A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Lebrikizumab When Used in Combination With Topical Corticosteroid Treatment in Japanese Patients With Moderate-to-Severe Atopic Dermatitis
Phase: PHASE3
Conditions: Dermatitis, Atopic, Dermatitis, Eczema, Skin Diseases, Skin Diseases, Genetic
Sponsor: Eli Lilly and Company

 
 
 
Protocol J2T-JE-KGAL (a)  
 
 
A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of 
Lebrikizumab When Used in Combination with Topical Corticosteroid Treatment in Japanese 
Patients with Moderate-to-Severe Atopic Dermatitis 
  
 
NCT04760314 
 
Approval Date: 22-Jan-2021 
 
 

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
1
Title Page
Confidential Information
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of lebrikizumab (LY3650150), unless such persons are bound by a confidentiality agreement with Eli Lilly 
and Company or its subsidiaries. 
Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential information 
exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any public release. 
In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be reproduced or 
otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries.
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy 
and Safety of Lebrikizumab When Used in Combination with Topical Corticosteroid 
Treatment in Japanese Patients with Moderate-to-Severe Atopic Dermatitis
Protocol Number: J2T-JE-KGAL
Amendment Number: a
Compound: Lebrikizumab (LY3650150)
Study Phase: 3
Short Title: Safety and Efficacy of Lebrikizumab in Combination with Topical Corticosteroids
in Japanese Patients with Moderate-to-Severe Atopic Dermatitis
Acronym: ADhere-J
Sponsor Name: Eli Lilly Japan K.K.
Legal Registered Address: Eli Lilly Japan K.K., Kobe Hyogo Japan
Regulatory Agency Identifier Number(s): Not available
Approval Date: Protocol Electronically Signed and Approved by Lilly on 19 November 2020.
Protocol Amendment (a) Electronically Signed and Approved by Lilly on date provided below.
Medical Monitor Name and Contact Information will be provided separately
Approval Date: 22-Jan-2021 GMT

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
2
Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Original Protocol
19-Nov-2020
Amendment [a]
Overall Rationale for the Amendment:
The overall changes and rationale for changes made to this protocol are described in the 
following table. Note that minor edits have been made throughout the protocol, which are not 
captured in the table.
Section # and Name
Description of Change
Brief Rationale
1.3. Schedule of 
Activities; Induction 
Period
Days from Randomization for 
Visit 2 has been revised from 
1 to 0.
Definition of Days from 
Randomization for Visit 2 changed.
1.3. Schedule of 
Activities; Induction 
Period, Health 
Outcome Measures 
and Other 
Questionnaires
Definitions of baseline for 
Itch, Sleep-Loss, Skin Pain 
and POEM have been added.
Clarification
1.3. Schedule of 
Activities; Induction 
Period, Laboratory 
Testing
and
8.2.7. Hepatitis B 
Testing and 
Monitoring
Language describing the 
participants who will not be 
required to undergo HBV 
DNA monitoring at screening 
has been revised from “or” to 
“and” and now states: 
“Participants who are HBsAg 
negative, HBcAb negative, 
and HBsAb positive with a 
documented history of 
hepatitis B vaccination will 
not be required to undergo 
HBV DNA monitoring at 
screening”
To correct the definition of 
participants who will be required the 
hepatitis B DNA monitoring.
8.2.8.
Hepatic Safety
Language describing the 
hepatic monitoring for 
pediatric participants has been 
added.
Threshold for performing 
close hepatic monitoring and 
comprehensive hepatic 
To follow the latest Lilly safety 
monitoring standards for hepatic 
monitoring.

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
3
Section # and Name
Description of Change
Brief Rationale
elevation has been updated in 
total bilirubin.
9.4.2.4. Treatment 
Compliance
Definition of treatment 
compliance has been added.
Clarification
10.1.6.
Data Quality 
Assurance
Language related to quality 
tolerance limits has been 
added.
To follow the latest Lilly requirement 
for quality tolerance limits.
10.4. Appendix 4: 
Contraceptive 
Guidance and 
Collection of 
Pregnancy
Information
Language describing still birth 
in the collection of pregnancy 
information has been revised 
from “>20 weeks gestational 
age” to “≥20 weeks gestational 
age” and now states: “A 
spontaneous abortion 
(occurring at <20 weeks 
gestational age) or still birth 
(occurring at ≥20 weeks 
gestational age) is always 
considered to be an SAE and 
will be reported as such”
To follow the latest Lilly required 
language for still birth.

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
4
Table of Contents
1.
Protocol Summary......................................................................................................7
1.1.
Synopsis.......................................................................................................................7
1.2.
Schema.......................................................................................................................10
1.3.
Schedule of Activities (SoA) ......................................................................................11
2.
Introduction..............................................................................................................25
2.1.
Study Rationale ..........................................................................................................25
2.2.
Background ................................................................................................................25
2.3.
Benefit/Risk Assessment ............................................................................................27
3.
Objectives and Endpoints.........................................................................................29
4.
Study Design .............................................................................................................32
4.1.
Overall Design............................................................................................................32
4.2.
Scientific Rationale for Study Design .........................................................................35
4.3.
Justification for Dose..................................................................................................35
4.4.
End of Study Definition..............................................................................................36
5.
Study Population ......................................................................................................37
5.1.
Inclusion Criteria........................................................................................................37
5.2.
Exclusion Criteria.......................................................................................................39
5.3.
Lifestyle Considerations .............................................................................................43
5.4.
Screen Failures...........................................................................................................43
6.
Study Intervention....................................................................................................44
6.1.
Study Intervention(s) Administered ............................................................................44
6.1.1.
Background Medication (Topical Treatment for AD)..................................................46
6.2.
Preparation/Handling/Storage/Accountability.............................................................47
6.3.
Measures to Minimize Bias: Randomization and Blinding..........................................47
6.4.
Study Intervention Compliance...................................................................................48
6.5.
Concomitant Therapy .................................................................................................48
6.5.1.
Permitted and Prohibited Treatments and Procedures..................................................49
6.5.2.
Moisturizers................................................................................................................49
6.5.3.
Rescue Treatment for Atopic Dermatitis .....................................................................49
6.6.
Dose Modification......................................................................................................50
6.7.
Intervention after the End of the Study........................................................................50
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................51
7.1.
Discontinuation of Study Intervention ........................................................................51
7.1.1.
Criteria for Permanent Discontinuation of Study Intervention.....................................51
7.1.2.
Criteria for Temporary Discontinuation of Study Intervention ....................................53
7.2.
Participant Discontinuation/Withdrawal from the Study .............................................54
7.2.1.
Discontinuation of Inadvertently Enrolled Participants ...............................................55
7.3.
Lost to Follow-Up ......................................................................................................55
8.
Study Assessments and Procedures .........................................................................56
8.1.
Efficacy and Health Outcome Assessments.................................................................56
8.1.1.
Efficacy Assessments .................................................................................................56

