A Phase 1, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Single-Ascending Dose Study of LY3872386 in Healthy Participants, a Multiple-Ascending Dose Study of LY3872386 in Patients With Atopic Dermatitis, and an Open-Label Multiple-Dose Evaluation of the Safety and Tolerability of Prednisone in Healthy Participants.
Phase: PHASE1
Conditions: Healthy, Atopic Dermatitis
Sponsor: Eli Lilly and Company

Protocol: J4L-MC-KMAA 
 
 
A Phase 1, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Single-Ascending Dose 
Study of LY3872386 in Healthy Participants, a Multiple-Ascending Dose Study of LY3872386 
in Patients with Atopic Dermatitis, and an Open-Label Multiple-Dose Evaluation of the Safety 
and Tolerability of Prednisone in Healthy Participants. 
 
 
NCT06119529 
 
 
Approval Date: 10-Nov-2023 
 

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J4L-MC-KMAA (b) 
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Title Page  
Confidential Information 
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of LY3872386 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 Phase 1, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Single-Ascending 
Dose Study of LY3872386 in Healthy Participants, a Multiple-Ascending Dose Study of 
LY3872386 in Patients with Atopic Dermatitis, and an Open-Label Multiple-Dose Evaluation of 
the Safety and Tolerability of Prednisone in Healthy Participants. 
Protocol Number: J4L-MC-KMAA 
Amendment Number: b 
Compound: LY3872386 
Brief Title:  
A Single-Ascending Dose Study of LY3872386 in Healthy Participants, a Multiple-Ascending 
Dose Study of LY3872386 in Patients with Atopic Dermatitis, and an Open-Label Multiple-Dose 
Evaluation of Prednisone in Healthy Participants. 
Study Phase: 1 
Sponsor Name: Eli Lilly and Company  
Legal Registered Address: Eli Lilly and Company, Indianapolis, Indiana USA 46285. 
Regulatory Agency Identifier Number(s)  
IND: 166698 
Approval Date: Protocol Amendment (b) Electronically Signed and Approved by Lilly on date 
provided below. 
 
 
Document ID: VV-CLIN-091227 
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Medical Monitor Name and Contact Information will be provided separately.  
 
 
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Protocol Amendment Summary of Changes Table  
 
DOCUMENT HISTORY 
Document 
Date 
Amendment a 
16-October 2023 
Original Protocol 
01-September-2023 
Amendment: b  
This amendment is considered to be nonsubstantial. 
Overall Rationale for the Amendment: 
This protocol has been amended to primarily address the FDA clinical non-hold comments 
regarding ophthalmological examinations, blood glucose monitoring, and treatment stopping 
criteria. 
Minor editorial changes have also been made and are not presented in the summary of changes 
table. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3.1: Part A: 
Single-Ascending Dose of 
LY3872386 in Healthy 
Participants 
Added line item for bedside glucose 
monitoring to include time points on 
Day -1, Day 1, Day 2, and Day 7. 
 
Added line item for hemoglobin A1c to 
include time points at screening, Day -
1, Day 29 ± 1d, Day 85 ± 3d, and ED. 
 
Added an ocular pressure, visual 
acuity, and cataract evaluation time 
point to Day 15 ± 1d and 43 ± 1d. 
Provided additional to indicate that for 
follow-up Visit 802 and Visit 805, an 
ocular pressure assessment is required; 
additional visual acuity assessment may 
be conducted.   
Updated to address FDA comments. 
 
 
Updated to address FDA comments and 
support additional treatment 
discontinuation and interruption 
criteria. 
 
Updated to address FDA comments. 
 
Section 1.3.2: Part B: 
Multiple-Ascending Dose of 
LY3872386 in Patients with 
Atopic Dermatitis 
 Dosing 
Schedule: 
Added line item for hemoglobin A1c to 
include time points at screening, Day 1, 
Day 29 ± 1d, Day 85 ± 1d, Day 183 ± 
3d, and ED. 
Updated to address FDA comments and 
support additional treatment 
discontinuation and interruption 
criteria. 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
Added an ocular pressure, visual 
acuity, and cataract evaluation time 
point to Day 29 ± 1d, Day 57 ± 1d, and 
Day 88 ± 1d. Provided additional notes 
to state that for Visit 4, Visit 6, and 
follow-up Visit 801, an ocular pressure 
assessment is required; additional 
visual acuity and cataract assessment 
may be conducted.   
 
 Dosing 
Schedule: 
Added line item for hemoglobin A1c to 
include time points at screening, Day 1, 
Day 29 ± 1d, Day 85 ± 1d, Day 183 ± 
3d, and ED. 
 
Added an ocular pressure, visual 
acuity, and cataract evaluation time 
point to Day 29 ± 1d, Day 57 ± 1d, and 
Day 88 ± 1d. Provided additional notes 
to state that for Visit 4, Visit 6, and 
follow-up Visit 801, an ocular pressure 
assessment is required; additional 
visual acuity and cataract assessments 
may be conducted. 
Updated to address FDA comments. 
 
 
 
 
 
 
 
Updated to address FDA comments and 
support additional treatment 
discontinuation and interruption 
criteria. 
 
 
 
Updated to address FDA comments. 
 
Section 1.3.3: Part C: Open-
Label Multiple Dose of 
Prednisone in Healthy 
Participants 
Prednisone 
 mg and  mg Dosing 
Schedule: 
Added line item for hemoglobin A1c to 
include a time point at screening. 
 
Prednisone 
 mg Dosing Schedule: 
Added line item for hemoglobin A1c to 
include a time point at screening. 
Updated to address FDA comments and 
support additional screening criteria. 
 
 
 
Updated to address FDA comments and 
support additional screening criteria. 
Section 5.2: Exclusion 
Criteria 
Added Criterion #50 to exclude 
participants with a known history of 
diabetes. 
 
Added Criterion #51 to exclude 
participants with a fasting glucose level 
of ≥126 mg/dL and glycated 
hemoglobin ≥6.5% and/or taking 
antidiabetes medications at screening. 
Updated given that participants could 
have a higher risk to develop serious 
glucocorticoid related effects. 
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Section # and Name 
Description of Change 
Brief Rationale 
Added Criterion #52 to exclude 
participants with a known history of 
osteoporosis. 
Section 6.9: Prior and 
Concomitant Therapy 
Updated the text to state that 
acetaminophen may be administered at 
the discretion of the investigator for the 
treatment of headache and so on. 
 
Updated the text to state that 
antihistamine may be administered as a 
premedication for infusion at the 
discretion of the investigator. 
 
Updated the text to state that if a need 
for concomitant medication arises, the 
inclusion or continuation of the 
participant may be at the discretion of 
the investigator after consultation with 
the sponsor. 
Corrections to clarify the role of the 
investigator as opposed to the medical 
monitor. 
Section 7.1: Discontinuation 
of Study Intervention 
Updated the section to include 
additional cardiovascular stopping 
criteria, ocular pressure interruption 
criteria, additional serious and 
opportunistic infections discontinuation 
and interruption criteria, abnormal 
laboratory parameters of special 
interest, including adrenal insufficiency 
criteria. 
Updated to address FDA comments. 
 
Section 8.2.4: 
Ophthalmological 
Examinations 
Added text to state that all 
ophthalmological examinations may be 
completed within a 2-week window. 
 
Clarified that postdose evaluations in 
Parts A and B can be conducted 
anytime within 1 week of each time 
point as indicated in the SoA. 
Updated to address FDA comments. 
 
 
 
 
 
Section 10.2: Appendix 2: 
Clinical Laboratory Tests 
Added a line item for hemoglobin A1c. 
 
Updated to address FDA comments and 
support additional screening and/or 
treatment discontinuation and 
interruption criteria. 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
Added a line item for bedside glucose 
monitoring (fasting) with footnote f to 
indicate that bedside glucose 
monitoring is performed using standard 
glucose monitors and capillary blood 
taken from fingerstick. Fasting should 
be approximately 2 hours, at a 
minimum. 
Updated to address FDA comments. 
 
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Table of Contents  
 
1. 
Protocol Summary ........................................................................................................11 
1.1. 
Synopsis ..........................................................................................................................11 
1.2. 
Schema ............................................................................................................................15 
1.3. 
Schedule of Activities (SoA) ..........................................................................................16 
1.3.1. 
Part A: Single-Ascending Dose of LY3872386 in Healthy 
Participants ......................................................................................................................16 
1.3.2. 
Part B: Multiple-Ascending Dose of LY3872386 in Patients with 
Atopic Dermatitis ............................................................................................................22 
1.3.3. 
Part C: Open-Label Multiple Dose of Prednisone in Healthy 
Participants ......................................................................................................................32 
2. 
Introduction ...................................................................................................................38 
2.1. 
Study Rationale ...............................................................................................................38 
2.2. 
Background .....................................................................................................................38 
2.3. 
Benefit/Risk Assessment ................................................................................................42 
3. 
Objectives and Endpoints ............................................................................................44 
4. 
Study Design ..................................................................................................................46 
4.1. 
Overall Design ................................................................................................................46 
4.2. 
Scientific Rationale for Study Design ............................................................................50 
4.3. 
Justification for Dose ......................................................................................................50 
4.4. 
End of Study Definition ..................................................................................................54 
5. 
Study Population ...........................................................................................................55 
5.1. 
Inclusion Criteria ............................................................................................................55 
5.1.1. 
Additional Inclusion Criteria for Part B (Patients with Atopic 
Dermatitis) ......................................................................................................................56 
5.2. 
Exclusion Criteria ...........................................................................................................56 
5.2.1. 
Additional Exclusion Criteria for Part B (Patients with Atopic 
Dermatitis) ......................................................................................................................59 
5.3. 
Lifestyle Considerations .................................................................................................61 
5.3.1. 
Meals and Dietary Restrictions .......................................................................................61 
5.3.2. 
Substance Use: Caffeine, Alcohol, and Tobacco ............................................................61 
5.3.3. 
Activity ...........................................................................................................................62 
5.4. 
Screen Failures ................................................................................................................62 
5.5. 
Criteria for Temporarily Delaying Enrollment/Randomization/ 
Administration of Study Intervention of a Participant....................................................62 
6. 
Study Interventions and Concomitant Therapy ........................................................63 
6.1. 
Study Interventions Administered ..................................................................................63 
6.1.1. 
Administration Details ....................................................................................................63 
6.1.2. 
Premedication for Infusions ............................................................................................64 
6.1.3. 
Management of Infusion Reactions ................................................................................64 
6.2. 
Preparation, Handling, Storage, and Accountability ......................................................65 
6.3. 
Assignment to Study Intervention ..................................................................................65 
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6.4. 
Blinding ..........................................................................................................................66 
6.4.1. 
Part A: Single-Ascending Dose of LY3872386..............................................................66 
6.4.2. 
Part B: Multiple-Ascending Dose of LY3872386 ..........................................................66 
6.4.3. 
Part C: Open-Label of Prednisone ..................................................................................66 
6.5. 
Study Intervention Compliance ......................................................................................67 
6.6. 
Dose Modification ..........................................................................................................67 
6.6.1. 
Dose Decision/Escalation ...............................................................................................67 
6.7. 
Continued Access to Study Intervention after the End of the 
Study ...............................................................................................................................70 
6.8. 
Treatment of Overdose ...................................................................................................70 
6.9. 
Prior and Concomitant Therapy ......................................................................................71 
6.9.1. 
Rescue Medicine .............................................................................................................71 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................73 
7.1. 
Discontinuation of Study Intervention ............................................................................73 
7.1.1. 
Rules for Stopping Dosing and Enrollment in a Cohort .................................................73 
7.1.2. 
Hepatic Criteria for Study Drug Interruption or Discontinuation ...................................74 
7.1.3. 
Cardiovascular Stopping Criteria ....................................................................................74 
7.1.4. 
Ocular Pressure Interruption Criteria ..............................................................................74 
7.1.5. 
Serious and Opportunistic Infections Discontinuation and 
Interruption Criteria ........................................................................................................74 
7.1.6. 
Abnormal Laboratory Parameters of Special Interest .....................................................75 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................76 
7.2.1. 
Discontinuation of Inadvertently Enrolled Participants ..................................................77 
7.3. 
Lost to Follow-up............................................................................................................77 
8. 
Study Assessments and Procedures.............................................................................78 
8.1. 
Efficacy Assessments .....................................................................................................78 
8.2. 
Safety Assessments .........................................................................................................80 
8.2.1. 
Physical Examinations ....................................................................................................80 
8.2.2. 
Vital Signs .......................................................................................................................80 
8.2.3. 
Electrocardiograms .........................................................................................................80 
 
 
8.2.5. 
Clinical Safety Laboratory Tests ....................................................................................82 
8.2.6. 
Injection-site Reactions ...................................................................................................83 
8.2.7. 
Safety Monitoring ...........................................................................................................84 
8.2.8. 
Hepatic Safety Monitoring, Evaluation, and Criteria for Study 
Drug Interruption or Discontinuation .............................................................................85 
8.2.9. 
Immunological Status Assessments ................................................................................88 
8.2.10. Hepatitis B Testing and Monitoring ...............................................................................88 
8.2.11. Hepatitis C Testing .........................................................................................................89 
8.2.12. Pregnancy Testing ...........................................................................................................89 
8.3. 
Adverse Events, Serious Adverse Events, and Product 
Complaints ......................................................................................................................89 
8.3.1. 
Timing and Mechanism for Collecting Events ...............................................................91 
8.3.2. 
Pregnancy ........................................................................................................................92 
8.3.3. 
Adverse Events of Special Interest .................................................................................93 
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8.4. 
Pharmacokinetics ............................................................................................................93 
8.4.1. 
Pharmacokinetics of LY3872386 in Part A and Part B ..................................................93 
8.4.2. 
Pharmacokinetics of Prednisone in Part C ......................................................................94 
8.4.3. 
Bioanalysis ......................................................................................................................94 
8.5. 
Pharmacodynamics .........................................................................................................95 
8.5.1. 
Pharmacodynamics of LY3872386.................................................................................95 
8.5.2. 
Pharmacodynamics of Prednisone ..................................................................................95 
8.6. 
Genetics ..........................................................................................................................95 
 
 
 
 
8.8. 
Immunogenicity Assessments.........................................................................................97 
8.9. 
Health Economics OR Medical Resource Utilization and Health 
Economics .......................................................................................................................97 
9. 
Statistical Considerations .............................................................................................98 
9.1. 
Statistical Hypotheses .....................................................................................................98 
9.1.1. 
Multiplicity Adjustment ..................................................................................................98 
9.2. 
Analyses Sets ..................................................................................................................98 
9.3. 
Statistical Analyses .........................................................................................................98 
9.3.1. 
General Considerations ...................................................................................................98 
9.3.2. 
Primary Endpoint Analysis .............................................................................................99 
9.3.3. 
Secondary Endpoint Analysis .......................................................................................100 
9.3.4. 
Exploratory Endpoints Analysis ...................................................................................100 
9.3.5. 
Other Analyses ..............................................................................................................101 
9.4. 
Interim Analyses ...........................................................................................................102 
9.4.1. 
Interim Access to Data During the Study .....................................................................102 
9.5. 
Sample Size Determination ..........................................................................................103 
10. 
Supporting Documentation and Operational Considerations ................................104 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ..............................................................................................................104 
10.1.1. Regulatory and Ethical Considerations .........................................................................104 
10.1.2. Financial Disclosure......................................................................................................104 
10.1.3. Informed Consent Process ............................................................................................105 
10.1.4. Data Protection..............................................................................................................105 
10.1.5. Committees Structure....................................................................................................106 
10.1.6. Dissemination of Clinical Study Data...........................................................................106 
10.1.7. Data Quality Assurance ................................................................................................106 
10.1.8. Source Documents ........................................................................................................108 
10.1.9. Trial and Site Start and Closure ....................................................................................108 
10.1.10. Publication Policy .........................................................................................................109 
10.1.11. Investigator Information ...............................................................................................109 
10.1.12. Sample Retention ..........................................................................................................109 
10.2. 
Appendix 2: Clinical Laboratory Tests .........................................................................110 
10.2.1. Blood Sampling Summary ............................................................................................113 
10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting ..........................................................................................................119 
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10.3.1. Definition of AE ...........................................................................................................119 
10.3.2. Definition of SAE .........................................................................................................120 
10.3.3. Definition of Product Complaint ..................................................................................121 
10.3.4. Recording and Follow-Up of AE and/or SAE and Product 
Complaints ....................................................................................................................121 
10.3.5. Reporting of SAEs ........................................................................................................123 
10.3.6. Regulatory Reporting Requirements .............................................................................124 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ........................................................125 
10.4.1. Definitions.....................................................................................................................125 
10.4.2. Contraception Guidance................................................................................................126 
10.5. 
Appendix 5: Genetics....................................................................................................129 
10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments ..................................................................................................................130 
10.7. 
Appendix 7: Abbreviations and Definitions .................................................................132 
10.8. 
Appendix 8: Protocol Amendment History ..................................................................137 
11. 
References ....................................................................................................................145 
 
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1. 
Protocol Summary  
1.1. 
Synopsis  
Protocol Title:  
A Phase 1, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Single-Ascending 
Dose Study of LY3872386 in Healthy Participants, a Multiple-Ascending Dose Study of 
LY3872386 in Patients with Atopic Dermatitis, and an Open-Label Multiple-Dose Evaluation of 
the Safety and Tolerability of Prednisone in Healthy Participants. 
Brief Title:  
A Single-Ascending Dose Study of LY3872386 in Healthy Participants, a Multiple-Ascending 
Dose Study of LY3872386 in Patients with Atopic Dermatitis, and an Open-Label Multiple-Dose 
Evaluation of Prednisone in Healthy Participants. 
Regulatory Agency Identifier Number(s): IND: 166698 
Rationale: 
LY3872386 is an ADC consisting of an anti-IL-4R antagonist mAb covalently conjugated via a 
linker to a small molecule GC (payload or LY3558533, also known as LSN3558533). Study J4L-
MC-KMAA (KMAA) is a first-in-human study to characterize the safety, tolerability, and 
pharmacokinetics (PK) of single doses of LY3872386 in healthy participants and repeat doses in 
patients with atopic dermatitis (AD). Additionally, this study will assess the safety, tolerability, 
and PK of multiple dose levels of prednisone in healthy participants who will receive prednisone 
by mouth (PO) once daily (QD). The data generated in this study will guide the design of 
subsequent clinical trials. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 
To characterize the safety of LY3872386 after single dose 
administration in healthy participants and after repeat dose 
administration in patients with atopic dermatitis. 
 
 
To assess the safety of prednisone in healthy participants 
receiving multiple PO QD doses in various dosing groups. 
 
Number and incidence of AEs, TEAEs, and 
SAEs 
 
 
Number and incidence of AEs, TEAEs, and 
SAEs 
Secondary 
 
To characterize the PK of LY3872386, total antibody, and 
LY3558533 (free payload) following single dose 
administration in healthy participants and after repeat 
dosing in patients with atopic dermatitis. 
 
 
To characterize the PK of prednisone in healthy participants 
receiving multiple PO QD doses in various dosing groups. 
 
Cmax and AUC of LY3872386, total antibody, 
and LY3558533 (free payload) 
 
 
Cmax and AUC of prednisone and 
prednisolone 
Abbreviations: AE = adverse event; AUC = area under the concentration versus time curve; Cmax = maximum 
observed drug concentration; PK = pharmacokinetics; PO = oral administration; QD = once daily; SAE = serious 
adverse event; TEAE = treatment-emergent adverse event 
 
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Statistical Considerations: 
Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events 
(AEs) for each IP will be listed and, if the frequency of events allows, descriptive statistics will 
summarize the safety data per race and ethnicity. Symptoms, their incidence, severity, and 
association with investigational product, as perceived by the investigator, will be reported 
separately for each treatment and IP. All TEAEs will be summarized across each part of the 
study by system organ class and by decreasing frequency according to the Medical Dictionary 
for Regulatory Activities. 
Overall Design: 
Study KMAA is a first-in-human trial designed to characterize the safety and tolerability of 
LY3872386 as well as the PK of LY3872386, total antibody, and LY3558533 (free payload) in 
healthy participants and in patients with AD. Additionally, this study will assess the safety, 
tolerability, PK, and pharmacodynamics (PD) of various dose levels of prednisone in healthy 
participants. The study will enroll participants of any ethnicity.
 
 
 
The study will be conducted following 3 parts: 
 Part A (single-ascending dose [SAD] of LY3872386) will characterize the safety, 
tolerability, PK, and PD after single intravenous (IV) and subcutaneous (SC) dose 
administration of LY3872386 in healthy participants. 
 Part B (multiple-ascending dose [MAD] of LY3872386) will characterize the safety, 
tolerability, PK, and PD after multiple SC and/or IV dose administrations of LY3872386 
in patients with AD. 
 Part C 
 will assess the safety, tolerability, PK, and PD 
after repeat PO administration of prednisone in healthy participants. 
Brief Summary: 
Part A is a randomized, placebo-controlled, sponsor-unblinded, investigator- and participant-
blinded SAD study in healthy participants for LY3872386. Part B is a randomized,  
placebo-controlled, sponsor-unblinded, investigator- and participant-blinded, repeat, MAD study 
in patients with AD for LY3872386. Part C is an open-label study in healthy participants who 
will receive multiple doses PO QD of prednisone.  
Study details include: 
Treatment Arms, Duration, and Visit Frequency: 
Part A: SAD of LY3872386 in Healthy Participants 
Eligible participants will be admitted to the clinical research unit (CRU) on Day -1. Participants 
will receive a single-dose administration on Day 1 and will remain inpatient for approximately 7 
days followed by visits at regular intervals. 
A total of IV dose cohorts (
 mg) and  SC dose cohorts 
 mg and 
 mg) are planned. Cohort 4 will include Japanese participants and Cohorts 6, 7, 
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and 8 will include Japanese and Chinese participants. The study intervention will be 
administered as a single dose on Day 1, followed by a 12-week follow-up period (Section 1.2). 
Within each dose cohort, treatment-matched placebo will be given using the same time, 
frequency, and route as LY3872386, as applicable. 
Part B: MAD of LY3872386 in Patients with Atopic Dermatitis 
Eligible patients with AD will receive multiple doses of LY3872386 within a 12-week treatment 
period, with administration at an interval of at most 
 and/or at least 
. Each dosing and discharge are at the discretion of the investigator, 
with visits in between the doses and at regular intervals following the last dose of the study drug. 
At least 2 IV and/or SC dose cohorts (
 mg and 
 mg) are planned. The study 
intervention is planned to be administered on Day 1, followed by dose administration 
 
and/or 
 for up to 12 weeks in patients with AD. The route and frequency of administration 
are planned to be the same for all participants within a cohort. The dose, route, and frequency of 
administration will be confirmed based on emerging data from the safety and PK data of 
previous SAD and MAD cohorts. Participants will be followed up for 14 weeks after the last 
dose (Section 1.2). 
Within each dose cohort, treatment-matched placebo will be given using the same time, 
frequency, and route as LY3872386, as applicable. 
Part C: Open-label Multiple Doses of Prednisone in Healthy Participants 
Eligible participants will be admitted to the CRU on Day -2. Participants will receive multiple 
doses of either 
 mg of prednisone during 1 treatment period. 
One cohort with 3 dose levels (
 mg) is planned. A prednisone tablet is planned to 
be administered to healthy participants and taken PO on Day 1, followed by QD PO dose 
administration. The 
 mg and 
 mg prednisone groups’ safety and PD data will be reviewed to 
determine if the 1 mg prednisone group will be conducted and/or if the dose may be altered. 
Participants in the 
 mg and the  mg (if conducted) groups will receive prednisone for a total 
of 30 days. Participants in the 
 mg group will receive prednisone for a total of 7 days. 
Participants in all groups will be followed up for 2 weeks after the last dose of prednisone 
(Section 1.2). The 
 mg and 
mg prednisone dose groups may occur in parallel with each 
other as well as in parallel to Part A SAD or Part B MAD. 
 
 mg or  mg dose levels 
o PO QD dosing in healthy participants for a total of 30 days, then a 2-week follow-
up period after each dose level 
o Inpatient for approximately 30 days with follow-up period following the last dose 
of each dose level. 
 
 mg dose level 
o PO QD dosing in healthy participants for a total of 7 days, then a 2-week follow-
up period 
o Inpatient for approximately 7 days with follow-up period following the last dose. 
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Number of Participants: 
 participants (healthy participants and patients with AD) may be enrolled to 
ensure that 
 evaluable participants (
 healthy participants 
and up to 
 patients with AD) complete the study. Participants will include: 
 
 healthy participants enrolled in Part A (SAD cohorts) on LY3872386 
o 
 evaluable healthy participants 
o 
 replacements  
 Up to 
 patients with AD enrolled in Part B (MAD cohorts) on LY3872386 
o Up to 
 evaluable patients with AD) 
o 
 replacements  
o Japanese patients are not intended to exceed more than approximately 
% of the 
total evaluable patients with AD (for example up to approximately 
 patients 
with AD)  
 
 healthy participants enrolled in Part C (multiple dose cohort) on prednisone  
o 
 evaluable participants 
o 
 replacements  
Ethical Considerations of Benefit/Risk: Not applicable 
Data Monitoring Committee: No 
 
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J4L-MC-KMAA (b) 
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1.2. 
Schema  
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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1.3. 
Schedule of Activities (SoA)  
1.3.1. 
Part A: Single-Ascending Dose of LY3872386 in Healthy Participants  
Part A: Single-Ascending Dose of LY3872386 in Healthy Participants 
Procedures / 
Assessments 
Screening 
Treatment Period 
Follow-up 
E
D 
Comments 
Visit Number 
V1 
V2 
V 
801 
V 
802 
V 
803 
V 
804 
V 
805 
V 
806 
V 
807 
V 
808 
 
 
Study Day 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review/confirm I/E 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to CRU 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
 
P 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from 
CRU 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Outpatient visit 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Clinical Assessments 
 
Complete medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review AEs 
X 
X 
P 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant 
medications 
X 
X 
P 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Substance use 
(alcohol and 
tobacco use) 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
Physical 
examination 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
X 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Part A: Single-Ascending Dose of LY3872386 in Healthy Participants 
Procedures / 
Assessments 
Screening 
Treatment Period 
Follow-up 
E
D 
Comments 
Visit Number 
V1 
V2 
V 
801 
V 
802 
V 
803 
V 
804 
V 
805 
V 
806 
V 
807 
V 
808 
 
