A Phase 2, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, 52 Week Study to Evaluate the Efficacy and Safety of LY3454738 in the Treatment of Adult Patients With Moderate-to-Severe Atopic Dermatitis
Phase: PHASE2
Conditions: Atopic Dermatitis
Sponsor: Eli Lilly and Company

Protocol Addendum 
 ( ) 
A Phase , Randomized, Double-Blind, Parallel
, Placebo-Controlled
 Study 
of 
 in
 Patients with 
Moderate to Severe
NCT0
Approval Date: 
-Ma -20

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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 LY3454738, 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. 
Master Protocol Title: A Master Protocol for Randomized, Controlled, Phase 2 Clinical Trials 
of Multiple Interventions for the Treatment of Adults with Moderate-to-Severe Atopic 
Dermatitis 
Master Protocol Number: J4E-MC-IMMB(b) 
ISA Title: A Phase 2, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, 52-Week 
Study to Evaluate the Efficacy and Safety of LY3454738 in the Treatment of Adult Patients with 
Moderate-to-Severe Atopic Dermatitis 
ISA Number: J4E-MC-FR01 
ISA Amendment Number: c 
Compound: LY3454738 
ISA Brief Title: A Phase 2, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, 
52-Week Study to Evaluate the Efficacy and Safety of LY3454738 in the Treatment of Adult
Patients with Moderate-to-Severe Atopic Dermatitis
Study Phase: 2 
Sponsor Name: Eli Lilly and Company 
Legal Registered Address: Eli Lilly and Company, Indianapolis, Indiana, USA 46285 
Regulatory Agency Identifier Numbers: 
IND: 163615 
EU trial number: 2022-502888-38-00 
Approval Date: ISA Amendment (c) Electronically Signed and Approved by Lilly on date 
provided below. 
Document ID: VV-CLIN-150737 

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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 (b)
12-Sep-2023
Amendment (a)
13-Mar-2023
Original Protocol
09-Dec-2022
Amendment [c] 
This amendment is considered to be substantial. 
The amendment is considered to be substantial because it is likely to have a significant impact on 
the 
 safety or rights of the study participants 
 reliability and robustness of the data generated in the clinical study, and  
 conduct or management of the trial. 
Overall Rationale for the Amendment 
The main purpose of this amendment is to 
 collect more data in 
patients, and 
 revise the interim plan.
Section # and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis 
(Objectives, 
Endpoints, and 
Estimands) 
3. Objectives, 
Endpoints, and 
Estimands 
The secondary endpoint for 
efficacy is 
studied for that objective.
 
Added additional secondary 
objective and endpoint for 
participants 
EASI-75 at Week 16.
To collect more information about 
 
  

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Section # and Name 
Description of Change 
Brief Rationale 
9.3.3. Secondary 
Endpoints/Estimands 
Analysis 
Added the analyses methods 
 
EASI-75 at Week 16. 
1.1. Synopsis (Study 
Population) 
4.1. Overall Design 
9.5. Sample Size 
Determination 
 
The text is updated to include 
the change in study population 
which is an addition of 60 
 
 
To collect more information about 
 in atopic 
dermatitis. 
9.2. Analyses Sets 
Added 
population in Maintenance 
Analysis Set.  
9.5. Sample Size 
Determination 
With the updated planned 
sample size, the text is updated 

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Section # and Name 
Description of Change 
Brief Rationale 
as an EASI-75 response at 
Week 16 of 
 
98% power for pairwise 
comparisons with placebo.  
1.1. Synopsis (Study 
Population) 
9.5. Sample Size 
Determination 
 
Up to
To allow to over enroll if needed. 
1.1. Synopsis 
(Number of 
Participants) 
9.5. Sample Size 
Determination 
 
Up to approximately 260 
participants will be 
randomized to study 
intervention.  
1.3. Schedule of 
Activities 
A new row for estimated 
glomerular filtration rate 
(eGFR) is added which will be 
determined at Week 16, 
Week 40, and ED Visits.
To monitor kidney function 
throughout the study. 
4.1. Overall Design  
The randomization text is 
updated and the text below is 
added to include the changes 
in the
  
 
 
 

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Section # and Name 
Description of Change 
Brief Rationale 
 
 
4.1. Overall Design 
9.5. Sample Size 
Determination 
The table is revised to include 
the updated planned sample 
 
 

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Section # and Name 
Description of Change 
Brief Rationale 

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Table of Contents  
1. 
Protocol Summary ........................................................................................................11 
1.1. 
Synopsis ..........................................................................................................................11 
1.3. 
Schedule of Activities (SoA) ..........................................................................................18 
2. 
Introduction ...................................................................................................................33 
2.1. 
Study Rationale ...............................................................................................................33 
2.2. 
Background .....................................................................................................................33 
2.3. 
Benefit/Risk Assessment ................................................................................................33 
2.3.1. 
Risk Assessment .............................................................................................................33 
2.3.2. 
Benefit Assessment .........................................................................................................34 
2.3.3. 
Overall Benefit Risk Conclusion ....................................................................................34 
3. 
Objectives, Endpoints, and Estimands .......................................................................35 
3.1. 
Estimands ........................................................................................................................36 
4. 
Study Design ..................................................................................................................38 
4.1. 
Overall Design ................................................................................................................38 
4.2. 
Scientific Rationale for Study Design ............................................................................40 
4.2.1. 
Patient Input into Design ................................................................................................41 
4.3. 
Justification for Dose ......................................................................................................41 
4.4. 
End of Study Definition ..................................................................................................42 
5. 
Study Population ...........................................................................................................43 
5.1. 
ISA-Specific Inclusion Criteria ......................................................................................43 
5.2. 
ISA-Specific Exclusion Criteria .....................................................................................43 
5.3. 
Lifestyle Considerations .................................................................................................46 
5.4. 
Screen Failures ................................................................................................................46 
5.5. 
Criteria for Temporarily Delaying Randomization of a 
Participant .......................................................................................................................46 
6. 
Study Intervention(s) and Concomitant Therapy .....................................................47 
6.1. 
Study Intervention(s) Administered................................................................................47 
6.1.1. 
Medical Devices..............................................................................................................48 
6.1.2. 
Background Therapy .......................................................................................................48 
6.2. 
Preparation, Handling, Storage, and Accountability ......................................................48 
6.3. 
Assignment to Study Intervention ..................................................................................48 
6.4. 
Blinding ..........................................................................................................................48 
6.5. 
Study Intervention Compliance ......................................................................................49 
6.6. 
Dose Modification ..........................................................................................................49 
6.7. 
Continued Access to Study Intervention after the End of the 
Study ...............................................................................................................................49 
6.8. 
Treatment of Overdose ...................................................................................................49 
6.9. 
Prior and Concomitant Therapy ......................................................................................50 
6.9.1. 
Rescue Medication ..........................................................................................................50 
6.9.2. 
Permitted Concomitant Therapy .....................................................................................51 
6.9.3. 
Prohibited Concomitant Therapy ....................................................................................51 

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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................53 
7.1. 
Discontinuation of Study Intervention ............................................................................53 
7.1.1. 
Temporary Discontinuation of Study Intervention .........................................................53 
7.1.2. 
Permanent Discontinuation of Study Intervention ..........................................................53 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................53 
7.3. 
Lost to Follow up ............................................................................................................53 
8. 
Study Assessments and Procedures.............................................................................54 
8.1. 
Efficacy Assessments .....................................................................................................54 
8.2. 
Safety Assessments .........................................................................................................55 
8.2.1. 
Vital Signs .......................................................................................................................55 
8.2.2. 
Physical Examinations ....................................................................................................55 
8.2.3. 
Skin Assessment with Fitzpatrick Scale of Skin Phototypes ..........................................55 
8.2.4. 
Electrocardiograms .........................................................................................................55 
8.2.5. 
Chest Imaging .................................................................................................................56 
8.2.6. 
Clinical Safety Laboratory Tests ....................................................................................56 
8.2.7. 
Pregnancy Testing ...........................................................................................................57 
8.2.8. 
Tuberculosis Testing and Monitoring .............................................................................57 
8.2.9. 
Hepatitis B Testing and Monitoring. ..............................................................................57 
8.2.10. Hepatitis C Testing .........................................................................................................57 
8.2.11. Hepatic Safety Testing and Monitoring ..........................................................................57 
8.2.12. Suicidal Ideation and Behavior Risk Screening and Monitoring....................................57 
8.3. 
Adverse Events, Serious Adverse Events, and Product 
Complaints ......................................................................................................................58 
8.3.1.
Adverse Events of Special Interest .................................................................................58 
8.5. 
Pharmacodynamics .........................................................................................................60 
8.6.
Genetics ..........................................................................................................................60 
8.8.
Immunogenicity Assessments.........................................................................................60 
8.9. 
Medical Resource Utilization and Health Economics ....................................................61 
9. 
Statistical Considerations .............................................................................................62 
9.1. 
Statistical Hypotheses .....................................................................................................62 
9.1.1. 
Multiplicity Adjustment ..................................................................................................62 
9.2. 
Analyses Sets ..................................................................................................................62 
9.3. 
Statistical Analyses .........................................................................................................63 
9.3.1. 
General Considerations ...................................................................................................63 
9.3.2.
Primary Endpoints/Estimands Analysis..........................................................................65
9.3.5.
Safety Analyses ...............................................................................................................66
9.3.6. 
Other Analyses................................................................................................................66 
9.5. 
Sample Size Determination ............................................................................................68 
10. 
Attachments to the ISA ................................................................................................69 

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10.1. 
Attachment 1: Clinical Laboratory Tests ........................................................................69 
10.1.1. Clinical Laboratory Tests Performed During This ISA..................................................70 
10.2. 
Attachment 2: Contraceptive and Barrier Guidance .......................................................75 
10.2.1. Definitions.......................................................................................................................75 
10.2.2. Contraception Guidance..................................................................................................75 
10.2.3. Pregnancy Testing Guidance ..........................................................................................76 
10.3. 
Attachment 3: ISA-Specific Stopping Rules ..................................................................77 
10.4. 
Attachment 4: Country-specific Requirements...............................................................78 
10.5. 
Attachment 5: Provisions for Changes in Study Conduct During 
Exceptional Circumstances .............................................................................................79 
10.8.
Attachment 8: Abbreviations and Definitions ................................................................86 
10.9. 
Attachment 9: ISA Amendment History ........................................................................90 
11. 
References ......................................................................................................................93 
 

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1. 
Protocol Summary  
1.1. 
Synopsis  
ISA Title: A Phase 2, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, 52-Week 
Study to Evaluate the Efficacy and Safety of LY3454738 in the Treatment of Adult Patients with 
Moderate-to-Severe Atopic Dermatitis 
ISA Brief Title: A Phase 2, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, 
52-Week Study to Evaluate the Efficacy and Safety of LY3454738 in the Treatment of Adult 
Patients with Moderate-to-Severe Atopic Dermatitis 
Regulatory Agency Identifier Number(s): 
IND: 163615 
EU trial number: 2022-502888-38-00 
Rationale: 
LY3454738 is a humanized IgG4-variant monoclonal antibody (mAb) that binds to and agonizes 
the human inhibitory checkpoint CD200R. CD200R is expressed on many cell types involved in 
the pathogenesis of atopic dermatitis (AD). 
Activating CD200R 
with an agonist mAb is a potential therapeutic strategy for AD and other inflammatory disorders. 
This study will evaluate the safety and efficacy of LY3454738 in adults with moderate-to-severe 
AD. 
Study J4E-MC-FR01 (FR01) is a Phase 2 study to evaluate the efficacy and describe the safety 
of LY3454738 in adult patients with moderate-to-severe AD. Results of this study will be used to 
guide the dose selection for future studies and to further characterize the benefit/risk profile of 
LY3454738. Study FR01 is an ISA of the master IMMB protocol. 
 
