label.  
Added text and a new table to 
describe the sentinel dosing for 
treatment arms 16 and 17.
New treatment arms and primary endpoint.
Treatment arms 16 and 17 will evaluate 
shorter infusion times using sentinel dosing 
to ensure safety is acceptable.
4.1.1 Design Outline
Added text to describe that 
treatment arm 18 will be an 
active comparator, and for the 
safety review for treatment arm 
19
Participants will no longer receive placebo.
A safety review will occur for participants 
in treatment arm 19 receiving SQ dose
4.1.1 Design Outline
Added new treatment arms for 
visit types
Addition of new treatment arms
4.2 Scientific Rationale for 
Study Design
Added text for participants no 
longer receiving placebo and 
description of open-label 
treatment arms. Added text for 
the multiple safety reviews for 
treatment arms 16-19
Emerging data.
Safety reviews to minimize the risk of any 
unanticipated safety concerns before fully 
enrolling the treatment arms.
4.3 Justification for Dose
Added treatment arm 18 to the 
justification of the 700/1400 
dose.  Added treatment arms 16 
and 17 for the 350/700 dose.  
Added treatment arm 19 for SQ 
dose.
Addition of new treatment arms.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
114
Section # and Name
Description of Change
Brief Rationale
5.1 Inclusion Criteria
Added new treatment arms for 
Criteria #27 and #28.
Addition of new treatment arms
5.1 Inclusion Criteria
Added “are pregnant” to criteria 
#27 and #28
Emerging data indicate that being pregnant 
is a risk factor for COVID-19 illness
6.1 Study Intervention(s) 
Administered
Updated first sentence to broaden 
scope
Introduction of SQ dosing in addition to IV 
infusion
6.1 Study Intervention(s) 
Administered
Updated the Study Intervention 
table with new dose levels
Addition of new treatment arms
6.1 Study Intervention(s) 
Administered
Added text for subcutaneous 
dosing
Addition of treatment arm 19
6.1.2 Temporary Stopping 
Criteria
Added stopping criteria for 
treatment arms 16-17 and 19.
These treatment arms will evaluate faster 
infusion times and SQ dosing.
6.2 Preparation/Handling/
Storage/Accountability
Updated text to accommodate 
new open-label treatment arms
Addition of new treatment arms.
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding
Updated Blinding sub-section to 
accommodate new open-label 
treatment arms
Addition of new treatment arms
8.2.2 Vital Signs
Updated text for data collection 
on the CRF for new treatment 
arms
Addition of new treatment arms
8.3.8 Injection Site Reactions
New section for SQ dose
Addition of SQ dosing
8.3.9 Product Complaints
Renumbered section to 8.3.9 
with addition of new Section 
8.3.8 Injection Stie Reactions
9.1 Statistical Hypotheses
Updated and added text for 
treatment arms 14, 16-18.
Addition of new treatment arms and new 
primary objective
9.2 Sample Size 
Determination
Updated sample size for 
treatment arms 13 and 14
New strategy for objectives and endpoints 
and analyses
9.2 Sample Size 
Determination
Added sample size for new 
treatment arms 16-19
Addition of new treatment arms
9.2 Sample Size 
Determination
Removed simulation information 
for previous treatment arms 13 
and 14, and added simulation 
information for treatment arms 
14, 16-19
Addition of new treatment arms
9.3 Populations for Analyses
Removed the row for Modified 
Efficacy population
No longer needed
9.4 Statistical Analyses
Updated treatment arms for 
analyses
Addition of new treatment arms
9.4.2 Primary Endpoint
Updated endpoint for treatment 
arms 14, 16-18
Treatment arm 13 is no longer needed for 
the primary endpoint.  
The addition of treatment arms.
9.4.3.1 Key Secondary 
Endpoints
Updated for new treatment arms
New endpoints per emerging data
9.4.3.2 Safety
Added text for new treatment 
arms
Post-administration observations and AEs 
will be evaluated for the new treatment 
arms.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
115
Section # and Name
Description of Change
Brief Rationale
Injection site reactions will be 
characterized.
9.4.3.3 Additional Secondary 
Endpoints
Added separate section for new 
treatment arms for clarity as 
some endpoints are different for 
the new treatment arms.
New treatment arms and endpoints
9.4.6 Subgroup Analyses
Added SARS-CoV-2 vaccine 
status
Participants who received a vaccine are 
allowed in the study
9.5 Interim Analyses
Updated for new treatment arms
Addition of new treatment arms
9.6 Data Monitoring 
Committee
Updated for new treatment arms
Addition of new treatment arms
Throughout the protocol
Minor editorial and formatting 
changes
Minor, therefore not described
Amendment k: 20 January 2021
Overall Rationale for the Amendment:
This amendment allows participants in the study who have received the SARS-CoV-2 vaccine.  
SARS-CoV-2 vaccines are now available to the public and those who received a vaccine or have 
participated in a SARS-CoV-2 vaccine study are allowed in the study.
Section # and Name
Description of Change
Brief Rationale
Section 1.3.2 Schedule of 
Activities for Treatment Arms 
7-9,13-14
Updated Prior treatments of 
special interest to allow the 
SARS-CoV-2 vaccine
The SARS-CoV-2 vaccine is now allowed
2.3 Benefit/Risk Assessment
Updated risk information for 
LY3819253
Emerging data
4.2 Scientific Rationale for 
Study Design
Added a sub-section for 
participants who have received 
the SARS-CoV-2 vaccine
Vaccines are now available to the public 
and those who received a vaccine are 
allowed in the study
5.2 Exclusion Criteria
Criterion #21 is removed
SARS-CoV-2 vaccines are now available to 
the public and those who received a vaccine 
or have participated in a SARS-CoV-2 
vaccine study are allowed in the study
6.5 Concomitant Therapy
Added vaccines to prior 
treatment list that should be 
recorded.
Added “non-SARS-CoV-2” to 
clarify what vaccines are 
recorded for adolescents.  
Need a record of those who received a 
SARS-Cov-2 vaccine.
Need a record of non-SARS-CoV-2 
vaccines that adolescents received 90 days 
prior to signing informed consent.
9.2 Sample Size
Added clarification that there is 
no set sample size for 
participants with prior vaccine 
use.
Those who received a SARS-CoV-2 
vaccine are allowed in the study.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
116
Section # and Name
Description of Change
Brief Rationale
Added stratification factor for 
whether a participant received a 
vaccine or not prior to screening
9.3 Populations for Analyses
Added the Modified Efficacy 
population to table
To distinguish a population for analysis that 
will not include those that received a 
SARS-CoV-2 vaccine.
Throughout the protocol
Minor editorial and formatting 
changes
Minor, therefore not described