 
Study Day 
 
 
Weight 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECGs 
X 
 
P 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Chest x-ray, if 
indicated (posterior-
anterior view) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
QuantiFERON®-TB 
Gold test or TST 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IP administration 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory Assessments 
 
Serologies, syphilis, 
and FSH  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid-stimulating 
hormone, including 
T3/T4 tests 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Serum  
immunoglobulins 
X 
 
P 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Part A: Single-Ascending Dose of LY3872386 in Healthy Participants 
Procedures / 
Assessments 
Screening 
Treatment Period 
Follow-up 
E
D 
Comments 
Visit Number 
V1 
V2 
V 
801 
V 
802 
V 
803 
V 
804 
V 
805 
V 
806 
V 
807 
V 
808 
 
 
Study Day 
 
 
 
 
 
 
 
<1-, 15-, 
120-, and 
240-min 
post 
injection 
24 
hr 
X 
X 
 
 
X 
 
X 
 
X 
 
 
 
 
 
 
Urinary drug screen 
(including ethanol 
breath test) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Clinical chemistry  
X 
X 
P 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Bedside glucose 
monitoring 
 
X 
P and 
 12 hr  
24 hr 
and 
36 hr  
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Fasting lipid panel 
 
 
P 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
Hematology 
 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Hemoglobin A1c 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
Urinalysis 
 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
 
X 
X 
 
Approved on 10 Nov 2023 GMT
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Part A: Single-Ascending Dose of LY3872386 in Healthy Participants 
Procedures / 
Assessments 
Screening 
Treatment Period 
Follow-up 
E
D 
Comments 
Visit Number 
V1 
V2 
V 
801 
V 
802 
V 
803 
V 
804 
V 
805 
V 
806 
V 
807 
V 
808 
 
 
Study Day 
 
 
Pharmacogenetics  
 
 
 
P 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity 
 
 
P 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
LY3872386, total 
antibody, and 
LY3558533 (free 
payload) 
concentration (PK) 
 
 
P, EOI,  
3 hr,  
6 hr, and 
12 hr  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
P 
X 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
P 
X 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
P 
X 
 
 
 
 
X 
 
X 
 
 
 
 
 
X 
X 
 
 
P 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
 
P 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
X 
 
 
 
 
 
 
X 
 
X 
X 
X 
 
X 
 
X 
X 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Part A: Single-Ascending Dose of LY3872386 in Healthy Participants 
Procedures / 
Assessments 
Screening 
Treatment Period 
Follow-up 
E
D 
Comments 
Visit Number 
V1 
V2 
V 
801 
V 
802 
V 
803 
V 
804 
V 
805 
V 
806 
V 
807 
V 
808 
 
 
Study Day 
 
 
Cortisol  
 
X 
P and  
12 hr 
X 
X  X 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
  
 
X 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Part A: Single-Ascending Dose of LY3872386 in Healthy Participants 
Procedures / 
Assessments 
Screening 
Treatment Period 
Follow-up 
E
D 
Comments 
Visit Number 
V1 
V2 
V 
801 
V 
802 
V 
803 
V 
804 
V 
805 
V 
806 
V 
807 
V 
808 
 
 
Study Day 
 
 
Ocular pressure, 
visual acuity, and 
cataract evaluation  
X 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
Abbreviations: AE = adverse event; CRU = clinical research unit; 
 CXR = chest x-ray; d = day(s); ECG = electrocardiogram; 
ED = early discontinuation; EOI = end of IV infusion or subcutaneous dose administration; FSH = follicle-stimulating hormone; hr = hours; I/E = 
inclusion/exclusion; IP = investigational product; min = minutes; P = predose before IP administration; 
 PK = pharmacokinetic; SAD = 
single-ascending dose; TB = tuberculosis; TST = tuberculin skin test; V = visit.
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J4L-MC-KMAA (b) 
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1.3.2. 
Part B: Multiple-Ascending Dose of LY3872386 in Patients with Atopic Dermatitis  
1.3.2.1. 
Part B: LY3872386 
 Dosing Schedule  
Part B: LY3872386 
 Dosing Schedule 
Procedures/ 
Assessments 
Screening 
Treatment Period 
Follow-up 
ED 
Comments 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V 
801 
V 
802 
V 
803 
V 
804 
 
 
Study Day(s) 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review/confirm I/E 
criteria 
X 
P 
 
 
 
 
 
 
 
 
 
 
 
 
IWRS randomization 
 
P 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Assessments 
 
Complete medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review preexisting 
conditions/AEs 
X 
P 
P 
P 
P 
P 
P 
P 
X 
X 
X 
X 
X 
 
Concomitant 
medications 
X 
P 
P 
P 
P 
P 
P 
P 
X 
X 
X 
X 
X 
 
Previous and current 
AD treatments 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Substance use (alcohol 
and tobacco use) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
Weight 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
P 
P 
P 
P 
P 
P 
P 
X 
X 
X 
X 
X 
ECGs 
X 
P 
P 
P 
P 
P 
P 
P 
 
 
 
X 
X 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Part B: LY3872386 
 Dosing Schedule 
Procedures/ 
Assessments 
Screening 
Treatment Period 
Follow-up 
ED 
Comments 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V 
801 
V 
802 
V 
803 
V 
804 
 
 
Study Day(s) 
 
 
Chest x-ray, if 
indicated (posterior-
anterior view) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
IP administration 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
QuantiFERON®-TB 
Gold test or TST 
X 
 
 
 
 
 
 
 
 
 
 
 
 
vIGA-AD 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
EASI 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
SCORAD 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
POEM 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
DLQI 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Itch numeric rating 
scale 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
Laboratory Assessments 
 
Beta-D-glucan 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Serologies, syphilis, 
and FSH 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid-stimulating 
hormone, including 
T3/T4 tests 
 
P 
 
 
 
 
 
X 
 
 
 
X 
X 
Serum 
immunoglobulins 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
X 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Part B: LY3872386 
 Dosing Schedule 
Procedures/ 
Assessments 
Screening 
Treatment Period 
Follow-up 
ED 
Comments 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V 
801 
V 
802 
V 
803 
V 
804 
 
 
Study Day(s) 
 
 
Subcutaneous local 
injection-site 
assessment 
 
P 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
Urinary drug screen 
(including ethanol 
breath test) 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Pregnancy test 
X 
P 
P 
P 
P 
P 
P 
P 
 
 
 
X 
X 
Clinical chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Fasting lipid panel 
 
P 
 
P 
 
P 
 
 
X 
 
 
 
X 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hemoglobin A1c 
X 
X 
 
X 
 
 
 
X 
 
 
 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacogenetics 
 
P 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity 
 
P 
P 
P 
 
P 
 
P 
 
 
 
X 
X 
LY3872386, total 
antibody, and 
LY3558533 (free 
payload) concentration 
(PK) 
 
P, 
 EOI, 1 hr, 
and 3 hr 
P 
and 
EOI  
P 
 and 
EOI 
P  
and 
EOI  
P  
and 
EOI  
P 
and 
EOI  
P, 
EOI, 1 hr, 
and 3 hr 
X 
X 
X 
X 
X 
 
P  
and  
3 hr 
P 
P 
P 
P 
P 
P 
 
X 
X 
X 
X 
 
P 
P 
P 
P 
P 
P 
P 
 
 
 
X 
X 
 
P 
 
P 
 
P 
 
P 
 
 
 
 
X 
 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Part B: LY3872386 
 Dosing Schedule 
Procedures/ 
Assessments 
Screening 
Treatment Period 
Follow-up 
ED 
Comments 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V 
801 
V 
802 
V 
803 
V 
804 
 
 
Study Day(s) 
 
 
 
P 
P 
P 
 
P 
 
P 
 
X 
X 
X 
X 
 
P 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
P 
 
P 
 
 
 
X 
 
 
 
 
X 
 
P 
 
P 
 
 
P 
 
 
X 
 
X 
X 
 
P 
P 
P 
P 
P 
P 
P 
 
X 
X 
X 
X 
Ocular pressure, visual 
acuity, and cataract 
evaluation  
X 
 
 
X 
 
X 
 
 
X 
 
 
X 
X 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
26 
 
Abbreviations: AE = adverse event; AD = atopic dermatitis; 
d = day(s); DLQI = Dermatology Life Quality Index; EASI = 
Eczema Area and Severity Index; ECG = electrocardiogram; ED = early discontinuation; EOI = end of IV infusion or subcutaneous dose administration; 
FSH = follicle-stimulating hormone; I/E = inclusion/exclusion; IL-13 = interleukin 13; IP = investigational product; IWRS = Interactive Web Response 
System; MDC = Macrophage-derived chemokine; P = predose before IP administration; P1NP = Procollagen 1; PK = pharmacokinetic; POEM = Patient-
Oriented Eczema Measure; SCORAD = SCORing Atopic Dermatitis; TARC = Thymus- and activation-regulated chemokine; TB = tuberculosis; TST = 
tuberculin skin test; V = visit; vIGA-AD = Validated Investigator’s Global Assessment for Atopic Dermatitis.
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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1.3.2.2. 
Part B: LY3872386 
 Dosing Schedule  
Part B: LY3872386 
 Dosing Schedule 
Procedures/ 
Assessments 
Screening 
Treatment Period 
Follow-up 
E 
D 
Comments 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V 
801 
V 
802 
V 
803 
V 
804 
V 
805 
 
 
Study Day(s) 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review/confirm I/E 
criteria 
X 
P 
 
 
 
 
 
 
 
 
 
 
 
 
 
IWRS randomization 
 
P 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Assessments 
Complete medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review preexisting 
conditions/AEs 
X 
P 
X 
P 
X 
P 
X 
P 
 
X 
X 
X 
X 
X 
 
Concomitant 
medications 
X 
P 
X 
P 
X 
P 
X 
P 
 
X 
X 
X 
X 
X 
 
Previous and current 
AD treatments 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Substance use (alcohol 
and tobacco use) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
 
 
X 
 
X 
 
X 
 
 
X 
 
X 
X 
Weight 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
P 
X 
P 
X 
P 
X 
P 
 
X 
X 
X 
X 
X 
ECGs 
X 
P 
 
P 
 
P 
 
P 
 
 
 
 
X 
X 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Part B: LY3872386 
 Dosing Schedule 
Procedures/ 
Assessments 
Screening 
Treatment Period 
Follow-up 
E 
D 
Comments 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V 
801 
V 
802 
V 
803 
V 
804 
V 
805 
 
 
Study Day(s) 
 
 
Chest x-ray, if 
indicated (posterior-
anterior view) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
IP administration 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
QuantiFERON®-TB 
Gold test or TST 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
vIGA-AD 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
EASI 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
SCORAD 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
POEM 
X 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
DLQI 
X 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
Itch numeric rating 
scale 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
Laboratory Assessments 
Beta-D-glucan 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serologies, syphilis, 
and FSH 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid-stimulating 
hormone, including 
T3/T4 tests 
 
P 
 
 
 
 
 
X 
 
 
 
 
X 
X 
Serum 
immunoglobulins 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Part B: LY3872386 
 Dosing Schedule 
Procedures/ 
Assessments 
Screening 
Treatment Period 
Follow-up 
E 
D 
Comments 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V 
801 
V 
802 
V 
803 
V 
804 
V 
805 
 
 
Study Day(s) 
 
 
Subcutaneous local 
injection-site 
assessment 
 
P 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
See Section 8.2.6. 
Urinary drug screen 
(including ethanol 
breath test) 
X 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
Pregnancy test 
X 
P 
 
P 
 
P 
 
P 
 
 
 
 
X 
X 
Clinical chemistry 
X 
X 
X 
X 
 
X 
X 
X 
 
 
X 
X 
X 
X 
Fasting lipid panel 
 
P 
 
P 
 
P 
 
P 
 
 
 
 
 
X 
Hematology 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
Hemoglobin A1c 
X 
X 
 
X 
 
 
 
X 
 
 
 
 
X 
X 
Urinalysis 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
Pharmacogenetics 
 
P 
 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity 
 
P 
X 
P 
X 
P 
X 
P 
 
X 
X 
X 
X 
X 
LY3872386, total 
antibody, and 
LY3558533 (free 
payload) concentration 
(PK) 
 
P, 
 EOI,  
1 hr, and 
3 hr 
X 
P 
 and 
EOI 
X 
P  
and 
EOI 
X 
P,  
EOI, 
1 hr, and 
3 hr 
X 
X 
X 
X 
X 
X 
 
P  
and  
3 hr 
X 
P 
X 
P 
X 
P 
 
X 
X 
X 
X 
X 
 
P 
X 
P 
X 
P 
X 
P 
 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Part B: LY3872386 
 Dosing Schedule 
Procedures/ 
Assessments 
Screening 
Treatment Period 
Follow-up 
E 
D 
Comments 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V 
801 
V 
802 
V 
803 
V 
804 
V 
805 
 
 
Study Day(s) 
 
 
 
P 
X 
P 
 
P 
 
P 
 
X 
X 
X 
X 
X 
 
P 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
P 
 
P 
 
 
 
X 
 
 
 
 
 
X 
 
P 
 
P 
 
 
X 
 
 
 
X 
 
X 
X 
 
P 
 
P 
 
P 
 
P 
 
 
X 
 
X 
X 
Ocular pressure, visual 
acuity, and cataract 
evaluation  
X 
 
 
X 
 
X 
 
 
X 
 
 
 
X 
X 
Approved on 10 Nov 2023 GMT
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J4L-MC-KMAA (b) 
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Abbreviations: AE = adverse event; AD = atopic dermatitis; 
 d = day(s); DLQI = Dermatology Life Quality Index; EASI = 
Eczema Area and Severity Index; ECG = electrocardiogram; ED = early discontinuation; EOI = end of IV infusion or subcutaneous dose administration; 
FSH = follicle-stimulating hormone; I/E = inclusion/exclusion; IL-13 = interleukin 13; IP = investigational product; IWRS = Interactive Web Response 
System; MDC = Macrophage-derived chemokine; P = predose before IP administration; P1NP = Procollagen 1; PK = pharmacokinetic; POEM = Patient-
Oriented Eczema Measure; SCORAD = SCORing Atopic Dermatitis; TARC = Thymus- and activation-regulated chemokine; TB = tuberculosis; TST = 
tuberculin skin test; V = visit; vIGA-AD = Validated Investigator’s Global Assessment for Atopic Dermatitis. 
Approved on 10 Nov 2023 GMT
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1.3.3. 
Part C: Open-Label Multiple Dose of Prednisone in Healthy Participants  
1.3.3.1. 
Part C: Prednisone 
 mg and  mg Dosing Schedule  
Part C: Prednisone 
 mg and mg Dosing Schedule 
Procedures/ 
Assessments 
Screening 
Dosing Period 
Follow-up 
ED 
Comments 
Visit Number 
V1 
V2 
V801 
 
 
Study Day 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Review/confirm I/E 
criteria 
X 
 
X 
 
 
 
 
 
 
 
 
 
Admission to CRU 
 
X 
 
 
 
 
 
 
 
 
 
Discharge from 
CRU 
 
 
 
 
 
 
 
 
X 
 
 
Outpatient visit 
 
 
 
 
 
 
 
 
 
X 
X 
 
Clinical Assessments 
Complete medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
Review AEs 
X 
X 
X 
P 
P 
P 
P 
P 
X 
X 
X 
 
Concomitant 
medications 
X 
X 
X 
P 
P 
P 
P 
P 
X 
X 
X 
 
Substance use 
(alcohol and 
tobacco use) 
X 
 
X 
 
 
 
 
 
 
 
X 
Physical 
examination 
X 
 
X 
 
 
 
 
 
X 
X 
X 
Weight 
X 
 
X 
 
 
 
 
 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X 
P 
P 
P 
P 
P 
X 
X 
X 
ECGs 
X 
 
X 
 
 
 
 
 
X 
X 
X 
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Chest x-ray, if 
indicated (posterior-
anterior view) 
X 
 
 
 
 
 
 
 
 
 
 
QuantiFERON®-TB 
Gold test or TST 
X 
 
 
 
 
 
 
 
 
 
 
IP administration 
 
 
 
X 
X 
X 
X 
X 
 
 
 
Laboratory Assessments 
Serologies, syphilis, 
and FSH 
X 
 
 
 
 
 
 
 
 
 
 
Thyroid-stimulating 
hormone, including 
T3/T4 tests 
 
 
X 
 
 
 
 
 
 
X 
X 
Serum 
immunoglobulins 
X 
 
 
P 
 
P 
 
P 
 
X 
X 
Urinary drug screen 
(including ethanol 
breath test) 
X 
 
X 
 
 
 
 
 
 
 
 
Pregnancy test 
X 
 
X 
 
 
 
 
 
 
X 
 
Clinical chemistry  
X 
 
X 
 
Day 2 and 
Day 7 (P) 
P 
Day 21 
(P) 
P 
 
X 
X 
Fasting lipid panel 
 
 
 
P 
 
 
 
P 
 
 
X 
Hematology 
X 
 
X 
 
Day 2 and 
Day 7 (P) 
P 
Day 21 
(P) 
P 
 
X 
X 
Hemoglobin A1c 
X 
 
 
 
 
 
 
 
 
 
 
Urinalysis 
X 
 
X 
 
Day 2 and 
Day 7 (P) 
P 
Day 21 
(P) 
P 
 
X 
X 
Pharmacogenetics  
 
 
 
P 
 
 
 
 
 
 
 
Prednisone and 
prednisolone 
concentrations (PK) 
 
 
 
P, 0.5, 1, 
1.5, 2, 3, 4, 
6, 8, 10, 
and 12 hr 
X 
X 
X 
P, 
0.5, 1, 1.5, 2, 
3, 4, 6, 8, 10, 
and 12 hr 
X  
 
X 
 
 
 
P 
 
X 
 
X 
 
 
X 
 
 
 
P 
 
X 
 
X 
 
 
X 
 
 
 
P 
 
X 
 
X 
 
 
X 
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Abbreviations: AE = adverse event; CRU = clinical research unit; CT = computed tomography; 
 d = day(s); ECG = 
electrocardiogram; ED = early discontinuation; FSH = follicle-stimulating hormone; hr = hour(s); I/E = inclusion/exclusion; IP = investigational product; P = 
predose before IP administration; 
 PK = pharmacokinetic; PO = oral administration; TB = tuberculosis; TST = tuberculin skin test; V = 
visit.
 
 
 
P 
Day 7 (P) 
P 
Day 21 
(P) 
P 
 
X 
X 
 
 
X 
P and 12 hr 
P 
 
P 
 
X 
 
 
 
 
 
P 
P 
P 
P 
P 
 
 
 
 
 
X 
 
Day 7 (P) 
P 
 
P 
 
X 
X 
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1.3.3.2. 
Part C: Prednisone 
 mg Dosing Schedule  
Part C: Prednisone 
 mg Dosing Schedule 
Procedures/Assessments 
Screening 
Dosing Period 
Follow-up 
E
D 
Comments 
Visit Number 
V1 
V2 
V801 
V802 
V803 
 
 
Study Day 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review/confirm I/E criteria 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to CRU 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from CRU 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Outpatient visit 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
 
Clinical Assessments 
Complete medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review AEs 
X 
X 
X 
P 
P 
P 
P 
P 
P 
P 
X 
X 
X 
X 
 
Concomitant medications 
X 
X 
X 
P 
P 
P 
P 
P 
P 
X 
X 
X 
X 
X 
 
Substance use (alcohol and 
tobacco use) 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
Physical examination 
X 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
Weight 
X 
 
X 
 
 
 
 
X 
 
 
 
 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X 
P 
P 
P 
P 
P 
P 
P 
X 
X 
X 
X 
ECGs 
X 
 
X 
 
 
 
 
 
 
X 
 
 
X 
X 
Chest x-ray, if indicated 
(posterior-anterior view) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
QuantiFERON®-TB 
Gold test or TST 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
IP administration 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
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Laboratory Assessments 
Serologies, syphilis, and 
FSH 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.2. 
Thyroid-stimulating 
hormone, including T3/T4 
tests 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
Serum immunoglobulins 
X 
 
 
P 
 
 
 
 
 
P 
 
P 
P 
P 
Urinary drug screen 
(including ethanol breath 
test) 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
Clinical chemistry  
X 
 
X 
 
P 
P 
 
P 
 
P 
 
X 
X 
X 
Hematology 
X 
 
X 
 
P 
P 
 
P 
 
P 
 
X 
X 
X 
Hemoglobin A1c 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysis 
X 
 
X 
 
P 
P 
 
P 
 
P 
 
X 
 
X 
Pharmacogenetics  
 
 
 
P 
 
 
 
 
 
 
 
 
 
 
Prednisone and 
prednisolone concentration 
(PK) 
 
 
 
P, 0.5, 1, 
1.5, 2, 3, 4, 
6, 8, 10, 
and  
12 hr 
P 
P 
P 
P 
P 
P, 
0.5, 1, 
1.5, 2, 3, 
4, 6, 8, 
10, and  
12 hr 
X 
X 
X 
X 
 
 
 
P 
X 
 
X 
 
 
X 
 
 
X 
X 
 
 
 
P 
X 
 
 
 
 
X 
 
 
X 
X 
 
 
 
P 
X 
 
X 
 
 
X 
 
 
X 
X 
 
 
 
P 
 
 
X 
 
 
X 
 
 
X 
X 
 
 
 
P 
 
 
 
 
 
P 
 
X 
X 
X 
 
 
X 
P and 12 hr 
P 
P 
P 
P 
P 
 
 
 
 
 
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Abbreviations: AE = adverse event; CRU = clinical research unit; CT = computed tomography; 
 d = day(s);  
ECG = electrocardiogram; ED = early discontinuation; FSH = follicle-stimulating hormone; hr = hour(s); I/E = inclusion/exclusion; IP = investigational 
product; P = predose before IP administration; P1NP = Procollagen 1; PD = pharmacodynamic; PK = pharmacokinetic; PO = oral administration; 
TB = tuberculosis; TST = tuberculin skin test; V = visit.
 
 
 
P 
 
 
 
 
P 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
P 
 
 
X 
X 
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2. 
Introduction  
LY3872386 is an ADC consisting of an anti-IL-4R antagonist mAb covalently conjugated via a 
linker to a small molecule GC (payload or LY3558533, also known as LSN3558533). Once 
LY3872386 is internalized by cells, cleavage of the linker is expected to release the GC payload, 
which can activate the GR. The mAb component (LY3842708) of the ADC is a fully human 
IgG4 that specifically recognizes human IL-4Rα subunit (IL-4Rα) with high affinity and 
antagonizes type 1 and type 2 IL-4R activity from both IL-4 and IL-13 cytokines. The payload is 
a novel and potent GR agonist with selectivity over other nuclear hormone receptors. 
The IL-4R pathway is clinically validated in several Type 2 inflammatory diseases, such as AD, 
asthma, and nasal polyposis (Bachert et al. 2019). In addition, GCs are known to be potent anti-
inflammatory agents and are used in a number of inflammatory diseases, including AD. 
However, the pleiotropic effects of GCs lead to multiple undesired effects that limit their use 
(Rhen and Cidlowski 2005). LY3872386 has the potential to provide anti-inflammatory effects 
from both the activation of the GR pathway and the inhibition of the IL-4R pathway, while 
targeting the delivery of the GC payload to IL-4R-expressing cells which are pathogenic in 
various inflammatory disorders, including AD. 
2.1. 
Study Rationale  
Study J4L-MC-KMAA (KMAA) is the first-in-human study that will investigate the safety, 
tolerability, and PK of single doses of LY3872386 in healthy participants and repeat doses in 
patients with AD. An exploratory evaluation of target engagement through IL-4R RO will be 
conducted following single doses of LY3872386 in healthy participants and repeat dose in 
patients with AD. Exploratory assessments of clinical PD and efficacy in patients with AD are 
also included. Additionally, this study will assess the safety, tolerability, and PK 
 
 of prednisone in healthy participants 
 
The prednisone treatment will not be blinded with a placebo. 
 
 
2.2. 
Background  
IL-4 and IL-13 cytokines play a key role in the initiation, amplification, and downstream tissue 
effects that result in Type 2 inflammatory disease. The IL-4R pathway is a clinically validated 
pathway in several Type 2 inflammatory diseases (for example, AD, asthma, and nasal 
polyposis). The two types of receptors formed with the IL-4Rα subunit are type 1 IL-4R and type 
2 IL-4R. Type 1 IL-4R is composed of IL-4Rα and common γ chain, whereas type 2 IL-4R is 
composed of IL-4Rα and the IL-13R α1 chain (IL-13Rα1). Hematopoietic or immune cells 
mainly express type 1 IL-4R, whereas type 2 IL-4R/IL-13R is more widely expressed on non-
hematopoietic/immune cells or tissue-resident cells. The IL-4/IL-13/IL-4R axis has been 
evaluated with antagonist antibody therapies such as dupilumab and tralokinumab which are 
approved for the treatment of various inflammatory disorders. GCs have pleiotropic effects, 
including involvement in the metabolism of various macromolecules, including carbohydrates, 
fats, and proteins. GCs are also widely known for their anti-inflammatory properties and are 
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commonly used for the treatment and management of various immunological diseases. While 
GCs can be highly effective anti-inflammatory mediators, they are known to have various 
undesirable short- and long-term effects, such as adrenal insufficiency, osteoporosis, and 
diabetes, which limit their use. By targeting these 2 mechanisms of action through an IL-4R 
antagonist mAb conjugated to a GC, the ADC inhibits IL-4R signaling and potentially delivers 
GCs to IL-4R expressing cells. Therefore, the ADC provides additional anti-inflammatory 
effects above the inhibition of the IL-4R pathway while potentially reducing undesired GC-
related effects. 
 