 

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Objectives, Endpoints, and Estimands: 
Objectives 
Endpoints
Primary
To compare the efficacy of LY3454738 versus 
placebo as measured by EASI-75 in the treatment of 
moderate-to-severe AD
Proportion of participants achieving EASI-75 at 
Week 16 
Estimands 
The primary estimand is treatment difference between each dosing regimen of LY3454738 and placebo 
 
in achieving a successful response at Week 16 without 
use of any prohibited or rescue medication for AD or early permanent discontinuation.
Abbreviations: AD = atopic dermatitis;
EASI = Eczema Area and Severity Index; 
 
 
 

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Overall Design 
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 
outpatient dose-ranging study to evaluate the efficacy and describe the safety of LY3454738 as 
compared to placebo during a 16-week induction period in adult participants with moderate-to-
severe AD using these induction dosing regimens given
: 
 LY3454738 
 mg 
 LY3454738 
 mg 
 LY3454738 
 mg
and 
 placebo
. 
The blinded
-week maintenance treatment period begins
 Participants having at least an 
 response at Week 16 will receive a 
maintenance dosing regimen, also
as listed here. 
Week 16 responders who were originally 
randomized to this induction regimen...
 
Will receive this maintenance regimen:
LY3454738 
mg 
by rerandomization in 
 ratio: 
  LY3454738 
 mg 
 or 
 placebo
LY3454738 
mg 
 LY3454738 
mg 
LY3454738 
mg 
 LY3454738 
mg 
placebo
 placebo
 response 
suggests the need for a higher dose. The escape therapy is LY3454738
mg
 
A participant will receive this escape therapy under the conditions listed here. 
Begin LY3454738 
 mg 
 as escape therapy...
if the participant...
At Week 16
has not achieved an 
response at Week 16.
At Weeks
 
has not achieved an 
 response at Weeks 
 
A participant receiving escape therapy will continue receiving escape therapy through the last 
dosing visit of the study (Week 
 unless the participant is discontinued from study 
intervention. 
Topical rescue medication is permitted (not required) in the induction period from Week 8 until 
Week 16 for participants who do not achieve an 
response. In the maintenance period, 
use of topical rescue medication is permitted (not required) from Week
until the end of the 
study for participants who do not achieve an
response. Participants who receive at least 
2 doses of escape therapy at 2 consecutive visits will be permanently discontinued from study 
intervention if they fail to achieve an 
 response. 
This study design includes investigator and participant blinding (masking). An internal 
assessment committee (IAC) will exist for the purpose of reviewing safety data in an unblinded 
fashion. 

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In summary, Study FR01 includes 4 study periods over a total study duration of approximately 
weeks: 
 Screening: from 
days prior to randomization at Week 0 (Study Day 1) 
 Treatment Period  Induction: from randomization at Week 0 (Study Day 1) 
through assessments at Week 16 
 Treatment Period Maintenance: from dose administration at Week 16 
 
, and 
 Posttreatment Follow-Up: 2 visits, the last visit being
after 
randomization 
. 
Brief Summary: 
Activating CD200R with an agonist monoclonal antibody is a potential therapeutic strategy for 
atopic dermatitis and other inflammatory disorders.
The purpose of this study is to measure improvement in atopic dermatitis signs and symptoms 
after treatment with various dosing regimens of 
 administered LY3454738 
compared to placebo in adult participants with moderate-to-severe atopic dermatitis. 
 The LY3454738 dosing regimens to be compared to placebo in this study are 
these: 
Induction Period
Maintenance Period
LY3454738 
mg 
LY3454738 
mg 
LY3454738 
 mg 
LY3454738 
mg 
LY3454738 
 mg 
LY3454738 
mg 
 
 The total study duration for a participant is approximately 
 weeks, 
inclusive of the screening period, treatment periods, and posttreatment follow-up 
period. 
 Treatment is administered from Study Day 1 (randomization visit [Week 0]) 
through the last dose given at Week
in the maintenance period. 
 After Study Day 1, the visit frequency is approximately 
 for the first 
16 weeks, specifically, at Weeks
 Note: Not every visit includes 
administration of a treatment dose. Posttreatment follow-up visits occur at Week 

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Study Population: 
The study population of Study FR01 includes adult male or female participants from 18 to 70 
years of age, inclusive, who have a diagnosis of atopic dermatitis which is moderate to severe as 
measured by 
 Eczema Area and Severity Index (EASI) scor
 
 vIGA-AD
® 
 
 
. 
Based on the entry criteria of the master IMMB protocol, participants in Study FR01 must also 
be candidates for systemic therapy and have a history of inadequate response to, or intolerance 
to, topical medications. 
Participants will be excluded from Study FR01 if they 
 have used certain atopic dermatitis treatments during a specified time period 
before the first dose of study intervention 
 are unstable with respect to use of chronic treatments to improve sleep, and 
 are unsuitable for study participation due to medical history or a current serious 
health condition. 
 
 
Number of Participants: 
Approximately 260 participants will be randomized to study intervention. 
Intervention Groups and Duration: 
The study includes 4 periods over a total study duration of approximately 
weeks. These 
are the treatment groups from randomization at Week 0 and until Week 16:
 LY3454738 
 mg 
 LY3454738 
 mg 
 
 LY3454738 
 mg 
and 
 placebo
 
Participants having at least an 
 response at Week 16 will receive a maintenance dosing 
regimen, as listed here. 

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Week 16 responders who were originally 
randomized to this induction regimen...
 
Will receive this maintenance regimen:
LY3454738 
mg 
by rerandomization in 
 ratio: 
  LY3454738 
 mg 
 or 
 placebo
LY3454738 
mg 
 LY3454738 
mg 
LY3454738 
mg 
 LY3454738 
mg 
placebo
 placebo 
Maintenance dosing continues up to and including Week
 
Participants will receive LY3454738 
 mg 
as 
 they 
 have not achieved an 
 response at Week 16, or 
 have not achieved an
 response at Weeks 
Once started, escape therapy continues through the last dosing visit of the maintenance period. 
Topical rescue medication is permitted from Week 8 until Week 16 for participants who do not 
achieve an
 response; topical rescue medication started during the induction period 
should be stopped at, or before, Week 16. Likewise, during the maintenance period, topical 
rescue medication is permitted from Week
 until the end of the study for participants who do 
not achieve an 
 response. 
Ethical Considerations of Benefit/Risk: 
Based on available clinical and nonclinical data, there are no anticipated risks that would require 
safety monitoring in this study beyond what is typical for clinical studies involving humanized 
mAbs. The administration of therapeutic monoclonal antibodies to humans can be associated 
with 
 
 Efficacy results from a Phase 1 study support the hypothesis that LY3454738 
has the potential to treat atopic dermatitis. Taking into account the measures taken to minimize 
risk to participants in this study, and in the context of the cumulative knowledge of LY3454738, 
the benefit/risk balance for participants in this Phase 2 study is assessed to be acceptable. 
Data Monitoring Committee: Yes (Internal Assessment Committee). 
 

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1.3. 
Schedule of Activities (SoA)  
Table 1. Activities for screening/baseline and induction treatment periods of Study J4E-MC-FR01. 
For activities at unscheduled visit or early discontinuation visit, see Table 2. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
 
 
Study Day 
1 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Minimum interval between Visit 401 of the 
master IMMB protocol and Study Day 1: 
 Participants doing
15 days 
 All other participants: 8 days 
CRF visit number 
V0 
 
Consent and demographics 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
(X) 
 
 
 
 
 
 
 
 
 
 
Signed, documented consent for ISA FR01 
must be obtained before any ISA-specific tests 
or procedures are performed. Relevant ICF may 
be signed up to 90 days before Study Day 1. 
Inclusion and exclusion 
criteria: confirmation of 
eligibility 
 
X 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion criteria of both the 
master IMMB protocol and this ISA must be 
confirmed before participant is randomized to a 
study intervention and receives a first dose. See 
Section 5 of this ISA. See also Section 5 of the 
master IMMB protocol. 
Prespecified medical history 
 
X 
 
 
 
 
 
 
 
 
 
Eye Disease History form. 
Concomitant medications 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Rescue medication and background emollients 
are documented as concomitant medications. 
Adverse events (AEs) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE collection begins when the master protocol 
ICF is signed. 
events will be 
solicited at each visit. For AESIs, additional 
data are collected. See Section 8.3.1. 
Physical evaluation 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
 
X 
 
 
 
 
 
 
 
 
X 
 

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Table 1. Activities for screening/baseline and induction treatment periods of Study J4E-MC-FR01. 
For activities at unscheduled visit or early discontinuation visit, see Table 2. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
 
 
Study Day 
1 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Minimum interval between Visit 401 of the 
master IMMB protocol and Study Day 1: 
 Participants doing
15 days 
 All other participants: 8 days 
CRF visit number 
V0 
 
Symptom-directed physical 
assessment 
 
X 
 
 
 
 
 
 
 
 
X 
Perform as shown here and as needed based on 
participant status and standard of care. May be 
performed by qualified personnel per local 
regulations. Assess for TB risk factors, and for 
signs and symptoms of active TB, including an 
assessment of peripheral lymph nodes. See 
Sections 8.2.2 and 8.2.8 of the master IMMB 
protocol. 
Vital signs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Includes pulse rate, blood pressure, respiratory 
rate, and body temperature. Measured after the 
participant has been sitting at least 5 minutes. 
See Section 8.2.1 of the master IMMB 
protocol. 
ECG 12-lead (single) (local) 
 
 
 
 
 
 
 
 
 
 
X 
A local ECG will be collected according to 
instructions in Section 8.2.4 of the master 
IMMB protocol. 
Patient-reported outcomes 
(electronic) 
 
