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

 
  
 J2W-MC-PYAB Addendum (2.2)  
 
 
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: 12-Mar-2021 
 
 

CONFIDENTIAL
J2W-MC-PYAB (2.2)
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Title Page
Confidential Information
The information contained in this document is confidential and is intended for the use of clinical investigators.  It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of LY3819253 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
Addendum Number: 2.2
Addendum Statement:  This addendum is to be performed in addition to all procedures required 
by protocol J2W-MC-PYAB or any subsequent amendments to that protocol. Participants 
enrolled in this addendum will follow the specified sections in this addendum in place of the 
corresponding sections in the main PYAB protocol.
Compound(s): LY3819253, LY3832479
Sponsor Name: Eli Lilly and Company
Legal Registered Address: Indianapolis, Indiana USA 46285
Regulatory Agency Identifier Number(s)
IND:  150440
Approval Date: Protocol Addendum (2.2) Electronically Signed and Approved by Lilly on date 
provided below.
Approval Date: 12-Mar-2021 GMT

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J2W-MC-PYAB (2.2)
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Protocol Addendum Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Revision 2.1
9-February-2021
Original Protocol Addendum
19-January-2021
Revision 2.2
Overall Rationale for the Changes:
The purpose of this addendum revision is to incorporate regulatory agency feedback and provide 
clarifications for operational efficiency.
Section # and Name
Description of Change
Brief Rationale
Title Page; 2. Protocol 
Additions
Added statement that sections in the 
addendum are to be used in place of 
corresponding sections in parent protocol.
Clarification
Throughout
Changed addendum arm from 15 to 22
Operational/administrative
2.0 Protocol Additions
Added statement that participants enrolled 
in this addendum will follow the specified 
sections in this addendum in place of the 
main PYAB protocol
clarification
2.1 Schema
Updated schema to include all treatment 
arms included in the parent protocol and 
addenda.
Updated notes to figure.
Updated to reflect current study 
design
2.2. Schedule of Activities
2.2.1 Treatment arm 22
Hematology:
Removed instructions for hospitalized 
patients
Instructions not needed for 
pediatric participants
2.3 Objectives and Endpoints
Removed windows from secondary 
endpoints
Not needed for these analyses
2.3 Objectives and Endpoints
Exploratory:
Added emergence of viral resistance and
Added safety endpoint of MIS-C
Added new objectives to 
addendum
2.4.1 Design Outline
Removed reference to arms outside of 
addendum
Arms not applicable to addendum
2.6 Justification for Dose
Updated doses of LY3819253 and 
LY3832479
Regulatory feedback
2.7. Study Population
Added information pertaining to the 
eligibility criteria
To match what is stated in the main 
protocol
2.7.1 Inclusion Criteria and
2.7.2 Exclusion Criteria
Included full list of inclusion and 
exclusion criteria from main PYAB
protocol and identified if criteria from the 
main protocol are not applicable to this 
addendum.
Operational/administrative
2.7.1 Inclusion Criteria
Criterion 3 – removed criterion
Created new criterion 35 with

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J2W-MC-PYAB (2.2)
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Section # and Name
Description of Change
Brief Rationale
symptoms for pediatric participants
2.7.1 Inclusion Criteria
Criterion 5 – updated to indicate that these 
are agreements and “requirements” in 
Section 10.4, Appendix 4.
Clarification
2.7.1 Inclusion Criteria
Criterion 30 – Added clarification that this 
is a list of risk factors
Added “are pregnant” to list
Added examples of neurodevelopmental 
disorders 
Clarifications
2.7.1 Inclusion Crite
Criterion 35 added
Updated symptoms for pediatric 
participants
2.7.2 Exclusion Criteria
Criteria 9 and 10 - Added ‘due to COVID-
19’ 
Clarification
2.7.2 Exclusion Criteria
Criterion 24- specified this applies to 
mothers who are breast feeding
Clarification that this does not 
include infants who are 
breastfeeding
2.9.2 Sample Size 
Determination
Updated sample size and minimum 
enrollment numbers for particular age 
groups
Updated to reflect study addendum 
strategy and regulatory feedback
2.9.4.1 General Considerations
Updated analyses age groups to match 
changes for minimum sample size 
enrollment
For consistency
2.9.5 Interim Analyses
Broadened language of when interim 
analysis may occur
Operational/administrative
2.13 Section 10.10. Appendix 
10: Blood Collection 
Restrictions and Guidance
Added pediatric guidance and restrictions 
for blood collection
Added to provide clarification and 
guidance for sites
3 References
Added 2 new references
editorial
Throughout
Minor editorial and formatting changes
Minor, therefore not detailed

