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 
 
NCT0
Approval Date: 1 -
-20

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Master Protocol J4E-MC-IMMB(b) 
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Title Page 
Confidential Information 
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of the investigational interventions included in this master protocol and its associated intervention-specific appendices, 
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 
Master Protocol Amendment Number: b 
Compound: Multi-molecule code LY900030 
Master Protocol Brief 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 
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 
Approval Date: Protocol Amendment (b) Electronically Signed and Approved by Lilly on date 
provided below. 
Document ID: VV-CLIN-080391 

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Master Protocol J4E-MC-IMMB(b) 
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Medical monitor name and contact information will be provided separately. 
 
 

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Master Protocol J4E-MC-IMMB(b) 
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Protocol Amendment Summary of Changes Table  
 
DOCUMENT HISTORY
Document 
Date
Amendment (a)
13 Mar 2023
Original Protocol
09 Dec 2022
Amendment [b]  
This amendment is considered to be nonsubstantial. 
Overall Rationale for the Amendment: 
The purpose of this amendment is to remove topical corticosteroid (TCS) question. 
Section # and Name 
Description of Change
Brief Rationale
1.1. Synopsis
Removed EU trial number 
Correction
1.3. Schedule of Activities 
(SoA)  
8.1. Efficacy Assessments 
10.6. Appendix 6: 
Assessments of Disease 
Activity, Patient Reported 
Outcomes, and Quality of 
Life 
Removed TCS question 
The TCS question was removed to 
reduce burden to sites and to 
participants, and to avoid 
duplicated data collection with the 
concomitant medication forms. 
10.3.6. Regulatory 
Reporting Requirements 
Updated the language 
To clarify for EU CTR compliance 
10.5. Appendix 5: 
Contraceptive and Barrier 
Guidance
 in 
definition of Women not of childbearing 
potential (WNOCBP) 
For better clarity 
10.9. Appendix 9: Liver 
Safety: Suggested Action 
and Follow-up Assessments
 
For better clarity 
10.14. Appendix 14: 
Abbreviations and 
Definitions 
Added definition of SUSARs 
To clarify for EU CTR compliance 
10.15. Appendix 15: Master 
Protocol Amendment 
History
Inserted date, rationale, and summary of 
changes from amendment (a). 
To update document history 
 
 
 

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Master Protocol J4E-MC-IMMB(b) 
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Table of Contents  
1. 
Protocol Summary ..........................................................................................................8 
1.1. 
Synopsis............................................................................................................................8 
 
 
1.3. 
Schedule of Activities (SoA) ..........................................................................................11 
2. 
Introduction ...................................................................................................................15 
2.1. 
Study Rationale ...............................................................................................................16 
2.2. 
Background .....................................................................................................................17 
2.2.1. 
Intervention Selection: Adding or Stopping Intervention-Specific 
Investigations ..................................................................................................................17 
2.2.2. 
Governance .....................................................................................................................17 
2.3. 
Benefit/Risk Assessment ................................................................................................17 
3. 
Objectives, Endpoints, and Estimands .......................................................................18 
4. 
Study Design ..................................................................................................................19 
4.1. 
Overall Design ................................................................................................................19 
4.2. 
Scientific Rationale for Study Design ............................................................................20 
4.2.1. 
Rationale for Collection of Race and Ethnicity ..............................................................21 
4.2.2. 
Patient Input into Design ................................................................................................21 
4.3. 
Justification for Dose ......................................................................................................21 
4.4. 
End of Study Definition ..................................................................................................21 
5. 
Study Population ...........................................................................................................23 
5.1. 
Inclusion Criteria ............................................................................................................23 
5.2. 
Exclusion Criteria ...........................................................................................................24 
5.3. 
Lifestyle Considerations .................................................................................................29 
5.4. 
Screen Failures ................................................................................................................29 
5.4.1. 
Rescreening of Individuals Who Failed Screening for the Master 
Protocol ...........................................................................................................................30 
5.4.2. 
Rescreening of Individuals Who Failed Screening for an ISA .......................................30 
5.4.3. 
Allowed Retesting of Screening Laboratory Tests .........................................................30 
5.5. 
Criteria for Temporarily Delaying Randomization of a 
Participant .......................................................................................................................30 
6. 
Study Intervention(s) and Concomitant Therapy .....................................................31 
6.1. 
Study Intervention(s) Administered................................................................................31 
6.1.1. 
Medical Devices..............................................................................................................31 
6.1.2. 
Background Therapy .......................................................................................................31 
6.2. 
Preparation, Handling, Storage, and Accountability ......................................................31 
6.3. 
Assignment to Study Intervention ..................................................................................32 
6.4. 
Blinding ..........................................................................................................................32 
6.5. 
Study Intervention Compliance ......................................................................................33 
6.6. 
Dose Modification ..........................................................................................................33 
6.7. 
Continued Access to Study Intervention after the End of the 
Study ...............................................................................................................................33 
6.8. 
Treatment of Overdose ...................................................................................................34 
6.9. 
Prior and Concomitant Therapy ......................................................................................34 

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6.9.1. 
Rescue Medication ..........................................................................................................34 
6.9.2. 
Permitted Concomitant Therapy .....................................................................................34 
6.9.3. 
Prohibited Concomitant Therapy ....................................................................................34 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................35 
7.1. 
Discontinuation of Study Intervention ............................................................................35 
7.1.1. 
Temporary Discontinuation of Study Intervention .........................................................35 
7.1.2. 
Permanent Discontinuation of Study Intervention ..........................................................37 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................39 
7.3. 
Lost to Follow up ............................................................................................................40 
8. 
Study Assessments and Procedures.............................................................................41 
8.1. 
Efficacy Assessments .....................................................................................................41 
8.2. 
Safety Assessments .........................................................................................................42 
8.2.1. 
Vital Signs .......................................................................................................................42 
8.2.2. 
Physical Examinations ....................................................................................................43 
8.2.3. 
Skin Assessment with Fitzpatrick Scale of Skin Phototypes ..........................................44 
8.2.4. 
Electrocardiograms .........................................................................................................44 
8.2.5. 
Chest Imaging .................................................................................................................45 
8.2.6. 
Clinical Safety Laboratory Tests ....................................................................................45 
8.2.7. 
Pregnancy Testing ...........................................................................................................46 
8.2.8. 
Tuberculosis Testing and Monitoring .............................................................................47 
8.2.9. 
Hepatitis B Testing and Monitoring ...............................................................................48 
8.2.10. Hepatitis C Testing .........................................................................................................48 
8.2.11. Hepatic Safety Testing and Monitoring ..........................................................................49 
8.2.12. Suicidal Ideation and Behavior Risk Screening and Monitoring....................................50 
8.2.13. Systemic Hypersensitivity Reactions ..............................................................................51 
8.2.14. Additional Safety Data and Sample Collections .............................................................51 
8.3. 
Adverse Events, Serious Adverse Events, and Product 
Complaints ......................................................................................................................52 
8.3.1. 
Timing and Mechanism for Collecting Events ...............................................................52 
8.3.2. 
Pregnancy ........................................................................................................................54 
8.3.3. 
Adverse Events of Special Interest .................................................................................55 
8.4. 
Pharmacokinetics ............................................................................................................55 
8.5. 
Pharmacodynamics .........................................................................................................56 
8.6. 
Genetics ..........................................................................................................................56 
8.7. 
Exploratory Biomarkers ..................................................................................................57 
8.8. 
Immunogenicity Assessments.........................................................................................58 
8.9. 
Medical Resource Utilization and Health Economics ....................................................59 
9. 
Statistical Considerations .............................................................................................60 
9.1. 
Statistical Hypotheses .....................................................................................................60 
9.1.1. 
Multiplicity Adjustment ..................................................................................................60 
9.2. 
Analyses Sets ..................................................................................................................60 
9.3. 
Statistical Analyses .........................................................................................................61 
9.3.1. 
General Considerations ...................................................................................................61 
9.3.2. 
Primary Endpoint/Estimand Analysis .............................................................................62 

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9.3.3. 
Secondary Endpoints/Estimands Analysis ......................................................................62 
9.3.4. 
Exploratory Endpoints Analysis .....................................................................................62 
9.3.5. 
Safety Analyses ...............................................................................................................62 
9.3.6. 
Other Analyses ................................................................................................................63 
9.4. 
Interim Analyses .............................................................................................................65 
9.5. 
Sample Size Determination ............................................................................................65 
10. 
Supporting Documentation and Operational Considerations ..................................66 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................66 
10.1.1. Regulatory and Ethical Considerations ...........................................................................66 
10.1.2. Financial Disclosure........................................................................................................66 
10.1.3. Informed Consent Process ..............................................................................................67 
10.1.4. Data Protection................................................................................................................67 
10.1.5. Committees Structure......................................................................................................68 
10.1.6. Dissemination of Clinical Study Data.............................................................................68 
10.1.7. Data Quality Assurance ..................................................................................................69 
10.1.8. Source Documents ..........................................................................................................71 
10.1.9. Study and Site Start and Closure ....................................................................................71 
10.1.10. Publication Policy ...........................................................................................................72 
10.1.11. Investigator Information .................................................................................................72 
10.1.12. Sample Retention ............................................................................................................72 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................73 
10.2.1. Clinical Laboratory Tests Performed at Visit 401 ..........................................................74 
10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting ............................................................................................................77 
10.3.1. Definition of AE .............................................................................................................77 
10.3.2. Definition of SAE ...........................................................................................................78 
10.3.3. Definition of Product Complaints ...................................................................................79 
10.3.4. Recording and Follow-Up of AE and/or SAE and Product 
Complaints ......................................................................................................................80 
10.3.5. Reporting of SAEs ..........................................................................................................82 
10.3.6. Regulatory Reporting Requirements ...............................................................................82 
10.4. 
Appendix 4: Medical Device Adverse Events (AEs), Adverse 
Device Effects (ADEs), Serious Adverse Events (SAEs), and 
Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ............................................................................84 
10.5. 
Appendix 5: Contraceptive and Barrier Guidance ..........................................................85 
10.5.1. Definitions.......................................................................................................................85 
10.5.2. Contraception Guidance..................................................................................................85 
10.5.3. Pregnancy Testing Guidance ..........................................................................................85 
10.6. 
Appendix 6: Assessments of Disease Activity, Patient-Reported 
Outcomes, and Quality of Life .......................................................................................86 
10.6.1. Eczema Area and Severity Index (EASI) .......................................................................86 
10.6.2. vIGA-AD ........................................................................................................................86 
10.6.3. SCORing Atopic Dermatitis (SCORAD) .......................................................................87 

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10.6.4. Patient-Oriented Eczema Measure (POEM) ...................................................................87 
10.6.5. Dermatology Life Quality Index (DLQI) .......................................................................87 
10.6.6. Atopic Dermatitis Control Tool (ADCT) .......................................................................87 
10.6.7. Itch Numeric Rating Scale (Itch NRS) ...........................................................................88 
10.6.8. Atopic Dermatitis Sleep Scale (ADSS) ..........................................................................88 
10.6.9. Skin Pain Numeric Rating Scale (Skin Pain NRS) .........................................................88 
10.7. 
Appendix 7: Tuberculosis Testing ..................................................................................89 
 
 
10.9. 
Appendix 9: Liver Safety: Suggested Actions and Follow-up 
Assessments ....................................................................................................................93 
10.10. 
Appendix 10: Genetics....................................................................................................95 
10.11. 
Appendix 11: Country-specific Requirements ...............................................................96 
10.12. 
Appendix 12: Provisions for Changes in Study Conduct During 
Exceptional Circumstances .............................................................................................97 
10.13. 
Appendix 13: Requirements for ISA Design ................................................................101 
10.13.1. Activities During the Induction Period .........................................................................101 
10.13.2. Activities During a Maintenance Period .......................................................................102 
10.13.3. Activities During a Posttreatment Follow-up Period ....................................................102 
10.13.4. Activities During an Early Discontinuation Visit .........................................................103 
10.14. 
Appendix 14: Abbreviations and Definitions ...............................................................104 
10.15. 
Appendix 15: Master Protocol Amendment History ....................................................111 
11. 
References ....................................................................................................................112 
 

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Master Protocol J4E-MC-IMMB(b) 
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1. 
Protocol Summary  
1.1. 
Synopsis  
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 Brief 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 
Regulatory Agency Identifier Numbers: 
IND: 163615 
Rationale: Study J4E-MC-IMMB (IMMB) is designed as a platform trial to efficiently 
investigate the efficacy and safety of multiple investigational interventions for AD. 
Objectives, Endpoints, and Estimands: 
The purpose of this master protocol is to create a framework to evaluate the efficacy and safety 
of investigational interventions for AD as hypotheses emerge. In general, each ISA will assess at 
least 1 intervention relative to control with respect to 
 efficacy as measured by assessments of disease activity (for example, EASI, SCORAD, 
and vIGA-AD
®), patient-reported outcomes (for example, POEM), and quality of life (for 
example, DLQI), and 
 safety, using standard assessments and measures, such as physical examinations, clinical 
safety laboratory tests, vital signs, and AEs. 
The clinical research objectives, endpoints, and estimands for specific investigations are detailed 
in the relevant ISA. 
Overall Design 
This is a multinational, multicenter, randomized, double-blind, controlled, platform-type master 
protocol with ISAs to investigate multiple interventions for AD at the same time or serially over 
time. 
The master protocol (IMMB) contains protocol elements common to every investigation in the 
platform, including but are not limited to, master protocol entry criteria, safety monitoring 
activities and criteria for discontinuation applicable to every ISA, and statistical analysis 
methods applicable to every ISA. It also contains administrative information applicable to all 
ISAs, such as an appendix describing standards for the design of ISAs to support use of a 
common clinical trial database. 
The ISAs contain study elements specific to the interventions under study, such as dosing 
regimen, benefit/risk information, and intervention-specific eligibility criteria and assessments. 
Brief Summary: Study participants will be adults with moderate-to-severe AD. Each ISA 
provides a brief summary of the health measurements/outcomes, study interventions, treatment 
durations, and overall study duration for that ISA. 

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Study Population: Individuals included in this study will be at least 18 years old and have a 
diagnosis of AD for at least 12 months before screening (Visit 401), have moderate-to-severe 
AD 
-
Visit 401; 
and be candidates for systemic therapy, having a documented history of inadequate response to 
existing topical medications within 6 months before screening or a history of intolerance to 
topical therapy. 
Number of Participants: Each ISA specifies the planned number of participants for that ISA. 
Intervention Groups and Duration: Each ISA specifies the intervention groups and study 
duration for that ISA. 
Ethical Considerations of Benefit/Risk: Each ISA provides intervention-specific benefit/risk 
information for that ISA. 
Data Monitoring Committee: Yes (Internal Assessment Committee). 
 
 

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1.3. 
Schedule of Activities (SoA)  
Activities for the master protocol screening period can be conducted over more than 1 day as long as the activities are completed 
within the window. Decentralized capabilities, such as telephone, IT-assisted virtual visit, mobile health care, or a combination 
thereof, may be used for activities, if allowed by local regulations and if the sponsor provides written approval for such capabilities. 
Table 1. Screening Period of the Master IMMB Protocol (Study J4E-MC-IMMB) 
 
 
Comment 
Visit interval tolerance 
(window) in days 
 
Study Day 1 
Study Day 1 is the day of first dose of study intervention. The first dose is given to eligible participants 
after all screening and baseline evaluations of both the master IMMB protocol and the relevant ISA have 
been completed. See the relevant ISA for screening/baseline activities. 
CRF Visit number 
V401 
 
Consent and demographics 
 
 
Informed consent 
X 
Informed consent for the master IMMB protocol must be obtained before any master protocol-specific tests 
or procedures are performed. Informed consent must also be obtained before any ISA-specific tests or 
procedures are performed (Appendix 1, Section 10.1.3). 
Inclusion and exclusion 
criteria: confirmation of 
eligibility 
X 
The inclusion and exclusion criteria of both the master IMMB protocol (Section 5) and the relevant ISA 
must be confirmed before the participant is randomized to a study intervention and receives a first dose. See 
the relevant ISA for ISA-specific inclusion and exclusion criteria. 
Demographics 
X 
Includes year of birth, sex, ethnicity (where permissible), and race (Section 4.2.1). 
Preexisting conditions and 
medical history 
X 
All conditions ongoing and relevant medical history should be collected. 
Prespecified medical history 
X 
Prespecified medical history includes, but is not limited to, conjunctivitis, allergic rhinitis, allergies, 
asthma, depression, insomnia, and herpes infection, including herpes zoster. 
Concomitant medications 
X 
All ongoing medications at the time of consent should be collected. Background emollients are to be 
documented as concomitant medications. 
Adverse events (AEs) 
X 
AE collection begins when the ICF for this master protocol is signed (Section 8.3.1). For AESIs, additional 
data may be collected per the ISA; see the relevant ISA for information about AESIs. 
Physical evaluation 
 
 
Height 
X 
 
Weight 
X 
 

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Table 1. Screening Period of the Master IMMB Protocol (Study J4E-MC-IMMB) 
 
 
Comment 
Visit interval tolerance 
(window) in days 
 
Study Day 1 
Study Day 1 is the day of first dose of study intervention. The first dose is given to eligible participants 
after all screening and baseline evaluations of both the master IMMB protocol and the relevant ISA have 
been completed. See the relevant ISA for screening/baseline activities. 
CRF Visit number 
V401 
 
Physical examination 
X 
The physical examination excludes pelvic, rectal, and breast examinations unless clinically indicated 
(Section 8.2.2). Assess for tuberculosis (TB) risk factors, and for signs and symptoms of active TB, 
including an assessment of peripheral lymph nodes (Sections 8.2.2 and 8.2.8). 
Vital signs 
X 
Includes pulse rate, blood pressure, respiratory rate, and body temperature. Measured after the participant 
has been sitting at least 5 minutes (Section 8.2.1). 
ECG 12-lead (single) (local) 
X 
A local ECG will be collected according to instructions in Section 8.2.4. 
X-ray of chest 
X 
Posterior anterior view and, if needed, lateral view. Locally performed. Interpreted and reported by a 
radiologist or pulmonologist. Chest x-ray is not required if one was performed within 90 days before Visit 
401 and sufficient documentation exists for the TB evaluation (Sections 8.2.5 and 8.2.8). A chest CT scan 
can be used instead of a chest x-ray if the chest CT scan was performed within the same time window 
(Section 8.2.5). 
Patient-reported outcomes 
(electronic) 
 
Complete prior to any clinician-administered assessments. 
Dermatology Life Quality 
Index (DLQI) 
X 
 
Patient-Oriented Eczema 
Measure (POEM) 
X 
 
SCORing Atopic Dermatitis 
(subjective) (SCORAD) 
X 
 
Clinician-administered 
assessments (electronic) 
 
 
vIGA-AD 
X 
 
Eczema Area and Severity 
Index (EASI) 
X 
 
SCORing Atopic Dermatitis 
(objective) (SCORAD) 
X 
 

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Table 1. Screening Period of the Master IMMB Protocol (Study J4E-MC-IMMB) 
 
 
Comment 
Visit interval tolerance 
(window) in days 
 
Study Day 1 
Study Day 1 is the day of first dose of study intervention. The first dose is given to eligible participants 
after all screening and baseline evaluations of both the master IMMB protocol and the relevant ISA have 
been completed. See the relevant ISA for screening/baseline activities. 
CRF Visit number 
V401 
 
Clinician-administered 
assessments (paper) 
 
 
Columbia-Suicide Severity 
Rating Scale 
Baseline/Screening (C-SSRS) 
X 
AE collection should occur prior to the collection of the C-SSRS. Adapted for the assessment of ideation 
and behavior categories only. 
Participant diary (electronic) 
 
 
Dispense diary 
X 
Diary contains the following assessments: Itch Numeric Rating Scale (Itch NRS), Atopic Dermatitis Sleep 
Scale (ADSS), and Skin Pain Numeric Rating Scale (Skin Pain NRS). 
Participant education 
 
 
Diary education 
X 
 
Laboratory tests and sample 
collections 
 
 
Hematology 
X 
 
Clinical chemistry 
X 
 
Follicle-stimulating hormone 
(FSH) 
X 
Optional; performed as needed to confirm postmenopausal status (Section 8.2.7.1). 
Serum pregnancy 
X 
Only for WOCBP (Section 8.2.7). 
Urinalysis 
X 
 
Hepatitis B virus (HBV) 
screening tests 
X 
Screening includes anti-HBc and HBsAg. 
If anti-HBc is positive, it will be followed by an HBV DNA test (Section 8.2.9). 
Hepatitis B virus (HBV) DNA 
X 
401 (Section 8.2.9). 
Hepatitis C virus (HCV) 
screening tests 
X 
If HCV antibody test is positive, an HCV RNA test will be run by the testing laboratory (Section 8.2.10). 