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
5
8.1.2.
Participant Reported Outcomes and Health-Related Quality of 
Life.............................................................................................................................57
8.2.
Safety Assessments ....................................................................................................59
8.2.1.
Physical Examinations................................................................................................60
8.2.2.
Vital Signs..................................................................................................................60
8.2.3.
Electrocardiograms.....................................................................................................60
8.2.4.
Clinical Safety Laboratory Assessments .....................................................................60
8.2.5.
Chest Radiography .....................................................................................................61
8.2.6.
Tuberculosis Testing and Monitoring..........................................................................61
8.2.7.
Hepatitis B Testing and Monitoring ............................................................................62
8.2.8.
Hepatic Safety ............................................................................................................62
8.2.9.
Growth Monitoring.....................................................................................................65
8.3.
Adverse Events and Serious Adverse Events ..............................................................65
8.3.1.
Time Period and Frequency for Collecting Adverse Event and 
Serious Adverse Event Information ............................................................................65
8.3.2.
Method of Detecting Adverse Events and Serious Adverse 
Events.........................................................................................................................66
8.3.3.
Follow-Up of Adverse Events and Serious Adverse Events.........................................66
8.3.4.
Regulatory Reporting Requirements for Serious Adverse Events................................66
8.3.5.
Pregnancy...................................................................................................................66
8.3.6.
Adverse Events of Special Interest..............................................................................67
8.3.7.
Hypersensitivity Events ..............................................................................................67
8.3.8.
Product Complaints ....................................................................................................67
8.4.
Treatment of Overdose ...............................................................................................68
8.5.
Pharmacokinetics........................................................................................................69
8.5.1.
Bioanalysis .................................................................................................................69
8.6.
Pharmacodynamics.....................................................................................................69
8.7.
Genetics .....................................................................................................................69
8.8.
Biomarkers.................................................................................................................69
8.9.
Immunogenicity Assessments.....................................................................................70
8.10.
Health Economics.......................................................................................................70
9.
Statistical Considerations.........................................................................................71
9.1.
Statistical Hypotheses.................................................................................................71
9.2.
Sample Size Determination.........................................................................................71
9.3.
Populations for Analyses ............................................................................................71
9.4.
Statistical Analyses.....................................................................................................73
9.4.1.
General Considerations...............................................................................................73
9.4.2.
Treatment Group Comparability .................................................................................74
9.4.3.
Efficacy Analyses.......................................................................................................75
9.4.4.
Safety Analyses ..........................................................................................................75
9.4.5.
Pharmacokinetic/Pharmacodynamic Analyses ............................................................76
9.4.6.
Evaluation of Immunogenicity....................................................................................76
9.4.7.
Subgroup, Supplemental, and Other Exploratory Analyses .........................................77
9.5.
Interim Analyses.........................................................................................................77
9.6.
Data Monitoring Committee .......................................................................................78
10.
Supporting Documentation and Operational Considerations ................................79

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
6
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................................79
10.1.1.
Regulatory and Ethical Considerations........................................................................79
10.1.2.
Financial Disclosure ...................................................................................................79
10.1.3.
Informed Consent Process ..........................................................................................80
10.1.4.
Data Protection...........................................................................................................80
10.1.5.
Dissemination of Clinical Study Data .........................................................................81
10.1.6.
Data Quality Assurance ..............................................................................................81
10.1.7.
Source Documents......................................................................................................83
10.1.8.
Study and Site Start and Closure.................................................................................83
10.1.9.
Publication Policy.......................................................................................................83
10.1.10. Investigator Information .............................................................................................84
10.1.11. Long-Term Sample Retention.....................................................................................84
10.2.
Appendix 2: Clinical Laboratory Tests........................................................................85
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-Up, and Reporting......................................................88
10.3.1.
Definition of AE.........................................................................................................88
10.3.2.
Definition of SAE.......................................................................................................89
10.3.3.
Recording and Follow-Up of AEs and/or SAEs ..........................................................90
10.3.4.
Reporting of SAEs......................................................................................................92
10.4.
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information ...............................................................................................93
10.5.
Appendix 5: Genetics .................................................................................................95
10.6.
Appendix 6: Liver Safety: Suggested Actions and Follow-Up 
Assessments ...............................................................................................................96
10.7.
Appendix 7: American Academy of Dermatology: Criteria for 
the Diagnosis and Assessment of Atopic Dermatitis ...................................................98
10.8.
Appendix 8: Provisions for Changes in Study Conduct During 
Exceptional Circumstances.........................................................................................99
10.9.
Appendix 9: Abbreviations .......................................................................................103
11.
References...............................................................................................................108

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
7
1.
Protocol Summary
1.1.
Synopsis
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the 
Efficacy and Safety of Lebrikizumab When used in Combination with Topical 
Corticosteroid Treatment in Japanese Patients with Moderate-to-Severe 
Atopic Dermatitis
Short Title:
Safety and Efficacy of Lebrikizumab in Combination with Topical 
Corticosteroids in Japanese Patients with Moderate-to-Severe Atopic Dermatitis
Rationale:
The use of lebrikizumab for atopic dermatitis (AD) is supported by numerous preclinical studies 
demonstrating that AD is characterized by the increased expression of interleukin (IL)-13 in skin. 
Moreover, clinical studies (Phase 2a Study GS29250 and Phase 2b Study DRM0-AD01) with 
lebrikizumab demonstrated significant clinical benefit in participants with AD. Additional 
detailed discussion of the lebrikizumab studies is provided in the lebrikizumab Investigator’s 
Brochure (IB).
Objectives and Endpoints
Objective
Endpoints
Primary

To test the hypothesis that lebrikizumab 
250 mg Q2W or lebrikizumab 250 mg Q4W 
is superior to placebo in reducing signs and 
symptoms of AD at Week 16 in Japanese 
participants with moderate-to-severe 
AD when used in combination with 
TCS treatment

Proportion of participants achieving EASI-75 
at Week 16

Proportion of participants achieving an IGA 
score of 0 or 1 and a reduction of ≥2 points 
from baseline to Week 16
Major Secondary

To compare the efficacy and health 
outcome measures of lebrikizumab 250 mg 
Q2W or lebrikizumab 250 mg Q4W to 
placebo during the 16-week Induction 
Period in Japanese participants with 
moderate-to-severe AD when used in 
combination with TCS treatment

Percentage change in EASI score from 
baseline to Week 16

Proportion of participants achieving EASI-90 
at Week 16

Proportion of participants with an Itch NRS 
score of ≥4 points at baseline who achieve a 
≥4-point reduction from baseline to Weeks 1, 
2, 4 and 16
Abbreviations: AD = atopic dermatitis; EASI = Eczema Area and Severity Index; EASI-75 = ≥75% reduction 
from baseline in EASI score; EASI-90 = ≥90% reduction from baseline in EASI score; IGA = Investigator’s 
Global Assessment; NRS = numeric rating scale; Q2W = every 2 weeks; Q4W = every 4 weeks; TCS = topical 
corticosteroid.

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
8
Overall Design
Study J2T-JE-KGAL is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group 
study, which is 68 weeks in treatment duration. The study is designed to evaluate the safety and 
efficacy of lebrikizumab when used in combination with topical corticosteroid (TCS) treatment 
compared with placebo in combination with TCS treatment using a 16-week induction treatment 
and a 52-week Long-Term Maintenance Period of lebrikizumab for Japanese participants with 
moderate-to-severe AD.
The 16-week Induction Period will be double blinded and double dummy. All study intervention
injections in the Induction Period will be administered by site staff in the clinic. After completion 
of the Week 16 visit, participants (responders) originally assigned to lebrikizumab 250 mg every 
2 weeks (Q2W) will be re-randomized to either lebrikizumab 250 mg Q2W or lebrikizumab 
250 mg every 4 weeks (Q4W), and participants originally assigned to 250 mg lebrikizumab 
Q4W or placebo will stay on the originally assigned treatment for the Maintenance Period.
Non-responders at Week 16 and participants who used rescue therapy in the Induction Period 
will move to the Escape Arm from Week 16.
Treatment regimen assignment will remain blinded during the Maintenance Period. 
Participants who do not maintain a ≥50% reduction from baseline in Eczema Area and Severity 
Index score (EASI-50) response at certain time points in the Maintenance Period will be assigned 
to an Escape Arm and will receive lebrikizumab 250 mg Q2W as open-label treatment through
Week 68.
During the Maintenance Period, participants will be instructed to self-administer study 
intervention. Administration by the participants or caregiver is recommended. If the participant
or caregiver is not able to administer any dose throughout the study, study site staff may 
administer the injection.
Participants who terminate early or complete the 68-week treatment period will receive a safety 
follow-up visit, which includes vital signs, Columbia-Suicide Severity Rating Scale (C-SSRS),
self-harm supplement and self-harm follow-up form, and pharmacokinetic (PK) and 
immunogenicity samples.
Disclosure Statement: This is a parallel-group treatment study with 3 arms that is participant 
and investigator blinded.
Number of Participants:
Approximately 280 participants will be randomized in a 3:2:2 ratio to lebrikizumab 250 mg 
Q2W, lebrikizumab 250 mg Q4W, or placebo (120 participants: 80 participants:80 participants).
Intervention Groups and Duration:
The study treatment period is 68 weeks followed by a safety follow-up visit 10 weeks later
(78 weeks in total).