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J2W-MC-PYAB (2.2)
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Table of Contents
Protocol Addendum Summary of Changes Table......................................................................2
1.
Rationale for Addendum ..................................................................................................5
2.
Protocol Additions.............................................................................................................6
2.1.
Section 1.2. Schema .......................................................................................................6
2.2.
Section 1.3. Schedule of Activities .................................................................................7
2.2.1. Section 1.3.3. Treatment arm 22.....................................................................................7
2.3.
Section 3.0. Objective and Endpoints ...........................................................................16
2.4.
Section 4.0. Study Design ............................................................................................17
2.4.1. Section 4.1.1. Design Outline .......................................................................................17
2.5.
Section 4.2. Scientific Rationale for Study Design........................................................17
2.6.
Section 4.3. Justification for Dose ................................................................................18
2.7.
Section 5.0. Study Population.......................................................................................18
2.7.1. Section 5.1. Inclusion Criteria ......................................................................................18
2.7.2. Section 5.2. Exclusion Criteria .....................................................................................20
2.8.
Section 8.1. Efficacy Assessments................................................................................21
2.8.1. Section 8.1.2. Symptom Assessment for Pediatric Participants .....................................21
2.9.
Section 9.0. Statistical Considerations ..........................................................................22
2.9.1. Section 9.1. Statistical Hypotheses ...............................................................................22
2.9.2. Section 9.2. Sample Size Determination.......................................................................22
2.9.3. Section 9.3. Populations for Analyses...........................................................................22
2.9.4. Section 9.4. Statistical Analyses ...................................................................................23
2.9.4.1.
Section 9.4.1. General Considerations ..................................................................23
2.9.4.2.
Section 9.4.2. Primary Endpoint...........................................................................23
2.9.4.3.
Section 9.4.3. Secondary Endpoints......................................................................23
2.9.4.4.
Section 9.4.3.4. Pharmacokinetic and Pharmacodynamic 
Analyses ......................................................................................................................23
2.9.5. Section 9.5. Interim Analyses.......................................................................................24
2.10. Section 10.1.11. Investigator Information.....................................................................24
2.11. Section 10.6. Appendix 6: Recommended Laboratory Testing for 
Hypersensitivity Events................................................................................................25
2.12. Section 10.7. Appendix 7: Liver Safety Suggested Actions and 
Follow-up Assessments................................................................................................26
2.13. Section 10.10. Appendix 10: Blood Collection Restrictions and 
Guidance for Pediatric Participants...............................................................................29
3.
References .......................................................................................................................31
4.
Appendix 1:  Protocol Addendum Revision History ..........................................................33

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J2W-MC-PYAB (2.2)
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1.
Rationale for Addendum
The rationale for this addendum is to allow pediatric participants ≤17 years old in the study, in a
new open-label treatment arm 22.

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J2W-MC-PYAB (2.2)
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2.
Protocol Additions
Participants enrolled in this addendum will follow the specified sections in this addendum in 
place of the corresponding sections in the main PYAB protocol.
2.1.
Section 1.2. Schema
Participants enrolled into this addendum will enter treatment arm 22.
Abbreviations:  LY = Lilly study intervention; PYAA = J2W-MC-PYAA; PYAB = 
J2W-MC-PYAB; TBD = to be determined.
Note:  Treatment arm 22 dose levels are weight dependent.
Addendum 3 contains information for treatment arms 20 and 21.
The main PYAB protocol contains information for treatment arms 1-19.
Figure 1.
Study J2W-MC-PYAB schema 

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J2W-MC-PYAB (2.2)
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2.2.
Section 1.3. Schedule of Activities
2.2.1. Section 1.3.3. Treatment arm 22
This SoA is for participants in treatment arm 22.  Please see Section 2.13, Appendix 10 for pediatric blood collection restrictions and 
guidance. 

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J2W-MC-PYAB (2.2)
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Schedule of Activities for Treatment Arm 22 – Pediatric Participants
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 pediatric 
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. 
Prespecified 
medical history
for COVID-19
X
Includes COVID-19 diagnosis date and 
onset of COVID-19 symptoms.
Prior treatments 
of special interest 
within the last 30 
days
X
NSAIDs, antivirals, antibiotics, anti-
malarials, corticosteroids, 
immunomodulators or any
investigational treatments.

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J2W-MC-PYAB (2.2)
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Schedule of Activities for Treatment Arm 22 – Pediatric Participants
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 non-COVID 
vaccine 
treatments within 
the last 90 days
X
Substance use 
(Tobacco)
X
Includes use of e-cigarettes, such as 
vaping
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events 
(AEs)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Any events that occur after signing the 
informed consent are considered AEs 
as defined in Section 10.3.
Additional details regarding reporting 
frequency and method of detecting 
AEs and SAEs can be found in Section 
8.3.
Physical Evaluation or Clinical Assessments
Physical 
examination
X
Symptom-directed 
physical exam
X
X
X
As indicated based on participant 
status and standard of care.  May be 
performed by qualified personnel per 
local regulations.