The key characteristics of LY3872386 are listed below. 
Nonclinical Biology/Pharmacology Data 
 LY3872386 has high affinity (in vitro binding) for human IL-4R (KD = 
 pM) and 
cynomolgus monkey IL-4R (KD=
 pM) and blocks IL-4 and IL-13 mediated IL-4R 
signaling in cells.  
 LY3872386 inhibits IL-4R signaling and induces GC responses in myeloid cells, 
demonstrating dual activity of LY3872386 within the same cells.  
 LY3872386 inhibits IL-5 and IL-13 cytokine secretion and induces GC/GR-mediated 
gene expression in Th2 differentiated T cells, which are key mediators of type 2 
inflammation.    
 LY3872386 inhibits IL-4R-dependent and IL-4R-independent cytokine secretion from 
human peripheral blood mononuclear cells, indicating added anti-inflammatory effects of 
the ADC above the inhibition of the IL-4R pathway alone. 
 LY3872386 more robustly reduces antigen-challenged-induced inflammation compared 
to the IL-4R mAb in a humanized mouse model of inflammation. This supports the dual 
activity of LY3872386, resulting in superior efficacy compared to the antagonist IL-4R 
mAb alone in vivo.  
 LY3558533 (payload) is a highly potent novel activator of the GR. In a cell-based in vitro 
assay, the payload (LY3558533) EC50 were 
 nM 
 for CD4+ T cells, 
 nM 
 for CD19+ B cells, and 
 nM 
 for CD33+ myeloid cells (geometric mean 
± standard error of the mean). 
 LY3558533 (payload) has higher selectivity towards the GR compared to the 
progesterone, androgen, estrogen, and mineralocorticoid receptors:  
o The IC50 for competition displacement of the radioligand from the receptor was 
 nM for the GR, 
 µM for the progesterone receptor, and over 
 µM for 
the androgen and estrogen receptors. 
o The EC50 in the cell-based translocation assay was 
 nM for the GR and 
 µM 
for the progesterone and mineralocorticoid receptors.  
Nonclinical Toxicology Data 
In support of Phase 1 clinical development, the following nonclinical toxicity studies were 
conducted with LY3872386 (ADC) or with LY3558533 (payload): 
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LY3872386 (ADC) 
A 3-month repeat-dose study in monkeys, including an evaluation of safety pharmacology, was 
conducted. The key findings in the monkey study were dose-dependent decreases in circulating 
lymphocytes, and decreases in lymphocytes or lymphoid follicle centers, in thymus, spleen, and 
lymph nodes. Other important findings were atrophy of skin hair follicles, especially near 
injection sites, and effects suggestive of suppression of the HPA axis. These effects were 
generally consistent with the intended pharmacology of the ADC. The immunosuppressive 
effects on lymphocytes were considered contributory to a severe Staphylococcus aureus 
ulcerative dermatitis, leading to clinical decline and euthanasia in 1 monkey administered the 
highest dose of LY3872386.  
A cross-reactivity study of LY3872386 in tissues from humans and non-human primates 
demonstrated binding consistent with the reported expression of IL-4R in mononuclear cell 
populations and generally consistent with the findings in the toxicology study.  
LY3558533 (Payload) 
General toxicity 
One-month repeat-dose toxicology studies with LY3558533 were conducted in rats and 
monkeys. There were no adverse findings in either study, up to the highest dose tested. Observed 
effects were generally consistent with known effects of GC in animal species. 
Safety pharmacology 
In an in vitro hERG assay, the IC50 for the inhibitory effect of LY3558533 on hERG potassium 
current was estimated to be greater than  µM, an unbound plasma concentration that would not 
be achievable in humans.   
Genotoxicity 
LY3558533 was evaluated for mutagenicity in an Ames assay, and for effects on chromosomes 
in human TK6 cells and in rats. There were no effects observed in any study, up to the highest 
concentration or dose tested. 
 
Nonclinical Drug Disposition and Pharmacokinetics 
LY3872386 (ADC) 
 The PK of LY3872386 (fully intact DAR4) and total antibody (includes unconjugated Ab 
and Ab conjugated to at least 1 payload) were evaluated in PK study in monkeys after IV 
and SC doses of LY3872386. The plasma clearance of LY3872386 or total antibody was 
low in monkeys based on comparison to hepatic blood flow. The relative SC 
bioavailability of LY3872386 was approximately 
%. 
 The TK of LY3872386, total antibody, and LY3558533 (unconjugated payload) were 
evaluated in the 3-month GLP toxicology study. The exposure to LY3872386 and total 
antibody increased with increasing dose in an approximately dose-proportional manner on 
Day 1 and in a greater than dose-proportional manner on Day 85. The exposure to 
LY3558533 increased in an approximately dose-proportional manner. Based on mean 
exposures including all animals, no to minimal accumulation of LY3872386, total 
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antibody, or LY3558533 (unconjugated payload) was observed following repeat SC or IV 
administration of LY3872386. ADA positive response was detected in multiple animals 
after repeat SC dosing and contributed to the decrease in exposure of LY3872386 and total 
antibody on Day 85. The presence of ADA had no impact on the exposure to LY3558533 
(unconjugated payload). 
 The stability of fully intact LY3872386 (DAR4, containing all 4 GC payloads) was 
evaluated in vivo using PK plasma samples and by in vitro incubations with plasma and 
serum. The percent remaining of intact LY3872386 in vivo in monkey plasma remained 
≥90% for IV and SC by 168 hours and 
% IV and 
% SC by 336 hours postdose, 
demonstrating adequate stability of LY3872386 in vivo. The in vitro stability in human 
plasma or serum was generally comparable to that in preclinical species.  
 
LY3558533 (Payload) 
 The PK of LY3558533 were evaluated in rats and monkeys after IV or SC doses of 
LY3558533. The plasma clearance of LY3558533 was high in rat and moderate in 
monkey based on comparison to hepatic blood flow. The SC bioavailability of 
LY3558533 was approximately 
% with half-life ranging from  to  hours across 
species after SC dose.   
 The TK of LY3558533 were evaluated in rats and monkeys in GLP toxicology studies 
after IV or SC doses of LY3558533. The exposure to LY3558533 increased with dose, 
but the increase was not always dose-proportional. No gender difference was observed. 
After repeated daily, there was no or minimal accumulation of LY3558533 in rats and 
monkeys.   
 The in vitro plasma protein binding of LY3558533 ranged from 
% to 
% in 
mouse, rat, dog, monkey, and humans. 
 Based on preliminary metabolite identification and qualitative profiling, LY3558533 was 
the most prominent component circulating in rat and monkey plasma. The metabolic 
pathways include oxidations, direct or secondary glucuronidation and N-acetylation. The 
in vitro metabolite profile was generally similar between nonclinical species and human. 
 Excretion data from rats and monkeys suggest that LY3558533 is cleared via hepatic 
metabolism with minimal contribution of biliary excretion.  
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Additional information regarding the in vitro and in vivo mechanism of action, toxicological, and 
drug disposition assessments of LY3872386 or LY3558533 are available in the IB. 
2.3. 
Benefit/Risk Assessment  
The toxicology data for LY3872386 demonstrate an acceptable nonclinical safety profile and 
margin of safety to support the transition from preclinical status to a clinical single-dose study in 
healthy participants and a multiple-dose study in patients with AD.  
The nonclinical safety profile of LY3872386 is generally consistent with its intended 
pharmacology. Primary safety concerns predicted from studies with the ADC and the payload are 
bacterial and other infections, secondary to decreases in lymphoid tissue lymphocytes and 
circulating blood lymphocytes. Other potential risks identified for LY3872386 in toxicology 
studies and consistent with GC pharmacology are 
 atrophy of skin hair follicles, especially near SC injection sites, potentially leading to 
thinning hair or hair loss 
 suppression of the HPA axis 
 increased serum triglycerides, and 
 increased serum glucose. 
The safety and efficacy associated with modulation of the IL-4/IL-13/IL-4R axis have been 
evaluated with approved drugs such as dupilumab and tralokinumab, and the safety and efficacy 
of GCs as a class are well-established. The key safety concerns and PD effects of LY3872386, 
including infection, conjunctivitis, hypersensitivity reactions, local injection site reactions, and 
systemic GC exposure from LY3558533 (free payload), will be closely monitored during the 
clinical study. 
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As with other immunomodulatory therapies, LY3872386 and prednisone may increase the risk of 
developing infections, increase the risk of an infection becoming more serious, and/or change the 
effectiveness of vaccines administered. LY3872386 may also increase the risk of opportunistic 
infections and the reactivation of latent infections. Participants will therefore be screened for 
hepatitis B, hepatitis C, HIV, and TB. In addition, all participants should be monitored for 
symptoms and signs of infection after administration of LY3872386 or prednisone. 
Infusion reactions and hypersensitivity reactions are potential risks for all biologics. These risks 
will be carefully monitored during the dosing period in Parts A and B (the LY3872386 portions 
of the study), with close observation after infusion and stopping rules that prevent re-challenge 
of patients/participants with significant hypersensitivity reactions. 
There is no anticipated therapeutic benefit for the healthy participants in this trial. However, 
healthy participants may benefit from the screening procedures (through detection of unknown 
health issues) even if they receive no therapeutic benefit from the study. In addition, patients 
with AD may derive therapeutic benefit from the trial. 
LY3872386 has not been administered to humans previously. Therefore, this study has been 
designed in accordance with the Guideline on Strategies to Identify and Mitigate Risks for First‐ 
in‐human Clinical Trials with Investigational Medicinal Products (EMA 2017). More 
information about the known and expected benefits, risks, SAEs, and reasonably anticipated AEs 
of LY3872386 is to be found in the IB. 
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3. 
Objectives and Endpoints  
Objectives 
Endpoints 
Primary 
 
To characterize the safety of LY3872386 after single 
dose administration in healthy participants and after 
repeat dose administration in patients with AD. 
 
To characterize the safety of prednisone in healthy 
participants receiving multiple PO QD doses in various 
dosing groups. 
 
Number and incidence of AEs, TEAEs, and 
SAEs 
 
 
Number and incidence of AEs, TEAEs, and 
SAEs 
Secondary 
 
To characterize the PK of LY3872386, total antibody, 
and the LY3558533 (free payload) following single dose 
administration in healthy participants and after repeat 
dosing in patients with AD. 
 
To characterize the PK of prednisone in healthy 
participants receiving multiple PO QD doses in various 
dosing groups. 
 
Cmax and AUC of LY3872386, total 
antibody, and LY3558533 (free payload) 
 
 
Cmax and AUC of prednisone and 
prednisolone  
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Objectives 
Endpoints 
Abbreviations: AE = adverse event; AD = atopic dermatitis; AUC = area under the concentration versus time curve; 
Cmax = maximum observed drug concentration; 
 
 
 PK = pharmacokinetics; PO = oral 
administration; 
 QD = once daily; SAE = serious adverse event; 
SC = subcutaneous;
 
Primary Endpoint Analysis 
TEAEs, SAEs, and AEs for each IP will be listed, and if the frequency of events allows, 
descriptive statistics will summarize the safety data per race and ethnicity. Symptoms, their 
incidence, severity, and association with the IP, as perceived by the investigator, will be reported 
separately for each treatment and IP. All TEAEs will be summarized across each part of the 
study by system organ class and by decreasing frequency according to the Medical Dictionary 
for Regulatory Activities. 
 
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4. 
Study Design  
4.1. 
Overall Design  
Study KMAA is a first-in-human trial designed to characterize the safety and tolerability of 
LY3872386 as well as the PK of LY3872386, total antibody, and LY3558533 (free payload) in 
healthy participants and in patients with AD. Additionally, this study will assess the safety, PK, 
tolerability, and PD of various dose levels of prednisone in healthy participants. The study will 
enroll participants of any ethnicity. The inclusion of healthy Japanese and Chinese participants in 
Part A, the LY3872386 SAD portion of this study, will facilitate the inclusion of Japanese and 
Chinese participants in subsequent clinical trials. The study will be conducted in 3 parts as 
follows: 
 Part A (SAD of LY3872386) will characterize the safety, tolerability, PK, and PD after 
single IV and SC dose administration of LY3872386 in healthy participants. 
 Part B (MAD of LY3872386) will characterize the safety, tolerability, PK, and PD after 
multiple SC and/or IV dose administrations of LY3872386 in patients with AD.  
 Part C 
 will assess the safety, tolerability, PK, and PD 
after repeat PO administration of prednisone in healthy participants. 
Section 1.2 illustrates the study schema and demonstrates the relationship among Parts A, B, and 
C. Section 1.2 also provides details on dosing and the inclusion of healthy Chinese and Japanese 
participants. Part A will begin first and will inform and thereby trigger the initiation of Parts B 
and C. 
Screening Period 
Screening may occur up to 35 days prior to Day 1 of the study. After obtaining informed 
consent, participants will be screened for eligibility as detailed in Section 5. Screening 
procedures will be performed as outlined in the SoA (Section 1.3). 
Participants who are not enrolled within 35 days of screening may be subjected to an additional 
medical assessment and/or clinical measurements to confirm their eligibility. The assessments 
will be repeated at the discretion of the investigator. 
Treatment Period and Visit Frequency 
Part A: SAD of LY3872386 in Healthy Participants 
Part A will be a SAD study of LY3872386 in healthy participants and will be comprised of 8 
cohorts. SAD Cohorts 1 to 5 will consist of 
 healthy participants each who will 
be randomly assigned to receive LY3872386:placebo in a 
manner. SAD Cohorts 6 to 8 will 
consist of 
 participants who will be randomly assigned to receive 
LY3872386:placebo in a 
 manner. See Table KMAA.1 for further details.  
The planned doses are 
mg IV (Cohort 1), 
 mg IV (Cohort 2), 
 mg IV (Cohort 3), 
 
mg IV (Cohort 4), 
 mg SC (Cohort 5), 
 mg IV (Cohort 6), 
 mg SC (Cohort 7), and 
 
mg IV (Cohort 8). The study intervention will be administered as a single dose on Day 1, 
followed by a 12-week follow-up period. Dose escalation will be based on the review of 
available data from the ongoing cohorts. Refer to Section 6.6.1 for further details on dose 
escalation. 
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he maximal concentration of LY3872386 following IV 
administration is expected to occur immediately following the single dose, while the maximal 
concentration of LY3872386 following SC administration is uncertain and is projected to occur 
approximately 1 to 4 days after the dose following single administration, which is similar to 
reports for mAb therapies (Ryman and Meibohm 2017). However, the maximal concentration of 
LY3558533 (free payload) following administration is uncertain and is projected to occur 
approximately  to  days after dose following a single SC administration. 
 
 
  
Refer to Sections 6.1.1 and 6.6.1.1 for details on administration and data review prior to dosing. 
Participants will be inpatient 
, followed by visits at regular intervals. 
Participants will be monitored for safety, 
 and samples will be collected as 
outlined in Section 1.3.1. Participants will be discharged from the CRU 
 after all the 
study assessments have been completed during the treatment period and in agreement with the 
investigator. 
Part B: MAD of LY3872386 in Patients with Atopic Dermatitis 
Part B will be a MAD study in patients with AD and will be comprised of 2 cohorts. Each cohort 
will consist of at least 
 randomized participants. 
The planned doses are 
 mg IV or SC (Cohort 1) and 
 mg IV or SC (Cohort 2). The 
study intervention will be administered 
 
 for up to 12 weeks. See Table KMAA.1 for further details. 
Participants will be followed on an outpatient basis by visits at regular intervals.  
Refer to Sections 6.1.1 and 6.6.1.2 for details on administration, commencement of Part B, and 
data review prior to dosing. 
Part C: Open-label Multiple Dose of Prednisone in Healthy Participants 
Part C will be an open-label multiple dose study of prednisone in 1 cohort of healthy 
participants. Participants will receive either 
 mg of prednisone (Table KMAA.2). 
 
 mg or  mg prednisone PO QD for a total of 
 doses 
 
  
 
 mg prednisone PO QD for a total of  doses 
 
 
Refer to Sections 6.1.1and 6.6.1.3 for details on administration and the commencement of Part C. 
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For all study parts 
The timings and procedures are outlined in Section 1.3. If the investigator deems it necessary, 
participants may remain in the CRU for a longer duration. Any changes to the planned discharge 
day will be made in consultation with the sponsor. 
Follow-up Period  
Participants will be required to return to the CRU for clinical assessments and blood samples on 
an outpatient basis (Section 1.3). The final follow-up visit will be approximately 12 weeks after 
the single dose of the study intervention in Part A, 14 weeks after the last dose of the study 
intervention in Part B, and 2 weeks after the last dose of prednisone in Part C. 
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Table KMAA.1. Summary of Participants in Cohorts Dosed with LY3872386  
Part A: SAD of LY3872386 in Healthy Participantsa 
Cohort # 
Planned Dose / 
Administration 
Route 
Number of 
Planned Non-
Japanese / 
Non-Chinese 
Participants 
Number of 
Planned 
Japanese 
Participants 
Number of 
Planned 
Chinese 
Participants 
Total Number 
of Planned 
Completers 
LY 
PBO 
LY 
PBO 
LY 
PBO 
 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 5 
 mg IV 
 mg IV 
 mg IV 
 mg SC 
 LY:  PBO 
 per cohort 
Cohort 4b 
 mg IV 
 
 
 
 
 
 
 
Cohort 6c 
Cohort 7c 
Cohort 8c 
 mg IV 
 mg SC 
 mg IV 
 
 
 
 
 
 
per cohort 
Part B: MAD of LY3872386 in Patients with AD 
Cohort # 
Planned Dose/ 
Administration 
Route 
Number of Planned Patients 
Total Number 
of Planned 
Randomized 
Patients 
Cohort 1 
mg IV or SC 
 LY:  PBO 
 
Cohort 2 
 mg IV or SC 
 LY:  PBO 
 
Abbreviations: AD = atopic dermatitis; IV = intravenous; LY = LY3872386; MAD = multiple-ascending dose, 
PBO = placebo; SAD = single-ascending dose; SC = subcutaneous. 
a Sentinel dosing will be used. 
b Sentinel pair must be non-Japanese and non-Chinese participants OR Sentinel pair must be mixed ethnicities (  
non-Japanese/non-Chinese participant and  Japanese participant). 
c Sentinel pair must be non-Japanese and non-Chinese participants.  
 
Table KMAA.2. Summary of Participants Dosed with Prednisone  
Part C: Multiple Doses of Prednisone in Healthy Participants 
Dosing Group 
Planned Dose/Administration Route 
Total Number of Planned Completers 
Group 1 
 mg PO  
 
Group 2 
 mg PO 
 
Group 3 
 mg PO 
 
Abbreviation: PO = oral administration. 
 
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4.2. 
Scientific Rationale for Study Design  
Study KMAA is the first-in-human dose study that will characterize the safety, tolerability, and 
PK of single doses of LY3872386 in healthy participants, multiple doses of LY3872386 in 
patients with AD, and multiple dose levels of prednisone in healthy participants. Participants 
receiving prednisone PO QD will not be blinded with a placebo. Blinding of subjects to 
prednisone was not deemed necessary as only objective safety and PD biomarker results 
following prednisone or LY3872386 administration will be compared. A lack of blinding would 
not be expected to affect these results. The data generated in this study will guide the design of 
the subsequent clinical trials. 
4.3. 
Justification for Dose  
Dose ranges from 
 mg IV to 
 mg IV and from 
 mg SC to 
 mg SC LY3872386 was 
selected to evaluate in the SAD and MAD portions of the study, respectively, based on current 
nonclinical pharmacology and toxicology data.  
Human Pharmacokinetics and Dose Prediction  
 
Human PK parameters were determined using allometric scaling (Deng et al. 2011).  
According to the model, the projected desired efficacious dose range to meet expected outcome 
measures on EASI disease score percent change from baseline ranged from 
 mg to 
 mg 
 SC. Based on the emerging safety, PK, and PD from SAD Part A, 
 SC and/or IV 
dosing may be investigated to evaluate clinical effects in the MAD. The MAD Part B dosing 
paradigm will be confirmed based on emerging SAD data. 
The investigational dose range of 
 mg LY3872386 is intended to assess the dose-
response relationship and fully characterize safety and tolerability in humans for subsequent 
studies. This range is supported by a 3-month study in monkeys, 
 
 
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These effects are monitorable in humans and would be expected to be reversible with the 
cessation of dosing. The adverse clinical decline from infection, observed at the highest dose in a 
single monkey, was considered secondary to decreased lymphocytes and would be expected to 
be avoidable with clinical monitoring and intervention. Therefore, clinical doses approaching the 
NOAEL in monkeys would be considered safe. 
SAD Starting Dose 
The proposed SAD starting dose is 
 mg IV, which is supported by 
 a 
-fold dose multiple to the NOAEL in the 3-month repeat-dose toxicology study in 
monkeys 
 a predicted 
-fold exposure multiple to the NOAEL in the 3-month repeat-dose 
toxicology study in monkeys, and 
 the expectation that this dose is below a minimum anticipated biological effect level. 
SAD Maximum Dose 
The proposed SAD maximum dose is 
mg IV (Table KMAA.3), which is supported by 
 a -fold dose multiple to the NOAEL in the 3-month repeat-dose toxicology study in 
monkeys 
 a predicted 
-fold exposure multiple to the NOAEL in the 3-month repeat-dose 
toxicology study in monkeys, and 
 the monitorability of the effects of LY3872386 pharmacology. 
MAD Dosing 
The dose for MAD Cohort 1 is planned to be
 mg with dose and route to be confirmed 
based on emerging SAD data. The dose for MAD Cohort 2 is planned to be 
 mg with dose 
and route to be confirmed based on SAD data and data from MAD cohort 1.  
The planned dose of 
 mg for MAD Cohort 1 (Table KMAA.4) is supported by 
 a 
-fold dose multiple to the NOAEL in the 3-month repeat-dose toxicology study in 
monkeys 
 predicted 
fold exposure multiples (depending on dosing route and frequency) to 
the NOAEL in the 3-month repeat-dose toxicology study in monkeys, and 
 the monitorability of the effects of LY3872386 pharmacology. 
The maximum planned dose of 
 mg for MAD Cohort 2 is supported by 
 a 
-fold dose multiple to the NOAEL in the 3-month repeat-dose toxicology study in 
monkeys 
 predicted 
fold exposure multiples (depending on dosing route and frequency) 
to the NOAEL in the 3-month repeat-dose toxicology study in monkeys, and 
 the monitorability of the effects of LY3872386 pharmacology. 
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Table KMAA.3. 
NOAEL-Based Dose and Model-Predicted Exposure Multiples 
for Proposed Single Administrations of LY3872386 to Human 
Participants  
 
 
Dose 
(mg) 
Dosea 
(mg/kg) 
Dose 
Multipleb 
AUC0-inf 
(µg·hr/mL) 
Exposure Multipleb 
Human Starting Dose 
 
 
 
 
 
 
Human Maximum Dose 
Monkey NOAELc 
Abbreviations: AUC = area under the plasma concentration versus time curve; AUC0-168hr,ss = area under the 
plasma concentration versus time curve from time 0 to 168 hour, at steady state; AUC0-inf = area under the 
plasma concentration versus time curve from time 0 to infinity; CL = clearance; IB = Investigator’s Brochure;  
IV = intravenous; NOAEL = no-observed-adverse-effect level; PK = pharmacokinetic; SAD = single-ascending 
dose; SC = subcutaneous. 
a Calculations based on 
kg patient. 
b Dose multiple is the dose in animals divided by the dose in humans based on mg/kg. Exposure multiple is the 
calculated AUC in animals/predicted AUC in humans (The mean human dose projection PK parameter of linear 
CL =
 L/h and SC bioavailability = 
% was used to calculate the human predicted AUC.) 
(Note: The route of administration if different between species). For single-dose administration in the SAD 
portion of the first-in-human study, monkey AUC0-168hr,ss /predicted human AUC0-inf is used to calculate a 
conservative estimate of exposure multiple. 
c NOAEL determined in a 3-month repeat-dose toxicity study (Study 20341655). 
d  Mean AUC value is inclusive of all animals, including 2 in which exposure was impacted by the presence of anti-
drug antibodies (see Section 4 of the IB). This value results in a more conservative estimate of exposure at the 
NOAEL.  
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Table KMAA.4. 
NOAEL-Based Dose and Model-Predicted Exposure Multiples 
for Proposed Repeat Administrations of LY3872386 to Human 
Participants  
 
 
Dose (mg) 
and 
Frequency 
Dosea 
(mg/kg) 
Dose 
Multipleb 
AUC0-336hr  
(ug*h/mL) 
AUC0-672hr 
(ug*h/mL) 
 
Cav,ssc 
(ug/mL) 
Exposure 
Multipled 
Human 
Multiple Dose 
 
 
 
 
 
 
 
Monkey 
NOAELe 
Abbreviations: AUC = area under the plasma concentration versus time curve; AUC0-336hr = area under the plasma 
concentration versus time curve from time 0 to 336 hour (2 weeks); AUC0-672hr = area under the plasma 
concentration versus time curve from time 0 to 672 hour (4 weeks); IV = intravenous; Cav,ss = average plasma 
concentration over the dosing interval, at steady state; N/A = not applicable; NOAEL = no-observed-adverse-
effect level; 
 SC = subcutaneous.  
a Calculations based on 
kg patient. 
b Dose multiple is the dose in animals divided by the dose in humans based on mg/kg. 
c AUC value is expressed as average plasma concentration (Cav,ss) to normalize for differences in the dosing 
interval between studies in humans and monkeys, and is calculated by dividing the AUC value by the number of 
hours in the dosing interval.  
d Monkey Cav,ss/predicted human Cav,ss is used to calculate a conservative estimate of exposure multiple. 
e NOAEL determined in a 3-month repeat-dose toxicity study (Study 20341655). Cav,ss is calculated from the 
AUC of
 ng*hr/mL.  
 
Prednisone Dose Justification: 
Doses of 
 mg and sometimes up to 
 mg of prednisone are common in 
inflammatory diseases to treat acute flares for short durations (≤3 months).
 
