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

Protocol Addendum 4: J2X-MC-PYAH 
 
A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and 
Safety of Mono and Combination Therapy with Monoclonal Antibodies in Participants with Mild 
to Moderate COVID-19 Illness (BLAZE-4) 
NCT04634409 
Approval Date: 16-Mar-2021 

CONFIDENTIAL
Protocol J2X-MC-PYAH(4)
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, LY3832479, and LY3853113, unless such persons are bound by a confidentiality agreement with Eli 
Lilly and Company or its subsidiaries.  
Note to Regulatory Authorities:  This document may contain protected personal data and/or commercially confidential 
information exempt from public disclosure.  Eli Lilly and Company requests consultation regarding release/redaction prior to any 
public release.  In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be 
reproduced or otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries.
Protocol Title:
A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and 
Safety of Mono and Combination Therapy with Monoclonal Antibodies in Participants with Mild 
to Moderate COVID-19 Illness (BLAZE-4)
Protocol Number: J2X-MC-PYAH
Addendum Number: 4
Addendum Statement:  This addendum is to be performed in addition to all procedures required 
by protocol J2X-MC-PYAH or any subsequent amendments to that protocol.
Compound: LY3819253, LY3832479, LY3853113
Sponsor Name: Eli Lilly and Company
Legal Registered Address: Indianapolis, Indiana USA 46285
Regulatory Agency Identifier Number(s)
IND:  150440
Approval Date: Protocol Addendum (4) Electronically Signed and Approved by Lilly on date 
provided below.
Approval Date: 16-Mar-2021 GMT

CONFIDENTIAL
Protocol J2X-MC-PYAH(4)
2
Table of Contents
1.
Rationale for Addendum ..................................................................................................3
2.
Protocol Additions.............................................................................................................4
2.1.
Addendum Schema ........................................................................................................4
2.2.
Schedule of Activities ....................................................................................................5
2.3.
Benefit/Risk Assessment..............................................................................................13
2.4.
Objectives and Endpoints.............................................................................................13
2.5.
Study Design................................................................................................................14
2.6.
Justification of Dose.....................................................................................................15
2.7.
Study Population..........................................................................................................16
2.7.1.
Inclusion Criteria .................................................................................................16
2.7.2.
Exclusion Criteria ................................................................................................16
2.8.
Cohort Escalation Criteria...........................................................................................17
2.9.
Temporary Stopping Criteria........................................................................................18
2.10. Study Interventions(s) Administered ............................................................................18
2.10.1
Injection volumes and formulation concentrations................................................19
2.11. Injection Site Reactions................................................................................................19
2.12. Study Assessments and Procedures ..............................................................................20
2.12.1
Vital Signs ...........................................................................................................20
2.13. Statistics.......................................................................................................................21
3.
References .......................................................................................................................22

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Protocol J2X-MC-PYAH(4)
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1.
Rationale for Addendum
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.
Recently, emergence of mutations to the spike protein of SARS-CoV-2 threaten to render current 
treatments and vaccines not as effective.  
LY3853113 is a novel, highly potent IgG1 neutralizing mAb targeting the spike protein of 
SARS-CoV-2 that was created in partnership with AbCellera.  It binds an epitope within the 
receptor binding domain that is distinct from those bound by LY3819253 and LY3832479.  
LY3853113 can neutralize the Wuhan reference strain as well as individual residues present in 
recent variants of concern (i.e. L452R, D614G, N501Y, N439K, K417N, and E484K).  
Critically, pseudovirus assays demonstrate that LY3853113 can neutralize variants with the 
specific combination of receptor binding domain residues of the B.1.1.351 (South African) and 
B.1.1.28 (P.1/Brazil origin) strains.  These variants were recently reported in the United States 
(CDC 2021), thus it is imperative that new treatments for these emerging variants are developed 
and deployed quickly.
The purpose of this Phase 1, double-blind, randomized, placebo-controlled, ascending dose
substudy is to characterize the safety and tolerability of LY3853113 alone by intravenous 
infusion or subcutaneous injection, and in combination with LY3819253 and LY3832479 by 
intravenous infusion.