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Table 1. Screening Period of the Master IMMB Protocol (Study J4E-MC-IMMB) 
 
 
Comment 
Visit interval tolerance 
(window) in days 
 
Study Day 1 
Study Day 1 is the day of first dose of study intervention. The first dose is given to eligible participants 
after all screening and baseline evaluations of both the master IMMB protocol and the relevant ISA have 
been completed. See the relevant ISA for screening/baseline activities. 
CRF Visit number 
V401 
 
Tuberculosis (TB) test 
X 
Participants who had a tuberculin skin test (TST) must have the test read 48 to 72 hr after placement. The 
TST test does not need to be read at the site but must be read by a trained professional and results must be 
presented to the site prior to first dose of study intervention in an ISA (Section 8.2.8). 
HIV testing 
X 
 
Estimated glomerular 
filtration rate (eGFR) 
X 
Calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation 
(2021). 
Randomization and 
dosing-related activities 
 
See the relevant ISA for randomization and dosing-related activities. 
Register visit with IWRS 
X 
When this visit is registered in IWRS, the participant receives a unique participant number. 
After 
eligibility for an ISA, register 
the participant in IWRS for 
the selected ISA 
X 
In IWRS, a participant can be registered for only 1 ISA at a time (Section 4.1). Before this activity is 
performed, r
 eligibility according to inclusion and exclusion criteria of 
both the master protocol and the selected ISA. See Section 5 of this document for inclusion and exclusion 
criteria of this master protocol. See the relevant ISA for ISA-specific inclusion and exclusion criteria. 
Abbreviations: AESI = adverse event of special interest; 
CRF = case report form; CT = computed (or computerized) 
tomography; ECG = electrocardiogram; HBV = hepatitis B virus; HIV = human immunodeficiency virus; ICF(s) = informed consent form(s); 
ISA = intervention-specific appendix; IWRS = interactive web-response system; JAK = Janus kinase; RNA = ribonucleic acid; V = case report form visit; 
WOCBP = women of childbearing potential. 
 

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Master Protocol J4E-MC-IMMB(b) 
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2. 
Introduction  
AD, also called atopic eczema, is a common noncontagious, chronic, relapsing, pruritic 
inflammatory skin disease. Clinically AD is characterized by severe pruritus and eczematous 
dermatitis and can be distinguished from other skin diseases by such factors as age of onset, 
distribution on the body, xerosis, lichenification, and atopy (Barrett and Luu 2017; Bieber 2021). 
AD may present with dry itchy skin and may be complicated by rashes that blister or weep. This 
may lead to an unrelenting itch scratch cycle (Frazier and Bhardwaj 2020). Various factors have 
been implicated in the ongoing inflammation associated with AD, including genetics, 
environment, and pro-Th2 cytokines. Numerous cytokines, including IL-25, IL-33, IL-4, IL-13, 
IL-5, IL-31, and IL-10, have been shown to drive T helper response. Skin breakdown may be due 
to mutations in the filaggrin gene, leading to itch, and bacterial colonization may also contribute 
to the pro-inflammatory state (Brandt and Sivaprasad 2011). 
Patients with AD have a high burden of disease, and their quality of life is significantly affected 
(Galli et al. 2020). In the Global Burden of Disease Study 1990-2017, AD had the highest 
disease burden among skin diseases as measured by disability-adjusted life years (Laughter 
et al. 2021). Because of pruritus and skin pain, patients with moderate-to-severe AD can 
experience severe and frequent disturbances of sleep, which can play a role in overall health 
(Silverberg et al. 2021a). In 1 study, AD was shown to have a greater negative effect on patient 
mental health than diabetes and hypertension (Kiebert et al. 2002). Symptoms of AD can impact 
-esteem, social activities and relationships, and performance at work or school 
(Sibbald and Drucker 2017). The economic burden of AD can include increased sick leave, job 
changes, or job loss due to symptoms (Nørreslet et al. 2018). 
Currently, there is no cure for AD. Common therapies for mild-to-moderate AD include 
avoidance of irritants; use of wet wraps, soaking baths, and emollients; and use of TCS and TCI. 
Topical medications provide some symptomatic relief for many patients but do not always 
adequately control the disease. In patients with persistent moderate-to-severe disease, step-up 
options include phototherapy and systemic immunosuppressives, such as oral 
glucocorticosteroids, azathioprine, cyclosporine, methotrexate, and mycophenolate mofetil 
(Simpson et al. 2017; Wollenberg et al. 2018; Bieber 2021). 
Recent advances in the understanding of the molecular pathogenesis of AD have led to the 
development and approval of more targeted therapies for AD (Worm et al. 2020). Some 
examples are listed in this table. 
Therapy
Description
Indication
Citation
Dupilumab 
Human anti-IL-4R alpha 
monoclonal antibody that inhibits 
signaling for both IL-4 and IL-13 
Moderate-to-severe AD 
Boguniewicz 2020 
Dupixent package insert 2022 
Dupixent summary of product 
characteristics
Tralokinumab 
Human monoclonal antibody that 
binds to IL-13 and inhibits its 
interaction with IL-
IL-
Moderate-to-severe AD 
Adbry package insert 2021 
Adtralza summary of product 
characteristics 

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Master Protocol J4E-MC-IMMB(b) 
16 
Therapy
Description
Indication
Citation
Baricitinib 
Oral JAK1/2 inhibitor 
Moderate-to-severe AD 
Olumiant summary of product 
characteristics
Upadacitinib 
Oral JAK1 inhibitor 
Moderate-to-severe AD 
Rinvoq package insert 2022 
Rinvoq summary of product 
characteristics 
Guttman-Yassky et al. 2021
Abrocitinib 
Oral JAK1 inhibitor 
Moderate-to-severe AD 
Cibinqo package insert 2022 
Cibinqo summary of product 
characteristics 
Simpson et al. 2020a 
Silverberg et al. 2020
Ruxolitinib 
Topical JAK1/2 inhibitor
Mild-to-moderate AD 
Opzelura package insert 2022
Nevertheless AD remains a major burden for patients and society. More efficacious and durable 
therapies with a favorable safety profile are needed. 
2.1. 
Study Rationale  
Variations in key parameters in the design and conduct of clinical trials for AD can have an 
impact on the interpretation of treatment efficacy and can complicate efforts to compare the trial 
outcomes, such that Silverberg et al. (2022) have called 
 
One approach to harmonizing a series of 
As described by Woodcock and LaVange (2017), a platform study uses a master protocol to 
establish an overarching structure for testing many interventions over time. 
Studies employing master protocols have been used in many therapeutic areas, as shown in this 
table. 
Therapeutic Area or Indication
Study Acronym (if available) 
Citation
Oncology
I-SPY-2
Barker et al. 2009
Oncology
Lung-MAP
Herbst et al. 2015
Oncology
GBM AGILE
Alexander et al. 2018
EPAD
Ritchie et al. 2016
DIAN-TU
Bateman et al. 2017
COVID-19
ACTIV
LaVange et al. 2021
COVID-19
RECOVERY and REMAP-CAP
Goossens et al. 2022
Osteoarthritis
CPMP
NCT05080660
Hidradenitis suppurativa 
NCT03827798
NCT04988087
Systemic lupus erythematosus
WILLOW
NCT05162586
Systemic lupus erythematosus
IMMA
NCT05123586
Immune thrombocytopenia 
NCT05086744
PRISM
NCT04102111
Chronic spontaneous urticaria
LIBERTY-CSU CUPID 
NCT04180488
Studies of new treatments for AD could benefit from the harmonization that a platform design 
can bring. See the ISAs for rationales to investigate particular interventions in this platform. 

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2.2. 
Background  
2.2.1. 
Intervention Selection: Adding or Stopping Intervention-Specific Investigations  
This platform trial is designed to enable the investigation of many interventions for AD by 
means of the introduction of new ISAs over time. 
At the inception of this platform trial, at least 1 ISA will be available. 
Additional ISAs will be added to the platform trial over time based on 
 availability of safety, tolerability, and PK data to support the clinical development of a 
particular intervention for AD, and 
 regulatory and ERB approval to add the new ISAs to the platform trial. 
An ISA may be stopped early for the reasons stated in Appendix 1, Section 10.1.9. 
2.2.2. 
Governance  
Selection of new interventions for investigation 
Eli Lilly and Company will be responsible for the selection of interventions to be included in this 
platform trial. 
Periodic assessment of data from intervention-specific investigations 
An IAC will be established to make periodic assessments of ISA data and to make 
recommendations for protocol modifications or other actions. This internal committee will be 
independent of the Lilly study team responsible for the master protocol and its ISAs. The IAC is 
described in Appendix 1, Section 10.1.5. 
Considerations for use of a common database in this platform trial 
Data collected for the master protocol and for each ISA will be stored in a common database for 
the platform trial. To be included in this master protocol, investigations of new interventions 
must be amenable to trial designs that conform to the standard activity structure of the common 
database, as described in Appendix 13, Section 10.13. 
2.3. 
Benefit/Risk Assessment  
Study interventions are not administered during Visit 401. The screening procedures of Visit 401 
generally present little risk. Participants may benefit by receiving personal health information 
from the physical examination and other safety assessments. 
Intervention-specific benefit/risk information is provided in the relevant ISA. More detailed 
information about the known and expected benefits and risks and reasonably expected AEs of an 
intervention also may be found in the IB for the intervention. 

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3. 
Objectives, Endpoints, and Estimands  
The purpose of this master protocol is to create a framework to evaluate the efficacy and safety 
of investigational interventions for AD as hypotheses emerge. In general, each ISA will assess at 
least 1 investigational intervention relative to control with respect to 
 efficacy as measured by assessments of disease activity (for example, EASI, SCORAD, 
and vIGA-AD), patient-reported outcomes (for example, POEM), and quality of life (for 
example, DLQI), and 
 safety, using standard assessments and measures, such as physical examinations, clinical 
safety laboratory tests, vital signs, and AEs. 
The clinical research objectives, endpoints, and estimands for specific investigations are detailed 
in the relevant ISA. 

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Master Protocol J4E-MC-IMMB(b) 
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4. 
Study Design  
4.1. 
Overall Design  
This is a multinational, multicenter, randomized, double-blind, controlled, platform-type master 
protocol with ISAs to investigate multiple interventions for AD at the same time or serially over 
time. The figure in Section 1.2 illustrates the schema. 
The ISAs can begin independently of one another as interventions become available for clinical 
testing. The ISAs can also finish independently of one another, ending, for example, when the 
ISA has reached its full planned duration or when 
criteria for futility or success have been met. 
Master protocol and ISAs 
The overall design includes 2 components which, used together, constitute the complete protocol 
for study conduct: 
 
The master protocol (IMMB) document explains the platform and contains protocol 
elements common to every investigation in the platform. Common elements include, but 
are not limited to, the master protocol screening period and master protocol entry criteria; 
safety monitoring activities and criteria for discontinuation applicable to every ISA; and 
statistical analysis methods applicable to every ISA. The document also contains 
administrative information applicable to all ISAs, such as an appendix describing 
standards for the design of ISAs to support use of a common clinical trial database. 
 
The ISAs provide information on the interventions to be studied, for example, 
intervention-specific screening activities, background information, benefit/risk, and dose 
justification; intervention-specific study objectives, endpoints, and estimands; and 
intervention-specific outcomes measurements and statistical analysis methods. Each ISA 
includes an SoA listing study activities from Week 0 (Visit 0) through the last planned 
study visit. 
Informed consent 
Informed consent must be obtained from a potential study participant 
 before any master protocol-specific tests or procedures are performed, and 
 before any ISA-specific tests or procedures are performed. 
The ICF(s) must meet the regulatory and ethical requirements stated in Appendix 1, 
Sections 10.1.1 and 10.1.3. 
Screening periods 
The master protocol and the ISAs each have screening periods. This approach to screening 
enables an ISA to have screening/baseline activities that are different from the screening/baseline 
activities of other ISAs. 
The screening periods have windows that flexibly enable an investigator to begin screening a 
participant for an ISA either 
 after screening the participant for the master protocol, or 

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Master Protocol J4E-MC-IMMB(b) 
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 while still screening the participant for the master protocol 
as long as 
 the date of signing the master protocol ICF is earlier than or same as the date of signing 
the relevant ISA ICF, and 
 the screening windows in the relevant SoAs are observed. 
If a study site has more than 1 active ISA, the participant can be screened for multiple ISAs 
serially or in parallel, at the discretion of the investigator. 
See Section 1.3 for procedures of the master protocol screening period. See the relevant ISAs for 
procedures of the ISA-specific screening/baseline period. 
Participant assignment to an ISA 
Before being randomized to a study intervention, a participant must be assigned to an ISA in 
IWRS. The assignment occurs in this manner. 
Step 1 
Assess 
 according to all study entry criteria, including those of the master 
IMMB protocol and the available ISA(s).
Step 2 
Determine which ISA the participant is to be assigned to
the 
applicable ISA.
Step 3 
I
the selected ISA. 
In IWRS, the participant can be registered for only 1 ISA at a time. 
to an ISA is not blinded. 
Treatment and posttreatment periods of ISAs 
After being assigned to an ISA, eligible participants will be randomized to a study intervention 
within that ISA. Randomization to interventions within an ISA will be blinded (Section 6.4). 
The duration of the treatment period depends on the design of the ISA. Some ISAs may have 
longer treatment periods than other ISAs, and some ISAs may have multiple treatment periods. 
Every ISA will include at least 1 posttreatment follow-up visit. 
See the relevant ISA for procedures conducted during ISA-specific treatment and posttreatment 
study periods. 
Early discontinuation of study intervention 
Participants who permanently discontinue the study intervention early will have no additional 
treatment period visits but will remain in the study to complete procedures for an ED visit and 
the ISA-specified posttreatment follow-up visits (Section 7.1.2). 
4.2. 
Scientific Rationale for Study Design  
Platform trial design 
A platform trial can enable harmonization of key elements of a series of related clinical trials, 
thereby easing the interpretation of treatment efficacy and aiding efforts to compare the trial 
outcomes. 

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This platform trial is intended to provide these and other clinical development efficiencies: 
 
using a common clinical trial database built on a standard visit structure that requires 
key assessments and procedures to be conducted at standard visits, while also flexibly 
enabling additional visits, assessments, and procedures if needed to support 
intervention-specific objectives and endpoints 
 
harmonizing certain elements study design by, for example, defining a core set of study 
entry criteria in the master protocol, and 
 
establishing a network of clinical study sites to enable a continuous stream of potential 
study participants over time, with sites potentially benefiting from streamlined and 
coordinated trial logistics. 
Appropriateness of study population 
The master protocol inclusion criteria will enable enrollment of patients who are representative 
of the general population with at least moderately severe AD at initial screening (Visit 401). 
Scores of EASI 12 and IGA 3, with AD involvement of 
 of BSA, at screening have been 
used among the inclusion criteria of other studies of AD (Thaçi et al. 2016; Wollenberg et al. 
2021). An ISA, as part of its inclusion criteria, may specify criteria resulting in a population with 
greater disease severity. 
Type of control group 
To enable ISA designs in which use of placebo might not be necessary or appropriate, this 
master protocol does not specify what is to be used as control in every ISA. Each ISA will 
specify and justify the type of control (for example, placebo or an active intervention) used in 
that ISA. 
4.2.1. Rationale for Collection of Race and Ethnicity  
In this study, collection of demographic information includes ethnicity, where permissible 
according to local regulations, and race. The scientific rationale is based on the need to assess 
variable response in safety or efficacy, or both, based on race or ethnicity. Such a need can be 
addressed only if all the relevant data are collected. 
4.2.2. Patient Input into Design  
See the relevant ISA. 
4.3. 
Justification for Dose  
See the relevant ISA. 
4.4. 
End of Study Definition  
The end of the master protocol will occur when all ISAs are complete and no new ISAs 
are planned. 
For each ISA, the end of the study is defined as the date of the last scheduled procedure of the 
last participant assigned to treatment in that ISA. 

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Consistent with local law and regulations, the competent authority and relevant ethics 
committees in each participating country will be notified about the completion or early 
termination of each ISA. 

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Master Protocol J4E-MC-IMMB(b) 
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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 relevant ISA, 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. 
Note: An ISA may have additional entry criteria that are more restrictive than the criteria listed 
in this master protocol. R
 before interacting with 
IWRS for the purpose of registering 
assignment. 
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. 
Inclusion Criteria  
Participants are eligible to be included in the study only if all of the following criteria apply. 
Informed consent 
[1] 
Are capable of giving, and have given, signed informed consent as described in 
Appendix 1, Section 10.1.3, which includes consent to compliance with the 
requirements and restrictions listed in the ICF(s) and in this protocol, including 
compliance with the use of contraceptives. 
Note: Contraceptive use should be consistent with local regulations regarding the 
methods of contraception for persons participating in clinical studies. For 
contraception requirements, see the relevant ISA. 
Participant characteristics 
[2] 
Are male or female and at least 18 years of age at the time of signing the ICF(s). 
Note: In some jurisdictions, the legal age of consent for study participation is 
greater than 18 years. For sites in such jurisdictions, the legal age of consent will 
be used for this criterion. 
Disease-specific characteristics 
[3] 
Present with a diagnosis of AD at least 12 months prior to screening (Visit 401), 
elines of care for the 
management of atopic dermatitis: Section 1. Diagnosis and assessment of atopic 
Eichenfield et al. 2014), as well as the following, at Visit 401: 
[3a] 
12 
[3b] 
vIGA-
 
[3c] 
 EASI BSA) 

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Master Protocol J4E-MC-IMMB(b) 
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[4] 
Are candidates for systemic therapy, and have a history, documented by a 
physician and/or the investigator, of inadequate response to existing topical 
medications within 6 months preceding screening (Visit 401) or a history of 
intolerance to topical therapy, as defined by at least 1 of the following: 
[4a] inability to achieve good disease control defined as mild disease or better, 
for example, IGA 2, after use of at least a medium-potency TCS for at 
least 4 weeks, or for the maximum duration recommended by the product 
prescribing information, for example, 14 days for super-potent TCS, 
whichever is shorter. Note: For the purpose of this criterion, a TCS may be 
used with or without TCI. 
Note: Failing a systemic therapy intended to treat AD, for example, 
dupilumab, cyclosporine, methotrexate, azathioprine, mycophenolate 
mofetil, or other small molecules, within 6 months before screening 
(Visit 401) will be considered a surrogate for inadequate response to 
existing topical medications. 
[4b] a history of clinically significant adverse reaction with the use of TCS, for 
example, skin atrophy, allergic reaction, or systemic effects, that, in the 
opinion of the investigator, outweigh the benefits of retreatment 
[5] 
Agree to daily use of at least 1 emollient continuously throughout the study. 
5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply at screening 
(Visit 401): 
Previous or current skin conditions 
[6] 
Have a history of eczema herpeticum: 
[6a] 
any episode within 12 months prior to screening (Visit 401), or 
[6b] 
2 or more episodes during lifetime 
[7] 
Are currently experiencing or have a history of concomitant skin conditions other 
than AD, for example, psoriasis or cutaneous lupus, that, in the opinion of the 
investigator, would interfere with evaluations of the effect of study intervention 
on AD. 
[8] 
Are currently experiencing or have a history of erythrodermic, refractory, or 
unstable skin disease which requires frequent hospitalizations or IV treatment 
and, in the opinion of the investigator, could interfere with study participation. 
[9] 
Are currently experiencing a skin infection that requires treatment with, or is 
currently being treated with, topical or systemic antibiotics. 
Note: Participants who fail screening due to this criterion should not be 
rescreened until at least 4 weeks after screen failure and at least 2 weeks after 
resolution of the infection. 

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Previous or current therapies 
[10] 
Have a history of TCS use suggestive of a high risk for TCS withdrawal, for 
example, a history of prolonged or frequent use of moderate- to high-potency 
TCS, especially on the face (Hajar et al. 2015), such that, in the opinion of the 
investigator, the participant will be unable to withdraw and abstain from TCS for 
several weeks during the study. 
Previous or current infections 
[11] 
Have a current or recent acute, active infection. For at least 30 days before 
screening (Visit 401) and up to the first dosing visit of the ISA, participants must 
have no symptoms or signs of confirmed or suspected infection and must have 
completed any appropriate anti-infective treatment. 
Note: Participants who have an upper respiratory infection, a vaginal candida 
infection, or an oral candida infection and who are being treated only 
symptomatically and not requiring systemic anti-infectives may be considered for 
enrollment if other study eligibility criteria are met. Enrollment of participants 
with other 
designated medical monitor. 
[12] 
Have had any of the following types of infection within 12 weeks before 
screening (Visit 401) or develop any of these infections before the first dosing 
visit of the ISA: 
[12a] serious (requiring hospitalization, or IV or equivalent oral antibiotic 
treatment, or both) 
[12b] opportunistic, as defined in Winthrop et al. 2015; see Appendix 8, 
Section 10.8 for examples 
 
Note: Herpes zoster is considered active and ongoing until all vesicles are 
dry and crusted over. 
[12c] chronic (duration of symptoms, signs, and/or treatment of 6 weeks or 
longer) 
[12d] recurring, including, but not limited to, herpes simplex, herpes zoster, 
recurring cellulitis, and chronic osteomyelitis 
 
Note: Participants with only recurrent, mild, and uncomplicated orolabial 
herpes or genital herpes, or both, may be discussed 
designated medical monitor and considered for enrollment if other study 
eligibility criteria are met. 
[13] 
Have active TB (see Section 8.2.8). 
[14] 
Have or have had LTBI that has not been treated with a complete course of 
appropriate therapy as defined by the WHO and the United States CDC, unless 
such treatment is underway (see Section 8.2.8). 

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Master Protocol J4E-MC-IMMB(b) 
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[15] 
Have a current infection with HBV, that is, positive for HBsAg and/or PCR 
positive for HBV DNA (see Section 8.2.9). 
[16] 
Have a current infection with HCV, that is, positive for HCV RNA (see 
Section 8.2.10). 
[17] 
Have HIV infection. 
Diagnostic assessments 
[18] 
Have any of the following specific abnormalities on the Visit 401 screening 
laboratory tests: 
[18a] serum creatinine, 
s ULN 
[18b] ALP 
 
[18c] TBL 
 
[18d] hemoglobin <10.0 g/dL 
[18e] neutropenia  ANC <1.2 × 103/µL 
[18f] lymphopenia  lymphocyte count <0.75 × 103/µL 
[18g] thrombocytopenia  platelets <100 × 103/µL 
[18h] eGFR <60 mL/min/1.73 m
2 (CKD-EPI Creatinine Equation [2021]) (FDA 
2020; NKF [WWW]). 
 