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4.4. 
End of Study Definition  
The end of the study is defined as the date of the last visit of the last participant in the study or 
the last scheduled procedure shown in the SoA (Section 1.3) for the last participant in the trial 
globally. 
A participant is considered to have completed the study if the participant has completed all 
periods of the study, including the last visit or the last scheduled procedure shown in the SoA 
(Section 1.3). 
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5. 
Study Population  
Participant eligibility for enrollment in the study is based on the criteria listed in this section. The 
inclusion and exclusion criteria used to determine eligibility should only apply at screening or 
other specified visits, and not continuously throughout the study. 
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 at 
screening and/or enrollment: 
Age 
1. Participant must be 18 to 65 years of age inclusive, at the time of signing the informed 
consent. 
Type of Participant and Characteristics 
2. Overtly healthy for Part A and Part C as determined by medical evaluation, including 
medical history, physical examination, laboratory tests, and cardiac monitoring (including 
ECGs). 
a. To qualify as Japanese for the purpose of this study, the participant must be first-
generation Japanese, defined as the participant’s biological parents and all of the 
participant’s biological grandparents must be of exclusive Japanese descent, and must 
have been born in Japan.   
b. To qualify as Chinese for the purpose of this study, the participant must be, at a 
minimum, third-generation Chinese, defined as all 4 of the participant’s biological 
grandparents must be of exclusive Chinese descent and born in China. 
3. Have clinical laboratory test results within the normal reference range for the population 
or investigative site or results with acceptable abnormalities that are judged to be not 
clinically significant by the investigator. 
4. Have venous access sufficient to allow for blood sampling and administration of IP for 
IV administration as per the protocol. 
5. Are reliable, willing to make themselves available for the duration of the study, 
and willing to follow study procedures. 
Body Mass Index and Weight 
6. Have a body mass index of 18.0 to 32.0 kg/m2, inclusive, for Parts A and C, and 18.0 to 
38.0 kg/m2, inclusive, for Part B. 
Sex and Contraceptive/Barrier Requirements 
7. Male or Female 
a. Male participants: 
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i. Refer to Appendix 4 (Section 10.4) for definitions and additional guidance related 
to contraception. 
b. Female participants: 
ii. WNOCBP may participate in this trial. Refer to Section 10.4 for definitions and 
additional guidance related to contraception. 
Informed Consent 
8. Are capable of giving signed informed consent as described in Appendix 1 (Section 
10.1.3), which includes compliance with the requirements and restrictions listed in the 
informed consent form (ICF) and in this protocol. 
5.1.1. 
Additional Inclusion Criteria for Part B (Patients with Atopic Dermatitis)  
9. Female Participants 
a. WNOCBP and WOCBP may participate in Part B of this study. Please refer to 
Appendix 4 (Section 10.4) for definitions and additional guidance related to 
contraception. 
10. Have a diagnosis of AD at least 12 months prior to screening as defined by the American 
Academy of Dermatology (Eichenfield et al. 2014). 
11. Have AD, including all of the following: 
a. EASI score ≥12 at screening (Visit 1) and at randomization (Visit 2) 
b. vIGA-AD score of ≥3 at screening (Visit 1) and at randomization (Visit 2) 
c. ≥7% of body surface area involvement at screening (Visit 1) and at randomization 
(Visit 2) 
12. Have a history, documented by a physician and/or investigator, of inadequate response to 
existing topical medications within 6 months preceding screening, or participants who 
failed systemic therapies intended to treat AD (such as cyclosporine, methotrexate, 
azathioprine, and mycophenolate mofetil, within 6 months preceding screening), or a 
history of intolerance to topical therapy as defined by at least 1 of the following: 
a. Inability to achieve good disease control defined as mild disease or better (for 
example, vIGA-AD ≤2) after use of at least a medium potency TCS for at least 
4 weeks or for the maximum duration recommended by the product prescribing 
information (for example, 14 days for super-potent TCS), whichever is shorter. 
TCSs may be used with or without TCNIs. 
b. History of clinically significant adverse reactions with the use of TCS, such as 
skin atrophy, allergic reactions, or systemic effects that, in the opinion of the 
investigator, outweigh the benefits of retreatment. 
13. Participants who have applied emollients daily for at least 14 days prior to randomization 
and agree to use emollient daily throughout the treatment period. 
14. Participants who are receiving chronic treatments to improve sleep should be on a stable 
dose for at least 2 weeks prior to screening as determined by the investigator. 
5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
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15. women who are pregnant and/or lactating. 
16. are investigative site personnel directly affiliated with this study and their immediate 
families. Immediate family is defined as a spouse, biological or legal guardian, child, or 
sibling. 
17. are Lilly employees or are employees of a third-party organization involved with the 
study. 
18. are currently enrolled in a clinical study involving an IP or any other type of medical 
research judged not to be scientifically or medically compatible with this study or have 
received any nonbiologic or biologic agent (such as monoclonal antibodies, including 
marketed drugs) within 30 days or 5 half-lives (whichever is longer) of randomization. 
19. have a current or recent acute, active infection. For at least 30 days before screening and 
up to the randomization visit, participants must have no symptoms or signs of infection in 
the absence of any, anti-infective treatment. 
20. have had any of the following types of infection within 3 months prior to the 
screening visit or develops any of these infections before the randomization visit: 
 Serious (requiring hospitalization or IV or equivalent oral antibiotic treatment, or 
both) 
 Opportunistic (as defined in Winthrop et al. 2015) 
Note: Herpes zoster is considered active and ongoing until all vesicles are dry and 
crusted over. 
 Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer) 
 Recurring (including, but not limited to, herpes simplex, herpes zoster, and 
recurring cellulitis). Participants with only recurrent, mild, and uncomplicated 
orolabial herpes and/or genital herpes may be discussed with the sponsor’s 
designated medical monitor and considered for enrollment if other study 
eligibility requirements are met. 
 Have syphilis, as shown by positive results for both rapid plasma reagin and 
Treponema pallidum hemagglutination tests. 
21. have received live vaccine(s) (including attenuated live vaccines) or Bacillus Calmette-
Guérin within 35 days of screening or intend to receive them during the study (non-live 
or inactivated vaccinations are allowed) or within 14 weeks after receiving the last dose 
of study intervention. 
22. show evidence of active or latent TB, as documented through medical history and 
examination, chest x-rays (posterior to anterior, read by a radiologist, pulmonologist, or 
designee; a lateral chest x-ray may be performed if clinically or radiologically indicated), 
and TB testing, either a positive tuberculin skin test (TST; defined as a skin induration 
>5 mm at 48 to 72 hours, regardless of Bacillus Calmette-Guérin or other vaccination 
history) or a positive QuantiFERON®-TB Gold test. If the QuantiFERON-TB Gold test 
result is indeterminate, it may be repeated only once, and if the repeat test is 
indeterminate, the participant will be deemed ineligible. The choice to perform a TST or 
a QuantiFERON-TB Gold test will be made by the investigator according to local 
standard of care. Please note that if a chest x-ray has been performed in the past 6 
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months, found to be normal and the report is available, a further chest x-ray is not 
required, provided there has been no known TB exposure since the x-ray was performed. 
Note: Results of a chest CT scan or other imaging study similar to a chest x-ray may be 
substituted in place of the chest x-ray as described above, in consultation with the 
sponsor’s medical monitor. 
23. have 1 of the following viral infections: 
a. a current infection with HBV (that is, positive for HBsAg and/or 
polymerase chain reaction positive for HBV DNA; Section 8.2.10). 
b. a current infection with HCV (that is, positive for HCV RNA; Section 
8.2.11). 
c.  HIV infection. 
24. had any surgical procedure (except for minor surgery requiring local or no anesthesia and 
without any complications or sequelae) within 12 weeks prior to screening or any 
planned surgical procedure scheduled to occur during the study. 
25. have a history or presence of multiple or severe allergies or an anaphylactic reaction to 
prescription or nonprescription drugs. 
26. have a history or presence of allergy or reactions to ADC, mAbs, systemic GCs or have 
clinically significant multiple or severe drug allergies, intolerance to TCSs (for healthy 
participants only), or a history of severe posttreatment hypersensitivity reactions 
(including, but not limited to, erythema multiforme major, linear immunoglobulin A 
dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis). 
27. had any malignancy within the past 5 years. Exceptions: successfully treated basal cell 
skin carcinoma or squamous cell skin carcinoma with no evidence of recurrence or 
metastatic disease within the 3 years prior to baseline. 
28. current smoker using >10 cigarettes or other tobacco products per day and are 
unable/unwilling to stop smoking tobacco products while in the study unit and have a 
positive cotinine test. 
29. are regular users of known drugs of abuse and/or have positive findings on urinary drug 
tests at screening, OR 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 
during study visits/time in the research unit (1 unit of alcohol = 12 oz or 360 mL of beer, 
5 oz or 150 mL of wine, and 1.5 oz or 45 mL of distilled spirits). 
30. are regular users of cannabis (legal or medical). 
31. have received blood products within 6 months before screening or donated blood of more 
than 500 mL within the previous 30 days of study screening. 
a. For Chinese participants: 
i. Have donated blood of more than 400 mL within the previous 30 days of 
study screening. 
32. have known hypogammaglobulinemia or a screening serum immunoglobulin G or 
immunoglobulin M below the reference range. 
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33. have a history of a primary immunodeficiency, splenectomy, or any underlying condition 
that predisposes the participant to infection that, in the opinion of the sponsor or 
investigator, poses an unacceptable risk to the participant. 
34. have presence of significant uncontrolled cerebro-cardiovascular (for example, 
myocardial infarction, unstable angina, hypertension, moderate-to-severe [New York 
Heart Association Class III/IV] heart failure, or cerebrovascular accident), respiratory, 
hepatic, renal, gastrointestinal, endocrine, hematologic, neurologic or neuropsychiatric 
disorders, or abnormal laboratory values at screening that, in the opinion of the sponsor 
or investigator, pose an unacceptable risk to the participant if participating in the study or 
interfering with the interpretation of data. 
35. use or intend to use herbal, over-the-counter, or prescription medication within 14 days 
prior to dosing and during the study, other than estrogen/progesterone as a form of 
hormone replacement therapy and/or oral contraceptives. Certain medications (for 
example, vitamin supplements or prescription medications) may be permitted at the 
discretion of the investigator and in agreement with the sponsor.  
36. Diagnosed with active endoparasitic infections; suspected or at high risk of 
endoparasitic infection, unless clinical and (if necessary) laboratory assessment 
have ruled out active infection before randomization. 
37. History of preexisting glaucoma, severe acne, osteonecrosis, uncontrolled 
hypertension, or peripheral edema.  
38. in the opinion of the investigator or sponsor, are unsuitable for inclusion in the 
study. 
50. Known history of diabetes.  
51. Fasting glucose level of ≥126 mg/dL and glycated hemoglobin ≥6.5% and/or 
taking anti-diabetes medications at screening. 
52. Known history of osteoporosis. 
5.2.1. 
Additional Exclusion Criteria for Part B (Patients with Atopic Dermatitis)  
39. Are currently experiencing or have a history of other concomitant skin conditions 
(for example, psoriasis or cutaneous lupus) that would interfere with the 
evaluation of the effect of the study medication on AD. 
40. participants who, in the opinion of the investigator, are currently experiencing or have a 
history of erythrodermic, refractory, or unstable skin disease that requires frequent 
hospitalizations and/or IV treatment for skin infections that may interfere with their 
participation in the study. 
41. Have a history of eczema herpeticum 
a.  within 6 months prior to screening, or 
b.  2 or more episodes during lifetime. 
42. participants who are currently experiencing a skin infection that requires treatment or is 
currently being treated with topical or systemic antibiotics. 
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Note: Participants may not be rescreened until at least 4 weeks after the date of their 
previous screen failure and at least 2 weeks after the resolution of the infection. 
43. Have a history of TCS use suggestive of a high risk for TCS withdrawal, for example, a 
history of prolonged or frequent use of moderate- to high-potency TCS, especially on the 
face (Hajar et al. 2015), such that, in the opinion of the investigator, the participant will 
be unable to withdraw and abstain from TCS for several weeks during the study. 
44. have any serious concomitant illness that is anticipated to require the use of systemic 
corticosteroids or otherwise interfere with study participation or require active, frequent 
monitoring (for example, unstable chronic asthma requiring hospitalization and/or 
systemic corticosteroids in the 6 months prior to screening). 
45. have been treated with the following therapies: 
a. Other mAb (for example, ustekinumab, omalizumab, dupilumab, tralokinumab, 
and lebrikizumab (whether approved or investigational) within 5 half-lives prior 
to randomization (Visit 2). 
b. Received any parenteral corticosteroid administered by intramuscular or IV 
injection within 2 weeks prior to study entry (Visit 1) or within 6 weeks prior to 
planned randomization (Visit 2) or are anticipated to require parenteral injection 
of corticosteroids during the study. 
c. Have had an intra-articular corticosteroid injection within 2 weeks prior to study 
entry (Visit 1) or within 6 weeks prior to planned randomization (Visit 2). 
d. Have used any of the following topical medications within 1 week prior to 
randomization (Visit 2): 
 topical corticosteroids or topical immune modulators (for example, 
tacrolimus or pimecrolimus) 
Note: pimecrolimus may not be available in all regions, including Japan. 
 topical phosphodiesterase type 4 inhibitor, or 
 topical Janus kinase inhibitor. 
Note: Intranasal or inhaled steroid use is allowed during the trial. 
46. have received the following excluded medications/treatments within 4 weeks prior to 
randomization (Visit 2) or plan to use during the study: 
a. oral systemic corticosteroids and leukotriene inhibitors. 
b. systemic immunomodulators, including, but not limited to, cyclosporine, 
methotrexate, mycophenolate mofetil, azathioprine, and Janus kinase inhibitors 
(such as tofacitinib, ruxolitinib, baricitinib, upadacitinib or abrocitinib). 
c. sedating antihistamines including, but not limited to, alimemazine, 
chlorphenamine, clemastine, cyproheptadine, diphenhydramine, hydroxyzine, 
ketotifen, and promethazine. 
Note: Participants may use newer, less sedating antihistamines (for 
example, fexofenadine, loratadine, and cetirizine). 
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d. any other systemic therapy used to treat AD or symptoms of AD (approved or off-
label use). 
e. phototherapy, including therapeutic phototherapy (psoralen plus ultraviolet-A and 
ultraviolet-B), excimer laser, or tanning beds. 
47. patients with a positive beta-D-glucan test at screening and a confirmed diagnosis of 
pneumocystis pneumonia will be excluded. 
48. have experienced hypersensitivity to the active substance or to any of the excipients. 
49. For Japanese participants only: have evidence of, or a positive test for, HBV infection, 
defined as: 
a. positive for hepatitis B surface antigen (HBsAg), or 
b. positive for hepatitis B core antibody (HBcAb) and positive HBV DNA, or 
c. positive for hepatitis B surface antibody (HBsAb) and positive for HBV DNA. 
Note: Patients who are positive for HBcAb or HBsAb and negative for HBV DNA 
may be enrolled in Part B of the study. In this case, repeat testing for HBV DNA is 
required at least once every month during the study. 
5.3. 
Lifestyle Considerations  
Throughout the study, participants must adhere to lifestyle restrictions as outlined by the CRU 
and in the study procedures. Participants may undergo medical assessments and a review of 
compliance with requirements before continuing in the study. 
5.3.1. 
Meals and Dietary Restrictions  
During the confinement period (where applicable), participants will consume only food and 
beverages that are provided to them by the CRU staff. Standard meals (for example, breakfast, 
lunch, dinner, and snack) will be provided to the participants while resident at the CRU. 
In Part A (SAD) and Part B (MAD), participants will be required to fast for approximately 
4 hours before study intervention administration. Water is permitted. Participants may eat 
approximately 2 hours postdose. A normal diet may be consumed at all other times during the 
study. 
In Part C (PO QD prednisone), the participants will be fasted overnight (at least 10 hours) prior 
to dosing and refrain from consuming water from 1-hour predose until 2-hour postdose, 
excluding the amount of water consumed at dosing. Food is allowed 4 hours postdose. At all 
other times during the study, participants may consume water ad libitum.  
For all outpatient visits in Parts A, B, and C, participants will be required to fast approximately 
10 hours before visits that include clinical chemistry testing. Water is permitted. 
5.3.2. 
Substance Use: Caffeine, Alcohol, and Tobacco  
For Parts A, B, and C, consumption of caffeine‑containing beverages is permitted during the 
outpatient portions of the study. For Parts A and C, participants will abstain from ingesting 
caffeine- or xanthine-containing products (for example, coffee, tea, cola drinks, and chocolate) 
from check-in and through discharge from the CRU. 
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For Parts A and C, participants will not consume alcohol from check-in and through discharge 
from the CRU. For Part B, participants should not consume alcohol for at least 24 hours prior to 
dosing and at least 2 days postdose. During outpatient periods, all participants should be advised 
to limit alcohol consumption to no more than 2 units per day. 
Participants should be willing and be able to abide by smoking restrictions at the CRU during 
both the inpatient period and outpatient visits. 
Study participants should be instructed not to donate blood, blood products, and/or tissue during 
the study or for 14 weeks following the final visit of the study. 
5.3.3. 
Activity  
Participants will abstain from strenuous exercise for approximately 5 days before each blood 
collection for clinical laboratory tests. Participants may participate in light recreational activities 
during studies (for example, watching television and reading). 
5.4. 
Screen Failures  
A screen failure occurs when a participant consents to participate in the clinical study but is not 
subsequently assigned to the study intervention or enrolled in the study. A participant who is an 
alternate in a study group/cohort may be enrolled in the next group/cohort if within the screening 
window or may screen for a subsequent group, unless the participant was a screen fail. 
As Part A and Part C are healthy participant-only studies, individuals who do not meet the 
criteria for participation in this study (screen failure) may not be rescreened, although screening 
tests such as clinical laboratory tests and vital signs or ECGs may be repeated at the discretion of 
the investigator. If subjects have minor deviations in screening assessments (for example, vital 
signs), these may be repeated at the investigator’s discretion to confirm eligibility. 
As Part B participants are patients with AD, individuals who do not meet the eligibility criteria 
for participation in this study (screen failure) may not be rescreened until at least 4 weeks after 
the date of their previous screen failure and at least 2 weeks after resolution of a skin infection, 
unless the rescreening is for administrative reasons (see below). Blood tests may be repeated at 
the discretion of the investigator during screening without being considered a screen failure. 
Participants may be rescreened once. When rescreening is performed, the individual must sign a 
new ICF and will be assigned a new identification number. 
Allowed Rescreening for Administrative Reasons 
An individual may be rescreened once for an administrative reason, such as falling out of the 
screening window because of scheduling conflicts. The sponsor does not need to approve 
rescreening for administrative reasons. The rescreening can start immediately after the 
administrative reason has been resolved. 
5.5. 
Criteria for Temporarily Delaying Enrollment/Randomization/ 
Administration of Study Intervention of a Participant  
Not applicable. 
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6. 
Study Interventions and Concomitant Therapy  
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to or used by a study participant 
according to the study protocol.  
6.1. 
Study Interventions Administered  
This table lists the interventions used in this clinical study. 
Intervention 
Name 
LY3872386 
Placebo (0.9% sodium 
chloride solution) 
Prednisone 
Dosage 
Level(s) 
 mg/vial (single 
administration, 
 for 
12 weeks, and 
 for 
12 weeks) 
N/A 
 mg 
 x 30 days), 
 
mg (
 x 30 days), and 
mg (
 x 7 days) 
Route of 
Administration 
IV and SC 
Approximately 
 min 
IV infusion 
Same as LY3872386 
administration 
Oral 
Authorized as 
defined by EU 
Clinical Trial 
Regulation 
Not authorized in EU 
Authorized, not used 
according to authorization 
Authorized, not used 
according to authorization 
Abbreviations: EU = European Union; IV = intravenous; SC = subcutaneous; 
.  
 
Packaging and Labeling 
LY3872386 will be supplied by the sponsor in accordance with the current Good Manufacturing 
Practice. The study interventions will be labeled as appropriate for country requirements. 
6.1.1. 
Administration Details  
Part A and Part B: LY3872386 Administration 
In IV dosing cohorts, LY3872386 will be administered as a slow IV infusion over 
approximately 
 to 
 minutes. Resuscitation equipment, emergency drugs, and appropriately 
trained staff must be available while the participant is staying at the investigation site.  
In SC dosing cohorts, all LY3872386 injections will be administered into the SC tissue of the 
abdominal wall. Injection sites will be alternated between 4 sites (that is, right and left upper 
quadrants and the right and left lower quadrants) on the abdominal wall (where 
applicable). Whenever possible, study drug administration should be carried out by the same 
personnel.
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Part C:  Prednisone Administration 
All doses of prednisone will be administered with approximately 
 mL of room temperature 
water while in a sitting position.  
Prednisone tablets should be swallowed whole. Participants should not break, crush, or chew the 
study intervention. 
On dosing days, participants will adhere to meal restrictions as outlined in Section 5.3.1. 
6.1.2. 
Premedication for Infusions  
Premedication for the infusions is not planned. However, if an infusion reaction occurs, 
appropriate medication may be used as determined by the study investigator(s). If infusion 
reactions are observed, but review of the data suggests that dose escalation may continue, 
administration of acetaminophen 500 to 1000 mg and/or an antihistamine may be administered 
orally 30 to 60 minutes prior to the start of infusion for subsequent participants.  
The decision to implement premedication for infusions in subsequent cohorts will be made by 
the investigator and the sponsor, and recorded in the study documentation, along with the dose-
escalation decision.  
Any premedication given will be documented as a concomitant therapy (see Section 6.9).  
6.1.3. 
Management of Infusion Reactions  
There is a risk of an infusion reaction with any biological agent. Therefore, all 
participants should be monitored closely.  
Symptoms and signs that may occur as part of an infusion reaction include, but are not limited 
to:  
 fever 
 chills 
 nausea 
 headache 
 bronchospasm 
 hypotension 
 angioedema 
 throat irritation 
 rash 
 pruritus 
 myalgia, and 
 dizziness. 
In the event that a significant infusion reaction occurs, the following guidance should be 
followed:  
 
The investigational product infusion should be slowed (for example, reduce the 
infusion rate by 50% [for example, an infusion rate of 12 mL/h becomes 6 mL/h or 
slower]) or stopped, depending on the symptoms/signs present:  
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o if slowed, the infusion should be completed at the slower rate, as tolerated, 
and  
o if determined by the investigator that the infusion should no longer 
continue, no further attempts to dose the participant should be made. 
 
Supportive care should be employed in accordance with the symptoms/signs and 
consistent with local guidelines. 
 
If a participant’s infusion reaction is sufficiently severe to discontinue the infusion, 
subsequent infusions may be administered with premedication at the discretion of the 
investigator, following agreement with the Lilly CRP or clinical pharmacologist  
 
If a participant’s infusion rate is reduced due to an infusion reaction, subsequent 
infusions may be administered at the discretion of the investigator, following 
agreement with the Lilly CRP or clinical pharmacologist. If further infusions are 
administered, the infusion rate must not exceed the slowest rate used to complete the 
infusion on the occasion when the infusion reaction occurred. Premedication may be 
administered at the discretion of the investigator.  
 
If it is determined that the participant should not receive further doses of the 
investigational product, the participant should complete AE and other follow-up 
procedures per the SoA (Section 1.3) of this protocol.  
6.2. 
Preparation, Handling, Storage, and Accountability  
The investigator or designee must confirm appropriate storage conditions have been maintained 
during transit for all study intervention received and any discrepancies are reported and resolved 
before use of the study intervention. 
Only participants enrolled in the study may receive study intervention. Only authorized study 
personnel may supply, prepare, 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 study personnel. 
The investigator or authorized study personnel are responsible for study intervention 
accountability, reconciliation, and record maintenance, that is, receipt, reconciliation, and final 
disposition records. 
Further guidance and information for the preparation, handling, storage, and final disposition of 
unused study interventions are provided in the Pharmacy Manual/Pharmacy Preparation 
Instructions. 
Where applicable, the study intervention will be prepared by an unblinded pharmacy staff or a 
pharmacist who is not involved in any other study-related procedures.  
6.3. 
Assignment to Study Intervention  
For Part A and Part B, this is a double-blinded, randomized study of LY3872386 in healthy 
participants and in patients with AD. For Part C, this is an open-label study of prednisone in 
healthy participants. 
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6.4. 
Blinding  
6.4.1. 
Part A: Single-Ascending Dose of LY3872386  
This is a double-blind study in which participants and investigators are blinded to the study 
intervention. Emergency codes regarding treatment assignment will be available to 
the investigator, and in case of an emergency, the investigator has the sole responsibility for 
determining if unblinding of a participant’s intervention assignment is warranted. Participant 
safety must always be the first consideration in making such a determination. If the investigator 
decides that unblinding is warranted, the investigator should make every effort to contact the 
sponsor to discuss the situation prior to unblinding a participant’s intervention assignment, 
unless this could delay the emergency treatment for the participant. If a participant’s intervention 
assignment is unblinded, the sponsor must be notified within 24 hours of this occurrence.  
Investigators will remain blinded to each participant’s assigned study intervention throughout the 
course of the study. To maintain this blind, an otherwise uninvolved third party will be 
responsible for the reconstitution and dispensation of all study interventions and will endeavor to 
ensure that there are no differences in the time taken to dispense following the randomization. 
In the event of a quality assurance audit, the auditor(s) will be allowed access to unblinded study 
intervention records at the site(s) to verify that randomization/dispensing has been done 
accurately. 
If an investigator, site personnel performing assessments, or participant is unblinded, the 
participant must be discontinued from the study. In cases where there are ethical reasons to have 
the participant remain in the study, the investigator must obtain specific approval from a sponsor 
CRP for the participant to continue in the study. 
6.4.2. 
Part B: Multiple-Ascending Dose of LY3872386  
For MAD Part B only, all participants will be centrally assigned to the randomized study 
intervention using an IWRS. Before the study is initiated, log-in information and directions for 
the IWRS will be provided to each site. IWRS will not be used for the dispensing of study 
intervention and will only be used for randomization. 
This is a double-blind study in which participants and investigators are blinded to the study 
intervention. The IWRS will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if the unblinding of a 
participant’s intervention assignment is warranted. Participant safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the sponsor to discuss the 
situation prior to unblinding a participant’s intervention assignment, unless this could delay 
emergency treatment for the participant. If a participant’s intervention assignment is unblinded, 
the sponsor must be notified immediately within 24 hours of this occurrence. The date and 
reason that the blind was broken must be recorded. 
6.4.3. 
Part C: Open-Label of Prednisone  
This is an open-label study. 
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6.5. 
Study Intervention Compliance  
The study intervention will be administered under medical supervision by the investigator or 
designee. The dose of the study intervention and study participant identification will be 
confirmed prior to the time of dosing. The date and time of each dose administered will be 
recorded in the source documents and will be provided to the sponsor as requested.   
6.6. 
Dose Modification  
6.6.1. Dose Decision/Escalation  
By nature of being a dose-escalation study, data will be evaluated on an ongoing basis. 
Safety data, in particular AEs, SAEs, and laboratory abnormalities, will be independently 
assessed by the investigator. 
Safety and tolerability data will be the primary criteria for the dose escalation in Part A (SAD of 
LY3872386) and Part B (MAD of LY3872386) (Section 8.2). 
 