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J2W-MC-PYAB (2.2)
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Schedule of Activities for Treatment Arm 22 – Pediatric Participants
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
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.
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.  
Only record temperature, 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. 

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J2W-MC-PYAB (2.2)
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Schedule of Activities for Treatment Arm 22 – Pediatric Participants
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
Height
X
For participants ≥2 years of age
Length
X
Only for participants <2 years of age
Weight
X
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, 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)

Additional organ support (e.g. 
ECMO, pressors, renal
replacement)

Supplemental oxygen and any 
means of ventilatory support, and

Vital signs.

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J2W-MC-PYAB (2.2)
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Schedule of Activities for Treatment Arm 22 – Pediatric Participants
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
Lilly-designated central laboratory
Local laboratory acceptable for 
participants <4.4 kg.
Clinical 
Chemistry
X
X
X
X
X
Day 1: before treatment administration
All other days: sample may occur at 
any time during the day.
If participant is hospitalized and if 
sample is available, collect sample, 
otherwise sample is not required 
during hospitalization.  
Lilly-designated central laboratory
Local laboratory acceptable for 
participants <4.4 kg.
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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J2W-MC-PYAB (2.2)
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Schedule of Activities for Treatment Arm 22 – Pediatric Participants
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
Urine or serum 
pregnancy 
X
X
X
Pregnancy tests prior to the first dose 
of investigational product for females 
if

aged ≥10 years 

<10 years at investigator’s 
discretion 

menarche is reached or

there is reason to believe that the 
patient is sexually active.
Local laboratory
Pharmacokinetic 
(PK) sample
X
X
X
X
X
X
Day 1: immediately after end of 
infusion.
All other scheduled samples may occur 
at any time during the day.
Pharmacokinetic samples for 
participants <12 kg may be collected 
using alternative techniques.
If participant is hospitalized and if 
sample is available, collect sample.
Lilly-designated central laboratory

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J2W-MC-PYAB (2.2)
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Schedule of Activities for Treatment Arm 22 – Pediatric Participants
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 samples needed if participant is 
hospitalized or <12 kg.
Lilly-designated central laboratory
Pharmacodynamic 
(PD) swab 
X
X
X
X
X
X
X
Swab is taken from both nostrils. 
Day 1: swab before treatment 
administration.
Methods include nasopharyngeal 
(preferred) or mid-turbinate.
The same method of sample collection 
must be used per participant for the 
duration of the study.  Switching 
methods is not allowed. 
Lilly-designated central laboratory
Treatment Assignment and Dosing
Treatment 
assignment
X

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Schedule of Activities for Treatment Arm 22 – Pediatric Participants
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
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 Symptom Assessment
COVID-19 
Symptoms 
Daily on Days 1-11 for outpatients only
X
X
X
X
X
Day 1: assess prior to dosing
The presence of absence of symptoms 
are collected from the participants or 
their parents/legal guardian.
Abbreviations:  ACVPU = alert, consciousness, verbal, pain, unresponsive scale; ADA = anti-drug antibody; AEs = adverse events; BP = blood pressure; CRF = case report form; 
ECMO = Extracorporeal membrane oxygenation; ED = early discontinuation visit; FiO2 = fraction of inspired oxygen in the air; ICU = intensive care unit; NP = nasopharyngeal; 
NSAIDS = non-steroidal anti-inflammatory drugs; SAEs = serious adverse events; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SpO2 = saturation of 
peripheral oxygen. 

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J2W-MC-PYAB (2.2)
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2.3.
Section 3.0. Objective and Endpoints
Objectives
Endpoints
Primary
Characterize the pharmacokinetics of LY3819253 in 
combination with LY3832479 after intravenous 
infusion
Area under the concentration-time curve (AUC) from 0 
to infinity for both LY3819253 and LY3832479
Secondary
Characterize the effect of LY3819253 in combination 
with LY3832479 after intravenous infusion on…

Safety

Safety assessments such as AEs and SAEs

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

the reduction of SARS-CoV-2 viral load

Change from baseline to Day 7

persistently high SARS-CoV-2 viral load

Proportion of participants with SARS-CoV-2 viral 
load greater than 5.27 on Day 7

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

SARS-CoV-2 viral load reduction

Change from baseline to 
o
Day 3
o
Day 5

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 

symptoms and resolution

Presence or absence of a symptom 

Absence of all symptoms

Time to absence of all symptoms

Time to sustained absence of all symptoms

Proportion of participants demonstrating absence 
of symptoms on Days 2-11

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J2W-MC-PYAB (2.2)
17
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 emergence of viral resistance to 
LY3819253 in combination with LY3832479