 
 
 
 
 
 
 
 
 
 
Complete prior to any clinician-administered 
assessments. 
Dermatology Life Quality 
Index (DLQI) 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Patient-Oriented Eczema 
Measure (POEM) 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
SCORing Atopic Dermatitis 
(subjective) (SCORAD) 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 

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Table 1. Activities for screening/baseline and induction treatment periods of Study J4E-MC-FR01. 
For activities at unscheduled visit or early discontinuation visit, see Table 2. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
 
 
Study Day 
1 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Minimum interval between Visit 401 of the 
master IMMB protocol and Study Day 1: 
 Participants doing 
 15 days 
 All other participants: 8 days 
CRF visit number 
V0 
 
Atopic Dermatitis Control 
Tool (ADCT) 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Hospital Anxiety 
Depression Scale (HADS) 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Patient-reported outcomes 
(paper) 
 
 
 
 
 
 
 
 
 
 
 
 
Asthma Control 
Questionnaire-5 (ACQ-5) 
 
X 
 
 
 
 
 
 
 
 
X 
 
Clinician-administered 
assessments (electronic) 
 
 
 
 
 
 
 
 
 
 
 
 
vIGA-AD 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Eczema Area and Severity 
Index (EASI) 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
SCORing Atopic Dermatitis 
(objective) (SCORAD) 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Fitzpatrick Scale of Skin 
Phototypes 
 
X 
 
 
 
 
 
 
 
 
 
 
Clinician-administered 
assessments (paper) 
 
 
 
 
 
 
 
 
 
 
 
 
Columbia-Suicide Severity 
Rating Scale (C-SSRS) 
Since Last Assessed 
 
X 
 
 
X 
 
X 
 
X 
 
X 
AE collection should occur prior to collection 
of the C-SSRS. Adapted for the assessment of 
ideation and behavior categories only. 

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Table 1. Activities for screening/baseline and induction treatment periods of Study J4E-MC-FR01. 
For activities at unscheduled visit or early discontinuation visit, see Table 2. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
 
 
Study Day 
1 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Minimum interval between Visit 401 of the 
master IMMB protocol and Study Day 1: 
 Participants doing 
15 days 
 All other participants: 8 days 
CRF visit number 
V0 
 
Participant diary (electronic) 
 
 
 
 
 
 
 
 
 
 
 
 
Diary dispense 
 
 
 
 
 
 
 
 
 
 
 
Diary is dispensed during Visit 401 of the 
master IMMB protocol. Diary contains the 
following assessments:
Atopic Dermatitis Sleep Scale, and Skin 
Pain Numeric Rating Scale. 
Diary review 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Diary contains the following assessments:
Atopic 
Dermatitis Sleep Scale (ADSS), and Skin Pain 
Numeric Rating Scale (Skin Pain NRS). 

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Table 1. Activities for screening/baseline and induction treatment periods of Study J4E-MC-FR01. 
For activities at unscheduled visit or early discontinuation visit, see Table 2. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
 
 
Study Day 
1 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Minimum interval between Visit 401 of the 
master IMMB protocol and Study Day 1: 
 Participants doing 
 15 days 
 All other participants: 8 days 
CRF visit number 
V0 
 
Diary return 
 
(X) 
 
 
 
 
 
 
 
 
 
Collect diary only from participants who are 
not eligible for randomization (screen failed). 
Participant education 
 
 
 
 
 
 
 
 
 
 
 
 
Diary education 
(X) 
 
 
 
 
 
 
 
 
X 
 
Education is provided at Visit 401 of the master 
IMMB protocol and as shown for this ISA. 
Additional education can be provided as needed 
at any time. 
Laboratory tests and sample 
collections 
 
 
 
 
 
 
 
 
 
 
 
Collect before dosing unless otherwise 
specified. 
Hematology 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Clinical chemistry 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Urine or serum pregnancy 
test (local) 
 
X 
 
 
X 
 
X 
 
X 
 
X 
For WOCBP, a pregnancy test must be 
performed, with the result available within 24 
hours prior to dosing (see Section 8.2.7 of this 
ISA and Section 8.2.7 of the master IMMB 
protocol). Additional pregnancy tests should be 
performed at any time if a menstrual period is 
missed, or there is clinical suspicion of 
pregnancy, or as required by local law or 
regulation. 

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Table 1. Activities for screening/baseline and induction treatment periods of Study J4E-MC-FR01. 
For activities at unscheduled visit or early discontinuation visit, see Table 2. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
 
 
Study Day 
1 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Minimum interval between Visit 401 of the 
master IMMB protocol and Study Day 1: 
 Participants doing
15 days 
 All other participants: 8 days 
CRF visit number 
V0 
 
Urinalysis 
 
X 
 
 
 
 
 
 
 
 
X 
 
Estimated glomerular 
filtration rate (eGFR) 
 
 
 
 
 
 
 
 
 
 
X 
Calculated using Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) 
Creatinine Equation (2021). 
Hepatitis B virus (HBV) 
DNA 
 
X 
 
 
 
 
 
 
X 
 
 
Only for participants who are anti-HBc positive 
at Visit 401 (see Section 8.2.9 of the master 
IMMB protocol). 

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Table 1. Activities for screening/baseline and induction treatment periods of Study J4E-MC-FR01. 
For activities at unscheduled visit or early discontinuation visit, see Table 2. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
 
 
Study Day 
1 
 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Minimum interval between Visit 401 of the 
master IMMB protocol and Study Day 1: 
 Participants doing
15 days 
 All other participants: 8 days 
CRF visit number 
V0 
 
Immunogenicity (ADA) 
samples 
 
X 
X 
 
X 
 
 
 
X 
 
X 
On dosing visits, collect samples before dosing. 
Collect additional samples at specified times 
relative to onset of 
events (see 
Section 8.3.1.1 and Attachment 1, 
Section 10.1.2). 
Stored samples 
 
 
 
 
 
 
 
 
 
 
 
 
Genetics sample 
 
X 
 
 
 
 
 
 
 
 
 
Sample can be obtained at or after Study Day 1. 
Randomization and 
dosing-related activities 
 
 
 
 
 
 
 
 
 
 
 
 
Register visit with IWRS 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Randomization to study 
intervention via IWRS 
 
X 
 
 
 
 
 
 
 
 
 
 
Rerandomization via IWRS 
 
 
 
 
 
 
 
 
 
 
X 
 
Dispense study intervention 
via IWRS 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
No dose is given at Week 1. The dose 
dispensed at Week 16 is the first dose of the 
maintenance period. 
Administer study 
intervention 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
No dose is given at Week 1. 

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Table 2. Activities for maintenance and posttreatment follow-up periods, early discontinuation visit, and unscheduled visit (Study J4E-MC-FR01). 
Note: The posttreatment follow-up visits are required for all randomized participants. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
±7 
±7 
 
CRF visit number 
ED 
 
V808 
V812 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Rescue medication and 
background emollients are 
documented as concomitant 
medications. 
Adverse events (AEs) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE collection begins when the 
master protocol ICF is signed. 
events will be 
solicited at each visit. For 
AESIs, additional data are 
collected. See Section 8.3.1. 
Physical evaluation 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
 
 
X 
 
 
X 
 
X 
 
 
X 
 
Symptom-directed physical 
assessment 
 
 
X 
 
 
X 
 
X 
X 
 
X 
Perform as shown here and as 
needed based on participant 
status and standard of care. 
May be performed by qualified 
personnel per local regulations. 
Assess for TB risk factors, and 
for signs and symptoms of 
active TB, including an 
assessment of peripheral lymph 
nodes. See Sections 8.2.2 and 
8.2.8 of the master IMMB 
protocol. 

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Table 2. Activities for maintenance and posttreatment follow-up periods, early discontinuation visit, and unscheduled visit (Study J4E-MC-FR01). 
Note: The posttreatment follow-up visits are required for all randomized participants. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
±7 
±7 
 
CRF visit number 
ED 
 
V808 
V812 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Includes pulse rate, blood 
pressure, respiratory rate, and 
body temperature. Measured 
after the participant has been 
sitting at least 5 minutes. See 
Section 8.2.1 of the master 
IMMB protocol. 
ECG 12-lead (single) (local) 
 
 
X 
 
 
 
X 
X 
 
 
X 
A local ECG will be collected 
according to instructions in 
Section 8.2.4 of the master 
IMMB protocol. 
Patient-reported outcomes 
(electronic) 
 
 
 
 
 
 
 
 
 
 
 
Complete prior to any 
clinician-administered 
assessments. 
Dermatology Life Quality 
Index (DLQI) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Patient-Oriented Eczema 
Measure (POEM) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
SCORing Atopic Dermatitis 
(subjective) (SCORAD) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Atopic Dermatitis Control 
Tool (ADCT) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Hospital Anxiety Depression 
Scale (HADS) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 

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Table 2. Activities for maintenance and posttreatment follow-up periods, early discontinuation visit, and unscheduled visit (Study J4E-MC-FR01). 
Note: The posttreatment follow-up visits are required for all randomized participants. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
±7 
±7 
 
CRF visit number 
ED 
 
V808 
V812 
 
Patient-reported outcomes 
(paper) 
 
 
 
 
 
 
 
 
 
 
 
 
Asthma Control 
Questionnaire-5 (ACQ-5) 
 
 
 
 
 
X 
 
 
 
 
X 
 
Clinician-administered 
assessments (electronic) 
 
 
 
 
 
 
 
 
 
 
 
 
vIGA-AD 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Eczema Area and Severity 
Index (EASI) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
SCORing Atopic Dermatitis 
(objective) (SCORAD) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Fitzpatrick Scale of Skin 
Phototypes 
 
 
 
 
 
 
 
 
 
 
 
Not performed in these study 
periods. 
Clinician-administered 
assessments (paper) 
 
 
 
 
 
 
 
 
 
 
 
 
Columbia-Suicide Severity 
Rating Scale (C-SSRS) Since 
Last Assessed 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE collection should occur 
prior to collection of the 
C-SSRS. Adapted for the 
assessment of ideation and 
behavior categories only. 
Participant diary (electronic) 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 2. Activities for maintenance and posttreatment follow-up periods, early discontinuation visit, and unscheduled visit (Study J4E-MC-FR01). 
Note: The posttreatment follow-up visits are required for all randomized participants. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
±7 
±7 
 
CRF visit number 
ED 
 
V808 
V812 
 
Diary review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Diary contains the following 
assessments: 
Atopic Dermatitis Sleep Scale 
(ADSS), and Skin Pain 
Numeric Rating Scale (Skin 
Pain NRS). 
Diary return 
 
 
 
 
 
 
 
X 
 
 
X 
 
Participant education 
 
 
 
 
 
 
 
 
 
 
 
 
Diary education 
 
 
 
 
 
 
 
 
 
 
 
Education can be provided as 
needed at any time. 