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
117
Amendment j: 07 January 2021
Overall Rationale for the Amendment:
This amendment addresses changes in response to emerging data, discussions with the FDA and the 
addition of treatment arms 13 and 14.  Treatment arms 10-12 were skipped due to internal 
programming capabilities.  
Section # and Name
Description of Change
Brief Rationale
Throughout protocol
Added treatment arms 13-14 
identifiers where applicable
Addition of treatment arms 13 and 14
1.1 Synopsis 
Updated treatment arms 7-9 
Objectives and Endpoint table. 
This table is now also applicable 
for treatment arms 13-14.
Alignment with FDA feedback and 
emerging data.  Identified key secondary 
objectives, updated other secondary 
endpoints.
1.1 Synopsis
Updated Disclosure Statement to 
accommodate all treatment arms
Statement applies to all treatment arms
1.1 Synopsis
Updated Number of Participants 
for treatment arms 7-9 and 13-14
Correction of sample size for 7-9 and 
addition of treatment arms 13 and 14
1.1 Synopsis
Updated Intervention Groups and 
Duration table with new 
treatment arms.
Added information about placebo 
control for treatment arms 13 and 
14.
Addition of treatment arms 13 and 14.
1.1 Synopsis
Updated Data Monitoring 
Committee to include treatment 
arms 13 and 14
Addition of treatment arms 13 and 14.
1.2 Schema
Updated Schema and Figure title
Addition of treatment arms 13 and 14.
1.3.2 Schedule of Activities 
(SoA) for 7-9
Will use this SoA for treatment 
arms 7-9, 13-14
Addition of treatment arms 13 and 14.
1.3.2 Schedule of Activities 
(SoA) for 7-9, 13-14
Clarified collection of prior 
“non-COVID” vaccine 
treatments for adolescents
clarification
1.3.2 Schedule of Activities 
(SoA) for 7-9, 13-14
Updated vital signs and Oxygen 
Support timing for Day 1 for an 
infusion that is <15 minutes
Addition of treatment arms 13 and 14.
1.3.2 Schedule of Activities 
(SoA) for 7-9, 13-14
Added clarification that 
pregnancy testing is not 
applicable for females pregnant 
at screening
Pregnant females are eligible in this study.
2.3 Benefit/Risk Assessment
Updated the risk associated with 
administration of LY3819253 
From emerging clinical data
2.3 Benefit/Risk Assessment
Added benefit/risk information 
for the pregnant population
Pregnant females are eligible in this study.
3.2 Objectives and Endpoints 
for Treatment arms 7-9, 13-14
Added treatment arms 13-14.  
Identified key secondary 
objectives, updated other 
secondary and exploratory 
endpoints.
Addition of treatment arms 13 and 14.  
Alignment with FDA feedback and 
emerging data.  

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
118
Section # and Name
Description of Change
Brief Rationale
4.1.1 Design Outline
Updated treatment arm table with 
new treatment arms.
Added information about placebo 
control for treatment arms 13 and 
14.
Addition of treatment arms 13 and 14.
4.2 Scientific Rationale for 
Study Design
Added information for pregnant 
participants
Pregnant females are eligible in this study
4.3 Justification for Dose
Added information for new 
treatment arms
Addition of treatment arms 13 and 14.
5.1 Inclusion Criteria
Updated Criterion #5 to include 
pregnant females
Pregnant females are eligible in this study
5.1 Inclusion Criteria
Added “requires daily 
medication for control” to 
Criterion #28
Per the Emergency Use Authorization 
(EUA) for adolescents
5.2 Exclusion Criteria
Added “or have received a 
SARS-CoV-2 vaccine” to 
Criterion #21
Clarification of criterion because of the 
availability of the vaccine.
5.2 Exclusion Criteria
Removed “pregnant or” from 
Criterion #24
Pregnant females are eligible in this study
6.1 Study Intervention(s) 
Administered
Added new dose levels to Study 
Intervention table
Addition of treatment arm 14.
6.1 Study Intervention(s) 
Administered
Replaced “pharmacy preparation 
instructions” for “pharmacy 
manual”
Correction.  Infusion information may be 
found in the pharmacy preparation 
instructions.
6.1.1.2. Management of 
Infusion Reactions
Removed duplicate text about 
premedication for infusions
This information is located in Section 
6.1.1.1. and was inadvertently repeated in 
Section 6.1.1.2.
7.2 Participant 
Discontinuation/Withdrawal 
from Study
Removed “if the participant 
becomes pregnant during the 
study” from the bulleted list
Pregnant females are eligible in this study
8.2.2 Vital Signs
Updated Treatment arms 7-9, 13-
14 table for Day 1 data collection 
for an infusion that is <15 
minutes
Addition of treatment arms 13 and 14.
8.2.3 Clinical Laboratory 
Assessments
Removed text from Pregnancy 
testing sub-section “Participants 
who are pregnant will be 
discontinued from the study
Pregnant females are eligible in this study
8.3.5 Pregnancy
Removed text from section so 
that it is aligned with Section 
10.4, Appendix 4.
Correction
8.3.6 Hypersensitivity 
Reactions
Removed text about the risk of 
systemic hypersensitivity 
reactions
The risks are outlined in Section 2.3. 
Benefit/Risk Assessment
9.1 Statistical Hypotheses
Updated text according to 
changes to primary endpoint and 
added text for new treatment 
arms
Alignment with FDA feedback and 
emerging data.
Addition of treatment arms 13 and 14.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
119
Section # and Name
Description of Change
Brief Rationale
9.2 Sample Size 
Determination
Added sub-headers for clarity.  
Updated sample size for 
treatment arms 7-9.
Added sample size and 
randomization for treatment arms 
13-14.
Statistician decision and addition of 
treatment arms 13 and 14.
9.4 Statistical Analyses
Added treatment arms 13 and 14 
Addition of treatment arms 13 and 14.
9.4.2 Primary Endpoints
Updated text according to 
changes to primary endpoint and 
for new treatment arms
Alignment with FDA feedback and 
emerging data.
Addition of treatment arms 13 and 14.
9.4.3.1 Key Secondary 
Endpoints
New Section
Alignment with FDA feedback and 
emerging data.
9.4.3.2 Safety
This section is renumbered
Section moved down due to new Key 
Secondary Endpoints section
9.4.3.3 Additional Secondary 
Endpoints
This section is renumbered.  
Updated endpoints for treatment 
arms 7-9 and added arms 13 and 
14
Renumbered due to new Key Secondary 
Endpoints section.
Alignment with FDA feedback and 
emerging data.
9.4.3.4 Pharmacokinetic 
Analyses
This section is renumbered.  
Renumbered due to new Key Secondary 
Endpoints section.
9.4.6 Subgroup Analyses
Removed incorrect text
Correction
9.5 Interim Analyses
Added sub-headers and updated 
text for treatment arms 7-9. 
Added text for new treatment 
arms
Updates made for clarification and addition 
of treatment arms 13 and 14.
9.6 Data Monitoring 
Committee
Added treatment arms 13-14 to 
Treatment Arms 7-9 sub-header 
and updated first sentence under 
this header
Removed text that was not applicable to 
these treatment arms.
10.4 Appendix 4 
Contraceptive Guidance and 
Collection of Pregnancy 
Information
Updated text for the inclusion of 
pregnant females 
Pregnant females are eligible in this study
11 References
Added Chen et.al.2020 reference
Source for information in Section 2.3
Throughout the protocol
Minor editorial and formatting 
changes
Minor, therefore not described