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Protocol J2X-MC-PYAH(4)
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2.
Protocol Additions
2.1.
Addendum Schema
Participants enrolled into this addendum will follow the schema below in place of the schema in 
the main protocol.
Note: Safety data from participants administered LY3819253 and LY3832479, expected prior to the start of the 
addendum, are informing on a maximum rate not exceeding 350 mg/min. The rate from Doses 2b, 2c, and Dose 3 
will be defined in the pharmacy preparation instructions.
The first 2 participants in each cohort will be sentinel (LY3853113:placebo). Subsequent participants will be 
randomized to the remaining treatment allocations, 5 to LY3853113 or LY3853113 in combination with 
LY3819253 and LY3832479, and 1 to placebo.  
Additional participants may be enrolled in case of discontinuation. In case of discontinuation, a newly enrolled 
participant will have the same treatment assignment as the corresponding discontinued participant.
Abbreviations: IV = intravenous; n = number of participants; SC = subcutaneous.

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Protocol J2X-MC-PYAH(4)
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2.2.
Schedule of Activities
Participants enrolled into this addendum will follow the Schedule of Activities below in place of the main protocol schedule(s).
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.
J2X-MC-PYAH
Addendum 4
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-
treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Procedures
Informed Consent
X
Inclusion and 
exclusion criteria 
review
X
Demographics
X
Including age, gender, race, ethnicity
Preexisting 
conditions and 
medical history
X
Obtained from interview or available 
information.
Includes:  vaccination history (including
SARS-CoV-2 vaccinations), risk factors and 
comorbidities associated with severe COVID-
19 illness, such as living in a nursing home or 
long-term care facility. 
Prespecified 
medical history: 
COVID-19
X
Includes COVID-19 diagnosis date and onset 
of COVID-19 symptoms.
Height
X
Weight
X

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

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Protocol J2X-MC-PYAH(4)
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J2X-MC-PYAH
Addendum 4
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-
treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Vital signs and 
Oxygen Support
X
X
X
X
X
X
X
X
X
X
X
Documentation of hospital-based exam is 
acceptable.
Includes: body temperature, pulse rate, BP, 
respiratory rate, SpO2, and supplemental 
oxygen flow rate, FiO2 if known, method 
of delivery, if applicable, and oxygen 
support procedures. 
Record SpO2 while participant is at rest.
Screening visit only: SpO2 while 
breathing room air. Data not collected on 
CRF.
Day 1 timing:

immediately before administration

immediately following completion of 
infusion if infusion is <15 minutes

every 15 minutes during the infusion, 
as possible and applicable

every 30 minutes for 1 hour after the 
end of infusion
See Section 2.12.1 for data collected on 
CRF.
All other study days: once daily. 

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

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

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Protocol J2X-MC-PYAH(4)
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J2X-MC-PYAH
Addendum 4
Screen
Double-blind treatment and assessments
ED
Follow-up if 
hospital 
inpatient on 
Day 29
Post-
treatment 
follow-up
Comments
Study Day
1
2*
3
4*
5
6*
7
11
22*
29
ED
Every 7 days 
until discharge 
or Day 60
60
85
Screening and Day 1 procedures may occur on 
the same day.
* = telephone visit(s) for all treatment arms
Visit window 
(number of days)
--
--
+1
--
+1
--
+1
-2/+3
±3
±3
±2
±2
±4
±4
Visits may not be combined.
Urine or serum 
pregnancy 
X
X
X
Only for WOCBP as defined in the main 
protocol, Section 10.4 Appendix 4.
Local laboratory
Pharmacokinetic 
(PK) sample
X
X
X
X
X
X
X
X
X
Day 1: 
No pre-dose sample needed.
IV - one post-dose sample within 30 minutes 
after the end of IV infusion (may include the 
flush). 
SC - one post-dose sample taken as close to the 
end of the visit as possible.
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 treatment administration. 
All other scheduled and unscheduled 
immunogenicity samples should be collected 
with a time-matched PK sample.
No samples needed if participant is hospitalized
Lilly-designated central laboratory
Pharmacodynamic 
(PD) NP swab 
X
X
X
X
X
X
X
Swab is taken from both nostrils. 
Day 1: swab before treatment administration.
No samples needed if participant is hospitalized
Lilly-designated central laboratory

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

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Protocol J2X-MC-PYAH(4)
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Abbreviations: ADA = anti-drug antibody; AEs = adverse events; BP = blood pressure; CRF = case report form; ED = early discontinuation visit; FiO2 = 
fraction of inspired oxygen in the air; ICU = intensive care unit; NP = nasopharyngeal; NSAIDS = non-steroidal anti-inflammatory drugs; PK = 
pharmacokinetics; SAEs = serious adverse events; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SpO2 = saturation of peripheral oxygen; 
SC = subcutaneous; WOCBP = women of child-bearing potential.

