Clinical trial NCT04537910
Conditions: Healthy
Sponsor: Eli Lilly and Company
Start date: 2020-09-02; Completion date: 2020-12-28
Enrollment: 25 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to test the safety and tolerability of LY3819253 when it is given by injection just under the skin to healthy participants. Blood tests will be done to check how much LY3819253 is in the bloodstream and how long the body takes to eliminate it. Participation could last up to 16 weeks and may include up to six visits to the study center, with a one-week overnight stay.

Detailed description:

Arms: arm 1: Participants received single subcutaneous (SC) doses of 150 milligram (mg), 350 mg or 700 mg LY3819253. arm 2: Participants received a single SC dose of Placebo.
Interventions: intervention 1: LY3819253 intervention 2: Placebo
Intervention descriptions: intervention 1: Administered SC. intervention 2: Administered SC.

Protocol documents:
Prot_000.pdf: 
 
 
 
 
 
 
 
Protocol J2X-MC-PYAG (b) 
 
 
A Randomized, Placebo-Controlled, Participant- and Investigator-
Blind, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and 
Tolerability of LY3819253 Administered Subcutaneously to Healthy 
Participants 
 
 
NCT04537910 
 
 
Approval Date: 14-Oct-2020 


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
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, 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, Placebo-Controlled, Participant- and Investigator-Blind, Phase 1 
Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of LY3819253
Administered Subcutaneously to Healthy Participants
Protocol Number: J2X-MC-PYAG
Amendment Number: b
Compound: LY3819253
Study Phase: 1
Short Title: A Randomized, Placebo-Controlled, Phase 1 Study to Evaluate the 
Pharmacokinetics, Safety, and Tolerability of LY3819253 Administered 
Subcutaneously to Healthy Participants
Sponsor Name: Eli Lilly and Company
Legal Registered Address: Indianapolis, Indiana USA 46285
Regulatory Agency Identifier Number:
IND: 150440
Approval Date: Protocol Electronically Signed and Approved by Lilly on date provided below.
Approval Date: 14-Oct-2020 GMT


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
2
Medical Monitor Name and Contact Information will be provided separately.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
3
Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Original Protocol 
17-Aug-2020
Protocol amendment (a)
02-Sep-2020
Amendment (b)
Overall Rationale for the Amendment:
This protocol is being amended to remove the requirement that the optional Cohort 3 must enroll
at least 9 participants. 
Section # 
and Name
Description of Change
Brief Rationale

Section 1.1,
Synopsis

Section 4.1.1, 
Screening and 
Enrollment

Section 9.2,
Sample Size 
Determination
Specified that only Cohorts 1 and 2 have 
an intended minimum number of 
participants with evaluable data. 
Optional Cohort 3 does not feature a 
safety review for purposes of moving 
to a subsequent cohort, and therefore 
does not have the same requirement
for minimum participant numbers.

Section 1.2
Schema
Added a note to the schema to clarify 
that the LY:PBO ratio for Cohort 3 is an 
intention only.
As above.

Section 6.1.1, 
Injection 
volumes and 
formulation 
concentrations
Added a note to clarify that the number 
and volume of injections will be 
adjusted if any dose levels are modified.
Mistakenly omitted from earlier 
versions of the protocol.

Section 10.3.3, 
Recording 
and Follow-
Up of AE 
and/or SAE
Removed reference to the Division of 
AIDS (DAIDS) table for grading AEs 
and SAEs.
The DAIDS table will not be used for 
this study.

Section 11, 
References
Removed DAIDS reference.
As above.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
4
Table of Contents
1.
Protocol Summary......................................................................................................7
1.1.
Synopsis.......................................................................................................................7
1.2.
Schema.........................................................................................................................8
1.3.
Schedule of Activities (SoA) ........................................................................................9
2.
Introduction..............................................................................................................15
2.1.
Study Rationale ..........................................................................................................15
2.2.
Background ................................................................................................................15
2.2.1.
Summary Information from LY3819253 Program to Date ..........................................15
2.3.
Benefit/Risk Assessment ............................................................................................16
3.
Objectives and Endpoints.........................................................................................17
4.
Study Design .............................................................................................................18
4.1.
Overall Design............................................................................................................18
4.1.1.
Screening and enrollment ...........................................................................................18
4.1.2.
Inpatient stay..............................................................................................................18
4.1.3.
Outpatient follow-up...................................................................................................19
4.2.
Scientific Rationale for Study Design .........................................................................19
4.3.
Justification for Dose..................................................................................................19
4.4.
End of Study Definition..............................................................................................20
5.
Study Population ......................................................................................................21
5.1.
Inclusion Criteria........................................................................................................21
5.2.
Exclusion Criteria.......................................................................................................21
5.3.
Lifestyle Considerations .............................................................................................24
5.3.1.
Meals and Dietary Restrictions ...................................................................................24
5.3.2.
Caffeine, Alcohol, and Tobacco..................................................................................24
5.3.3.
Activity ......................................................................................................................24
5.4.
Screen Failures...........................................................................................................24
6.
Study Intervention....................................................................................................26
6.1.
Study Interventions Administered...............................................................................26
6.1.1.
Injection volumes and formulation concentrations ......................................................27
6.1.2.
In the Event of a Retrospective Positive Sterility Finding from 
Prepared Study Intervention........................................................................................27
6.2.
Preparation/Handling/Storage/Accountability.............................................................27
6.3.
Measures to Minimize Bias: Randomization and Blinding..........................................28
6.4.
Study Intervention Compliance...................................................................................28
6.5.
Concomitant Therapy .................................................................................................28
6.6.
Dose Modification......................................................................................................29
6.6.1.
Dose-Escalation Criteria .............................................................................................29
6.6.2.
Access to Data during the Study .................................................................................29
6.6.3.
Temporary Stopping Criteria ......................................................................................29
6.7.
Intervention after the End of the Study........................................................................30
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................31


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
5
7.1.
Discontinuation of Study Intervention ........................................................................31
7.2.
Participant Discontinuation/Withdrawal from the Study .............................................31
7.2.1.
Discontinuation of Inadvertently Enrolled Participants ...............................................31
7.3.
Lost to Follow up .......................................................................................................32
8.
Study Assessments and Procedures .........................................................................33
8.1.
Efficacy Assessments .................................................................................................33
8.2.
Safety Assessments ....................................................................................................33
8.2.1.
Physical Examinations................................................................................................33
8.2.2.
Vital Signs..................................................................................................................33
8.2.3.
Electrocardiograms.....................................................................................................33
8.2.4.
Clinical Safety Laboratory Assessments .....................................................................34
8.2.5.
Injection Site Reaction Assessment.............................................................................34
8.3.
Adverse Events and Serious Adverse Events ..............................................................34
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information.................................................................................................................35
8.3.2.
Method of Detecting AEs and SAEs ...........................................................................35
8.3.3.
Follow-up of AEs and SAEs.......................................................................................35
8.3.4.
Regulatory Reporting Requirements for SAEs............................................................36
8.3.5.
Pregnancy...................................................................................................................36
8.3.6.
Hypersensitivity Reactions .........................................................................................36
8.3.7.
SARS-CoV-2 Infection...............................................................................................36
8.3.8.
Product Complaints ....................................................................................................37
8.4.
Treatment of Overdose ...............................................................................................37
8.5.
Pharmacokinetics........................................................................................................38
8.5.1.
Bioanalytical ..............................................................................................................38
8.6.
Pharmacodynamics.....................................................................................................38
8.7.
Genetics .....................................................................................................................38
8.8.
Biomarkers.................................................................................................................38
8.9.
Immunogenicity Assessments.....................................................................................39
8.10.
Health Economics.......................................................................................................39
9.
Statistical Considerations.........................................................................................40
9.1.
Statistical Hypotheses.................................................................................................40
9.2.
Sample Size Determination.........................................................................................40
9.3.
Populations for Analyses ............................................................................................40
9.4.
Statistical Analyses.....................................................................................................40
9.4.1.
General Considerations...............................................................................................41
9.4.2.
Primary Endpoint: Pharmacokinetics ..........................................................................41
9.4.3.
Secondary Endpoint: Safety........................................................................................41
9.4.4.
Exploratory Endpoint: Injection Site Reaction Assessments........................................42
9.5.
Interim Analyses.........................................................................................................42
9.6.
Data Monitoring Committee (DMC)...........................................................................42
10.
Supporting Documentation and Operational Considerations ................................43
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................................43
10.1.1.
Regulatory and Ethical Considerations........................................................................43


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
6
10.1.2.
Informed Consent Process ..........................................................................................43
10.1.3.
Data Protection...........................................................................................................44
10.1.4.
Dissemination of Clinical Study Data .........................................................................44
10.1.5.
Data Quality Assurance ..............................................................................................44
10.1.6.
Source Documents......................................................................................................46
10.1.7.
Study and Site Start and Closure.................................................................................46
10.1.8.
Publication Policy.......................................................................................................47
10.1.9.
Investigator Information .............................................................................................47
10.1.10. Long-Term Sample Retention.....................................................................................47
10.2.
Appendix 2: Clinical Laboratory Tests........................................................................48
10.2.1.
Blood Sampling Summary..........................................................................................50
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting.......................................................51
10.3.1.
Definition of AE.........................................................................................................51
10.3.2.
Definition of SAE.......................................................................................................52
10.3.3.
Recording and Follow-Up of AE and/or SAE .............................................................53
10.3.4.
Reporting of SAEs......................................................................................................55
10.4.
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information ...............................................................................................56
10.4.1.
Women.......................................................................................................................56
10.4.2.
Men............................................................................................................................56
10.4.3.
Collection of Pregnancy Information ..........................................................................57
10.5.
Appendix 5: Genetics .................................................................................................59
10.6.
Appendix 6: Recommended Laboratory Testing for 
Hypersensitivity Events..............................................................................................60
10.7.
Appendix 7: Abbreviations .........................................................................................62
10.8.
Appendix 8: Protocol Amendment History .................................................................65
11.
References.................................................................................................................66


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
7
1.
Protocol Summary
1.1.
Synopsis
Protocol Title: A Randomized, Placebo-Controlled, Participant- and Investigator-Blind, Phase 1 
Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of LY3819253 Administered 
Subcutaneously to Healthy Participants
Short Title: A Randomized, Placebo-Controlled, Phase 1 Study to Evaluate the 
Pharmacokinetics, Safety, and Tolerability of LY3819253 Administered Subcutaneously to 
Healthy Participants
Rationale: The clinical program for LY3819253 so far has involved IV dosing of LY3819253.
Study PYAG will investigate SC dosing of LY3819253. Single SC doses of LY3819253, 350 mg 
and 700 mg, will be administered to establish the PK, safety, and tolerability profiles in healthy 
participants.
Objectives and Endpoints
Objectives
Endpoints
Primary
To determine the PK of single SC doses of 
LY3819253 in healthy participants
AUC(0-∞)
Secondary
To describe safety and tolerability following 
single SC doses of LY3819253 in healthy 
participants
Incidence of spontaneously reported AEs, 
TEAEs, and SAEs; vital signs; clinical 
laboratory results
Exploratory
To assess ISRs following single SC doses of 
LY3819253 in healthy participants
Characterization and measurement of 
incidence and severity of ISRs, including 
injection site pain, using data collected from 
the ISR assessment, and the exploratory tool
(Scarletred)
To determine the immunogenicity of
LY3819253 following single SC doses in 
healthy participants
Incidence of TEADA
Abbreviations: AE = adverse event; AUC(0-∞) = area under the concentration versus time curve from time 0 to 
infinity; ISR = injection site reaction; PK = pharmacokinetics; SAE = serious adverse event; SC = subcutaneous; 
TEADA = treatment-emergent antidrug antibodies; TEAE = treatment-emergent adverse event.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
8
Overall Design
This is a single-site study in healthy participants who will receive a single SC dose of 
LY3819253. The study will be participant- and investigator-blinded, randomized, and placebo
controlled.
Disclosure Statement: This is a PK and safety study to test LY3819253 and placebo in up to 3 
dose cohorts.
Number of Participants:
A maximum of 36 participants will be enrolled to study intervention, with the intention that at 
least 6 participants randomized to LY3819253 have sufficient evaluable data in each of Cohorts 
1 and 2.
Intervention Groups and Duration:
This is a single-dose study with an estimated duration for each participant of up to 16 weeks 
from screening through follow-up.
Data Monitoring Committee: No
1.2.
Schema
Abbreviations: LY = LY3819253; PBO = placebo; SC = subcutaneous.
Note: The LY:PBO ratio for the optional Cohort 3 is an intention and may change subject to enrollment numbers.  
The planned dose for Cohort 3 may change based on data review during the study.
Cohort 2
7 LY : 2 PBO
Cohort 1
7 LY : 2 PBO
Optional 
Cohort 3
7 LY : 2 PBO
Dose Level 1
350 mg LY or PBO, SC
Dose Level 2
700 mg LY or PBO, SC
Dose Level 3
700 mg LY or PBO, SC
(alternative injection 
volumes)
Week
1
2
3