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
120
Amendment i: 30 November 2020
Overall Rationale for the Amendment:
This amendment addresses changes in response to discussions with the FDA to enable independent 
confirmation of the safety and efficacy of LY3819253 in combination with LY3832479 for the 
treatment of COVID-19.  The decision was made to remove treatment arms 10 and 11, and change 
the primary objective, statistical methods and sample size for treatment arms 7-9.  
Section # and Name
Description of Change
Brief Rationale
Title Page
Updated Phase 2 to Phase 2/3
Per FDA feedback to more accurately 
describe study
1.1 Synopsis 
Updated protocol title to Phase 
2/3
Per FDA feedback to more accurately 
describe study
1.1 Synopsis
Updated Objectives and 
Endpoints table for treatment 
arms 7-9 to reflect changes in 
Section 3.
Removed treatment arm 10, updated the 
primary objective for treatment arms 7-9, 
moved reduction in viral load from primary 
to first secondary endpoint, and added Day 
29 to symptom resolution and symptom 
improvement endpoints.
1.1 Synopsis
Removed treatment arm 11 
objectives and endpoints table
Treatment arm 11 is removed from this 
study 
1.1 Synopsis
Updated Overall Design to say 
Phase 2/3
Per FDA feedback to more accurately 
describe study 
1.1 Synopsis
Updated visit type table
Treatment arms 10 and 11 are removed 
from this study
1.1 Synopsis
Updated Disclosure Statement
Treatment arms 10 and 11 are removed 
from this study
1.1 Synopsis 
Updated Number of Participants
Treatment arms 10 and 11 are removed 
from this study and the sample size 
increased for treatment arms 7-9 
1.1 Synopsis
Removed treatment arms 10 and 
11 and updated placebo control 
information in Intervention 
Groups and Duration 
Treatment arms 10 and 11 are removed 
from this study
1.1 Synopsis
Removed treatment arms 10 and 
11 from Data Monitoring 
Committee
Treatment arms 10 and 11 are removed 
from this study
1.2 Schema
Updated existing figure for 
treatment arms 1-9 and removed 
treatment arm 11 figure
Treatment arms 10 and 11 are removed 
from this study
1.3.2. Schedule of Activities
Removed reference to treatment 
arms 10 and 11
Treatment arms 10 and 11 are removed 
from this study
1.3.2. Schedule of Activities
Changed visit window for Study 
Day 11 to -2/+3 from ±3
In order to avoid overlapping visits with 
study day 7 and more flexibility with study 
day 11 visit
2.3 Benefit/Risk Assessment
Removed text for Risks and 
Benefits Associated with Faster 
Rates of Infusion and removed 
text related to treatment arm 11
Removed treatment arm 11

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
121
Section # and Name
Description of Change
Brief Rationale
3.2 Objectives and Endpoints
Updated table for treatment arms 
7-9. 
Removed treatment arm 10, updated the 
primary objective for treatment arms 7-9, 
moved reduction in viral load from primary 
to first secondary endpoint, and added Day 
29 to symptom resolution and symptom 
improvement endpoints.
3 Objectives and Endpoints
Removed treatment arm 11 
objectives and endpoints table
Treatment arm 11 is removed from this 
study 
4.1 Overall Design
Updated Overall Design to say 
Phase 2/3
Per FDA feedback to more accurately 
describe study 
4.1.1 Design Outline
Removed treatment arms 10 and 
11 from Treatment Arm table 
and text
Treatment arms 10 and 11 are removed 
from this study
4.1.1 Design Outline
Updated text to describe that 
treatment arm 8 will be the 
corresponding placebo control 
for treatment arms 7 and 9
Will increase the sample size for 8 and 
enroll with both treatment arms 7 and 9.
4.1.1 Design Outline
Removed information for 
treatment arms 10 and 11 for 
visit types
Treatment arms 10 and 11 are removed 
from this study
4.2 Scientific Rationale for 
Study Design
Removed rationale for treatment 
arm 11 and updated text to 
remove reference to treatment 
arms 10 and 11
Treatment arms 10 and 11 are removed 
from this study
4.3 Justification for Dose
Removed references to treatment 
arms 10 and 11
Treatment arms 10 and 11 are removed 
from this study
5.1 Inclusion Criteria
Removed reference to treatment 
arms 10 and 11 for inclusion 
criteria #27 and #28
Treatment arms 10 and 11 are removed 
from this study
5.1 Inclusion Criteria
Added “have chronic kidney 
disease” to criterion #28
Medical decision
6.1.1.2 Management of 
Infusion Reactions
Added footnote and source back 
to table describing the severity of 
reactions according to Division 
of Allergy and Infectious 
Diseases (DAIDS)
This information was inadvertently 
removed in a previous version of the 
protocol
6.1.2 Temporary Stopping 
Criteria
Removed reference to treatment 
arms 10 and 11 and removed 
specific stopping criteria for 
treatment arm 11
Treatment arms 10 and 11 are removed 
from this study
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding
Removed reference to treatment 
arms 10 and 11
Treatment arms 10 and 11 are removed 
from this study
8.2.2 Vital Signs
Removed reference to treatment 
arms 10 and 11 for vital signs 
data collection table
Treatment arms 10 and 11 are removed 
from this study

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
122
Section # and Name
Description of Change
Brief Rationale
9.1 Statistical Hypotheses
Removed reference to treatment 
arms 10 and 11 and updated 
hypothesis for treatment arm 9
Treatment arms 10 and 11 are removed 
from this study, and updates reflect changes 
for the primary objective and endpoint.
9.2 Sample Size 
Determination
Removed reference to treatment 
arms 10 and 11 and updated 
sample size information for 
treatment arms 7 - 9
Change in strategy per discussions with 
FDA 
9.4 Statistical Analyses
Removed reference to treatment 
arms 10 and 11 and updated 
information for treatment arms 7 
- 9
Treatment arms 10 and 11 are removed 
from this study, and updates reflect changes 
in analyses
9.4.2 Primary Endpoints
Removed reference to treatment 
arms 10 and 11 and updated 
information for treatment arms 7 
- 9
Treatment arms 10 and 11 are removed 
from this study, and updates reflect changes 
in analyses
9.4.3.2 Additional Secondary 
Endpoints
Removed reference to treatment 
arms 10 and 11 and updated 
information for treatment arms 7 
- 9
Treatment arms 10 and 11 are removed 
from this study, and updates reflect the 
move of viral load from primary to 
secondary endpoint, and the addition of Day 
29 to symptom improvement and symptom 
resolution endpoints
9.4.6 Subgroup Analyses
Removed reference to treatment 
arms 10 and 11
Treatment arms 10 and 11 are removed 
from this study
9.5 Interim Analyses
Removed reference to treatment 
arms 10 and 11 and updated 
information for treatment arms 7 
- 9
Treatment arms 10 and 11 are removed 
from this study, and updates reflect changes 
in analyses
9.6 Data Monitoring 
Committee (DMC)
Removed reference to treatment 
arms 10 and 11
Treatment arms 10 and 11 are removed 
from this study
Throughout the protocol
Minor editorial and formatting 
changes
Minor, therefore not described
Amendment g: 17 November 2020
Overall Rationale for the Amendment:
This amendment addresses the addition of treatment arms 9-11.  Treatment arm 9 will explore a 
lower dose level of the combination of LY3819253 and LY3832479.  Treatment arm 10 will provide 
a bridge to the existing placebo arms.  Treatment arm 11 is an open-label sub-study comprised of two 
cohorts to evaluate a faster IV infusion rate of the combination of LY3819253 and LY3832479.   
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis
Added Objectives and Endpoints 
tables for treatment arms 9-11
Addition of new treatments
1.1 Synopsis
Updated sub-headings under 
Design Outline to remove 
“double-blind”
Addition of the open-label treatment arm 11