 
After review of these data, an agreement on the appropriate dose will be made by the investigator 
and sponsor for the next cohort/dose level. The magnitude of dose escalations may be reduced 
following data review, 
 
 
No dose decision can occur without prior discussion and agreement between the investigators 
and the sponsor. 
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6.7. 
Continued Access to Study Intervention after the End of the Study  
LY3872386 and prednisone will not be made available to participants after the conclusion of the 
study. 
6.8. 
Treatment of Overdose  
For this study, an overdose of LY3872386 or prednisone is considered any dose higher than the 
dose assigned through randomization. Treatment for overdose is the best supportive care. 
The sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator/treating physician should 
 contact the Lilly Clinical Pharmacologist immediately 
 evaluate the participant to determine, in consultation with the medical monitor, whether the 
study intervention should be interrupted or the dose should be reduced 
 closely monitor the participant for any AE/SAE and laboratory abnormalities for 
approximately 12 weeks or 5 half-lives (whichever is longer) 
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 obtain a blood sample for PK analysis if requested by the Lilly Clinical Pharmacologist 
(determined on a case-by-case basis), and 
 document the quantity of the excess dose as well as the duration of the overdose in the CRF. 
6.9. 
Prior and Concomitant Therapy  
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements or other specific categories of interest) that the participant is receiving 
at the time of enrollment or receives during the study must be recorded along with 
 reason for use 
 dates of administration, including start and end dates, and 
 dosage information, including dose and frequency for concomitant therapy of special 
interest. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
In general, concomitant medication should be avoided. The use of chronic, stable doses of 
thyroid hormone, or hormone replacement therapy is allowed. Acetaminophen (1 g, maximum 4 
g/24 hours) may be administered at the discretion of the investigator for the treatment of 
headache and so on. Antihistamine may be administered as a premedication for infusion at the 
discretion of the investigator. Other concomitant medications may be considered on a case-by-
case basis by the medical monitor in consultation with the Lilly CP/CRP or designee. If the need 
for concomitant medication (other than acetaminophen) arises, the inclusion or continuation of 
the participant may be at the discretion of the investigator after consultation with the sponsor. 
Any medication used during the course of the study must be documented.  
For AD therapies permitted as part of rescue therapy see below. 
6.9.1. 
Rescue Medicine  
Criteria for rescue therapy initiation 
 Investigators should attempt to manage participants with emollients. However, 
investigators are allowed to rescue participants who are experiencing unacceptable or 
worsening symptoms of AD after Week 8. Prior to rescue, it is recommended that an 
increased frequency of emollient use is attempted to at least twice a day or more in an 
effort to control symptoms. The rationale for rescue will be documented. 
Choice of rescue therapy treatment 
 Triamcinolone 0.1% cream and/or hydrocortisone 2.5% ointment. In the event that 
providing 1 or both of these topical formulations is not possible, an alternate, equivalent 
potency TCS cream and/or ointment may be provided. 
o Commercially available triamcinolone 0.1% cream and/or hydrocortisone 2.5% 
ointment may be supplied by the clinical site.  
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 Investigators may elect to use TCNIs and/or crisaborole where approved, although use of 
either of them during the study is not encouraged. If TCNIs are prescribed, use should be 
limited to problem areas only (for example, face, neck, skin folds, and genital areas). 
 On the days of study visits, topical therapy should not be applied before the participant 
has undergone all study procedures and clinical evaluations to allow adequate assessment 
of skin dryness. 
 Participants receiving topical therapy will remain on the study and continue to take IP. 
The use of rescue therapy will be documented in the eCRF. 
In participants who do not improve sufficiently with the provided rescue topical therapy after 7 
days, a higher potency TCS may be used, and IP may continue. It is recommended that if a 
participant achieves “clear” to “almost clear” skin after topical rescue, medium- and/or high-
potency TCSs and TCNIs should be stopped, and low-potency TCSs (for example, 
hydrocortisone 2.5% ointment) should be used once daily for an additional 7 days, then stopped. 
If lesions return, participants can be retreated with TCSs with or without TCNIs and/or 
crisaborole as before, at the discretion of the investigator.  
If topical rescue therapy as described above fails to sufficiently control AD symptoms, then oral 
systemic medications may be used as rescue (for example, corticosteroids, cyclosporine, and 
methotrexate). However, IP will be required to be permanently discontinued for the remainder of 
the 12-week study duration. If these medications are needed for other medical conditions (for 
example, asthma flare), they will still be treated as rescue medications.  
Investigators should make every attempt to conduct efficacy and safety assessments immediately 
before administering any rescue treatment. An unscheduled visit can be used for this purpose if 
necessary. 
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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal  
Participants discontinuing from the study intervention prematurely for any reason should 
complete AE and other follow-up procedures per Section 1.3 of this protocol.  
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 1 
(Section 10.1). 
7.1. 
Discontinuation of Study Intervention  
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) study intervention. If study intervention is definitively discontinued, the 
participant will remain in the study for additional data collection, consistent with routine safety 
monitoring. See the SoA (Section 1.3) for data to be collected at the time of discontinuation of 
study intervention and follow-up and for any further evaluations that need to be completed. 
The following infections lead to study intervention discontinuation: confirmed diagnosis of 
pneumocystis pneumonia, HIV, and active TB, including hepatitis B and C (as further described 
in Section 7.1.2). 
A participant should be permanently discontinued from the study intervention 
● 
if the participant becomes pregnant during the study 
● 
for safety reasons, in the opinion of the investigator, or 
● 
if the investigator determines that a systemic hypersensitivity reaction has occurred 
related to study intervention administration, the participant may be permanently 
discontinued from the study intervention, and the sponsor’s designated medical monitor 
should be notified. If the investigator is uncertain about whether a systemic 
hypersensitivity reaction has occurred and whether discontinuation of study 
intervention is warranted, the investigator may consult the sponsor. 
7.1.1. 
Rules for Stopping Dosing and Enrollment in a Cohort  
If any of the following scenarios occur, dosing at the current level and further dose escalation 
will be interrupted and may resume only following written approval from the sponsor medical 
monitor: 
 A single participant experiences an SAE unless obviously unrelated to LY3872386 
administration. 
 Severe nonserious AEs considered at least possibly related to the study intervention 
occurring in 2 participants in Parts A or B within the same cohort, independent of 
whether or not the events are in the same system organ class. 
 Two or more participants per cohort in Parts A or B develop TEAEs or clinically 
significant changes in laboratory safety that are graded as at least moderate, 
unless there is an obvious explanation other than study intervention or study 
procedures for the event(s). 
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 One or more participants present severe AEs related to IV infusion that are related 
to LY3872386, and the TEAE does not resolve with a reduced IV infusion rate or 
supportive care. 
7.1.2. 
Hepatic Criteria for Study Drug Interruption or Discontinuation  
See Section 8.2.8 for hepatic criteria for study drug interruption or discontinuation. 
7.1.3. 
Cardiovascular Stopping Criteria  
7.1.3.1. 
QTc Stopping Criteria  
If a clinically significant QTc finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment), the investigator or qualified designee will determine if the 
participant can continue in the study and if any change in participant management is needed. 
This review of the ECG printed at the time of collection must be documented. Any new 
clinically relevant finding should be reported as an AE.  
Discontinuation of IP should be considered by the investigator and the sponsor if any of the 
following occur in a participant: 
● QTcF >500 msec 
● increase from baseline in QTc >60 msec, from at least 2 consecutive readings 
7.1.3.2. 
Hypertension Stopping Criteria  
If 2 consecutive systolic blood pressure >160 mm Hg or if 2 consecutive diastolic blood pressure 
>100 mm Hg; medical intervention indicated. 
7.1.4. 
Ocular Pressure Interruption Criteria  
The following criteria will lead to study intervention interruption: 
 >10 points over baseline confirmed by an additional, consecutive assessment conducted 
prior to treatment administration, or 
 >25 mmHg confirmed by an additional, consecutive assessment conducted prior to 
treatment administration, or 
 develops signs of glaucoma  
Therapy may resume when ocular pressure is within normal limits and/or sign of glaucoma 
resolve. 
7.1.5. 
Serious and Opportunistic Infections Discontinuation and Interruption Criteria  
7.1.5.1. 
Discontinuation: The Following Infections Lead to Study Intervention 
Discontinuation  
HBV or HCV: The participant tests positive for HBV DNA (see Section 8.2.10) or tests positive 
for HCV RNA (Section 8.2.11). 
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Note: The HBV DNA result is to be confirmed if initial test result is positive but below the level 
of quantification (Section 7.1.5.2). Prior to discontinuation of any immunomodulatory and/or 
immunosuppressive therapy, including study intervention, the participant is to be referred to, 
evaluated, and managed by a specialist physician with expertise in evaluation and management 
of viral hepatitis. The timing of discontinuation from study intervention relative to the initiation 
of any antiviral treatment for hepatitis is to be based on the recommendation of the consulting 
specialist physician, in conjunction with the investigator, and aligned with medical guidelines 
and standard of care. 
Certain AEs: 
 The participant develops HIV infection. 
 The participant develops active TB or has untreated LTBI. 
7.1.5.2. 
Infection-Related Criteria for Temporary Withholding  
Temporary withholding of study intervention is required if the participant meets any of the 
following infection-related criteria during the study: 
 Serious or opportunistic infections, as defined in Section 5.2. Study intervention has to be 
withheld until resolution of all acute clinical signs and symptoms, and completion of all 
appropriate anti-infective treatment (exception for LTBI, noted below). 
 A participant diagnosed with LTBI during the study has to be permanently discontinued 
from study intervention unless the participant is a candidate for LTBI treatment, and is 
treated for LTBI as follows: 
o Study intervention is temporarily withheld for at least the first 4 weeks of 
LTBI treatment. 
o After receiving at least 4 weeks of appropriate LTBI therapy (as per World 
Health Organization or US Centers for Disease Control and Prevention 
guidelines), if there is no evidence of hepatotoxicity (ALT/AST level must 
remain ≤2 times ULN) or other treatment intolerance, study intervention 
may be resumed. 
o The participant must complete appropriate LTBI therapy to remain eligible 
to receive study intervention. 
 HBV DNA results that are reported as positive, or as detecting HBV DNA, but HBV 
DNA is below the level of quantification. In this situation, the sponsor’s designated 
medical monitor should be contacted regarding the participant’s status. HBV DNA 
testing is to be repeated as soon as it is feasible. If HBV DNA is confirmed as positive, 
the participant must be permanently discontinued from study intervention. 
7.1.6. 
Abnormal Laboratory Parameters of Special Interest  
7.1.6.1. 
Hematological Values for Permanent Discontinuation  
Any of these laboratory results with no other obvious cause in the opinion of the investigator: 
 hemoglobin level <8 g/dL 
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 neutrophil count <1 x 109 /L 
 total lymphocyte count <0.5 x 109/L, or 
 platelet number <50K/mcL 
7.1.6.2. 
Glucose and HbA1c Values for Permanent Discontinuation  
Any of these laboratory results with no other obvious cause in the opinion of the investigator: 
 If 2 fasting glucose measures are >126 mg/dL  
 If 1 fasting glucose measure is >126 mg/dL and glycated hemoglobin level is >6.5% (48 
mmol/mol) (ElSayed et al. 2023) 
7.1.6.3. 
Adrenal Insufficiency Criteria for Permanent Discontinuation in Part B Only  
Morning blood cortisol levels of <83 nmol/L, confirmed by a consecutive test conducted within 
3 to 5 days of initial value or fail to respond to cosyntropin (or ACTH) assessment within normal 
limits. 
Sponsor should be contacted, and participant may be referred to a health care provider for 
additional assessments, monitoring and/or management. 
7.2. 
Participant Discontinuation/Withdrawal from the Study  
Discontinuation is expected to be uncommon. 
A participant may withdraw from the study 
● at any time at the participant’s own request for any reason or without providing 
any reason 
● at the request of the participant’s designee (for example, parents or legal 
guardian) 
● at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons 
● if enrolled in any other clinical study involving an IP or enrolled in any other type 
of medical research judged not to be scientifically or medically compatible with 
this study, and 
● if the participant, for any reason, requires treatment with a therapeutic agent that 
is prohibited by the protocol and has been demonstrated to be effective for the 
treatment of the study indication. In this case, discontinuation from the study 
occurs prior to the introduction of the new agent. 
At the time of discontinuing from the study, if possible, the participant will complete procedures 
for an early discontinuation visit as shown in the SoA (Section 1.3). If the participant has not 
already discontinued the study intervention, the participant will be permanently discontinued 
from the study intervention at the time of the decision to discontinue the study. 
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 
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withdraws from the study, the participant 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, a discussion must occur between the Lilly clinical pharmacologist 
and the investigator to determine if the participant may continue in the study. If both agree that it 
is medically appropriate to continue, the investigator must obtain documented approval from the 
sponsor to allow the inadvertently enrolled participant to continue in the study, with or without 
continued treatment with IP. 
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 or designee are 
expected to make diligent attempts to contact participants who fail to return for a scheduled visit 
or were otherwise unable to be followed up by the site. 
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants randomized, including those 
who did not get the investigational product. Public sources may be searched for vital status 
information. If vital status is determined to be deceased, this will be documented, and the 
participant will not be considered lost to follow-up. Sponsor personnel will not be involved in 
any attempts to collect vital status information. 
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8. 
Study Assessments and Procedures  
Study procedures and their timing are summarized in the SoA (Section 1.3).  
● Immediate safety concerns should be discussed with the sponsor immediately 
upon occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
● Adherence to the study design requirements, including those specified in the SoA, 
is essential and required for study conduct. 
● All screening evaluations must be completed and reviewed to confirm that 
potential participants meet all eligibility criteria. The investigator will maintain a 
screening log to record details of all participants screened and to confirm 
eligibility or record reasons for screening failure, as applicable. 
 Section 1.3 lists the SoA, detailing the study procedures and their timing (including 
tolerance limits for timing). The specifications in this protocol for the timings of safety 
and sample collection are given as targets to be achieved within reasonable 
limits. Modifications may be made to the time points based on emerging clinical 
information. The scheduled time points may be subject to minor alterations. However, the 
actual time must be correctly recorded in the CRF. 
 Appendix 2 (Section 10.2) lists the laboratory tests that will be performed for this study.  
 Appendix 2 (Section 10.2.1) provides a summary of the maximum number and volume of 
invasive samples, for all sampling, during the study. 
 Unless otherwise stated in the subsections below, all samples collected for specified 
laboratory tests will be destroyed within 60 days of receipt of confirmed test 
results. Certain samples may be retained for a longer period, if necessary, to comply with 
applicable laws, regulations, or laboratory certification standards. 
 Failures or delays that are outside stipulated time allowances in performing procedures or 
obtaining samples due to legitimate clinical issues (for example, equipment technical 
problems, venous access difficulty, or subject defaulting or turning up late on an agreed 
scheduled procedure) will not be considered as protocol deviations, but the CRU will still 
be required to notify the sponsor. 
8.1. 
Efficacy Assessments  
In Part B of the trial, the following efficacy assessments will be performed: 
Clinician-rated scales 
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Participant-rated scales 
The following assessments should be completed prior to any clinical assessments being 
performed on days when study visits occur: 
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8.2. 
Safety Assessments  
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1. 
Physical Examinations  
A complete physical examination will be completed only at screening, the last scheduled follow-
up visit, and at early discontinuation. At admission, a medical assessment is performed, which 
includes a medical review and a brief physical examination. Symptom-directed physical 
examinations may be conducted at any time during the study, as deemed necessary by the 
investigator. 
A complete physical examination will include, at a minimum, assessments of the cardiovascular, 
respiratory, gastrointestinal, skin, lymph nodes, and neurological systems. Weight will also be 
measured and recorded. Height will only be measured and recorded at screening. 
A brief physical examination will include, at a minimum, assessments of the skin, lungs, 
cardiovascular system, and abdomen (liver and spleen). 
Investigators should pay special attention to the clinical signs related to previous serious 
illnesses. 
8.2.2. 
Vital Signs  
For each participant, vital sign measurements should be conducted according to the SoA (Section 
1.3) and follow the study-specific recommendations included in the Manual of Operations for the 
study. 
On Day 1 in Part A, blood pressure and PR will be assessed at predose, end of infusion (for IV 
only), and 3-, 6-, and 12-hour postdose. Blood pressure and PR should be measured after resting 
for at least 5 minutes in a supine position. 
Temperature and oxygen saturation will be measured. Temperature and oxygen saturation are 
required only at screening, baseline, last scheduled visit, and early discontinuation. 
In the case of AEs suggestive for orthostatic measurements, participants should be in a supine 
position for at least 5 minutes and stand for at least 2 minutes.  
If the participant is unable to stand, only supine vital signs will be recorded. 
Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of dizziness or 
posture-induced symptoms. Additional vital signs may be measured during each study period if 
warranted.  
Additional vital signs may be measured during each study period if warranted and agreed upon 
between the investigator and sponsor. 
On days with concurrent ECG and/or PK sampling, these measurements should occur at 
approximately the same time. Vital sign measurements should occur prior to the blood draw.  
8.2.3. 
Electrocardiograms  
For each participant, ECGs should be collected according to the SoA (Section 1.3). 
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For Part A, a single ECG will be obtained at screening and at the last scheduled follow-up visit, 
but not transmitted to the central ECG vendor. At all other time points in Part A, consecutive 
ECGs are to be obtained in triplicate at approximately 1-min intervals. Additional tracings may 
be taken at each time point to obtain high quality data, when needed. Times are referenced to the 
end of dosing. ECGs will be obtained on Day 1 (predose [any time prior to dosing on the day of 
dosing but within approximately 90 minutes prior to the predose blood draw], end of infusion 
[approximately 6 hours after the end of infusion for the IV cohort and predose only for the SC 
cohort], Day 2 [approximately 24 hours after the end of dosing for both the IV and SC cohorts], 
and at any time on other specified visits [but prior to any blood draws at the same visit]). 
For MAD Part B, a single ECG will be collected locally and stored at the investigator’s site, 
unless the ECG values for participants in SAD Part A cohorts show clinically significant changes 
(for example, an increase in PR or QT interval). In this situation, triplicate 12-lead digital ECGs 
will be collected for participants in Part B cohorts. 
For Part C, a single ECG will be collected prior to dosing locally and stored at the investigator’s 
site unless the ECG values for participants show clinically significant changes (for example, an 
increase in PR or QT interval). In this situation, triplicate 12-lead digital ECGs will be collected 
for participants in Part C cohorts. 
Any clinically significant findings from ECGs that result in a diagnosis and that occur after the 
subject receives the first dose of the study intervention should be reported to Lilly, or its 
designee, as an AE via eCRF. 
When scheduled at the same time point, ECGs must be recorded before collecting any blood 
samples. Participants must be in a supine position for at least 5 minutes before ECG collection 
and remain supine but awake during ECG collection. Consecutive replicate ECGs will be 
obtained at approximately 1-minute intervals. ECGs may be obtained at additional times when 
deemed clinically necessary. 
ECGs will be interpreted by a qualified investigator (the physician or qualified designee) at the 
site soon after the time of ECG collection as possible, and ideally while the subject is still 
present, to determine whether the subject meets entry criteria at the relevant visit(s) and for 
immediate subject management should any clinically relevant findings be identified. 
If a clinically significant quantitative or qualitative change from baseline is identified after the 
enrollment, the investigator will assess the participant for symptoms (for example, palpitations, 
near syncope, and syncope) to determine whether the participant can continue in the study. The 
investigator or qualified designee is responsible for determining if any change in participant 
management is needed and must document review of the ECG as soon as possible after the time 
of collection from at least one of the replicate ECGs from each time point. 
Triplicate digital ECGs will be electronically transmitted to a central ECG laboratory designated 
by Lilly. The central ECG laboratory will perform a basic quality control check (for example, 
demographics and study details) and then store the ECGs in a database. At a future time, the 
stored ECG data may be overread at the central ECG laboratory for further evaluation of 
machine-read measurements or to meet regulatory requirements. 
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The machine-read ECG intervals and heart rate may be used for data analysis and report writing 
purposes, unless a cardiologist’s overread of the ECGs is conducted prior to the completion of 
the final study report (in which case the overread data would be used). 
8.2.5. 
Clinical Safety Laboratory Tests  
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and the 
SoA (Section 1.3) for the timing and frequency. 
The investigator must review the laboratory results, document this review, and report any 
clinically relevant changes occurring during the study as an AE. The laboratory results must be 
retained with source documents unless a source document agreement or comparable document 
cites an electronic location that accommodates the expected retention duration. Clinically 
significant abnormal laboratory findings are those that are not associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the participant's 
condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within the follow-up after the last dose of study intervention should be repeated 
until the values return to normal or baseline or are no longer considered clinically significant by 
the investigator or medical monitor. 
 If such values do not return to normal/baseline within a period of time judged reasonable 
by the investigator, the etiology should be identified and the sponsor notified. 
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 All protocol-required laboratory assessments, as defined in Appendix 2 (Section 10.2), 
must be conducted in accordance with the SoA (Section 1.3), standard collection 
requirements, and laboratory manual. 
If laboratory values from non-protocol specified laboratory assessments performed at an 
investigator-designated 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 report the information as an AE. 
8.2.6. 
Injection-site Reactions  
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8.2.6.2. 
Injection-Site Bleeding Assessment  
All injection sites will be observed within 1 minute after each injection by the investigator or 
designee, and the presence of visible bleeding will be recorded on the eCRF (Injection Procedure 
Evaluation Form). 
A bandage may be placed on the injection site after assessment. In addition, if pain is present, 
participants will be asked if they can distinguish the cause of the pain (that is, needle insertion or 
fluid injection). 
8.2.6.3. 
Injection-Site Bruising Assessment  
Any spontaneously reported or clinically significant finding of injection-site bruising, as deemed 
by the Principal Investigator or designee, will be reported as an AE with additional information 
about the bruise (for example, maximum width). 
8.2.7. 
Safety Monitoring  
The sponsor will monitor safety data throughout the course of the study. Lilly will review SAEs 
within time frames mandated by company procedures.  
The sponsor will periodically review  
 trends in safety data,  
 laboratory analytes, including hematology and chemistry, and 
 AEs.  
When appropriate, the sponsor will consult with the functionally independent Global Patient 
Safety therapeutic area physician or clinical research physician.  
8.2.7.1. 
Other Safety Monitoring  
8.2.7.1.1. Pregnancy Testing   
In this study, a serum pregnancy test will be conducted at screening only. A urine pregnancy test 
will be used at all other time points. For all female participants, follicle-stimulating hormone 
should be drawn to confirm status as defined in the Inclusion Criterion [7b] and to be considered 
exempt for further pregnancy tests during the study. 
8.2.7.1.2. Infusion-related Reactions  
IRR are systemic events temporally related to infusion (for example, IV or large volume SC) of a 
therapeutic agent for which an etiology is yet to be identified. IRRs may encompass a wide range 
of clinical events, including anaphylaxis and other events that may not be directly related to 
antibody responses, such as cytokine release syndrome. 
Signs and symptoms of IRR shall be captured in the eCRF. 
8.2.7.1.3. Hypersensitivity  
Many drugs, but particularly biologic agents, carry the risk of systemic hypersensitivity 
reactions. If such a reaction occurs, additional data describing each symptom should be provided 
to the sponsor in the eCRF. 
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Sites should have appropriately trained medical staff and appropriate medical equipment 
available when study participants are receiving the study drug. It is recommended that 
participants who experience a systemic hypersensitivity reaction be treated per the local standard 
of care. 
If the investigator determines that a systemic hypersensitivity reaction has occurred related to 
study intervention administration, the participant may be permanently discontinued from the 
study intervention, and the sponsor’s designated medical monitor should be notified. If the 
investigator is uncertain about whether a systemic hypersensitivity reaction has occurred and 
whether discontinuation of study intervention is warranted, the investigator may consult the 
sponsor. 
In case of systemic hypersensitivity reactions, defined as anaphylaxis or generalized urticaria, 
additional blood samples should be collected as described in Appendix 2 (Section 10.2). 
Laboratory results are provided to the sponsor via the central laboratory. 
In the event of drug hypersensitivity reactions (immediate or nonimmediate), up to 3 additional 
samples will be collected each for PK and immunogenicity at the following time points: as close 
to the onset of the reaction event as possible, at the resolution of the event if possible, and 
approximately 30 days following the event. 
8.2.8. 
Hepatic Safety Monitoring, Evaluation, and Criteria for Study Drug 
Interruption or Discontinuation  
This table summarizes actions to take based on abnormal hepatic laboratory or clinical changes. 
If this laboratory value is observed… 
Then… 
Initiate or 
continue 
close hepatic 
monitoring 
Initiate  
comprehensive 
evaluation 
Interrupt or 
discontinue  
study drug 
ALT or AST ≥3x ULN 
X 
 
 
ALP ≥2x ULN  
X 
 
 
TBL ≥2x ULNa 
X 
 
 
ALT or AST ≥5x ULN 
X 
X 
 
ALP ≥2.5x ULN 
X 
X 
 
ALT or AST ≥3x ULN with hepatic signs or symptomsb 
X 
X 
X 
ALT or AST ≥5x ULN for more than 2 weeks  
X 
X 
X 
ALT or AST ≥8x ULN 
X 
X 
X 
ALT or AST ≥3x ULN and TBL ≥2x ULNa 
X 
X 
X 
ALP ≥3x ULN  
X 
X 
X 
ALP ≥2.5x ULN and TBL ≥2x ULNa 
X 
X 
X 
ALP ≥2.5x ULN with hepatic signs or symptomsb 
X 
X 
X 
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a In participants with Gilbert’s syndrome, the threshold for TBL may be higher. 
b  Examples of hepatic signs or symptoms: severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, 
fever, rash, and/or eosinophilia >5%. 
8.2.8.1.1. Close Hepatic Monitoring  
If a participant develops any one of these changes, initiate close hepatic monitoring: 
ALT or AST ≥3x ULN or 
ALP ≥2x ULN or 
TBL ≥2x ULNa 
a In participants with Gilbert’s syndrome, the threshold for TBL may be higher. 
Close hepatic monitoring should include the following actions: 
 
Laboratory tests described in Appendix 6 (Section 10.6), including ALT, AST, ALP, TBL, 
direct bilirubin, gamma-glutamyl transferase, creatine kinase, and complete blood count 
with differential, should be checked within 48 to 72 hours of the detection of elevated 
liver tests to confirm the abnormality and determine if it is increasing or decreasing. 
 