Note: For repeat testing of the Visit 401 screening laboratory tests, see 
Section 5.4.3 of this master protocol. 
[19] 
Have other laboratory test results at screening (Visit 401) which are outside the 
normal reference range for the population or study site and, in the opinion of the 
 
[20] 
Have screening ECG abnormalities that, in the opinion of the investigator, are 
y 
in the study. 
Other previous or current medical conditions 
[21] 
Have a history of a primary immunodeficiency, splenectomy, or any underlying 
condition that predisposes the participant to infection. 
[22] 
Have a history of organ or bone marrow transplant, or will require such a 
transplant during the study. 
[23] 
Have any serious concomitant illness that 
[23a] requires treatment with systemic corticosteroids 
[23b] requires active frequent monitoring, for example, unstable chronic asthma, 
or 

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Master Protocol J4E-MC-IMMB(b) 
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[23c] would otherwise interfere with study participation, in the opinion of the 
investigator 
[24] 
Have a history of any major surgery within 12 weeks before screening (Visit 401) 
or will require major surgery during the study. 
[25] 
Have a history of a thrombotic event within 24 weeks before screening (Visit 401) 
or are on anticoagulants and in the opinion of the investigator are not 
well-controlled regarding management of hypercoagulable risk. 
[26] 
Have a history of any of the following within 12 months before screening 
(Visit 401): 
[26a] 
myocardial infarction 
[26b] 
unstable ischemic heart disease 
[26c] 
cerebrovascular accident 
[26d] 
stroke, or 
[26e] 
New York Heart Association Stage III or IV heart failure 
[27] 
Have significant and uncontrolled disease, in the opinion of the investigator, such 
as 
[27a] cardiovascular disease, for example, uncontrolled hypertension, angina, or 
congestive heart failure 
[27b] endocrine disorder, for example, diabetes, or thyroid dysfunction 
[27c] respiratory, hepatic, renal, gastrointestinal, hematologic, or 
neuropsychiatric disorder 
[27d] any other serious or unstable illness that could constitute an unacceptable 
risk to the participant when taking an IMP or could interfere with the 
interpretation of study data 
[28] 
Have a diagnosis or history of malignant disease within 5 years before screening 
(Visit 401), with the following exceptions: 
 basal cell or squamous epithelial carcinomas of the skin that have been 
resected with no evidence of metastatic disease for 3 years, and 
 cervical carcinoma in situ, with no evidence of recurrence within 5 years 
before screening (Visit 401). 

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Master Protocol J4E-MC-IMMB(b) 
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[29] 
Are at risk for suicide, defined as at least 1 of the following: 
[29a] are, in the judgment of the investigator, actively suicidal and therefore 
deemed to be at significant risk for suicide 
[29b] 
-SSRS and the ideation occurred within the past 
month, or 
 
-related behaviors on the 
Suicidal Behavior
-SSRS, and the behavior occurred 
within the past month. 
[30] 
Have a condition suggesting a possibly greater risk of clinically significant drug 
hypersensitivity reactions, for example: 
[30a] clinically significant multiple or severe drug allergies, or 
[30b] a history of severe posttreatment hypersensitivity reactions, including, but 
not limited to, erythema multiforme major, linear IgA dermatosis, toxic 
epidermal necrolysis, or exfoliative dermatitis. 
Previous or concurrent clinical study participation 
[31] 
Have received an active study intervention in any clinical study within the last 
30 days, including an active study intervention in any ISA of this master protocol. 
Note: If the previous study intervention has a long half-life, at least 5 half-lives or 
30 days (whichever is longer) should be used for this criterion. 
Note: Participants are not excluded by this criterion if they received only placebo in a 
previous clinical investigation, whether that investigation was an ISA of Study IMMB or 
a separate clinical study. 
[32] 
Were randomized to a study intervention in an ISA of this master protocol but 
prematurely stopped participating in that ISA for any reason, including but not 
limited to, early discontinuation from study intervention, early discontinuation 
(withdrawal) from the ISA, or being lost to follow-up. 
[33] 
Are currently receiving a study intervention in any other clinical study, or are 
participating in any other type of medical research judged not to be scientifically 
or medically compatible with this study. 
Other reasons for exclusion 
[34] 
Are pregnant or are intending to become pregnant or breastfeed at any time during 
the study. 
Note: WOCBP must test negative for pregnancy as indicated by a negative serum 
pregnancy test at screening (Visit 401) followed by a negative urine pregnancy 
test within 24 hours prior to the first exposure to study intervention in an ISA. 

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[35] 
Have evidence of current or a recent history (that is, within 6 months before 
Visit 401) of any substance use disorders, including but not limited to, cannabis 
use disorder, of any severity as defined by the DSM-V (APA 2013), in the 
opinion of the investigator, excepting disorders of nicotine or caffeine use. 
Note: Participants are to be excluded by this criterion if there is evidence (per 
-report) of use of marijuana, marijuana 
extract, or THC-containing products as self-medication for symptoms of AD or 
other conditions. See the relevant ISA for any prohibitions on the concomitant use 
of CBD products or medically prescribed marijuana, marijuana extract, or 
THC-containing products for the treatment of AD symptoms or other conditions 
during the study. 
[36] 
Have received blood products within 6 months before screening (Visit 401). 
[37] 
Have donated more than a single unit of blood within 4 weeks before screening 
(Visit 401) or intend to donate blood during the study. 
[38] 
Are largely or wholly incapacitated, permitting little or no self-care, such as being 
bedridden or confined to wheelchair. 
[39] 
Have insufficient venous access for the study-required blood sampling. 
[40] 
Are investigative site personnel directly affiliated with this study or are their 
immediate families. Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted. 
[41] 
Are employees of Eli Lilly and Company or are employees of a third-party 
organization that is involved in the study and requires exclusion of their 
employees. 
[42] 
Are unable or unwilling to make themselves available for the required study visits 
or are unwilling to follow study restrictions and procedures. 
[43] 
Are for any reason, in the opini
medical monitor, unsuitable for inclusion in the study. 
5.3. 
Lifestyle Considerations  
See the relevant ISA for any applicable lifestyle considerations, such as restrictions on 
 diet or meals 
 exercise or activity, or 
 use of caffeine, alcohol, or tobacco. 
For some ISAs, there may be no such restrictions. 
5.4. 
Screen Failures  
A screen failure occurs when a participant who consents to participate in the clinical study is not 
subsequently assigned to a study intervention. A minimal set of screen failure information is 

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required to ensure transparent reporting of screen failure participants to meet the CONSORT 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any SAE. 
5.4.1. 
Rescreening of Individuals Who Failed Screening for the Master Protocol  
Individuals who do not meet the criteria for participation in this master protocol according to 
Sections 5.1 and 5.2 of this master IMMB protocol (screen failure at the master protocol level) 
may be rescreened 2 times after the reason for the screen failure has resolved. 
At each rescreening for the master protocol, the individual will first sign an ICF for the master 
protocol (Appendix 1, Section 10.1.3), and the individual will receive a new participant number. 
5.4.2. 
Rescreening of Individuals Who Failed Screening for an ISA  
Individuals who do not meet the eligibility criteria for participation in a particular ISA cannot be 
rescreened for the same ISA using the same participant number. 
However, if they are still within the master protocol screening window and if they still meet the 
master protocol eligibility criteria, they can be consented to, and screened for, participation in 
another ISA (Section 5.5). 
Individuals will not be given a new participant number when they are consented to another ISA. 
5.4.3. 
Allowed Retesting of Screening Laboratory Tests  
Repeating laboratory tests 1 time during the screening period is permitted. Additional repeat 
testing of laboratory tests may be permitted in consultation with the 
designated 
medical monitor. Repeating screening tests to comply with the protocol-designated screening 
period or for any other reason does not constitute rescreening. 
Results of screening laboratory tests are valid for 60 days during the screening period. If a 
participant is still in screening after 60 days, the screening laboratory tests should be repeated 
(Section 8.2.6). 
See Appendix 7, Section 10.7, for guidance on retesting for TB. 
5.5. 
Criteria for Temporarily Delaying Randomization of a Participant  
Not applicable for the master IMMB protocol. 
A study site could experience a period of time in which no ISA is active at that site. During that 
time period, screening for the master protocol may continue, but the screening window of the 
master protocol, defined in Section 1.3, must still be observed. Participants who have not been 
assigned to an active ISA before the end of the master protocol screening window must undergo 
rescreening if they wish to continue their study participation. 

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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  
Study interventions are described in the ISAs. 
Supply and labeling of study interventions 
The sponsor or its designee will supply study interventions in accordance with current Good 
Manufacturing Practice. 
Study interventions will be labeled as appropriate for country requirements. 
6.1.1. 
Medical Devices  
See the relevant ISA for information about medical devices, if applicable. 
All PCs, including malfunction, use error, and inadequate labeling, will be documented and 
reported by the investigator throughout the study and will be appropriately managed by the 
sponsor. 
6.1.2. 
Background Therapy  
At least 1 emollient should be used daily throughout the study as background therapy. 
Moisturizers with additives such as antipruritics or antiseptics are not permitted. 
Background therapies should be used according to their local product labeling. 
On the days of study visits, emollients should not be applied until after the participant has 
undergone all study procedures and clinical evaluations. This is to allow adequate assessment of 
skin dryness at the visit. 
Emollient therapy must be recorded as stated in Section 6.9. 
6.2. 
Preparation, Handling, Storage, and Accountability  
Sponsor responsibilities 
The sponsor will provide instructions on the preparation, handling, and storage of the study 
interventions, including site responsibility and accountability for the administered study 
interventions. 
Site responsibilities and accountability 
Investigators and authorized site personnel will consult the information provided by the sponsor 
for information on the administration of study interventions, including warnings, precautions, 
contraindications, adverse reactions, and dose modifications. 
The following are additional responsibilities of the investigator or 
 designee: 

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 The investigator or designee must confirm appropriate storage conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention. 
 Only participants enrolled in the study may receive study intervention. Only authorized 
study personnel may supply, prepare, or administer study intervention. All study 
intervention must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized study personnel. 
Note: In some ISAs, enrolled participants may receive study intervention for 
self-administration during intervals between study visits. Such participants will receive 
appropriate instructions for the storage and use of study intervention, and, if applicable, 
for the return of unused of study intervention. 
 The investigator or authorized study personnel are responsible for study intervention 
accountability, reconciliation, and record maintenance, that is, receipt, reconciliation, and 
final disposition records. 
Further guidance and information for the final disposition of unused study interventions will be 
provided by the sponsor. 
The investigator or designee is also responsible for 
 explaining the correct use of the study interventions 
 verifying that instructions are followed properly 
 maintaining accurate records of study intervention dispensing and collection, and 
 returning all unused medication to Lilly or its designee at the end of the study. 
Note: In some cases, sites may destroy the material if, during the investigative site selection, 
the evaluator has verified and documented that the site has appropriate facilities and written 
procedures to dispose of clinical materials. 
6.3. 
Assignment to Study Intervention  
For ISAs having multiple intervention groups and random assignment of participants to those 
groups, the randomization will be determined by a computer-generated random sequence using 
an IWRS. The randomization ratio and, if applicable, randomization stratification factors will be 
specified in the relevant ISA. 
6.4. 
Blinding  
Blinding will be maintained throughout the conduct of the study as described in the separate 
unblinding plan. 
Method of assignment to an ISA 
assignment to a particular ISA will not be blinded (Section 4.1). 

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Method of assignment to study intervention within an ISA 
Within an ISA, 
assignment to a particular study intervention will be determined 
by a computer-generated random sequence using an IWRS. Unless otherwise specified in the 
ISA, this assignment will be blinded to participants, to investigators and other site personnel, and 
to sponsor staff who are involved in the treatment or clinical evaluation of the participants. 
Emergency unblinding 
Emergency unblinding for AEs may be performed through the IWRS. This option may be used 
only 
-being requires knowledge 
intervention 
assignment. All actions resulting in an unblinding event are recorded and reported by the IWRS. 
T
intervention assignment is warranted. Participant safety must always be the first consideration in 
making such a determination. If the investigator decides that the unblinding is warranted, it is the 
responsibility of the investigator to promptly document the decision and rationale and notify the 
sponsor as soon as possible. 
intervention assignment is unblinded 
to the participant or to blinded site personnel who are performing assessments, including the 
investigator, the participant must be discontinued from study drug (Section 7.1.2). 
Additional measures to minimize bias 
Additional measures to minimize bias may be described in the ISAs. 
6.5. 
Study Intervention Compliance  
Deviations from the prescribed dosage regimen should be recorded in the CRF. The investigator 
should verify that participants have the ability to understand and comply with study instructions. 
Before enrolling a participant, the investigator is responsible for discussing with the participant 
methods to attain high compliance with study procedures, including administration of study 
intervention. 
If a participant is noncompliant with study procedures, with administration of study intervention, 
or both, the investigator should assess the participant for the cause of the noncompliance and to 
educate or manage the participant as appropriate to improve compliance. 
If, in consultation with the sponsor or its designee, the noncompliance is deemed to be 
significant or further noncompliance occurs, the participant may be permanently discontinued 
from study intervention or from the study (Sections 7.1 and 7.2). If there are additional measures 
to assure or assess compliance or adherence, these measures will be described in the ISAs. 
6.6. 
Dose Modification  
Dose modifications, if allowed, are described in the relevant ISA. 
6.7. 
Continued Access to Study Intervention after the End of the Study  
If any study interventions are available after the 
, those 
interventions will be described in the relevant ISA. 

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6.8. 
Treatment of Overdose  
See the relevant ISA. 
6.9. 
Prior and Concomitant Therapy  
Prior therapy 
Relevant prior therapies, as defined in the SoA (Section 1.3), are to be assessed and recorded 
according to the instructions of the CRF. 
Concomitant therapy 
Any vaccine, therapy, or medication, including over-the-counter medicines, prescription 
medicines, vitamins, and herbal supplements, that the participant receives during the study must 
be identified and at a minimum assessed and recorded at the visits specified in the SoA, along 
with 
 reason for their use 
 dates of administration, including start and end dates, and 
 dosage information for concomitant therapies of special interest, including rescue 
medication. 
e contacted if there are any questions 
regarding concomitant therapy. 
6.9.1. 
Rescue Medication  
See the relevant ISA. 
6.9.2. 
Permitted Concomitant Therapy  
See the relevant ISA. 
6.9.3. 
Prohibited Concomitant Therapy  
See the relevant ISA. 

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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal  
This section describes 
 
 temporary or permanent discontinuation of study intervention (Section 7.1), or 
 discontinuation (withdrawal) from the study (Section 7.2). 
Discontinuation of specific sites or the study as a whole is handled as part of Appendix 1, 
Section 10.1.9. 
7.1. 
Discontinuation of Study Intervention  
7.1.1. 
Temporary Discontinuation of Study Intervention  
A participant may need to have study drug temporarily interrupted (withheld) during the study. 
Except in an 
monitor 
 before temporarily interrupting study drug for reasons not specified in this protocol or the 
relevant ISA, and 
 before resuming interrupted study drug, unless otherwise specified in this protocol or the 
relevant ISA. 
This table lists some reasons for temporary interruption (withholding) of study drug and 
conditions necessary for resumption of study drug. 
Temporarily interrupt study drug if the participant...
Conditions for resuming study drug
has an AE or abnormal laboratory value which, in the 
opinion of the investigator, may have an unclear 
relationship to study drug 
ated 
medical monitor agree that resumption of study 
drug is appropriate for the participant
has neutropenia ANC <1.0 0.5 × 103/µL
ANC 1.0 × 103/µL
has hepatic events or liver test abnormalities as described 
in Section 7.1.1.1 
As described in Section 7.1.1.1, resumption of 
study drug can be considered only in consultation 
only if the liver test results return to baseline or 
near baseline values and if a self-limited nondrug 
etiology is identified
is a candidate for LTBI treatment and is treated for LTBI 
Withhold study drug for at least the first 4 wk of 
LTBI treatment. Study drug may be resumed 
 
after participant has received at least 4 wk of 
appropriate LTBI therapy as per WHO or 
US CDC guidelines, and 
 
if there is no evidence of hepatotoxicity 
other treatment intolerance. 
The participant must complete appropriate LTBI 
therapy to remain eligible to receive study drug

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Temporarily interrupt study drug if the participant...
Conditions for resuming study drug
has a serious or opportunistic infection, as defined in 
Section 5.2 (for LTBI, see preceding row) 
After resolution of all acute clinical signs and 
symptoms, and completion of all appropriate 
anti-infective treatment
has HBV DNA results that are reported as positive, or as 
detecting HBV DNA, but HBV DNA is below the level of 
medical monitor should be contacted regarding the 
soon as is feasible
Negative for HBV DNA. If HBV DNA is 
confirmed as positive, the participant must be 
permanently discontinued from study drug (see 
Section 7.1.2) 
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
CDC = Centers for Disease Control and Prevention; DNA = deoxyribonucleic acid; HBV = hepatitis B virus; 
LTBI = latent tuberculosis infection; ULN = upper limit of normal; US = United States; WHO = World Health 
Organization. 
7.1.1.1. 
Elevated Liver Test Results  
Interrupting study drug based on liver test elevations in participants with normal or 
near-normal baseline liver tests 
In study participants with normal or near-normal baseline liver tests (ALT, AST, ALP <1.5 times 
ULN), the study drug should be interrupted and close hepatic monitoring initiated (see 
Section 8.2.11) if 1 or more of these conditions occur: 
Elevation 
Exception
ALT or AST >8 times ULN
ALT or AST >5 times ULN for more than 2 wk
ALT or AST >3 times ULN and either TBL >2 times ULN or 
INR >1.5  
 
If baseline direct bilirubin is >0.5 mg/dL, 
then doubling of direct bilirubin should be 
used for drug interruption decisions rather 
than TBL >2 times ULN
ALT or AST >3 times ULN with the appearance of fatigue, 
nausea, vomiting, right upper quadrant pain or tenderness, fever, 
or rash
 
ALP >3 times ULN, when the source of increased ALP is the 
liver
 
ALP >2.5 times ULN and TBL >2 times ULN  
For participants with Gilbert
 
If baseline direct bilirubin is >0.5 mg/dL, 
then doubling of direct bilirubin should be 
used for drug interruption decisions rather 
than TBL>2 times ULN
ALP >2.5 times ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, or rash
 
Source: FDA 2009 and other consensus guidelines, with minor modifications.
 

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Interrupting study drug based on elevated liver tests in participants with abnormal 
baseline liver tests 
5 times ULN), the 
study drug should be interrupted if 1 or more of these conditions occur: 
Elevation 
Exception
ALT or AST >4 times baseline
ALT or AST >3 times baseline for more than 2 wk
ALT or AST >2 times baseline and either TBL >2 times ULN or 
INR >1.5  
 
If baseline direct bilirubin is >0.5 mg/dL, 
then doubling of direct bilirubin should be 
used for drug interruption decisions rather 
than TBL>2 times ULN
ALT or AST >2 times baseline with the appearance of fatigue, 
nausea, vomiting, right upper quadrant pain or tenderness, fever, 
or rash
 
ALP >2.5 times baseline, when the source of increased ALP is the 
liver
 
ALP >2 times baseline and TBL >2 times ULN  
 
If baseline direct bilirubin is >0.5 mg/dL, 
then doubling of direct bilirubin should be 
used for drug interruption decisions rather 
than TBL >2 times ULN
ALP >2 times baseline with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, or rash
 
Source: FDA 2009 and other consensus guidelines, with minor modifications.
 
Resuming study drug after elevated liver tests 
Resumption of the study drug can be considered only in consultation with the 
designated medical monitor and only if the liver test results return to baseline or near baseline 
values and if a self-limited nondrug etiology is identified. Otherwise, the study drug should be 
discontinued (Section 7.1.2). 
7.1.2. 
Permanent Discontinuation of Study Intervention  
When necessary, a participant may be permanently discontinued from study intervention. If so, 
the participant will discontinue the study intervention (treatment), thereby discontinuing the 
treatment period, and will remain in the study to complete procedures for 
 an ED visit, and 
 posttreatment follow-up visits, if applicable, as shown in the SoA of the relevant ISA. 
Possible reasons for permanent discontinuation of study drug include, but are not limited to, the 
reasons listed here: 
Participant decision: The participant asks to stop receiving study drug. 
Pregnancy: The participant becomes pregnant (Sections 8.2.7 and 8.3.2). 