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Table 2. Activities for maintenance and posttreatment follow-up periods, early discontinuation visit, and unscheduled visit (Study J4E-MC-FR01). 
Note: The posttreatment follow-up visits are required for all randomized participants. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
±7 
±7 
 
CRF visit number 
ED 
 
V808 
V812 
 
Laboratory tests and sample 
collections 
 
 
 
 
 
 
 
 
 
 
 
Collect before dosing unless 
otherwise specified. 
Hematology 
 
 
X 
 
 
X 
 
X 
 
X 
X 
 
Clinical chemistry 
 
 
X 
 
 
X 
 
X 
 
X 
X 
 
Urine or serum pregnancy 
test (local) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
For WOCBP, a pregnancy test 
must be performed, with the 
result available within 24 
hours prior to dosing (see 
Section 8.2.7 of this ISA and 
Section 8.2.7 of the master 
IMMB protocol). Additional 
pregnancy tests should be 
performed at any time if a 
menstrual period is missed, or 
there is clinical suspicion of 
pregnancy, or as required by 
local law or regulation. 
Urinalysis 
 
 
 
 
 
X 
 
X 
 
 
X 
 
Estimated glomerular 
filtration rate (eGFR) 
 
 
 
 
 
X 
 
X 
 
 
 
Calculated using Chronic 
Kidney Disease Epidemiology 
Collaboration (CKD-EPI) 
Creatinine Equation (2021). 

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Table 2. Activities for maintenance and posttreatment follow-up periods, early discontinuation visit, and unscheduled visit (Study J4E-MC-FR01). 
Note: The posttreatment follow-up visits are required for all randomized participants. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
±7 
±7 
 
CRF visit number 
ED 
 
V808 
V812 
 
Hepatitis B virus (HBV) 
DNA 
 
X 
 
 
X 
 
 
X 
 
 
X 
Only for participants who are 
anti-HBc positive at Visit 401 
(see Section 8.2.9 of the master 
IMMB protocol). 

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Table 2. Activities for maintenance and posttreatment follow-up periods, early discontinuation visit, and unscheduled visit (Study J4E-MC-FR01). 
Note: The posttreatment follow-up visits are required for all randomized participants. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
±7 
±7 
 
CRF visit number 
ED 
 
V808 
V812 
 
Immunogenicity (ADA) 
samples 
 
 
X 
 
 
X 
 
X 
 
 
X 
On dosing visits, collect 
samples before dosing. Collect 
additional samples at specified 
times relative to onset of 
events (see 
Section 8.3.1.1 and 
Attachment 1, Section 10.1.2). 
Stored samples 
 
 
 
 
 
 
 
 
 
 
 
 
Genetics sample 
 
 
 
 
 
 
 
 
 
 
 
Sample can be obtained at or 
after Study Day 1. 
Randomization and 
dosing-related activities 
 
 
 
 
 
 
 
 
 
 
 
 
Register visit with IWRS 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Dispense study intervention 
via IWRS 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
The last dose is given at 
Week 40. 

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Table 2. Activities for maintenance and posttreatment follow-up periods, early discontinuation visit, and unscheduled visit (Study J4E-MC-FR01). 
Note: The posttreatment follow-up visits are required for all randomized participants. 
Week 
Comment 
Study day 
Study Day 1 is day of first dose. 
Visit interval tolerance  
(window) in days 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
 
 
±7 
±7 
 
CRF visit number 
ED 
 
V808 
V812 
 
Administer study 
intervention 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
The last dose is given at 
Week
 
Abbreviations: ADA = anti-drug antibodies; AESI = adverse event of special interest; anti-HBc = hepatitis B core antibody; CRF = case report form; 
DNA = deoxyribonucleic acid; ECG = electrocardiogram; ED = early discontinuation visit; ICF = informed consent form; ISA = intervention-specific 
appendix; IWRS = interactive web-response system; TB = tuberculosis; UV = unscheduled visit; V = case report form visit; WOCBP = women of 
childbearing potential. 
 

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2. 
Introduction  
2.1. 
Study Rationale  
LY3454738 is a humanized IgG4-variant mAb that binds to and agonizes the human inhibitory 
checkpoint CD200R. CD200R is expressed on many cell types involved in the pathogenesis of 
AD. 
Activating CD200R with an agonist mAb is a potential 
therapeutic strategy for AD and other inflammatory disorders. This study will evaluate the safety 
and efficacy of LY3454738 in adults with moderate-to-severe AD. 
2.2. 
Background  
Immune checkpoint regulators such as CD200R are critical modulators of the immune system, 
allowing the initiation of a productive immune response and preventing the onset of 
autoimmunity by negatively regulating the response once the pathogen is eliminated. 
CD200R is expressed on multiple cell types. Specifically, CD200R is expressed on the surface of 
myeloid cells (mast cells, basophils, macrophages, and dendritic cells), and on T cells, B cells, 
neutrophils, microglia, and retina (Broderick et al. 2002; Wright et al. 2003). The CD200R 
ligand, CD200, is expressed on the surface of a variety of cell types, including vascular 
endothelial cells, fibroblasts, T and B cell subsets, and neurons (Wright et al. 2003). 
The pathogenesis of AD involves dysregulation of adaptive and innate immune responses. 
Skin-resident cells such as dendritic cells, mast cells, keratinocytes, macrophages, and innate 
lymphoid cells contribute to the inflammation of skin in AD. Likewise, T cells, plasmacytoid 
dendritic cells, monocytes, and granulocytes also contribute to AD pathology (Egawa and 
Weniger 2015). CD200R is expressed on many of these cell types. Hence, activating CD200R 
with an agonist mAb such as LY3454738 is a potential strategy for the treatment of AD. 
2.3. 
Benefit/Risk Assessment  
2.3.1. 
Risk Assessment  
Risks associated with LY3454738 
No dose-limiting safety issues have been identified in clinical studies of participants receiving 
single or repeat doses of LY3454738. In a Phase 1 study comparing LY3454738 versus placebo 
in AD (Study FRCC),
 
Based on these data and on other available clinical and nonclinical 
data, there are no anticipated risks that would require safety monitoring in this study beyond 
what is typical for clinical studies involving humanized mAbs. 
The administration of therapeutic mAbs to humans can be associated with 

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Risks and discomforts associated with study procedures 
Participants will use additive-free emollients during the study but will refrain from other topical 
AD treatments, with the exception of rescue medication as described in Section 6.9.1. 
Participants accustomed to using TCS and other topical treatments may experience increased 
discomfort due to itching during the study. 
Risk mitigations 
The study entry criteria of the master IMMB protocol and of this ISA exclude potential 
participants who may be at greater risk of developing infections,
 or malignancies. Participants who may be at greater risk for adverse effects related to 
TCS withdrawal (Hajar et al. 2015) are also excluded. 
To reduce the burden of untreated AD symptoms, qualifying participants are permitted to receive 
rescue medication during certain study periods (Sections 4.1 and 6.9.1). 
All participants will have appropriate predose safety assessments, including symptom-directed 
physical assessments, clinical safety laboratory tests, suicidality/self-harm evaluations, vital 
signs, and evaluation of reported AEs, during the treatment period. The design includes 
posttreatment follow-up visits at which safety assessments are also conducted. 
 Ongoing study-level monitoring of safety data will be 
performed, as described in Section 8.2 of the master IMMB protocol. Interim analyses of 
unblinded safety data will also be conducted, as described in Section 9.4 and Attachment 3, 
Section 10.3, of this ISA. 
2.3.2. Benefit Assessment  
Efficacy results from Study FRCC support the hypothesis that LY3454738 has the potential to 
treat AD.
 
Participants may benefit by receiving personal health information from the physical 
examinations and from other routine safety assessments performed in this study. 
2.3.3. Overall Benefit Risk Conclusion  
Taking into account the measures taken to minimize risk to participants in this study, and in the 
context of the cumulative knowledge of LY3454738, the benefit/risk balance for participants in 
this Phase 2 study is assessed to be acceptable. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of LY3454738 may be found in the IB. 

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3. 
Objectives, Endpoints, and Estimands  
This table lists objectives and endpoints for the evaluation of LY3454738 versus placebo. 
Objectives 
Endpoints
Primary
To compare the efficacy of LY3454738 versus 
placebo as measured by EASI-75 in the treatment of 
moderate-to-severe AD
Proportion of participants achieving EASI-75 at 
Week 16 

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Abbreviations: 
AD = atopic dermatitis; 
 EASI = Eczema Area and Severity Index;
 
3.1. 
Estimands  
The primary clinical question of interest is: in the target patient population, what is the difference 
between each dosing regimen of LY3454738 and placebo in achieving a successful response at 
Week 16 without use of any prohibited or rescue medication for AD or early permanent 
discontinuation? 
The estimand is described by the following attributes: 
 Population: 
 participants with moderate-to-
severe AD. 
 Endpoint: The primary endpoint and all secondary efficacy endpoints, that is, 
EASI-75
 
 
 How to account for ICEs: 
o A composite strategy will be used for all types of ICEs of interest,
 
 
 
o 
  
o 
 
  

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 Population-level summary: 
o For binary endpoints 
the population-level summary will be the unconditional difference 
in response rate at Week 16 between each dosing regimen of LY3454738 and 
placebo. 
o For continuous endpoints (percent change from baseline in EASI 
 mean difference at Week 16 between 
each dosing regimen and placebo.
 Rationale for estimand: The composite estimand is the standard from prior AD 
studies 
From the 
perspective of ICEs:
o If a participant used any prohibited or rescue medication for AD, the 
participant was not receiving sufficient benefits from study intervention. 
o If a participant early discontinued study intervention, the participant experienced a 
burden of study intervention that outweighed its benefits. 
 

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4. 
Study Design  
4.1. 
Overall Design  
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 
outpatient dose-ranging study to evaluate the efficacy and describe the safety of multiple 
LY3454738 induction and maintenance dosing regimens in adult participants with moderate-to-
severe AD. The study population includes
participants, all with diagnosed AD which is 
moderate to severe as measured by 
-
 of BSA 
involvement at randomization. 
Study periods 
A schematic of the design of this ISA is presented 
 Assessments, sample 
collections, and study drug administrations occur at the visits shown in the SoA (Section 1.3). 
Screening period and randomization to treatment within this ISA (Visit 0) 
Screening for this ISA can begin up to 
days before Study Day 1 (day of first dose). Informed 
consent for participation in this ISA must be obtained before any ISA-specific tests or procedures 
are performed. Screening activities for this ISA are listed in the SoA (Section 1.3) in the columns 
for CRF Visit 0 (V0). 
ty according 
to the study entry criteria of both the master IMMB protocol (Section 5) and this FR01 ISA 
(Section 5) must be confirmed.  
 