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
123
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis
Updated Disclosure Statement 
for treatment arms 7-11
Addition of new treatments
1.1 Synopsis
Added Number of Participants 
for treatment arms 9-11
Addition of new treatments
1.1 Synopsis 
Added information for treatment 
arms 9-11 to Intervention Groups 
and Duration
Addition of new treatments
1.1 Synopsis
Updated text under Data 
Monitoring Committee
Addition of new treatments
1.2 Schema
Updated existing figure and
added figure for treatment arm 
11
Addition of new treatments
1.3.2. Schedule of Activities
Updated to include the new 
treatments
New treatments will use the same SoA as 
treatment arms 7-8
2.3 Benefit/Risk
Added sub-headings for 
clarification of information.  
Added the potential benefit/risks 
associated with an increased rate 
of infusion
Treatment arm 11 will use a faster infusion 
rate than the other treatment arms
3 Objectives and Endpoints
Added new sub-headings for the 
separate tables for the different 
treatment arms
Easier document navigation
3 Objectives and Endpoints
The table for treatment arms 7-8 
is now applicable for treatment 
arms 7-10.  
Added clarifying text for 
secondary objectives in this table 
to describe differences between 
treatment arms 7-8 versus 9-10
Treatment arms 9-10 will have basically the 
same objectives and endpoints, but will 
need more flexibility for the secondary 
objectives.
3 Objectives and Endpoints
Added a new table for treatment 
arm 11
Addition of new treatment
4.1.1 Design Outline 
Added sub-headings for 
clarification
Addition of new treatments
4.1.1 Design Outline 
Updated sub-headings to remove 
“double-blind”
Addition of the open-label treatment arm 11
4.1.1 Design Outline
Added information for treatment 
arms 9-11 in treatment arm table 
and text
Addition of new treatments
4.1.1 Design Outline
Added information for treatment 
arms 9-11 for visit types
Addition of new treatments
4.2 Scientific Rationale for 
Study Design
Added rationale for the addition 
of treatment arm 11
This treatment arm is an open-label sub-
study to evaluate a faster infusion rate.
4.2 Scientific Rationale for 
Study Design
Updated participant 
characteristics to add new 
treatment arms
Addition of new treatments
4.3 Justification for Dose
Section was updated to include 
the new treatment information
Addition of new treatments

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
124
Section # and Name
Description of Change
Brief Rationale
5.1 Inclusion Criteria
Added sub-headings for criteria 
#27 and #28
Addition of new treatments
6.1 Study Intervention(s) 
Administered
Added new dose level for 
LY3832479
Addition of new treatments
6.1.2 Temporary Stopping 
Criteria
Added sub-headings for 
treatment arms 1-10 and criteria 
for treatment arm 11
Addition of new treatments and the 2 
cohorts in treatment arm 11
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding
Added sub-headings for 
treatment arms 1-11 and indicate 
that treatment arm 11 is open 
label
Addition of new treatment
8.2.2 Vital Signs
Added new treatment arms to 
table outlining Day 1 vital signs 
data collection and added the 90 
and 120 minute collection to the 
treatment arms 7-11 table
Addition of new treatments
9.1 Statistical Hypotheses
Added information for treatment 
arms 9-10
Addition of new treatments
9.2 Sample Size 
Determination
Added sample size for new 
treatment arms
Added text to clarify 
stratification is not applicable for 
treatment arm 11.
Addition of new treatments
9.2 Sample Size 
Determination
Added information for treatment 
arm 11 under stratification
Stratification is not applicable to treatment 
arm 11.
9.4 Statistical Analyses
Added information for treatment 
arms 9-11
Addition of new treatments
9.4.2 Primary Endpoints
Added information for new 
treatment arms
Addition of new treatments
9.4.3.2 Additional Secondary 
Endpoints
Updates made to include 
treatment arms 9-10 and added 
text for treatment arm 11
Addition of new treatments
9.4.3.3 Pharmacokinetic 
Analyses
Removed reference to 
noncompartmental analysis and 
replaced with descriptive 
summary.  
Number of study participants with 
evaluable PK concentration data has 
increased.
9.4.6 Subgroup Analyses
Updates made to include 
treatment arms 9-10 and added 
text for treatment arm 11
Addition of new treatments
9.5 Interim Analyses
Updates made to include 
treatment arms 9-10, added text 
to explain that unblinded 
assessments will be done 
separately for treatment arms 7 
and 8, and 9 and 10, and added 
text for treatment arm 11
Addition of new treatments

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
125
Section # and Name
Description of Change
Brief Rationale
9.6 Data Monitoring 
Committee (DMC)
Updates made to include 
treatment arms 9-10 and added 
text for treatment arm 11
Addition of new treatments
11 References
Added FDA EUA fact sheet for 
bamlanivimab
Addition of reference.
Throughout the protocol
Minor editorial and formatting 
changes
Minor, therefore not described
Amendment f: 20 October 2020
Overall Rationale for the Amendment:
This amendment addresses changes requested by the Food and Drug Administration (FDA) for 
treatment arms 7 and 8.  Treatment arms 7 and 8 will now include adolescent participants at higher 
risk for severe disease and hospitalization, and the primary and secondary endpoints will be updated.  
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis
Updated treatment arms 7 and 8 
objectives and endpoints
Per FDA request to capture primary and 
secondary clinical endpoints until Day 29
1.1 Synopsis
Added child/adolescent assent to 
the screening procedure
Addition of adolescent participants
1.1 Synopsis
Added text in Number of 
Participants to say that adult and 
adolescent participants with at 
least 1 risk factor are in treatment 
arms 7 and 8
Addition of adolescent participants
1.3.2 Schedule of Activities 
for Treatment Arms 7 and 8
Added a row for informed assent
For adolescent participants
1.3.2 Schedule of Activities 
for Treatment Arms 7 and 8
Added a row to collect 
information on vaccines at 
screening
For adolescent participants
1.3.2 Schedule of Activities 
for Treatment Arms 7 and 8
Updated comments for the 
SARS-CoV-2 Test Panel 
This panel is for adults only to reduce 
invasive procedures and blood volume 
collection in adolescent participants
1.3.2 Schedule of Activities 
for Treatment Arms 7 and 8
Updated comments for 
pharmacokinetics Day 1 predose 
sample
Predose sample is for adults only to reduce 
invasive procedures and blood volume 
collection in adolescent participants
1.3.2 Schedule of Activities 
for Treatment Arms 7 and 8
Updated comments for 
pharmacogenetics sample
This sample is for adults only to reduce 
invasive procedures and blood volume 
collection in adolescent participants
2.3 Benefit/Risk Assessment
Added text for adolescents
Addition of adolescent participants
3 Objectives and Endpoints
Updated endpoints for Treatment 
Arms 7 and 8
Per FDA feedback
4.1.1 Design Outline
Added child/adolescent assent to 
the screening procedure
Addition of adolescent participants
4.2 Scientific Rationale for 
Study Design
Added rationale for including 
adolescent participants
Addition of adolescent participants