If the abnormality persists, clinical and laboratory monitoring should continue at a 
frequency of 1-2 times weekly until levels normalize or return to approximate baseline 
values.  
 
In addition to lab tests, a basic evaluation for possible causes of abnormal liver tests 
should be initiated by the investigator in consultation with the Lilly-designated medical 
monitor. At a minimum, this evaluation should include physical examination and a 
thorough medical history, including current symptoms, recent illnesses (for example, 
heart failure, systemic infection, hypotension, or seizures), recent travel, concomitant 
medications (including over-the-counter), herbal and dietary supplements, history of 
alcohol drinking, and other substance abuse. 
8.2.8.1.2. Comprehensive Hepatic Monitoring  
If a participant develops any one of the following laboratory or clinical changes, initiate a 
comprehensive hepatic evaluation:  
ALT or AST ≥5x ULN or 
ALP ≥2.5x ULN or 
ALT or AST ≥3x ULN with hepatic signs or symptomsa or 
ALT or AST ≥5x ULN for more than 2 weeks or 
ALT or AST ≥8x ULN or 
ALT or AST ≥3x ULN and TBL ≥2x ULNb or INR≥ 1.5 
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a Examples of hepatic signs/symptoms: severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, 
fever, rash, and/or eosinophilia >5%. 
b In participants with Gilbert’s syndrome, the threshold for TBL may be higher. 
Comprehensive hepatic evaluation should include the following actions: 
 
At a minimum, comprehensive hepatic evaluation should include a physical examination 
and a thorough medical history, as outlined above, as well as tests for PT-INR; tests for 
viral hepatitis A, B, C, and E; tests for autoimmune hepatitis; and an abdominal imaging 
study (for example, an ultrasound or CT scan).  
 
Based on the participant’s history and initial results, further testing should be considered 
in consultation with the Lilly-designated medical monitor, including tests for hepatitis D 
virus, cytomegalovirus, Epstein-Barr virus, acetaminophen levels, acetaminophen protein 
adducts, a urine toxicology screen, Wilson’s disease, blood alcohol levels, urinary ethyl 
glucuronide, and blood phosphatidylethanol.  
 
Based on the circumstances and the investigator’s assessment of the participant’s clinical 
condition, the investigator should consider referring the participant for a hepatologist or 
gastroenterologist consultation, and additional tests, including magnetic resonance 
cholangiopancreatography, endoscopic retrograde cholangiopancreatography, cardiac 
echocardiogram, or a liver biopsy.  
 
Clinical and laboratory monitoring should continue at a frequency of approximately 1 to 
2 times weekly until levels normalize or return to approximate baseline values.  
 
All the medical information and test results related to hepatic monitoring and 
comprehensive hepatic evaluation should be collected and recorded in a hepatic safety 
CRF.  
8.2.8.1.3. Study Drug Interruption or Discontinuation  
If a participant develops any one of the following laboratory or clinical changes, interrupt the 
study-drug and continue close monitoring and comprehensive hepatic evaluation as described in 
Section 8.2.8.1.1. and 8.2.8.1.2. 
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ALT or AST ≥3x ULN with hepatic signs/ symptomsa or 
ALT or AST ≥5x ULN for more than 2 weeks or 
ALT or AST ≥8x ULN or 
ALT or AST ≥3x ULN and TBL ≥2x ULNb or INR ≥1.5 or 
ALP ≥3x ULN or 
ALP ≥2.5x ULN and TBL ≥2x ULNb or 
ALP ≥2.5x ULN with hepatic signs or symptomsa 
a Examples of hepatic signs or symptoms: severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, 
fever, rash, and/or eosinophilia >5%. 
b In participants with Gilbert’s syndrome, the threshold for TBL may be higher. 
Interruption or discontinuation of study drug should include the following actions: 
 
While the participant is not receiving the study drug, clinical and laboratory monitoring 
should continue at a frequency of 1 to 2 times weekly until liver tests normalize or return 
to approximate baseline values.  
 
If the hepatic event continues past the anticipated end of the study (that is, data lock), the 
investigator should consult with the Lilly-designated medical monitor to determine the 
need for further data collection beyond the end date of the study (that is, data lock date). 
 
All the medical information and test results related to close hepatic monitoring and 
comprehensive hepatic evaluation should be collected and recorded in a hepatic safety 
CRF.  
 
Resumption of the study drug after interruption for a hepatic reason can be considered 
only in consultation with the Lilly designated medical monitor, only if the liver test 
results returned to near baseline, and if a self-limited non-study-drug etiology is 
identified. Otherwise, the study drug should be permanently discontinued. 
8.2.9. 
Immunological Status Assessments  
WBC subpopulations (including, but not limited to, total B cells, total T cells, and NK cells) in 
blood samples collected at visits and times specified in the SoA (Section 1.3) will be measured 
using flow cytometry as part of immunophenotyping assessment in Parts A, B, and C. A 
maximum of 3 samples may be collected at additional time points during the study (as 
unscheduled samples) if warranted and agreed upon between both the investigator and sponsor. 
Instructions for the collection and handling of blood samples will be provided by the sponsor. 
The actual date and 24-hour clock time of each sampling will be recorded. Immunoglobulin 
samples will also be collected as specified in the SoA (Section 1.3) as part of safety assessment. 
8.2.10. 
Hepatitis B Testing and Monitoring  
Testing 
Testing for HBV infection includes HBsAg and anti-HBc. 
 If HBsAg is positive, the participant is excluded. 
 If HBsAg is negative and anti-HBc is negative, the participant is not excluded. 
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 If HBsAg is negative and anti-HBc is positive, further testing for HBV DNA is required. 
o If the screening HBV DNA is positive, the participant is excluded. 
o If the screening HBV DNA is negative, the participant is not excluded.  
Monitoring 
If the screening HBV DNA is negative, and proof of HBV vaccination cannot be provided, 
repeat testing for HBV DNA is required at least every 3 months during the study. 
8.2.11. 
Hepatitis C Testing  
Testing for HCV infection includes anti-HCV. 
 If anti-HCV is positive, a test for circulating HCV RNA is required. 
o If HCV RNA test is positive, the participant is excluded. 
8.2.12. 
Pregnancy Testing  
In this study, pregnancy testing will be carried out at time points indicated in the SoA (Section 
1.3). Testing will be performed on all female participants. A serum pregnancy test will be 
conducted at screening, and a urine pregnancy test will be conducted at all other time points, 
including discharge. 
8.3. 
Adverse Events, Serious Adverse Events, and Product Complaints  
The definitions of the following events can be found in Appendix 3 (Section 10.3): 
 AEs 
 SAEs, and 
 PCs. 
These events will be reported by the participant or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative. 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet these definitions and remain responsible for following up on events 
that are serious, considered related to the study intervention or study procedures, or that caused 
the participant to discontinue the study (Section 7). 
Care will be taken not to introduce bias when detecting events. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about event occurrences. 
After the initial report, the investigator is required to proactively follow each participant at 
subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event is 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
For product complaints, the investigator is responsible for ensuring that follow-up includes any 
supplemental investigations, as indicated, to elucidate the nature or causality. Further 
information on follow-up procedures is provided in Appendix 3 (Section 10.3). 
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Investigators are responsible for monitoring the safety of participants who have entered this 
study and alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the participant. 
The investigator is responsible for the appropriate medical care of participants during the study. 
Adverse Events 
Investigators must document their review of each laboratory safety report. The investigator 
remains responsible for following through an appropriate healthcare option, AEs that are serious 
or otherwise medically important, considered related to the study intervention or the study, or 
that caused the participant to discontinue the study intervention before completing the study. The 
participant should be followed up until the event resolves, stabilizes with appropriate diagnostic 
evaluation, or is reasonably explained. The frequency of follow-up evaluations of the AE is left 
to the discretion of the investigator. After the ICF is signed, study-site personnel will record, via 
eCRF, the occurrence and nature of each participant’s preexisting conditions. Additionally, site 
personnel will record any change in the condition(s) and the occurrence and nature of any AEs. 
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to the study treatment or a study procedure, considering the disease, concomitant 
treatment, or pathologies. 
A “reasonable possibility” means that there is a potential cause-and-effect relationship between 
the IP, study device and/or study procedure, and the AE. 
Planned surgeries should not be reported as AEs unless the underlying medical condition has 
worsened during the course of the study. 
If a participant’s study intervention is discontinued due to an AE, study-site personnel must 
report this to Lilly or its designee via eCRF. 
Serious Adverse Events 
Study-site personnel must alert the sponsor, or its designee, of any SAE as soon as practically 
possible. 
Additionally, study-site personnel must alert Lilly Global Patient Safety, or its designee, of any 
SAE within 24 hours of investigator awareness of the event via a sponsor-approved method. If 
alerts are issued via telephone, they are to be immediately followed up with official notification 
on study-specific SAE forms. This 24‑hour notification requirement refers to the initial SAE 
information and all follow-up SAE information. 
Although all AEs are recorded in the eCRF after signing the informed consent, SAE reporting to 
the sponsor begins after the participant has signed informed consent and has received the study 
intervention. However, if an SAE occurs after signing informed consent but prior to receiving 
study intervention AND is considered reasonably possibly related to a study procedure, then it 
must be reported. 
Investigators are not obligated to actively seek AEs or SAEs in participants once they have 
discontinued from and/or completed the study (the subject summary eCRF has been completed). 
However, if the investigator learns of any SAE, including a death, at any time after a participant 
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has been discharged from the study and he/she considers the event reasonably possibly related to 
the study intervention or study participation, the investigator must promptly notify Lilly. 
8.3.1. 
Timing and Mechanism for Collecting Events  
This table describes the timing, deadlines, and mechanism for collecting events. 
Event 
Collection 
Start 
Collection 
Stop 
Timing for Reporting 
to Sponsor or 
Designee 
Mechanism for 
Reporting 
Back-up 
Method of 
Reporting 
Adverse Event 
AE 
Signing of 
ICF 
Participation 
in study has 
ended 
As soon as possible 
upon site awareness 
AE CRF 
NA 
Serious Adverse Event 
SAE and SAE 
updates – prior 
to start of study 
intervention and 
deemed 
reasonably 
possibly related 
to study 
procedures 
Signing of 
ICF 
Start of 
intervention 
Within 24 hours of 
awareness 
SAE CRF for 
mechanism of 
reporting and for 
back up SAE paper 
form 
SAE CRF 
for 
mechanism 
of 
reporting 
and for 
back up 
SAE paper 
form 
SAE and SAE 
updates – after 
start of study 
intervention 
Start of 
intervention 
Participation 
in study has 
ended 
Within 24 hours of 
awareness 
LSS SAE reporting 
process 
NA 
SAE* – after 
participant’s 
study 
participation has 
ended and the 
investigator 
becomes aware 
After 
participant’s 
study 
participation 
has ended 
NA 
Promptly 
SAE paper form 
NA 
Pregnancy 
Pregnancy in 
female 
participants and 
female partners 
of male 
participants 
After the 
start of study 
intervention 
Part A: 12 
weeks after 
last dose. 
Part B: 14 
weeks after 
last dose. 
Part C: 2 
weeks after 
last dose. 
Within 24 hours (see 
Section 8.3.2) 
Pregnancy paper 
form 
Pregnancy 
paper form 
Product Complaints 
PC associated 
with an SAE or 
might have led 
to an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 24 hours of 
awareness 
Product Complaint 
form 
NA 
PC not 
associated with 
an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 1 business day 
of awareness 
Product Complaint 
form 
NA 
Updated PC 
information 
— 
— 
As soon as possible 
upon site awareness 
Originally 
completed Product 
NA 
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Abbreviations: AE = adverse event; CRF = case report form; ICF = informed consent form; LSS = Lilly Safety 
System; NA = not applicable; PC = product complaint; SAE = serious adverse event. 
* Serious adverse events should not be reported unless the investigator deems them to be possibly related to study 
treatment or study participation. 
8.3.2. 
Pregnancy  
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 the study intervention. 
After learning of a pregnancy in the female partner of a study participant, the investigator 
 will obtain consent to release information from the pregnant female partner directly, and 
 within 24 hours after obtaining this consent, will record pregnancy information on the 
appropriate form and submit it to the sponsor. 
The female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the sponsor. Generally, the follow-up 
will be no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of gestational age, fetal status (presence or absence of 
anomalies), or indication for the procedure. 
Female Participants Who Become Pregnant  
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a participant's 
pregnancy. 
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate, and the information will be 
forwarded to the sponsor. Generally, 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, regardless of 
gestational age, fetal status (presence or absence of anomalies), or indication for the procedure. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
A spontaneous abortion (occurring at <20 weeks gestational age) or still birth (occurring at ≥20 
weeks gestational age) is always considered to be an SAE and will be reported as such. 
Complaint form 
with all changes 
signed and dated by 
the investigator 
PC (if 
investigator 
becomes aware) 
Participation 
in study has 
ended 
NA 
Promptly 
Product Complaint 
form 
 
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Any post-study pregnancy-related SAE, considered reasonably related to the study intervention 
by the investigator, will be reported to the sponsor as described in protocol Section 8.3.1. While 
the investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting. 
Any female participant who becomes pregnant while participating in the study will discontinue 
the study intervention. If the participant is discontinued from the study, follow the standard 
discontinuation process and continue directly to the follow-up phase. The follow-up on the 
pregnancy outcome should continue independent of intervention or study discontinuation. 
Consult the appropriate medically qualified team member if unsure if this section is applicable 
for a particular protocol. 
8.3.3. Adverse Events of Special Interest  
Not applicable. 
8.4. 
Pharmacokinetics  
For Parts A, B, and C, a maximum of 3 additional blood samples may be collected as additional 
unscheduled time points during the study, if warranted and agreed upon between both the 
investigator and sponsor. Refer to Section 10.2.1 for details. Instructions for the collection and 
handling of blood samples will be provided by the sponsor. Times are referenced at the start of 
dosing. The actual date and time (24-hour clock time) of each sampling will be recorded. 
Samples are requested to be taken at the specified time. However, aberrations from the specified 
sampling times will not be considered protocol deviations as long as the samples are taken, and 
the actual sampling time is recorded. It is essential that the actual times of doses and samples are 
recorded accurately on the appropriate forms.  
Drug concentration information that may unblind the study will not be reported to CRU or 
blinded personnel until the study has been unblinded. 
In the event of the early discontinuation of a participant in any part of the study, a PK sample 
will be taken at the early discontinuation visit as an unscheduled sample. The actual date and 
time of the collection must be recorded. 
8.4.1. 
Pharmacokinetics of LY3872386 in Part A and Part B  
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8.4.2. 
Pharmacokinetics of Prednisone in Part C  
At the visits and times specified in the SoA (Section 1.3), venous blood samples of 
approximately 3 mL will be collected to determine the concentrations of prednisone and its 
metabolite, prednisolone.  
Predose assessments should be completed before IP administration. All other PK time points 
should be collected 24 hours post previous day’s administration of prednisone. On days where 
applicable, collection should be prior to receiving prednisone administration.  
8.4.3. 
Bioanalysis  
Plasma samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor. Analyses of samples collected from placebo-treated participants are 
not planned. 
Bioanalytical samples collected to measure IP concentrations for Parts A, B, and C will be 
retained for a maximum of 1 year following the last participant visit for the study. During this 
time, samples remaining after the bioanalyses may be used for exploratory analyses, such as 
metabolism, protein binding, or bioanalytical development. 
For Parts A and B, concentrations of LY3872386 (ADC), total antibody, and LY3558533 
(unconjugated payload) will be analyzed using validated LC-MS methods. Analyses of samples 
collected from the placebo-treated participants are not planned.  
Drug concentration information that may unblind the study will not be reported to CRU or 
blinded personnel until the study has been unblinded. 
For Part C, concentrations of prednisone and its metabolite prednisolone will be analyzed using 
validated LC-MS methods. 
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8.5. 
Pharmacodynamics  
8.5.1. 
Pharmacodynamics of LY3872386  
At the times specified in the SoA (Section 1.3), venous blood samples will be collected and used 
to determine both the target engagement effects and the effects on cytokines (IL-4, IL-5, IL-13 
[Part B only], and sCD163) and/or immunoglobulins by LY3872386. Blood will be collected to 
evaluate target engagement, biological activity, and cytokine and/or immunoglobulin levels. 
RO supplies required for the collection and shipment of the participants’ samples will be 
supplied by the sponsor. RO sample handling and shipment to the central laboratory will occur 
per the instructions given to the study site. The actual date and 24-hour clock time of each RO 
sampling will be recorded. Samples are requested to be taken at the specified time. However, 
aberrations from the specified sampling times will not be considered protocol deviations as long 
as the samples are taken and the actual sampling time is recorded. It is essential that the actual 
times of doses and samples are recorded accurately on the appropriate forms. Samples will be 
analyzed at a laboratory approved by the sponsor using validated assays. Any unused blood 
samples will be destroyed in accordance with local regulations. The biological activity of 
LY3872386 will be assessed using a whole blood ex vivo stimulation assay (TSTIM) using 
cytokine concentrations as the readout. Changes in selected markers will be assessed by 
measurement from serum and/or bulk RNA analysis from peripheral blood samples. Instructions 
for the collection and handling of blood samples will be supplied by the sponsor. 
8.5.2. 
Pharmacodynamics of Prednisone  
At the times specified in the SoA (Section 1.3), venous blood samples will be collected to 
evaluate biological activity and cytokine levels. The biological activity of prednisone will be 
assessed using a whole blood ex vivo stimulation assay (TSTIM, Lipopolysaccharide) to 
measure changes in cytokine concentrations as the readout depending on exposure. Changes in 
selected markers will be assessed by biomarker measurement from serum and/or bulk RNA 
analysis and slide-based staining protocols from peripheral blood samples. Instructions for the 
collection and handling of blood samples will be supplied by the sponsor. 
8.6. 
Genetics  
A blood sample will be collected for pharmacogenetic analysis as specified in the SoA 
(Section 1.3), where local regulations allow. 
Samples will not be used to conduct unspecified disease or population genetic research, either 
now or in the future. Samples will be used to investigate variable exposure or response to 
LY3872386 and/or prednisone and to investigate genetic variants thought to play a role in 
disease. Assessment of variable responses may include evaluation of AEs or differences in 
efficacy. 
All samples will be coded with the subject number. These samples and any data generated can be 
linked back to the participant only by CRU personnel. 
Samples will be retained for a maximum of 15 years after the last participant visit for the study at 
a facility selected by Lilly or its designee. This retention period enables the use of new 
technologies, response to regulatory questions, and investigation of variable responses that may 
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not be observed until later in the development of LY3872386 or after it is commercially 
available. 
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named. However, existing approaches include whole genome or exome 
sequencing, genome-wide association studies, multiplex assays, and candidate gene studies. 
Regardless of the technology utilized, the data generated will be used only for the specific 
research scope described in this section. 
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8.8. 
Immunogenicity Assessments  
For SAD Part A and MAD Part B, at the visits and times specified in the SoA (Section 1.3), 
venous blood samples will be collected and stored for potential future immunogenicity analyses. 
To interpret the results of immunogenicity, a venous blood sample will be collected at the same 
time points to determine the plasma PK concentrations of LY3872386, total antibody, and 
LY3558533 (free payload). Samples for immunogenicity should be taken predose when 
applicable and possible.  
TE ADAs are defined in Section 9.3.4.4.  
Samples will be retained for a maximum of 15 years after the last participant visit at a facility 
selected by the sponsor. The duration allows the sponsor to respond to future regulatory requests 
related to LY3872386. Any samples remaining after 15 years will be destroyed. 
8.9. 
Health Economics OR Medical Resource Utilization and Health 
Economics  
Health economics or medical resource utilization and health economics parameters are not 
evaluated in this study. 
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9. 
Statistical Considerations  
The statistical analysis plan will be finalized prior to the first 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. 
9.1. 
Statistical Hypotheses  
No formal hypotheses will be employed. 
9.1.1. 
Multiplicity Adjustment  
There will be no formal hypothesis testing, and therefore, no multiplicity adjustment is planned. 
9.2. 
Analyses Sets  
For purposes of analysis, the following populations are defined: 
Participant Analysis Set 
Description 
Full analysis set (FAS) 
 
All randomized participants. 
Modified Intent-to-Treat (mITT)  
 
All randomized participants who receive at least 1 dose of study treatment. 
Participants will be analyzed according to the treatment to which they were 
assigned (regardless of whether the participant fails to receive the correct 
treatment, or otherwise fails to follow the protocol).  
Safety analysis set 
 
All randomized patients who receive at least 1 dose of study drug will be 
included according to the treatment they actually received, regardless of 
whether they have completed all protocol requirements. 
PK analysis set  
 
All participants who receive at least 1 dose of the study drug and have 
evaluable PK data  
 
A detailed description of participant disposition will be provided at the end of the study. All 
participants who discontinue the study will be identified, and the extent of their participation in 
the study will be reported. If known, a reason for their discontinuation will be given.  
The participant’s baseline characteristics and other demographic characteristics will be recorded, 
listed, and summarized by treatment group and overall. 
9.3. 
Statistical Analyses  
9.3.1. General Considerations  
Handling of missing, unused, and spurious data is addressed prospectively in the overall 
statistical methods described in the protocol and in the SAP, where appropriate. Adjustments to 
the planned analyses are described in the final CSR. 
Statistical analyses of this study will be the responsibility of Lilly or its designee.  
PK analyses will be conducted on data from all participants who receive at least 1 dose of the 
study drug and have evaluable PK data.  
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Safety analyses will be conducted for all participants who are exposed to study intervention. 
Summary statistics, data tabulations, and data graphs by population will be provided as 
appropriate.  
Summary statistics, data tabulations, and data graphs may be presented separately by race and 
ethnicity (for example, Japanese, Chinese, and non-Japanese/non-Chinese), as appropriate. 
Continuous variables will be summarized by the number of observations, mean, standard 
deviation, and median minimum and maximum values. Categorical variables will be summarized 
by counts and percentages. Summary statistics, data tabulations, and data graphs will be provided 
and may be separated by population, as appropriate. No tests to assess statistical significance are 
planned due to the small sample size per treatment group. Additional exploratory analyses of the 
data will be conducted as deemed appropriate. 
The data from placebo groups will be pooled across cohorts as 1 placebo group. 
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 CSR. Additional exploratory analyses of the data will be conducted as deemed appropriate. 
Complete details of the planned analyses will be documented in the SAP. 
Statistical considerations and methodology for handling missing data will be detailed in the SAP. 
9.3.2. 
Primary Endpoint Analysis  
The primary objectives for this study are to assess the safety and tolerability following a single 
dose of LY3872386 in healthy participants and multiple doses of the same in patients with AD, 
as well as the safety and tolerability of prednisone in healthy participants receiving multiple PO 
QD doses at various dose levels. The primary endpoints are the frequency of AEs, TEAEs, and 
SAEs for LY3872386 and prednisone.  
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 symptoms for each treatment and each IP will be presented by severity and by 
association with the study drug as perceived by the investigator. Symptoms reported to have 
occurred prior to enrollment will be distinguished from those reported as new or increased in 
severity during the study. Each symptom will be classified according to the Medical Dictionary 
for Regulatory Activities.  
The number of participants who experience a TEAE and/or SAE will be summarized by both 
study treatment and IP, both for all causalities and TEAEs/SAEs related to the study drug. All 
TEAEs will be summarized by system organ class and by decreasing frequency within system 
organ class.  
The number of drug-related SAEs and AEs will be reported. 
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9.3.3. 
Secondary Endpoint Analysis  
9.3.3.1. 
Pharmacokinetic Parameter Estimation  
PK parameter estimates for LY3872386 (ADC), total antibody, LY3558533 (free payload), 
prednisone, and prednisolone will be calculated using standard noncompartmental methods of 
analysis. 
9.3.3.2. 
Pharmacokinetic Statistical Inference  
The descriptive statistics for the PK parameters will be provided for each dose level or route of 
administration. Where appropriate, the geometric mean and geometric coefficient of variation 
will be reported. If data allows, the dose proportionality for LY3872386 may be assessed for 
AUC and Cmax using a power model to estimate the slope of the power model, which represents 
the ratio of dose-normalized geometric means. 
9.3.4. 
Exploratory Endpoints Analysis  
9.3.4.1. 
Efficacy Endpoints  
Efficacy analyses will be conducted on the mITT population. Due to the small sample size, 
statistical hypothesis tests will not be performed for any efficacy analysis. Instead, efficacy 
outcomes will be summarized with descriptive statistics. Binary efficacy outcomes will be 
summarized with the frequency and percent of responders in each treatment group
 
 All 
efficacy analyses will only be performed for MAD Part B of the study. The exploratory efficacy 
analyses will estimate the effect of the treatment on the exploratory endpoints. 
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9.3.4.2. 
Receptor Occupancy, White Blood Cell Subpopulations, and Pharmacodynamics  
RO, WBC subpopulations, and PD consequences (including 
 PD 
markers and immunoglobulins) will be explored using several methods. The measures of 
concentrations will be graphically evaluated across dose levels and explored as a surrogate for 
target engagement and/or mechanism of action. Model-based analyses to utilize the data to 
estimate RO, relationships with PK, and/or safety may also be performed, if appropriate. 
Exploratory analyses of dose and/or exposure relationships between LY3872386 and RO, WBC 
subpopulations, and PD may be conducted.  
9.3.4.3. 
Injection Site Reactions  
 
 
 
9.3.4.4. 
Evaluation of Immunogenicity  
ADAs may be characterized. The frequency and percentage of subjects with preexisting ADA 
and with TE ADA to LY3872386 may be tabulated.  
TE ADAs are defined as those with  
 
a titer 2-fold (1 dilution) greater than the minimum required dilution if no ADA were 
detected at baseline (treatment-induced ADA), or 
 
a 4-fold (2 dilutions) increase in titer compared to baseline if ADA were detected at 
baseline (treatment-boosted ADA).  
The frequency of neutralizing antibodies and/or LY3872386 and LY3558533 cross-reactive 
antibodies may also be tabulated in TE ADA+ subjects, when available. 
The relationship between the presence of antibodies and the PK parameters, RO, and PD 
response, including safety and efficacy to LY3872386, may be assessed.  
9.3.4.5. 
Pharmacodynamic Parameter Estimation  
PD parameter estimates for 
 and other biomarkers 
will be calculated using standard noncompartmental methods of analysis or other approaches 
deemed necessary by the sponsor. 
9.3.5. 
Other Analyses  
9.3.5.1. 
Other Safety Analyses  
9.3.5.1.1. Clinical Laboratory Parameters, Vital Signs, and Electrocardiograms  
Safety parameters that will be assessed include safety laboratory parameters, vital signs, and 
ECG parameters. The parameters will be listed and summarized using standard descriptive 
statistics. 
Prior to any statistical analyses of the QT interval, QT values will be corrected for heart rate 
based on QTcF. The relationship between concentrations of LY3872386 and changes from 
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baseline QTcF will be explored to assess the effect of LY3872386 concentration on changes 
from baseline QTcF. 
Additional analyses will be performed if warranted upon review of the data. 
The baseline for safety parameters will be defined as the last evaluable value before the first 
dose. 
9.4. 
Interim Analyses  
If an unplanned interim analysis is deemed necessary, the Lilly clinical pharmacologist, 
investigator, or designee will consult with the appropriate medical director or designee to 
determine if it is necessary to amend the protocol. 
9.4.1. 
Interim Access to Data During the Study  
The Lilly sponsor team is not blinded, while the investigator will remain blinded during these 
reviews. Interim access to safety and tolerability data is scheduled to occur after every dosing 
session. The purpose of these reviews is to guide dose selection for future dosing sessions and/or 
inform the design of subsequent studies. 
Access to PK data will also occur on a rolling basis during dose escalation as it becomes 
available. However, IADs are planned to evaluate exposure and available RO data. A review of 
these data will help guide implementation of this study (such as adjustment to blood sampling 
time) and support subsequent studies. 
Four IADs to facilitate AD cohorts and progression to Phase II trial are planned. IADs are 
planned at the following time points: 
 First IAD: 30 days post dose from Part A SAD Cohorts 4 and 5 
o dose justification for Part B MAD Cohort 1, Period 1 
 Second IAD: 30 days post dose from Part A SAD Cohorts 6 and 7 
o dose justification for Part B MAD Cohort 2, Period 1 
 Third IAD: end of Part A SAD cohorts and 30 days post dosing of half of the participants 
from Part B MAD Cohort 1, Period 1  
o dose justification for Part B MAD Cohort 1, Period 2, and 
 Fourth IAD: End of Part C. 
Since PK and RO data will be evaluated on a rolling basis as data become available, review of 
these data is not limited to the IADs mentioned earlier. These periodic reviews of PK and RO 
data are not considered as formal interim analyses. Any IAD may be skipped, and additional 
analysis may be added. If an unplanned IAD is deemed necessary, the Lilly clinical 
pharmacologist, investigator, or designee will consult with the appropriate medical director or 
designee to determine if it is necessary to amend the protocol.  
The investigator and the Lilly clinical pharmacologist or sponsor team will determine dose 
escalation based upon their review of the safety data and PK data when available and/or required. 
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9.5. 
Sample Size Determination  
The study will enroll up to 
 evaluable participants (
 healthy volunteers and 
up to 
 patients with AD). 
 