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Hypersensitivity: The investigator determines that a systemic hypersensitivity reaction has 
occurred related to study drug administration. In this case, the participant may be 
permanently di
monitor should be notified. If the investigator is uncertain about whether a systemic 
hypersensitivity reaction has occurred and whether discontinuation of study intervention is 
w
ated medical monitor. 
Suicidal ideation and behavior: The participant 
 becomes actively suicidal, in the judgment of the investigator, or 
 
C-SSRS, or 
 
-related behaviors on the Suicidal Behavior portion of 
the C-SSRS. 
Note: A psychiatrist or appropriately trained professional may assist in the decision to 
discontinue the participant. 
Malignancy: The participant develops a malignancy (except for successfully treated basal or 
squamous cell skin carcinoma). 
HIV or AIDS: The participant develops HIV infection or AIDS. 
Active TB or untreated LTBI: The participant develops active TB or has untreated LTBI 
(Section 8.2.8). For temporary discontinuation of study drug while the participant is being 
treated for LTBI, see Section 7.1.1. 
HBV: The participant tests positive for HBV DNA (Section 8.2.9). 
Note: The HBV DNA result is to be confirmed if initial positive test result is positive but 
below the level of quantification (Section 7.1.1). Prior to discontinuation of any 
immunomodulatory and/or immunosuppressive therapy, including study drug, the 
participant is to be referred to, evaluated, and managed by a specialist physician with 
expertise in evaluation and management of viral hepatitis. The timing of discontinuation 
from study drug relative to the initiation of any antiviral treatment for hepatitis is to be 
based on the recommendation of the consulting specialist physician, in conjunction with 
the investigator, and aligned with medical guidelines and standard of care. 
HCV: The participant tests positive for HCV RNA (Section 8.2.10). 
Clinically significant ECG finding: Discontinuation of study drug may occur after consultation 
designated medical monitor (see Section 8.2.4). 
Liver test abnormality: Section 7.1.1.1 describes temporary interruption of study drug based on 
liver test abnormalities. If, after temporary interruption of study drug, liver test results fail to 
return to baseline or near baseline and a self-limited nondrug etiology is not identified, study 
drug is to be permanently discontinued. 
Abnormal hematology laboratory values: The participant has any of the following results on 
2 consecutive samples taken at least 48 hours, but no more than 1 week, apart: 
 hemoglobin <8.0 g/dL 

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 neutropenia  ANC <0.5 × 103/µL 
 lymphopenia  lymphocyte count <0.5 × 103/µL 
 thrombocytopenia  platelets <50.0 × 103/µL 
 eosinophil counts >5.0 × 103/µL with signs and/or symptoms of target organ involvement 
, and 
 eGFR <30 mL/min/1.73 m
2 (CKD-EPI Creatinine Equation [2021]) (FDA 2020; NKF 
[WWW]). 
For laboratory values that meet permanent discontinuation thresholds, study intervention should 
be discontinued. However, if, in the opinion of the investigator, the laboratory abnormality is due 
to intercurrent illness, laboratory tests may be repeated. When the laboratory value returns to 
baseline and the intercurrent illness or other identified factor has resolved, then the investigator 
may restart study intervention after consultation with the 
designated medical monitor. 
Other AEs or changes in laboratory values: The participant has an AE, an SAE, or a clinically 
significant change in a laboratory value that, in the opinion of the investigator, merits the 
permanent discontinuation of study drug and appropriate measures being taken. 
Noncompliance: The investigator decides the participant is noncompliant with study drug 
administration or any other study procedure. 
Unblinding: If an investigator, blinded site personnel, or blinded designees who are performing 
assessments, or the participant is unblinded to the partici
intervention assignment 
because of an emergency unblinding as described in Section 6.4, the participant must be 
permanently discontinued from study drug. In cases where there are ethical reasons for the 
participant to continue in the study and continue to receive study drug, the investigator must 
continue. 
7.2. 
Participant Discontinuation/Withdrawal from the Study  
Discontinuation (withdrawal) from the study is expected to be uncommon. 
A participant may withdraw from the study in these circumstances: 
 
 for any reason or without providing any 
reason 
 
, for example, parents or legal guardian 
 at the discretion of the investigator for safety, behavioral, compliance, or administrative 
reasons, or 
 if enrolled in any other clinical study involving an investigational product, or enrolled in 
any other type of medical research judged not to be scientifically or medically compatible 
with this study. 
Data collection and follow-up for participants who discontinue the study 
At the time of discontinuing from the study, if possible, the participant will complete procedures 
for an ED visit and posttreatment follow-up, as shown in the SoA of the relevant ISA. If the 

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participant has not already discontinued the study intervention, the participant will be 
permanently discontinued from the study intervention at the time of the decision to discontinue 
the study. 
Withdrawal of consent for disclosure 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, the participant may request destruction of any samples taken and not 
tested, and the investigator must document this in the site study records. 
7.3. 
Lost to Follow up  
A participant will be considered lost to follow-up if the participant repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel or designees are 
expected to make diligent attempts to contact participants who fail to return for a scheduled visit 
or were otherwise unable to be followed up by the site. 

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8. 
Study Assessments and Procedures  
Study procedures and their timing are summarized in the IMMB SoA (Section 1.3) and in the 
SoA of the relevant ISA. Adherence to the study design requirements, including those specified 
in the SoAs, 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 relevant ISA, all blinded assessments and sample collections 
should be completed before a dose is administered at the dosing visits. 
Patient-reported outcomes assessments should be completed prior to any clinician-administered 
assessments. 
If multiple safety assessments are scheduled to occur at the same visit, the preferred order of 
completion is 
1. ECGs and then vital signs 
2. other safety assessments, including physical examinations and nonleading 
(spontaneous) AE collection, followed by C-SSRS, if the C-SSRS is applicable 
(Sections 8.2.12 and 8.3.1.1), and finally 
3. sample collections for clinical safety laboratory testing, PK, immunogenicity, 
biomarkers, and other sample testing specified in the applicable SoA. 
8.1. 
Efficacy Assessments  
Efficacy-related assessments occur at visits specified in the IMMB SoA (Section 1.3) and in the 
relevant ISA. 
Efficacy endpoints 
Efficacy endpoints are described in the relevant ISA. 
Participant diary 
The diary contains the following assessments: 
 Itch NRS 
 ADSS, and 
 Skin Pain NRS. 
Descriptions of efficacy-related assessments 
See Appendix 6, Section 10.6, for descriptions of efficacy-related assessments, including 
assessments of 
 disease activity 
 patient-reported outcomes, and 
 quality of life. 

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8.2. 
Safety Assessments  
Visits and order of safety assessments 
Safety assessments occur at visits specified in the IMMB SoA (Section 1.3) and in the relevant 
ISA. 
Safety monitoring 
The investigator will monitor the participant safety data throughout the study. Immediate safety 
concerns should be discussed with the sponsor immediately upon occurrence or awareness to 
determine if the participant should continue or discontinue the study intervention. 
The sponsor will monitor the trial safety data, including AEs, SAEs, discontinuations, vital signs, 
and clinical laboratory results by means of periodic blinded reviews and other appropriate 
methods. These methods include reviews by a functionally independent safety physician and/or 
clinical research scientist who regularly reviews SAE reports in real time and across studies, and 
who reviews applicable clinical safety and epidemiological publications from the literature. If 
this safety monitoring uncovers an issue that needs to be addressed by unblinding at the 
individual or group level, the IAC can conduct additional analyses of the safety data. The IAC is 
an advisory group for this study formed to protect the integrity of the study in unblinded safety 
data reviews. See Appendix 1, Section 10.1.5. 
Safety data collection and reporting 
The AE data collection and reporting requirements are described in Section 8.3 and Appendix 3, 
Section 10.3. 
For some interventions studied under this master protocol, there may be predefined AESIs. If so, 
any additional sample or data collections for AESIs will be specified in the relevant ISAs. 
Appropriateness of safety assessments 
The safety assessments used in this study are routine elements of clinical health assessment and 
Phase 2 drug development. 
Safety assessments described in this master protocol and in ISAs 
The following sections describe safety assessments applicable to all ISAs. See the relevant ISAs 
for any additional safety assessments that may be applicable. 
8.2.1. 
Vital Signs  
Vital signs, including pulse rate, blood pressure, respiratory rate, and body temperature, will be 
measured as specified in the IMMB SoA (Section 1.3) and in the relevant ISA, and as well as 
whenever clinically indicated. Additional vital signs may be measured whenever warranted, as 
determined by the investigator. 
Timing of collection of vital signs 
Vital signs should be measured after the participant has been sitting for at least 5 minutes. When 
possible, measurements of blood pressure and pulse rate should be performed at approximately 
the same time of day at each scheduled time point. See the relevant ISA for additional timings, if 
any. 

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Unscheduled orthostatic vital signs 
Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of dizziness or 
posture-induced symptoms. If the participant feels unable to stand, sitting or supine vital signs 
will be recorded. See the relevant ISA for any additional orthostatic vital signs requirements. 
8.2.2. 
Physical Examinations  
Complete physical examinations and symptom-directed physical examinations will be conducted 
as specified in the IMMB SoA (Section 1.3) and in the relevant ISA. 
Symptom-directed physical assessments may also be conducted at other visits, as specified in the 
ISA and as determined by the investigator, if a participant presents with complaints or as needed 
based on participant status and local standard of care. 
TB assessments 
At screening and approximately every 3 to 4 months thereafter, the specified physical evaluation, 
whether complete or symptom-directed, will include a documented assessment of TB risk factors 
and symptoms or signs of active TB, including an assessment of peripheral lymph nodes and 
body temperature (see Section 8.2.8). 
Complete physical examination 
The complete physical examination should include the following regions and body systems: 
 general appearance 
 skin 
 head, ears, eyes, nose, and throat 
 lymph nodes 
 cardiovascular 
 respiratory 
 abdominal 
 genitourinary (only as clinically indicated) 
 extremities, and 
 neurologic. 
Pelvic, rectal, and breast examinations are not required unless clinically indicated. 
Symptom-directed physical assessments 
After screening, physical assessments should include 
 a symptom-directed evaluation 
 evaluation of eyes, heart, lungs, and abdomen 
 visual evaluation of the skin, other than area covered by clothing or other 
material, and 
 examination for signs of active TB, including assessment of peripheral lymph 
nodes. 

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Height and weight 
Height and weight will be measured and recorded as specified in the IMMB SoA (Section 1.3) 
and, if applicable, in the relevant ISA. 
8.2.3. 
Skin Assessment with Fitzpatrick Scale of Skin Phototypes  
The skin type of each participant will be assessed using the Fitzpatrick Scale of Skin Phototypes, 
as specified in the relevant ISA. 
exposure and baseline skin pigmentation. Modern Fitzpatrick skin phototypes range from I to VI, 
with a score of I indicating white skin tone, always burns, and does not tan, and a score of VI 
indicating skin color black, never burns, and tans very easily (High et al. 2012). Investigators 
will follow the descriptive terms included in the scale when recording the Fitzpatrick skin 
phototype. Both sun sensitivity and skin tone must be evaluated for this study. Whichever value 
is higher is the Fitzpatrick scale score for each individual participant. 
8.2.4. 
Electrocardiograms  
A single, local 12-lead ECG will be collected for each participant as specified in the IMMB SoA 
(Section 1.3). ECGs may also be collected at visits specified in the relevant ISA and at additional 
visits or time points when deemed clinically necessary. 
Timing of collection of ECGs 
The ECGs should be collected before any blood or tissue samples are collected. Participants 
must be supine for at least approximately 5 to 10 minutes before ECG collection and remain 
supine, but awake, during ECG collection. 
Electrocardiograms may be obtained at additional times, when deemed clinically necessary. 
Interpretation of collected ECGs 
ECGs will be interpreted by a qualified physician (the investigator or a qualified designee) at the 
site as soon after the time of ECG collection as possible, and ideally while the participant is still 
present, to determine whether the participant meets the study entry criteria and for immediate 
participant management, should any clinically relevant finding be identified. 
Actions to be taken after a clinically significant finding on an ECG 
Any new clinically relevant finding should be reported as an AE (Section 8.3). 
If a clinically significant finding is identified (including, but not limited to changes from baseline 
in QT/QTc interval) after enrollment, the investigator or qualified designee, in conjunction with 
designated medical monitor, will determine if the participant can continue on study 
intervention and if any change in participant management is needed (Section 7.1.2). 
Documentation of review of ECGs 
The review of the ECG printed at the time of collection must be documented. All ECGs recorded 
should be stored at the investigational site. 

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8.2.5. 
Chest Imaging  
A high-quality, locally performed chest x-ray (posterior anterior view and, if needed, a lateral 
view), interpreted and reported by a radiologist or pulmonologist, will be obtained as specified in 
the IMMB SoA (Section 1.3) and, if applicable, in the relevant ISA. 
For each participant, the chest x-ray films, images, or a radiology report must be available to the 
investigator for review before the participant is randomized to a treatment in an ISA. 
Conditions for using a previous chest x-ray at screening 
Participants do not need to have a chest x-ray at screening if, in the opinion of the investigator, 
both of these conditions are met and, in the opinion of the investigator, there is no clinical 
indication for a repeated chest x-ray: 
 the chest x-ray was performed within 90 days before starting the initial screening 
period of this master protocol (Visit 401), and 
 documentation of that chest x-ray, read by a qualified radiologist or 
pulmonologist, is sufficient for TB evaluation according to local standard of care. 
Note: In some jurisdictions, the interval between x-rays must be greater than 90 days. 
If so, a chest x-ray performed within 6 months before Visit 401 can be used. 
Alternatives to chest x-ray 
designated medical monitor, results of a chest CT scan or 
other imaging study similar to a chest x-ray, if performed within the same time window, may be 
used instead of a chest x-ray for the TB evaluation. 
8.2.6. 
Clinical Safety Laboratory Tests  
In this master protocol, Appendix 2 (Section 10.2) and the SoA (Section 1.3) provide a list of 
clinical laboratory tests to be performed during the screening period of this master protocol. See 
the relevant ISA for clinical laboratory tests to be performed during the study periods of an ISA. 
All protocol-required laboratory assessments, as defined in the ISAs and in this master protocol, 
must be conducted in accordance with the SoAs, standard collection requirements, and the 
laboratory manuals. 
If laboratory values from non-protocol-specified laboratory assessments performed at an 
investigator-designated local laboratory require a change in participant management or are 
considered clinically significant by the investigator, for example, SAE or AE or dose 
modification, then report the information as an AE. 
Reviewing and recording test results 
The investigator must review the laboratory results, document this review, and report any 
clinically relevant changes occurring during the study as an AE. The laboratory results must be 
retained with source documents unless a Source Document Agreement or comparable document 
cites an electronic location that accommodates the expected retention duration. 
 

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Duration of validity of screening tests 
Results of screening laboratory tests are valid for 60 days during the screening period. If a 
participant is still in screening after 60 days, the screening laboratory tests should be repeated. 
Repeating screening laboratory tests does not by itself constitute rescreening (Section 5.4.3). 
Additional information 
See the relevant ISA for instructions about 
 repeat testing after a clinically significant abnormal finding 
 fasting visits 
 laboratory samples to be collected after a systemic hypersensitivity event, and 
 allowance for additional laboratory testing. 
8.2.7. 
Pregnancy Testing  
Pregnancy testing is to be performed for WOCBP, as defined in Appendix 5, Section 10.5. 
Pregnancy testing at Visit 401 
Serum pregnancy testing will be performed centrally during the screening period of this master 
protocol (Section 1.3 and Appendix 2, Section 10.2). 
Pregnancy testing after Visit 401 
Urine pregnancy testing after Visit 401 will be performed locally according to the SoA of the 
relevant ISA. If the specified visit includes administration of study intervention, the pregnancy 
 hours before the study intervention is administered. 
If a urine pregnancy test is not available, a local serum pregnancy test is an acceptable 
alternative. 
If a urine pregnancy test is inconclusive at any visit, an additional serum pregnancy test should 
be performed. 
Pregnancy testing at any time during the study 
Additional pregnancy testing may be performed at any time in the study, at the discretion of the 
investigator, if the particip
pregnancy, or as required by local law or regulation. 
Discontinuation of participants who are pregnant 
Participants who are pregnant will be permanently discontinued from the study intervention 
(Section 7.1.2). 
8.2.7.1. 
Optional FSH Testing  
A 
measured centrally at the discretion of the investigator at the 
Visit 401 screening (Section 1.3 and Appendix 2, Section 10.2). The FSH level can also be 
measured locally after screening at the discretion of the investigator. The purpose of this optional 
FSH testing is to assist the investigator in determining whether a participant can be considered 
postmenopausal  for the purposes of pregnancy testing and contraception requirements. 

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8.2.8. 
Tuberculosis Testing and Monitoring  
Screening 
During the screening period of this master protocol, all participants are to be assessed for risk 
factors, symptoms, and signs of TB with all of the following: 
 thorough history to determine the lifetime risk factors for TB infection, for TB 
progression, and for symptoms and/or signs of active TB, and 
 signs of previous or active TB by means of 
 thorough physical examination for signs of active TB, including measurement 
of body temperature (Section 8.2.1) and assessment of peripheral lymph nodes 
(Section 8.2.2), and 
 a high-quality chest x-ray (posterior anterior view, including a lateral view if 
needed) interpreted and reported by a radiologist or pulmonologist (Section 
8.2.5 ). 
All participants with no history of LTBI or active TB, and no history of positive Mantoux TST 
using PPD or positive Mycobacterium tuberculosis IGRA must have 1 of the following tests: 
 PPD TST, or 
 IGRA for M tuberculosis. 
For details about these tests, see Appendix 7, Section 10.7. 
Diagnosed LTBI 
Participants diagnosed with LTBI are excluded (Section 5.2) unless they are candidates for LTBI 
treatment, are treated for LTBI, and the following criteria are met: 
 After receiving at least 4 weeks of appropriate LTBI therapy, as per WHO or the 
United States CDC guidelines, there is no evidence of hepatotoxicity (ALT/AST 
participant may be rescreened (Section 5.4.1) and is not excluded due to LTBI. 
 The participant must continue and complete appropriate LTBI therapy to remain 
eligible to continue to receive study intervention (Sections 7.1.1 and 7.1.2). 
Monitoring during the study 
For all participants, monitoring for TB is to be continuous throughout the study. At a minimum, 
each participant is to have the following documented approximately every 3 to 4 months: 
 Thorough history to determine any risk factors for TB infection and for TB 
progression, symptoms or signs of active TB (Section 8.2.2), and 
 Thorough physical examination for signs of active TB, including measurement of 
body temperature (Section 8.2.1) and assessment of peripheral lymph nodes 
(Section 8.2.2). 

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8.2.9. 
Hepatitis B Testing and Monitoring  
As specified in the IMMB SoA (Section 1.3), initial testing for HBV infection includes HBsAg 
and anti-HBc. 
 If HBsAg is positive, the participant is excluded. 
 If HBsAg is negative and anti-HBc is negative, the participant is not excluded. 
 If HBsAg is negative and anti-HBc is positive, further testing for HBV DNA is 
required: 
 If the screening HBV DNA is positive, the participant is excluded. 
 If the screening HBV DNA is negative, the participant is not excluded. Repeat 
testing for HBV DNA is required at least approximately every 3 to 4 months 
during the study, as specified in the relevant ISA. 
Management of enrolled participants with detectable HBV DNA during the study 
If HBV DNA is detected, study intervention will be temporarily withheld or permanently 
discontinued, as described in Sections 7.1.1 and 7.1.2, and the participant should receive 
appropriate follow-up medical care. 
8.2.10. 
Hepatitis C Testing  
As specified in the IMMB SoA (Section 1.3), initial testing for HCV infection includes testing 
for anti-HCV. 
 If anti-HCV is positive, a test for circulating HCV RNA is required. 
 If HCV RNA test is negative, the participant is not excluded. 
 If HCV RNA test is positive, the participant is excluded (Section 5.2). 
Participants who have had HCV infection and have been successfully treated, defined as a 
sustained virologic response (HCV RNA by PCR negative for at least 24 weeks following 
treatment completion) are not excluded on the basis of HCV as long as HCV RNA test is 
negative at screening. 
If HCV RNA is detected during the study, the study intervention will be discontinued, as 
described in Section 7.1.2, and the participant should receive appropriate follow-up medical care. 
 
 

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8.2.11. 
Hepatic Safety Testing and Monitoring  
Close hepatic monitoring 
Laboratory tests (Appendix 9, Section 10.9), including ALT, AST, ALP, TBL, direct bilirubin, 
gamma-glutamyl transferase, and creatine kinase, should be repeated within 48 to 72 hours to 
confirm the abnormality and to determine if it is increasing or decreasing, if 1 or more of these 
conditions occur: 
If a participant with baseline results 
of... 
develops the following elevations: 
ALT or AST <1.5 times ULN 
times ULN
ALP <1.5 times ULN 
2 times ULN
TBL <1.5 times ULN 
2 times ULN,
5 times ULN
2 times baseline
5 times ULN 
2 times baseline
5 times ULN 
5 times baseline, 
syndrome
If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for 
possible causes of abnormal liver tests should be initiated by the investigator in consultation with 
the 
designated medical monitor. At a minimum, this evaluation should include 
physical examination and a thorough medical history, including symptoms, recent illnesses (for 
example, heart failure, systemic infection, hypotension, or seizures), recent travel, a history of 
concomitant medications (including over-the-counter), herbal and dietary supplements, a history 
of alcohol drinking, and other substance abuse. 
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
oratory results stabilize. Monitoring of ALT, AST, ALP, 
and TBL should continue until levels normalize or return to approximate baseline levels. 
Comprehensive hepatic evaluation 
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
1 or more of these conditions occur: 
If a participant with baseline results of...  develops the following elevations: 
ALT or AST <1.5 times ULN 
3 times ULN with hepatic signs/symptomsa, or 
5 times ULN
ALP <1.5 times ULN 
3 times ULN
TBL <1.5 times ULN 
times ULN,
5 times ULN 
2 times baseline with hepatic signs/symptomsa, or 
3 times baseline
5 times ULN 
times baseline
5 times ULN 
2 times baseline,
a Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, or rash. 