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
9
1.3.
Schedule of Activities (SoA)
Procedure / 
Assessments
Screening
Treatment Period
Follow-up Visits
Comment
Visit Number
V1
V2
V3
V4
V5
V6/
ED
Week(s)
0
2
4
8
12
Study Day
-14
to –1
-1
1
2
3
4
5
6
7
15
±2d
29
±3d
60
±3d
85
±3d
Informed 
consent 
(written)
X
Review/
confirm I/E 
criteria
X
X
After screening, ensure 
participants continue to meet 
I/E criteria.
Medical 
history
including pre-
existing 
conditions
X
Weight/height
X
X
Height at screening only.
Urinalysis
X
X
COVID-19 
clinical 
screening
X
X
X
X
X
X
Symptoms and recent 
contact (see Section 5.2 for a 
description of symptoms and 
close contact). At designated 
timepoints and as needed 
during the study.
SARS-CoV-2 
serology
X
X
X
X
X
Serology results are not 
needed before dosing.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
10
Procedure / 
Assessments
Screening
Treatment Period
Follow-up Visits
Comment
Visit Number
V1
V2
V3
V4
V5
V6/
ED
Week(s)
0
2
4
8
12
Study Day
-14
to –1
-1
1
2
3
4
5
6
7
15
±2d
29
±3d
60
±3d
85
±3d
SARS-CoV-2 
point-of-care 
test
X
X
Additional point-of-care 
tests may be conducted at 
the investigator’s discretion. 
See Section 8.3.7.
Naso-
pharyngeal
swab
X
Can be before or after 
LY3819253 administration. 
For research purposes. See 
Section 8.3.7.
Nasal swab
X
For research purposes. This
swab may be taken if a 
point-of-care test is done 
during the study, as 
described in Section 8.3.7.
Admission to 
study site
X
Discharge 
from study
site
X
Physical 
examination
Medical 
assessment
X
X
Predose
X
X
As needed
X
Full PE/MA at screening 
and Visit 6/ED. Symptom-
directed PE/MA at all other
indicated time points and as 
deemed necessary by the 
investigator or designee.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
11
Procedure / 
Assessments
Screening
Treatment Period
Follow-up Visits
Comment
Visit Number
V1
V2
V3
V4
V5
V6/
ED
Week(s)
0
2
4
8
12
Study Day
-14
to –1
-1
1
2
3
4
5
6
7
15
±2d
29
±3d
60
±3d
85
±3d
Vital signs: 
blood pressure, 
body 
temperature, 
pulse ratea
X
X
Predose
24 h 
(±2 h)
X
X
X
X
X
X
Vital signs should be taken 
following at least 5-min rest 
in a supine position. Vital 
signs may be taken any time 
prior to dosing. If screening 
takes place on Day -1, there 
is no need to take vital signs 
twice on Day -1.
Single 12-lead 
ECG
X
Concomitant 
medications 
review
X
X
X
X
X
X
AE review
X
X
Predose
X
X
X
X
X
X
X
X
X
X
AEs to be reviewed only 
after participant has signed 
the study ICF.
HIV, hepatitis 
B/C serology
X


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
12
Procedure / 
Assessments
Screening
Treatment Period
Follow-up Visits
Comment
Visit Number
V1
V2
V3
V4
V5
V6/
ED
Week(s)
0
2
4
8
12
Study Day
-14
to –1
-1
1
2
3
4
5
6
7
15
±2d
29
±3d
60
±3d
85
±3d
Pregnancy test
(women only)b
X
X
X
Serum pregnancy test at 
screening, urine test at other 
timepoints. Day -1 urine test 
refers to test at admission; 
this is not needed if 
admissions is on the same 
day as screening. Postdose 
urine test(s) can be 
performed at the judgment 
of the investigator, if 
pregnancy is suspected.
Clinical 
laboratory
testsa
X
X
X
X
X
X
X
Fasting is not required for 
these tests. If screening takes 
place on Day -1, there is no 
need to conduct these tests 
twice on Day -1.
Breath or urine 
ethanol screen
X
Ethanol screen may be 
repeated at other time points 
at the discretion of the 
investigator.
Urine drug 
screen
X
X
Day -1 urine test refers to 
test at admission; this is not 
needed if admission occurs 
on the same day as 
screening. Drug screen may 
be repeated at other time 
points at the discretion of the 
investigator.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
13
Procedure / 
Assessments
Screening
Treatment Period
Follow-up Visits
Comment
Visit Number
V1
V2
V3
V4
V5
V6/
ED
Week(s)
0
2
4
8
12
Study Day
-14
to –1
-1
1
2
3
4
5
6
7
15
±2d
29
±3d
60
±3d
85
±3d
SC 
LY3819253 or 
placebo dosing
X
LY3819253
PK samplinga
X
X
X 
X
X
X
X
X
X
X
X
Day 1 collection should be 
taken up to 4h postdose ±4h. 
The exact time of draw must 
be recorded.
For Day 2 onwards, PK 
samples may be taken at any 
time after vital signs.
Injection site 
assessments 
Predose; 
1min ±1min, 
10min
±2min, 
30min 
±5min, 
240min 
± 10min
24h 
±4h 
X
X
X
X
X
X
X
X
X
Timepoints include ISR 
assessment, VAS, if pain is 
reported, and the exploratory 
Scarletred tool. Scarletred 
timing is flexible and not 
confined to the windows 
shown, except for predose.
See Section 8.2.5 for detail.
Immunogen-
icity
Predose
X
X
X
X
Serum sample 
for exploratory 
biomarkersa
Predose
X
X
X
X
X
Pharmaco-
genetics 
samplea
Predose
For storage only.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
14
Abbreviations: AE = adverse event; COVID-19 = Coronavirus disease-2019; ECG = electrocardiogram; ED = early discontinuation; h = hours; HIV = human 
immunodeficiency viruses; I/E = inclusion/exclusion; ICF = informed consent form; MA = medical assessment; ISR = injection site reaction; min = minutes;
PE = physical examination; PK = pharmacokinetics; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SC = subcutaneous; V = visit; VAS = 
visual analog scale.
a
When conducted on the same day, the order of procedures should be vital signs, ECG, and then blood sampling.
b
For women who are considered to be postmenopausal, follicle-stimulating hormone should be drawn to confirm postmenopausal status if necessary, according 
to Appendix 4 (Section 10.4).


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
15
2.
Introduction
2.1.
Study Rationale
The clinical program for LY3819253 so far has involved IV dosing of LY3819253.
Study PYAG, will investigate SC dosing of LY3819253. Single SC doses of LY3819253, 350 
mg and 700 mg, will be administered to establish the PK, safety, and tolerability profiles in 
healthy participants.
2.2.
Background
The efficient community spread of SARS-CoV-2 has resulted in the current pandemic of 
COVID-19. There are no approved therapies to date for the treatment of COVID-19; Remdesivir 
is available under an emergency use authorization in the US (Gilead Sciences 2020).
SARS-CoV-2 gains entry to cells through binding of the spike protein to angiotensin-converting 
enzyme 2 receptors on cells (Hoffmann et al. 2020). LY3819253 is a neutralizing
immunoglobulin G1 mAb to the spike protein of SARS-CoV-2. It is designed to block viral 
attachment and entry into human cells, and to neutralize the virus.
2.2.1.
Summary Information from LY3819253 Program to Date
Additional information can be found in the IB.
2.2.1.1.
Safety
The following blinded summaries of safety are as of 24 July 2020.
LY3819253 has been administered to humans in 2 clinical studies, Study PYAA and Study 
PYAB. 
No SAEs or deaths have been recorded to date in either study.
Study PYAA 
The first 3 cohorts of Study PYAA each consisted of 8 hospitalized participants with moderate or 
severe COVID-19 who were randomized to receive either a single IV dose of LY3819253 or 
placebo at a ratio of 6:2. The dose range was 700 mg to 7000 mg.
Sixteen out of 24 participants dosed with LY3819253 (across all doses) or placebo experienced 
at least 1 TEAE. Most TEAEs reported were mild to moderate severity. There have been no 
dose-limiting safety issues identified.
No AEs of infusion-related reaction have been reported.
Study PYAB
Enrollment is open for 700-mg (or placebo), 2800-mg, and 7000-mg cohorts. The treatment-
group assignment for each participant remains blinded since the study is ongoing.
Eighty-eight participants have been administered LY3819253 or placebo. There have been 
4 infusion reactions reported to date. Based on conversations with the site, these occurred within 


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
16
approximately 30 minutes after the infusion was started, and were considered related to study 
treatment.
2.2.1.2.
Pharmacokinetics
Preliminary data in a limited number of subjects suggest the PK profile of LY3819253 is 
consistent with the PK model-predicted profile and dose proportional following a single IV dose 
of 700 mg up to 7000 mg. Pharmacokinetic model-estimated IV clearance and half-life 
approximately 0.3 L/day and 2 to 4 weeks, respectively.
2.3.
Benefit/Risk Assessment
Anticipated risk is considered low and is based on the known mechanism of action for human 
derived neutralizing antibodies in acute viral disease states. LY3819253 consists of a highly 
specific mAb directed at foreign (non-human) epitope(s). The complementarity determining 
regions of the mAb were derived from B lymphocytes of a convalescent SARS-CoV-2-infected 
patient; and, thus, have undergone natural positive and negative selection pressures in vivo, 
unlike humanized antibodies generated in mice. Therefore, off-target binding and tissue cross-
reactivity are considered unlikely.
Nonclinical safety studies conducted to date using the IV route of administration have not
demonstrated safety concerns. Toxicity studies supporting LY3819253 clinical trials consist of a 
tissue cross reactivity study, a 21-day rat toxicity study (IV administration), and an evaluation of 
ADE in vitro and in African green monkeys. Tissue cross-reactivity data did not suggest off-
target binding of clinical relevance and supports use of the rat as the nonclinical safety model.
The treatment phase of the 21-day repeat-dose toxicity study in rats, including histopathology 
evaluation, is complete and did not demonstrate adverse findings. Lastly, no evidence for ADE 
was observed in vitro or in nonhuman primates. 
The maximum planned dose of LY3819253 in this study is 700 mg SC. This is lower than the 
maximum dose delivered IV in previous studies.
A theoretical risk is that LY3819253 may cause ADE of viral replication. This is based on 
responses observed to some mAb therapies used in other unrelated viral diseases. Unlike ADE 
associated with Dengue and Zika virus infections, this phenomenon has not been clearly 
established for coronavirus infections, and has not been reported to date with SARS-CoV-2.
Additionally, limited experience with the use of convalescent serum as a treatment for patients 
with severe COVID-19 disease has not indicated safety concerns (Duan et al. 2020; Shen et al.
2020).
Additional manageable risks associated with most therapeutic monoclonal antibodies are the 
potential for hypersensitivity and cytokine release reactions. In addition, there is a potential for 
ISRs. Study participants will be in-house for the first 7 days after dosing, which will enable close 
monitoring for hypersensitivity reactions and ISRs post-injection.
Given the totality of data on LY3819253 and the well-established safety profile of other 
therapeutic monoclonal antibodies, the overall benefit/risk assessment of this study is considered 
favorable.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of LY3819253 may be found in the IB.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
17
3.
Objectives and Endpoints
Objectives
Endpoints
Primary
To determine the PK of single SC doses of 
LY3819253 in healthy participants
AUC(0-∞)
Secondary
To describe safety and tolerability following 
single SC doses of LY3819253 in healthy 
participants
Incidence of spontaneously reported AEs, 
TEAEs, and SAEs; vital signs; clinical 
laboratory results
Exploratory
To assess ISRs following single SC doses of 
LY3819253 in healthy participants
Characterization and measurement of 
incidence and severity of ISRs (including 
injection site pain) using data collected from 
the ISR assessment, as well as the exploratory 
tool (Scarletred).
To determine the immunogenicity of 
LY3819253 following single SC doses in 
healthy participants.
Incidence of TEADA.
Abbreviations: AE = adverse event; AUC(0-∞) = area under the concentration versus time curve from time 0 to 
infinity; ISR = injection site reaction; PK = pharmacokinetics; SAE = serious adverse event; SC = subcutaneous; 
TEADA = treatment-emergent antidrug antibodies; TEAE = treatment-emergent adverse event.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
18
4.
Study Design
4.1.
Overall Design
This is a single-site study in healthy participants who will receive a single SC dose of 
LY3819253. The study will be participant- and investigator-blinded, randomized, and placebo
controlled.
4.1.1.
Screening and enrollment
Up to 3 cohorts may be enrolled. In Cohorts 1 and 2, there will be at least 9 participants per 
cohort (7 LY3819253:2 placebo), with the intention that at least 6 participants randomized to 
LY3819253 have sufficient evaluable data in each cohort.
For the optional Cohort 3, up to 9 participants will be enrolled and the cohort may be closed 
when at least 5 participants have been randomized to LY3819253. The number of participants
and the ratio of LY3819253 to placebo may change based on enrollment numbers. However, the 
number assigned to LY3819253 will not exceed 7, and the number assigned to placebo will not 
exceed 2.
Participants will be screened within 14 days prior to Day 1 of dosing for each cohort. 
Participants will be admitted to the CRU as part of an inpatient visit on Day -1 and will be 
sequentially enrolled and then randomized to treatment.
4.1.2.
Inpatient stay
Participants will be admitted to the study site on Day -1. They will remain inpatient until 
discharge on Day 7 after study procedures are complete.
Dosing
Dosing will occur on Day 1. Intended doses of LY3819253 are as follows:

Cohort 1: 350 mg

Cohort 2: 700 mg

Cohort 3 (optional): 700 mg (alternative injection volumes)
See Section 6.1 for detail of injection volumes.
Participants will undergo PK sampling and safety assessment after dosing.
For Cohorts 1 and 2, a safety review will be conducted to determine whether it is appropriate to 
proceed with dosing of the next cohort. This safety review will be conducted based on data from 
at least 4 participants, after at least 4 days after dosing.
Sentinel dosing
Cohort 1 will include sentinel dosing. The first 2 participants will be randomized and dosed
(1 LY3819253:1 placebo). 
The investigator and the Lilly sponsor team are responsible for determining if safety and 
tolerability is acceptable to continue with dosing subsequent participants.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
19
Tolerability as measured by ISRs and their severity is anticipated to be the main safety 
consideration for this assessment. While no serious systemic reactions have been seen with 
LY3819253 to date, participants will be closely monitored.
If the investigator and Lilly sponsor team determine that safety and tolerability is acceptable, the 
remaining participants in the cohort will be dosed on the next day. 
Cohort 2 and the optional Cohort 3 will not include sentinel dosing.
Postdose sampling
On Days 1 through 7, participants will undergo PK sampling and safety assessment as shown in 
the SoA (Section 1.3).
4.1.3.
Outpatient follow-up
Follow-up visits will be conducted through Day 85, as shown in the SoA (Section 1.3). 
In the event a participant has suspected or confirmed SARS-CoV-2 infection, follow-up visits 
may be conducted at the participant’s home.
4.2.
Scientific Rationale for Study Design
This is the first study to evaluate a new formulation via SC route of administration in humans. 
This study will be conducted with healthy participants, rather than patients with COVID-19,
because the important biopharmaceutic questions related to the new SC route of administration, 
such as PK and tolerability, will be more efficiently investigated in the healthy human 
population. 
The 4-day safety review together with in-patient status after dosing is sufficient to detect an 
acute adverse systemic response that would preclude dose escalation.
Placebo will be used as a comparator to allow interpretation of safety and tolerability data 
following administration of LY3819253.
4.3.
Justification for Dose
Previous studies have evaluated LY3819253 IV doses in a range of 700 mg to 7000 mg and 
shown to be safe and well tolerated. 
For Study PYAG, the planned doses of LY3819253 350 mg and 700 mg have been chosen to 
evaluate PK following this new SC route of administration.
The calculated human AUC(0-∞) following a single IV dose at 700 mg was 54000 hr*µg/mL 
which is 14-fold lower than the AUC at the no-observed-adverse-effect level in the 21-day rat IV 
toxicology study [AUC(0-168hr) in rats at 500 mg/kg = 755000 hr*µg/mL].
The starting dose of 350 mg dose is expected to result in lower plasma concentrations (maximum 
drug concentration [Cmax] and area under the concentration versus time curve [AUC]) tested 
with IV dosing in previous studies with LY3819253. The concentrations following 350-mg and 
700-mg SC dosing are expected to be quantifiable for pharmacokinetic evaluation, including a
model-based estimate of bioavailability.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
20
4.4.
End of Study Definition
A participant is considered to have completed the study if he/she has completed all required
phases of the study including the last scheduled procedure shown in the SoA.
The end of the study is defined as the date of last scheduled procedure shown in the SoA for the 
last participant.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
21
5.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. are aged 18 to 60 years at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. are overtly healthy as determined by medical evaluation including medical history and 
physical examination
3. have safety laboratory test results within the reference range for the population at the
study site, or results with acceptable deviations that are judged to be not clinically 
significant by the investigator
4. have venous access sufficient to allow for blood sampling as described in this protocol 
(SoA, Section 1.3)
5. are reliable and willing to make themselves available for the duration of the study
6. are willing to follow study procedures, including having nasal or nasopharyngeal 
swabs collected as described in this protocol (SoA, Section 1.3).
Weight
7. have a BMI within the range ≥18.5 to <35 kg/m2.
Sex
8. are male or female
a.
male participants must agree to adhere to contraception restrictions
b. female participants must be of non-childbearing potential
Contraception requirements and definition of non-childbearing potential are detailed in 
Appendix 4 (Section 10.4).
Informed Consent
9. are capable of giving signed informed consent as described in Appendix 1 (Section 10.1),
which includes compliance with the requirements and restrictions listed in the ICF and in 
this protocol
5.2.
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
10. have current SARS-CoV-2 infection confirmed by nasal or nasal pharyngeal swab results 
at screening or Day -1.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
22
11. have had prior SARS-CoV-2 infection within 6 weeks before screening, confirmed by 
either previous nucleic acid-based test, or previous serology
12. have suspected current SARS-CoV-2 infection, in the opinion of the investigator, based 
on either or both of the following:
a.
a recent exposure to SARS-CoV-2, defined as:

living in the same household as a person with SARS-CoV-2;

having had direct physical contact with a person with SARS-CoV-2 (for 
example, shaking hands);

having unprotected direct contact with infectious secretions of a person with 
SARS-CoV-2 (for example, being coughed on or touching used paper tissues 
with a bare hand);

having had face-to-face contact with a person with SARS-CoV-2, within 
2 meters and for more than 15 minutes
b. signs or symptoms that, in the opinion of the investigator, are suggestive of 
infection (for example, fever, dry cough, shortness of breath, hypoxia, etc.)
13. have a history or presence of cardiovascular (including hypertension), respiratory, 
hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological 
disorders that, in the opinion of the investigator, are capable of 
a.
significantly altering the absorption, metabolism, or elimination of drugs
b. constituting a risk while taking the investigational product, or
c.
interfering with the interpretation of data
14. have clinically significant abnormal ECG results constituting a risk while taking the 
investigational product, as determined by the investigator
15. have an abnormal blood pressure as determined by the investigator. In case blood 
pressure appears to be abnormally high during the screening period, it is possible to 
repeat the measure(s) 1 time in a quiet room to avoid an exclusion due to the white coat 
effect
16. have significant allergies to humanized mAbs
17. have any of the following that are clinically significant:
a.
multiple or severe drug allergies 
b. intolerance to topical corticosteroids, or 
c.
severe posttreatment hypersensitivity reactions (including, but not limited to, 
erythema multiforme major, linear immunoglobulin A dermatosis, toxic 
epidermal necrolysis, or exfoliative dermatitis)
18. have known allergies to LY3819253, related compounds, or any components of the 
formulation
19. have had lymphoma, leukemia, or any malignancy within the past 5 years, except for 
basal cell or squamous epithelial carcinomas of the skin that have been resected with no 
evidence of metastatic disease for 3 years 
20. have had breast cancer within the past 10 years
21. show evidence of HIV infection and/or positive human HIV antibodies
22. show evidence of current hepatitis C (that is, test positive for anti-hepatitis C antibody 
with confirmed presence of HCV RNA)


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
23
Note: Patients with a previous diagnosis of hepatitis C who received antiviral therapy and 
achieved a sustained virological response may be eligible for inclusion in the study, 
provided that they have no detectable HCV RNA on the screening HCV polymerase 
chain reaction test for this protocol. A sustained virological response is defined as an 
undetectable HCV RNA level 24 weeks after completion of a full, documented course of 
an approved antiviral therapy for HCV.
Patients who have spontaneously cleared HCV infection, defined as (1) a positive HCV
antibody test and (2) a negative HCV RNA test, with no history of HCV antibody (anti-
HCV) treatment, may be eligible for inclusion in the study, provided that they have no
detectable HCV RNA at screening for this study.
23. have history of hepatitis B infection, or show evidence of current hepatitis B:
a.
test positive for hepatitis B surface antigen, and/or
b. test positive for hepatitis B core antibody and negative for hepatitis B surface 
antibody
Prior/Concomitant Therapy
24. have received treatment with biologic agents (such as mAbs, including marketed drugs) 
within 3 months or 5 half-lives (whichever is longer) prior to dosing
25. have previously completed or withdrawn from this study and have previously received 
the investigational product
26. intend to use over-the-counter medication in the 7 days prior to dose administration or 
prescription medication in the 14 days prior to dose administration, with the exception of 
hormone replacement therapy, thyroid replacement medications, vitamin and mineral 
supplements and occasional use of acetaminophen. Note that acetaminophen is NOT 
allowed within 24 hours before dosing.
Prior/Concurrent Clinical Study Experience
27. are currently enrolled in a clinical study involving an investigational product or any other 
type of medical research judged not to be scientifically or medically compatible with this 
study
28. have participated in a clinical study involving an investigational product, with last dose
within the past 30 days or 5 half-lives, whichever is longer, prior to dosing
Other Exclusions
29. are pregnant or breast feeding
30. have donated blood of more than 500 mL within the previous 3 months of study 
screening, or intend to donate blood during the course of the study
31. have an average weekly alcohol intake that exceeds 21 units per week (males) or 14 units 
per week (females), or are unwilling to stop alcohol consumption from 48 hours prior to 
admission to and while resident at the CRU (1 unit = 12 oz or 360 mL of beer; 5 oz or 
150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
32. currently smoke in excess of 10 cigarettes per day or are unwilling to abide by CRU 
smoking restrictions


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
24
33. regularly use known drugs of abuse and/or show positive findings on drug screening 
unless they were prescribed by a physician (for example, benzodiazepines).
34. are Lilly employees or are employees of a third-party organization involved with the 
study that requires exclusion of its employees are study site personnel directly affiliated 
with this study or their immediate families. Immediate family is defined as a spouse, 
biological or legal guardian, child, or sibling.
35. have tattoos or scars over the abdomen, or other factors (for example, rash or excessive 
folds of skin) that, in the investigator's opinion, would interfere with injection site 
assessments
36. in the opinion of the investigator or sponsor, are unsuitable for inclusion in the study
5.3.
Lifestyle Considerations
Reproductive and contraceptive guidance is provided in Appendix 4 (Section 10.4).
5.3.1.
Meals and Dietary Restrictions
Participants will be required to fast for at least 2 hours before being given a dose of LY3819253
(see SoA, Section 1.3). Per oral intake, should be limited to clear liquids for 4 hours prior to 
dosing. Standard meals will be administered while participants are resident at the study site.
5.3.2.
Caffeine, Alcohol, and Tobacco
Participants must abide by the CRU restriction policy regarding consumption of alcohol and 
tobacco.
5.3.3.
Activity
Participants should follow all site procedures and local guidelines for measures intended to 
prevent Covid-19 infection.
Participants should not engage in strenuous physical exercise or activities from 48 hours prior to
dosing until discharge from the study or completion of all study procedures. When certain study
procedures are in progress at the site, participants may be required to remain supine or sitting.
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study, but are 
not subsequently enrolled in the study. 
Individuals who fulfill eligibility criteria, but are not randomized within the 14-day screening 
window, may still enroll in the study provided randomization occurs within 28 days of the first 
screening visit, and provided that they repeat site procedures to confirm Covid-19 status. These 
subjects do not need to be documented as screen failures. Subjects who are eligible, but are not 
enrolled within 28 days of their initial screening visit, will need to follow re-screen procedures 
described below. 
For the purposes of assessing eligibility, screening clinical laboratory tests may be repeated if the 
result is considered likely due to a technical or handling error.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
25
Individuals who do not meet the criteria for participation in this study (screen failure) due to a 
transient minor illness or concomitant medication may be re-screened if and when they later 
meet eligibility criteria.
Re-screened participants should be assigned a new screening number. When re-screening, all
screening tests and procedures should be repeated (except safety laboratory analyses, if 
randomization is to occur within 28 days of the first screening tests). Individuals may be re-
screened once, and must sign a new ICF.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
26
6.
Study Intervention
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol.
The SC injection site(s) will be peri-umbilical. 
The study intervention will be given in the CRU by qualified CRU personnel as designated by 
the investigator. Study injections should be given by a limited number of personnel for 
consistency. 
The site of administration of each injection will be recorded; when there is more than 1 injection, 
the same site will not be used, but another quadrant will be used.
6.1.
Study Interventions Administered
Intervention
LY3819253 
Placebo
Type 
Biologic
Not applicable
Dose Formulation
solution
0.9% sodium chloride solution
Unit Dose Strength(s)
262.5 mg/2.1 mL vial (125 mg/mL)
Placebo
Planned Dosage Level(s)
Cohort 1: 350 mg
Cohort 2: 700 mg
Cohort 3: 700 mg
Not applicable
Route of Administration
SC injection
SC injection
Use
experimental
placebo
IMP and NIMP
IMP
IMP
Sourcing
From Lilly
Commercially available 0.9% sodium 
chloride solution
Packaging and Labeling
Study Intervention will be provided in 
glass vials and will be labeled 
appropriately
Commercially available 0.9% sodium 
chloride solution will be used as a 
placebo for this study
Abbreviations: IMP = investigational medicinal product; NIMP = non-investigational medicinal product; 
SC = subcutaneous.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
27
6.1.1.
Injection volumes and formulation concentrations
Injection volumes are as follows:
Cohort (LY3819253 dose)
Number of injections and volumes
Cohort 1 (350 mg)
2x 1.4 mL
Cohort 2 (700 mg)
1x 1.4 mL + 2x 2.1 mL
Optional Cohort 3 (700 mg)
2x 1.9 mL + 1x 1.8 mL*
* Doses may be adjusted based on data review during the study, as described in Section 6.6. In this event, the 
number or volume of injections, or both, will be adjusted accordingly.
The LY3819253 formulation concentration will be 125 mg/mL in all cases.
6.1.2.
In the Event of a Retrospective Positive Sterility Finding from Prepared Study
Intervention
If a positive sterility finding occurs in the terminally sterile filtered study intervention, the
participants who were dosed from the impacted batch should be contacted immediately and
undergo a full physical examination including, but not limited to, blood pressure, pulse rate, and
body temperature.
A blood sample should be collected for culture and assayed for inflammatory markers such as
C-reactive protein and elevations in white blood cell counts.
If the signs and symptoms indicated a participant has a possible infection, they will be clinically
managed, treated, and followed up until resolution. Any AEs will be recorded as appropriate.
6.2.
Preparation/Handling/Storage/Accountability
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received, and any discrepancies are reported 
and resolved before use of the study intervention.
To protect blinding, the interventions must be prepared by unblinded site personnel qualified to 
prepare study intervention who are not involved in any other study-related procedures.
Instructions for preparation will be provided by the sponsor.
Only participants enrolled in the study may receive study intervention, and only authorized site 
staff may supply or administer study intervention. 
All study intervention must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access limited 
to the investigator and authorized site staff.
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records).
Further guidance and information for the final disposition of unused study interventions are 
provided in the pharmacy manual.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
28
6.3.
Measures to Minimize Bias: Randomization and Blinding
Randomization tables for allocation of either LY3819253 or placebo will be prepared by the 
statistician or their designee.
This study will be participant- and investigator-blind.
Blinding will be maintained throughout the conduct of the study as described in the separate 
Blinding Plan.
Emergency codes will be available to the investigator. A code, which reveals the treatment group 
for a specific study subject, may be opened during the study only if the subject’s well-being 
requires knowledge of the subject’s treatment assignment.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a subject’s treatment assignment is warranted for medical management of the event. The 
subject’s safety must always be the first consideration in making such a determination. If the 
investigator decides that unblinding is warranted, it is the responsibility of the investigator to 
promptly document the decision and rationale and notify Lilly as soon as possible.
If an investigator, site personnel performing assessments, or participant is unblinded during 
dosing, the participant must be withdrawn from further study intervention. If any amount of 
study intervention was administered, follow procedures according to the SoA, as described in 
Section 7.1.
Upon completion of the study, all codes must be returned to Lilly or its designee.
6.4.
Study Intervention Compliance
Participants will receive study intervention directly from the investigator or designee, under 
medical supervision. The date and time of dosing in the clinic will be recorded in the source 
documents and in the CRF. The dose of study intervention and study participant identification 
will be confirmed at the time of dosing by a member of the study site personnel other than the 
person administering the study intervention.
6.5.
Concomitant Therapy
All concomitant medications, whether prescription or over the counter, used at baseline and/or 
during the course of the trial, must be recorded on the Concomitant Medication eCRF.
Participants will be instructed to consult the investigator or other appropriate study personnel at 
the study site before taking any new medications or supplements during the study.
In general, concomitant medication should be avoided. Use of chronic, stable doses of hormone 
replacement therapy, thyroid replacement medications, or vitamin and mineral supplements is 
allowed. 
Acetaminophen (1 g, maximum 3 g/24 hours) may be administered at the discretion of the 
investigator for treatment of headache, etc. However, acetaminophen may not be given within 
24 hours before dosing.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
29
If the need for concomitant medication (other than acetaminophen) arises, inclusion or 
continuation of the participant may be at the discretion of the investigator after consultation with 
a Lilly clinical pharmacologist or CRP. 
Any medication used during the course of the study must be documented.
All vaccines are prohibited until study completion.
6.6.
Dose Modification
Depending on the results of a given trial-level safety review, the dose of the subsequent cohort(s) 
may be adjusted. Because these adjustments to dose levels are allowable changes permitted by 
the protocol, they would not require a protocol amendment.
6.6.1.
Dose-Escalation Criteria
Data will be evaluated on an ongoing basis.
After at least 4 participants assigned to LY3819253 have completed Day 4 in a given cohort, all 
safety data up to this cutoff date will be reviewed to determine whether the next cohort can be
randomized after agreement between Lilly’s medical monitor and the investigator. Safety and 
tolerability data will be the primary criteria guiding dose escalation.
The investigator and the Lilly sponsor team are responsible for determining any dose decisions. 
The investigator(s) will remain blinded and the Lilly sponsor team will be unblinded during these 
reviews. All available data from previous cohorts will be reviewed.
If temporary stopping criteria are met (Section 6.6.3), dosing will be temporarily halted and no 
further participants will be dosed until a full safety review of the study has taken place.
6.6.2.
Access to Data during the Study
A limited number of unblinded Lilly study team personnel will have access to safety and/or PK 
data during the study.
6.6.3.
Temporary Stopping Criteria 
Dosing will be temporarily halted, and no further participants will be dosed until safety data 
available at that point have been reviewed:

pending discussion between the investigator and sponsor, if 3 or more participants 
develop AEs that are considered to be related to study treatment;

if 1 or more participants develop AEs that are considered to be related to study treatment
and that are serious (SAEs) or graded as severe.
This table describes the location of AE-related information in this protocol.
Topic
Location
Definition of AEs 
Section 10.3.1
Assessment of Intensity/Severity 
Section 10.3.3


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
30
Changes to the planned dosing schedule must be appropriately documented and communicated 
with the study personnel and the IRB/IEC before dosing continues.
6.7.
Intervention after the End of the Study
Not applicable.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
31
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
These sections describe reasons for a participant’s

permanent or temporary discontinuation of study intervention, or

discontinuation (withdrawal) from the study.
Discontinuation of the trial as a whole is handled as part of regulatory, ethical, and trial oversight 
considerations in Appendix 1 (Section 10.1).
7.1.
Discontinuation of Study Intervention
Not applicable.
7.2.
Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study
●
at any time at his/her own request 
●
at the request of his/her designee (for example, parents or legal guardian)
●
at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons
●
if the participant becomes pregnant during the study 
●
if enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be scientifically or 
medically compatible with this study
At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA. See SoA for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. The 
participant will be permanently discontinued both from the study intervention and from the study 
at that time.
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, he/she may request destruction of any samples taken and not tested, 
and the investigator must document this in the site study records.
7.2.1.
Discontinuation of Inadvertently Enrolled Participants
If the sponsor or investigator identifies a participant who did not meet enrollment criteria and 
was inadvertently enrolled, then the participant should be discontinued from study treatment and 
safety follow-up should be performed as outlined in

Section 1.3 (SoA), 

Section 8.2 (Safety Assessments), and 

Section 8.3 (Adverse Events and Serious Adverse Events).


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
32
7.3.
Lost to Follow up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel are expected to 
make diligent attempts to contact participants who fail to return for a scheduled visit or were 
otherwise unable to be followed up by the site.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
33
8.
Study Assessments and Procedures
Study procedures and their timing are summarized in the SoA (Section 1.3). 
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The investigator or designee will maintain a screening log to record 
details of all participants screened and to confirm eligibility or record reasons for screening 
failure, as applicable.
8.1.
Efficacy Assessments
Not applicable.
8.2.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA.
8.2.1.
Physical Examinations
A complete physical examination will include, at a minimum, assessments of the cardiovascular, 
respiratory, gastrointestinal, dermatological, and neurological systems. Height and weight will 
also be measured and recorded at screening.
Investigators should pay special attention to clinical signs related to COVID-19.
8.2.2.
Vital Signs
For each participant, vital sign measurements should be conducted according to the SoA
(Section 1.3). Additional vital signs may be measured during each study period at the 
investigator’s judgment. Blood pressure and pulse rate should be measured after at least 
5 minutes supine.
Orthostatic vital signs should be assessed, if possible, during any AE of dizziness or 
posture-induced symptoms. If orthostatic measurements are required, participants should be 
supine for at least 5 minutes and stand for at least 3 minutes. If the participant feels unable to 
stand, supine vital signs only will be recorded.
Additional vital signs may be measured during each study period, if warranted.
8.2.3.
Electrocardiograms
A single, local, 12-lead ECG will be obtained as shown in the SoA, using an ECG machine that 
automatically calculates the heart rate and measures pulse rate, QRS, QT, and corrected QT 
intervals. Additional ECG readings may occur at investigator discretion.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
34
8.2.4.
Clinical Safety Laboratory Assessments
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and to the 
SoA for the timing and frequency.
All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted in 
accordance with the laboratory manual and the SoA.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents.
If laboratory values from nonprotocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (for example, SAE or AE or dose modification), then the 
results must be recorded in the CRF.
8.2.5.
Injection Site Reaction Assessment
Injection site assessments using the ISR CRF, VAS if required (see below), and an exploratory 
tool (Scarletred) will be performed at times specified in the SoA (Section 1.3). 
Injection site pain assessments are part of the solicited and spontaneous ISR assessments. The 
baseline assessment, and all positive responses of pain from then on, will require an additional 
assessment using the Pain VAS.
As there are multiple injections for each dose, ISR assessments will be done for each injection.
Manifestations of a local ISR may include erythema, induration, pain, pruritus, and edema. 
Injection site findings will be captured on the eCRF. 
Injection site reactions, if recorded as a result of the prespecified (or solicited) assessment, will 
be recorded as AEs only if they qualify as SAEs. 
If a spontaneous (or unsolicited) ISR is reported by a participant or investigator, the ISR CRF 
will be used to capture additional information about this reaction (for example, degree and area 
of erythema) at additional visits until resolution of the event.
The VAS is a well-validated tool (Williamson and Hoggart 2005) to assess injection site pain; it 
is presented as a 100-mm line anchored by verbal descriptors, usually “no pain” and “worst 
imaginable pain.” The participant will be asked to rate any pain at the injection site on a scale of 
0 to 100 on the line, as soon as possible following each injection.
In addition, the exploratory tool (Scarletred) will be used to acquire exploratory ISR data at each 
of the time points where the ISR data is being collected by administration of the ISR CRF. 
Failure to take this assessment at any of the indicated time points will not result in a protocol 
deviation.
8.3.
Adverse Events and Serious Adverse Events
Adverse events will be reported by the participant.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
35
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study intervention or study.
Discontinuation information is in Section 7.
Detailed AE definitions and procedures are in Section 10.3.
8.3.1.
Time Period and Frequency for Collecting AE and SAE Information
All AEs and SAEs will be collected from the time of signing of the ICF until participation in the 
study has ended.
Adverse events that begin before the start of study intervention, but after signing of the ICF will 
be recorded on the AE CRF.
Although all AEs after signing the ICF are recorded by the site in the CRF/electronic data entry, 
SAE reporting to sponsor begins after the participant has signed the ICF and has received study 
intervention. However, if an SAE occurs after signing the ICF, but prior to receiving study 
intervention, it needs to be reported within the SAE reporting time frame if it is considered 
reasonably possibly related to study procedures.
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.3, Appendix 3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation (Day 85). However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the investigator must promptly 
notify the sponsor.
8.3.2.
Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.3, Appendix 3
Care will be taken not to introduce bias while detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about AE
occurrences.
8.3.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed up until resolution, stabilization, the 
event is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Further information on follow-up procedures is provided in Section 10.3, Appendix 3.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
36
8.3.4.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a study 
intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB/IEC, and investigators.
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (for example, summary or listing of SAEs) from the sponsor will review and 
then file it with the IB, and will notify the IRB/IEC, if appropriate according to local 
requirements.
8.3.5.
Pregnancy
Details of all pregnancies in female participants and female partners of male participants will be 
collected after the start of study intervention and until at least 5 months after the last dose.
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Section 10.4, Appendix 4
Abnormal pregnancy outcomes (for example, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs.
8.3.6.
Hypersensitivity Reactions
Many drugs, but particularly biologic agents, carry the risk of systemic hypersensitivity 
reactions. If such a reaction occurs, additional details describing each symptom should be 
provided to the sponsor in the Hypersensitivity/Anaphylactic/Infusion-Related Reaction CRF.
Sites should have appropriately trained medical personnel and appropriate medical equipment 
available when study participants are receiving intervention. It is recommended that participants 
who experience a systemic hypersensitivity reaction be treated per national and international 
guidance (Lieberman et al. 2015; Simons et al. 2015).
In the case of generalized urticaria or anaphylaxis, additional blood and urine samples should be 
collected as described in Section 10.6, Appendix 6, “Recommended Laboratory Testing for 
Hypersensitivity Events”. Laboratory results are provided to the sponsor via the central 
laboratory.
8.3.7.
SARS-CoV-2 Infection
Site procedures for participant management will be followed in the event of a suspected 
SARS-CoV-2 infection during the study.
A nasopharyngeal swab will be taken on Day 1 and shipped to the sponsor. This is for research 
purposes, such as viral sequencing.
In addition, SARS-CoV-2 point-of-care tests may be performed at specific timepoints during the 
study at the discretion of the investigator. Every time such a point-of-care test is performed post 


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
37
baseline, an additional nasal swab sample may be collected in parallel, for research purposes 
such as viral sequencing. This research swab sample will be shipped to the sponsor only if the 
point-of-care test is positive. If the point-of-care test is negative, the research swab sample 
should be discarded.
8.3.8. Product Complaints
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
trial intervention. 
The sponsor collects product complaints on study interventions used in clinical studies to ensure 
the safety of study participants, monitor quality, and to facilitate process and product 
improvements.
Participants will be instructed to contact the investigator as soon as possible if they have a 
complaint or problem with the study intervention so that the situation can be assessed.
NOTE: Any AEs or SAEs that are associated with a product complaint will follow the processes 
outlined in Section 8.3.3 and Section 10.3, Appendix 3, of the protocol.
Time Period for Detecting Product Complaints
Product complaints that result in an AE will be detected, documented, and reported to the 
sponsor during all periods of the study in which the study intervention is used.
If the investigator learns of any product complaint at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to the study 
intervention, the investigator will promptly notify the sponsor.
Prompt Reporting of Product Complaints to Sponsor
Product complaints will be reported to the sponsor within 24 hours after the investigator becomes 
aware of the complaint.
The Product Complaint Form will be sent to the sponsor by a method designated by the sponsor.
Follow-up of Product Complaints
Follow-up applies to all participants, including those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the product complaint.
New or updated information will be recorded on the originally completed form with all changes 
signed and dated by the investigator and submitted to the sponsor.
8.4.
Treatment of Overdose
For the purposes of this study, an overdose of LY3819253 is considered any dose higher than the 
dose assigned through randomization. In case of suspected overdose, participants should be 
monitored for any signs or symptoms of adverse reactions or effects, and supportive care should 
be provided as necessary.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
38
8.5.
Pharmacokinetics
Venous blood samples will be collected as specified in the SoA for determination of serum 
concentrations of LY3819253 used to evaluate the PK for LY3819253.
A maximum of 5 samples may be collected at additional time points during the study, if 
warranted and agreed upon between the investigator and the sponsor.
Instructions for the collection and handling of biological samples will be provided by Lilly. 
Site personnel will record

the date and time (24-hour clock time) of investigational drug administration, and