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
126
Section # and Name
Description of Change
Brief Rationale
4.3 Justification for Dose
Added justification for 
adolescents
Addition of adolescent participants
5.1 Inclusion Criteria
Removed note about new 
criterion #27
Not applicable any longer 
5.1 Inclusion Criteria
Updated Criterion #1 to include 
participants ≥12 years of age
Addition of adolescent participants
5.1 Inclusion Criteria
Updated Criterion #5 
nomenclature for participant sex 
from “men” and “women” to 
“male” and “female”
More appropriate terms for adolescent 
participants
5.1 Inclusion Criteria
Updated Criterion #8 to include 
assent
Addition of adolescent participants
5.1 Inclusion Criteria
Updated criterion #27 to indicate 
that it is for participants 18 years 
of age or older
To distinguish this criterion from the new 
#28 criterion for adolescents
5.1 Inclusion Criteria
Updated criterion #27 to 
state”type 1 or type 2” diabetes
Clarification of diabetes description
5.1 Inclusion Criteria
Added criterion #28
Addition of adolescent participants
5.2 Exclusion Criteria
Added criterion #29
Addition of adolescent participants
6.1 Study Intervention(s) 
Administered
Added that the site must have 
“age-approriate” resuscitation 
equipment
For the adolescent participants
6.3 Measures to Minimize 
Bias: Randomization
Added stratification by age
Addition of adolescent participants
6.5 Concomitant Therapy
Updated Prior Treatment to add 
recording vaccines for 
adolescents
Addition of adolescent participants
8.7 Genetics
Added clarification that sample 
collection will be collected in 
adults only
This sample is for adults only to reduce 
invasive procedures and blood volume 
collection in adolescent participants
9.1 Statistical Hypotheses
Minor change from “and” to “or”
9.2 Sample Size 
Determination
Added stratification by age
Addition of adolescent participants
9.2 Sample Size 
Determination
Updated justification for 
Treatment arms 7 and 8
Further clarifications for the sample size 
justification
9.4.2 Primary Endpoints
Updated according to objectives 
and endpoints table
Per FDA feedback
9.4.3.2 Additional Secondary 
Endpoints
Updated according to objectives 
and endpoints table
Per FDA feedback
9.5 Interim Analyses
Unblinded assessments of 
efficacy will not be conducted 
until participants complete Day 
29 visit, not Day 22.
correction
10.1.3. Informed Consent 
Process
Updated for adolescent 
population
Addition of adolescent participants
10.2 Appendix 2 Clinical 
Laboratory Tests
Added comments where sample 
collection is for adults only
Addition of adolescent participants

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
127
Section # and Name
Description of Change
Brief Rationale
10.4 Appendix 4 
Contraceptive Guidance and 
Collection of Pregnancy 
Information
Added women not of child-
bearing potential to those 
participating in the study.
Correction and addition of adolescent 
participants
10.4 Appendix 4 
Contraceptive Guidance and 
Collection of Pregnancy 
Information
Added assent to section about 
male participants with partners 
who become pregnant
Addition of adolescent participants
10.8 Abbreviations
Added “assent” and “legal 
representative”
Addition of adolescent participants
11 References
Added references used in new 
text
Additional references used in body of 
protocol.
Throughout the protocol
Minor editorial and formatting 
changes
Minor, therefore not described
Amendment e: 13 October 2020
Overall Rationale for the Amendment:
This amendment addresses changes for treatment arms 7 and 8.  This population is at higher risk 
for more severe disease and hospitalization.  The sample size is increased, and the objectives and 
endpoints are updated to support potential marketing applications.  The changes for treatment arms 
7 and 8 affect sections throughout the protocol. 
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis
Updated text to match the body 
of the protocol for the Objectives 
and Endpoints
See rationale for Section 3.
1.1 Synopsis
Updated information to match 
the body of the protocol for the 
Design Outline  
Updated visit type table and added another 
specifically for treatment arms 7 and 8
1.1 Synopsis
Updated text to match the body 
of the protocol for the Number of 
participants.
Increase in sample size for treatment arms 7 
and 8.  See rationale for Section 9.2.
1.1 Synopsis
Updated Data Monitoring 
Committee (DMC) information 
to match the body of the protocol
See rationale for Section 9.6
1.3 Schedule of Activities 
(SoA)
Removed information pertaining 
to treatment arms 7 and 8 in the 
existing SoA 
Participants enrolling into treatment arms 7 
and 8 will have a different visit and sample 
schedule than treatment arms 1-4 and 6.
1.3 Schedule of Activities 
(SoA)
Created a separate SoA for 
treatment arms 7 and 8
Participants enrolling into treatment arms 7 
and 8 will have a different visit and sample 
schedule.
2.2 Background
Removed information specific to 
a previous amendment
No longer applicable