 
For purposes of this study, a participant completes the study when all scheduled procedures 
shown in the SoA have been finished. Participants who withdraw before completing all dosing 
administrations may be replaced. A replacement participant will complete the entire study 
period. Participants who discontinued the study following the required dose administration(s) but 
before completing may be replaced at the discretion of the sponsor and investigator.
 
 
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10. 
Supporting Documentation and Operational Considerations  
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
10.1.1. 
Regulatory and Ethical Considerations  
This study will be conducted in accordance with the protocol and with the following: 
 consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
 applicable ICH Good Clinical Practice (GCP) Guidelines 
 applicable laws and regulations 
The protocol, protocol amendments, ICF, Investigator Brochure, 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. 
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation 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 
 providing oversight of study conduct for participants under their responsibility 
and adherence to requirements of 21 Code of Federal Regulations (CFR), ICH 
guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations 
 reporting to the sponsor or designee significant issues related to participant safety, 
participant rights, or data integrity 
● investigator sites are compensated for participation in the study as detailed in the 
clinical trial agreement. 
10.1.2. 
Financial Disclosure  
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
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certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.1.3. 
Informed Consent Process  
The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the potential participant or the potential participant’s 
legally authorized representative and answer all questions regarding the study. 
Potential participants must be informed that their participation is voluntary. Participants 
or their legally authorized representatives will be required to sign a statement of informed 
consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, 
privacy, and data protection 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 authorized person obtaining the informed consent must also sign the ICF. 
Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative and is kept on file. 
10.1.4. 
Data Protection  
Participants will be assigned a unique identifier by the sponsor to protect the participant’s 
personal data. Any participant information, such as records, datasets or tissue samples that are 
transferred to the sponsor will contain the identifier only. Participant names or any information 
which would make the participant identifiable will not be transferred. 
The participant must be informed that the participant’s 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. This is done by the site personnel through the informed 
consent process. 
The participant must be informed through the informed consent by the site personnel 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 information security, data integrity, and data 
protection. These processes address management of data transfer, and prevention and 
management of unauthorized access, disclosure, dissemination, alteration or loss of information 
or personal data. These processes include appropriate contingency plan(s) for appropriate and 
timely response in the event of a data security breach. 
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The transfer of personal data is subject to appropriate safeguards through contractual agreements 
and processes. The sponsor’s processes are compliant with local privacy laws and relevant 
legislations including the General Data Protection Regulation. 
10.1.5. 
Committees Structure  
No data monitoring committee will be involved in this study. 
10.1.6. 
Dissemination of Clinical Study Data  
Communication of Suspended or Terminated Dosing 
If a decision is taken to suspend or terminate dosing in the trial due to safety findings, this 
decision will be communicated by Lilly to all investigators (for example, by phone and/or email) 
as soon as possible. It will be a requirement that investigators respond upon receipt to confirm 
that they understand the communication and have taken the appropriate action prior to further 
dosing any participants with study intervention. Any investigator not responding will be 
followed up by Lilly personnel prior to any further planned dosing. If a dose is planned 
imminently, Lilly personnel will immediately, and continually, use all efforts to reach 
investigators until contact is made and instructions verified. 
Reports 
The sponsor will disclose a summary of study information, including tabular study results, on 
publicly available websites where required by local law or regulation. 
The summary of results will be posted within the time frame specified by local law or regulation. 
If the study remains ongoing in some countries and a statistical analysis of an incomplete data set 
would result in analyses lacking scientific rigor (for example, underpowered) or compromise the 
integrity of the overall analyses (for example, trial not yet unblinded), the summary of results 
will be submitted within 1 year after the end of the study globally or as soon as available, 
whichever is earlier. 
Data 
The sponsor does not proactively share data from Phase 1 clinical trials. Requests for access to 
Phase 1 clinical trial data are evaluated on a case by case basis taking into consideration the 
ability to anonymize the data and the nature of the data collected. 
10.1.7. 
Data Quality Assurance  
All participant data relating to the study will be recorded on printed or electronic CRFs 
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. This includes laboratory tests, medical records, and 
clinical notes. 
The investigator must review and confirm that data entries are accurate and complete 
throughout the duration of the study, by physically or electronically signing the CRF, as 
instructed by the sponsor. All completed CRFs must be signed prior to archival. 
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The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents. 
Monitoring details describing strategy (for example, risk-based initiatives in operations 
and quality such as risk management and mitigation strategies and analytical risk-based 
monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques are provided in the Monitoring Plan. 
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). 
The sponsor or designee will perform monitoring to confirm that data transcribed into the 
CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; 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 and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator for the time period outlined in the Clinical Trial 
Agreement (CTA) unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor. 
In addition, 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 Sponsor or its representatives, and/or 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 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 system(s) will be stored at third-party. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture system(s). Prior to decommissioning, the investigator will receive or access 
an archival copy of pertinent data for retention. 
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports or electronic transfers will be provided to the 
investigator for review and retention. Data will subsequently be transferred from the central 
vendor to the Sponsor data warehouse. 
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Data from complaint forms submitted to the Sponsor will be encoded and stored in the global 
product complaint management system. 
10.1.8. 
Source Documents  
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on or entered in the CRF and 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. Also, current medical records must be available. 
Definition of what constitutes source data can be found in Section 10.1.7. 
10.1.9. 
Trial and Site Start and Closure  
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open and will be the study start date. 
Trial or Site Termination 
The sponsor or sponsor’s 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 sufficient 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: 
For study termination: 
● Discontinuation of further study intervention development 
For site termination: 
● 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 (evaluated after a reasonable amount of time) of 
participants by the investigator 
● Total number of participants included earlier than expected. 
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 participant and should assure 
appropriate participant therapy and/or follow-up. 
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10.1.10. 
Publication Policy  
In accordance with the sponsor’s publication policy, the results of this study will be submitted 
for publication by a peer-reviewed journal if the results are deemed to be of significant medical 
importance. 
10.1.11. 
Investigator Information  
Researchers with appropriate education, training, and experience, as determined by the sponsor, 
will participate as investigators in this clinical trial. 
10.1.12. 
Sample Retention  
Samples will be retained at a facility selected by the sponsor or its designee. Sample retention 
enables the use of new technologies, response to regulatory questions, and investigation of 
variable responses that may not be observed until later in the development of LY3872386 or 
after LY3872386 becomes commercially available.  
This table lists the maximum retention period for sample types. 
Sample Type 
Custodian 
Maximum Retention Period After Last 
Participant Visit 
Genetic 
Sponsor or designee 
Up to 15 years 
Exploratory biomarkers 
Sponsor or designee 
Up to 15 years 
Skin biopsies 
Sponsor or designee 
Up to 15 years 
Pharmacokinetics 
Sponsor or designee 
Up to 1 year 
Immunogenicity 
Sponsor or designee 
Up to 15 years 
Any samples remaining after the retention period will be destroyed. 
 
 
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10.2. 
Appendix 2: Clinical Laboratory Tests  
The tests detailed in the table below will be performed by the central laboratory except for the 
following which will be performed at the local laboratory: 
 Safety testing for immediate participant assessment 
 Screening assessments in Part A and Part C. 
In circumstances where the sponsor approves local laboratory testing in lieu of central 
laboratory testing (in the table below), the local laboratory must be qualified in 
accordance with applicable local regulations. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol. 
Additional tests may be performed at any time during the study as determined necessary 
by the investigator to address any immediate patient safety concerns.  
Investigators must document their review of the laboratory safety results. 
Laboratory results that could unblind the study will not be reported to investigative sites or other 
blinded personnel.
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Safety Laboratory Tests 
Hematologya 
Clinical Chemistrya 
Hematocrit 
Sodium 
Hemoglobin 
Potassium 
Erythrocyte count (RBC) 
Bicarbonate 
Mean cell volume  
Chloride 
Mean cell hemoglobin  
Calcium (total)  
Mean cell hemoglobin concentration  
Phosphorus/Phosphate 
Leukocytes (white blood cells [WBCs])  
Glucose (fasting) 
Platelets 
Blood urea nitrogen (BUN) 
Differential WBC (absolute counts) of 
Creatinine  
Neutrophils 
Total protein 
Lymphocytes 
Albumin 
Monocytes 
Total bilirubin 
Eosinophils 
Alkaline phosphatase (ALP) 
Basophils 
Aspartate aminotransferase (AST) 
B Cells 
Alanine aminotransferase (ALT) 
T Cells 
Gamma-glutamyl transferase (GGT) 
NK cells 
Insuline 
 
 
Hemoglobin A1c 
Bedside Glucose Monitoring (fasting)f 
 
 
Urinalysisa 
Serum Immunoglobulinsa 
   Specific gravity 
IgA 
   pH 
IgM 
   Protein 
IgE 
   Glucose 
IgG 
   Ketones 
IgD 
   Bilirubin 
 
   Urobilinogen 
Fasting Lipid Panela 
   Leukocytes 
Total cholesterol 
Blood 
Triglycerides 
Nitrite 
Low-density lipoprotein (LDL) 
Microscopic examination of sedimentb 
High-density lipoprotein (HDL) 
 
LDL/HDL ratio 
 
 
Urine Drug Screenc 
Hepatitis B surface antigeng,h 
Amphetamine  
Barbiturates 
Benzodiazepines 
Cocaine 
Cannabis 
Methylenedioxymethamphetamine (MDMA) 
Opiates 
Oxycodone 
Phencyclidine 
Tricyclic antidepressants 
Cotinine (nicotine) 
Hepatitis B core antibodyg,h 
Hepatitis B surface antibodyg,h 
Hepatitis B DNAh 
Hepatitis C antibodyg,h 
 
 
Ethanol breath testingc 
HIV
g,h 
QuantiFERON®-TB Gold test or TST 
Pregnancy test
i 
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Beta D-glucand 
FSH
i 
Cortisol (serum, cosyntropin stim, and urine) 
Thyroid-stimulating hormone (including T3/T4 tests) 
Syphilis test (including RPR and TPPA as 
appropriate)
g 
Abbreviations: DNA = deoxyribonucleic acid; ED = early discontinuation; FSH = follicle-stimulating hormone; 
HIV = human immunodeficiency virus; Ig = immunoglobulin; NK cell = natural killer cell; RBC = red blood 
cell; RPR = Rapid Plasma Regain; TPPA = Treponema Pallidium Particle Agglutination. 
Note: Results of these assays will be validated by the local laboratory at the time of testing. Additional tests may 
be performed or auto calculated by the laboratory as part of its standard panel that cannot be removed. Some of 
the above parameters are calculated from measured values. The omission of calculated values will not be 
considered as a protocol violation. 
a To be done centrally. If needed for safety, site may also perform locally. 
b Test only if dipstick result is abnormal. 
c Urine drug screen and ethanol breath testing may be repeated prior to admission to the clinical research unit and 
at other times indicated in the Schedule of Activities. Unscheduled testing is allowed. 
d Evaluation of beta-D-glucan may be performed at a local laboratory. Beta-D-glucan is required at screening for 
Part B only (to be performed centrally), and if an investigator believes it is warranted, at subsequent visits (may 
be performed centrally or locally), a beta-D-glucan test may be included in the work up panel at any time during 
the study. If the beta-D-glucan test is positive, pneumocystis pneumonia (PCP) needs to be ruled out. If PCP is 
ruled out and the investigator deems the patient fit to continue, the patient may continue in the study. If a patient 
has a confirmed diagnosis of PCP during the study, the patient must discontinue the study. 
e Not performed at screening. 
f Bedside glucose monitoring is performed using standard glucose monitors and capillary blood taken from 
fingerstick. Fasting should be approximately 2 hours, at a minimum. 
g Performed at screening only. 
h These tests may be waived if performed within 6 months prior to screening, and if test results are available for 
“review” for hepatitis B, C, and HIV. 
i To be performed on all female participants. 
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10.2.1. 
Blood Sampling Summary  
These tables summarize the approximate number of venipunctures and blood volumes for all 
blood sampling (screening, safety laboratories, and bioanalytical assays) during the study. 
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10.2.1.1. Part A: SAD of LY3872386 in Healthy Participants  
 
Purpose 
Blood Volume per 
Sample (mL) 
Number of Blood 
Samples 
Total Volume 
(mL) 
Screening testsa 
45 
1 
45 
Clinical chemistrya, including insulin 
and fasting lipid panel 
4.5 
 
8 
36 
 
Clinical chemistrya, including insulin, 
fasting lipid panel, serum 
immunoglobulins 
8 
6 
48 
Hematology, including TBNK 
4 
12 
48 
TSH, T3/T4 
3.5 
2 
7 
Pharmacokineticsb 
6 
19 
114 
Cortisol 
2 
9 
18 
Cosyntropin stim – Cortisol  
(pre stim and 30-, 60-min post stim) 
2 
6 x 3 time points 
36 
Ex vivo stimulation 
1 
5 
5 
Cytokines 
(IL-4, IL-5, sCD163) 
2.5 
8 
20 
Blood discard for cannula patency 
1 
5 
5 
Blood samples for receptor occupancy 
flow cytometry 
2 
11 
22 
Immunogenicityb 
5 
5 
25 
Pharmacogenetics 
3 
1 
3 
Total 
 
 
501.5 
Total for clinical purposes (rounded up to nearest 10 mL)  
510 
Abbreviations: 
 IL = interleukin; IV = intravenous; 
 PK = 
pharmacokinetic; SC = subcutaneous; TBNK = T, B, and Natural Killer; TSH = thyroid-stimulating hormone. 
a Additional samples may be drawn if needed for safety purposes. 
b Additional 3 samples may be drawn if required. 
c If more than 1 laboratory blood draw is scheduled at the same time, these blood draws should be prioritized in 
the following order: (1) safety laboratory tests, (2) PK samples, (3) receptor occupancy samples, and (4) 
exploratory samples. 
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10.2.1.2. Part B: MAD of LY3872386 in Patients with AD (
 Dosing Schedule)  
 
Purpose 
Blood Volume per 
Sample (mL) 
Number of Blood 
Samples 
Total Volume (mL) 
Screening testsa 
45    
1 
45 
Clinical chemistrya, including insulin 
and fasting lipid panel 
4.5 
7 
31.5 
Clinical chemistrya, including insulin, 
fasting lipid panel, and serum 
immunoglobulins 
8 
4 
32 
Hematology, including TBNK 
4 
11 
44 
TSH, T3/T4 
3.5 
3 
10.5 
Pharmacokineticsb 
6 
22 
132 
Cosyntropin stim – Cortisol (pre stim 
and 30-, 60-min post stim) 
2 
10 x 3 time points 
60 
Cytokines (IL-4, IL-5, IL-13, sCD163) 
5 
8 
40 
Chemokine Panel (MSD V-Plex 
[TARC, MDC], Periostin) 
2.5 
4 
10 
Blood discard for cannula patency 
1 
6 
6 
Blood samples for receptor occupancy 
flow cytometry 
2 
11 
22 
Immunogenicityb 
5 
6 
30 
Pharmacogenetics 
3 
1 
3 
Total 
 
 
534 
Total for clinical purposes (rounded up to nearest 10 mL)  
540 
Abbreviations: 
 IL = interleukin; IV = intravenous; MDC = Macrophage-derived 
chemokine; 
 PK = pharmacokinetic; SC = subcutaneous; TARC = Thymus- and activation-
regulated chemokine; TBNK = T, B, and Natural Killer; TSH = thyroid-stimulating hormone. 
a Additional samples may be drawn if needed for safety purposes. 
b Additional 3 samples may be drawn if required. 
c If more than 1 laboratory blood draw is scheduled at the same time, these blood draws should be prioritized in 
the following order: (1) safety laboratory tests, (2) PK samples, (3) receptor occupancy samples, and (4) 
exploratory samples. 
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10.2.1.3. Part B: MAD of LY3872386 in Patients with AD (
 Dosing Schedule)  
 
Purpose 
Blood Volume per 
Sample (mL) 
Number of Blood 
Samples 
Total Volume 
(mL) 
Screening testsa 
45 
1 
45 
Clinical chemistrya, including 
insulin and fasting lipid panel 
4.5  
 
5  
22.5 
Clinical chemistrya, including 
insulin, fasting lipid panel, and 
serum immunoglobulins 
8 
4 
32 
Hematology, including TBNK 
4 
8 
32 
TSH, T3/T4 
3.5 
3 
10.5 
Pharmacokineticsb 
6 
20 
120 
Cosyntropin stim – Cortisol (pre 
stim and 30-, 60-min post stim) 
2 
6 x 3 time points 
36 
Cytokines (IL-4, IL-5, IL-13, 
sCD163) 
5 
8 
40 
Chemokine Panel (MSD V-Plex 
[TARC, MDC], Periostin) 
2.5 
4 
10 
Blood discard for cannula patency 
1 
6 
6 
Blood samples for receptor 
occupancy flow cytometry 
2 
12 
24 
Immunogenicityb 
5 
11 
55 
Pharmacogenetics 
3 
1 
3 
Total 
 
 
509 
Total for clinical purposes (rounded up to nearest 10 mL)  
510 
Abbreviations: 
 IL = interleukin; IV = intravenous; MDC = Macrophage-derived 
chemokine; 
 PK = pharmacokinetic; SC = subcutaneous; TARC = Thymus- and activation-
regulated chemokine; TBNK = T, B, and Natural Killer; TSH = thyroid-stimulating hormone. 
a Additional samples may be drawn if needed for safety purposes. 
b Additional 3 samples may be drawn if required. 
c If more than 1 laboratory blood draw is scheduled at the same time, these blood draws should be prioritized in 
the following order: (1) safety laboratory tests, (2) PK samples, (3) receptor occupancy samples, and (4) 
exploratory samples.
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10.2.1.4. Part C: Prednisone in Healthy Participants - 
 Dosing Groups  
 
Purpose 
Blood Volume 
per Sample 
(mL) 
Number of Blood Samples 
Total 
Volume 
(mL) 
Screening testsa 
45 
1 
45 
Clinical chemistrya, including insulin and Day 
30 fasting lipid panel 
4.5 
7 
31.5 
Fasting lipid panel (Day 1) 
2.5 
2 
5 
Hematology, including TBNK 
4 
7 
28 
TSH, T3/T4 
3.5 
2 
7 
Serum immunoglobulins 
5 
4 
20 
Pharmacokineticsb 
3 
51 
153 
 
 
 
 
Cortisol 
2 
30 
60 
Cosyntropin stim – Cortisol (pre stim and  
30-, 60-min post stim) 
2 
5 x 3 time points 
30 
Cytokines (IL-4, IL-5, sCD163) 
5 
3 
15 
Blood discard for cannula patency 
1 
21 
21 
Pharmacogenetics 
3 
1 
3 
Total 
 
 
465 
Total for clinical purposes (rounded up to nearest 10 mL)  
470 
Abbreviations: 
 IL = interleukin; IV = intravenous; 
 PK = 
pharmacokinetic; SC = subcutaneous; TBNK = T, B, and Natural Killer; TSH = thyroid-stimulating hormone. 
a Additional samples may be drawn if needed for safety purposes. 
b Additional 3 samples may be drawn if required. 
c If more than 1 laboratory blood draw is scheduled at the same time, these blood draws should be prioritized in 
the following order: (1) safety laboratory tests, (2) PK samples, (3) receptor occupancy samples, and (4) 
exploratory samples. 
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10.2.1.5. Part C: Prednisone in Healthy Participants - 
 Dosing Group  
Abbreviations: 
 IL = interleukin; IV = intravenous; 
 PK = 
pharmacokinetic; SC = subcutaneous; TBNK = T, B, and Natural Killer; TSH = thyroid-stimulating hormone. 
a Additional samples may be drawn if needed for safety purposes. 
b Additional 3 samples may be drawn if required. 
c If more than 1 laboratory blood draw is scheduled at the same time, these blood draws should be prioritized in 
the following order: (1) safety laboratory tests, (2) PK samples, (3) receptor occupancy samples, and (4) 
exploratory samples. 
 
 
Purpose 
Blood Volume per 
Sample (mL) 
Number of Blood 
Samples 
Total Volume 
(mL) 
Screening testsa 
45 
1 
45 
Clinical chemistrya, including insulin 
4.5 
7 
31.5 
Hematology, including TBNK 
4 
7 
28 
TSH, T3/T4 
3.5 
2 
7 
Serum immunoglobulins 
5 
4 
20 
Pharmacokineticsb 
3 
30 
90 
Cortisol 
2 
7 
14 
Cosyntropin stim – Cortisol  
(pre stim and 30-, 60-min post stim) 
2 
3 x 3 time points 
18 
Cytokines 
(IL-4, IL-5, sCD163) 
5 
5 
25 
Ex vivo stimulation 
13 
4 
52 
Blood discard for cannula patency 
1 
21 
21 
Pharmacogenetics 
3 
1 
3 
Total 
 
 
407.5 
Total for clinical purposes (rounded up to nearest 10 mL)  
410 
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10.3. 
Appendix 3: Adverse Events and Serious 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 participant administered a pharmaceutical 
product and which does not necessarily have a causal relationship with the study intervention. 
An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. 
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 (that is, 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 condition 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. 
Medication error, misuse, or abuse of IMP, including signs, symptoms, or clinical sequelae. 
Lack of efficacy or failure of expected pharmacological action per se will not be reported as an 
AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE 
if they fulfill the definition of an AE or SAE. 
Events NOT Meeting the AE Definition 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments that 
are associated with the underlying disease, unless judged by the investigator to be more severe 
than expected for the participant’s condition. 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s condition. 
Medical or surgical procedure (for example, endoscopy, appendectomy): the condition that leads 
to the procedure is the AE. 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
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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  
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of 
the criteria listed: 
a) Results in death 
b) Is life-threatening 
o 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 
o In general, hospitalization signifies that the participant has been admitted to 
hospital or emergency ward (usually involving at least an overnight stay) for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
hospitalization occurred or was necessary, the AE should be considered serious. 
o 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 
o The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
o This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, 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 
o Abnormal pregnancy outcomes (for example, spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs. 
f) Other situations: 
o Medical or scientific judgment should be exercised by the investigator 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. 
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o Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
10.3.3. 
Definition of Product Complaint  
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 
study intervention. When the ability to use the study intervention safely is impacted, the 
following are also product complaints: 
 Deficiencies in labeling information, and 
 Use errors for device or drug-device combination products due to ergonomic design 
elements of the product. 
Product complaints related to study interventions used in clinical trials are collected in order to 
ensure the safety of participants, monitor quality, and to facilitate process and product 
improvements. 
Investigators will instruct participants to contact the site as soon as possible if he or she has a 
product complaint or problem with the study intervention so that the situation can be assessed. 
An event may meet the definition of both a product complaint and an AE/SAE. In such cases, it 
should be reported as both a product complaint and as an AE/SAE. 
10.3.4. 
Recording and Follow-Up of AE and/or SAE and Product Complaints  
AE, SAE, and Product Complaint Recording 
When an AE/SAE/product complaint 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/product complaint information in the 
participant’s medical records, in accordance with the investigator’s normal clinical practice. 
AE/SAE information is reported on the appropriate CRF page and product complaint information 
is reported on the Product Complaint Form.  
Note: An event may meet the definition of both a product complaint and an AE/SAE. In such 
cases, it should be reported as both a product complaint and as an AE/SAE. 
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 CRF page for AE/SAE and the Product 
Complaint Form for product complaints. 
There may be instances when copies of medical records for certain cases are requested by 
Sponsor or designee. In this case, all participant identifiers, with the exception of the participant 
number, will be redacted on the copies of the medical records before submission to Sponsor or 
designee. 
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The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to one of the following categories:  
 Mild: A type of adverse event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with usual 
activities of daily living. 
 Moderate: A type of adverse event that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research participant. 
 Severe: A type of adverse event that interrupts usual activities of daily living, or 
significantly affects clinical status, or may require intensive therapeutic intervention. An 
AE that is assessed as severe should not be confused with a SAE. Severe is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be assessed as 
severe. An event is defined as ‘serious’ when it meets at least one 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. The investigator will use clinical judgment to determine the 
relationship. 
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. 
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 in their assessment. 
For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Sponsor or designee. However, it is very important 
that the investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to Sponsor or designee. 
The investigator may change their opinion of causality in light of follow-up information and send 
a SAE follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
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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 Sponsor or designee with a copy of any postmortem findings including 
histopathology. 
10.3.5. 
Reporting of SAEs  
SAE Reporting via Paper Form 
Facsimile transmission of the SAE paper form is the preferred method to transmit this 
information to the Lilly clinical pharmacologist. 
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 will be provided to the site. 
 