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
9
Approximately 280 participants, including approximately 15 adolescent participants (≥12 to 
<18 years and weighing ≥40 kg) will be randomized in a 3:2:2 ratio to treatment:

250 mg lebrikizumab (loading dose of 500 mg given at baseline and Week 2) 
by subcutaneous (SC) injection Q2W

250 mg lebrikizumab (loading dose of 500 mg given at baseline) by SC injection 
Q4W, or

placebo.
Data Monitoring Committee: Yes

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
10
1.2.
Schema

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
11
1.3.
Schedule of Activities (SoA)
Study Schedule Protocol J2T-JE-KGAL
Induction Period: Screening Through Week 16
Screening
Induction Period
Comments
Visit Number
1
2
3
4
5
6
7
8
9
10
Weeks from Randomization
–
0
2
4
6
8
10
12
14
16
Days from Randomization
–
0
14
28
42
56
70
84
98
112
Visit Tolerance Interval (days)
-7 to -30
–
±3
±3
±3
±3
±3
±3
±3
±3
Informed consent/assent
X
Inclusion and exclusion criteria
X
X
Medical history
X
X
Demography
X
X
Review of immunization record
X
Adolescents only
IWRS entry
X
X
X
X
X
X
X
X
X
X
Randomization
X
X
Dispense background TCS
X
X
X
X
X
X
X
X
X
X
Weigh (tube with cap) and record 
returned background TCS
X
X
X
X
X
X
X
X
Administer study intervention
X
X
X
X
X
X
X
X
X
Administered by site personnel.
At Visit 10, participants or 
their caregiver will administer 
study intervention under site 
personnel supervision.
At Visits 2 and 3: 2 injections
At Visit 10 for participants in 
the Escape Arm: 2 injections
All other visits: 1 injection

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
12
Study Schedule Protocol J2T-JE-KGAL
Induction Period: Screening Through Week 16
Screening
Induction Period
Comments
Visit Number
1
2
3
4
5
6
7
8
9
10
Weeks from Randomization
–
0
2
4
6
8
10
12
14
16
Days from Randomization
–
1
14
28
42
56
70
84
98
112
Visit Tolerance Interval (days)
-7 to -30
–
±3
±3
±3
±3
±3
±3
±3
±3
Safety
Vital signs
X
X
X
X
X
X
X
X
X
X
Physical examination including 
height and weight
X
X
12-lead ECG (single)
X
Performed locally. 
Abnormalities recorded as AEs.
Chest x-ray (posterior-anterior view)
X
Will be performed locally at 
screening if applicable
(Section 8.2.5). Abnormalities 
recorded as AEs.
Prior therapy
X
Concomitant medications/procedures
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
Investigator Scales
IGA, EASI
X
X
X
X
X
X
X
X
X
X
SCORAD
X
X
X
X
X
X
X
X
X

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
13
Study Schedule Protocol J2T-JE-KGAL
Induction Period: Screening Through Week 16
Screening
Induction Period
Comments
Visit Number
1
2
3
4
5
6
7
8
9
10
Weeks from Randomization
–
0
2
4
6
8
10
12
14
16
Days from Randomization
–
1
14
28
42
56
70
84
98
112
Visit Tolerance Interval (days)
-7 to -30
–
±3
±3
±3
±3
±3
±3
±3
±3
Health Outcome Measures and Other Questionnaires
Itch, Sleep-Loss, Skin Pain (daily)
X
X (Will be collected daily via an electronic participant diary)
The baseline for the daily
assessments will be the average 
score of the 7 days prior to 
randomization.
POEM (weekly)
X
X (Will be collected weekly via an electronic participant diary)
The baseline for the weekly
assessments will be the score 
acquired closest to randomization.
DLQI/CDLQI
X
X
X
X
X
Will be collected as eCOA data.
Will be completed by the participant 
prior to any clinical assessments on 
days of study visits.
WPAI-AD
X
X
X
Will be collected as eCOA data.
Will be completed by the participant 
prior to any clinical assessments on 
days of study visits.
HADS
X
X
X
X
X
X
Will be collected as eCOA data.
Will be completed by the participant 
prior to any clinical assessments on 
days of study visits.
C-SSRS ‘Baseline/Screening’
X
C-SSRS ‘Since Last Visit’
X
X
X
X
X
X
X
X
X
Self-Harm Supplement Form
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-up Form
X
X
X
X
X
X
X
X
X
X
Only required if triggered by the 
Self-Harm Supplement Form.

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
14
Study Schedule Protocol J2T-JE-KGAL
Induction Period: Screening Through Week 16
Screening
Induction Period
Comments
Visit Number
1
2
3
4
5
6
7
8
9
10
Weeks from Randomization
–
0
2
4
6
8
10
12
14
16
Days from Randomization
–
1
14
28
42
56
70
84
98
112
Visit Tolerance Interval (days)
-7 to -30
–
±3
±3
±3
±3
±3
±3
±3
±3
Health Outcome Measures and Other Questionnaires
ACQ-5
X
X
X
Participants who report comorbid 
asthma prior to enrollment only.
Will be collected as eCOA data.
Will be completed by the 
participant prior to any clinical 
assessments on days of 
study visits.
Laboratory Testing
TB test
X
TB test(s), including PPD, 
QuantiFERON®-TB Gold, and T-
SPOT®. See Exclusion Criterion 
[17] for description of TB testing.
Performed locally and not 
captured in eCRF.
Read PPD if applicable 
(48-72 hours post PPD)
X
Participant must return and PPD 
test read 48 to 72 hours after 
Visit 1 (post PPD).

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
15
Study Schedule Protocol J2T-JE-KGAL
Induction Period: Screening Through Week 16
Screening
Induction Period
Comments
Visit Number
1
2
3
4
5
6
7
8
9
10
Weeks from Randomization
–
0
2
4
6
8
10
12
14
16
Days from Randomization
–
1
14
28
42
56
70
84
98
112
Visit Tolerance Interval (days)
-7 to -30
–
±3
±3
±3
±3
±3
±3
±3
±3
Laboratory Testing
Hematology, clinical chemistry
X
X
X
X
X
X
See Appendix 2, Clinical 
Laboratory Tests, for details.
Estradiol or testosterone
X
X
Collect estradiol in adolescent 
female participants only.
Collect testosterone in adolescent 
male participants only.
Lipids (fasting)
X
X
Participants should not eat or 
drink anything except water for 
12 hours prior before sample 
collection. If a participant attends 
these visits in a nonfasting state, 
this will not be considered a 
protocol violation.
Pregnancy test
serum
urine
urine
urine
urine
urine
For all women of childbearing 
potential, a serum pregnancy test 
(central laboratory) will be 
performed at Visit 1. Urine 
pregnancy tests will be performed 
locally and not captured in eCRF.
FSH
X
For female participants who are 
>40 to ≤55 years of age.

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
16
Study Schedule Protocol J2T-JE-KGAL
Induction Period: Screening Through Week 16
Screening
Induction Period
Comments
Visit Number
1
2
3
4
5
6
7
8
9
10
Weeks from Randomization
–
0
2
4
6
8
10
12
14
16
Days from Randomization
–
1
14
28
42
56
70
84
98
112
Visit Tolerance Interval (days)
-7 to -30
–
±3
±3
±3
±3
±3
±3
±3
±3
Laboratory Testing
HIV, HCV, HBV screening tests
X
For participants who are positive 
for HCV antibody, a follow-up test 
for HCV RNA will be performed 
automatically.
Participants who are positive for 
HCV antibody and negative for 
HCV RNA may be enrolled.
HBV DNA
X
X
X
X
X
Participants who are HBsAg 
negative and positive for HBcAb 
(and/or HBsAb) will automatically 
have an HBV DNA test performed 
at screening.
Participants who are HBsAg 
negative, HBcAb negative, and
HBsAb positive with a 
documented history of hepatitis B 
vaccination will not be required to 
undergo HBV DNA monitoring at 
screening.
If screening HBV DNA is 
negative, defined as undetectable 
HBV DNA, the participant is not 
excluded, and HBV DNA 
monitoring is required per the 
schedule. (Section 8.2.7).