Comparison from baseline to the last evaluable 
time point up to Day 29

safety

Proportion (percentage) of participants who 
experience MIS-C
Abbreviations:  AE = adverse event; SAE =serious adverse event; MIS-C = multisystem inflammatory syndrome in 
children; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. 
2.4.
Section 4.0. Study Design
This addendum adds a single, open-label treatment arm 22 to evaluate the combination of 
LY3819253 and LY3832479 administered as an intravenous infusion to pediatric participants.
2.4.1. Section 4.1.1. Design Outline
This table describes the visit types for treatment arm 22.
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 symptom assessment
Telephone visits
Early discontinuation and follow-up
Follow SoA
May be conducted as outpatient 
clinic or home visits
2.5.
Section 4.2. Scientific Rationale for Study Design
COVID-19 is a severe viral respiratory infection caused by SARS-CoV-2 that affects all age 
groups (Hoang et al. 2020).
SARS-CoV-2 Incidence in the Pediatric Population
Children of all ages may be infected with SARS-CoV-2, but there is a bimodal pattern to 
infections, with higher incidence in adolescents, neonates, infants, and young children (AAP 
2020; DeBiasi et al. 2020). For reasons that are unknown, school age children (roughly 4 to 12 
years of age) appear least likely to be infected and have the least severe outcomes of any age 
group, pediatric or adult (DeBiasi et al. 2020; Woolf et al. 2020).  
Severity of Disease
While the disease is generally less severe in the pediatric population than in adults, there are still 
individual pediatric patients who are infected with SARS-CoV-2 that become symptomatic, and 

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in some cases die (AAP 2020).  There are also concerns about potential later term sequela that 
may result in pediatric patients from SARS-CoV-2 infections (Hertting et al. 2021). This 
includes Multisystem Inflammatory Syndrome in Children (MIS-C) which occurs 2 to 4 weeks 
after infection, is uncommon (2 in 100,000 persons <21 years of age, approximately 1/161 the 
infection rate), and is sometimes fatal but may include less severe cases (Levin 2020).  
As in adults, outcomes in pediatric patients of all ages are generally worse in the presence of a 
number of comorbid conditions, such as medical complexity requiring long-term technological 
support, immune suppression or malignancy, obesity, diabetes, seizures, congenital heart disease, 
or chronic lung disease (Shekerdemian et al. 2020).  Such groups are more likely to be 
hospitalized and require intensive care unit (ICU) admission (Zachariah et al. 2020).
Unmet Need for Treatment
Currently, there are no FDA-approved therapies for the treatment of COVID-19 in non-
hospitalized pediatric patients, which necessitates the urgent need to have access to experimental 
therapies, especially for patients under 12 years of age.
2.6.
Section 4.3. Justification for Dose
In treatment arm 22, participants will receive weight category-based doses that are predicted to 
match exposure in adults of 700 mg LY3819253 and 1400 mg LY3832479 administered 
together.  These adult doses were selected based on PK/PD modeling, interim PK, viral load, 
symptoms, and clinical outcome and safety data from Study J2X-MC-PYAH (BLAZE-4).  
This table describes the weight categories and dose levels.
Pediatric Weight Category (kg)
LY3819253 and LY3832479 Dose
≥40
700 mg and 1400 mg
>20 to <40
350 mg and 700 mg
>12 to 20
175 mg and 350 mg
1.5 to 12
15 mg/kg and 30 mg/kg
2.7.
Section 5.0. 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.
2.7.1. Section 5.1. Inclusion Criteria
Participants are eligible to be included in this addendum only if all of the following criteria 
apply:
1. This criterion is not applicable to participants in this addendum
2. This criterion is not applicable to participants in this addendum

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3. This criterion is not applicable to participants in this addendum
4. Must have sample collection for first positive SARS-CoV-2 viral infection determination 
≤3 days prior to start of the infusion
5. Are males or females, including pregnant females
Reproductive and Contraceptive requirements are provided in the main PYAB protocol, 
Section 10.4, Appendix 4.  Contraceptive use by males or females should be consistent 
with local regulations for those participating in clinical studies. 
6. Understand and agree to comply with planned study procedures
7. Agree to the collection of nasopharyngeal swabs and venous blood
8. The participant or legally authorized representative give signed informed consent and/or 
assent as described in the main PYAB protocol, Section 10.1.3 which includes 
compliance with the requirements and restrictions listed in the informed consent form 
(ICF) and in this protocol. 
27. This criterion is not applicable for participants in this addendum
28. This criterion is not applicable for participants in this addendum 
30. Are 0 (≥32 weeks gestational age AND ≥ 1.5 kg) to 17 years of age (inclusive) AND 
satisfy at least one of the following risk factors 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, autism, or 
Down syndrome (FAIR Health 2020; Spreat et al. 2020)

Have a medical-related technological dependence, for example, tracheostomy, 
gastrostomy, or positive pressure ventilation (not related to COVID-19)

Have asthma, cystic fibrosis, reactive airways disease 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, or

Are <1 year of age. 