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
128
Section # and Name
Description of Change
Brief Rationale
3 Objectives and Endpoints
Updated the table for treatment 
arms 7 and 8
Changed the primary endpoints and updated 
the secondary endpoints based on emerging 
data
3 Objectives and Endpoints
Added pharmacokinetic endpoint 
for treatment arms 7 and 8
Will analyze the pharmacokinetics
4.1.1 Design Outline
Removed treatment arms 7 and 8 
information from the visit type 
information table
Treatment arms 7 and 8 will have a 
different visit structure
4.1.1 Design Outline
Created a separate visit type 
information table for treatment 
arms 7 and 8
To match the new SoA specific to treatment 
arms 7 and 8 
4.2 Scientific Rationale for 
Study Design
Added text for treatments 7 and 8 
participant characteristics
Additional rationale for studying the 
population
5.1 Inclusion Criteria
Updated criterion #27 to include 
other chronic respiratory diseases
To broaden the population with high risk 
factors
6.1 Study Intervention(s) 
Administered
Changed monitoring from 2 
hours after completion of the 
infusion to 1 hour
Based on available safety data
6.1.2 Temporary Stopping 
Criteria
Added information for DMC’s 
role
An external DMC will review safety for 
treatment arms 7 and 8
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding
Updated the Unblinding (IWRS) 
table to remove ‘case report 
form’
A case report form is not used to record 
unblinding.
8.1 Efficacy Assessments
Removed specific endpoint dates
Endpoints are not the same across all 
treatment arms.  Removed text to make 
more general.  The information is also 
located in other sections of the protocol.
8.2.2 Vital Signs
Added clarifications for 
treatment arms 1-4 and 6 versus 
7 and 8.  Added a table for 
treatment arms 7 and 8.
Treatment arms 7 and 8 have different 
collection times for Day 1
8.5.1 Bioanalytical
Generalized text for remaining 
sample usage
To optimize the amount of information 
from sample collection, samples may be 
used for exploratory analyses beyond just 
metabolism or bioanalytical experiments
8.9 Immunogenicity
Generalized text for remaining 
sample usage
To optimize the amount of information 
from sample collection, samples may be 
used for exploratory analyses
9.1 Statistical Hypotheses
Added statistical hypothesis for 
treatment arms 7 and 8
New information to match the updated 
primary endpoints
9.2 Sample Size 
Determination
Updated sample size for 
treatment arms 7 and 8
Increase in sample size to provide statistical 
power for updated primary endpoints
9.2 Sample Size 
Determination
Updated section, moved text 
within section and added 
clarifications for treatment arms 
1-4 and 6 versus 7 and 8.  
Updated sample size rationale for 
treatments 7 and 8 sample size
9.4 Statistical Analyses
Updated section with new 
analyses
Aligned analysis plan with updated primary 
endpoints

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
129
Section # and Name
Description of Change
Brief Rationale
9.4.2 Primary Endpoints
Updated treatment arms 7 and 8 
primary endpoints
New endpoints based on emerging data
9.4.3.2 Additional Secondary 
Endpoints
Updated treatment arms 7 and 8 
secondary endpoints
Changes made to the primary endpoints 
dictated a change in secondary endpoints.
Day 15 endpoints were removed per the 
new SoA.
9.4.6 Subgroup Analyses
Added clarifying text
Last bullet only applicable to treatment 
arms 1-4 and 6
9.5 Interim Analyses
Added clarifying text for 
treatment arms 7 and 8 
Interim analyses will be different compared 
to treatment arms 1-4 and 6
9.6 Data Monitoring 
Committee (DMC)
Added clarifying text for 
treatment arms 7 and 8
The sponsor will form an external DMC to 
analyze safety data
10.1.3 Informed Consent 
Process
Added text to re-consenting 
information
Clarification
10.1.5 Committees Structure
Added clarifying text for 
treatment arms 7 and 8
The sponsor will form an external DMC to 
analyze safety data
Appendix 4: Contraceptive 
Guidance and Collection of 
Pregnancy Information
Updated text for collection of 
information on infants after a 
woman gives birth
Per FDA feedback on pediatric 
development of LY3819253
Throughout the protocol
Minor editorial and formatting 
changes
Minor, therefore not described
Amendment d: 18 September 2020
Overall Rationale for the Amendment:
This amendment broadens the definition of patients with COVID-19 who are at a high risk of 
hospitalization.
Section # and Name
Description of Change
Brief Rationale
5.1 Inclusion Criteria
Updated inclusion criterion 27.
Broadened definition of patients with 
COVID-19 at high risk for hospitalization.  
Amendment c: 31 August 2020
Overall Rationale for the Amendment:
The sponsor is activating the optional treatment arm 7 with the combination of LY3819253 and 
LY3832479.  Treatment arm 7 will consist of a population with risk factors for severe COVID-
19 illness.  Treatment arm 8 is added to the study as the corresponding placebo control.  The 
primary and key secondary endpoints for treatment arms 7 and 8 are different than treatments 1-4 
and 6.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
130
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis
Updated text to match the body 
of the protocol for the Number of 
participants.
Updates were made to Section 9.2 to more 
accurately describe the sample sizes for the 
different treatment arms.
1.1 Synopsis
Updated text to match the body 
of the protocol for the
Intervention Groups and 
Duration.
Activation of treatment arm 7 and addition 
of treatment arm 8.
1.1 Synopsis
Updated text to match the body 
of the protocol for the Objectives 
and Endpoints
See rationale for Section 3 below.
1.1 Synopsis
Updated text to match the body 
of the protocol for the Study Day
and Visit Type table
Several study days had different visit types 
for treatment arms 1-4 and 6 versus 
treatment arms 7 and 8
1.1 Synopsis
Added text to clarify the 
corresponding placebo control 
treatment arm
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.
1.2 Schema
Updated treatment arm 7 
information and added treatment 
arm 8.
Activation of treatment arm 7 and addition 
of treatment arm 8.
1.3 Schedule of Activities
Added a sentence to beginning 
paragraph to refer to the study 
day and visit type table in 
Section 4.1.1.
The referenced table provides additional 
clarifications.
1.3 Schedule of Activities
Days 4-6 were separated to 
accommodate procedures 
specific to treatment arms 7 and 
8
Activation of treatment arm 7 and addition 
of treatment arm 8.
1.3 Schedule of Activities
Added footnotes in the Study 
Day row to indicate when 
telephone visits are allowed for 
the different treatment arms
Clarification
1.3 Schedule of Activities
Days 18 and 25 are telephone 
visits for treatment arms 7 and 8 
only
Nasopharyngeal swabs and vital signs not 
collected on these days for treatment arms 7 
and 8
1.3 Schedule of Activities
Day 5 is still a telephone visit for 
treatment arms 1-4 and 6
Clarification 
1.3 Schedule of Activities
Updated visit windows for Days 
5 and 7
To avoid overlap
1.3 Schedule of Activities
Added Day 5 vital sign collection 
only for treatment arms 7 and 8
Collection for participants with risk factors 
for severe disease
1.3 Schedule of Activities
Vital signs not collected on Days 
18 and 25 for treatment arms 7 
and 8
To accommodate a telephone visit.
1.3 Schedule of Activities
Added a nasopharyngeal (NP) 
swab on Day 5 only for treatment 
arms 7 and 8
Collect additional data to inform future 
clinical development