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At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for PT-INR; tests for viral hepatitis A, B, C, or E; tests 
for autoimmune hepatitis; and an abdominal imaging study, for example, ultrasound or CT scan. 
 history and initial results, further testing should be considered in 
consultation with the 
designated medical monitor, including tests for hepatitis D virus, 
cytomegalovirus, Epstein-Barr virus, acetaminophen levels, acetaminophen protein adducts, 
ider referring the participant for a 
hepatologist or gastroenterologist consultation, magnetic resonance cholangiopancreatography, 
endoscopic retrograde cholangiopancreatography, cardiac echocardiogram, or a liver biopsy. 
8.2.11.1. Additional Hepatic Data Collection (Hepatic Safety CRF) in Study Participants 
Who Have Abnormal Liver Tests during the Study  
Additional hepatic safety data collection in hepatic safety CRFs should be performed in study 
participants who meet 1 or more of the following 5 conditions: 
 e
 times ULN on 2 or more consecutive blood tests, if 
baseline ALT <1.5 times ULN 
 
5 times ULN, t
3 
times baseline on 2 or more consecutive tests 
 e
2 times ULN, if baseline TBL <1.5 times ULN (except for 
 
 
5 times ULN, the threshold should be 
TBL 2 times baseline 
 e
 times ULN on 2 or more consecutive blood tests, if 
baseline ALP <1.5 times ULN 
 
5 times 
 
times baseline on 2 or more consecutive blood tests 
 hepatic event considered to be an SAE, and 
 discontinuation of study drug due to a hepatic event. 
Note: The interval between the 2 consecutive blood tests should be at least 2 days. 
8.2.12. 
Suicidal Ideation and Behavior Risk Screening and Monitoring  
Screening for suicidal ideation or behavior 
As specified in the IMMB SoA (Section 1.3), screening for suicidal ideation or behavior includes 
the C-SSRS. 

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Monitoring for suicidal ideation and behavior and depressive symptomatology 
Throughout the study, participants should be monitored appropriately and observed closely for 
suicidal ideation and behavior or any other unusual changes in behavior, especially at the 
beginning and end of the course of study intervention. 
During the treatment and posttreatment periods of the ISAs, suicidal ideation and behavior and 
depressive symptomatology may be assessed; see the relevant ISA for details. 
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). 
8.2.12.1. Columbia-Suicide Severity Rating Scale (C-SSRS)  
The C-SSRS is a scale that captures the occurrence, severity, and frequency of suicidal ideation 
and behavior during the assessment period via a questionnaire. The scale was developed by the 
National Institute of Mental Health trial group for the purpose of being counterpart to the 
Columbia Classification Algorithm of Suicide Assessment categorization of suicidal events. For 
this study, the C-SSRS is adapted for the assessment of the ideation and behavior categories 
only. The Intensity of Ideation and Lethality of Behavior sections are removed. 
See Section 8.3.1.1 for the collection of the C-SSRS relative to nonleading (spontaneous) AE 
collection. 
8.2.13. 
Systemic Hypersensitivity Reactions  
Many drugs, including oral agents and biologic agents, carry the risk of systemic hypersensitivity 
reactions. If such a reaction occurs, additional data should be provided to the sponsor in the 
designated CRFs. 
Sites should have appropriately trained medical staff and appropriate medical equipment 
available when study participants are receiving study intervention. It is recommended that 
participants who experience a systemic hypersensitivity reaction be treated per national and 
international guidelines. 
In the case of a suspected systemic hypersensitivity event, additional blood samples should be 
collected as described in the relevant ISA. Laboratory results are provided to the sponsor via the 
central laboratory. 
8.2.14. 
Additional Safety Data and Sample Collections  
For some interventions, some additional data or sample collections may be necessary for the 
assessment of safety. See the relevant ISA for any additional instructions. 

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8.3. 
Adverse Events, Serious Adverse Events, and Product Complaints  
The definitions of the following events can be found in Appendix 3, Section 10.3: 
 AEs 
 SAEs, and 
 PCs. 
These events will be reported by the participant (or, when appropriate, by a caregiver or 
 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet these definitions and remain responsible for following up events that 
are serious, considered related to the study intervention or study procedures, or that caused the 
participant to discontinue the study intervention or the study (see Section 7). 
Care will be taken not to introduce bias when detecting events. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about event occurrences. 
After the initial report, the investigator is required to proactively follow each participant at 
subsequent visits or contacts. All SAEs and, if applicable, all AESIs as defined in the ISAs, will 
be followed until resolution, stabilization, the event is otherwise explained, or the participant is 
lost to follow-up (as defined in Section 7.3). For PCs, the investigator is responsible for ensuring 
that follow-up includes any supplemental investigations as indicated to elucidate the nature or 
causality, or both. Further information on follow-up procedures is provided in Appendix 3, 
Section 10.3. 
8.3.1. 
Timing and Mechanism for Collecting Events  
This table describes the timing, deadlines, and mechanism for collecting events. 
Event 
Collection 
Start 
Collection Stop 
Timing for 
Reporting to 
Sponsor or 
Designee 
Mechanism 
for 
Reporting 
Back-up 
Method of 
Reporting 
Adverse Event 
AE 
Signing of 
the ICF 
Participation in 
study has ended 
As soon as 
possible upon 
site awareness 
AE CRF 
N/A 
Serious Adverse Event 
SAE and SAE updates  
prior to start of study 
intervention and deemed 
reasonably possibly 
related to study 
procedures 
Signing of 
the ICF 
Start of 
intervention 
Within 24 hr of 
awareness 
SAE CRF 
SAE paper 
form 

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Event 
Collection 
Start 
Collection Stop 
Timing for 
Reporting to 
Sponsor or 
Designee 
Mechanism 
for 
Reporting 
Back-up 
Method of 
Reporting 
SAE and SAE updates  
after start of study 
intervention 
Start of 
intervention 
Participation in 
study has ended 
Within 24 hr of 
awareness 
SAE CRF 
SAE paper 
form 
SAEa  
study participation has 
ended and the investigator 
becomes aware 
After 
study 
participation 
has ended 
N/A 
Promptly 
SAE paper 
form 
N/A 
Pregnancy 
Pregnancy in female 
participants and female 
partners of male 
participants 
After the 
start of study 
intervention 
End of period 
equal to at least 
5 terminal 
half-lives after 
last dose of 
study 
intervention; 
consult the IB or 
medical monitor 
Within 24 hr 
(see Section 
8.3.2) 
Pregnancy 
paper form 
Pregnancy 
paper form 
Product Complaints 
PC associated with an 
SAE or might have led to 
an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 24 hr of 
awareness 
PC form 
N/A 
PC not associated with an 
SAE 
Start of study 
intervention 
End of study 
intervention 
Within 1 
business day of 
awareness 
PC form 
N/A 
Updated PC information 
 
 
As soon as 
possible upon 
site awareness 
Originally 
completed 
PC form 
with all 
changes 
signed and 
dated by the 
investigator 
N/A 

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Event 
Collection 
Start 
Collection Stop 
Timing for 
Reporting to 
Sponsor or 
Designee 
Mechanism 
for 
Reporting 
Back-up 
Method of 
Reporting 
PC (if investigator 
becomes aware) 
Participation 
in study has 
ended 
N/A 
Promptly 
PC form 
 
Abbreviations: AE = adverse event; CRF = case report form; IB = 
; ICF = informed consent 
form; N/A = not applicable; PC = product complaint; SAE = serious adverse event. 
a These SAEs should not be reported unless the investigator deems them to be possibly related to study treatment or 
study participation. 
8.3.1.1. 
Adverse Event Monitoring with a Systematic Questionnaire  
Nonleading (spontaneous) AE collection should occur before the collection of the C-SSRS. 
If a suicide-related event is discovered during the C-SSRS collection but was not captured during 
the nonleading AE collection, sites should not change the AE form. 
However, if an AE is serious or leads to discontinuation, the AE should be included on the AE 
form, and the process for reporting SAEs should be followed. 
8.3.2. 
Pregnancy  
Collection of pregnancy information 
Male participants with partners who become pregnant 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive study intervention. 
After learning of a pregnancy in the female partner of a study participant, the investigator  
 will obtain a consent to release information from the pregnant female partner 
directly, and 
 within 24 hours after obtaining this consent will record pregnancy information on 
the appropriate form and submit it to the sponsor. 
The female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the sponsor. Generally, the follow-up 
will be no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of gestational age, fetal status (presence or absence of 
anomalies), or indication for the procedure. 
Female participants who become pregnant 
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information will be recorded on the 

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appropriate form and submitted to the sponsor within 24 hours 
pregnancy. 
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate, and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, regardless of 
gestational age, fetal status (presence or absence of anomalies), or indication for the procedure. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
weeks gestational age) is always considered to be an SAE and will be reported as such. 
Any post-study pregnancy-related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the sponsor as described in Section 8.3.1. While the 
investigator is not obligated to actively seek this information in former study participants, the 
investigator may learn of an SAE through spontaneous reporting. 
Any female participant who becomes pregnant while participating in the study will permanently 
discontinue study intervention (Section 7.1.2). When discontinued, the participant will follow the 
standard discontinuation process and continue directly to the posttreatment follow-up phase. The 
follow-up on the pregnancy outcome should continue independent of intervention or study 
discontinuation. 
8.3.3. Adverse Events of Special Interest  
See the relevant ISA for 
 a list of intervention-specific AESIs, if any, and 
 additional actions to take, if any, when a listed AESI occurs. 
8.4. 
Pharmacokinetics  
If specified in the relevant ISA, blood samples will be collected for the purpose of determining 
the plasma or serum concentrations of the study intervention. 
Collection visits and times 
The visits and times for collecting PK samples will be specified in the relevant ISA, if 
applicable. The actual date and time (24-hour clock time) of dosing and PK sample collections 
must be recorded accurately on the appropriate forms. See the ISA for instructions about when to 
record the date and time of dosing relative to PK sample collections. 
Handling and analysis of samples 
Instructions for the collection and handling of blood samples will be provided by the sponsor. 
Samples will be analyzed at a laboratory approved by the sponsor. Concentrations of the study 
intervention will be assayed using a validated PK assay. 

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Additional and excess samples 
A maximum of 3 extra samples may be collected at additional time points during 
treatment and posttreatment follow-up periods, if the collection of additional samples is 
warranted and agreed upon between both the investigator and sponsor. 
In the case of systemic hypersensitivity reactions, additional blood samples may be obtained for 
PK analyses (see Section 8.2.13 and the relevant ISA). 
All unused excess samples collected for PK testing may be used for exploratory analyses such as 
 bioanalytical methods development 
 assay validation or cross-validation exercises 
 protein binding 
 additional biomarker analysis, and/or 
 metabolism work. 
Blinding 
Drug concentration information that may unblind the study will not be reported to investigative 
sites or to personnel who are blinded to study data. 
Sample retention 
The purpose of retention and maximum duration of retention for long-term storage of samples is 
described in Appendix 1, Section 10.1.12. 
8.5. 
Pharmacodynamics  
If specified in the relevant ISA, blood samples will be collected for the purpose of determining 
PD, and the visits and times for collecting these samples will be specified in the relevant ISA, if 
applicable. See the ISA for statements about sample use, if PD samples are collected. The 
duration of sample retention is specified in Appendix 1, Section 10.1.12. 
Any PD results which could unblind the study will not be reported to investigative sites or to 
personnel who are blinded to study data. 
8.6. 
Genetics  
Where local regulations and the IRB or IEC allow, a whole blood sample will be collected from 
consenting participants for pharmacogenetic/DNA analysis. This sample collection may occur at 
the randomization visit or at any later visit, as specified in the SoA of the relevant ISA. 
Sample use 
Samples may be used for research related to the study intervention and its mechanism of action, 
the drug target, genetic variants thought to play a role in AD, on the disease process and 
pathways associated with the disease or related diseases. The samples may also be used to 
develop tests or diagnostic tools or assays related to AD or to the study intervention. The 
samples may also be used to investigate variable exposure or response to study intervention. The 
assessment of variable response may include evaluation of AEs or differences in efficacy. 
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future. Genetic 
the study 

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intervention (as specified in the individual ISA), susceptibility to, and severity and progression 
of disease. Variable response to study intervention may be due to 
 genetic determinants that impact drug absorption, distribution, metabolism, and 
excretion 
 mechanism of action of the drug 
 disease etiology, and/or 
 molecular subtype of the disease being treated. 
Molecular technologies are expected to improve during the storage period and therefore cannot 
be specifically named. However, existing genetic research approaches include whole genome or 
exome sequencing, genome-wide association studies, and candidate gene studies. Regardless of 
technology utilized, genotyping data generated will be used only for the specific research scope 
described in this protocol. The samples may be analyzed as part of a single or multi-study 
assessment of genetic factors involved in the response to the study intervention or to other 
molecules in the same class to improve understanding of the disease or related conditions, and 
additional analyses may be conducted if necessary to further understand the clinical data of this 
study. The results of genetic analyses may be reported in a CSR or in a separate study summary. 
Sample confidentiality 
All samples will be coded with the participant number. These samples and any data generated 
can be linked back to the participant only by the investigative site personnel. The sponsor will 
store the blood and/or DNA samples in a secure storage space with adequate measures to protect 
confidentiality. 
Sample retention 
Samples will be retained at a facility selected by the sponsor or its designee. Samples will be 
retained while research on the study indication, study intervention, or the class of study 
intervention continues, but no longer than the maximum retention time specified in Appendix 1, 
Section 10.1.12. 
8.7. 
Exploratory Biomarkers  
If specified in the relevant ISA, samples will be collected for exploratory non-pharmacogenetic 
biomarker research. 
Collection visits and times 
The visits and times for collecting samples for non-pharmacogenetic biomarker research will be 
specified in the relevant ISA, if applicable. 
Sample use 
Samples may be used for research on the 
 drug target 
 disease state 
 variable response to treatment with the study intervention, as specified in the individual 
ISA 
 pathways associated with AD 

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 mechanism of action of the study intervention, and/or 
 development and/or validation of diagnostic tools or assays related to AD or the study 
intervention. 
Sample confidentiality 
All samples will be coded with the participant number. These samples and any data generated 
can be linked back to the participant only by the investigative site personnel. 
Sample retention 
Samples will be retained at a facility selected by the sponsor or its designee. Samples will be 
retained while research on the study indication, study intervention, or the class of study 
intervention continues, but no longer than the maximum retention time specified in Appendix 1, 
Section 10.1.12. 
8.8. 
Immunogenicity Assessments  
Immunogenicity may be evaluated in an ISA. Information on immunogenicity sample collection 
and assessment will be described in the ISA, as applicable. See Appendix 1, Section 10.1.12 for 
details on sample retention. 
If specified in the relevant ISA, 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 will be specified in the relevant ISA, 
if applicable. The actual date and time (24-hour clock time) of each sample collection will be 
recorded. 
To aid interpretation of these results, a predose blood sample for PK analysis will be collected at 
time points after baseline. 
Handling and analysis of samples 
Instructions for the collection and handling of blood samples will be provided by the sponsor. 
Immunogenicity will be assessed by a validated assay designed to detect ADAs in the presence 
of the study intervention at a laboratory approved by the sponsor. If applicable, antibodies may 
be further characterized for cross-reactive binding, as well as their ability to neutralize the 
activity of the study intervention and/or a relevant native cytokine. 
Additional samples 
If specified in the ISA, when the immunogenicity sample at the last scheduled assessment or 
discontinuation visit is TE ADA positive and, if applicable, the ADA cross-reactively bind an 
endogenous counterpart, then additional samples may be taken every 3 months for up to 1 year 
from last dose or until the ADA signal returns to baseline (that is, no longer TE ADA positive), 
whichever is less. 
In the case of systemic hypersensitivity reactions, additional blood samples may be obtained for 
ADA analyses (see Section 8.2.13 and the relevant ISA). 

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Sample retention 
Samples will be retained at a facility selected by the sponsor or its designee. Samples will be 
retained while research on the study indication, study intervention, or the class of study 
intervention continues, but no longer than the maximum retention time specified in Appendix 1, 
Section 10.1.12. 
8.9. 
Medical Resource Utilization and Health Economics  
See the relevant ISA. 

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9. 
Statistical Considerations  
The SAP for this master protocol (MP-SAP) will be finalized prior to the first unblinding. The 
SAP will include a more technical and detailed description of the statistical analyses described in 
this section. This section is a summary of key aspects of the planned analyses. 
9.1. 
Statistical Hypotheses  
For each ISA of this master protocol, the primary null hypothesis is that there is no difference 
between the intervention and the control on the primary endpoint. Intervention-specific details 
regarding hypotheses and statistical testing are in its respective ISA. 
9.1.1. 
Multiplicity Adjustment  
No adjustments for multiplicity will be performed. 
9.2. 
Analyses Sets  
This table describes analysis sets defined for all ISAs unless otherwise specified in the ISA: 
Participant Analysis Set
Description 
Used to Analyze Endpoints 
Related to...
Modified intent-to-treat 
(mITT) 
All randomized participants receiving at least 1 
dose of study intervention. Participants will be 
included in the analysis set according to their 
randomly assigned intervention.
 
efficacy objectives, and 
 
patient-reported outcomes, 
if applicable 
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.
 
safety 
Pharmacokinetics (PK) 
All randomized participants receiving at least 1 
dose of study intervention and have PK data 
available.
 
PK 
Additional intervention-specific analyses sets may be described in respective ISAs. 

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9.3. 
Statistical Analyses  
9.3.1. General Considerations  
Statistical analysis of this study will be the responsibility of Eli Lilly and Company or its 
designee. 
Unless otherwise indicated in ISA-specific analyses, the following general considerations apply 
to the analyses: 
 Primary and secondary endpoint analyses will be tested at a 2-sided  level of 0.05 for 
frequentist analyses and a probability threshold of 97.5% for Bayesian Analyses. 
 Baseline values will be defined as the last available value before the first dose of study 
intervention. 
 Efficacy and PRO analysis models may contain independent variables. These variables 
may include, but are not limited to, treatment group, baseline disease activity, and 
geographic region. 
 Estimands and the corresponding imputation methods will be specified in the ISAs. 
Changes to the data analysis methods 
An ISA can change any data analysis method described in this master protocol without 
necessitating an amendment to this master protocol. Any change to the data analysis methods 
described in this master protocol and not further clarified in the ISA will require an amendment 
to this master protocol only if (a) the change affects a principal feature of the protocol, and (b) 
the ISA(s) are not amended to clarify the change. Any other change to the data analysis methods 
described in the protocol and the justification for making the change will be described in the 

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CSR. Additional exploratory analyses of the data will be conducted as deemed appropriate. 
Complete details of the planned analyses will be documented in the MP-SAP and ISA-SAP. 
Handling of missing, unused, and spurious data 
Handling of missing, unused, and spurious data are addressed prospectively in the overall 
statistical methods described in the protocol and in the SAP, where appropriate. Adjustments to 
the planned analyses are described in the final CSR. 
9.3.2. 
Primary Endpoint/Estimand Analysis  
See the relevant ISA. 
9.3.3. 
Secondary Endpoints/Estimands Analysis  
See the relevant ISA. 
9.3.4. 
Exploratory Endpoints Analysis  
See the relevant ISA. 
9.3.5. 
Safety Analyses  
Safety analyses will include, but not be limited to, evaluation of all reported AEs, AESIs, C-
SSRS, ECGs, vital signs, and laboratory analytes. Unless otherwise specified in the ISA, safety 
analyses will compare the intervention to all available control data at time of analysis. Exposure 
to each study intervention will be calculated for each participant and summarized by treatment 
group for each ISA. Categorical safety measures will be summarized by treatment for each ISA 
with incidence rates. The mean change of the continuous safety measures will be summarized for 
each ISA by visit. 
Safety analyses will be summarized overall and separately for the induction period, maintenance 
period (if applicable to the ISA), and posttreatment follow-up period. If applicable to the ISA, 
safety analyses during the maintenance period will use the last available value before the first 
dose of study intervention during the maintenance period. Safety analyses during the 
posttreatment follow-up period will use the last nonmissing assessment on or prior to entering 
the posttreatment period. Additionally, some ISAs may combine the maintenance period and the 
posttreatment follow-up period for safety analyses, and these analyses will use the last available 
value before the first dose of study intervention during the maintenance period. 
9.3.5.1. 
Adverse Events  
AEs will be coded according to MedDRA and summarized by system organ class, preferred 
term, severity, and relationship to the study intervention. A TEAE is defined as an event that first 
occurs or worsens in severity after baseline, with baseline defined as all preexisting conditions 
recorded at Visit 401 and any AEs recorded before the first dose of study intervention, that is, 
during Visit 401 and Visit 0 and recorded with the time of onset before the first dose of study 
intervention). The postbaseline period for the analysis will include the treatment period and the 
posttreatment follow-up period. For events that are sex specific, the denominator and 
computation of the percentage will only include participants of the given sex. 