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Protocol J2X-MC-PYAH(4)
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2.3.
Benefit/Risk Assessment
The administration of therapeutic mAbs has the potential for injection site reactions and
hypersensitivity, including anaphylaxis and infusion related reactions.  Increased rates of 
administration may be associated with an increased risk of such 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 or the infusion stopped, if 
indicated.  Additional information regarding infusion reaction management options is in Section 
6.1.1 of the main protocol.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of LY3819253, LY3832479, and LY3853113 may be found in each 
respective IB.
2.4.
Objectives and Endpoints
Objectives
Endpoints
Primary
Characterize the safety and tolerability of 
LY3853113 alone (after IV infusion or SC
injection) and in combination with 
LY3819253 and LY3832479 (after IV 
infusion)

Safety assessments such as AEs and SAEs
Secondary
Characterize the pharmacokinetics of 
LY3853113 after intravenous infusion or SC
injection

LY3853113 mean concentration on Day 29
Characterize the pharmacodynamics of 
LY3853113 alone (after IV infusion or SC
injection) and in combination with 
LY3819253 and LY3832479 (after IV 
infusion)

Change from baseline in SARS-CoV-2 viral 
load (Days 3, 5, 7, and 11)

Proportion of participants with SARS-CoV-2 
viral load greater than 5.27 on Day 7

SARS-CoV-2 viral load AUC assessed 
through Day 11

Time to SARS-CoV-2 clearance 
Tertiary/Exploratory
Characterize the participant’s clinical status

Duration (days) of hospitalization

Proportion (percentage) of participants 
admitted to ICU

Proportion (percentage) of participants 
requiring mechanical ventilation
Characterize the pharmacodynamics of 
LY3853113 alone (after IV infusion or SC
injection) and in combination with 

Proportion of participants that achieve SARS-
CoV-2 clearance (Days 3, 5, 7, 11, 29) 

75th percentile of SARS-CoV-2 viral load at 
Day 7

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Protocol J2X-MC-PYAH(4)
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LY3819253 and LY3832479 (after IV 
infusion)
Characterize emergence of viral resistance to 
LY3853113

Comparison from baseline to the last 
evaluable time point up to Day 29
Abbreviations: AE = adverse event; ICU = intensive care unit;  IV = intravenous; SAE = serious adverse event; 
SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SC = subcutaneous.
2.5.
Study Design
This is a Phase 1, double-blind, randomized, placebo-controlled, ascending dose substudy that 
may progress to a Phase 2, double-blind, randomized, placebo-controlled phase. 
Screening
Interested participants will sign the appropriate informed consent document(s) prior to 
completion of any procedures. Screening may be performed up to 48 hours prior to dosing.  
Screening and Day 1 may occur on the same day.
Treatment and Assessment Period
This is the general sequence of events during the treatment and assessment period:

Participants are randomized to intervention group

Baseline procedures and sample collection are completed

Participants receive study intervention, and

All safety monitoring and post-administration sample and data collection are performed. 
Remote follow-up visits may be conducted to remove the burden of return visits to the clinic and 
clinical trial staff reflecting limited medical resources in the COVID-19 pandemic.
This addendum will comprise up to 5 dose cohorts to receive study intervention by IV infusion
and 2 dose cohorts to receive study intervention by SC injection.
Cohorts will comprise at least 8 participants each: 

6 randomized to LY3853113 alone or in combination with LY3819253 and LY3832479, 
and 

2 randomized to placebo.  
Sentinel dosing will be used in each dose cohort that represents a dose increase or infusion rate 
change (increase in mg/minute) from the preceding cohort.  The first 2 participants in each 
cohort will be randomized 1:1 to LY3853113 and placebo. 
Safety and tolerability will be reviewed for sentinel participants up to 24 hours after dosing.  The 
investigator and the Lilly sponsor team are responsible for determining if safety and tolerability 
is acceptable to continue with dosing subsequent participants. 
Subsequent participants will be randomized to the remaining treatment allocations, 5 to 
LY3853113 and 1 to placebo.  