 
 
 
Induction regimen 
Approximate total 
number of participants 
planned 
LY3454738 
 mg 
 
96  
LY3454738 
 mg 
 
68 
LY3454738 
 mg 
 
28 
Placebo
68
 
 

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Blinded induction period 
Randomized participants will begin the double-blind, placebo-controlled, 16-week induction 
period when the initial dose is administered on Study Day 1. 
Topical rescue medication is permitted from Week 8 until Week 16 for participants who do not 
achieve an
 response, as described in Section 6.9.1. Topical rescue medication started 
during the induction period should be stopped at, or before, Week 16. 
Blinded maintenance period 
The blinded 
-week maintenance treatment period begins with the dose administered at 
Week 16. Participants having at least an 
response at Week 16 will receive a 
maintenance dosing regimen, as listed here. 
Week 16 responders who were originally 
randomized to this induction regimen...
 
Will receive this maintenance regimen:
LY3454738 
mg 
by rerandomization in 
 ratio: 
  LY3454738 
 mg 
 or 
 placebo
LY3454738 
mg 
 LY3454738 
mg 
LY3454738 
mg 
 LY3454738 
mg 
placebo
 Placebo
 response 
suggests the need for a higher dose. The escape therapy is LY3454738
mg 
. 
A participant will receive this escape therapy under the conditions listed here. 
Begin LY3454738 
 mg 
 as escape therapy...
if the participant...
At Week 16
has not achieved an
response at Week 16.
At Weeks
 
has not achieved an
response at Weeks 
 
A participant receiving escape therapy will continue receiving escape therapy through the last 
dosing visit of the study (Week 
 unless the participant is discontinued from study 
intervention. 
Topical rescue medication in the maintenance period is permitted from Week
until the end of 
the study for participants who do not achieve an
response, as described in Section 6.9.1. 
Posttreatment follow-up period 
All participants are expected to have 2 follow-up visits after the last dosing visit, as listed here. 
Condition
First follow-up visit
Second follow-up visit
If the participant did not discontinue 
study intervention early... 
occurs approximately 8 wk after 
last dosing visit
occurs approximately 12 wk after 
last dosing visit
If the participant did discontinue study 
intervention early... 
occurs after ED and with an 
approximately 8-week interval 
between the last dose and this 
visit 
occurs after ED and with an 
approximately 12-week interval 
between the last dose and this visit 
Blinding 

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This study design includes investigator and participant blinding (masking) (Section 6.4). 
original induction and maintenance treatments will continue until all 
participants have completed their last posttreatment follow-up visit or have discontinued the 
study. All blinded assessments and sample collections should be completed before a dose is 
administered at the dosing visits. 
Internal assessment committee 
During the study, an IAC will review the safety data in an unblinded fashion, as described in the 
master IMMB protocol, Appendix 1, Section 10.1.5. 
4.2. 
Scientific Rationale for Study Design  
EASI-75 as the primary endpoint measure 
The EASI and SCORAD are both regarded as acceptable instruments to measure the clinical 
signs of AD (Schmitt et al. 2013). Study FR01 uses a 75% reduction relative to the baseline 
EASI score (EASI-75) as the primary measure of efficacy. The EASI is a validated measure used 
in clinical practice and clinical trials to assess the severity and extent of AD (Hanifin et al. 2001). 
Duration of treatment period and posttreatment follow-up 
The duration of the induction period (16 weeks) and the primary endpoint at Week 16 is based 
on previous clinical trials of systemic therapies in AD (Simpson et al. 2016). The remaining 
duration of the study is intended to allow exploratory assessments of various LY3454738 

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maintenance dosing regimens. To reduce participant burden, topical rescue medication is 
permitted under certain circumstances (Section 6.9.1). 
The posttreatment follow-up period allows for continued monitoring of safety and maintenance 
of response after the last dose. The duration of this period is considered sufficient to wash out 
LY3454738 based on the half-life of the 
mg dose,
Appropriateness of study population 
The study inclusion criteria will enable enrollment of patients who are representative of the 
general population with moderate-to-
IGA 
 of BSA involvement at baseline have been used as inclusion criteria in other studies of AD 
(Simpson et al. 2016). 
Choice of placebo control, number of treatment groups, and escape arm 
A double-blind, placebo-controlled design limits bias for the participant assessments and 
investigator assessments and enables a clearer interpretation of the effects of the active study 
intervention. 
The multiple dosing regimens enable an evaluation of safety and efficacy across several doses 
and frequencies, thereby providing information to guide the selection of dosing regimens for 
future studies. 
the study and receive potential benefit from a higher dose. 
4.2.1. Patient Input into Design  
Not applicable. 
4.3. 
Justification for Dose  
The LY3454738 dose range of 
mg to 
mg 
 is based on clinical safety data from the 
Phase I Study FRCC,
 The chosen dose 
levels and regimens are anticipated to provide an exposure range that is pharmacologically active 
and cover a range of clinical response. 
In the Phase I study FRCC, 
 
 
 
 
 

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In the maintenance period, 
 regimens of LY3454738 and placebo are included to determine 
whether less frequent dosing can maintain the response attained with 
induction dosing 
regimens. 
4.4. 
End of Study Definition  
A participant is considered to have completed this FR01 ISA if the participant has completed all 
periods of the study, including the last scheduled procedure shown in the SoA of this ISA 
(Section 1.3). 
The end of this ISA is defined as the date of the last scheduled procedure of the last participant in 
Study FR01 globally. 

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5. 
Study Population  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
All screening evaluations, including those specified in the master IMMB protocol, must be 
completed and reviewed to confirm that each potential participant meets all eligibility criteria 
(that is, both master protocol and ISA-specific criteria) before the participant is randomized and 
receives the first dose of study intervention in this ISA. 
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. 
5.1. 
ISA-Specific Inclusion Criteria  
Participants are eligible to be included in this ISA only if all of the following criteria apply. 
Informed consent 
[1000] 
Are capable of giving, and have given, signed informed consent, which 
includes consent to compliance with the requirements and restrictions listed in 
the ICF(s) and in this ISA, including compliance with the use of contraceptives 
as specified in this ISA (see Attachment 2, Section 10.2.2). 
[1001] 
Are considering and capable of undergoing the study procedures applicable to 
. 
Participant characteristics 
[1002] 
Are from 18 to 70 years of age (inclusive) at the time of signing the ICF(s). 
Disease-specific characteristics 
[1003] 
Have moderate-to-severe AD, defined as meeting all of the following criteria, 
at the first dosing visit: 
[1003a] 
 
[1003b] 
vIGA-
 
[1003c] 
 
[1004] 
Have applied at least 1 emollient every day for at least 2 weeks before the day 
of the first dose of study intervention in this ISA and agree to daily use of at 
least 1 emollient continuously throughout the study. 
5.2. 
ISA-Specific Exclusion Criteria  
Participants are excluded from this ISA if any of the following criteria apply. 
[1005] 
Have, in the screening period (Visit 0), any of the skin conditions, infections, 
or medical conditions listed in Section 5.2 of the master IMMB protocol. 

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Previous or current therapies 
[1006] 
Have received any of the following therapies during the specified time period 
 
Criterion 
Therapy 
before the first dose of 
study interventiona
Note 
[1006b] 
Corticosteroids that are
intra-articular, intramuscular, or IV 
route), or 
suppositories)
6 weeks 
Intranasal, inhaled, 
or ophthalmic 
(ocular) steroids 
are allowed at any 
time. 
[1006c]
Oral systemic corticosteroids 
4 weeks 
[1006e] 
Other systemic therapy used to treat AD or 
symptoms of AD, whether 
approved/marketed or off-label use
4 weeks  
  
[1006f] 
Any investigational 
 
4 weeks or 5 half-lives  
(whichever is longer)
  
[1006g] 
Phototherapy, including 
ultraviolet A, ultraviolet B) 
excimer laser, or 
 
4 weeks  
  
[1006h] 
Topical immune modulators, including TCIs 
(for example, tacrolimus, pimecrolimus), and 
JAK inhibitors (for example, ruxolitinib, 
delgocitinib)
2 weeks  
 
[1006i] 
PDE4 inhibitors (for example, crisaborole)
2 weeks
[1006j] 
Bleach bath
2 weeks
[1006k]
TCS 
2 weeks

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a The washout period in this table includes the day of the first dose of study intervention. 
[1007] 
Have received any live vaccine (that is, live attenuated) within less than 
4 weeks before the day of the first dose of study intervention in this ISA, or 
intend to receive a live vaccine during the study, or within 14 weeks (about 
5 half-lives) after receiving the last dose of study intervention. 
Note: The following are not considered live vaccines: RNA vaccines, vaccines 
with inactive viral elements, and/or nonreplicating viral vector vaccines. 
Nonlive SARS-CoV-2 vaccines authorized by local regulatory bodies are 
allowed during or after the study. 
[1008] 
Have received a BCG vaccination or treatment within less than 4 weeks 
before the day of the first dose of study intervention in this ISA, or intend to 
receive BCG vaccination or treatment during the study, or within 14 weeks 
after receiving the last dose of study intervention. 
[1009] 
Are unstable with respect to use of chronic treatments to improve sleep: 
[1009a] 
Have started or restarted using a prescription sleep medication 
during the 2 weeks before the day of the first dose of study 
intervention in this ISA 
[1009b] 
Have changed the dose of a prescription sleep medication during 
the 2 weeks before the day of the first dose of study intervention 
in this ISA, or 
[1009c] 
Are likely to need to start or change the dose of prescription sleep 
medication during this ISA, in the opinion of the investigator. 
 
Note: Individuals on a stable dose of prescription sleep 
medication at screening may be eligible to be enrolled if other 
study entry criteria are met, but such individuals should remain on 
opinion, the dose should be changed or stopped to address a safety 
concern (Section 6.9.2). 
Other previous or current medical conditions 
[1010] 
Have 1 or more of the following conditions suggesting a possibly greater risk 
of clinically significant 
 reactions: 
[1010a] known 
 LY3454738, related compounds, or any 
components of the formulation, or 
[1010b] history of 
reactions that in the opinion of the 
investigator may predispose the participant to a clinically significant 
 to LY3454738 or to any components of the 
formulation.
Previous or concurrent clinical trial participation 
[1011] 
Have received LY3454738 in any other clinical study. 

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Other 
[1012] 
Are unable or unwilling to make themselves available for the required number 
of study visits or are unwilling to follow study restrictions and procedures, 
including restrictions on the use of concomitant therapies for AD, such as TCS. 
5.3. 
Lifestyle Considerations  
Participants should be instructed not to donate blood or blood products for 18 weeks after their 
last dose of study intervention. 
Participants must agree to the contraception criteria detailed in Attachment 2, Section 10.2.2, of 
this ISA, and they must agree not to breastfeed at any time during the study. 
5.4. 
Screen Failures  
Individuals who do not meet the criteria for participation in this ISA (screen failure at the ISA 
level) cannot be rescreened for this same ISA (FR01) using the same participant number. 
See the master IMMB protocol for additional information. 
5.5. 
Criteria for Temporarily Delaying Randomization of a Participant  
Not applicable. See the master IMMB protocol. 