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35. Have one or more COVID-19 symptoms (CDC December 2020, FDA February 2021) 

shortness of breath or 
difficulty breathing

nasal congestion or runny 
nose

fever

chills

sore throat

stomachache

nausea

vomiting

diarrhea

cough

tiredness

muscle or body aches and 
pain

headache

new loss of smell, or

new loss of taste

poor appetite or poor 
feeding (in babies).
2.7.2. Section 5.2. Exclusion Criteria
Participants are excluded from this addendum if any of the following criteria apply:
9. Have SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 < 300, respiratory rate ≥30 per 
minute, heart rate ≥125 per minute due to COVID-19 (FDA February 2021) 
10. Require mechanical ventilation or anticipated impending need for mechanical ventilation 
due to COVID-19
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 

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21. Exclusion criterion [21] removed 
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. Mothers who are breast feeding
25. Are investigator site personnel directly affiliated with this study
29. This criterion is not applicable for participants in this addendum 
31. Have a diagnosis of MIS-C in the opinion of the investigator
32. This criterion is not applicable for participants in this addendum
33. This criterion is not applicable for participants in this addendum, and
34. Are currently hospitalized for treatment of COVID-19.  Other reasons for hospitalization
are acceptable.
2.8.
Section 8.1. Efficacy Assessments
2.8.1. Section 8.1.2. Symptom Assessment for Pediatric Participants
The presence or absence of symptoms associated with COVID-19, within the past 24 hours, will 
be collected from participants or their parents/legal guardian.  
Signs and symptoms associated with COVID-19 should not be captured as AEs, unless more 
severe than expected.  
Symptoms include

shortness of breath or difficulty 
breathing

diarrhea

nasal congestion or runny nose

cough

fever

tiredness

chills

muscle or body aches and pain 

sore throat

headache

stomachache

new loss of smell

nausea

new loss of taste, and

vomiting

poor appetite or poor feeding, 
especially in babies under 1 year old.
Source: Centers for Disease Control (CDC) resource page; COVID-19 in Children and Teens, 2020.

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2.9.
Section 9.0. Statistical Considerations
2.9.1. Section 9.1. Statistical Hypotheses
This is an open-label addendum with a primary objective of assessing PK and secondary 
objective of safety and tolerability. No hypothesis testing is planned.
2.9.2. Section 9.2. Sample Size Determination
The planned sample size is approximately 85 participants with a minimum of 5 participants in 
each of these age groups

0 to <2

2 to <6, and 

6 to <12 years.
Participant PK profiles were simulated using the current PK model with established allometric 
relationships (Betts et al. 2018) for a typical monoclonal antibody to enable a Monte Carlo 
assessment to achieve adequate power of the trial to estimate population PK model in pediatrics 
across the weight range.
2.9.3. Section 9.3. Populations for Analyses
The pediatric populations for analysis include the adolescent participants from Study PYAB and 
the participants in this addendum who are ≤17 years old at the time of screening. This table 
defines the pediatric populations for analysis.
Pediatric Population for Analysis
Description
Pharmacokinetic
All pediatric participants who received study 
intervention and have evaluable PK sample.
Safety
All pediatric participants who received study 
intervention. Participants will be analyzed according to 
the intervention they actually received.
Efficacy
All pediatric participants who received study 
intervention and provided at least one post-baseline 
measure for the relevant endpoint. Participants will be 
analyzed according to the intervention to which they 
were randomized or assigned.

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2.9.4. Section 9.4. Statistical Analyses
2.9.4.1.
Section 9.4.1. General Considerations
Statistical analysis of this addendum will be the responsibility of the sponsor or its designee.
Unless otherwise specified, all endpoints will be summarized descriptively. Descriptive 
summaries will include

number of participants

mean, standard deviation, median, minimum and maximum for continuous measures, and

frequency counts and percentages for categorical measures.
Analyses will be performed overall and separately by age group.  The age groups are defined as