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The number, percentage, and incidence rate of participants who experienced TEAEs, TEAEs by 
maximum severity, deaths, SAEs, TEAEs related to study intervention, discontinuations from the 
treatment due to an AE, and AESIs will be summarized. TEAEs (all, by maximum severity), 
SAEs (including deaths), and AEs that lead to treatment discontinuation will be summarized and 
analyzed by MedDRA system organ class and preferred term. 
Treatment-related TEAEs (TEAEs related to study intervention) are defined as events that are 
indicated by the investigator on the CRF to be related to treatment. 
In addition to general safety parameters, safety information on specific topics of AESIs may also 
be presented. Potential AESIs will be identified by a standardized MedDRA query or a 
Lilly-defined MedDRA preferred term listing. 
Follow-up emergent AEs, SAEs (including death
discontinuation from study intervention or discontinuation from study will be summarized. 
All AEs, including preexisting conditions, will be listed by participant, preferred term, treatment 
group, severity (intensity), and relationship to the study intervention. 
9.3.5.2. 
Columbia Suicide Severity Rating Scale  
Suicide-related thoughts and behaviors occurring during treatment will be summarized based on 
responses to the C-SSRS consistent with the C-SSRS Scoring and Data Analysis Guide (CSSRS 
WWW). Suicidal ideation and/or behavior and self-injurious behavior with no suicidal intent, on 
the basis of the C-SSRS, will be listed by participant. 
9.3.6. 
Other Analyses  
9.3.6.1. 
Participant Disposition  
A detailed description of participant disposition will be provided, including a summary of the 
number and percentage of participants entered into the study and randomized, and number and 
percentage of participants who complete the study or discontinue, both overall and by reason for 
discontinuation for each ISA at the end of the study. Intervention-specific analyses are described 
in the respective ISAs. A summary of important protocol deviations will be provided for each 
ISA. 
9.3.6.2. 
Participant Characteristics  
Participant characteristics and baseline clinical measures will be summarized for each treatment 
period. Baseline characteristics will include sex assigned at birth, age, age category, weight, race, 
geographic region, country, and baseline disease activity, including vIGA-AD, EASI, SCORAD, 
and Itch NRS. Intervention-specific analyses are described in the respective ISAs. 
Demographic data are collected and summarized to demonstrate that the study population 
represents the target patient population. A summary of baseline participant characteristics, 
historical diagnoses, preexisting conditions, and prior therapies will be reported by treatment 
group using descriptive statistics. Other participant characteristics will be summarized by 
treatment group as deemed appropriate within each ISA. 

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9.3.6.3. 
Concomitant Therapy  
Previous and concomitant medications will be summarized by treatment for each ISA and will 
be presented by Anatomical Therapeutic Chemical drug classes using the latest version of the 
WHO drug dictionary. 
9.3.6.4. 
Treatment Compliance  
Treatment compliance with investigational product will be summarized by treatment for each 
ISA. Intervention-specific analyses are described in the relevant ISA. 
9.3.6.5. 
Pharmacokinetic/Pharmacodynamic Analyses  
When applicable, sample concentrations of the active study intervention, that is, other than 
placebo or other control, will be listed by time point and dosing regimen using descriptive 
statistics. The PK of the study drug may
 
Analyses of exposure-response relationships may be conducted
 
. Evaluations may be 
performed for PD, efficacy, and/or safety endpoints contingent on review of the data. 
Data from the ISAs may be combined with other study data, if appropriate. Further details on PK 
and PK/PD analyses will be provided in an ISA-SAP or a separate ISA PK/PD analysis plan. 
9.3.6.6. 
Immunogenicity Analyses  
Immunogenicity analyses will be described in the ISAs as applicable. 
9.3.6.7. 
Patient-Reported Outcomes  
Intervention-specific analyses of PROs, if applicable, are described in the relevant ISA. 
9.3.6.8. 
Subgroup Analyses  
Subgroup analyses may be conducted for endpoints of interest. Subgroups that may be evaluated 
include, but are not limited to, sex, race, geographic region, weight, baseline disease severity, 
duration since AD onset, and previous therapies. 
Additional intervention-specific analyses of subgroups may be described in the relevant ISA or 
ISA-SAP. 
9.3.6.9. 
Sensitivity Analyses  
Sensitivity analyses may be performed for alternative approaches to, for example, nonresponder 
criteria, prohibited medication use, or other intercurrent events of interest. 
 
 Details of sensitivity 
analyses and alternative models are specified in the ISA and/or ISA-SAP. 

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9.4. 
Interim Analyses  
Interim analyses of the master protocol 
Master protocol interim analyses may occur when an ISA has a primary database lock, an 
efficacy interim database lock (if applicable), and/or a final database lock as specified in its 
respective ISA. These analyses will be conducted to assess ISA objectives and to compare the 
intervention data to placebo data and may include placebo data collected for more than 1 ISA. 
Analysis details will be provided in the ISA and its SAP. 
Interim analyses of the ISAs 
Prior to the primary analysis for each ISA, there may be planned interim analyses to assess drug 
safety, PK, and/or efficacy. If so, details for the planned interim analysis will be provided in the 
respective ISAs or in the respective ISA-SAPs. 
Futility or efficacy stopping rules 
See the relevant ISA and/or ISA-SAP for information about interim analyses and about stopping 
rules for futility or efficacy, if applicable. 
Unblinding plan 
Intervention-specific unblinding details are provided in the respective ISA-SAP or in a separate 
unblinding plan document. 
Evaluation of unblinded interim analyses 
Only the IAC is authorized to evaluate unblinded interim efficacy and safety analyses 
(Section 10.1.5). 
9.5. 
Sample Size Determination  
Details of sample size and power assumptions and calculations for each intervention are in 
respective ISAs. 

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10. 
Supporting Documentation and Operational Considerations  
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
10.1.1. 
Regulatory and Ethical Considerations  
This study will be conducted in accordance with the protocol and with the following: 
 consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines 
 applicable ICH GCP guidelines 
 for ISAs having a device: International Organization for Standardization (ISO) 
14155, and 
 applicable laws and regulations. 
The protocol, protocol amendments, protocol addenda, ICF, IB, and other relevant documents, 
for example, advertisements, must be submitted to an IRB or IEC by the investigator and 
reviewed and approved by the IRB or IEC before the study is initiated. 
Any amendments to the protocol will require IRB or IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
Protocols and any substantial amendments to the protocol will require health authority approval 
prior to initiation except for changes necessary to eliminate an immediate hazard to study 
participants. 
The investigator will be responsible for the following: 
 providing written summaries of the status of the study to the IRB or IEC annually 
or more frequently in accordance with the requirements, policies, and procedures 
established by the IRB or IEC 
 notifying the IRB or IEC of SAEs or other significant safety findings as required 
by IRB or IEC procedures 
 providing oversight of study conduct for participants under their responsibility 
and adherence to requirements of 21 CFR, ICH guidelines, the IRB or IEC, 
European regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations, and 
 reporting to the sponsor or designee significant issues related to participant safety, 
participant rights, or data integrity. 
Investigator sites are compensated for participation in the study as detailed in the CTA. 
10.1.2. 
Financial Disclosure  
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 

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certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests for the master protocol and each ISA 
in which the investigator participates, and for 1 year after completion. 
10.1.3. 
Informed Consent Process  
including the risks and benefits, to the potential participant and answer all questions regarding 
the master protocol and relevant ISAs. 
Potential participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, privacy and data protection requirements, where applicable, and the 
IRB or IEC or study center. 
The medical record must include a statement that written informed consent was obtained before 
the participant was entered into the master protocol and into any ISA, and the date the written 
consent was obtained. The authorized person obtaining the informed consent must also sign the 
ICF. 
Revised consents must be appropriately obtained using the correct approved ICFs for applicable 
study participants in accordance with sponsor and ERB consenting guidance. 
A copy of the ICF(s) must be provided to the participant and is kept on file. 
Participants who are rescreened are required to sign a new ICF (Section 5.4). 
10.1.4. 
Data Protection  
Participants will be assigned a unique identifier (participant number) by the sponsor to protect 
. Any participant records, datasets, or tissue samples that are 
transferred to the sponsor will contain the identifier only; participant names or any information 
which would make the participant identifiable will not be transferred. 
sonal study-related data will be used 
by the sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent. This is done by the site personnel through the informed 
consent process. 
The participant must be informed through the informed consent by the site personnel that their 
medical records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB or IEC members, and by inspectors from 
regulatory authorities. 
The sponsor has processes in place to ensure information security, data integrity, and data 
protection. These processes address the management of data transfer, and prevention and 
management of unauthorized access, disclosure, dissemination, alteration, or the loss of 
information or personal data. These processes include appropriate contingency plans for 
appropriate and timely response in the event of a data security breach. The transfer of personal 
data is subject to appropriate safeguards through contractual agreements and processes. The 

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are compliant with local privacy laws and relevant legislations, including 
General Data Protection Regulation and the EU CTR. 
10.1.5. 
Committees Structure  
Internal assessment committee 
In addition to the safety reviews routinely performed by the blinded study team as described in 
Section 8.2, an IAC will exist for the purpose of reviewing safety data in an unblinded fashion 
periodically or on an ad hoc basis. The IAC will determine whether any changes to the study, for 
example, dose reductions or other protocol modifications, should be made (Section 10.1.5.1). 
The IAC will be fully independent from the study team and will include, at a minimum, a 
Lilly medical physician, a statistician, and a representative from the Lilly Global Patient Safety 
organization. Details about IAC membership, purpose, responsibilities, and operation will be 
described in an IAC charter, which will be approved prior to the first unblinding. 
If an efficacy interim analysis is considered necessary, the IAC will be responsible for review of 
the efficacy data. See Section 9.4 for general information about interim analyses. Details of 
interim analyses will be provided in the SAP. 
Study sites will receive information about interim results only if they need to know for the safety 
of their study participants. 
10.1.5.1. Stopping Rules  
Each ISA will describe ISA-specific stopping rules. The IAC will convene periodically but also 
when the accumulated safety data triggers one of the stopping rules specified in the ISA. Further 
enrollment in that ISA, or further dosing in that ISA, or both may be stopped, pending a decision 
of the IAC. 
10.1.6. 
Dissemination of Clinical Study Data  
CSRs 
A CSR will be provided for each ISA. 
Reports 
The sponsor will disclose a summary of study information, including tabular study results, on 
publicly available websites where required by local law or regulation. 
The summary of results will be posted within the time frame specified by local law or regulation. 
If the study remains ongoing in some countries and a statistical analysis of an incomplete dataset 
would result in analyses lacking scientific rigor (for example, underpowered) or compromise the 
integrity of the overall analyses (for example, trial not yet unblinded), the summary of results 
will be submitted within 1 year after the end of the study globally or as soon as available, 
whichever is earlier. 
Data 
The sponsor provides access to all individual participant data collected during the study, after 
anonymization, with the exception of PK or genetic data. Data are available to request 6 months 
after the indication studied has been approved in the US and EU and after primary publication 

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acceptance, whichever is later. No expiration date of data requests is currently set once data are 
made available. 
Access is provided after a proposal has been approved by an independent review committee 
identified for this purpose and after receipt of a signed data-sharing agreement. Data and 
documents, including the study protocol, SAP, CSR, and blank or annotated CRFs, will be 
provided in a secure data-sharing environment for up to 2 years per proposal. 
For details on submitting a request, see the instructions provided at www.vivli.org. 
10.1.7. 
Data Quality Assurance  
Investigator responsibilities 
All participant data relating to the study will be recorded on printed or electronic CRFs unless 
transmitted to the sponsor or designee electronically, for example, laboratory data. The 
investigator is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. This might include laboratory tests, medical records, and clinical 
notes. 
The investigator must review and confirm that data entries are accurate and complete throughout 
the duration of the study, by physically or electronically signing the CRF, as instructed by the 
sponsor. All completed CRFs must be signed prior to archival. 
The investigator must permit study-related monitoring, audits, IRB or IEC review, and 
regulatory agency inspections and provide direct access to source documents. 
Data monitoring and management 
When applicable, QTLs will be predefined to identify systematic issues that can impact 
participant safety or reliability of study results, or both. These predefined parameters will be 
monitored during the study and important excursions from the QTLs and remedial actions taken 
will be summarized in the CSR. 
Monitoring details describing strategy (for example, risk-based initiatives in operations and 
quality, such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques, are provided in the Monitoring Plan. 
The sponsor or designee is responsible for the data management of this study, including quality 
checking of the data. 
The sponsor assumes accountability for actions delegated to other individuals, for example, 
CROs. 
The sponsor or designee will perform monitoring to confirm that data transcribed into the CRF 
by authorized site personnel are accurate, complete, and verifiable from source documents; that 
the safety and rights of participants are being protected; and that the study is being conducted in 
accordance with the currently approved protocol and any other study agreements, ICH GCP, and 
all applicable regulatory requirements. 

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Records retention and audits 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for the time period outlined in the CTA unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor. 
In addition, the sponsor or its representatives will periodically check a sample of the participant 
data recorded against source documents at the study site. The study may be audited by the 
sponsor or its representatives, by regulatory agencies, or both at any time. Investigators will be 
given notice before an audit occurs. 
Data capture system 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor. 
Electronic data capture system 
An EDC system will be used in this study for the collection of CRF data. The investigator 
maintains a separate source for the data entered by the investigator or designee into the 
sponsor-provided EDC system. The investigator is responsible for the identification of any data 
to be considered source and for the confirmation that data reported are accurate and complete by 
signing the CRF. 
Clinical outcome assessments 
Additionally, COA data (participant-focused outcome instrument) and other data will be 
collected by authorized study personnel via a paper source document and will be transcribed by 
the authorized study personnel into the EDC system. 
Additionally, eCOA data per the SoA (participant-focused outcome instrument, and clinician 
assessments) will be directly recorded by the participant or investigator site personnel into an 
instrument, for example, handheld smart phone or tablet). The eCOA data will serve as the 
source documentation, and the investigator does not maintain a separate written or electronic 
record of these data. Therefore, the data must be recorded contemporaneously. 
Data storage and access 
Data collected via the sponsor-provided data capture systems will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture systems. Prior to decommissioning, the investigator will receive or access an 
archival copy of pertinent data for retention. 
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
, and reports will be provided to the investigator for review 
and retention. Data will subsequently be transferred from the central vendor to the sponsor data 
warehouse. 
Data from complaint forms submitted to the sponsor will be encoded and stored in the global 
PC management system. 

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10.1.8. 
Source Documents  
Source documents provide evidence for the existence of the participant and substantiate the 
 
Data reported on or entered in the CRF and are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The investigator 
may need to request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 
The definition of what constitutes source data can be found in Section 10.1.7. 
10.1.9. 
Study and Site Start and Closure  
First act of recruitment 
The study start date and the first act of recruitment is the date on which the clinical study will be 
open for recruitment of participants. 
Study or site termination 
The sponsor 
designee reserves the right to close a study site, or to terminate either 
the master protocol as a whole or only 1 particular ISA, at any time for any reason at the sole 
discretion of the sponsor. 
Study sites will be closed upon study completion. A study site is considered closed when all 
required documents and study supplies have been collected and a study-site closure visit has 
been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to 
 For study termination: 
 discontinuation of further study intervention development, and 
 decision of the IAC (Section 10.1.5.1). 
 For site termination: 
 failure of the investigator to comply with the protocol, the requirements of the 
IRB or 
guidelines 
 inadequate recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator, and 
 total number of participants included earlier than expected. 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs or IRBs, the regulatory authorities, and any CROs used in the study of the 
reason for termination or suspension, as specified by the applicable regulatory requirements. The 

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investigator shall promptly inform the participants and should assure appropriate participant 
therapy and/or follow-up. 
10.1.10. 
Publication Policy  
the ISAs conducted as part of 
this master protocol will be submitted for publication by a peer-reviewed journal. 
10.1.11. 
Investigator Information  
Researchers with appropriate education, training, and experience, as determined by the sponsor, 
will participate as investigators. 
10.1.12. 
Sample Retention  
Sample retention enables use of new technologies, response to regulatory requests or questions, 
and investigation of variable responses that may not be observed until later in the development 
of the study intervention or after the study intervention becomes commercially available. 
This table lists the maximum retention period for sample types. The retention period begins after 
ISA. 
Sample Type 
Custodian 
Maximum Retention Period 
after the Last Participant Visit
PK 
Sponsor or designee 
2 years for radiolabeled PK samples 
1 year for all other PK samples
Exploratory biomarkers, including but not 
limited to PD and genetics samples
Sponsor or designee 
Up to 15 years 
Immunogenicity 
Sponsor or designee 
Up to 15 years
Any samples remaining after the retention period will be destroyed. 
The sample retention facility will be selected by the sponsor or its designee. 
 
 

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10.2. 
Appendix 2: 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 appendix. 
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 or exclusion of potential study participants 
See Section 5 of this master protocol for laboratory tests that are part of the master protocol 
eligibility criteria. See Section 5 of the relevant ISA for any additional laboratory testing 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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10.2.1. 
Clinical Laboratory Tests Performed at Visit 401  
This section lists the clinical laboratory tests performed at Visit 401. 
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)
 
Follicle-stimulating hormone (FSH) 
Assayed by Lilly-designated laboratory at Visit 401 
screening. See Section 8.2.7.1.
Serum pregnancy
Assayed by Lilly-designated laboratory at Visit 401 
screening. For WOCBP only. See Section 8.2.7.
 
 
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
TB, HIV, and Hepatitis Serology
 
Tuberculosis (TB) testing:
TB test based on local standard of care.
     QuantiFERON®-TB Gold 
Assayed by Lilly-designated laboratory.
     T-SPOT®.TB 
May be tested and evaluated locally. Local laboratory 
must be qualified by local regulations.
      Tuberculin skin test (TST)
Tested and evaluated locally. Local staff must be 
qualified to administer and interpret the test.
Human immunodeficiency virus (HIV)
Assayed by Lilly-designated laboratory.
Hepatitis C virus (HCV) testing:
Assayed by Lilly-designated laboratory.
      HCV antibody
 
      HCV RNA 
Performed only for participants who test positive for 
hepatitis C antibody.
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.
      Hepatitis B core antibody (anti-HBc)
 
      Hepatitis B surface antigen (HBsAg)
 
 
 
Notes
Calculations 
Generated by Lilly-designated laboratory.
Estimated glomerular filtration rate (eGFR)
CKD-EPI Creatinine Equation (2021).
Abbreviations: CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; DNA = deoxyribonucleic acid; 
RNA = ribonucleic acid; WOCBP = women of childbearing potential. 
 
 

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10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: Definitions 
and Procedures for Recording, Evaluating, Follow-up, and 
Reporting  
The definitions and procedures detailed in this appendix are in accordance with ISO 14155. 
If an ISA involves a medical device, both the investigator and the sponsor will comply with all 
local medical device reporting requirements. The detection and documentation procedures 
described in this protocol apply to all sponsor medical devices provided for use in the study. See 
the relevant ISA for the list of sponsor medical devices, if any. 
10.3.1. 
Definition of AE  
AE Definition 
For drug-only clinical studies: An AE is any untoward medical occurrence in a 
participant administered a pharmaceutical product and which does not necessarily 
have a causal relationship with the study intervention. An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product. 
 For clinical studies that include a medical device: An AE is any untoward medical 
occurrence, unintended disease or injury, or untoward clinical signs (including 
abnormal laboratory finding) in study participants, users, or other persons, whether 
or not related to the investigational medical device. This definition includes events 
related to the investigational medical device or comparator and events related to 
the procedures involved except for events in users or other persons, which only 
include events related to investigational devices. 
 
Events Meeting the AE Definition 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (for example, ECG, radiological scans, 
and vital signs measurements), including those that worsen from baseline, 
considered clinically significant in the medical and scientific judgment of the 
investigator, that is, not related to progression of underlying disease. 
 Exacerbation of a chronic or intermittent preexisting condition, including either 
an increase in frequency and/or intensity of the condition. 
 New condition detected or diagnosed after study intervention administration 
even though it may have been present before the start of the study. 
 Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 Medication error, misuse, or abuse of IMP, including signs, symptoms, or 
clinical sequelae. 

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 Lack of efficacy or failure of expected pharmacological action per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy 
will be reported as AE or SAE if they fulfill the definition of an AE or SAE. 
 
Events NOT Meeting the AE Definition 
Any clinically significant abnormal laboratory findings or other abnormal 
safety assessments that are associated with the underlying disease, unless 
condition. 
 The disease or disorder being studied or expected progression, signs, or 
symptoms of the disease or disorder being studied, unless more severe than 
 
 Medical or surgical procedure, for example, endoscopy and appendectomy: the 
condition that leads to the procedure is the AE. 
 Situations in which an untoward medical occurrence did not occur (social 
and/or convenience admission to a hospital). 
 Anticipated day-to-day fluctuations of preexisting diseases or conditions 
present or detected at the start of the study that do not worsen. 
10.3.2. 
Definition of SAE  
An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or 
more of the criteria listed: 
a. 
Results in death 
b. 
Is life-threatening 
The term life-threatening in the definition of serious refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event which hypothetically 
might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 In general, hospitalization signifies that the participant has been admitted to 
hospital or emergency ward (usually involving at least an overnight stay) for 
observation and/or treatment that would not have been appropriate in the 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether 
hospitalization occurred or was necessary, the AE should be considered serious. 

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Hospitalization for elective treatment of a preexisting condition that did not 
worsen from baseline is not considered an AE. 
d. 
Results in persistent disability or incapacity 
 The term disability 
conduct normal life functions. 
 This definition is not intended to include experiences of relatively minor 
medical significance, such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma, for example, sprained ankle, which 
may interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. 
Is a congenital anomaly or birth defect 
 Abnormal pregnancy outcomes, for example, spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, and ectopic pregnancy, are considered SAEs. 
f. 
Other situations 
 Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations, such as 
important medical events that may not be immediately life-threatening or result 
in death or hospitalization but may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
 Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development 
of drug dependency or drug abuse. 
g. 
For studies that include a medical device: 
Resulted in medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
 
10.3.3. 
Definition of Product Complaints  
Product Complaint 
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
study intervention. When the ability to use the study intervention safely is impacted, the 
following are also product complaints: 
 deficiencies in labeling information, and 

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 use errors for device or drug-device combination products due to ergonomic 
design elements of the product. 
Product complaints related to study interventions used in clinical trials are collected to ensure 
the safety of participants, monitor quality, and to facilitate process and product improvements. 
Investigators will instruct participants to contact the site as soon as possible if he or she has a 
product complaint or problem with the study intervention so that the situation can be assessed. 
An event may meet the definition of both a product complaint and an AE/SAE. In such cases, 
it should be reported as both a product complaint and as an AE/SAE. 
 