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6. 
Study Intervention(s) and Concomitant Therapy  
Study intervention is defined as any medicinal product or medical device intended to be 
administered to or used by a study participant according to the study protocol. 
6.1. 
Study Intervention(s) Administered  
This study involves placebo and  dose levels of LY3454738 administered with 
, as 
shown in this table. 
Intervention Name
LY3454738
Placebo 
Nominal Dose Levels 
 mg 
 mg 
 mg 
 mg
Not applicable
Frequency of Administration 
 
 and as needed to maintain the blind 
Route of Administration
Authorized as defined by EU 
Clinical Trial Regulation
Not authorized 
Authorized and not used according to 
authorization
Abbreviations: EU = European Union; 
 
Background therapy will be used as shown in this table. 
Intervention Name 
Background therapy: emollient without additives such as 
antipruritics or antiseptics, as described in Section 6.1.2 of the 
master IMMB protocol
Dose Levels
Per local approved label, if applicable
Frequency of Administration
Daily or per local approved label, if applicable
Route of Administration
Topical
Authorized as defined by EU Clinical 
Trial Regulation
Not authorizeda 
Abbreviation: EU = European Union. 
a This medicinal product is not authorized in accordance with Directive 2001/83/EC and Regulation (EC) 
No 726/2004 of the European Parliament and of the Council. However, emollients are authorized according to 
EU Regulation 1223/2009 and are being used according to their authorization. 
LY3454738 will be supplied for clinical trial use as a 
 The drug product vials will be supplied in cartons, with the appropriate quantity 
specific to the planned dispensing schedule. 
Preparing the study interventions for dosing 
An unblinded pharmacist or other unblinded qualified individual will prepare the study 
interventions
(see Section 6.4). 

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Monitoring of participants after dosing 
All participants should be monitored for 30 minutes or longer after dosing, according to 
investigator practice or local standard of care. Sites must have resuscitation equipment, 
emergency drugs, and appropriately trained staff available during the
 and until 
completion of all required postdosing activities. 
Supply and labeling of study interventions 
See the master IMMB protocol. 
6.1.1. 
Medical Devices  
Not applicable to this ISA. 
6.1.2. 
Background Therapy  
See the master IMMB protocol. 
6.2. 
Preparation, Handling, Storage, and Accountability  
See the master IMMB protocol. 
6.3. 
Assignment to Study Intervention  
Assignment to treatment groups within this ISA will be determined by a computer-generated 
random sequence using an IWRS. The randomization ratios are described in Section 4.1. 
The randomization will be stratified based on the following factors: 
 baseline disease severity: baseline vIGA-AD 3 versus baseline vIGA-AD 4, and 
 sex assigned at birth: male or female. 
6.4. 
Blinding  
This is a double-blind study. Participants, investigators, and all individuals involved in the 
treatment or clinical evaluation of the participants 
original induction and maintenance treatments until all participants have completed their last 
posttreatment follow-up visit or have discontinued the study. 

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The switching of an individual participant to the escape arm is not blinded. The investigator will 
be aware 
that participants meeting certain 
EASI criteria (specified in Section 4.1) will be switched to LY3454738 
mg 
 as escape 
therapy. The 
induction and maintenance treatments will nevertheless 
remain blinded until all participants have completed their last posttreatment follow-up visit or 
have discontinued the study. 
Use of an unblinded pharmacist 
To maintain the blind, persons otherwise uninvolved in the study, for example, unblinded 
pharmacists or other unblinded qualified individuals, will prepare the study interventions 
When LY3454738 is prepared for dosing according to the detailed instructions 
provided by the sponsor, it will not be possible to distinguish LY3454738 from placebo. 
Blinded study personnel will administer the study intervention to the participants. 
Emergency unblinding 
See the master IMMB protocol. 
6.5. 
Study Intervention Compliance  
The date and time of each dose administered will be recorded in the source documents and will 
be recorded in the CRF. The dose of study intervention and study participant identification will 
be confirmed prior to the time of dosing. Deviations from the prescribed dosage regimen are 
identifiable via the CRF. 
6.6. 
Dose Modification  
The dosing regimens used in this study are described in Sections 4.1 and 6.1. No modifications 
to the specified regimens (dose or frequency) are permitted, except for reasons of immediate 
participant safety. 
6.7. 
Continued Access to Study Intervention after the End of the Study  
Continued access to the study interventions of this ISA will not be provided to participants after 
they have finished participating in this ISA. 
6.8. 
Treatment of Overdose  
An overdose of LY3454738 is considered to be any dose greater than the highest dose of 
LY3454738 planned for use in this study. 
In the event of an actual or suspected overdose, the investigator should 
 contact the medical monitor immediately 
 evaluate the participant to determine, in consultation with the medical monitor, 
whether study intervention should be interrupted or whether the dose should be 
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 closely monitor the participant for any AE/SAE and laboratory abnormalities as 
medically appropriate for at least 14 weeks. Hematology, chemistry, vital signs, 
and oxygen saturation should be monitored and supportive care should be 
provided as necessary (see the IB for LY3454738). 
6.9. 
Prior and Concomitant Therapy  
See the master IMMB protocol for general instructions about recording any vaccine, therapy, or 
medication that the participant receives during the study. 
6.9.1. 
Rescue Medication  
Rescue medication during induction period 
If a participant meets this criterion during this time period, the 
decision to implement rescue medication 
requirement. Rescue medication started during this period must be stopped at the Week 16 visit. 
Rescue medication during maintenance and posttreatment follow-up periods 
Use of rescue medication is permitted starting at Week
and until the end of the study for 
participants who do not achieve an
 response. If a participant meets this criterion 
during this time period, the decision to implement rescue medication 
judgment and is not a protocol requirement. 
Medications for use as rescue 
This table lists the allowed rescue medications. 
Allowed as rescue medicationa
Alternative or limitation
 
triamcinolone 0.1% cream 
 
hydrocortisone 2.5% ointment, or  
both
If these are not available, an alternate, equivalent potency TCS 
cream or ointment can be used.  
 
TCIs 
 
crisaborole, or  
both
If these are prescribed, their use should be limited to problem 
areas only, for example, face, neck, skin folds, and genital areas. 
a Rescue medications should be used according to their local product labeling. 
Abbreviations: TCI = topical calcineurin inhibitor; TCS = topical corticosteroid. 
 
Additional medications and considerations for use as rescue 
This table describes additional medications and considerations for use as rescue. 
If a participant...
then...
does not improve sufficiently after using 
the specified rescue medication for 7 days
a higher potency TCS may be used. 
after rescue with medium- and/or 
high-potency TCS and TCI 
the medium- and/or high-potency TCS and TCI should be 
stopped, and a low-potency TCS, for example, hydrocortisone 
2.5% ointment, should be used once daily for an additional 
7 days, and then stopped. 

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If a participant...
then...
has lesions return after stopping rescue 
retreat with TCS with or without TCIs and/or crisaborole as 
before, at the discretion of the investigator.
Time of administration of rescue medication 
Investigators should make every attempt to conduct efficacy and safety assessments immediately 
before administering any rescue medication. An unscheduled visit can be used for this purpose if 
necessary. This is to allow adequate assessment of skin dryness at the visit. 
Documentation of rescue medication 
Rescue medication must be recorded as stated in Section 6.9 of the master IMMB protocol. 
Discontinuation due to inadequate control with rescue medication 
Participants receiving rescue medication will continue to receive the assigned study 
interventions. A participant should be discontinued from study intervention and proceed to the 
posttreatment follow-up period 
 inadequate response to 
rescue medication, as specified in Section 7.1.2. 
6.9.2. 
Permitted Concomitant Therapy  
Permitted concomitant therapies for AD 
Concomitant therapies for AD during the study are permitted only as described here: 
 Daily use of emollients is required as background therapy, as described in 
Section 6.1 and Section 6.1.2 of the master IMMB protocol. 
 Rescue medication (for example, triamcinolone 0.1% cream and/or 
hydrocortisone 2.5% ointment; TCIs and/or crisaborole; medium- and/or 
high-potency TCS and TCI) is permitted but not required, as described in 
Section 6.9.1. 
 Use of topical and oral nonsedating antihistamines is permitted. 
Permitted concomitant therapies for other conditions 
Concomitant therapies for conditions other than AD are generally allowed unless described as 
prohibited in Section 6.9.3. Here is guidance for some of the permitted concomitant therapies: 
 Intranasal or inhaled steroids: Use of intranasal or inhaled steroids is allowed at 
any time for participants with such conditions as asthma and allergic rhinitis. 
 Prescription sleep medications: Individuals on a stable dose of prescription sleep 
medication at screening should remain on this stable dose throughout the study 
address a safety concern. 
6.9.3. 
Prohibited Concomitant Therapy  
Medications and treatments prohibited before randomization to a study intervention are listed in 
the exclusion criteria of this ISA (Section 5.2). 

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This table lists therapies prohibited throughout the study, that is, from randomization until the 
last posttreatment follow-up visit of this ISA. 
Prohibited Concomitant Therapy
Note
Systemic corticosteroids, including, but not limited to, 
oral or parenteral corticosteroids (intra-articular, 
intramuscular, IV, or rectally administered) 
Note: Intranasal or inhaled or ophthalmic (ocular) 
steroid use is allowed at any time (Section 6.9.2). 
Phototherapy, including therapeutic phototherapy 
(psoralen plus ultraviolet A, ultraviolet B), excimer 
laser, and tanning beds 
 
Any investigational therapy except the study 
interventions used in this ISA 
 
CBD products and any of the following substances if 
medically prescribed for the treatment of symptoms of 
AD or other conditions: marijuana, marijuana extract, 
and THCs-containing products
 
Bleach baths
Allergen immunotherapy
Live vaccines or BCG vaccination 
 The following are not considered live vaccines: 
RNA vaccines, vaccines with inactive viral 
elements, and/or nonreplicating viral vector 
vaccines. 
 Nonlive SARS-CoV-2 vaccines authorized by local 
regulatory bodies are allowed during or after the 
study. 
 Live vaccines and BCG vaccination are prohibited 
both during the study and within 14 weeks after the 
last dose of study intervention.
Abbreviations: AD = atopic dermatitis; BCG = Bacillus Calmette-Guerin; CBD = cannabidiol; IV = intravenous; 
JAK = Janus kinase; RNA = ribonucleic acid; TCS = topical corticosteroid; THC = tetrahydrocannabinol. 
 