0 to <2

2 to <6 

6 to <12 years, and

12 to ≤17 years.
For endpoints that are common between Study PYAB Arms 7-9, 13-14, and the PYAB 
Addendum, analyses will also be performed by treatment arm.
Additional details may be provided in the statistical analysis plan (SAP).
2.9.4.2.
Section 9.4.2. Primary Endpoint
Treatment Arm 22
The primary objective is to assess PK in the pediatric pharmacokinetic population. The primary 
parameter for analysis is the area under the concentration-time curve (AUC) from 0 to infinity.  
Other parameters, such as half-life, apparent clearance, and apparent volume of distribution, may 
be reported.  
2.9.4.3.
Section 9.4.3. Secondary Endpoints
The secondary objective is to assess safety and tolerability. The pediatric safety population is 
described in Section 2.9.3.  Safety analyses will be conducted as stated in Section 2.9.4 and as 
stated in the main PYAB protocol.
2.9.4.4.
Section 9.4.3.4. Pharmacokinetic and Pharmacodynamic Analyses
LY3819253 and LY3832479 concentration data will be analyzed using a population PK 
approach via nonlinear mixed-effects modeling with the NONMEM software.  In addition, the 
effects of participant factors, such as weight, age and gender on PK parameters may be 
evaluated.  If antidrug antibody is detected from immunogenicity testing, its impact on 
LY3819253 and LY3832479 PK may also be evaluated. 

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Pharmacodynamic endpoints will be summarized using descriptive methodology.  The SARS-
CoV-2 viral dynamics will include evaluation of

change from baseline in SARS-CoV-2 viral load (Days 3, 5 and 7)

AUC, and

time to SARS-CoV-2 clearance.
Additional PK/PD concentration-response analysis may be performed. 
2.9.5. Section 9.5. Interim Analyses
An interim analysis may occur to evaluate safety or efficacy in support of regulatory interactions.
This interim may include all pediatric data available at that time and relevant analyses.
Early review of PK data may be planned but is not considered a formal interim analysis.
The approximate timing, decision criteria, and statistical methods associated with each possible 
modification to this addendum will be fully described in the SAP.
2.10.
Section 10.1.11. Investigator Information
Physicians with specialties, including, but not limited to pediatrics, infectious disease, acute or 
critical care, pulmonary disease, immunology, or other appropriate specialties may participate as 
investigators for this addendum.
An investigator or sub-investigator must also confirm that they have clinical experience to 
adequately manage participants in a particular age range in order for the site to enroll participants
in that respective age range. The age ranges are

less than 1 year of age

1 to 11 years of age, and

12 to 17 years of age.
This addendum will be conducted at a diverse group of sites that may include academic and 
community affiliated outpatient clinics and emergency departments, as well as other locations 
where children may be seen for outpatient care.  Clinicians providing care in such settings may 
include pediatricians, neonatologists, family practitioners, emergency room specialists, and other 
physicians.  The investigator requirements are written to reflect this reality of pediatric patient
care in outpatient settings during the pandemic.

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2.11.
Section 10.6. Appendix 6: Recommended Laboratory Testing for 
Hypersensitivity Events
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 or local 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 or local 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 or local laboratory*. 
Results will not be provided to the investigative sites.
Cytokine panel
Assayed by Lilly-designated laboratory or local laboratory*. 
Results will not be provided to the investigative sites.
Abbreviations: ADA = anti-drug antibody; IgE = immunoglobulin E; PK = pharmacokinetic.
* The priority of testing and use of a Lilly-designated laboratory or local laboratory, is determined based on the
participants age, weight, in consultation with the investigator and the medical monitor.

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2.12.
Section 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 ≥1.5x baseline (except for participants with 
Gilbert’s syndrome)
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase;
TBL = total bilirubin.
Notes: All ULN values should be age adjusted (AAULN).
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 Lilly designated medical monitor.
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, or seizures) recent travel, history of concomitant medications (including over-the-
counter), herbal and dietary supplements, history of alcohol drinking, 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.   
Special care should be taken to minimize the volume of blood taken during hepatic monitoring.

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Comprehensive Hepatic Evaluation  
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
one or more of these conditions occur:
If a participant with baseline 
results of... 
develops the following elevations…
ALT or AST <1.5x 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 ≥2x baseline (except for participants with Gilbert’s syndrome) 
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
TBL = total bilirubin.
*Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, and/or 
eosinophilia >5%.
Notes:  All ULN values should be age adjusted (AAULN).
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for PT-INR and direct bilirubin, if total bilirubin was 
elevated. 
Based on the participant’s age and weight, medical history and initial results, further testing 
should be considered in consultation with the Lilly-designated medical monitor, including tests 
for viral hepatitis A, B, C, E, autoimmune hepatitis, or an abdominal imaging study (for 
example, ultrasound, MRI, or CT scan). Consider additional tests, based on the medical history 
and clinical picture, 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 blood
phosphatidylethanol. 
Special care should be taken to prioritize more pertinent blood tests and minimize the volume of 
blood taken during hepatic evaluation. Based on the circumstances and the investigator’s 
assessment of the participant’s clinical condition, the investigator should consider referring the 
participant for a pediatric hepatologist or gastroenterologist consultation, magnetic resonance 
cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), 
cardiac echocardiogram, or a liver biopsy as deemed appropriate for the clinical condition and 
participant’s age.  