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Protocol J2X-MC-PYAH(4)
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The decision to dose the next cohort will be made when all participants from the previous cohort 
have been dosed and safety data is assessed for at least 48 hours after the IV infusion or SC
injection by the investigator(s) and Lilly sponsor team.
2.6.
Justification of Dose
Intravenous dosing for LY3853113
The 175mg dose is the intended target dose for the Phase 2 portion of the study. 
The target therapeutic dose of 175 mg was selected using PK/PD modeling in a manner similar 
to the approaches that were used for LY3819253 and LY3832479. The PK/PD modeling 
approach includes in vitro potency data (i.e. IC90), predicted human PK, and the expected 
response in terms of maximal reduction in viral load. The 175 mg dose is expected to result in at 
least 90% of the population achieving drug concentrations above IC90 through at least 28 days 
after drug administration, and results in maximum reduction in viral load based on a PK-viral 
dynamic model. 
This Phase 1 addendum will evaluate 3 IV dose levels. 
The first dose level is approximately 3 times lower than the target dose level (70 mg). The third 
dose level is approximately 10 times higher than the target dose (1750 mg) to further evaluate the 
safety of LY3853113. Based on current knowledge of similar neutralizing mAbs (LY3819253
and LY3832479) that have been studied at doses of up to 7000 mg, the third dose level is 
anticipated to have an acceptable safety profile. Based on preliminary non-clinical PK results, 
the PK profile of LY3853113 is similar to that of LY3819253.
Further details about dose selection and coverage of variants of interest may be found in the IB. 
These doses may be amended if necessary, based on emerging data.
Intravenous dosing for LY3819253 and LY3832479
The IV doses for LY3819253 and LY3832479 will be 700 mg and 1400 mg, respectively. These 
doses are currently the authorized doses in the EUA.
Subcutaneous dosing for LY3853113
This Phase 1 addendum will evaluate 2 subcutaneous dose levels. The first dose level is 280 mg 
via 2 × 2 mL injections.  This dose is the intended therapeutic dose that would result in viral load 
reduction similar to IV administration as described above.  The upper dose level is 560 mg via 4 
× 2 mL injections, and is driven by the feasibility of multiple injections.

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Protocol J2X-MC-PYAH(4)
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2.7.
Study Population
2.7.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Are ≥18 and <65 years of age at the time of randomization
Disease Characteristics
2. Are currently not hospitalized
3. Have one or more mild or moderate COVID-19 symptoms (CDC 2020; FDA 2021)
i. Fever
ii. Cough
iii. Sore throat
iv. Malaise
v. Headache
vi. Muscle pain 
vii. Gastrointestinal symptoms
viii. Shortness of breath with exertion
ix. Nasal congestion or runny nose
x. New loss of smell
xi. Chills
4. Must have sample collection for first positive SARS-CoV-2 viral infection determination 
≤3 days prior to the administration of study drug
Sex
5. Men or non-pregnant women
Reproductive and Contraceptive agreements and requirements are provided in the main 
protocol, Section 10.4, Appendix 4. Contraceptive use by men or women should be 
consistent with local regulations for those participating in clinical studies. 
Study Procedures
6. Understand and agree to comply with planned study procedures
7. Agree to the collection of nasopharyngeal swabs and venous blood
Informed Consent
8. The participant or legally authorized representative gives signed informed consent as 
described in the main protocol, Section 10.1.3, which includes compliance with the 
requirements and restrictions listed in the informed consent form (ICF) and in this 
protocol.
2.7.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:

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Protocol J2X-MC-PYAH(4)
17
Medical Conditions
9. Have a BMI ≥35
10. Have SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 <300, respiratory rate ≥30 per 
minute, heart rate ≥125 per minute (FDA resource page, WWW) 
11. Require mechanical ventilation or anticipated impending need for mechanical ventilation 
12. Have known allergies to any of the components used in the formulation of the 
interventions
13. Have hemodynamic instability requiring use of pressors within 24 hours of 
randomization 
14. Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides 
COVID-19) that in the opinion of the investigator could constitute a risk when taking 
intervention
15. Have any co-morbidity requiring surgery within <7 days, or that is considered life-
threatening within 29 days
16. Have any serious concomitant systemic disease, condition or disorder that, in the opinion 
of the investigator, should preclude participation in this study
Other Exclusions
17. Have a history of a positive SARS-CoV-2 serology test
18. Have a history of a positive SARS-CoV-2 test prior to the one serving as eligibility for 
this study
19. Have received an investigational intervention for SARS-CoV-2 prophylaxis within 30 
days before dosing
20. Have received treatment with a SARS-CoV-2 specific monoclonal antibody
21. Have received convalescent COVID-19 plasma treatment 
22. Have participated in a previous SARS-CoV-2 vaccine study or have received a SARS-
CoV-2 vaccine
23. Have participated, within the last 30 days, in a clinical study involving an investigational 
intervention. If the previous investigational intervention has a long half-life, 5 half-lives 
or 30 days, whichever is longer, should have passed.
24. Are concurrently enrolled in any other type of medical research judged not to be 
scientifically or medically compatible with this study
25. Are pregnant or breast feeding
26. Are investigator site personnel directly affiliated with this study.
2.8.
Cohort Escalation Criteria
Data will be evaluated on an ongoing basis until the highest planned dose has been administered.
The decision to dose the next cohort in the addendum will be made when all participants from 
the previous cohort have been dosed and safety data, including safety laboratory data, AEs and 
vital signs, are assessed for at least 48 hours after study drug administration by the investigator(s) 
and Lilly sponsor team.

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Available PK and PD data may also be used to guide dose adjustment. 
If temporary stopping criteria are met (Section 2.9), dosing will be temporarily stopped and no 
further participants will be dosed until a full safety review of the study has taken place.  The
assessment committee (see Section 6.1.2 of main protocol) will be engaged for the full safety 
review with the sponsor and investigator.
2.9.
Temporary Stopping Criteria
Dosing will be temporarily halted, and no further participants will be dosed until a safety review 
of the study has taken place if:  

Two or more participants at a given dose level develop severe or severe/potentially life-
threatening acute AEs related to the administration of study drug (see table in main 
protocol, Section 6.1.1.2), during or within 2 hours of completion of the administration, 
that do not resolve with a reduced infusion rate and/or supportive care. 
OR

Two or more participants at a given dose level develop severe AEs within 4 days of 
dosing which, in the opinion of the investigator, cannot be attributed to the primary 
disease, concomitant medications or extraneous circumstances with a reasonable 
possibility.
Topic
Location in Main Protocol
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
Changes to the planned dosing schedule must be appropriately documented and communicated 
with the study personnel and the IRB/IEC before dosing continues.
2.10.
Study Interventions(s) Administered
Intervention Name
Placebo
LY3853113
LY3853113
LY3853113 + 
LY3819253 + 
LY3832479
Dose Formulation
0.9% sodium 
chloride solution
Solution
Solution
Solution
Dosage Level(s) (mg)
Not applicable
70, 175, 1750
280, 560
175 + 700 + 1400
Route of 
Administration
IV infusion, SC 
injection
IV infusion
SC injection
IV infusion
Use
Placebo
Experimental
Experimental
Experimental
IMP and NIMP
IMP
IMP
IMP
IMP
Sourcing
Commercially 
available 0.9% 
sodium chloride 
solution
From Lilly
From Lilly
From Lilly

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Packaging and 
Labeling
Commercially 
available 0.9% 
sodium chloride 
solution
Study Intervention 
will be provided in 
glass vials and will 
be labeled 
appropriately.
Study Intervention 
will be provided in 
glass vials and will 
be labeled 
appropriately.
Study Intervention 
will be provided in 
glass vials and will 
be labeled 
appropriately.
Note: Depending on the results of a given internal data review, doses may be adjusted.
Infusion and subcutaneous dose preparation information may be found in the pharmacy 
preparation instructions.
Arm A IV administration
Single Administration
Participants should be monitored for at least 1 hour after completion of infusion. The infusion 
rate may be reduced as deemed necessary if an infusion reaction is observed (main protocol, 
Section 6.1.1.2).
Multiple Administrations
In the event of multiple administrations, participants should receive LY3819253 and LY3832479 
or placebo first and should be monitored for at least 30 minutes after completion of the first 
administration and before administration of LY3853113 or placebo. Participants should be 
monitored for at least 1 hour after second administration. Further details will be included in the 
pharmacy preparation incstructions. The infusion rate may be reduced as deemed necessary if an 
infusion reaction is observed (main protocol, Section 6.1.1.2).
Arm B SC administration
Subcutaneous injections will be administered in the abdomen.  The dose will be administered as 
up to 4 injections of 2-mL each.  Different quadrants of the abdomen should be used for each 
injection.
The site must have resuscitation equipment, emergency drugs and appropriately training staff 
available  for at least 1 hour after the completion of the infusion or SC injection.
2.10.1
Injection volumes and formulation concentrations
Injection volumes are as follows:
Cohort (LY3853113 dose)
Number of injections and volumes
SC Dose Level 1 (280 mg)
2 × 2 mL
SC Dose Level 2 (560 mg)
4 × 2 mL
The LY3853113 formulation concentration will be 70 mg/mL in all cases.
2.11.
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 