the date and time (24-hour clock time) of each PK sample.
It is essential that the times are recorded accurately.
8.5.1.
Bioanalytical
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor. Concentrations of LY3819253 will be assayed using a validated 
bioanalytical method. Analyses of samples collected from placebo-treated subjects are not 
planned.
Sample retention is described in Appendix 1, Section 10.1.10. Remaining samples used for PK 
may be pooled and used for exploratory metabolism or bioanalytical method experiments as 
deemed appropriate.
8.6.
Pharmacodynamics
Pharmacodynamic parameters will not be evaluated in this study.
8.7.
Genetics
A whole blood sample will be collected for pharmacogenetic analysis where local regulations 
allow. 
See Section 10.2, Clinical Laboratory Tests, and Section 1.3 SoA for sample collection 
information. 
See Section 10.5 for genetic research, custody, and sample retention information.
8.8.
Biomarkers
Serum samples for exploratory biomarker research will be collected at the time specified in the 
SoA where local regulations allow. 
Samples will be stored and analysis may be performed on biomarkers thought to play a role in 
immune system-related responses to viral infection or administration of LY3819253 including, 
but not limited to, immune pathways or serum analytes to evaluate their association with
LY3819253 administration.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
39
Samples may be used for research to develop methods, assays, prognostics, and/or companion 
diagnostics related to the intervention target (spike protein), pathways associated with disease, 
and/or the mechanism of action of the study intervention.
Swab samples taken during the study may be used for research purposes, such as viral 
sequencing.
Sample retention is described in Section 10.1.10.
8.9.
Immunogenicity Assessments
Visits and times
At the visits and times specified in the SoA, predose venous blood samples will be collected to 
determine antibody production against LY3819253. The actual date and time (24-hour clock 
time) of each sample collection will be recorded. To aid interpretation of these results, the 
immunogenicity sampling timepoints all coincide with a PK sampling timepoint.
Sample collection, handling, and use
Instructions for the collection and handling of blood samples will be provided by the sponsor.
Immunogenicity will be assessed using a validated assay designed to detect ADAs in the 
presence of LY3819253 at a laboratory approved by the sponsor. Antibodies may be further 
characterized for their ability to neutralize the activity of LY3819253.
Sample retention
Sample retention is described in Section 10.1.10.
8.10.
Health Economics
Not applicable.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
40
9.
Statistical Considerations
9.1.
Statistical Hypotheses
Formal statistical hypothesis testing is not planned. Therefore, adjustments for multiple testing 
do not apply.
9.2.
Sample Size Determination
A maximum of 36 participants will be enrolled to study intervention with the intention that at 
least 6 participants randomized to LY3819253 have sufficient evaluable data in each of Cohorts 
1 and 2.
This would mean at least 12 participants with evaluable data if Cohorts 1 and 2 only are enrolled.  
If the optional Cohort 3 is used, the total number of participants in the study with evaluable data 
will depend on enrollment numbers for that cohort.
The sample size is not powered on the basis of statistical hypothesis testing. However, based on 
an assumption of 40% CV for between subject variability in a PK parameter of interest, 
6 subjects on active treatment per cohort may provide approximately 70% chance to ensure that a 
PK parameter’s 90% confidence interval falls within (0.7, 1.43) over the corresponding 
geometric mean, such as AUC(0-∞).
A participant will be considered evaluable when the participant completes up to 29 days of study 
procedures. When a participant does not complete up to 29 days of study procedures, the sponsor 
will be consulted if the participant will need to be replaced.
9.3.
Populations for Analyses
The following populations are defined:
Population
Description
Entered
All participants who sign the ICF
Enrolled/Intent-to-Treat
All participants assigned to treatment, regardless of whether they 
received study treatment, or if they took the correct treatment. 
Participants will be analyzed according to the treatment group to 
which they were assigned.
Safety
All participants randomly assigned to study intervention and who 
received study intervention. Participants will be analyzed 
according to the intervention they actually received.
Pharmacokinetic Analysis
All treated participants who received study intervention and have 
sufficient evaluable PK samples.
Abbreviations: ICF = informed consent form; PK = pharmacokinetic.
9.4.
Statistical Analyses
Statistical analysis of this study will be the responsibility of sponsor or its designee.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
41
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.1, unless otherwise 
stated, and all confidence intervals will be given at a 2-sided 90% level.
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the SAP and the clinical study report. Additional exploratory analyses of the data will be 
conducted as deemed appropriate.
The SAP will be finalized prior to unblinding and it will include a more technical and detailed 
description of the statistical analyses described in this section. This section is a summary of the 
planned statistical analyses of the most important endpoints including primary and key secondary 
endpoints.
9.4.1. General Considerations
Statistical analyses will be performed using SAS® Version 9.4 or higher.
For continuous measures, summary statistics will include sample size, mean, standard deviation, 
minimum, median, and maximum. For categorical measures, summary statistics will include the 
sample size, frequency count, and percentage.
For all safety analyses, baseline will be defined as the last evaluable value before dosing.
9.4.2.
Primary Endpoint: Pharmacokinetics
Pharmacokinetic parameter estimates for LY3819253 will be calculated by standard 
noncompartmental methods of analysis.
The primary parameters for analysis will be AUC(0-∞) of LY3819253 following SC 
administration. Other noncompartmental parameters, such as half-life, tmax, apparent clearance, 
and volume of distribution following SC administration may be reported.
In addition to noncompartmental analysis, the data may be combined with data from other 
studies to be analyzed using non-linear mixed-effect modelling of the PK data. This model will 
enable estimation of mean and variability (variances) of LY3819253 PK parameters, including 
bioavailability, following SC administration and to investigate potential covariates explaining 
that variability.
9.4.3.
Secondary Endpoint: Safety
9.4.3.1.
Clinical Evaluation of Safety
All investigational product and protocol procedure AEs will be listed, and if the frequency of 
events allows, safety data will be summarized using descriptive methodology.
The incidence of AEs for each treatment will be presented by severity and by association with 
investigational product as perceived by the investigator. Adverse events reported to occur prior 
to randomization will be distinguished from those reported as new or increased in severity during 
the study. Each AE will be classified by the most suitable term from the medical regulatory 
dictionary.
All SAEs will be reported.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
42
9.4.3.2.
Statistical Evaluation of Safety
Safety parameters that will be assessed include safety laboratory parameters and vital sign
measurements. The parameters will be listed, and summarized using standard descriptive 
statistics. Additional analysis will be performed if warranted upon review of the data.
9.4.4.
Exploratory Endpoint: Injection Site Reaction Assessments
Injection site reactions will be listed and may be summarized by dose if data warrant. 
9.5.
Interim Analyses 
No interim analyses are planned for this study. If an unplanned interim analysis is deemed 
necessary, the Lilly CP, CRP/investigator, or designee will consult with the appropriate medical 
director or designee to determine if it is necessary to amend the protocol.
9.6.
Data Monitoring Committee (DMC)
Not applicable.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
43
10.
Supporting Documentation and Operational Considerations
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
10.1.1.
Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines

Applicable ICH GCP Guidelines, and

Applicable laws and regulations.
The protocol, protocol amendments, ICF, IB, and other relevant documents (for example, 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and approved 
by the IRB/IEC before the study is initiated.
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC

Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures, and

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC, and all other applicable local regulations.
Study sites are compensated for participation in the study as detailed in the clinical trial 
agreement.
10.1.2.
Informed Consent Process
The investigator or their representative will explain the nature of the study, including the risks 
and benefits, to the participant or their legally authorized representative and answer all questions 
regarding the study.
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representative will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act requirements, where applicable, and the IRB/IEC or study center.
The medical record must include a statement that written informed consent was obtained before 
the participant was entered in the study and the date the written consent was obtained. The 


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
44
authorized person obtaining the informed consent and, if applicable, the individual designated to 
witness a verbal consent, must also sign the ICF.
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study.
A copy of the ICF(s) must be provided to the participant or the participant’s legally authorized 
representative and is kept on file.
10.1.3.
Data Protection
Participants will be assigned a unique identifier by the sponsor. Any participant records, datasets
or tissue samples that are transferred to the sponsor will contain the identifier only; participant 
names or any information that would make the participant identifiable will not be transferred.
The participant must be informed that their personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent.
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
The sponsor has processes in place to ensure data protection, information security, and data 
integrity. These processes include appropriate contingency plan(s) for appropriate and timely 
response in the event of a data security breach.
10.1.4.
Dissemination of Clinical Study Data
A clinical study report will be provided for this study and a summary of study information 
provided on publicly available websites.
10.1.5.
Data Quality Assurance
Investigator responsibilities
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (for example, laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. Source data may include laboratory tests, medical records, and 
clinical notes.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.
Data monitoring and management
The Monitoring Plan includes


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
45

monitoring details describing strategy, for example, risk-based initiatives in operations 
and quality such as risk management and mitigation strategies and analytical risk-based 
monitoring 

methods 

responsibilities 

requirements 

handling of noncompliance issues, and 

monitoring techniques.
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data. The sponsor assumes accountability for actions delegated to other 
individuals (for example, contract research organizations).
Study monitors will perform ongoing source data verification to confirm that data entered in the 
CRF by authorized site personnel are accurate, complete, and verifiable from source documents. 
They will also ensure that the safety and rights of participants are being protected, and that the 
study is being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records retention and audits
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for the time period outlined in the clinical trial agreement unless 
local regulations or institutional policies require a longer retention period.
No records may be destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without written notification 
to the sponsor.
The sponsor or its representatives will periodically check a sample of the participant data 
recorded against source documents at the study site. The study may be audited by the sponsor or 
its representatives, and by regulatory agencies at any time. Investigators will be given notice 
before an audit occurs.
Data Capture System
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor.
An EDC system will be used in this study for the collection of CRF data. The investigator 
maintains a separate source for the data entered by the investigator or designee into the 
sponsor-provided EDC system. The investigator is responsible for the identification of any data 
to be considered source and for the confirmation that data reported are accurate and complete by 
signing the CRF.
Data collected via the sponsor-provided data capture systems will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture systems. Prior to decommissioning, the investigator will receive an archival 
copy of pertinent data for retention.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
46
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports will be provided to the investigator for review 
and retention. Data will subsequently be transferred from the central vendor to the sponsor data 
warehouse.
Data from complaint forms submitted to the sponsor will be encoded and stored in the global 
product complaint management system.
10.1.6.
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The investigator may need to 
request previous medical records or transfer records, depending on the study. Current medical 
records must be available.
The definition of what constitutes source data can be found in Section 10.1.5.
10.1.7.
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and enough notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to

failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor’s procedures, or GCP guidelines

inadequate recruitment of participants by the investigator, or

discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participants and assure 
appropriate participant therapy and/or follow-up.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
47
10.1.8.
Publication Policy
In accordance with the sponsor’s publication policy, the results of this study will be submitted 
for publication by a peer-reviewed journal if the results are deemed to be of significant medical 
importance.
10.1.9.
Investigator Information
Physicians with a specialty in infectious disease, critical care, or pulmonary disease may
participate as investigators.
10.1.10.
Long-Term Sample Retention
Sample retention enables use of new technologies, response to regulatory questions, and 
investigation of variable response that may not be observed until later in the development of the 
intervention or after the intervention becomes commercially available.
This table describes the retention period for potential sample types.
Sample Type
Custodian
Retention Period after Last Participant Visit
Pharmacogenetics sample
Sponsor or designee
up to 15 years
Exploratory Biomarker Samples
Sponsor or designee
up to 15 years
PK sample
Sponsor or designee
up to 2 years
Immunogenicity (ADA) sample
Sponsor or designee
up to 15 years


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
48
10.2.
Appendix 2: Clinical Laboratory Tests

Clinical laboratory tests will be performed according to the SoA. Additional details are 
provided in the following table for specific laboratory tests.

Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations.

Pregnancy testing will be performed according to the SoA.

The following table describes when the local or central laboratory will be used.

If the local laboratory results are used to make either a study intervention decision or 
response evaluation, the results must be recorded in the CRF.

Laboratory results that could unblind the study will not be reported to study sites or other 
blinded personnel.

Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol.

Investigators must document their review of each laboratory safety report.
Clinical Laboratory Tests
Comments
Hematology
Assayed by local laboratory
Hemoglobin
Hematocrit
Erythrocyte count (RBCs - red blood cells)
Mean cell volume 
Mean cell hemoglobin
Leukocytes (WBCs - white blood cells) 
Differential
Neutrophils, segmented
Lymphocytes
Monocytes
Eosinophils
Basophils
Platelets
Cell morphology (RBC and WBC)
Clinical Chemistry
Assayed by local laboratory
Sodium
Potassium
Chloride
Bicarbonate
Total bilirubin
Direct bilirubin
Record on Day -1 and repeat if significantly abnormal value
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Blood urea nitrogen (BUN)
Creatinine 


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
49
Clinical Laboratory Tests
Comments
Uric acid
Record on Day -1 and repeat if significantly abnormal value
Total protein
Albumin
Calcium
Phosphorus
Random glucose
Calculations
Completed locally
Hepatitis B surface antigen
Hepatitis B surface antibody
Hepatitis B core antibody (HBcAb) 
Hepatitis C antibody
HIV
SARS-Cov-2 viral infection determination
Local laboratory
SARS-Cov-2 point of care
SARS-Cov-2 nasal or nasopharyngeal sample for 
research purposes
Day 1 sample assayed by Lilly-designated laboratory. Subsequent 
samples sent to Lilly-designated laboratory for analysis only if the 
SARS-Cov-2 point of care test performed in parallel is positive 
SARS-Cov-2 serology
Assayed by Lilly-designated laboratory.
Urinalysis
Assayed by local laboratory
Specific gravity
pH
Protein
Glucose
Ketones
Bilirubin
Urobilinogen
Blood
Nitrite
Microscopy
If dipstick test is abnormal.
Hormones (female)
Assayed by local laboratory.
Serum pregnancy 
Urine pregnancy
Ethanol/drug screening
Assayed by local laboratory.
Urine or breath ethanol screen
Urine drug screen
Pharmacokinetic (PK) Samples
Assayed by Lilly-designated laboratory. 
Results will not be provided to the study sites.
Pharmacogenetic sample
Assayed by Lilly-designated laboratory. 
Results will not be provided to the study sites.
Exploratory Biomarker Serum Sample
Assayed by Lilly-designated laboratory. 
Results will not be provided to the study sites.
Abbreviations: HIV = human immunodeficiency virus; SARS-Cov-2 = severe acute respiratory syndrome 
coronavirus 2.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
50
10.2.1.
Blood Sampling Summary
This table summarizes the approximate number of venipunctures and blood volumes for all 
blood sampling (screening, safety laboratories, and bioanalytical assays) during the study. 
Purpose
Blood Volume per 
Sample (mL)
Number of Blood 
Samples
Total Volume 
(mL)
Screening testsa
45
1
45
Clinical laboratory testsa
15
SARS-CoV-2 serology
10
5
50
Pharmacokinetics 
4
12
48
Immunogenicity
10
5
50
Blood discard for cannula patency
1
5
5
Pharmacogenetics
10
1
10
Serum for exploratory biomarkers
10
6
60
Total
268
Total for clinical purposes (rounded up to nearest 10 mL)
270
a
Additional samples may be drawn if needed for safety purposes.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
51
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
10.3.1.
Definition of AE
AE Definition
An AE is any untoward medical occurrence in a clinical study participant temporally 
associated with the use of study intervention, whether or not considered related to the study 
intervention.
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (for example, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not related to 
progression of underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdose should be reported regardless of sequelae.
Events NOT Meeting the AE Definition

Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical 
study is to establish treatment effect.