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Hepatic Evaluation Testing
Please refer to main protocol for the complete list of tests for evaluation.  
For participants ≥4.4 kg, assays will use a Lilly-designated laboratory or local laboratory.
For participants <4.4 kg assays will use only a local laboratory.
The microbiology blood and urine assay must use a local laboratory.
Additional hepatic data collection in study participants who have abnormal liver tests
Additional hepatic safety data collection in hepatic safety case report forms (CRF) should be 
performed in study participants if one or more of these conditions occur during the study:
If a participant with baseline 
results of... 
develops the following elevations…
ALT <1.5x ULN
Serum ALT to ≥5x ULN on 2 or more consecutive blood tests
ALT ≥1.5x ULN
Serum ALT to ≥3x ULN on 2 or more consecutive blood tests
TBL <1.5x ULN
TBL to ≥2x ULN (except for participants with Gilbert’s syndrome)
TBL ≥1.5x ULN
TBL to ≥2x baseline
ALP <1.5x ULN
Serum ALP to ≥2x ULN on 2 or more consecutive blood tests
ALP ≥1.5x ULN
Serum ALP ≥2x baseline on 2 or more consecutive blood tests
Or
If a hepatic event is considered a serious adverse event, or
If discontinuation of intervention is due to a hepatic event.
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; TBL = total bilirubin.
Notes:  All ULN values should be age adjusted (AAULN).
The interval between the 2 consecutive blood tests should be at least 2 days.
  

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2.13. Section 10.10. Appendix 10: Blood Collection Restrictions and 
Guidance for Pediatric Participants
Sampling Restrictions
Blood draws are not allowed from dialysis shunts or catheters, apheresis catheters or arterial 
catheters.
No ADA samples for participants <12 kg
Due to blood volume restrictions participants <12 kg will not have immunogenicity (ADA) 
samples taken.  
Minimizing the number of blood draws and venipunctures
Blood draws should be consolidated, and the number of attempts should be kept to the minimum 
number required and in keeping with local guidelines and procedures.  
To avoid multiple venipunctures in a single day, blood samples may be obtained via a peripheral 
intravenous (IV) catheter.  For this study, a peripherally inserted central catheter (PICC) is not 
considered to be a peripheral IV catheter.  
Use of existing central line
If a participant in this addendum already has central venous access, for example, via a port or 
PICC line, as part of their non-COVID-19 clinical care, intervention may be infused (single 
infusion) via this route if these requirements are met:

The participant’s parents or legal guardians give their permission to use the established 
central intravenous access route to administer study intervention, AND 

The site consults with the medical team that is using the established central intravenous 
access route to provide clinical care and obtains their permission to use this route to 
administer study intervention, AND 

The site investigator determines who is appropriately trained and qualified to access and 
infuse study intervention via central venous access routes in pediatric participants and 
delegates the authority to do such procedures to those individuals, AND 

The delegated site personnel follow good clinical practices (GCPs) and the site’s 
established procedure for preventing infections and administering drugs via a central 
intravenous access route.
Use of existing central line for mobile study visits
During mobile study visits, study nurses may obtain blood samples via a central venous access 
route (for example, port or PICC line) if these requirements are met:

The participant’s parents or legal guardians give their permission to use the established 
central intravenous access route (for example, port or PICC line) to obtain blood samples 
during mobile study visits, AND 

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
The site staff consults with the medical team that is using the established central venous 
access route to provide clinical care and obtains their permission to use this route to 
obtain blood samples during mobile study visits, AND 

The site investigator determines who is appropriately trained and qualified to access and 
obtain blood samples via central venous access routes in pediatric participants and 
delegates the authority to do such procedures to those individuals, AND

The delegated site personnel follow GCPs and the site’s established procedure for 
preventing infections when obtaining blood samples via a central venous access route. 
Consult with the Lilly medical monitor if there are any questions about this requirement.
Use of anesthetics or devices to ease discomfort with venipunctures
To ease discomfort associated with venipunctures, these options are allowed in the study per 
local prescribing information, 

local anesthetic creams, for example, EMLA or ELA-max 

needleless devices for injecting local anesthetics, for example, a J-Tip, and

local vibration devices, for example, a Buzzy.  
Pharmacokinetic sampling
To avoid contamination with infused intervention, blood samples for pharmacokinetic purposes 
on the day of infusion should never be obtained using the same venous access site that is used for 
infusion of study intervention.  In addition, pharmacokinetic samples on the day of infusion 
should be obtained from a venous access site on the opposite side of the body from the site of 
intervention infusion.