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
17
Study Schedule Protocol J2T-JE-KGAL
Induction Period: Screening Through Week 16
Screening
Induction Period
Comments
Visit Number
1
2
3
4
5
6
7
8
9
10
Weeks from Randomization
–
0
2
4
6
8
10
12
14
16
Days from Randomization
–
1
14
28
42
56
70
84
98
112
Visit Tolerance Interval (days)
-7 to -30
–
±3
±3
±3
±3
±3
±3
±3
±3
Laboratory Testing
Beta-D-glucan
X
Urinalysis
X
X
X
Lebrikizumab PK samples
X
X
X
X
PK samples should be collected 
prior to dosing on days of dosing. 
Additional samples can be
collected for any participants 
experiencing a hypersensitivity 
reaction during study
(Section 8.3.7).
Immunogenicity samples
X
X
X
X
Immunogenicity samples should 
be collected prior to dosing on 
days of dosing. Additional sample
can be collected for any 
participants experiencing a 
hypersensitivity reaction during 
study (Section 8.3.7).
Genetic samples
X
Collected at Visit 2. Sample 
collection can be rescheduled to 
any other visit if blood volume is 
limited at Visit 2.
TARC
X
X
X
X
X

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
18
Study Schedule Protocol J2T-JE-KGAL
Maintenance Period: Week 18 to Week 40/Escape Arm
Maintenance Period
Comments
Visit Number
11
12
13
14
15
16
17
Weeks from Randomization
18
20
24
28
32
36
40
Days from Randomization
126
140
168
196
224
252
280
Visit Tolerance Interval (days)
±5
±5
±5
±5
±5
±5
±5
IWRS entry
X
X
X
X
X
X
X
Dispense background TCS
X
X
X
X
X
X
X
Weigh (tube with cap) and record 
returned background TCS
X
X
X
X
X
X
X
Dispense IP for home treatment
X
X
X
X
X
X
IP returned and compliance assessed
X
X
X
X
X
Administer study intervention
X
X (every 2 weeks)
At Visit 11, participants or their caregiver will administer study 
intervention under site personnel supervision.
Subsequent administration will be administered by participants 
or their caregiver at home.
At Visit 11, for participants in the Escape Arm: 2 injections.
All other visits: 1 injection.
Safety
Vital signs
X
X
X
X
X
X
X
Physical examination including height 
and weight
X
Concomitant medications/procedures
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
Investigator Scales
IGA, EASI
X
X
X
X
X
X
X
SCORAD
X
X
X
X
X
X
X

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
19
Study Schedule Protocol J2T-JE-KGAL
Maintenance Period: Week 18 to Week 40/Escape Arm
Maintenance Period
Comments
Visit Number
11
12
13
14
15
16
17
Weeks from Randomization
18
20
24
28
32
36
40
Days from Randomization
126
140
168
196
224
252
280
Visit Tolerance Interval (days)
±5
±5
±5
±5
±5
±5
±5
Health Outcomes Measures and Other Questionnaires
Itch, Sleep-Loss, Skin Pain
X (Will be collected daily via an electronic participant diary)
POEM (weekly)
X (Will be collected weekly via an electronic participant diary)
Will be collected as eCOA data. Will be completed by the 
participant prior to any clinical assessments on days of 
study visits.
DLQI/CDLQI
X
X
X
X
X
X
Will be collected as eCOA data. Will be completed by the 
participant prior to any clinical assessments on days of 
study visits.
WPAI-AD
X
X
Will be collected as eCOA data. Will be completed by the 
participant prior to any clinical assessments on days of 
study visits.
HADS
X
X
X
X
X
X
Will be collected as eCOA data. Will be completed by the 
participant prior to any clinical assessments on days of 
study visits.
C-SSRS ‘Since Last Visit’
X
X
X
X
X
X
X
Self-Harm Supplement Form
X
X
X
X
X
X
X
Self-Harm Follow-up Form
X
X
X
X
X
X
X
Only required if triggered by the Self-Harm Supplement Form.
Laboratory Testing
Hematology, clinical chemistry
X
X
X
See Appendix 2, Clinical Laboratory Tests, for details.
Estradiol or testosterone
X
Collect estradiol in adolescent female participants only.
Collect testosterone in adolescent male participants only.
Lipids (fasting)
X
Participants should not eat or drink anything except water for 
12 hours prior to sample collection. If a participant attends 
these visits in a nonfasting state, this will not be considered a 
protocol violation.
Pregnancy test
urine
urine
urine
urine
urine
urine
urine
Urine pregnancy tests will be performed locally and not 
captured in the eCRF. If required per investigator judgment, 
local regulations, and/or institutional guidelines, additional 
pregnancy testing can occur during the study treatment period.

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
20
Study Schedule Protocol J2T-JE-KGAL
Maintenance Period: Week 18 to Week 40/Escape Arm
Maintenance Period
Comments
Visit Number
11
12
13
14
15
16
17
Weeks from Randomization
18
20
24
28
32
36
40
Days from Randomization
126
140
168
196
224
252
280
Visit Tolerance Interval (days)
±5
±5
±5
±5
±5
±5
±5
Laboratory Testing
HBV DNA
X
X
X
X
X
X
If screening HBV DNA is negative, defined as undetectable 
HBV DNA, the participant is not excluded, and HBV DNA 
monitoring is required per the schedule (Section 8.2.7).
Urinalysis
X
Lebrikizumab PK samples
X
X
PK samples should be collected prior to dosing on days of 
dosing. Additional sample can be collected for any participants 
experiencing a hypersensitivity reaction during the study
(Section 8.3.7).
Immunogenicity samples
X
X
Immunogenicity samples should be collected prior to dosing on 
days of dosing. Additional sample can be collected for any 
participants experiencing a hypersensitivity reaction during the 
study (Section 8.3.7).
TARC
X
X
X
X
X
X

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
21
Study Schedule Protocol J2T-JE-KGAL
Maintenance Period: Week 44 to Week 68/Escape Arm
Maintenance Period
Safety 
Follow-
Up
Comments
Visit Number
18
19
20
21
22
23
24/ET
801
Weeks from Randomization
44
48
52
56
60
64
68
78
Days from Randomization
308
336
364
392
420
448
476
546
Visit Tolerance Interval (days)
±5
±5
±5
±5
±5
±5
±5
±5
IWRS entry
X
X
X
X
X
X
X
X
Dispense background TCS
X
X
X
X
X
X
Weigh (tube with cap) and record 
returned background TCS
X
X
X
X
X
X
X
Dispense IP for home treatment
X
X
X
X
X
X
IP returned and compliance 
assessed
X
X
X
X
X
X
X
Administer study intervention
X (every 2 weeks)
Administered by participants or their caregiver.
No administration at Visit 24/ET (Week 68).
Safety
Vital signs
X
X
X
X
X
X
X
X
Chest x-ray (posterior-anterior 
view)
X
X
X-ray at Visit 20, Visit 24, and at ET will be 
performed locally if more than 12 weeks have 
elapsed since the previous x-ray was obtained 
and not captured in the eCRF.
Physical examination including 
height and weight
X
X
Concomitant 
medications/procedures
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
Investigator Scales
IGA, EASI
X
X
X
X
X
X
X
X
SCORAD
X
X
X
X
X
X
X
X