The following study-specific clinical events related to COVID-19 are exempt from AE
reporting unless the investigator deems the event to be related to the administration of 
intervention:
o
Hypoxemia due to COVID-19 requiring supplemental oxygen;
o
Hypoxemia due to COVID-19 requiring non-invasive ventilation or high flow 
oxygen devices;


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
52
o
Respiratory failure due to COVID-19 requiring invasive mechanical ventilation 
or ECMO

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease under study, unless 
judged by the investigator to be more severe than expected for the participant’s 
condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure, such as endoscopy or appendectomy. The condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.3.2.
Definition of SAE
Please note: If an event is not an AE per definition above, then it cannot be an SAE.
An SAE is defined as any AE that:
a.
Results in death
b.
Is immediately life-threatening
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization

In general, hospitalization signifies that the participant has been admitted to hospital
for >”23 hour observation” and/or treatment that would not have been appropriate in 
the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other 
serious criteria, the event is serious. When in doubt as to whether “hospitalization” 
occurred or was necessary, the AE should be considered serious.

Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.
d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
53
and accidental trauma (for example, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered 
serious.
o
Examples of such events include intensive treatment in an emergency room or 
at home for allergic bronchospasm, blood dyscrasias or convulsions that do not 
result in hospitalization, or development of drug dependency or drug abuse.
10.3.3.
Recording and Follow-Up of AE and/or SAE
AE and SAE Recording
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (for example, hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event.
The investigator will then record all relevant AE/SAE information in the CRF.
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Sponsor or designee in lieu of completion of the AE/SAE CRF page.
There may be instances when copies of medical records for certain cases are requested by 
Sponsor or designee. In this case, all participant identifiers, except the participant number, will 
be redacted on the copies of the medical records before submission to Sponsor or designee.
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity/Severity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to one of the following categories.
Mild: Mild symptoms causing no or minimal interference with usual social and functional 
activities, with intervention not indicated.
Moderate: Moderate symptoms causing greater than minimal interference with usual 
social and functional activities, with intervention indicated.
Severe: Severe symptoms causing inability to perform usual social and functional 
activities, with intervention or hospitalization indicated.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
54
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE.
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.
The investigator will use clinical judgment to determine the relationship.
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study intervention administration will be 
considered and investigated.
The investigator will also consult the IB and/or Product Information, for marketed products, in 
his/her assessment.
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.
There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report to Sponsor or designee. However, it is very 
important that the investigator always assess the causality for every event before the initial 
transmission of the SAE data to Sponsor or designee.
The investigator may change their opinion of causality after consideration of follow-up 
information and send a SAE follow-up report with the updated causality assessment.
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.
Follow-up of AEs and SAEs
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Sponsor or 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals.
If a participant dies during participation in the study or during a recognized follow-up period, 
the investigator will provide the sponsor or designee with a copy of any post-mortem findings 
including histopathology. 
New or updated information will be recorded in the originally completed CRF.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
55
The investigator will submit any updated SAE data to Sponsor or designee within 24 hours of 
receipt of the information.
10.3.4.
Reporting of SAEs
SAE Reporting via Paper CRF
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the sponsor.
Initial notification via telephone does not replace the need for the investigator to complete and 
sign the SAE CRF pages within the designated reporting time frames.
Contacts for SAE reporting can be found in site training documents.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
56
10.4.
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information
10.4.1.
Women
Only women of non-childbearing potential may participate in this study.
Definitions:
Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
If fertility is unclear (for example, amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should be 
considered.
Woman Not of Childbearing Potential
Women in the following categories are not considered woman of childbearing potential
1. Premenarchal
2. Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than the above, 
(for example, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation can come from the site personnel’s: review of the participant’s medical 
records, medical examination, or medical history interview.
3. Postmenopausal female is defined as, women with

12 months of amenorrhea for women >55 years, with no need for follicle-stimulating 
hormone

12 months of amenorrhea for women >40 years with FSH ≥40 mIU/mL and no other 
medical condition such as anorexia nervosa and not taking medications during the 
amenorrhea (for example, oral contraceptives, hormones, gonadotropin-releasing 
hormone, anti-estrogens, selective estrogen receptor modulators, or chemotherapy 
that induced amenorrhea)
10.4.2.
Men
Men, regardless of their fertility status, must agree to either remain abstinent (if this is their 
preferred and usual lifestyle) or use condoms as well as 1 additional highly effective method of 
contraception (less than 1% failure rate) or effective method of contraception with nonpregnant 
women of childbearing potential partners for the duration of the study and until their plasma 
concentrations are below the level that could result in a relevant potential exposure to a possible 
fetus, predicted to be 140 days after the last dose.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
57
Men with pregnant partners should use condoms during intercourse for the duration of the study 
and until the end of estimated relevant potential exposure to the fetus, predicted to be 140 days 
after the last dose.
Acceptable Methods of Contraception for Female Partners of Male Participants
Highly effective methods of contraception (less than 1% failure rate) comprise, but are not 
limited to

combination oral contraceptives

implanted contraceptives, or 

intrauterine devices. 
Effective methods of contraception comprise but are not limited to diaphragms with spermicide 
or cervical sponges.
Men and their partners may choose to use a double–barrier method of contraception that must 
include use of a spermicide.
10.4.3.
Collection of Pregnancy Information
Male participants with partners who become pregnant
The investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive study intervention.
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the investigator will record pregnancy information on the appropriate form and submit it to the 
sponsor within 24 hours of learning of the partner’s pregnancy.
The female partner will also be followed up to determine the outcome of the pregnancy.
Information on the status of the mother and child will be forwarded to the sponsor. Generally, the 
follow-up will be no longer than 6 to 8 weeks following the estimated delivery date. Any 
termination of the pregnancy will be reported including fetal status (presence or absence of 
anomalies) and indication for the procedure.
Female participants who become pregnant
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a participant’s 
pregnancy.
The participant will be followed up to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate, and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, including 
fetal status (presence or absence of anomalies) or indication for the procedure.
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
58
A spontaneous abortion (occurring at <20 weeks gestational age) or still birth (occurring at >20
weeks gestational age) is always considered to be an SAE and will be reported as such. 
Any poststudy pregnancy-related SAE considered reasonably related to the study intervention by 
the investigator will be reported to the sponsor as described in Section 8.3.4. While the 
investigator is not obligated to actively seek this information in former study participants, he or 
she may learn of an SAE through spontaneous reporting.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
59
10.5.
Appendix 5: Genetics
Sample collection information is found in Appendix 2, Section 10.2.
Genetic variation may impact a participant’s response to study intervention, susceptibility to, and 
severity and progression of disease. Variable response to study intervention may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease being 
treated. Therefore, where local regulations and IRB/IEC allow, a blood sample will be collected 
for DNA analysis from consenting participants.
DNA samples may be used for research related to SARS-CoV-2 and related diseases. They may 
also be used to develop tests/assays including diagnostic tests related to LY3819253 or 
SARS-CoV-2. Genetic research may consist of the analysis of 1 or more candidate genes or the 
analysis of genetic markers throughout the genome as appropriate.
The samples may be analyzed as part of a multistudy assessment of genetic factors involved in 
the response to LY3819253 or study interventions of this class to understand study disease or 
related conditions.
The results of genetic analyses may be reported in the clinical study report or in a separate study 
summary.
The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality.
The samples will be retained at a facility selected by the sponsor or its designee while research 
on SARS-CoV-2 continues, but no longer than 15 years or other period as per local 
requirements.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
60
10.6.
Appendix 6: Recommended Laboratory Testing for Hypersensitivity 
Events
Laboratory assessments should be performed if the participant experiences generalized urticaria 
or if anaphylaxis is suspected.

Collect sample after the participant has been stabilized, and within 1 to 2 hours of the 
event; however, samples may be obtained as late as 12 hours after the event as analytes 
can remain altered for an extended period of time. Record the time at which the sample 
was collected.

Obtain a follow-up sample after approximately 4 weeks.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
61
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 anti-drug 
antibodies 
(immunogenicity/ADA)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
LY3819253 concentrations 
(PK)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Tryptase
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Urine N-methylhistamine testing is performed in addition to 
tryptase testing. Collect the first void urine following the event. 
Collect a follow-up urine sample after approximately 4 weeks.
Note: If a tryptase sample is obtained more than 2 hours after the 
event (that is, within 2 to 12 hours), or is not obtained because more 
than 12 hours have lapsed since the event, collect a urine sample for 
N-methylhistamine testing. 
N-methylhistamine
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Drug-specific IgE
Will be performed if a validated assay is available.
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Basophil activation test
Will be performed if a validated assay is available.
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
NOTE: The basophil activation test is an in vitro cell based assay 
that only requires a serum sample. It is a surrogate assay for drug 
specific IgE, but is not specific for IgE.
Complement (C3, C3a, and 
C5a)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Cytokine panel
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Abbreviations: IgE = immunoglobulin E; PK = pharmacokinetic.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
62
10.7.
Appendix 7: Abbreviations
Term
Definition
ADE
antibody-dependent enhancement
AE
adverse event
AUC
area under the curve
AUC(0-) 
AUC(0-∞) area under the concentration versus time curve from zero to infinity
CFR
Code of Federal Regulations
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
Compliance
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements.
COVID-19
coronavirus disease-2019
CRF
case report form
CRP
clinical research physician: Individual responsible for the medical conduct of the study.
Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician or other medical officer.
CRU
clinical research unit
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
enroll
The act of assigning a participant to a treatment. Participants who are enrolled in the 
study are those who have been assigned to a treatment.
Enter
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives.
FDA
United States Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
good clinical practice
HCV
hepatitis C virus
HIV
human immunodeficiency virus


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
63
Term
Definition
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
independent ethics committee
Informed consent
A process by which a participant voluntarily confirms his or her willingness to 
participate in a particular study, after having been informed of all aspects of the study 
that are relevant to the participant’s decision to participate. Informed consent is 
documented by means of a written, signed and dated informed consent form.
Investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IRB
institutional review board
ISR
injection site reaction
IV
intravenous(ly)
mAb
monoclonal antibody
participant
Equivalent to CDISC term “subject”: an individual who participates in a clinical trial, 
either as recipient of an investigational medicinal product or as a control
PK
pharmacokinetics
PYAA
J2W-MC-PYAA
PYAB
J2W-MC-PYAB
PYAG
J2X-MC-PYAG
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SC
subcutaneous(ly)
screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SoA
Schedule of Activities


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
64
Term
Definition
TEAE
Treatment-emergent adverse event: An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, and does not necessarily have to have a causal relationship 
with this treatment.
tmax
time of maximum observed drug concentration
VAS
visual analog scale


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
65
10.8.
Appendix 8: Protocol Amendment History
Amendment (a)
Overall Rationale for the Amendment:
Following feedback from the U.S. Food and Drug Administration (FDA), typographical errors 
have been corrected. Additional changes described below have been made for clarity for clinical 
site activities.
Section # 
and Name
Description of Change
Brief Rationale
Section 1.3. 
Schedule of 
Activities
Physical Examination/Medical 
Assessment

Corrected “Visit 7/ED” to 
“Visit 6/ED”
Injection Site Assessments

Simplified language in Comments 
column to denote ISR assessement, 
pain VAS and Scarletred for all 
timepoints, and added clarification 
regarding predose Scarletred timing.
There is no Visit 7 per the Schedule of 
Activities. Typographical correction.
Scarletred will be assessed during the 
predose activities.
Section 5.2. 
Exclusion 
Criteria
Updated Criterion 12.a to correct for 
typo: “within 2 minutes” should be 
“within 2 meters.”
FDA feedback. Typographical 
correction.
Section 6.1. 
Study 
Interventions 
Administered
LY3819253 unit dose and strength 
updated to 262.5 mg/2.1 mL vial (125 
mg/mL).
Clarification added for vial fill volume 
(2.1 mL) and drug product 
concentration (125mg/mL).
Section 6.1.1. 
Injection 
Volumes and 
Formulation 
Concentrations
Updated Cohort 3 injection volumes to 
reflect syringe accuracy specification: 
“3x 1.86 mL” updated to “2x 1.9 mL + 
1x 1.8 mL.”
Due to limitations with syringe 
gradations, accurate measurement of 
0.06 mL with a 3-cc syringe is not 
possible. Therefore, the injection 
volume was rounded to 1 decimal to 
enable accurate volume for dosing.
Section 10.7.
Appendix 7, 
Abbreviations
Added FDA to list of abbreviations.
FDA used on this page.