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3. References
[AAP] American Academy of Pediatrics. Children and COVID-19: State-Level Data Report. 
Last updated August 03, 2020. Accessed 11 January 2021. Available at: 
https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-
covid-19-state-level-data-report/
Betts A, Keunecke A, van Steeg TJ, et al. Linear pharmacokinetic parameters for monoclonal 
antibodies are similar within a species and across different pharmacological targets: a 
comparison between human, cynomolgus monkey and hFcRn Tg32 transgenic mouse using a 
population-modeling approach. MAbs. 2018;10(5):751-764. 
https://doi.org/10.1080/19420862.2018.1462429
[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 January 13, 2021. Available at: 
https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/children/symptoms.html
[CDC] Centers for Disease Control and Prevention. National Center for Health Statistics, 
Clinical Growth Charts. Accessed March 11, 2021. Available at: 
https://www.cdc.gov/growthcharts/clinical_charts.htm
DeBiasi RL, Song X, Delaney M, et al. Severe Coronavirus Disease-2019 in Children and Young 
Adults in the Washington, DC, Metropolitan Region. J Pediatr. 2020;223:199-203.e1.
https://doi.org/10.1016/j.jpeds.2020.05.0076
FAIR Health. Risk factors for COVID-19 mortality among privately insured patients. Accessed 
February 28, 2021. Available at:
https://s3.amazonaws.com/media2.fairhealth.org/whitepaper/asset/Risk%20Factors%20for%2
0COVID-19%20Mortality%20among%20Privately%20Insured%20Patients%20-
%20A%20Claims%20Data%20Analysis%20-
%20A%20FAIR%20Health%20White%20Paper.pdf
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. 
Accessed: 11 March 2021. Available at: https://www.fda.gov/regulatory-information/search-
fda-guidance-documents/covid-19-developing-drugs-and-biological-products-treatment-or-
prevention. 
Hertting O. More research is needed on the long-term effects of COVID-19 on children and 
adolescents. Acta Paediatrica. 2020;00:1-2.
https://onlinelibrary.wiley.com/doi/10.1111/apa.15731
Hoang A, Chorath K, Moreira A, et al. COVID-19 in 7780 pediatric patients: A systematic 
review. EClinicalMedicine. 2020;24:100433. https://doi.org/10.1016/j.eclinm.2020.100433
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4.
Appendix 1:  Protocol Addendum Revision History
Revision 2.1 
Overall Rationale for the Changes:
The overall rationale for the changes to this protocol addendum are to

allow pediatric participants in the study if they are hospitalized for any reason except 
COVID-19

allow local testing for specific laboratory tests, and 

modify the hepatic monitoring language specifically for pediatric participants.
Section # and Name
Description of Change
Brief Rationale
2.7.1 Section 5.1 Inclusion 
Criteria
Added statement for 
criterion #2.  
Pediatric participants are allowed in the study if 
they are hospitalized for any reason except COVID-
19.
2.7.2. Section 5.2 Exclusion 
Criteria
Added criterion #34
Pediatric participants are not allowed in the study if 
they are hospitalized for treatment of COVID-19.
2.8.1 Section 8.1.2 Symptom 
Assessment for Pediatric 
Participants
Removed “chest pain or 
discomfort with 
breathing” symptom
Update to CDC resource page for COVID-19 in 
Children and Teens
2.9.2 Section 9.2 Sample Size 
Determination
Removed sentence “Data 
across all weight ranges 
will be combined for 
analysis.”
Originally entered in error.  Details of analyses are 
captured elsewhere. 
2.11 Section 10.6 Appendix 6: 
Recommended Laboratory 
Testing for Hypersensitivity 
Events
Added section
Needed to add pediatric specific language to the 
table about using local laboratories depending on 
the participants age and weight in consultation with 
the investigator and medical monitor.
3.1 Section 10.7 Appendix 7: 
Liver Safety Suggested Actions 
and Follow-up Assessments
Added section
Specific sponsor guidance for pediatric studies.
Added pediatric specific language about using local 
laboratories depending on the participants weight.
Throughout the addendum
Minor editorial and 
formatting changes
Minor, therefore not described

Leo Document ID = e6d3635b-2b1f-45f5-945a-dd2bc5c132af
Approver: 
Approval Date & Time: 12-Mar-2021 01:44:45 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 12-Mar-2021 01:50:45 GMT
Signature meaning: Approved
PPD
PPD