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
22
Study Schedule Protocol J2T-JE-KGAL
Maintenance Period: Week 44 to Week 68/Escape Arm
Maintenance Period
Safety 
Follow-Up
Comments
Visit Number
18
19
20
21
22
23
24/ET
801
Weeks from Randomization
44
48
52
56
60
64
68
78
Days from Randomization
308
336
364
392
420
448
476
546
Visit Tolerance Interval (days)
±5
±5
±5
±5
±5
±5
±5
±5
Health Outcome Measures and Other Questionnaires
Itch, Sleep-Loss, Skin Pain 
(daily)
X (Will be collected daily via an electronic participant diary)
Will be collected as eCOA data. Will be completed 
by the participant prior to any clinical assessments 
on days of study visits.
POEM (weekly)
  X (Will be collected weekly via an electronic participant diary)
Will be collected as eCOA data. Will be completed 
by the participant prior to any clinical assessments 
on days of study visits.
DLQI/CDLQI
X
X
X
X
X
X
X
X
Will be collected as eCOA data. Will be completed 
by the participant prior to any clinical assessments 
on days of study visits.
WPAI-AD
X
X
Will be collected as eCOA data. Will be completed 
by the participant prior to any clinical assessments 
on days of study visits.
HADS
X
X
X
X
X
X
X
X
Will be collected as eCOA data. Will be completed 
by the participant prior to any clinical assessments 
on days of study visits.
C-SSRS ‘Since Last Visit’
X
X
X
X
X
X
X
X
Self-Harm Supplement Form
X
X
X
X
X
X
X
X
Self-Harm Follow-up Form
X
X
X
X
X
X
X
X
Only required if triggered by the Self-Harm 
Supplement Form.
ACQ-5
X
X
Will be collected as eCOA data. Will be completed 
by the participant prior to any clinical assessments 
on days of study visits.

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
23
Study Schedule Protocol J2T-JE-KGAL
Maintenance Period: Week 44 to Week 68/Escape Arm
Maintenance Period
Safety 
Follow-Up
Comments
Visit Number
18
19
20
21
22
23
24/ET
801
Weeks from Randomization
44
48
52
56
60
64
68
78
Days from Randomization
308
336
364
392
420
448
476
546
Visit Tolerance Interval (days)
±5
±5
±5
±5
±5
±5
±5
±5
Laboratory Testing
Hematology, clinical chemistry
X
X
X
X
Estradiol or testosterone
X
X
Collect estradiol in adolescent female participants only.
Collect testosterone in adolescent male participants only.
Lipids (fasting)
X
X
Participants should not eat or drink anything except water 
for 12 hours prior to sample collection. If a participant 
attends these visits in a nonfasting state, this will not be
considered a protocol violation.
Pregnancy test
urine
urine
urine
urine
urine
urine
urine
urine
Urine pregnancy tests will be performed locally and not 
captured in the eCRF. If required per investigator 
judgment, local regulations, and/or institutional 
guidelines, additional pregnancy testing can occur during 
the study treatment period.
HBV DNA
X
X
X
If screening HBV DNA is negative, defined as 
undetectable HBV DNA, the participant is not excluded, 
and HBV DNA monitoring is required per the schedule
(Section 8.2.7).
Urinalysis
X
X

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
24
Study Schedule Protocol J2T-JE-KGAL
Maintenance Period: Week 44 to Week 68/Escape Arm
Maintenance Period
Safety 
Follow-Up
Comments
Visit Number
18
19
20
21
22
23
24/ET
801
Weeks from Randomization
44
48
52
56
60
64
68
78
Days from Randomization
308
336
364
392
420
448
476
546
Visit Tolerance Interval (days)
±5
±5
±5
±5
±5
±5
±5
±5
Laboratory Testing
Lebrikizumab PK samples
X
X
X
PK samples should be collected prior to dosing on 
days of dosing. Additional sample can be collected 
for any participants experiencing a hypersensitivity 
reaction during study (Section 8.3.7).
Immunogenicity samples
X
X
X
Immunogenicity samples should be collected prior 
to dosing on days of dosing. Additional sample can 
be collected for any participants experiencing a 
hypersensitivity reaction during study
(Section 8.3.7).
TARC
X
X
X
X
X
X
X
Abbreviations: ACQ-5 = Asthma Control Questionnaire-5; AE = adverse event; C-SSRS = Columbia-Suicide Severity Rating Scale; 
DLQI/CDLQI = Dermatology Life Quality Index/Children’s Dermatology Life Quality Index; EASI = Eczema Area and Severity Index; 
ECG = electrocardiogram; eCOA = electronic clinical outcome assessment; eCRF = electronic case report form; ET = early termination; 
FSH = follicle-stimulating hormone; HADS = Hospital Anxiety Depression Scale; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface 
antibody; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IGA = 
Investigator’s Global Assessment; IP = investigational product; IWRS = interactive web response system; PK = pharmacokinetic; POEM = Patient-Oriented 
Eczema Measure; PPD = purified protein derivative; SCORAD = SCORing Atopic Dermatitis; TARC = thymus and activation-regulated chemokine;
TB = tuberculosis; TCS = topical corticosteroids; WPAI-AD = Work Productivity and Activity Impairment-Atopic Dermatitis.

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
25
2.
Introduction
Lebrikizumab is a humanized monoclonal immunoglobulin (Ig) G4 antibody (huIgG4) currently 
under investigation for the treatment of AD.
2.1.
Study Rationale
The use of lebrikizumab for AD is supported by numerous preclinical studies demonstrating that
AD is characterized by the increased expression of IL-13 in skin. Moreover, clinical studies
(Phase 2a Study GS29250 and Phase 2b Study DRM06-AD01) with lebrikizumab demonstrated 
significant clinical benefit in participants with AD. Additional detailed discussion of the 
lebrikizumab studies is provided in the lebrikizumab IB.
2.2.
Background
Atopic dermatitis is a complex disease that is determined by genetic, environmental, and
immunologic factors (Werfel et al. 2016; Simon et al. 2019). Genetic studies of AD (Bieber 
2012; Auriemma et al. 2013; Weidinger et al. 2018) have shown that genes encoding for 
cytokines involved in the regulation of the immune system (IL-4, IL-5, and IL-13) are strongly 
associated with the development of AD (Novak et al. 2002; He et al. 2003; Hummelshoj et al. 
2003). In addition, variants of genes that encode for proteins involved in skin barrier function 
such as filaggrin (FLG) and loricrin (LOR) are also associated with AD (Van Bever and Llanora 
2011). Since FLG plays a central role in skin barrier integrity, loss of function mutations of the 
FLG gene are considered a major contributor to the development of early childhood AD (Bieber 
2008; Tanei 2009; Bieber 2012; Flohr and Irvine 2013).
Reduced epithelial barrier function, which represents the first line of protection against the
environment, is thought to lead to sensitization to environmental allergens, associated with
elevated IgE (present in about 50% to 80% of all patients with AD, particularly in children 
[Werfel et al. 2016]) and consistent with the presence in the skin of Type 2 cytokines (IL-4, IL-5, 
IL-9, IL-13, IL-25, IL-31, IL-33, and thymic stromal lymphopoietin) and inflammation. Type 2 
cytokines increase epidermal thickening, sensitization, inflammation, and pruritus and decrease 
the expression of antimicrobial peptides and the barrier proteins FLG, LOR, and involucrin. 
Interleukin 13 in particular can reduce epithelial integrity and barrier function through 
downregulation of FLG, LOR, and involucrin (Kim et al. 2008) and can act on keratinocytes in 
the skin to downregulate their differentiation (Howell et al. 2008). Interleukin 13 also induces 
T-cell chemoattractants that mediate T-cell infiltration into AD lesions (Purwar et al. 2006) and 
may also induce IL-5 expression and eosinophil infiltration through the induction of eosinophil
chemoattractants (Esche et al. 2004). Increased expression of IL-13 has consistently been 
reported in AD skin lesions and is associated with disease severity (Hamid et al. 1996; Jeong 
et al. 2003; Tazawa et al. 2004; La Grutta et al. 2005; Neis et al. 2006; Choy et al. 2012; 
Suárez-Fariñas et al. 2013). The elevation of IL-13 expression in the nonlesional skin of patients 
with AD supports the evaluation of anti-IL-13 therapies in patients with AD (Suárez-Fariñas 
et al. 2011).