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
131
Section # and Name
Description of Change
Brief Rationale
1.3 Schedule of Activities
NP swabs not collected on Days 
18 and 25 for treatment arms 7 
and 8
Based on emerging blinded data
1.3 Schedule of Activities
Added an exploratory biomarker 
sample on Day 5 for treatment 
arms 7 and 8
To help understand the correlation of 
emerging immune response to other 
parameters
3 Objectives and Endpoints
Created separate table for 
treatment arms 7 and 8
These treatment groups have different 
endpoints based on emerging data 
4.1.1 Design outline
Updated treatment arm 7 
information and added treatment 
arm 8.
Activation of treatment arm 7 and addition 
of treatment arm 8.
4.1.1 Design outline
Updated the Study Day and Visit 
Type table
Several study days had different visit types 
for treatment arms 1-4 and 6 versus 
treatment arms 7 and 8
4.1.1 Design outline
Added text to clarify the 
corresponding placebo control 
treatment arm
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.
4.2 Scientific Rationale for 
Study Design
Added participant characteristics 
for treatment arms 7 and 8
Activation of treatment arm 7 and addition 
of treatment arm 8.
5.1 Inclusion Criteria
Added criterion #27 specifically 
for treatment arms 7 and 8.
To focus on participants with risk factors 
for severe COVID-19 illness.  
5.2 Exclusion Criteria
Criterion #20, changed “a history 
of” to “received”
Clarification
6.1 Study Intervention(s) 
Administered
Removed information that 
described the optional treatment 
arm 7.
Treatment arm is now activated and dose 
levels are described in Section 4.1.1.
6.2 
Preparation/Handling/Storage/
Accountability
In first sentence, replaced 
‘temperature’ with ‘storage’.
In 5th paragraph, replaced text to 
say “The investigator or 
designee…”
Clarifications 
7.1 Discontinuation of Study 
Intervention
Clarified the days and 
assessments in SoA if 
discontinued
Clarification 
7.2 Participant 
Discontinuation/Withdrawal
from the Study
Clarifications at the time of 
discontinuation
Clarification
8.2.5 Procedures of Special 
Interest
Limitations on activities due to 
COVID-19 are measured with a 
patient global assessment for 
daily activities of physical 
function 
Clarification
9.2 Sample Size 
Determination
Updates to more accurately 
describe the sample sizes for the 
different treatment arms.
Added text titles to improve 
readability. 
Addition of treatment arms 7 and 8 and 
clarification for other treatment arms.

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
132
Section # and Name
Description of Change
Brief Rationale
9.4 Statistical Analyses
Added text for treatment arms 7 
and 8.
Clarification
9.4.2 Primary Endpoints
Added endpoint for treatment 
arms 7 and 8.
Based on preliminary blinded data.
9.4.3.2 Additional Secondary 
Endpoints
Added a sub-section for 
treatment arms 7 and 8. 
Secondary endpoints for treatments 7 and 8 
are based on changes to the study 
population to include participants with risk 
factors for severe illness and emerging 
blinded data.
9.4.6. Subgroup Analyses
Added text for treatment arms 7 
and 8.
Clarification
9.5 Interim Analyses
Updated first bullet in first 
paragraph
Not only applicable for LY3819253-only 
treatment arms
9.5 Interim Analyses
Clarification of timing for when 
the Assessment Committee is 
authorized to evaluate unblinded 
interim analyses and safety 
analyses.
Clarification
11 References
Removed irrelevant reference
Correction
Throughout the protocol
Minor editorial and formatting 
changes
Minor, therefore not described

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
133
Amendment b: 31 July 2020
Overall Rationale for Amendment b:
A new treatment is added to this study with the combination of LY3819253 and LY3832479.
Section # and Name
Description of Change
Brief Rationale
Title Page
Change in study title
Updated text for the addition of LY3832479
1.1 Synopsis
Updated text to match the body of 
the protocol.  

Rationale

Objectives and endpoints 
table

Design Outline

Number of participants

Intervention Groups and 
Duration - moved 
treatment group table here 
and updated content.
Updated text for the addition of LY3832479 and 
new combination treatment arm.  
Moved information to more appropriate section.  
1.2 Schema
Updated Schema and removed 
footnote that was no longer correct 
Addition of new combination treatment arm 
1.3 Schedule of 
Activities
Visit 3 visit window changed to +1
To avoid the possibility of too many blood 
draws for the participant
1.3 Schedule of 
Activities
Added assessment on Day 85 for 
participant questionnaire and 
instructions for Day 1
Needed to meet clinical status endpoint
2.0 Introduction
Updated text
For the addition of LY3832479
2.1 Study Rationale
Updated text
For the addition of LY3832479
2.2 Background
Updated text
For the addition of LY3832479
2.3 Benefit/Risk 
Assessment
Updated text
For the addition of LY3832479and availability 
of new data
3 Objectives and 
Endpoints
Objectives were restructured to add 
text for the combination with 
LY3832479
For the addition of LY3832479
3 Objectives and 
Endpoints
Changed SARS-CoV-2 viral load 
area under the concentration-time 
curve to area under the response-
time curve
Correction 
3 Objectives and 
Endpoints
Updated PK objective and 
endpoints
For the addition of LY3832479
4.1.1 Design outline
Updated text, moved text around 
and updated the treatment table
Moved text for better flow of information.  
Updated text and table for the addition of the 
new combination treatment.
4.2 Scientific Rationale 
for Study Design
Updated text
Addition of new combination treatment
4.3 Justification for 
Dose
Text was rearranged and added for 
LY3819253.
New text added for LY3832479. 
Addition of new combination treatment and 
availability of new data for LY3819253

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
134
Section # and Name
Description of Change
Brief Rationale
6.1 Study 
Intervention(s) 
Administered
Text was rearranged for 
LY3819253.
New text added for LY3832479.
For the addition of LY3832479
6.3 Measures to 
Minimize Bias: 
Randomization and 
Blinding
Added new text for additional 
placebo participants
Addition of new combination treatment and 
optional treatment arms
6.6 Dose Modification
New text added for LY3832479
For the addition of LY3832479
8.1 Efficacy 
Assessments
Updated text
Addition of new combination treatment arm
8.1 Efficacy 
Assessments
Added Day 11
Per objective endpoints
8.2.2 Vital Signs
Added clarifying text before table 
and text in table 
Clarifying the collection timepoints because the 
infusion times may vary
8.3.6 Hypersensitivity 
Reactions
Removed LY3819253-specific text
For the addition of LY3832479
8.3.7 Infusion-related 
Reactions
Removed LY3819253-specific text
For the addition of LY3832479
8.4 Treatment of 
Overdose
Updated text
For the addition of LY3832479
8.5 Pharmacokinetics
Updated text
For the addition of LY3832479
8.5.1 Bioanalytical
Updated text
For the addition of LY3832479
8.6 Pharmacodynamics
Updated text
For the addition of LY3832479
8.8 Biomarkers
Updated text
For the addition of LY3832479
8.9 Immunogenicity 
Assessments
Updated text
For the addition of LY3832479
9.2 Sample Size 
Determination
Updated text
Addition of new treatment arms
9.4.3.3 
Pharmacokinetic 
Analyses
Updated text
Details of the analyses added.
9.4.4 Exploratory 
Analyses
Updated text
Clarifications provided
9.4.5 Immunogenicity 
Analyses
Updated text
For the addition of LY3832479
9.5 Interim Analyses
Updated text
For the addition of the new treatment arms
10.1.7. Data Quality 
Assurance, Data 
Capture System
Added text for symptom 
assessment direct entry into EDC
To provide flexibility for data entry into the 
EDC
10.2 Appendix 2 
Clinical Laboratory 
Tests
Removed eGFR calculation
Not needed.
10.2 Appendix 2 
Clinical Laboratory 
Tests
Updated pharmacokinetic and 
immunogenicity samples
For the addition of LY3832479
10.5 Appendix 5 
Genetics
Updated text
For the addition of LY3832479