10.3.4. 
Recording and Follow-Up of AE and/or SAE and Product Complaints  
AE, SAE, and Product Complaint Recording 
When an AE/SAE/PC occurs, it is the responsibility of the investigator to review all 
documentation, for example, hospital progress notes, laboratory reports, and diagnostics 
reports, related to the event. 
The investigator will then record all relevant AE/SAE/PC 
information is reported on the appropriate CRF page, and PC information is reported on the 
Product Complaint Form. 
Note: An event may meet the definition of both a PC and an AE/SAE. In such cases, it should 
be reported as both a PC and as an AE/SAE. 
It is not 
records to the sponsor or designee in lieu of completion of the CRF page for an AE/SAE and 
the Product Complaint Form for a PC. 
There may be instances when copies of medical records for certain cases are requested by the 
sponsor or designee. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before submission to 
the sponsor or designee. 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual signs or 
symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories: 
 Mild: A type of adverse event that is usually transient and may require only 
minimal treatment or therapeutic intervention. The event does not generally 
interfere with usual activities of daily living. 

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Moderate: A type of adverse event that is usually alleviated with additional 
specific therapeutic intervention. The event interferes with usual activities of 
daily living, causing discomfort but poses no significant or permanent risk of 
harm to the research participant. 
 Severe: A type of adverse event that interrupts usual activities of daily living, or 
significantly affects clinical status, or may require intensive therapeutic 
intervention. An AE that is assessed as severe should not be confused with an 
SAE. Severe is a category utilized for rating the intensity of an event; and both 
AEs and SAEs can be assessed as severe. 
An event is defined as serious  when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, not when it is rated as severe. 
 
Assessment of Causality 
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. The investigator will use clinical judgment to determine the 
relationship. 
A reasonable possibility  of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
Alternative causes, such as underlying diseases, concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study intervention administration will be 
considered and investigated. 
The investigator will also consult the IB in their assessment. 
For each AE/SAE, the investigator must document in the medical notes that the investigator 
has reviewed the AE/SAE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the sponsor or designee. However, it is very 
important that the investigator always make an assessment of causality for every event before 
the initial transmission of the SAE data to the sponsor or designee. 
The investigator may change their opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-Up of AEs and SAEs 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor or 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 

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If a participant dies during participation in the study or during a recognized follow-up period,
the investigator will provide the sponsor or designee with a copy of any postmortem findings, 
including histopathology. 
10.3.5. 
Reporting of SAEs  
SAE Reporting via an Electronic Data Collection Tool 
The primary mechanism for reporting an SAE will be the electronic data collection tool. 
If the electronic system is unavailable, then the site will use the SAE paper form (see next 
section) to report the event within 24 hours. 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
After the study is completed at a given site, the electronic data collection tool will be taken 
offline to prevent the entry of new data or changes to existing data. 
If a site receives a report of a new SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken offline, then 
the site can report this information on an SAE paper form (see next section) or to the sponsor 
or designee by telephone. 
Contacts for SAE reporting can be found in the Global Patient Safety Clinical Trial SAE 
Transmission Cover Sheet and Form. 
 
SAE Reporting via Paper Form 
Facsimile transmission of the SAE paper form is the preferred method to transmit this 
information to the sponsor or designee. 
Initial notification via telephone does not replace the need for the investigator to complete and 
sign the SAE CRF pages within the designated reporting time frames. 
Contacts for SAE reporting can be found in the Global Patient Safety Clinical Trial SAE 
Transmission Cover Sheet and Form. 
10.3.6. 
Regulatory Reporting Requirements  
SAE Regulatory Reporting 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will evaluate the reported SAEs, including confirmation of relatedness and assessment 
of expectedness. The sponsor has processes for safety reports for identification, recording, and 
expedited reporting of SUSARs according to local regulatory requirements. The sponsor will 

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comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB or IEC, and investigators.  
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information, for example, summary or listing of SAEs, from the sponsor will review 
and then file it along with the IB and will notify the IRB or IEC, if appropriate according to 
local requirements.  
 
 
 

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10.4. 
Appendix 4: Medical Device Adverse Events (AEs), Adverse Device 
Effects (ADEs), Serious Adverse Events (SAEs), and Device 
Deficiencies: Definition and Procedures for Recording, Evaluating, 
Follow-up, and Reporting  
See Appendix 3, Section 10.3, for definitions and procedures for recording, evaluating, follow-
up, and reporting of all events. 

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10.5. 
Appendix 5: Contraceptive and Barrier Guidance  
10.5.1. 
Definitions  
Word/Phrase 
Definition 
Women of childbearing 
potential (WOCBP) 
Adult females are considered WOCBP unless they are WNOCBP. 
Women not of 
childbearing potential 
(WNOCBP) 
Females are considered WNOCBP if they 
 have a congenital anomaly such as Müllerian agenesis 
 are infertile due to surgical sterilization, or 
 are postmenopausal. 
Examples of surgical sterilization include hysterectomy, bilateral 
salpingo-oophorectomy, bilateral salpingectomy, or bilateral 
oophorectomy. 
Postmenopausal state 
The postmenopausal state is defined as a woman 
 at any age at least 6 wk postsurgical bilateral oophorectomy 
with or without hysterectomy, confirmed by operative note, 
or 
 aged at least 40 years and up to 55 years with an intact 
uterus, not on hormone therapya, who has had cessation of 
menses for at least 12 consecutive months without an 
alternative medical cause, AND with an FSH >40 mIU/mL, 
or 
 55 years or older not on hormone therapy, who has had at 
least 12 months of spontaneous amenorrhea, or 
 aged at least 55 years with a diagnosis of menopause prior 
to starting hormone replacement therapy. 
a Women should not be taking medications during amenorrhea, 
such as oral contraceptives, hormones, gonadotropin-releasing 
hormone, anti-estrogens, SERMs, or chemotherapy that could 
induce transient amenorrhea. 
10.5.2. 
Contraception Guidance  
See the ISA to which the participant is assigned. 
10.5.3. 
Pregnancy Testing Guidance  
See Sections 1.3 and 8.2.7 of this master protocol, and Section 1.3 of the relevant ISA. 
 
 

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10.6. 
Appendix 6: Assessments of Disease Activity, Patient-Reported 
Outcomes, and Quality of Life  
This appendix describes efficacy-related assessments which may appear in the IMMB SoA or in 
the SoA of an ISA. Additional efficacy-related assessments may be described in an ISA. 
10.6.1. 
Eczema Area and Severity Index (EASI)  
The EASI is an investigator-reported, 20-item scale that evaluates 2 dimensions of AD in 
participants: 
 extent of disease at 4 body regions (head/neck, trunk, upper and lower 
extremities), and 
 4 clinical signs (erythema, induration/papulation, excoriation, and lichenification). 
The clinical signs are assessed for severity on a scale of 0 (absent) to 3 (severe). 
The scores are added up for each of the 4 body regions. The assigned percentages of BSA for 
each section of the body are 
 10% for head/neck 
 20% for upper extremities 
 30% for trunk, and 
 40% for lower extremities. 
Each subtotal score is multiplied by the BSA represented by that region. 
In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage 
of AD-affected skin in that area: 
 0 (none) 
 1 (1% to 9%) 
 2 (10% to 29%) 
 3 (30% to 49%) 
 4 (50% to 69%) 
 5 (70% to 89%), or 
 6 (90% to 100%). 
Each of the body area scores is multiplied by the area affected. The resulting EASI score ranges 
from 0 to 72 points, with the highest score indicating worse severity of AD (Hanifin et al. 2001). 
The recall period of this scale is present time. 
10.6.2. 
vIGA-AD  
The vIGA-AD® 
severity of their AD, based on a single-item, numeric, 5-point scale from 0 (clear skin) to 
4 (severe disease) (Simpson et al. 2020b). The score is based on an overall assessment of the 
degree of erythema, papulation or induration, oozing or crusting, and lichenification. The recall 
period of this assessment is present time. 

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10.6.3. 
SCORing Atopic Dermatitis (SCORAD)  
The SCORAD index is an investigator- and participant-reported, 9-item assessment that assesses 
3 aspects as provided below: 
 The extent (1-item) of AD is assessed as a percentage of each defined body area 
and reported as the sum of all areas. The maximum score is 100%. 
 The severity of 6 specific symptoms of AD: erythema, edema or papulation, 
oozing or crusts, excoriation, lichenification, and dryness (6-items) is assessed by 
the investigator using a 4-point scale, that is, none = 0, mild = 1, moderate = 2, 
severe = 3, with a maximum possible total of 18 points. 
 The subjective symptoms of pruritus and sleep loss (2 items) is assessed by the 
participant via a 10-cm VAS. The symptoms (itch and sleeplessness) are recorded 
by the participant on a visual analog scale, where 0 is no symptoms and 10 is the 
worst imaginable symptom, with a maximum possible score of 20. 
The maximum possible SCORAD score calculated based on the above 3 aspects is 103. The 
higher scores indicate poorer or more severe condition (Stalder and Taïeb 1993; Kunz et al. 
1997; Oranje et al. 2007; Schram et al. 2012). The recall period is present time for extent and 
intensity, and average for the last 3 days/nights for subjective symptoms of AD. 
10.6.4. 
Patient-Oriented Eczema Measure (POEM)  
The POEM is a simple, participant-reported, 7-item scale that assesses disease severity in adults. 
Participants respond to questions about the frequency of 7 symptoms (itching, sleep disturbance, 
bleeding, weeping or oozing, cracking, flaking, and dryness or roughness) over the past week. 
-
-
-
with corresponding scores of 0, 1, 2, 3, and 4, respectively. Scores range from 0 to 28, with 
higher total scores indicating greater disease severity (Charman et al. 2004). 
10.6.5. 
Dermatology Life Quality Index (DLQI)  
The DLQI is a participant-reported, 10-
covers 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal 
c
 
. 
Scores range from 0 to 30 with higher scores indicating greater impairment of QoL. A DLQI 
2005), and a 4-point change from baseline is considered as the minimal clinically important 
difference threshold (Khilji et al. 2002; Basra et al. 2015). 
10.6.6. 
Atopic Dermatitis Control Tool (ADCT)  
The ADCT is a participant-reported, simple, brief tool for adults and adolescents, which 
evaluates 6 symptoms and effects associated with AD over the past week: 
 overall severity of symptoms 
 days with intense episodes of itching 

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 intensity of bother 
 problem with sleep 
 impact on daily activities, and 
 impact on mood or emotions. 
Each of the 6 ADCT items has a score range from 0 (no problem) to 4 (worst), rating the severity 
of each concept. The total score ranges from 0 to 24, which is the summation of the responses to 
con
-person change was estimated to be 5 points 
(Simpson et al. 2019; Pariser et al. 2020). 
10.6.7. 
Itch Numeric Rating Scale (Itch NRS)  
The Itch NRS is a participant-reported, single-item, 11-point scale anchored at 0 and 10, with 0 
describes the worst level of 
itching in the past 24 hours (Naegeli et al. 2015; Kimball et al. 2016; Newton et al. 2019; 
Silverberg et al. 2021b). 
10.6.8. 
Atopic Dermatitis Sleep Scale (ADSS)  
The ADSS is a participant-reported, 3-item questionnaire in adults developed to assess the 
impact of itch on sleep, including difficulty falling asleep, frequency of waking, and difficulty 
getting back to sleep last night. Participants rate their difficulty falling asleep and difficulty 
getting back to sleep, Items 1 and 3, respectively, using a 5-point Likert-type scale. Response 
options 
corresponding scores of 0, 1, 2, 3, and 4, respectively. Participants report their frequency of 
waking last night, Item 2, by selecting the number of times they woke up each night, ranging 
from 0 to 29 times. The ADSS is designed to be completed each day with respondents thinking 
 (Silverberg et al. 2021b). 
10.6.9. 
Skin Pain Numeric Rating Scale (Skin Pain NRS)  
The Skin Pain NRS is a participant-reported, 11-point scale anchored at 0 and 10, with 
0 
skin pain in the past 24 hours (Newton et al. 2019; Silverberg et al. 2021b). 
 
 

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10.7. 
Appendix 7: Tuberculosis Testing  
This table describes recommendations performing and interpreting TB tests. It also provides 
recommendations on TB retesting. 
TB test 
type 
How to perform the test 
How to interpret the test
When to retest
PPD TST 
1. Inject 0.1 mL of tuberculin 
PPD into the inner surface of 
the forearm. 
Notes: 
 The injection should be 
made with a tuberculin 
syringe. 
 The TST is an intradermal 
injection. When placed 
correctly, the injection 
should produce a pale 
elevation of the skin (a 
wheal) 6 to 10 mm in 
diameter. 
2. Measure induration at the site 
of intradermal injection from 
48 to 72 hr after intradermal 
injection. 
Notes: 
 Test must be read during 
this window of time. Test 
does not need to be read at 
the study site but must be 
read by a trained medical 
professional, and the result 
must be provided to the 
study site before 
randomization. 
 The reaction should be 
measured in millimeters of 
induration (palpable, 
raised, hardened area, or 
swelling). The reader 
should not measure 
erythema (redness). The 
diameter of the indurated 
area should be measured 
across the forearm 
(perpendicular to the long 
axis). 
An induration of 5 mm or 
more is considered positive 
in persons with 
 
HIV infection 
 
a recent contact with a 
person with TB 
disease 
 
fibrotic changes on 
chest radiograph 
consistent with 
prior TB 
 
organ transplants, or 
 
immunosuppression 
for other reasons, for 
example, taking the 
equivalent of >15 mg 
per day of prednisone 
for 1 month or longer, 
or taking TNF alpha 
antagonists 
 
An induration of 10 mm 
or more is considered 
positive in all other 
potential clinical trial 
participants. 
Two-step testing (that is, 
repeat TST from 1 to 3 wk 
after the first TST) is 
recommended for certain 
participant groups, 
including those 
 
receiving 
immunosuppressant 
treatment 
 
having a history of 
temporally remote 
increased risk of TB 
infection, or 
 
for whom the first 
test is negative, and 
retesting is 
recommended per 
local public health 
and/or professional 
medical society 
recommendations. 
 

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TB test 
type 
How to perform the test 
How to interpret the test
When to retest
IGRA for 
M 
tuberculosis 
Ensure that specimen handling, 
transport, timing, and laboratory 
procedures meet all requirements
per package insert. 
Results are provided by the 
laboratory assaying the test. 
The investigator may discuss 
designated medical monitor 
if 
 the investigator suspects a 
false-positive IGRA result 
in a participant with no 
increased risk of TB 
infection during lifetime, 
and 
 there is no evidence of 
prior or current TB on 
physical examination 
and/or on chest x-ray 
interpreted by radiologist 
and/or pulmonologist 
(investigator assessment 
by history and physical 
examination, and with 
documented chest x-ray 
report).
Abbreviations: IGRA = interferon gamma release assay; PPD = purified protein derivative; TB = tuberculosis; 
TNF = tumor necrosis factor; TST = tuberculin skin test. 
 

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10.9. 
Appendix 9: Liver Safety: Suggested Actions and Follow-up 
Assessments  
Hepatic evaluation testing 
See Section 8.2.11 for guidance on appropriate test selection. 
The Lilly-designated central laboratory should complete the analysis of all selected testing 
except for testing listed in the investigator-designated local laboratory table. The central 
laboratory will report results if a validated test or calculation is available. 
In circumstances where required in accordance with local regulations, local laboratory testing 
may be performed in lieu of Lilly-designated central laboratory testing (in the table below). 
Local testing may be performed in addition to central testing when necessary for immediate 
participant management. 
The local laboratory must be qualified in accordance with applicable local regulations. 
Tests assayed by Lilly-designated central laboratory 
Hepatic Hematology Panel 
Hepatitis A virus (HAV) testing:
  Hemoglobin 
   HAV total antibody
  Hematocrit 
   HAV IgM antibody 
  Erythrocytes (RBCs - red blood cells)
Hepatis B virus (HBV) testing:
  Leukocytes (WBCs - white blood cells)
   Hepatitis B surface antigen (HBsAg)
  Differential:
   Hepatitis B surface antibody (anti-HBs)
      Neutrophils 
   Hepatitis B core total antibody (anti-HBc)
      Lymphocytes
   Hepatitis B core IgM antibody
      Monocytes
   HBV DNAa
      Basophils
Hepatis C virus (HCV) testing:
      Eosinophils 
   HCV antibody
  Platelets
   HCV RNAa
  Cell morphology (RBC and WBC)
Hepatitis D virus (HDV) testing:
Hepatic Clinical Chemistry Panel
   HDV antibody
  Total bilirubin
Hepatitis E virus (HEV) testing:
  Direct bilirubin
   HEV IgG antibody
  Alkaline phosphatase (ALP)
   HEV IgM antibody
  Alanine aminotransferase (ALT)
   HEV RNAa
  Aspartate aminotransferase (AST)
Anti-nuclear antibody (ANA)
  Gamma-glutamyl transferase (GGT)
Anti-smooth muscle antibody (ASMA)b
  Creatine kinase (CK)
Anti-actin antibodyc
Hepatic Coagulation Panel
Immunoglobulin IgA (quantitative)
  Prothrombin time, INR (PT-INR)
Immunoglobulin IgG (quantitative)
Urine Chemistry
Immunoglobulin IgM (quantitative)
  Drug screen
Epstein-Barr virus (EBV) testing:
Haptoglobin
   EBV antibody
a Reflex or confirmation dependent on regulatory requirements or testing availability, or both. 
b Not required if anti-actin antibody is tested. 
c Not required if anti-smooth muscle antibody (ASMA) is tested. 
 
 

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Tests assayed ONLY by investigator-designated local laboratory 
Acetaminophen
Cytomegalovirus (CMV) testing:
Acetaminophen protein adducts 
   CMV antibody
Alkaline phosphatase isoenzymes
   CMV DNAa
Ceruloplasmin
Herpes simplex virus (HSV) testing:
Copper
   HSV (Type 1 and 2) antibody
Ethyl alcohol (EtOH) 
   HSV (Type 1 and 2) DNAa
Phosphatidylethanol (PEth) 
Liver kidney microsomal type 1 (LKM-1) antibody
Urine Chemistry
Microbiology 
   Ethyl glucuronide (EtG)
Culture:
Epstein-Barr virus (EBV) testing: 
   Blood
   EBV DNAa 
    Urine 
a Reflex or confirmation dependent on regulatory requirements, testing availability, or both. 
 
 
 

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10.10. 
Appendix 10: Genetics  
See Section 8.6. 
 
 

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10.11. 
Appendix 11: Country-specific Requirements  
For sites in EU Member States 
This appendix is not applicable at this time. 
For sites outside of EU Member States 
Country-specific requirements, if any, will be described in a separate protocol addendum. 
 
 

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10.12. 
Appendix 12: Provisions for Changes in Study Conduct During 
Exceptional Circumstances  
The following provisions are applicable to all ISAs unless otherwise specified. 
Implementation of this appendix 
The changes to procedures described in this appendix are temporary measures intended to be 
used only during specific time periods as directed by the sponsor in partnership with the 
investigator. 
Exceptional circumstances 
Exceptional circumstances are rare events that may cause disruptions to the conduct of the study. 
Examples include pandemics or natural disasters. These disruptions may limit the ability of the 
investigators or participants, or both, to attend on-site visits or to conduct planned study 
procedures. 
Implementing changes under exceptional circumstances 
implement changes if permitted by local regulations. 
After approval by local ERBs, regulatory bodies, and any other relevant local authorities, 
implementation of these exceptional circumstance changes will not typically require additional 
notification to these groups, unless they have specific requirements in which notification is 
required, for example, upon implementation and suspension of changes. All approvals and 
notifications must be retained in the study records. 
If the sponsor grants written approval for changes in study conduct, the sponsor will also provide 
additional written guidance, if needed. 
Considerations for making a change 
The prevailing consideration for making a change is ensuring the safety of study participants. 
Additional important considerations for making a change are compliance with GCP, enabling 
participants to continue safely in the study and maintaining the integrity of the study. 
Informed consent 
Additional consent from the participant will be obtained, if required and if applicable, for 
 participation in remote visits, as defined in Section 
 
 a change in the method of study intervention administration 
 dispensation of additional study intervention during an extended treatment period 
 alternate delivery of study intervention and ancillary supplies, and 
 provision of their personal or medical information required prior to 
implementation of these activities. 
See the relevant ISA for the additional informed consent requirements specific to that ISA. 

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Changes in study conduct during exceptional circumstances 
Changes in study conduct not described in this appendix or in an ISA, or not consistent with 
applicable local regulations, are not allowed. The following changes in study conduct will not be 
considered protocol deviations. 
Remote visits 
Types of remote visits for Visit 401 (master protocol screening period) 
Telemedicine: Telephone or technology-assisted virtual visits, or both, are acceptable to 
complete appropriate assessments. Procedures to be completed in this manner may 
include, but are not limited to, concomitant medication, AEs, participant diary education 
and compliance check, and PROs via a tablet and/or a web-based collection system. 
Mobile health care: Health care visits may be performed by a mobile health care 
provider at locations other than the study site when participants cannot travel to the site if 
written approval is provided by the sponsor. Procedures performed may include, but are 
not limited to, vital signs, concomitant medications, AEs, participant diary education and 
compliance check, symptom-directed physical assessments, ECGs, collection of blood 
and urine samples for clinical safety laboratory testing, C-SSRS Baseline/Screening, and 
PROs via a tablet and/or a web-based collection system. 
Other alternative locations: Procedures that could be done at an alternate location may 
include, but are not limited to, ECGs and collection of blood and urine samples for 
clinical safety laboratory testing. 
Types of remote visits for ISA screening period and thereafter 
See the relevant ISA. 
Data capture 
In source documents and the CRF, the study site should capture the visit method, with a specific 
explanation for any data missing because of missed in-person site visits. 
Safety reporting 
Regardless of the type of remote visits implemented, the protocol requirements regarding the 
reporting of AEs, SAEs, and PCs remain unchanged. 
Return to on-site visits 
Every effort should be made to enable participants to return to on-site visits as soon as 
reasonably possible, while ensuring the safety of both the participants and the site staff. 
Local laboratory testing option for Visit 401 (master protocol screening period) 
Central laboratory testing must be used for all samples collected at Visit 401 unless local testing 
is specified by the SoA (Section 1.3) and by Appendix 2, Section 10.2.1. 
Local laboratory testing option for Visit 0 (Week 0) and thereafter 
See the relevant ISA. A local laboratory must be qualified in accordance with applicable local 
regulations. 