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Protocol number J2T-JE-KGAL(a)
26
Epidemiology of Pediatric Atopic Dermatitis
Atopic dermatitis is one of the most common chronic medical diseases; 15% to 30% of children 
and 2% to 10% of adults are affected, and the prevalence appears to have increased over the past 
2 to 3 decades (Williams et al. 2008), with some geographic variability. With respect to disease 
severity, about 67% of pediatric patients with AD have mild disease, 14% to 26% have moderate 
disease, and 2% to 7% have severe disease (Silverberg 2017). Approximately 85% of all cases of 
AD begin before age 5, with up to 70% of children having spontaneous remission before 
adolescence (Illi et al. 2004; Bieber 2008; Hua et al. 2014).
Clinical Manifestations
Clinically, AD is characterized by xerosis, erythematous crusted eruption (dermatosis),
lichenification, and intense pruritus (Bieber 2008), which, along with the distribution, chronicity,
and history of skin lesions, form the basis for making a diagnosis of AD. Flares are frequently
triggered by exposure to environmental factors, irritants, and allergens (Bieber and Novak 2009). 
Several clinical patterns, with differing distributions of skin lesions in distinct age groups, have 
been noted (Weidinger and Novak 2016; Weidinger et al. 2018).
The infantile stage (up to 2 years of age) is characterized by eczema that is usually localized 
to the face, scalp, and extensor aspects of the arms and legs. The lesions are characterized 
by pruritic red eczematous plaques, erythema, papules, vesicles, excoriations, oozing, and
formation of crusts.
The adult stage (from age 2 years to puberty and onward) is less predictable. Affected patients 
may have had only a few outbreaks since infancy, or they may have had a chronic relapsing 
course. Lesions frequently localize to the face and neck (head-and-neck dermatitis), as well in 
the flexures of the elbows and knees, and a considerable portion of patients (around 30%) 
develop atopic hand eczema, which may interfere with workplace activities. Like affected 
children, adolescents and adults commonly have lichenification of the flexures and have 
facial dermatitis.
Patients with AD have a high disease burden, and their quality of life is significantly affected. In
one study, AD was shown to have a greater negative effect on patient mental health than diabetes
and hypertension (Zuberbier et al. 2006). Patients with moderate-to-severe AD have a higher
prevalence of social dysfunction and sleep impairment, which are directly related to the severity
of the disease (Williams et al. 2008). Depression, anxiety, and social dysfunction not only affect
patients with AD but also affect their caregivers (Zuberbier et al. 2006). Compared with 
patients with psoriasis, another common and debilitating skin disease, patients with AD have 
lower physical vitality, social functioning, role-emotional, and mental health scores (Kiebert 
et al. 2002).
Treatment for Atopic Dermatitis
The therapeutic approach to AD consists primarily of trigger avoidance, skin hydration with
bathing, and use of moisturizers and anti-inflammatory therapies consisting predominantly 
of TCS. In many patients, treatment with TCS provides some measure of symptomatic 
relief but does not always adequately control the disease. In patients with persistent 
moderate-to-severe disease not responding adequately to TCS, the step-up options include 
topical calcineurin inhibitors (TCIs), phototherapy, and immunosuppressive agents such as oral 

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
27
corticosteroids, cyclosporine, azathioprine, methotrexate (MTX), and mycophenolate mofetil
(MMF). Among these immunosuppressive agents, only cyclosporine is approved in Japan for the 
treatment of patients with severe adult AD who do not respond to conventional treatments and 
have eruptions with marked inflammation involving 30% or more of the body surface area 
(BSA). The use of cyclosporine is limited to short-term (8 to 12 weeks) and intermittent 
administration involving a 2-week or much longer period of discontinuation if long-term 
administration is necessary. Recently, in 2018, a clinically efficacious and relatively safe 
treatment, anti-IL-4R monoclonal antibody, dupilumab, was approved for the treatment of adult 
patients with moderate-to-severe AD. More recently, in 2020, the topical Janus kinase (JAK)
inhibitor delgocitinib was approved for the treatment of AD. Despite these treatments, there 
remains a major societal burden for those with AD and a significant unmet medical need
for treatment.
2.3.
Benefit/Risk Assessment
As of October 2019, lebrikizumab has been given to 311 healthy people and more than 
4200 study participants to study various diseases. More than 400 patients with AD have taken 
lebrikizumab. In Phase 2 studies, treatment-emergent adverse events (TEAEs) reported in 2% to 
10% of participants included nasopharyngitis, upper respiratory tract infection, all conjunctivitis, 
headache, herpes infections, injection site reactions, pruritus, diarrhea, and anxiety. No 
anaphylaxis or serious infections were reported as TEAEs in participants with AD.
Lebrikizumab may increase the risk of malignancy and serious infections. These have not been 
reported in the AD studies.
Serious adverse effects and death can occur in study participants. No deaths have been reported 
in AD studies with lebrikizumab.
In AD study participants, higher levels of eosinophils have been observed without resultant 
adverse events (AEs). Conjunctivitis, herpes infection or zoster, and parasitic infection or an 
infection related to an intracellular pathogen are the adverse events of special interest (AESI 
[Section 8.3.6]). These reactions, if they occur, will prompt additional testing and data collection 
and are among the reasons that a participant might be discontinued from study intervention.
To minimize study participant risk in this study (J2T-JE-KGAL), enrolled participants will 
receive study intervention doses at the clinic to enable appropriate predose safety assessments 
and postdose monitoring during the Induction Period.
The routine safety assessments include physical examinations, clinical safety laboratory tests
(including hematology and chemistry), suicidality/self-harm and depression evaluations, and
collection of vital signs and spontaneously reported AEs. The study design includes a
Posttreatment Follow-Up Period with at least 1 study visit for safety assessments.
Phase 2 efficacy studies of lebrikizumab (GS29250 [TREBLE], and DRM06-AD01) 
demonstrated significant clinical benefit in participants with AD.
In summary, in the context of the cumulative knowledge for lebrikizumab, the benefit/risk 
balance is assessed to be acceptable for testing in this Phase 3 study.
In this Phase 3 study, adolescent participants (≥12 to <18 years weighing ≥40 kg) will be 
included and will receive the same doses of lebrikizumab as adult participants. Pharmacokinetic 

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
28
analyses of SC doses of lebrikizumab reveal similar kinetics for adults and adolescents ≥12 to 
<18 years. Although maximal exposures are 
for any given dose in adolescent 
participants, due to their lower weight ranges, the safety profile observed in adolescent 
participants is comparable to the safety profile observed in adults. Therefore, we expect a similar 
exposure response relationship in this age group compared to adults based on partial 
extrapolation and propose to include adolescent participants in this study. We also expect that the 
adolescent AD participants ≥40 kg will respond to lebrikizumab with a similar overall safety 
profile as adult participants.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of lebrikizumab are in the IB. In Section 2.2, more details about pediatric 
populations are given.
CCI

CONFIDENTIAL
Protocol number J2T-JE-KGAL(a)
29
3.
Objectives and Endpoints
Objective
Endpoints
Primary

To test the hypothesis that lebrikizumab 250 
mg Q2W or lebrikizumab 250 mg Q4W is 
superior to placebo in reducing signs and 
symptoms of AD at Week 16 in Japanese 
participants with moderate-to-severe AD 
when used in combination with 
TCS treatment

Proportion of participants achieving EASI-75 
at Week 16

Proportion of participants achieving IGA score 
of 0 or 1 and a reduction of ≥2-points from 
baseline to Week 16
Major Secondary

To compare the efficacy and health 
outcome measures of lebrikizumab 250 mg 
Q2W or lebrikizumab 250 mg Q4W to 
placebo during the 16-week Induction 
Period in Japanese participants with 
moderate-to-severe AD when used in 
combination with TCS treatment

Percentage change in EASI score from 
baseline to Week 16

Proportion of participants achieving EASI-90 
at Week 16

Proportion of participants with an Itch NRS 
score of ≥4-points at baseline who achieve a 
≥4-point reduction from baseline to Weeks 1, 
2, 4 and 16
Other Secondary

To measure lebrikizumab exposure and 
assess the relationship between exposure 
and immunogenicity