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
135
Section # and Name
Description of Change
Brief Rationale
10.6 Appendix 6 
Recommended 
Laboratory Testing for 
Hypersensitivity Events
Updated table 
For the addition of LY3832479
Throughout the 
protocol
Minor editorial and formatting 
changes
Minor, therefore not described
Amendment a: 19 June 2020
Overall Rationale for the Amendment:
This amendment addresses the United States Food and Drug Administration (FDA) feedback and 
provides more clarity for clinical sites.
Section # and 
Name
Description of Change
Brief Rationale
1.1 Synopsis
Updated objectives and endpoints to 
match changes in Section 3.
Per FDA feedback
1.3 Schedule of 
Activities
Preexisting conditions and medical 
history – added information for risk 
factors and comorbidities associated 
with severe COVID-19 illness
Clarification of information collected
1.3 Schedule of 
Activities
Vital Signs – added an ‘X’ at 
screening for clarification that it 
would be done for inclusion/exclusion 
criteria, but the data will not be 
collected on the Case Report Form.
Updated Day 1 vital sign collection 
times.
Per FDA feedback
1.3 Schedule of 
Activities
Participant questionnaire – added Day 
1
Questionnaire should be completed for Days 1 –
29.
3 Objectives and 
Endpoints
Added Day 11 to proportion of 
participants that achieve SARS-CoV-2 
clearance endpoint
Analysis will include Day 11.
3 Objectives and 
Endpoints
Added Days 60 and 85 to secondary 
endpoint for clinical status.
Per FDA feedback
3 Objectives and 
Endpoints
Exploratory endpoint for viral 
resistance – updated description 
Clarification that assessment will be from 
baseline to the last evaluable timepoint up to 
Day 29
3 Objectives and 
Endpoints
Clarified for all applicable endpoints 
that AUC is assessed through Day 29
Clarification that AUC calculations are not for a 
specific day, but through Day 29
3 Objectives and 
Endpoints
Added an exploratory endpoint for 
overall improvement using the NIAID 
ordinal scale
For consistency across protocols
5.1 Inclusion 
Criteria
Added website URL for the FDA 
resource page
Per FDA

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
136
Section # and 
Name
Description of Change
Brief Rationale
8.2.2 Vital Signs
Added a table to explain what data 
will be collected on the CRF on Day 1
Clarity for sites
9.4.3.2. Additional 
Secondary 
Endpoints
Updated according to changes in 
Section 3
Consistency across sections.
9.4.6. Subgroup 
Analyses
Updated the subgroup analyses
New information available
10.1.11 Investigator 
Information
Updated description
Per feedback
Section 10.2. 
Clinical Laboratory 
Tests
Removed antibody neutralization
Assay is not available at this time
Throughout the 
protocol
Minor editorial and formatting 
changes
Minor, therefore not described

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
137
11.
References
Aoki FY, Macleod MD, Paggiaro P, Carewicz A, El Sawy A, Wat C, Griffiths M, Waalberg E, 
Ward P on behalf of the IMPACT Study Group. Early administration of oral oseltamivir 
increases the benefits of influenza treatment. J. Antimicrob Chemother. January 2003:123-129.
https://doi.org/10.1093/jac/dkg007.
CDC resource page. Coronavirus Disease 2019 (COVID-19) People Who Are at Increased Risk 
for Severe Illness. Centers for Disease Control and Prevention web site. Available at: 
https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-at-increased-
risk.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-
ncov%2Fneed-extra-precautions%2Fpeople-at-higher-risk.html. Accessed: 28 August 2020.
CDC growth charts.  National Center for Health Statistics, Clinical Growth Charts.  Centers for 
Disease Control and Prevention web site.  Available at: https://
www.cdc.gov/growthcharts/clinical_charts.htm. Accessed: 19 October 2020.
Chen P, Nirula A, Heller B, Gottlieb RL, et.al. SARS-CoV-2 Neutralizing antibody LY-CoV555 
in Outpatients with Covid-19. NEJM. Published 28 October 2020. DOI: 
10.1056/NEJMoa2029849.
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events. National Institute of Allergy and Infectious Diseases. National Institutes of Health. US 
Department of Health and Human Services. Corrected version 2.1. July 2017. Available at: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf. Accessed: 14 April 
2020.
FDA EUA fact sheet.  Fact sheet for health care providers, Emergency Use Authorization (EUA) 
of bamlanivimab. Available at: https://www.fda.gov/media/143603/download. Accessed: 16 
November 2020.
FDA resource page. COVID-19: Developing Drugs and Biological Products for Treatment or 
Prevention Guidance for Industry. Food and Drug Administration web site. May 2020. 
Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/covid-19-developing-drugs-and-biological-products-treatment-or-prevention. 
Accessed: 19 October 2020.
FDA resource page. Development of Anti-Infective Drug products for the Pediatric Population. 
Draft Guidance for Industry. Food and Drug Administration web site. June 2020. Available at: 
https://www.fda.gov/media/139586/download. Accessed: 19 October 2020.
Hoang A, Chorath K, Moreira A, Evans M, et.al. COVID-19 in 7780 pediatric patients: A 
systematic review. EClinicalMedicine 2020. 24:e100433. DOI: 
https://doi.org/10.1016/j.eclinm.2020.100433. 
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrier T, Erichsen S, Schiergens TS, 
Herrler G, Wu NH, Nitsche A, Müller M, Drosten C, Pöhlmann, S. SARS-CoV-2 Cell Entry 
Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. 
Cell. 2020;181:1-10. DOI:10.1016/j.cell.2020.02.052.
Kim L, Whitaker M, O’Halloran A, Kambhampati A, et.al. Hospitalization Rates and 
Characteristics of Children Aged <18 Years Hospitalized with Laboratory-Confirmed COVID-

CONFIDENTIAL
Protocol number J2W-MC-PYAB(m)
138
19 – COVID-NET, 14 States, March 1-July25,2020. US Department of Health and Human 
Services/Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report. 
2020;69(32): 1081-1088.
Liu Y, Sun W, Li J, Chen L, Wang Y, Zhang L, Yu L. Clinical features and progression of acute 
respiratory distress syndrome in coronavirus disease 2019. medRxiv. Posted 27February2020. 
preprint DOI: https://doi.org/10.1101/2020.02.17.20024166. 
Shekerdemian L, Mahmood NR, Wolfe KK, Riggs BJ, et al. International COVID-19 PICU 
Collaborative. Characteristics and outcomes of children with coronavirus disease 2019 
(COVID-19) infection admitted to US and Canadian pediatric intensive care units. JAMA 
Pediatr. 2020. 174(9):1-6. DOI: https://doi.org/10.1001/jamapediatrics.2020.1948.

Leo Document ID = 92915380-49a4-4e5f-9cd9-ad0612eb6ee6
Approver: 
Approval Date & Time: 02-Mar-2021 04:13:23 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 02-Mar-2021 04:15:23 GMT
Signature meaning: Approved
PPD
PPD