CONFIDENTIAL
Protocol J2X-MC-PYAG(b)
66
11.
References
Duan K, Liu B, Li, C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 
patients. Proc Natl Acad Sci USA. 2020;117(17):9490-9496. 
https://doi.org/10.1073/pnas.2004168117.
Gilead Sciences, Inc. Fact sheet for health care providers: emergency use authorization (EUA) of 
Veklury® (remdesivir). July 2020. Accessed August 13, 2020. 
https://www.fda.gov/media/137566/download. 
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-Cov-2 cell entry depends on ACE2 and 
TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-
280.e8. https://doi.org/10.1016/j.cell.2020.02.052.
Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis – a practice parameter update 2015. 
Ann Allergy Asthma Immunol. 2015;115(5):341-384.
https://doi.org/10.1016/j.anai.2015.07.019
Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically ill patients with COVID-19 with 
convalescent plasma. JAMA. 2020;323(16):1582-1589. 
https://doi.org/10.1001/jama.2020.4783
Simons FER, Ebisawa M, Sanchez-Borges M, et al. 2015 update of the evidence base: World 
Allergy Organization anaphylaxis guidelines. World Allergy Organ J. 2015;8(1):32.
https://doi.org/10.1186/s40413-015-0080-1
Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin 
Nurs. 2005;14(7):798-804. https://doi.org/10.1111/j.1365-2702.2005.01121.x


Leo Document ID = 239ccbb6-5683-4021-a38a-0427b5dce0d2
Approver: 
Approval Date & Time: 13-Oct-2020 19:12:05 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 14-Oct-2020 08:13:47 GMT
Signature meaning: Approved
PPD
PPD

SAP_001.pdf: 
 
 
 
 
 
Statistical Analysis Plan J2X-MC-PYAG 
 
 
A Randomized, Placebo-Controlled, Participant- and Investigator-
Blind, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and 
Tolerability of LY3819253 Administered Subcutaneously to Healthy 
Participants 
 
 
NCT04537910 
 
 
Approval Date: 01-Sep-2020 


Final, 28 August 2020
             Page 1 of 17
STATISTICAL ANALYSIS PLAN
A Randomized, Placebo-Controlled, Participant- and Investigator-Blind, Phase 1 Study to 
Evaluate the Pharmacokinetics, Safety, and Tolerability of LY3819253 Administered 
Subcutaneously to Healthy Participants
Statistical Analysis Plan Status: Final
Statistical Analysis Plan Date: 28 August 2020
Study Drug: LY3819253
Sponsor Reference: J2X-MC-PYAG
Covance CRU Study: 1000071-8450508
Clinical Phase I
Approval Date: 01-Sep-2020 GMT


Final, 28 August 2020
             Page 2 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
1. TABLE OF CONTENTS
1.
TABLE OF CONTENTS .....................................................................................................2
2.
ABBREVIATIONS..............................................................................................................4
3.
INTRODUCTION ...............................................................................................................6
4.
STUDY OBJECTIVES AND ENDPOINTS ........................................................................6
5.
STUDY DESIGN.................................................................................................................7
5.1
Overall Design ..............................................................................................................7
5.2
Screening and Enrollment..............................................................................................7
5.3
Inpatient Stay ................................................................................................................7
5.4
Outpatient Follow-up.....................................................................................................8
6.
TREATMENTS...................................................................................................................8
7.
SAMPLE SIZE JUSTIFICATION .......................................................................................9
8.
DEFINITION OF ANALYSIS POPULATIONS..................................................................9
9.
STATISTICAL METHODOLOGY .....................................................................................9
9.1
General..........................................................................................................................9
9.2
Demographics and Subject Disposition........................................................................10
9.3
Pharmacokinetic Assessment.......................................................................................10
9.3.1
Pharmacokinetic Analysis...................................................................................10
9.3.2
Pharmacokinetic Statistical Methodology ...........................................................14
9.4
Safety and Tolerability Assessments............................................................................15
9.4.1
Adverse events ...................................................................................................15
9.4.2
Concomitant medication.....................................................................................15
9.4.3
Clinical laboratory parameters............................................................................15
9.4.4
Vital signs ..........................................................................................................16
9.4.5
Electrocardiogram (ECG)...................................................................................16
9.4.6
Immunogenicity Assessments.............................................................................16
9.4.7
Injection-Site Reactions......................................................................................16
9.4.8
Visual Analog Scale (VAS) Analysis..................................................................16
9.4.9
Hypersensitivity reactions...................................................................................16
9.4.10
Other assessments...............................................................................................16
9.4.11
Safety and Tolerability Statistical Methodology..................................................17


Final, 28 August 2020
             Page 3 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
10. INTERIM ANALYSES .....................................................................................................17
11. CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES ............17
12. REFERENCES ..................................................................................................................17
13. DATA PRESENTATION ..................................................................................................17
13.1 Derived Parameters .....................................................................................................17
13.2 Missing Data ...............................................................................................................17
13.3 Insufficient Data for Presentation ................................................................................17


Final, 28 August 2020
             Page 4 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
2. ABBREVIATIONS
Abbreviations pertain to the Statistical Analysis Plan (SAP) only (not the tables, figures and 
listings [TFLs]).
%AUC(tlast-)
Percentage of AUC(0-∞) extrapolated
ADA
Antidrug antibody
AE
Adverse event
AUC
Area under the concentration versus time curve
AUC(0-∞)
Area under the concentration versus time curve from time zero to infinity
AUC(0-tlast)
Area under the concentration versus time curve from time zero to time t, 
where t is the last time point with a measurable concentration
BQL
Below the lower limit of quantitation
CL/F
Apparent total body clearance of drug calculated after extra-vascular
administration
Cmax
Maximum observed drug concentration
CRF
Case Report Form
CRU
Clinical Research Unit
CSR
Clinical Study Report
CV
Coefficient of variation
ECG
Electrocardiogram
ICH
International Conference on Harmonisation
ISR
Injection-site reaction
MedDRA
Medical Dictionary for Regulatory Activities
PK
Pharmacokinetic
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SARS-COV-2
Severe acute respiratory syndrome coronavirus 2
SC
Subcutaneous 
SD
Standard deviation
t1/2
Half-life associated with the terminal rate constant (λz) in non-
compartmental analysis
TE ADA
Treatment-emergent antidrug antibodies
TEAE
Treatment-emergent adverse event 


Final, 28 August 2020
             Page 5 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
TFLs
Tables, Figures, and Listings
tmax
Time of maximum observed drug concentration
VAS
Visual analog scale
Vz/F
Apparent volume of distribution during the terminal phase after extra-
vascular administration
WHO
World Health Organization


Final, 28 August 2020
             Page 6 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
3. INTRODUCTION
This SAP has been developed after review of the Clinical Study Protocol (final version dated 
17 August 2020).
This SAP describes the planned analysis of the safety, tolerability and pharmacokinetic (PK) data 
from this study. A detailed description of the planned TFLs to be presented in the clinical study 
report (CSR) is provided in the accompanying TFL shell document.
The intent of this document is to provide guidance for the statistical and PK analyses of data. In
general, the analyses are based on information from the protocol, unless they have been modified 
by agreement with Eli Lilly and Company. A limited amount of information concerning this 
study (e.g., objectives, study design) is given to help the reader’s interpretation. When the SAP 
and TFL shells are agreed upon and finalized, they will serve as the template for this study’s 
CSR.
This SAP supersedes the statistical considerations identified in the protocol; where 
considerations are substantially different, they will be so identified. If additional analyses are 
required to supplement the planned analyses described in this SAP, they may be performed and 
will be identified in the CSR. Any substantial deviations from this SAP will be agreed upon with
Eli Lilly and Company and identified in the CSR. Any minor deviations from the TFLs may not 
be documented in the CSR.
This SAP is written with consideration of the recommendations outlined in the International 
Conference on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials1 and the ICH E3 Guideline entitled Guidance for Industry: 
Structure and Content of Clinical Study Reports2.
4. STUDY OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
To determine the PK of single subcutaneous 
(SC) doses of LY3819253 in healthy 
participants
Area under the concentration versus time 
curve from time zero to infinity (AUC(0-∞))
Secondary
To describe safety and tolerability following 
single SC doses of LY3819253 in healthy 
participants
Incidence of spontaneously reported adverse 
events (AEs), treatment-emergent adverse 
events (TEAEs), and serious adverse events 
(SAEs); vital signs; clinical laboratory results
Exploratory
To assess injection-site reactions (ISRs) 
following single SC doses of LY3819253 in 
healthy participants
Characterization and measurement of 
incidence and severity of ISRs, including 
injection site pain, using data collected from 
the ISR assessment, as well as the exploratory 
tool (Scarletred).


Final, 28 August 2020
             Page 7 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
To determine the immunogenicity of 
LY3819253 following single SC doses in 
healthy participants.
Incidence of treatment-emergent antidrug 
antibodies (TE ADA).
5. STUDY DESIGN
5.1
Overall Design
This is a single-site study in healthy participants who will receive a single SC dose of 
LY3819253. The study will be participant- and investigator-blinded, randomized, and placebo 
controlled. A study schema for this study can be seen in Figure 1.
Figure 1: Study Schema for Study J2X-MC-PYAG
5.2
Screening and Enrollment
Up to 3 cohorts may be enrolled with at least 9 participants per cohort 
(7 LY3819253: 2 placebo), with the intention that at least 6 participants randomized to 
LY3819253 have sufficient evaluable data in each cohort.
Participants will be screened within 14 days prior to Day 1 of dosing for each cohort. 
Participants will be admitted to the clinical research unit (CRU) as part of an inpatient visit on 
Day -1 and will be sequentially enrolled and then randomized to treatment.
5.3
Inpatient Stay
Participants will be admitted to the study site on Day -1. They will remain inpatient until 
discharge on Day 7 after study procedures are complete.


Final, 28 August 2020
             Page 8 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
Dosing
Dosing will occur on Day 1. Intended doses of LY3819253 are as follows:

Cohort 1: 350 mg

Cohort 2: 700 mg

Cohort 3 (optional): 700 mg (alternative injection volumes) 
Participants will undergo PK sampling and safety assessment after dosing.
For Cohorts 1 and 2, a safety review will be conducted to determine whether it is appropriate to 
proceed with dosing of the next cohort. This safety review will be conducted based on data from 
at least 4 participants, after at least 4 days after dosing. 
Sentinel dosing
Cohort 1 will include sentinel dosing. The first 2 participants will be randomized and dosed 
(1 LY3819253: 1 placebo). 
The investigator and the Lilly sponsor team are responsible for determining if safety and 
tolerability is acceptable to continue with dosing subsequent participants.
Tolerability as measured by ISRs and their severity is anticipated to be the main safety 
consideration for this assessment. While no serious systemic reactions have been seen with 
LY3819253 to date, participants will be closely monitored.
If the investigator and Lilly sponsor team determine that safety and tolerability is acceptable, the 
remaining participants in the cohort will be dosed on the next day. 
Cohort 2 and the optional Cohort 3 will not include sentinel dosing.
Postdose sampling
On Days 1 through 7, participants will undergo PK sampling and safety assessment.
5.4
Outpatient Follow-up
Follow-up visits will be conducted through Day 85. 
In the event a participant has suspected or confirmed severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) infection, follow-up visits may be conducted at the participant’s 
home. 
6. TREATMENTS
The following is a list of the study treatment abbreviations that will be used in the TFLs.


Final, 28 August 2020
             Page 9 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
Cohort
Study Treatment Name*
Treatment order in TFL
All
Placebo SC
1
1
350 mg LY3819253 SC (2x 1.4 mL)
2
2
700 mg LY3819253 SC (1x 1.4 mL + 2x 2.1 mL)
3
3 (optional)
700 mg LY3819253 SC (1x1.8 mL + 2x 1.9 mL)
4
*The LY3819253 formulation concentration will be 125 mg/mL in all cases.
7. SAMPLE SIZE JUSTIFICATION
A maximum of 36 participants will be enrolled to study intervention with the intention that at 
least 6 participants randomized to LY3819253 have sufficient evaluable data in each cohort. 
This would mean at least 12 participants with evaluable data if Cohorts 1 and 2 only are enrolled, 
or 18 participants if the optional Cohort 3 is also enrolled.
The sample size is not powered on the basis of statistical hypothesis testing. However, based on 
an assumption of 40% coefficient of variation (CV) for between subject variability in a PK 
parameter of interest, 6 subjects on active treatment per cohort may provide approximately 70% 
chance to ensure that a PK parameter’s 90% confidence interval (CI) falls within (0.7, 1.43) over 
the corresponding geometric mean, such as AUC(0-∞).
A participant will be considered evaluable when the participant completes up to 29 days of study 
procedures. When a participant does not complete up to 29 days of study procedures, the sponsor 
will be consulted if the participant will need to be replaced.
8. DEFINITION OF ANALYSIS POPULATIONS
The “Safety” population will consist of all participants who were randomly assigned and who 
received study intervention (LY3819253 or placebo). Participants will be analyzed according to 
the intervention they actually received. 
The “Pharmacokinetic” population will consist of all treated participants who received study 
intervention (LY3819253) and have sufficient evaluable PK samples. 
All protocol deviations that occur during the study will be considered for their severity/impact 
and will be taken into consideration when subjects are assigned to analysis populations.
9. STATISTICAL METHODOLOGY
9.1
General
Data listings will be provided for all data that is databased. Summary statistics and statistical 
analysis will only be presented for data where detailed in this SAP. For continuous data, 
summary statistics will include the arithmetic mean, arithmetic standard deviation (SD), median, 
minimum, maximum and N; for log-normal data (e.g. the PK parameters: area under the 
concentration versus time curve [AUCs] and maximum observed drug concentration [Cmax]) the 
geometric mean and geometric CV will also be presented. For categorical data, frequency count 
and percentages will be presented. Data listings will be provided for all subjects up to the point 
of withdrawal, with any subjects excluded from the relevant population highlighted. Summary 


Final, 28 August 2020
             Page 10 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
statistics and statistical analyses will generally only be performed for subjects included in the 
relevant analysis population. For the calculation of summary statistics and statistical analysis, 
unrounded data will be used. 
Mean change from baseline is the mean of all individual subjects’ change from baseline values. 
Each individual change from baseline will be calculated by subtracting the individual subject’s 
baseline value from the value at the timepoint. The individual subject’s change from baseline 
values will be used to calculate the mean change from baseline using a SAS procedure such as 
Proc Univariate.
Data analysis will be performed using SAS® Version 9.4 or greater.
9.2
Demographics and Subject Disposition
Subject disposition will be listed. The demographic variables age, sex, race, ethnicity, body 
weight, height and body mass index will be summarized and listed. All other demographic 
variables will be listed only.
9.3
Pharmacokinetic Assessment
9.3.1
Pharmacokinetic Analysis
Noncompartmental methods applied with a validated software program, Phoenix WinNonlin 
(Certara, Version 8.1 or later) to the serum concentrations of LY3819253 will be used to 
determine the following PK parameters, when possible:


Final, 28 August 2020
             Page 11 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
Parameter
Units
Definition
AUC(0-∞)
µg*h/mL
area under the concentration versus time curve from time 
zero to infinity
%AUC(tlast-)
%
percentage of AUC(0-∞) extrapolated
AUC(0-tlast)
µg*h/mL
area under the concentration versus time curve from time 
zero to time t, where t is the last time point with a 
measurable concentration
Cmaxa
µg/mL
maximum observed drug concentration
tmax
h
time of maximum observed drug concentration
t1/2
h
half-life associated with the terminal rate constant (λz) in 
non-compartmental analysis
CL/F
L/h
apparent total body clearance of drug calculated after 
extra-vascular administration
Vz/F
L
apparent volume of distribution during the terminal phase 
after extra-vascular administration
a Serum LY3819253 drug concentration units will come in from the bioanalytical lab as ng/mL to one decimal place; 
the data will be transformed (unrounded) to µg/mL for analysis and reporting.
Additional PK parameters may be calculated, as appropriate. The software and version used for 
the final analyses will be specified in the CSR. Any exceptions or special handling of data will 
be clearly documented within the final study report.
Formatting of tables, figures and abbreviations will follow the Eli Lilly Global PK/PD/TS Tool: 
NON-COMPARTMENTAL PHARMACOKINETIC STYLE GUIDE. The version of the tool
effective at the time of PK analysis will be followed.
General PK Parameter Rules

Actual sampling times will be used in the final analyses of individual PK parameters, 
except for non-bolus pre-dose sampling times which will be set to zero.