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Study intervention and ancillary supplies (including participant diaries) 
When a participant is unable to go to the site to receive study supplies during normal on-site 
visits, the site should work with the sponsor to determine appropriate actions. These actions may 
include 
 asking the participant to go to the site and receive study supplies from site staff 
without completion of a full study visit 
 
 
 arranging delivery of study supplies, and 
 if applicable, working with the sponsor to determine how study intervention that 
is typically administered on-site will be administered to the participant, for 
example, during a mobile health care visit or at an alternate location, such as an 
infusion center. 
These requirements, if applicable, must be met before action is taken: 
 Alternate delivery of study intervention should be performed in a manner that 
does not compromise treatment blinding and ensures product integrity. The 
existing protocol requirements for product accountability remain unchanged, 
including verification of partic
supplies. 
 When delivering supplies to a location other than the study site, for example, 
or sponsor, or both, should ensure oversight 
of the shipping process to ensure accountability and product quality, that is, 
storage conditions maintained and intact packaging upon receipt. 
 Instructions may be provided to the participant or designee on the final disposition 
of any unused or completed study supplies. 
If study intervention will be administered to the participant during a mobile health care visit or at 
an alternate location, these additional requirements must be met: 
 Only authorized study personnel may supply, prepare, or administer study 
intervention. 
 See the relevant ISA for any intervention-specific instructions, for example, about 
having resuscitation equipment, emergency drugs, and appropriately trained 
medical staff available both during an infusion and for a designated number of 
hours after the completion of the infusion or in cases of hypersensitivity or 
infusion site reactions. 
Guidance for the screening periods of the master protocol and ISAs 
The following rules will be applied for active, nonrandomized participants whose participation in 
screening activities (in the master protocol or in an ISA, or both) must be paused due to 
exceptional circumstances: 
 If screening is paused for a brief period of time, such that 
screening 
activities can still be conducted within the allowed screening windows, and if the 

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participant is found to be eligible to participate in the master protocol and an ISA, the 
participant can continue in the study as usual. Due to the pause in screening, however, 
source documentation. 
 If screening is paused for a long period of time, such that 
 screening 
activities cannot be conducted within the allowed screening windows, the participant 
must be discontinued from the study because of screening interruption due to an 
exceptional circumstance. This is documented as a screen failure in the CRF. The 
participant can be reconsented and be rescreened as a new participant. This rescreen 
is in addition to the number of rescreenings already allowed by the main protocol. 
The screening procedures per the usual SoAs of the master protocol and the relevant 
ISA should be followed to ensure eligibility before the rescreened participant is 
randomized to study intervention. 
Adjustments to visit windows 
study 
procedures should be completed within the visit windows described in the relevant SoA. To 
maximize the possibility that these visits can be conducted as on-site visits, the windows for 
visits may be adjusted, upon further guidance from the sponsor. This minimizes missing data and 
preserves the intended conduct of the study. 
This table describes the allowed adjustments to visit windows. 
Visit Number
Tolerance
Visit 401 
No adjustment to the visit window described in the master protocol SoA
Visit 0 (Week 0) through the last 
posttreatment follow-up visit 
See Provisions for Changes in Study Conduct During Exceptional 
the relevant ISA
For participants whose visits have extended windows, additional study intervention may need to 
be provided to avoid interruption and maintain overall integrity of the study. 
Documentation 
Changes to study conduct will be documented 
Sites will identify and document the details of how participants, visit types, and conducted 
activities were affected by exceptional circumstances. Dispensing or shipment records of study 
intervention and relevant communications, including delegation, should be filed with site study 
records. 
Source documents at alternate locations 
Source documents generated at a location other than the study site should be part of the 
 source documentation and should be transferred to the site in a secure and timely 
manner. 
 
 

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10.13. 
Appendix 13: Requirements for ISA Design  
The ISAs of this master protocol will use a common clinical trial database. The common 
database is built on a standard visit structure, and certain activities are expected to occur at the 
standard visits. 
This appendix describes these standards. A study team developing an SoA for a new ISA will 
usual data collection requirements, for example, AE data collection at 
every visit, and may add visits and activities to the SoA as needed to support intervention-
specific objectives and endpoints. However, the required standards described in this appendix 
must also be incorporated into the SoA to support use of the common database. 
Investigators are to refer to the relevant ISA for ISA-specific details and actual assessments and 
procedures to perform in an ISA. 
10.13.1. 
Activities During the Induction Period  
The visit structure of the induction period must include a screening/baseline/randomization visit 
(Visit 0/Day 1/Week 0) as well as visits at 4-week intervals thereafter, for example, visits at 
Week 4, Week 8, and so on, until the end of the period. 
An ISA may include additional visits in this period to support ISA-specific objectives and 
endpoints. It is anticipated, but not required, that this period will end at either the Week 12 visit 
or the Week 16 visit. 
This table lists the timing and/or frequency of the required standard activities for this period. 
Activity 
Timing or Frequency in an Induction Period of an ISA
Patient-reported outcomes (electronic)
Dermatology Life Quality Index
At first visit and at visits every 4 wk thereafter
Patient-Oriented Eczema Measure
At first visit and at visits every 4 wk thereafter
SCORing Atopic Dermatitis (subjective)
At first visit and at visits every 4 wk thereafter
Atopic Dermatitis Control Tool 
At first visit and end of induction period 
Note: Atopic Dermatitis Control Tool is required only of 
ISAs having a maintenance period. 
Clinician-administered assessments (electronic)
vIGA-AD 
At first visit and at visits every 4 wk thereafter
Eczema Area and Severity Index
At first visit and at visits every 4 wk thereafter
SCORing Atopic Dermatitis (objective)
At first visit and at visits every 4 wk thereafter
Fitzpatrick Scale of Skin Phototypes 
At first visit
Laboratory tests and sample collections 
Hematology 
At first visit and at visits every 4 wk thereafter
Clinical chemistry
At first visit and at visits every 4 wk thereafter
Urine pregnancy test (local) 
At first visit and at visits every 4 wk thereafter
HBV DNA 
At a visit corresponding to an interval of approximately 
12 to 16 wk from the last HBV DNA test. Only for 
participants who are anti-HBc positive at Visit 401 of the 
master protocol [IMMB] and are enrolled in the ISA.

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Activity 
Timing or Frequency in an Induction Period of an ISA
10.13.2. 
Activities During a Maintenance Period  
An ISA is not required to have a maintenance period. If an ISA does have such a period, the ISA 
visit structure must include visits at Week 16 and at 12-week intervals thereafter until the end of 
the period. An ISA may include additional visits in this period to support ISA-specific objective 
and endpoints. 
This table lists the timing and/or frequency of the required standard activities for this period. 
Activity 
Timing or Frequency in a Maintenance Period of an ISA
Patient-reported outcomes (electronic)
Dermatology Life Quality Index
At the Week 16 visit, and at visits every 12 wk thereafter
Patient-Oriented Eczema Measure
At the Week 16 visit, and at visits every 12 wk thereafter
SCORing Atopic Dermatitis (subjective)
At the Week 16 visit, and at visits every 12 wk thereafter
Atopic Dermatitis Control Tool
At the Week 16 visit, and at visits every 12 wk thereafter
Clinician-administered assessments (electronic)
vIGA-AD 
At the Week 16 visit, and at visits every 12 wk thereafter
Eczema Area and Severity Index
At the Week 16 visit, and at visits every 12 wk thereafter
SCORing Atopic Dermatitis (objective)
At the Week 16 visit, and at visits every 12 wk thereafter
Laboratory tests and sample collections 
Hematology 
At the Week 16 visit, and at visits every 12 wk thereafter
Clinical chemistry
At the Week 16 visit, and at visits every 12 wk thereafter
Urine pregnancy test (local) 
At the Week 16 visit, and at a minimum every 4 to 12 wk 
thereafter, depending on the frequency of dosing in an ISA
HBV DNA 
At a visit corresponding to an interval of approximately 
12 to 16 wk from the last HBV DNA test. Only for 
participants who are anti-HBc positive at Visit 401 of the 
master protocol [IMMB] and are enrolled in the ISA.
10.13.3. 
Activities During a Posttreatment Follow-up Period  
An ISA is required to have a posttreatment follow-up period consisting of at least 1 visit. The 
duration of posttreatment follow-up is typically equal to, or greater than, 5 half-lives of a study 
intervention. Thus, the timing of this visit relative to the last administered dose of study 
intervention will vary across the ISAs. An ISA may include additional visits within this period. 
The number of added visits and the intervals between them will be determined by the ISA team. 
This table lists the timing and/or frequency of the required standard activities for this period. 
Activity 
Timing or Frequency in a Posttreatment Follow-up Period 
of an ISA
Patient-reported outcomes (electronic)
Dermatology Life Quality Index
At the final visit
Patient-Oriented Eczema Measure
At the final visit
SCORing Atopic Dermatitis (subjective)
At the final visit
Atopic Dermatitis Control Tool
At the final visit

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Activity 
Timing or Frequency in a Posttreatment Follow-up Period 
of an ISA
Clinician-administered assessments (electronic)
vIGA-AD 
At the final visit
Eczema Area and Severity Index
At the final visit
SCORing Atopic Dermatitis (objective)
At the final visit
Laboratory tests and sample collections 
Hematology 
At the final visit
Clinical chemistry
At the final visit
Urine pregnancy test (local) 
At the final visit
HBV DNA 
At intervals of approximately 12 to 16 wk during this period. 
Only for participants who are anti-HBc positive at Visit 401 of 
the master protocol [IMMB] and are enrolled in the ISA.
10.13.4. 
Activities During an Early Discontinuation Visit  
An ISA must specify which activities are to be performed at an ED visit. Some ED activities will 
be standard for all ISAs, but an ISA may include additional activities. This table lists the required 
standard activities for an ED visit. 
Activity 
Instruction
Patient-reported outcomes (electronic)
Dermatology Life Quality Index
Patient-Oriented Eczema Measure
SCORing Atopic Dermatitis (subjective)
Atopic Dermatitis Control Tool
Clinician-administered assessments (electronic)
vIGA-AD 
Eczema Area and Severity Index
SCORing Atopic Dermatitis (objective)
Laboratory tests and sample collections 
Hematology 
Clinical chemistry
Urine pregnancy test (local) 
HBV DNA 
Only for participants who are anti-HBc positive at Visit 401 of 
the master protocol (IMMB) and are enrolled in the ISA. 
Perform only if HBV DNA test has not been performed within 
16 wk or participant will not complete a posttreatment 
follow-up visit.
 
 

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10.14. 
Appendix 14: Abbreviations and Definitions  
 
Term 
Definition 
abuse 
use of a study intervention for recreational purposes or to maintain an addiction or 
dependence 
AD 
atopic dermatitis 
ADA 
anti-drug antibodies 
ADCT 
Atopic Dermatitis Control Tool 
ADSS 
Atopic Dermatitis Sleep Scale 
AE 
adverse event 
AESI 
adverse events of special interest 
AIDS 
acquired immune deficiency syndrome 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
anti-HBc 
hepatitis B core antibody 
anti-HCV 
antibodies to HCV 
AST 
aspartate aminotransferase 
authorized IMP 
applicable to the EU only: a medicinal product authorized in accordance with Regulation 
(EC) No 726/2004 or in any Member State concerned in accordance with Directive 
2001/83/EC, irrespective of changes to the labeling of the medicinal product, which is used 
as an investigational medicinal product 
authorized 
AxMP 
applicable to the EU only: a medicinal product authorized in accordance with Regulation 
(EC) No 726/2004, or in any Member State concerned in accordance with Directive 
2001/83/EC, irrespective of changes to the labeling of the medicinal product, which is used 
as an auxiliary medicinal product 
AxMP 
auxiliary medicinal product. See also NIMP. 
a medicinal product used for the needs of a clinical trial as described in the protocol, but not 
as an investigational medicinal product. Examples include rescue medication, challenge 
agents, agents to assess endpoints in the clinical trial, or background treatment. AxMP does 
not include investigational medicinal product (IMP) or concomitant medications. 
Concomitant medications are medications unrelated to the clinical trial and not relevant for 
the design of the clinical trial 

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BSA 
body surface area 
blinding 
A single-
of the treatment but the participant is not, or vice versa, or when the sponsor is aware of the 
 staff and the participant are not. 
A double-blind study is one in which neither the participant nor any of the investigator or 
sponsor staff who are involved in the treatment or clinical evaluation of the subjects are 
aware of the treatment received 
CBD 
cannabidiol 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
COA 
clinical outcome assessment 
complaint 
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system 
compliance 
adherence to all study-related requirements, GCP requirements, and applicable regulatory 
requirements 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
case report form; a printed, optical, or electronic document designed to record all of the 
protocol-required information to be reported to the sponsor for each trial participant 
CRO 
contract research organization 
CSR 
clinical study report 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CT 
computed (or computerized) tomography 
CTA 
clinical trial agreement 
CTR 
Clinical Trial Regulation 
device 
deficiencies 
equivalent to product complaint 
DLQI 
Dermatology Life Quality Index 

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DMC 
data monitoring committee. A data monitoring committee, or data monitoring board (DMB) 
is a group of independent scientists who are appointed to monitor the safety and scientific 
integrity of a human research intervention, and to make recommendations to the sponsor 
regarding the stopping of a study for efficacy, or for harms, or for futility. The composition 
of the committee is dependent upon the scientific skills and knowledge required for 
monitoring the particular study. 
DNA 
deoxyribonucleic acid 
DSM-V 
Diagnostic and Statistical Manual of Mental Disorders. 5th ed.  
EASI 
Eczema Area and Severity Index 
ECG 
electrocardiogram 
eCOA 
electronic clinical outcome assessment 
EDC 
electronic data capture 
ED 
early discontinuation 
eGFR 
estimated glomerular filtration rate 
enroll 
the act of assigning a participant to a treatment (study intervention). Participants who are 
enrolled in the study are those who have been assigned to a treatment 
enter 
Participants entered into a study are those who have signed the ICF directly or through their 
legally acceptable representative 
ERB 
ethics (or ethical) review board. An independent body constituted of medical, scientific, and 
non-scientific members, whose responsibility is to ensure the protection of the rights, safety, 
and well-being of human participants involved in a trial by, among other things, reviewing, 
approving, and providing continuing review of trials, of protocols and amendments, and of 
the methods and material to be used in obtaining and documenting informed consent of the 
trial participants 
EU 
European Union 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
hr 
hour, or hours 

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HRQoL 
health-related quality of life 
IAC 
Internal Assessment Committee 
IB 
 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
 
IgA 
immunoglobulin A 
IGA 
 
IGRA 
interferon gamma release assay 
IL 
interleukin 
IMP 
 
a medicinal product which is being tested or used as a reference, including as a placebo, in a 
clinical trial 
IND 
Investigational New Drug application 
informed consent 
a process by which participants voluntarily confirm their willingness to participate in a 
particular study, after having been informed of all aspects of the study that are relevant to 
 by means of a 
written, signed, and dated ICF 
INR 
international normalized ratio 
interim analysis 
an analysis of clinical trial data by intervention group that is conducted before the primary 
outcome database lock. Also, an analysis comparing intervention groups at any time before 
the final reporting database is locked 
investigational 
product (IP) 
a pharmaceutical form of an active ingredient or placebo being tested or used as a reference 
in a clinical trial, including products already on the market when used or assembled 
(formulated or packaged) in a way different from the authorized form, or marketed products 
used for an unauthorized indication, or marketed products used to gain further information 
 
IRB 
 
ISA 
intervention-specific appendix 
ISA-SAP 
statistical analysis plan for an intervention-specific appendix (ISA) 

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ITT 
intention to treat: The principle that asserts that the effect of a treatment policy can be best 
assessed by evaluating on the basis of the intention to treat a participant (that is, the planned 
treatment regimen) rather than the actual treatment given. It has the consequence that 
participant allocated to an intervention group should be followed up, assessed, and analyzed 
as members of that group irrespective of their compliance to the planned course of treatment 
IWRS 
interactive web-response system 
JAK 
Janus kinase 
LTBI 
latent tuberculosis infection 
MedDRA 
Medical Dictionary for Regulatory Activities 
medication error 
Errors in the prescribing, dispensing, or administration of a study intervention, regardless of 
whether or not the medication is administered to the participant or the error leads to an AE. 
Medication error generally involves a failure to uphold 1 or more of the 5 
medication use: the right participant, the right drug, the right dose, right route, at the right 
time. 
In addition to the core 5 rights, the following may also represent medication errors: 
dose omission associated with an AE or a product complaint 
 
-use date 
 
ration technique inconsistent with the 
, for example, Summary of Product Characteristics, IB, local label, 
protocol, or 
or prefilled pens, or both. 
misuse 
use of a study intervention for self-treatment that is inconsistent with either the prescribed 
dosing regimen or indication, or both, or is obtained without a prescription 
MP-SAP 
statistical analysis plan for the master protocol 
N/A 
not applicable 
NIMP 
noninvestigational medicinal product. See AxMP. 
a medicinal product used for the needs of a clinical trial as described in the protocol, but not 
as an investigational medicinal product. Examples include rescue medication, challenge 
agents, agents to assess endpoints in the clinical trial, or background treatment 
NRS 
numeric rating scale 
participant 
equivalent 
as recipient of an investigational medicinal product or as a control 
PC 
product complaint 

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PCR 
polymerase chain reaction 
PD 
pharmacodynamics 
PK 
pharmacokinetics 
POEM 
Patient-Oriented Eczema Measure 
PPD 
purified protein derivative 
PRO(s) 
patient-reported outcome(s) 
PT-INR 
prothrombin time, international normalized ratio 
QoL 
quality of life 
QTc 
corrected QT interval 
QTLs 
quality tolerance limits 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SCORAD 
SCORing Atopic Dermatitis 
screen 
the act of determining whether an individual meets minimum requirements to become part 
of a pool of potential candidates for participation in a clinical study 
SERMs 
selective estrogen receptor modulators 
SoA 
Schedule of Activities 
study drug 
 
study 
intervention 
any medicinal product or medical device intended to be administered to a study participant 
according to the study protocol 
SUSARs 
suspected unexpected serious adverse reactions 
Refers to an adverse event that occurs in a clinical trial participant, which is assessed by the 
sponsor and or study investigator as being unexpected, serious and as having a reasonable 
possibility of a causal relationship with the study intervention. 
TB 
tuberculosis 
TBL 
total bilirubin 
TCI 
topical calcineurin inhibitor 
TCS 
topical corticosteroid 

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TE ADA 
treatment-emergent anti-drug antibodies 
TEAE 
treatment-emergent adverse event: An untoward medical occurrence that emerges during a 
defined treatment period, having been absent pretreatment, or worsens relative to the 
pretreatment state, and does not necessarily have a causal relationship with this treatment 
THC 
tetrahydrocannabinol 
TST 
tuberculin skin test 
ULN 
upper limit of normal 
US or USA 
United States of America 
VAS 
visual analog scale 
wk 
week, or weeks 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
 
 

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10.15. 
Appendix 15: Master Protocol Amendment History  
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents.  
Amendment [a]: 13 Mar 2023 
Overall Rationale for the Amendment: 
The purpose of this amendment is to include language to address regulatory expectations. Minor 
editorial or formatting corrections are not represented in this table. 
Section # and Name 
Description of Change 
Brief Rationale 
1.3. Schedule of Activities 
Removed anti-HBs from the description of 
HBV screening tests 
Anti-HBs testing is not required 
for eligibility 
6. Study Intervention(s) and 
Concomitant Therapy 
Reworded the definition of study intervention 
To improve alignment with 
regulatory definitions 
8.2.9. Hepatitis B Testing 
and Monitoring 
Removed anti-HBs from the description of 
HBV screening tests 
To align with Section 1.3. 
8.7. Exploratory Biomarkers 
 
To simplify the text and reduce 
implicit redundancy 
10.1.4. Data Protection 
Added statements to clarify methods for 
protection of personal data and handling of 
data security breach 
To address an EU CTR 
(536/2014) requirement 
10.2. Appendix 2: Clinical 
Laboratory Tests 
Removed anti-HBs from the list of HBV 
screening tests 
To align with Section 1.3 
10.3.6. Regulatory 
Reporting Requirements 
Added a statement on the reporting SUSARs 
To address an EU CTR 
(536/2014) requirement 
10.13. Appendix 13: 
Requirements for ISA 
Design 
Removed requirement for ISAs to have 
sample collections for 
 
 
 
 
 
10.14. Appendix 14: 
Abbreviations and 
Definitions 
Reworded the definition of study intervention 
To improve alignment with 
regulatory definitions 
10.15. Appendix 15: Master 
Protocol Amendment 
History 
Revised statement about amendment history 
To ensure internal document 
consistency 
 

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