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Protocol J2X-MC-PYAH(4)
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used to capture additional information about this reaction, for example, injection-site pain, 
degree and area of erythema, induration, pruritis and edema.
2.12.
Study Assessments and Procedures
Study procedures and their timing are summarized in the SoA (Section 2.2).
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. 
2.12.1
Vital Signs
Vital signs will be measured as specified in the SoA (Section 2.2) 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.
These tables outline Day 1 vital signs data collection on the CRF in relation to the infusion(s). 
Infusion times may vary depending on the participant. 
Single Administration
Timepoint (minutes)
Collect data on CRF
Immediately before infusion
Yes
If infusion is <15 minutes, immediately following completion of infusion
Yes
During Infusions > 15 minutes, as possible (if applicable)
--
   15
No
   30
Yes
   45
No
   60 
Yes
After infusion – every 30 minutes for 1 hour after the end of the infusion
--
   end of infusion +30 minutes
Yes
   end of infusion +60 minutes
No

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Multiple Administrations
Timepoint (minutes)
Collect data on CRF
Immediately before infusion
Yes
If infusion is <15 minutes, immediately following completion of first infusion
Yes
During infusion > 15 minutes, as possible (if applicable)
--
   15
No
   30
Yes
   45
No
   60 
Yes
After last infusion – every 30 minutes for 1 hour after the end of the last infusion
--
   end of infusion +30 minutes
Yes
   end of infusion +60 minutes
No
2.13.
Statistics
Statistical analyses of this substudy will be the responsibility of the Sponsor or its designee.
Sample Size
The sample size for this addendum is customary for first-in-human studies to evaluate safety. 
Populations for Analyses
This table defines the populations for analysis.
Population
Description
Entered
All participants who sign the informed consent form for the addendum.
Efficacy -
Addendum
All participants who were allocated and received study intervention in the addendum and 
provided at least one post-baseline measure for the relevant endpoint. Participants will be 
analyzed according to the intervention to which they were randomized. (Intention to treat).
Safety - Addendum
All participants allocated to treatment in the addendum and who received study 
intervention. Participants will be analyzed according to the intervention they received.
Pharmacokinetic -
Addendum
All participants who were allocated and received addendum intervention in the study and 
have evaluable PK sample. Participants will be analyzed according to the intervention 
they received.
Statistical Analyses
All analyses in this addendum will be summarized by cohort and administration method, no 
inferential statistics will be performed.  Data from participants in this addendum will be 
summarized separately from participants in the main protocol.  Refer to the PYAH Statistical 
Analysis Plan for details on handling dropouts or missing data.  
Interim Analyses
An interim analysis of safety data may be conducted at any time for participants who have 
reached Day 3.

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3.
References
[CDC] Centers for Disease Control and Prevention. COVID-19 in children and teens. 
Information for parents and caregivers about COVID-19 in children and teens. Website page 
last updated December 18, 2020. Accessed March 16, 2021. Available at: 
https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/children/symptoms.html
[CDC] Centers for Disease Control and Prevention. US COVID-19 cases caused by variants. 
Updated February 21, 2021. Accessed February 21, 2021. 
https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html
FDA resource page. COVID-19: Developing Drugs and Biological Products for Treatment or 
Prevention Guidance for Industry. Food and Drug Administration web site. February 2021. 
Available at: https:// www.fda.gov/regulatory-information/search-fda-guidance-
documents/covid-19-developing-drugs-and-biological-products-treatment-or-prevention. 
Accessed 12 March 2021.

Leo Document ID = ef6e577b-7ace-47ec-b1f2-2e400a08c625
Approval Date & Time: 16-Mar-2021 21:05:11 GMT
Signature meaning: Approved
Approval Date & Time: 16-Mar-2021 21:14:37 GMT
Signature meaning: Approved
PPD
PPD