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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal  
7.1. 
Discontinuation of Study Intervention  
See the master IMMB protocol. 
7.1.1. 
Temporary Discontinuation of Study Intervention  
See the master IMMB protocol. 
7.1.1.1. 
Elevated Liver Test Results  
See the master IMMB protocol. 
7.1.2. 
Permanent Discontinuation of Study Intervention  
Possible reasons for permanent discontinuation of study drug include, but are not limited to, the 
reasons listed here as well as reasons listed in Section 7.1.2 of the master IMMB protocol. 
 Inadequate response to rescue medication in participants who have been receiving 
rescue medication: at the second of 2 consecutive visits, the investigator 
determines that rescue medication 
symptoms and the participant needs treatment with an AD therapy which is 
prohibited by the protocol. In such cases, the participant is to be discontinued 
from the study drug before starting the protocol-prohibited AD therapy. 
 Nonresponse in participants who are receiving escape therapy: Participant 
receiving at least 2 doses of escape therapy at 2 consecutive visits fails to achieve 
an 
 response. 
7.2. 
Participant Discontinuation/Withdrawal from the Study  
See the master IMMB protocol. 
7.3. 
Lost to Follow up  
See the master IMMB protocol. 

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8. 
Study Assessments and Procedures  
Study procedures and their timing are summarized in the SoAs of the master IMMB protocol and 
this ISA. Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. Since key efficacy and patient-reported outcomes data 
may be collected via an electronic tablet and/or diary, adherence to the data collection modality 
specified in the SoA is also essential and is required for study conduct. 
Unless otherwise specified in the SoA of this ISA, all blinded assessments and sample 
collections should be completed before a dose is administered at the dosing visits. 
8.1. 
Efficacy Assessments  
Efficacy-related assessments occur at visits specified in the SoA of this ISA (Section 1.3). 
See Appendix 6, Section 10.6, of the master IMMB protocol for descriptions of these 
assessments: 
 EASI 
 vIGA-AD 
 SCORAD 
 POEM 
 DLQI 
 ADCT 
 ADSS 
 Skin Pain NRS 
This ISA also includes the ACQ-5 and HADS, which are described here. 
Asthma Control Questionnaire-5 (ACQ-5) 
The ACQ-5 is a participant-reported, 5-item questionnaire that assesses the following domains: 
 awoken at night by symptoms 
 limitation of normal daily activities 
 morning symptoms 
 shortness of breath (dyspnea), and 
 wheezing. 
The 5 questions are scored on a 7-point Likert scale with a recall period of 1 week. The scores 
range from 0 to 6 (higher score = lower asthma control). The total ACQ-5 score is the mean 
score of all questions; a lower score represents better asthma control. The ACQ-5 has been 
shown to reliably measure asthma control and distinguish participants with well-controlled 
et 
al. 1999; Juniper et al. 2006). 
Hospital Anxiety Depression Scale (HADS) 
The HADS is a validated, participant-reported instrument that assesses both anxiety and 
depression for the previous week. Fourteen items are rated on a 4-point scale from 0 to 3 
(Zigmond and Snaith 1983; White et al. 1999). Higher numbers indicate greater dysfunction 
(Zigmond and Snaith 1983; Herrmann 1997; Snaith 2003). 

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This table describes the scoring. 
HADS Subscale 
Number of 
Questions
Rating Score for 
Each Question
Score 
Total Score Range 
Anxiety 
7 
0-3
Sum of odd items 
0-21
Depression
7 
0-3
Sum of the even items 
0-21
Total scores of each subscale greater than or equal to 8 are interpreted as potential cases. 
Total scores of each subscale greater than or equal to 11 are interpreted as clinically significant 
symptoms (Zigmond and Snaith 1983). 
8.2. 
Safety Assessments  
Visits and order of safety assessments 
Safety assessments occur at visits specified in the SoA (Section 1.3) of this ISA, in addition to 
the screening safety assessments specified in the SoA for the master IMMB protocol. 
See the master IMMB protocol for 
 the preferred order of completing multiple safety assessments at the same visit 
(IMMB Section 8) 
 general provisions for safety monitoring during the study (IMMB Section 8.2), 
and 
 safety data collection and reporting requirements (IMMB Section 8.3). 
8.2.1. 
Vital Signs  
See the master IMMB protocol. 
8.2.2. 
Physical Examinations  
See the master IMMB protocol for a description of 
 TB assessment 
 complete physical examination, and 
 symptom-directed physical assessments. 
Height and weight will be measured and recorded as specified in the SoA of this ISA. 
8.2.3. 
Skin Assessment with Fitzpatrick Scale of Skin Phototypes  
See the master IMMB protocol. 
8.2.4. 
Electrocardiograms  
For each participant, 12-lead ECGs will be collected as specified in the IMMB SoA (Section 1.3) 
and the SoA of this ISA. 

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See the master IMMB protocol for a description of the 
 timing of collection of ECGs 
 interpretation of collected ECGs 
 actions to be taken after a clinically significant finding on ECGs, and 
 documentation of review of ECGs. 
8.2.5. 
Chest Imaging  
See the master IMMB protocol. 
8.2.6. 
Clinical Safety Laboratory Tests  
In this ISA, Attachment 1 (Section 10.1) and the SoA (Section 1.3) provide a list of clinical 
laboratory tests to be performed during this ISA. See the master IMMB protocol for clinical 
laboratory tests performed at Visit 401. 
All protocol-required laboratory assessments, as defined in this ISA and as defined in the master 
IMMB protocol, must be conducted in accordance with the SoA, standard collection 
requirements, and the laboratory manual. 
Reviewing and recording test results 
See the master IMMB protocol for instructions about reviewing and recording clinical laboratory 
test results. 
Repeat testing after a clinically significant abnormal finding 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study, or within 14 weeks 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. 
Fasting visits 
Fasting is not required before any clinical trial visits in this study. 
Laboratory tests after
event 
See Attachment 1, Section 10.1.2, of this ISA for clinical laboratory samples to be collected after 
event. 
Allowance for additional laboratory testing 
Additional clinical laboratory tests may be performed at any time during the study as deemed 
necessary by the investigator or as required by local regulations. 

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8.2.7. 
Pregnancy Testing  
Pregnancy testing is to be performed for WOCBP at the visits specified in the SoA (Section 1.3). 
If the specified visit includes administration of study intervention, the pregnancy test must be 
within 24 hours before the study intervention is administered. 
See Section 8.2.7 of the master IMMB protocol for additional information. 
8.2.7.1. 
Optional FSH Testing  
See the master IMMB protocol. 
8.2.8. 
Tuberculosis Testing and Monitoring  
See the master IMMB protocol. 
8.2.9. 
Hepatitis B Testing and Monitoring.  
See the master IMMB protocol. 
8.2.10. 
Hepatitis C Testing  
See the master IMMB protocol. 
8.2.11. 
Hepatic Safety Testing and Monitoring  
See the master IMMB protocol for guidance about the close hepatic monitoring, comprehensive 
hepatic evaluation, and suggested actions and follow-up assessments. 
8.2.11.1. Additional Hepatic Data Collection (Hepatic Safety CRF) in Study Participants 
Who Have Abnormal Liver Tests During the Study  
See the master IMMB protocol. 
8.2.12. 
Suicidal Ideation and Behavior Risk Screening and Monitoring  
Screening for suicidal ideation or behavior 
Screening for suicidal ideation or behavior includes the C-SSRS, as specified in the SoA for the 
master IMMB protocol. 
Monitoring for suicidal ideation and behavior and depressive symptomatology 
During the treatment and posttreatment periods of this ISA as specified in the SoA (Section 1.3), 
the C-SSRS (adapted for the assessment of ideation and behavior categories only) will be used to 
monitor for suicidal ideation and behavior. See the master IMMB protocol for a description of 
the C-SSRS. 
Discontinuation of participants with signs of suicidal ideation or behavior 
Participants who have signs of suicidal ideation or behavior should be considered for 
discontinuation of study intervention, following a risk assessment (see Section 7.1.2 of the 
master IMMB protocol). 

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8.3. 
Adverse Events, Serious Adverse Events, and Product Complaints  
See the master IMMB protocol for instructions on 
 timing and mechanism for collecting adverse events and product complaints 
 adverse event monitoring with a systematic questionnaire, and 
 collection of pregnancy information. 
8.3.1. Adverse Events of Special Interest  
For this ISA, the AESIs include 
If these AESIs are reported, sites will be prompted to collect additional data as described in the 
following subsections. 
Nonleading (spontaneous) AE collection should occur before the collection of any solicited AE 
or AE follow-up questionnaires. 

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8.5. 
Pharmacodynamics  
 
8.6. 
Genetics  
Where local regulations and IRB/IEC allow, a whole blood sample will be collected from 
consenting participants, as specified in the SoA (Section 1.3) of this ISA, for pharmacogenetic 
analysis. 
Additional information 
See the master IMMB protocol for information about 
 use of genetics samples 
 confidentiality of genetics samples, and 
 retention of genetics samples. 
8.8. 
Immunogenicity Assessments  
Predose venous blood samples will be collected to determine antibody production against the 
study intervention. 
Collection visits and times 
The visits and times for collecting samples for ADA testing are specified in the SoA 
(Section 1.3) of this ISA. The actual date and time (24-hour clock time) of each sample 
collection must be recorded accurately on the appropriate forms. To aid interpretation of these 
results, a venous blood sample will be collected at same time points to determine the serum 
concentrations of LY3454738. All samples for immunogenicity should be taken predose when 
applicable and possible. 
Immunogenicity will be assessed by a validated assay designed to detect ADAs in the presence 
of LY3454738. Antibodies may be further characterized for their neutralizing ability. 

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Samples collection for
event 
If 
 event is suspected, additional blood samples will be obtained for 
ADA analyses, as described in Attachment 1, Section 10.1.2, of this ISA. 
Additional information 
See the master IMMB protocol for additional information about retention of ADA samples. 
8.9. 
Medical Resource Utilization and Health Economics  
Health economics or medical resource utilization and health economics parameters will not be 
collected in this ISA. 