Average serum lebrikizumab concentration at 
steady state

Lebrikizumab serum trough concentrations 
associated with ADA titer

To evaluate the efficacy and health outcome 
measures of lebrikizumab 250 mg Q2W and 
lebrikizumab 250 mg Q4W during the 16-
week Induction and 52-week Maintenance 
periods in Japanese participants with 
moderate-to-severe AD when used in 
combination with TCS treatment

Percentage change from baseline in EASI 
score by visit

Proportion of participants with EASI-50,
EASI-75, and EASI-90 by visit

Proportion of participants maintaining 
EASI-75 by visit during the 52-week 
Maintenance Period among those originally 
randomized to lebrikizumab 250 mg Q2W and 
lebrikizumab 250 mg Q4W who achieved 
EASI-75 at Week 16

Proportion of participants with an IGA score 
of 0 or 1 and a reduction of ≥2 points from 
baseline by visit

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Protocol number J2T-JE-KGAL(a)
30

Proportion of participants maintaining an IGA 
score of 0 or 1 with a ≥2-point improvement 
from baseline by visit during the 52-week 
Maintenance Period among those originally 
randomized to lebrikizumab 250 mg Q2W and 
lebrikizumab 250 mg Q4W who achieved and 
IGA score of 0 or 1 with a ≥2-point 
improvement from baseline at Week 16

Change from baseline in Itch NRS score by 
visit

Proportion of participants with an Itch NRS 
score of ≥4 points at baseline who achieve a 
≥4-point reduction from baseline by visit

Change from baseline in Skin Pain NRS score 
by visit

Number of Skin Pain-Free (Skin Pain 
NRS = 0) days

Proportion of participants with a Skin Pain 
NRS score of ≥4 points at baseline who 
achieve a ≥4-point reduction from baseline 
by visit

Change from baseline in percent BSA by visit

Change from baseline in Sleep-Loss score 
by visit

Proportion of participants achieving a ≥4-point 
improvement in DLQI/CDLQI score from 
baseline by visit

Proportion of participants achieving 
DLQI/CDLQI score of 0 or 1 by visit

Change from baseline in DLQI/CDLQI 
by visit

Change from baseline in POEM by visit

Change from baseline in WPAI-AD score by 
visit

Change from baseline in HADS score by visit

Change from Baseline in ACQ-5 score to 
Week 16 in participants who have self-
reported comorbid asthma

Percentage change from Baseline in SCORAD 
by visit

Proportion of TCS/TCI-free days over the 
16-week and 68-week study periods

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Protocol number J2T-JE-KGAL(a)
31

Total amount of TCS used over the 16-week 
and 68-week study periods

Time (days) to TCS/TCI-free use over the
16-week and 68-week study periods

To assess the growth of adolescent
participants treated with lebrikizumab

Mean changes in growth parameters (height,
weight, and BMI) over the course of treatment
Abbreviations: ACQ-5 = Asthma Control Questionnaire-5; AD = atopic dermatitis; ADA = anti-drug antibody; BMI 
= body mass index; BSA = body surface area; DLQI/CDLQI = Dermatology Life Quality Index/Children’s
Dermatology Life Quality Index; EASI = Eczema Area and Severity Index; EASI-50 = ≥50% reduction 
from baseline in EASI score; EASI-75 = ≥75% reduction from baseline in EASI score; EASI-90 = ≥90% 
reduction from baseline in EASI score; HADS = Hospital Anxiety Depression Scale; IGA = Investigator’s 
Global Assessment; NRS = numeric rating scale; POEM = Patient-Oriented Eczema Measure; Q2W = every 
2 weeks; Q4W = every 4 weeks; SCORAD = SCORing Atopic Dermatitis; TCS/TCI = topical 
corticosteroid/topical calcineurin inhibitor; WPAI-AD = Work Productivity and Activity Impairment – Atopic 
Dermatitis.

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Protocol number J2T-JE-KGAL(a)
32
4.
Study Design
4.1.
Overall Design
Study Design
Study KGAL is a randomized, double-blind, placebo-controlled, parallel-group study, which is 
68 weeks in treatment duration. The study is designed to evaluate the safety and efficacy of 
lebrikizumab when used in combination with TCS treatment compared with placebo in 
combination with TCS treatment using a 16-week induction treatment and a 52 week long-term 
Maintenance Period of lebrikizumab for Japanese participants with moderate-to-severe AD.
Study Population
Participants are eligible for the study if they

are ≥18 years or an adolescent (≥12 to <18 years of age and weighing ≥40 kg) with 
moderate-to-severe AD for at least 1 year, defined according to the American Academy 
of Dermatology Consensus Criteria (Eichenfield et al. 2014) (Appendix 7)

have an EASI score ≥16

have an Investigator’s Global Assessment (IGA) score ≥3, and

have an AD involvement in ≥10% of BSA
Investigators should review vaccination status in adolescent participants (≥12 to <18 years) and 
determine the benefit/risk of their participation. No changes in start or resumption of vaccine is 
required, and pediatric participants will follow the Japan immunization guidelines, with the 
exception of live vaccines. If a participant has received a live vaccine within 12 weeks of the 
baseline visit or intends to receive a live vaccine during the study or up to 125 days after the last 
dose of investigational product (IP), the participant is not eligible for the study (see exclusion 
criterion [29]).
Induction Period
During the 16-week Induction Period, approximately 280 participants, including approximately 
15 adolescent participants (≥12 to <18 years and weighing ≥40 kg), will be randomized in a 
3:2:2 ratio to treatment:

250 mg lebrikizumab (loading dose of 500 mg given at baseline and Week 2) by SC 
injection Q2W

250 mg lebrikizumab (loading dose of 500 mg given at baseline) by SC injection 
Q4W, or

placebo.
Participants will be stratified at randomization according to age (adolescent participants ≥12 to 
<18 years vs ≥18 years) and disease severity (IGA 3 vs 4). Daily use of mid-potency TCS
(low-potency TCS and/or TCI for sensitive areas) will be initiated at least 7 days prior to 
baseline in all participants (not allowed to be tapered or stopped during the Screening Period).
Mid-potency TCS, low-potency TCS, and TCIs may be tapered or stopped after baseline, as 
needed, based on treatment response.
All study intervention injections during the Induction Period will be administered by site staff at
the clinic.

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Protocol number J2T-JE-KGAL(a)
33
Maintenance Period
After completion of the Week 16 visit:

Participants receiving 250 mg lebrikizumab Q2W
i.
who achieve an IGA 0 or 1 and/or a ≥75% reduction in EASI score (≥EASI-75) 
response at Week 16 will be randomly allocated to receive 250 mg lebrikizumab 
Q2W or 250 mg lebrikizumab Q4W, in a 1:1 fashion;
ii.
who achieve neither an IGA 0 or 1 nor a <75% reduction in EASI score 
(<EASI-75) response at Week 16 will move to the Escape Arm.

Participants receiving 250 mg lebrikizumab Q4W
i.
who achieve an IGA 0 or 1 and/or an EASI-75 response (≥EASI-75) at Week 16 
will continue 250 mg lebrikizumab Q4W;
ii.
who achieve neither an IGA 0 or 1 nor an EASI-75 response (<EASI-75) at 
Week 16 will move to the Escape Arm.

Participants receiving placebo
i.
who achieve an IGA 0 or 1 and/or an EASI-75 response (≥EASI-75) at Week 16 
will 
continue to receive placebo;
ii.
who achieve neither an IGA 0 or 1 nor an EASI-75 response (<EASI-75) at 
Week 16 will move to the Escape Arm and will receive a loading dose of 500 mg 
lebrikizumab at Week 16 and Week 18.
Treatment regimen assignment will remain blinded during the Maintenance Period. Placebo 
injections will be utilized in order to maintain the blind and ensure that all participants receive 
the same number and frequency of injections regardless of treatment regimen assignment.
Escape Arm
In the Escape Arm, participants will receive 250 mg lebrikizumab Q2W.
Escape Arm from Week 16:

Participants who achieve neither an IGA 0 or 1 nor an EASI-75 response (<EASI-75) at 
Week 16 will move to the Escape Arm.