 
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10.3.6. 
Regulatory Reporting Requirements  
SAE Regulatory Reporting 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study intervention under clinical investigation are met. 
 The sponsor has a legal responsibility to notify both the local regulatory authority 
and other regulatory agencies about the safety of a study intervention under 
clinical investigation. The sponsor will comply with country-specific regulatory 
requirements relating to safety reporting to the regulatory authority, Institutional 
Review Boards (IRB)/Independent Ethics Committees (IEC), and investigators. 
 An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (for example, summary or listing of SAEs) from the sponsor 
will review and then file it along with the IB and will notify the IRB/IEC, if appropriate 
according to local requirements. 
 
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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions  
Word/Phrase  
Definition  
Women of 
childbearing potential 
(WOCBP)  
Adult females are considered WOCBP unless they are WNOCBP.  
 
Women not of 
childbearing potential 
(WNOCBP)  
Females are considered WNOCBP if they  
 have a congenital anomaly such as Müllerian agenesis  
 are infertile due to surgical sterilization, or  
 are postmenopausal.  
Examples of surgical sterilization include hysterectomy, bilateral tubal ligation, bilateral 
salpingo-oophorectomy, bilateral salpingectomy, or bilateral oophorectomy.  
Postmenopausal state  
The postmenopausal state is defined as a woman  
 at any age at least 6 weeks postsurgical bilateral oophorectomy with or 
without hysterectomy, confirmed by operative note; or   
 aged at least 40 years and up to 55 years with an intact uterus, not on 
hormone therapya, who has had cessation of menses for at least 12 consecutive 
months without an alternative medical cause, AND with a follicle-stimulating 
hormone >40 mIU/mL; or   
 55 years or older not on hormone therapy, who has had at least 12 months of 
spontaneous amenorrhea, or  
 aged at least 55 years with a diagnosis of menopause prior to starting 
hormone replacement therapy.  
a 
Women should not be taking medications during amenorrhea such as oral 
contraceptives, hormones, gonadotropin-releasing hormone, anti-estrogens, SERMs, or 
chemotherapy that could induce transient amenorrhea.  
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10.4.2. 
Contraception Guidance  
Males 
Topic  
Guidance  
For all men   
should refrain from sperm donation for the duration of the 
study and for 190 days after the last dose of the study 
intervention. 
Contraception for men with partners of childbearing 
potential   
either remain abstinent (if this is their preferred and usual 
lifestyle), or 
 must use condoms during intercourse for the 
duration of the study, and 
 for 190 days after the last dose of the study 
intervention.  
Contraception for men in exclusively same sex 
relationships, as their preferred and usual lifestyle  
Are not required to use contraception  
Females 
WOCBP who are completely abstinent as their preferred and usual lifestyle, or in a same-sex 
relationship as their preferred and usual lifestyle: 
 
Must… 
Must not… 
agree to either remain 
abstinent or stay in a 
same-sex relationship 
without sexual 
relationships with males, 
and not plan a pregnancy 
during the study 
use periodic abstinence methods 
o 
calendar  
o 
ovulation  
o 
symptothermal, or 
o 
postovulation  
declare abstinence just for the duration of a trial, or 
use the withdrawal method 
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WOCBP who are NOT completely abstinent as their preferred and usual lifestyle, or NOT in a 
same-sex relationship as their preferred and usual lifestyle, must do the following: 
Topic 
Condition 
Contraception 
Agree to use 2 methods of effective contraception, where at least 1 method must be 
highly effective. 
 
These methods of contraception must be used during the study and for at least 130 
days after the last dose of the study intervention. 
 
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Examples of different methods of contraception: 
Methods 
Examples 
Highly effective 
contraception (less than 1% 
failure rate) 
 
female sterilizationa (including fallopian tube ligation, bilateral tubal ligation, 
and hysteroscopic sterilization*) 
 
combination of oral contraceptive pill and mini pill* 
 
progestin-only contraceptive pill (mini-pill)* 
 
implanted contraceptives* 
 
injectable contraceptives* 
 
contraceptive patch* (only women <198 pounds or 90 kg) 
 
total abstinence 
 
vasectomy (for men in clinical trials and for female partner if only sexual 
partner) 
 
fallopian tube implants* (if confirmed by hysterosalpingogram) 
 
combined contraceptive vaginal ring*, or  
 
intrauterine devices 
Effective contraception 
 
male or female condoms with spermicide*  
 
diaphragms with spermicide or cervical sponges* 
 
barrier method with the use of a spermicide 
o 
condom with spermicide 
o 
diaphragm with spermicide*, or 
o 
female condom with spermicide* 
Note: Male and female condoms should not be used in combination. 
Ineffective methods of 
contraception whether used 
alone or in any combination 
 
spermicide alone 
 
periodic abstinence 
 
fertility awareness (calendar method, temperature method, cervical mucus, or 
symptothermal) 
 
withdrawal 
 
postcoital douche, or 
 
lactational amenorrhea 
Note: Contraception should be available. Contraception use by participants should be consistent with the local 
regulations regarding the methods of contraception for those participating in the clinical studies. 
* Not available in Japan. 
a Hysterectomy, bilateral salpingo-oophorectomy, bilateral tubal ligation, bilateral salpingectomy, or bilateral 
oophorectomy are the only types of permanent female sterilization that allow a participant to be a WNOCBP. 
 
 
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10.5. 
Appendix 5: Genetics  
Use/Analysis of DNA 
● Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Variable response to 
study intervention may be due to genetic determinants that impact drug 
absorption, distribution, metabolism, and excretion; mechanism of action of the 
drug; disease etiology; and/or molecular subtype of the disease being treated. 
Therefore, where local regulations and IRB/IEC allow, a blood sample will be 
collected for DNA analysis from consenting participants. 
● DNA samples will be used for research related to LY3872386 or autoimmune and 
inflammatory disorders and related diseases. They may also be used to develop 
tests/assays including diagnostic tests related to LY3872386 and/or interventions 
of this drug class and autoimmune and inflammatory disorders. Genetic research 
may consist of the analysis of one or more candidate genes or the analysis of 
genetic markers throughout the genome (as appropriate). 
● Analyses may be conducted if it is hypothesized that this may help further 
understand the clinical data. 
● The samples may be analyzed as part of a multi-study assessment of genetic 
factors involved in the response to LY3872386 or study interventions of this class 
to understand study disease or related conditions. 
● The results of genetic analyses may be reported in the CSR or in a separate study 
summary. 
● The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 
● The samples will be retained while research on LY3872386 or study interventions 
of this class or indication continues but no longer than 15 years or other period as 
per local requirements. 
 
 
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10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments  
Hepatic Evaluation Testing 
See Section 8.2.8 for guidance on appropriate test selection. 
The Lilly-designated central laboratory should complete the analysis of all selected testing 
except for the testing listed in the investigator-designated local laboratory table. The central 
laboratory will report results if a validated test or calculation is available. 
Local testing may be performed in addition to central testing when necessary for immediate 
participant management. 
The local laboratory must be qualified in accordance with applicable local regulations.
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Tests assayed by Lilly-designated central laboratory 
Hepatic Hematology Panel 
Hepatitis A virus (HAV) testing: 
   Hemoglobin 
    HAV total antibody 
   Hematocrit 
    HAV Immunoglobulin M (IgM) antibody 
   Erythrocytes (RBCs - red blood cells) 
Hepatitis B virus (HBV) testing: 
   Leukocytes (WBCs - white blood cells) 
    Hepatitis B surface antigen (HBsAg) 
   Differential: 
    Hepatitis B surface antibody (anti-HBs) 
       Neutrophils, segmented 
    Hepatitis B core total antibody (anti-HBc) 
       Lymphocytes 
    Hepatitis B core IgM antibody 
       Monocytes 
    HBV DNAa 
       Basophils 
Hepatitis C virus (HCV) testing: 
       Eosinophils 
    HCV antibody 
   Platelets 
    HCV RNAa 
   Cell morphology (RBC and WBC) 
Hepatitis D virus (HDV) testing: 
Hepatic Clinical Chemistry Panel 
    HDV antibody 
   Total bilirubin 
    HDV IgM antibody 
   Direct bilirubin 
Hepatitis E virus (HEV) testing: 
   Alkaline phosphatase (ALP) 
    HEV IgG antibody 
   Alanine aminotransferase (ALT) 
    HEV IgM antibody 
   Aspartate aminotransferase (AST) 
    HEV RNAa 
   Gamma-glutamyl transferase (GGT) 
Anti-nuclear antibody (ANA) 
   Creatine kinase (CK) 
Anti-smooth muscle antibody (ASMA)b 
Hepatic Coagulation Panel 
Anti-actin antibodyc 
   Prothrombin time, INR (PT-INR) 
IgA (quantitative) 
Urine Chemistry 
IgG (quantitative) 
   Drug screen 
IgM (quantitative) 
Haptoglobin 
  
 
 
Tests assayed ONLY by investigator-designated local laboratory  
Acetaminophen 
Cytomegalovirus (CMV) testing: 
Acetaminophen protein adducts 
    CMV antibody 
Alkaline phosphatase isoenzymes 
    CMV DNAa 
Ceruloplasmin 
Herpes simplex virus (HSV) testing: 
Copper 
    HSV (Type 1 and 2) antibody 
Ethyl alcohol (EtOH) 
    HSV (Type 1 and 2) DNAa 
Phosphatidylethanol (PEth) 
Liver kidney microsomal type 1 (LKM-1) antibody 
Urine Chemistry 
Microbiology Culture: 
    Ethyl glucuronide (EtG) 
    Blood 
Epstein-Barr virus (EBV) testing: 
    Urine 
    EBV antibody 
    
    EBV DNAa 
 
a Reflex/confirmation dependent on regulatory requirements, testing availability, or both. 
b Not required if anti-actin antibody is tested. 
c Not required if anti-smooth muscle antibody (ASMA) is tested. 
 
 
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10.7. 
Appendix 7: Abbreviations and Definitions  
 
Term 
Definition 
Ab 
antibody 
abuse 
Use of a study intervention for recreational purposes or to maintain an addiction or 
dependence 
AD 
atopic dermatitis 
ADA 
anti-drug antibodies 
ADC 
antibody drug conjugate 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the concentration curve 
blinding/masking 
A single-blind study is one in which the investigator and/or the investigator’s staff are 
aware of the treatment but the participant is not, or vice versa, or when the sponsor is 
aware of the treatment but the investigator and/the investigator’s staff and the 
participant are not. 
A double-blind study is one in which neither the participant nor any of the investigator 
or sponsor staff who are involved in the treatment or clinical evaluation of the subjects 
are aware of the treatment received. 
Cmax 
maximum observed drug concentration 
Companion diagnostic  
An in vitro diagnostic device (assay or test) that provides information that is essential 
for the safe and effective use of a corresponding therapeutic product 
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. 
CRF 
case report form; a printed, optical, or electronic document designed to record all of the 
protocol-required information to be reported to the sponsor for each trial participant. 
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. 
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Term 
Definition 
CRU 
clinical research unit 
CSR 
clinical study report 
CT 
computed tomography 
DAR 
drug to antibody ratio 
DDI 
drug-drug interaction 
DLQI 
Dermatology Life Quality Index 
DMC 
data monitoring committee. A data monitoring committee, or data monitoring board 
(DMB) is a group of independent scientists who are appointed to monitor the safety and 
scientific integrity of a human research intervention, and to make recommendations to 
the sponsor regarding the stopping of a study for efficacy, or for harm, or for futility. 
The composition of the committee is dependent upon the scientific skills and 
knowledge required for monitoring the particular study. 
 
 
EC50 
half maximal effective concentrations 
ECG 
electrocardiogram 
eCRF 
Electronic CRF 
enroll 
The act of assigning a participant to a treatment. Participants who are enrolled in the 
study are those who have been assigned to a treatment. 
enter 
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives. 
 
  
GCP 
good clinical practice 
GLP 
good laboratory practice 
GR 
glucocorticoid receptor 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
hERG 
human Ether-a-go-go Related Gene 
HIV 
human immunodeficiency virus 
HPA 
hypothalamic-pituitary-adrenal 
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Term 
Definition 
IB 
Investigator’s Brochure 
IAD 
interim access to data 
IC50 
half-maximal inhibitory concentration 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
Ig 
immunoglobulin 
IL 
interleukin 
IL-4R 
interleukin-4 receptor 
IMP 
Investigational Medicinal Product (see also “investigational product”) 
A medicinal product which is being tested or used as a reference, including as a 
placebo, in a clinical trial. 
informed consent 
A process by which a participant voluntarily confirms their 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. 
INR 
international normalized ratio 
interim analysis 
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked. 
investigational 
product (IP) 
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. See also “IMP.” 
IRB 
institutional review board 
IRR 
infusion-related reaction 
 
 
IV 
intravenous 
IWRS 
Interactive Web Response System 
LTBI 
latent tuberculosis infection 
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Term 
Definition 
KD 
equilibrium dissociation constant 
mAb 
monoclonal antibody  
MAD 
multiple-ascending dose 
mAb 
monoclonal antibody 
NOAEL 
no observed adverse effect level 
NRS 
numeric rating scale 
 
 
participant 
Equivalent to CDISC term “subject”: an individual who participates in a clinical trial, 
either as recipient of an investigational medicinal product or as a control 
PK/PD 
pharmacokinetics/pharmacodynamics 
PO 
oral administration 
 
 
PR 
pulse rate 
PT 
prothrombin time 
 
 
 
 
QD 
once daily 
QSP 
quantitative systems pharmacology 
RO 
receptor occupancy 
SAD 
single-ascending dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
 
 
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.  
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Term 
Definition 
TB 
tuberculosis 
TBL 
total bilirubin 
TCNI 
topical calcineurin inhibitors 
TCS 
topical corticosteroid 
TE 
treatment-emergent 
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. 
TK 
toxicokinetic  
ULN 
upper limit of normal 
 
 
 
 
WBC 
white blood cells 
WNOCBP 
women not of child-bearing potential 
WOCBP 
women of child-bearing potential 
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10.8. 
Appendix 8: Protocol Amendment History  
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents. 
Amendment a: 12 October 2023 
Overall Rationale for the Amendment: 
This protocol has been amended to correct previous errors in assessments and time points in the 
schedule of activities and to correct volume errors in the blood sampling summary. These 
changes are presented in the summary of changes table. 
Minor editorial changes have also been made and are not presented in the summary of changes 
table. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3.1: Part A: 
Single-Ascending Dose of 
LY3872386 in Healthy 
Participants 
Updated the vital signs assessment on 
Day 1 to indicate that it should not be 
predose only. 
Moved the thyroid-stimulating 
hormone, including T3/T4 test from 
screening to Day -1. 
Updated the cortisol assessment to no 
longer specify “basal,” moved the test 
from screening to Day -1, and added a 
predose and 12-hour cortisol 
assessment to Day 1. 
Added a cosyntropin stimulation test to 
Day 15 ± 1d. 
Corrections to previous errors. 
Section 1.3.2: Part B: 
Multiple-Ascending Dose of 
LY3872386 in Patients with 
Atopic Dermatitis 
 Dosing 
Schedule: 
Moved the thyroid-stimulating 
hormone, including T3/T4 test from 
screening to predose on Day 1. 
 
 Dosing 
Schedule: 
Moved the thyroid-stimulating 
hormone, including T3/T4 test from 
screening to predose on Day 1. 
 
Correction to previous error. 
 
 
 
 
 
Corrections to previous errors. 
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Section # and Name 
Description of Change 
Brief Rationale 
Updated the immunogenicity 
assessments on Day 15 ± 1d, Day 43 ± 
1d, and Day 71 ± 1d to indicate that it 
should not be predose. 
Updated the LY3872386, total 
antibody, and LY3558533 
concentration assessment on Day 15 ± 
1d, Day 43 ± 1d, and Day 71 ± 1d to 
indicate that it should not be predose. 
Updated the receptor occupancy 
assessment on Day 15 ± 1d, Day 43 ± 
1d, and Day 71 ± 1d to indicate that it 
should not be predose. 
Updated the cytokine panel assessment 
on Day 15 ± 1d, Day 43 ± 1d, and Day 
71 ± 1d to indicate that it should not be 
predose. 
Updated the 
 
assessment on Day 15 ±1d to indicate 
that it should not be predose. 
Section 1.3.3: Part C: Open-
Label Multiple Dose of 
Prednisone in Healthy 
Participants 
Prednisone 
-mg and -mg Dosing 
Schedule: 
Moved the thyroid-stimulating 
hormone, including T3/T4 test from 
screening to Day -1. 
Specified that a urinalysis assessment 
should be collected predose on Day 2 
and Day 7 during the Day 2 to 13 
window and predose on Day 21 during 
the Day 15 to 29 window and also 
added a urinalysis assessment to Day 
44 ± 4d. 
Added a predose prednisone and 
prednisolone concentration time point 
to Day 1. 
Updated the cortisol assessment to no 
longer specify “basal,” moved the test 
from screening to Day -1, added a 
predose and 12-hour cortisol 
Corrections to previous errors. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
assessment to Day 1, and specified that 
the Day 31 assessment is not predose. 
Removed the 24 hour urinary free 
cortisol assessment from Day 44 ± 4d 
and from ED. 
Added a predose cosyntropin 
stimulation test to Day 7. 
Prednisone 
-mg Dosing Schedule: 
Moved the thyroid-stimulating 
hormone, including T3/T4 test from 
screening to Day -1. 
Added a predose prednisone and 
prednisolone concentration time point 
to Day 1. 
Updated the cortisol assessment to no 
longer specify “basal,” moved the test 
from screening to Day -1, and added a 
12-hour cortisol time point to Day 1. 
 
Added a predose 24 hour urinary free 
cortisol assessment to Day 6 and 
removed the assessments from Day 14 
± 4d and ED. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Corrections to previous errors. 
Section 4.1: Overall Design 
Changed the dosing timing for the 
remaining non-sentinel participants in 
both IV and SC cohorts from 
“approximately 10 to 15 minutes after 
the completion of the administration” 
to “approximately 30 minutes after the 
start of the previous administration.” 
Correction to address FDA feedback. 
Section 4.3: Justification for 
Dose 
Updated the text to no longer specify 
“basal” cortisol. 
Correction to previous error. 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 5.2: Exclusion 
Criteria 
Updated Exclusion Criterion #28 to 
state that current smokers will be 
excluded if they use “>10 cigarettes or 
other tobacco products per day and are 
unable/unwilling to stop smoking 
tobacco products while in the study and 
have a positive cotinine test” as 
opposed to “or have a positive cotinine 
test.” 
Correction to previous errors. 
Section 5.2.1: Additional 
Exclusion Criteria for Part 
B (Patients with Atopic 
Dermatitis) 
Specified that Exclusion Criterion #49 
is only for Japanese participants. 
Correction to previous errors. 
Section 6.1: Study 
Interventions Administered 
Updated the study intervention table to 
include formulation details (0.9% 
sodium chloride solution) for placebo. 
Added dosing information (single 
administration, 
 for 12 weeks, and 
 for 12 weeks) for LY3872386 
administration. 
Correction to address FDA feedback. 
 
 
 
Correction to previous error. 
Section 6.2: Preparation, 
Handling, Storage, and 
Accountability 
Added text to include that preparation, 
handling, and storage information of 
study interventions could also be found 
in the Pharmacy Manual/Pharmacy 
Preparation Instructions.  
Correction to address FDA feedback. 
Section 8.2.2: Vital Signs 
Specified that the text “On Day 1, 
blood pressure and PR will be assessed 
at predose, end of infusion (for IV 
only), and 3-, 6-, and 12-hour 
postdose” applies only to Part A. 
Correction to previous error. 
Section 8.2.8: Hepatic 
Safety Monitoring, 
Evaluation, and Criteria for 
Study Drug Interruption or 
Discontinuation 
In the evaluation for possible causes of 
abnormal liver tests, clarified that 
recent illnesses include those of 
“systemic infection.” 
Correction to previous error. 
Section 10.2: Appendix 2: 
Clinical Laboratory Tests 
Added footnote e to insulin test to 
indicated that it will not be performed 
at screening. 
 
Specified that ethanol testing is a breath 
test in both the Safety Laboratory Tests 
table and in footnote c. 
Corrections to previous errors. 
 
 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
 
Moved ethanol breath testing from 
under the urine drug screen section to a 
separate, standalone laboratory test.  
Removed “propoxyphene” test from 
urine drug screen. 
 
 
 
 
 
 
Test is no longer part of the standard 
confirmation list and would require an 
additional monitoring service. 
Section 10.2.1: Blood 
Sampling Summary 
Part A: SAD of LY3872386 in 
Healthy Participants:  
Reduced the number of blood samples 
for clinical chemistry a, including 
insulin and fasting lipid panel from 14 
to 8. 
 
Added a separate line item for clinical 
chemistry a, including insulin, fasting 
lipid panel, serum immunoglobulins to 
state 8 mL for blood volume per 
sample, 6 for number of blood samples, 
and 48 mL for total volume. 
 
Increased the TSH, T3/T4 blood 
volume per sample from 2.5 mL to 3.5 
mL. 
 
Removed serum immunoglobulin line 
item. 
 
Reduced the 
 
volume per sample from mL to 
mL 
 
Additional updates in the blood 
sampling summary table (number of 
samples, total volume, etc.) have been 
made to reflect the changes in the 
Schedule of Activities for Part A. 
 
Corrections to previous errors. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
Part B: MAD of LY3872386 in 
Patients with AD (
 Dosing 
Schedule): 
Reduced the number of blood samples 
for clinical chemistry a, including 
insulin and fasting lipid panel from 11 
to 7. 
 
Added a line item for clinical chemistry 
a, including insulin, fasting lipid panel, 
and serum immunoglobulins to state 8 
mL for blood volume per sample, 4 for 
number of blood samples, and 32 mL 
for total volume. 
 
Increased the TSH, T3/T4 blood 
volume per sample from 2.5 mL to 3.5 
mL. 
 
Removed serum immunoglobulin line 
item. 
 
Reduced the immunogenicity blood 
volume per sample from 10 mL to 5 
mL. 
 
Additional updates in the blood 
sampling summary table (number of 
samples, total volume, etc.) have been 
made to reflect the changes in the 
Schedule of Activities for Part B 
. 
 
Part B: MAD of LY3872386 in 
Patients with AD (
 Dosing 
Schedule):  
Reduced the number of blood samples 
for clinical chemistry a, including 
insulin and fasting lipid panel from 9 to 
5. 
 
 
 
 
 
 
 
 
Corrections to previous errors. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
Added a line item for clinical chemistry 
a, including insulin, fasting lipid panel, 
and serum immunoglobulins to state 8 
mL for blood volume per sample, 4 for 
number of blood samples, and 32 mL 
for total volume. 
 
Increased the TSH, T3/T4 blood 
volume per sample from 2.5 mL to 3.5 
mL. 
 
Removed serum immunoglobulin line 
item. 
 
Reduced the immunogenicity blood 
volume per samples from 10 mL to 5 
mL. 
 
Additional updates in the blood 
sampling summary table (number of 
samples, total volume, etc.) have been 
made to reflect the changes in the 
Schedule of Activities for Part B 
. 
 
Part C: Prednisone in Healthy 
Participants 
-mg and -mg Dosing 
Groups:  
Increased the fasting lipid panel (Day 
1) number of samples from 1 to 2. 
Increased the TSH, T3/T4 blood 
volume per sample from 2.5 mL to 3.5 
mL. 
Additional updates in the blood 
sampling summary table (number of 
samples, total volume, etc.) have been 
made to reflect the changes in the 
Schedule of Activities for Part C
-
mg and -mg. 
 
 
 
 
 
 
Corrections to previous errors. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
Part C: Prednisone in Healthy 
Participants 
-mg Dosing Group:  
Increased the TSH, T3/T4 blood 
volume per sample from 2.5 mL to 3.5 
mL. 
 
Updated the serum immunoglobulin 
blood volume per sample from 4 mL to 
5 mL. 
 
Additional updates in the blood 
sampling summary table (number of 
samples, total volume, etc.) have been 
made to reflect the changes in the 
Schedule of Activities for Part C 
-
mg. 
 
 
 
 
 
 
Corrections to previous errors. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Corrections to previous errors. 
 
 
Approved on 10 Nov 2023 GMT
CCI
CCI

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11. 
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Approved on 10 Nov 2023 GMT

Signature Page for VV-CLIN-091227 v4.0
Signature Page for VV-CLIN-091227 v4.0
Approval
n
10-Nov-2023 15:18:50 GMT+0000
Approval
10-Nov-2023 17:23:21 GMT+0000
Approved on 10 Nov 2023 GMT
PPD
PPD