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9. 
Statistical Considerations  
This section is a summary of the planned statistical analyses of the most important endpoints, 
including primary and secondary endpoints, of this ISA. The MP-SAP and ISA-SAP will include 
a more technical and detailed description of the statistical analyses described in this section. The 
ISA-SAP will be finalized prior to the first unblinding. 
9.1. 
Statistical Hypotheses  
The null hypotheses corresponding to the primary and secondary estimands are these: there is no 
difference between LY3454738 and placebo in
participants 
with moderate-to-severe AD with respect to 
 proportion of participants achieving EASI-75 at Week 16 (primary) 
9.1.1. 
Multiplicity Adjustment  
No adjustments for multiplicity will be performed. 
9.2. 
Analyses Sets  
For the purposes of analysis, the following analysis sets are defined: 
Analysis Set 
Description 
Populations 
Analyses 
Conducted on 
This Analysis Set
Induction 
Analysis Set 
All randomized participants 
who receive at least 1 dose of 
study intervention. Participants 
will be included in the analysis 
set according to their randomly 
assigned intervention.
 Overall 
 vIGA-AD 
 EASI 
 SCORAD 
PROs
Maintenance 
Analysis Set 
All randomized participants 
who enter the maintenance 
period. Participants will be 
included in the analysis set 
according to their randomly 
assigned interventions at Week 
0 and Week 16.
 Overall 
 vIGA-AD 
 EASI 
 SCORAD 
 PROs

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Analysis Set 
Description 
Populations 
Analyses 
Conducted on 
This Analysis Set
Safety 
All randomized participants 
receiving at least 1 dose of 
study intervention. Participants 
will be included in the analysis 
set according to the 
intervention they actually 
received. 
 
Overall 
Safety data 
analyses for 
induction and/or 
maintenance 
period 
Pharmaco-
kinetics (PK) 
All randomized participants 
receiving at least 1 dose of 
study intervention and have 
PK data available. 
 Overall 
PK data analyses 
for induction 
and/or 
maintenance 
period
Abbreviations: EASI = Eczema Area and Severity Index; NRS = Numeric Rating Scale; PK = pharmacokinetic; 
PROs = patient-reported outcomes; SCORAD = SCORing Atopic Dermatitis. 
Additional analysis sets will be defined in the ISA-SAP to support exploratory analyses. 
9.3. 
Statistical Analyses  
9.3.1. General Considerations  
Statistical analysis of this study will be the responsibility of the sponsor or its designee. All 
statistical tests, unless otherwise noted, will be 2-sided and will be performed at a significance 
level of 0.05. Unless indicated otherwise in the ISA-SAP, the analyses will be conducted as 
described in this section. 
Changes to the data analysis methods 
Any change to the data analysis methods described in this ISA will require an amendment only if 
the change affects a principal feature of the ISA. Any other change to the data analysis methods 
described in the ISA 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 ISA-SAP. 
Summary of data 
Continuous data will be summarized in terms of mean, standard deviation, minimum, maximum, 
median, and number of observations. Categorical data will be summarized as frequency counts 
and percentage. Comparison between each LY3454738 dosing regimen and placebo will be 
performed for all efficacy and patient-reported endpoint analyses during the induction period 
with no adjustment for multiple comparisons. 
Induction dose selection 
Dose selection at the end of the induction period will be based on comparisons between each 
regimen and placebo using dose-response modeling. Dose selection rules and specifics will be 
detailed in the ISA-SAP. 

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Baseline definition 
For efficacy and PRO analyses, baseline will be defined as the last available value before the 
first dose of study intervention. In most cases, this value will be what is recorded at the 
randomization visit (Visit 0). For efficacy measures, if a participant does not take any study 
intervention, the last available value on or prior to randomization date will be used. Change from 
baseline will be calculated as the visit value of interest minus the baseline value. 
For induction period safety analyses, the baseline period is defined as the time from Visit 401 to 
the first dose of study intervention. For the safety analyses during the maintenance period, 
baseline is defined as the last available value before the first dose of study intervention during 
the maintenance period. In most cases, this will be the measure recorded at Week 16. For the 
safety analyses during the posttreatment follow-up period, baseline is defined as the last 
nonmissing assessment on or prior to entering the posttreatment period, that is, on or prior to 
Week 44 or ED visit. 
Missing data 
For the estimand defined in Section 3.1, missing data after accounting for ICEs is expected to be 
uncommon. Thus, the handling of any missing data remaining after accounting for ICEs will be 
specified in the ISA-SAP. Missing data imputation methods for supplementary estimands will be 
described in the ISA-SAP. 
Induction treatment comparisons 
For binary efficacy and PROs,
 
 
 
 
For continuous efficacy and patient-reported outcomes, 
 
 
 
Maintenance treatment comparisons 
The efficacy of different maintenance regimens will primarily be assessed with descriptive 
statistics across the maintenance period. Frequencies and percentages will summarize binary 
outcomes, and means and standard deviations will summarize continuous outcomes. The 
ISA-SAP may include additional exploratory analyses for maintenance efficacy, including, but 
not limited to, inferential efficacy analyses and the efficacy of different maintenance regimens 
across differing levels of response at induction, for example, 
EASI-75 
responders at Week 16. 

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9.3.2. 
Primary Endpoints/Estimands Analysis  
Treatment comparisons between each LY3454738 dosing regimen and placebo in proportion of 
 participants achieving EASI-75 at Week 16 will be 
conducted with
 at a significance level of 0.05. 
The analysis will be conducted using the induction analysis set
where participants who have ICEs of interest prior to 
Week 16 will be considered as nonresponders. 
Treatment response rates, treatment differences versus placebo, and their corresponding 95% CIs 
will be provided according to study intervention to which participants are randomized at Visit 0. 

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9.3.5. 
Safety Analyses  
See Section 9.3.5 of the master IMMB protocol for safety analyses, including but not limited to, 
AEs and SAEs. 
9.3.6. 
Other Analyses  
See the master IMMB protocol (Section 9.3.6) for participant disposition and characteristics, 
concomitant therapy, treatment compliance, PROs, subgroups, and sensitivity analyses. 
9.3.6.1. 
Pharmacokinetic/Pharmacodynamic Analyses  
Serum concentrations of LY3454738 will be listed by time point and dosing regimen using 
descriptive statistics. The PK of LY3454738 may also be characterized using graphical 
evaluations and mixed-effect (population PK) modeling approaches.
 
 
Data from this study may be combined with other study data, if appropriate. Details on PK and 
PK/PD analyses will be provided in an ISA-SAP or a separate ISA PK/PD analysis plan. 
9.3.6.2. 
Immunogenicity Analyses  
Upon assay validation, the frequency and percentage of participants with preexisting ADA and 
with TE ADA may be tabulated. TE ADAs are defined as those with a titer 2-fold (1 dilution) 
greater than the minimum required dilution, if no ADAs were detected at baseline 
(treatment-induced ADA) or those with a 4-fold (2 dilutions) increase in titer compared with 
baseline, if ADAs were detected at baseline (treatment-boosted ADA). 
The frequency of neutralizing antibodies may also be tabulated in TE ADA-positive participants, 
when available. 
The relationship between the presence of ADA and LY3454738 concentrations or PK parameters 
and PD response, including safety and efficacy, may be assessed. 

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9.5. 
Sample Size Determination  
Approximately 260 participants will be randomized to study intervention. 
The planned sample size for
participants is shown in this table by each induction dosing regimen.
With this planned sample size, an EASI-75 response at Week 16 of 52% and 12% for 
LY3454738 and placebo, respectively, 
 participants 
achieve at least 91% power for pairwise comparisons with placebo using a 2-sided chi-square 
test at the 0.05 significance level, with no adjustment for multiple comparisons. 

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10. 
Attachments to the ISA  
This section provides information specific to the FR01 ISA. For supporting documentation and 
operational considerations applicable to all ISAs, see Section 10 of the master IMMB protocol. 
10.1. 
Attachment 1: Clinical Laboratory Tests  
Use of central or local laboratories 
Clinical laboratory tests will be performed by a central laboratory or by a local laboratory as 
detailed in the tables in this attachment. 
In circumstances where the sponsor approves local laboratory testing in lieu of the central 
laboratory testing specified in the tables, the local laboratory must be qualified in accordance 
with applicable local regulations. 
Laboratory tests for inclusion/exclusion of potential study participants 
See Section 5 of the master IMMB protocol for laboratory tests that are part of the master IMMB 
protocol eligibility criteria. See Section 5 of this ISA for additional laboratory testing (if any) 
that may be required to assess eligibility. 
Allowance for additional laboratory testing 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 
Investigator responsibilities 
Investigators must document their review of the laboratory safety results. 
Provision of laboratory test results 
Laboratory test results that could unblind the study will not be reported to investigative 
sites or other blinded personnel. 
 
 

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10.1.1. 
Clinical Laboratory Tests Performed During This ISA  
This section lists the clinical laboratory tests performed at the visits specified in the SoA 
(Section 1.3) of this ISA. 
Notes
Hematology
Assayed by Lilly-designated laboratory.
Hemoglobin 
Hematocrit
Erythrocyte count (red blood cells [RBC])
Mean cell volume
Mean cell hemoglobin 
Mean cell hemoglobin concentration
Absolute neutrophil count (ANC) (segmented and 
bands) (calculated) 
Leukocytes (white blood cells [WBC])
Differential
Percent and absolute count of:
Neutrophils, segmented
Neutrophils, bands 
Report if detected.
Lymphocytes 
Monocytes
Eosinophils
Basophils
Platelets 
Cell morphology (RBC and WBC)
 

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Notes
Clinical Chemistry
Assayed by Lilly-designated laboratory.
Sodium
Potassium
Chloride
Bicarbonate
Total bilirubin (TBL)
Direct bilirubin
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT) 
Aspartate aminotransferase (AST)
Gamma-glutamyl transferase (GGT)
Blood urea nitrogen (BUN)
Creatinine
Creatine kinase (CK) 
Uric acid 
Total protein
Albumin 
Calcium 
Phosphorus
Glucose (random)
 
 
Notes
Hormones (females) 
Serum pregnancy
Performed locally. For WOCBP only. See Section 8.2.7.
Urine pregnancy
Performed locally. For WOCBP only. See Section 8.2.7.
Follicle-stimulating hormone (FSH) 
Optional. Performed locally. See Section 8.2.7.1.
 
 
Notes
Urinalysis
Assayed by Lilly-designated laboratory.
Specific gravity
pH
Protein 
Glucose
Ketones
Bilirubin
Urobilinogen
Blood
Nitrite
Urine leukocyte esterase 
Microscopic examination of sediment 
Perform if abnormalities were detected on urinalysis.
 

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Notes
Hepatitis Serology
Hepatitis B virus (HBV) testing:
Assayed by Lilly-designated laboratory.
Hepatitis B virus (HBV) DNA
Performed only for participants who test positive for 
anti-HBc at screening. 
 
 
Notes
Pharmacokinetics (PK) Samples
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
LY3454738 concentration
 
 
Notes
Immunogenicity Samples
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Anti-LY3454738 antibodies
anti-LY3454738 antibodies neutralization
 

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Notes
Genetics Sample
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
 
Abbreviations: DNA = deoxyribonucleic acid; EDTA = ethylenediaminetetraacetic acid; RNA = ribonucleic acid; 
WOCBP = women of childbearing potential.