Cmax and tmax will be reported from observed values. If Cmax occurs at more than 
one timepoint, tmax will be assigned to the first occurrence of Cmax. 

AUC parameters will be calculated using a combination of the linear and logarithmic 
trapezoidal methods (linear-log trapezoidal rule). The linear trapezoidal method will be 
applied up to tmax and then the logarithmic trapezoidal method will be used after tmax. The 
minimum requirement for the calculation of AUC will be the inclusion of at least three 
consecutive serum concentrations above the lower limit of quantification, with at least 
one of these concentrations following Cmax. AUC(0-) values where the percentage of 
the total area extrapolated is more than 20% will be flagged. Any AUC(0-) value 
excluded from summary statistics will be noted in the footnote of the summary table.

Half-life associated with the terminal rate constant (λz) in non-compartmental analysis
(t1/2) will be calculated, when appropriate, based on the apparent terminal log-linear 


Final, 28 August 2020
             Page 12 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
portion of the concentration-time curve. The start of the terminal elimination phase for 
each subject will be defined by visual inspection and generally will be the first point at 
which there is no systematic deviation from the log-linear decline in serum 
concentrations. Half-life will only be calculated when a reliable estimate for this 
parameter can be obtained comprising of at least 3 data points. If t1/2 is estimated over a 
time window of less than 2 half-lives, the values will be flagged in the data listings. Any 
t1/2 value excluded from summary statistics will be documented in the footnote of the 
summary table. 

A uniform weighting scheme will be used in the regression analysis of the terminal log-
linear portion of the concentration-time curve.

The parameters based on predicted last quantifiable drug concentration will be reported.
Individual PK Parameter Rules

Only quantifiable concentrations will be used to calculate PK parameters with the 
exception of special handling of certain concentrations reported below the lower limit of 
quantitation (BQL). Serum concentrations reported as BQL will be set to a value of zero 
when all of the following conditions are met: 
o
The compound is non-endogenous.
o
The samples are from the initial dose period for a subject or from a 
subsequent dose period following a suitable wash-out period.
o
The time points occur before the first quantifiable concentration.

All other BQL concentrations that do not meet the above criteria will be set to missing. 

Also, where two or more consecutive concentrations are BQL towards the end of a 
profile, the profile will be deemed to have terminated and therefore any further 
quantifiable concentrations will be set to missing for the calculation of the PK parameters 
unless it is considered to be a true characteristic of the profile of the drug.
Individual Concentration vs. Time Profiles

Individual concentrations will be plotted utilizing actual sampling times.

The terminal point selections will be indicated on a semi-logarithmic plot.
Average Concentration vs. Time Profiles

The average concentration profiles will be graphed using scheduled (nominal) 
sampling times. 


Final, 28 August 2020
             Page 13 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG

The average concentration profiles will be graphed using arithmetic average 
concentrations.

The pre-dose average concentration for single-dose data from non-endogenous 
compounds will be set to zero. Otherwise, only quantifiable concentrations will be 
used to calculate average concentrations.

Concentrations at a sampling time exceeding the sampling time window specified 
in the protocol, or ± 10%, will be excluded from the average concentration 
profiles.

Concentrations excluded from the mean calculation will be documented in the 
final study report.

A concentration average will be plotted for a given sampling time only if 2/3 of 
the individual data at the time point have quantifiable measurements that are 
within the sampling time window specified in the protocol or ± 10%. An average 
concentration estimated with less than 2/3 but more than 3 data points may be 
displayed on the mean concentration plot if determined to be appropriate and will 
be documented within the final study report.
Treatment of Outliers during Pharmacokinetic Analysis
Application of this procedure to all PK analyses is not a requirement. Rather, this procedure 
provides justification for exclusion of data when scientifically appropriate. This procedure 
describes the methodology for identifying an individual value as an outlier for potential 
exclusion, but does not require that the value be excluded from analysis. The following 
methodology will not be used to exclude complete profiles from analysis.
Data within an Individual Profile
A value within an individual profile may be excluded from analysis if any of the following 
criteria are met:

For PK profiles during multiple dosing, the concentration of the pre-dose sample exceeds 
all measured concentrations for that individual in the subsequent post-dose samples.

For PK profiles during single dosing of non-endogenous compounds, the concentration in 
a pre-dose sample is quantifiable.

For any questionable datum that does not satisfy the above criteria, the profile will be 
evaluated and results reported with and without the suspected datum. 
Data between Individual Profiles
1.
If n<6, then the dataset is too small to conduct a reliable range test. Data will be analyzed 
with and without the atypical value, and both sets of results will be reported.


Final, 28 August 2020
             Page 14 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
2.
If n6, then an objective outlier test will be used to compare the atypical value to other 
values included in that calculation:
a.
Transform all values in the calculation to the logarithmic domain.
b. Find the most extreme value from the arithmetic mean of the log transformed 
values and exclude that value from the dataset.
c.
Calculate the lower and upper bounds of the range defined by the arithmetic 
mean ±3*SD of the remaining log-transformed values.
d. If the extreme value is within the range of arithmetic mean ±3*SD, then it is 
not an outlier and will be retained in the dataset.
e.
If the extreme value is outside the range of arithmetic mean ±3*SD, then it is 
an outlier and will be excluded from analysis.
If the remaining dataset contains another atypical datum suspected to be an outlier and n ≥ 6 
following the exclusion, then repeat step 2 above. This evaluation may be repeated as many 
times as necessary, excluding only one suspected outlier in each iteration, until all data 
remaining in the dataset fall within the range of arithmetic mean ±3*SD of the log-transformed 
values.
Reporting of Excluded Values
Individual values excluded as outliers will be documented in the final report. Approval of the 
final report will connote approval of the exclusion.
9.3.2
Pharmacokinetic Statistical Methodology
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.1, unless otherwise 
stated, and all CIs will be given at a 2-sided 90% level.
The primary parameters for analysis will be AUC(0-∞) of LY3819253 following SC 
administration. Other noncompartmental parameters, such as half-life, tmax, apparent clearance, 
and volume of distribution following SC administration may be reported.
The natural log (ln)-transformed AUC(0-∞) will be analyzed using an analysis of variance
model. The model will include dose as a factor. Body weight may be tested as a covariate and 
kept if needed.
The least squares mean for each treatment, difference in least square means between the 
treatments, and corresponding 90% CI will be calculated; these values will then be 
back-transformed to give the geometric least square mean, ratio of geometric least square means,
and corresponding 90% CI. 


Final, 28 August 2020
             Page 15 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
Example SAS code for the analysis:
proc mixed data=pk;
  class dose;
  model log_pk = dose / alpha=0.1 cl residual ddfm=kr2;
  lsmeans dose / cl pdiff;
  ods output lsmeans=lsm;
  ods output diffs=diff;
  ods output tests3=tests;
run;
In addition to noncompartmental analysis, the data may be combined with data from other 
studies to be analyzed using non-linear mixed-effect modelling of the PK data. This analysis will 
be the responsibility of Eli Lilly PK/PD group.
9.4
Safety and Tolerability Assessments
9.4.1
Adverse events
Where changes in severity are recorded in the Case Report Form (CRF), each separate severity 
of the AE will be reported in the listings, only the most severe will be used in the summary 
tables. A pre-existing condition is defined as an AE that starts before the subject has provided 
written informed consent and is ongoing at consent. A non-treatment emergent AE is defined as 
an AE which starts after informed consent but prior to dosing. A TEAE is defined as an AE 
which occurs postdose or which is present prior to dosing and becomes more severe postdose. 
All AEs will be listed. All TEAEs will be summarized by treatment, severity and relationship to 
the study drug. The frequency (the number of AEs, the number of subjects experiencing an AE
and the percentage of subjects experiencing an AE) of TEAEs will be summarized by treatment, 
Medical Dictionary for Regulatory Activities (MedDRA) version 23.0 system organ class and 
preferred term. The summary and frequency AE tables will be presented for all causalities and 
those considered related to the study drug by the investigator. Any SAEs will be listed. 
Discontinuations due to AEs will be listed.
9.4.2
Concomitant medication
Concomitant medication will be coded using the WHO drug dictionary (Version March 2020 
B3). Concomitant medication will be listed.
9.4.3
Clinical laboratory parameters
All clinical chemistry and hematology data will be summarized by parameter and treatment,
together with changes from baseline, and listed. Baseline is defined as the Day -1 predose 
assessment. Urinalysis data will be listed. Additionally, clinical chemistry, hematology and 
urinalysis data outside the reference ranges will be listed and flagged on individual subject data 
listings.
Data from SARS-CoV-2 clinical screening, serology, and point-of-care test will be listed, if 
available.


Final, 28 August 2020
             Page 16 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
9.4.4
Vital signs
Vital signs data will be summarized by treatment together with changes from baseline, where 
baseline is defined as the Day 1 predose assessment. Figures of mean vital signs and mean 
changes from baseline profiles will be presented by treatment. 
Values for individual subjects will be listed.
9.4.5
Electrocardiogram (ECG)
ECGs will be performed for safety monitoring purposes only and will not be presented. Any 
clinically significant findings from ECGs will be reported as an AE.
9.4.6
Immunogenicity Assessments
The frequency and percentage of subjects with pre-existing antidrug antibody (ADA) and with 
TE ADAs to LY3819253 will be tabulated and listed only if the data is available. 
The frequency and percentage of subjects with cross-reactive and neutralizing antibodies, if 
measured, may also be tabulated for subjects with TE ADA.
9.4.7
Injection-Site Reactions
ISR data (including erythema, induration, pain, pruritus, and edema) will be listed and 
summarized by treatment in frequency tables. ISR will be listed and may be summarized if there 
are ≥3 subjects with ISR per dose. 
9.4.8
Visual Analog Scale (VAS) Analysis
The VAS is a well-validated tool to assess injection site pain; it is presented as a 100 mm line 
anchored by verbal descriptors, usually “no pain” and “worst imaginable pain.” The participant 
will be asked to rate any pain at the injection site on a scale of 0 to 100 on the line, as soon as 
possible following each injection.
The data will be listed and summarized by treatment and time point.
9.4.9
Hypersensitivity reactions
For all drug hypersensitivity reactions that occur, additional follow-up data will be collected to 
assess the patient’s medical history, alternative causes, and symptoms.
These data will be listed.
9.4.10
Other assessments
All other safety assessments not detailed in this section will be listed but not summarized or 
statistically analyzed.


Final, 28 August 2020
             Page 17 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8450508
Sponsor Reference J2X-MC-PYAG
9.4.11
Safety and Tolerability Statistical Methodology
No inferential statistical analyses are planned.
10.
INTERIM ANALYSES
No interim statistical analyses are planned.
11.
CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES
There were no changes from the protocol specified statistical analyses.
12.
REFERENCES
1. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Statistical Principles 
for Clinical Trials (E9), 5 February 1998.
2. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Structure and 
Content of Clinical Study Reports (E3), 30 November 1995.
13.
DATA PRESENTATION
13.1
Derived Parameters
Individual derived parameters (e.g. PK parameters) and appropriate summary statistics will be 
reported to three significant figures. Observed concentration data, e.g. Cmax, should be reported 
as received. Observed time data, e.g. tmax, should be reported as received. N and percentage 
values should be reported as whole numbers. Median values should be treated as an observed 
parameter and reported to the same number of decimal places as minimum and maximum values.
13.2
Missing Data
Missing data will not be displayed in listings.
13.3
Insufficient Data for Presentation
Some of the TFLs may not have sufficient numbers of subjects or data for presentation. If this 
occurs, the blank TFL shell will be presented with a message printed in the center of the table, 
such as, “No serious adverse events occurred for this study.”


Leo Document ID = 9dd5bad7-ce9f-410f-83e3-71987d96ac73
Approver: 
Approval Date & Time: 28-Aug-2020 16:17:08 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 28-Aug-2020 16:31:40 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 28-Aug-2020 16:44:39 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 01-Sep-2020 14:56:21 GMT
Signature meaning: Approved
PPD
PPD
PPD
PPD