Participants who receive rescue treatment in the Induction Period will also be eligible to 
continue to the Escape Arm at Week 16.

Participants who required systemic rescue medication in the Induction Period must 
discontinue study intervention and must wait for the rescue medication washout 
(≥5 half-lives of the medication) prior to entering the Escape Arm.

Only participants who receive placebo in the Induction Period will receive a loading 
dose of 500 mg lebrikizumab at Week 16 and Week 18 followed by 250 mg 
lebrikizumab Q2W. Participants not achieving an EASI-50 response at 2 consecutive 
visits in the Escape Arm after Week 32 of treatment will be discontinued from the study.

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Protocol number J2T-JE-KGAL(a)
34
Escape Arm after Week 20:

Participants who do not maintain an EASI-50 response at Week 20, 24, 28, 32, 36, 40, 
44, 48, 52, 56, 60 or 64 in the Maintenance Period will be assigned to an Escape Arm 
and receive lebrikizumab 250 mg Q2W as open-label treatment thorough Week 68. 

Participants not achieving an EASI-50 response at 2 consecutive visits in the Escape 
Arm after 8 weeks of treatment will be discontinued from the study.
During the Maintenance Period, participants will be instructed to self-administer study 
intervention. Administration by the participant or caregiver is recommended. If the participant or 
caregiver is not able to administer any dose throughout the study, study site staff may administer 
the injection.

At Week 16, site personnel will instruct participants or their caregiver on the proper 
injection technique.

At Week 16 and Week 18, participants or their caregiver will administer study 
intervention under site personnel supervision.

Subsequent administration will be administered by participants or their caregiver 
at home.
Efficacy, Health Outcomes, and Safety Assessments
Efficacy and health outcomes will be measured through

IGA

EASI

SCORing Atopic Dermatitis (SCORAD)

BSA involvement

Itch Numeric Rating Scale (NRS)

Sleep-Loss Scoring System

Skin Pain NRS

TCS/TCI use

C-SSRS self-harm assessment

Quality of life and impact of disease (these will be assessed using the Patient-Oriented 
Eczema Measure [POEM], Dermatology Life Quality Index/Children’s Dermatology Life 
Quality Index [DLQI/CDLQI], Work Productivity and Activity Impairment – Atopic 
Dermatitis [WPAI-AD], and Hospital Anxiety Depression Scale [HADS]), and

Asthma Control Questionnaire-5 (ACQ-5) (to be completed by participants reporting 
comorbid asthma at study entry).
Safety will be assessed in all participants by

AE monitoring

serum chemistry

hematology

urinalysis laboratory testing

physical examination

pulse and blood pressure (vital signs)

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Protocol number J2T-JE-KGAL(a)
35

chest x-ray

concomitant medications, and

monitoring of hormone levels and growth parameters (adolescents only).
Serum samples will be collected for PK analysis and immunogenicity.
Participants who terminate the study early or complete the 68-week treatment period will receive 
a safety follow-up visit at which vital signs will be measured, C-SSRS self-harm supplement and 
self-harm follow-up form will be completed, and PK and immunogenicity samples will be 
collected.
4.2.
Scientific Rationale for Study Design
The use of lebrikizumab for AD is supported by numerous preclinical studies demonstrating that
AD is characterized by the increased expression of IL-13 in skin. Moreover, clinical studies
(Phase 2a Study GS29250 and Phase 2b Study DRM06-AD01) with lebrikizumab demonstrated 
significant clinical benefit in participants with AD. Additional detailed discussion of the 
lebrikizumab studies is provided in the lebrikizumab IB.
4.3.
Justification for Dose
For Study KGAL, a dosing regimen of 500 mg lebrikizumab administered as a loading dose at 
baseline and Week 2, followed by 250 mg Q2W lebrikizumab and a dosing regimen of 500 mg 
lebrikizumab administered as a loading dose at baseline, followed by 250 mg Q4W lebrikizumab 
was selected for the Induction Period (baseline to Week 16) based on an evaluation of safety, 
efficacy, and PK data from the DRM06-AD01 and DRM06-AD03 studies. The DRM06-AD03 
PK study conducted in healthy adults demonstrated that a single 2-mL (250 mg) SC injection of 
lebrikizumab delivered comparable levels of lebrikizumab as two 1-mL (125 mg) SC injections. 
This simulated the conditions under which study intervention will be administered in Phase 3, 
further supporting the dose and treatment regimen for KGAL, lebrikizumab 250 mg Q2W with 
a loading dose of 500 mg given at baseline and Week 2 and lebrikizumab 250 mg Q4W with a 
loading dose of 500 mg given at baseline.
Following the Induction Period, Study KGAL will assess the long-term safety and efficacy of 
both a 250-mg lebrikizumab Q2W dosing regimen and a 250-mg lebrikizumab Q4W dosing 
regimen to determine whether one or both regimens, of which one involves less frequent dosing, 
may be effective in maintaining disease control over an extended period.
Adolescent Participants
Adolescent participants (≥12 to <18 years weighing ≥40 kg) will be included in Study KGAL 
and will receive the same doses of lebrikizumab described above for adults. The justification for 
this approach is described below.
Both adults and adolescent participants have similar disease characteristics, typified by 
prominent Type 2 skin inflammation and similar clinical manifestations. In addition, both groups 
tend to have similar efficacy outcomes in response to therapies, including dupilumab (Simpson
et al. 2018; Treister and Lio 2019). Pharmacokinetic modeling and simulations of lebrikizumab 
dosing (population PK modeling of pooled data from 2259 adult asthma participants and 
a subsequent external posterior predictive check with lebrikizumab PK data from the 

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Protocol number J2T-JE-KGAL(a)
36
DRM06-AD01 study in adult AD participants) revealed similar kinetics for adult and adolescent 
participants (≥12 to <18 years). The maximal exposures are predicted to be 
in adolescent participants than in adult participants for any given dose due to the lower 
adolescent weight ranges and lebrikizumab exposure dependence on weight; however, the safety 
profile in adolescent participants, based on the exposure-response relationship analysis and on 
partial extrapolation, is comparable to that observed in adults.
4.4.
End of Study Definition
A participant is considered to have completed the study if he/she has completed all required 
phases of the study including the last visit or the last scheduled procedure shown in the SoA.
The end of the study is defined as the date of the last visit of the last participant in the study or 
last scheduled procedure shown in the SoA for the last participant in the study.
CCI

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Protocol number J2T-JE-KGAL(a)
37
5.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Participant must be ≥12 years of age inclusive, at the time of signing the informed 
consent/assent.
Type of Participant and Disease Characteristics
2. Have chronic AD (according to American Academy of Dermatology Consensus 
Criteria) (Eichenfield et al. 2014) that has been present for ≥1 year before the 
screening visit (Visit 1).
3. Have moderate-to-severe AD, including all of the following:
a.
EASI score ≥16 at the baseline visit (Visit 2)
b. IGA score ≥3 (scale of 0 to 4) at the baseline visit (Visit 2), and
c.
AD involvement on ≥10% of BSA at the baseline visit (Visit 2).
4. Have a documented history provided by a physician and/or investigator of 
inadequate response to existing topical medications within 6 months preceding 
screening as defined by at least 1 of the following:
a.
Inability to achieve good disease control, defined as mild disease or better 
(for example, IGA ≤2) after use of at least a medium-potency topical 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. Topical corticosteroids may be used with or 
without TCIs and/or topical JAK inhibitors.
b. Participants who failed systemic therapies intended to treat AD within 
6 months preceding screening, such as cyclosporine, MTX, azathioprine, and 
mycophenolate MMF, will also be considered as surrogates for having 
inadequate response to topical therapy. 
5. Are willing and able to comply with all clinic visits and study-related procedures 
and questionnaires.

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Protocol number J2T-JE-KGAL(a)
38
Weight
6. Body weight ≥40 kg.
Sex
7. Male or non-pregnant, non-breastfeeding female.
Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies.
a.
For women of childbearing potential (WOCBP): agree to remain abstinent 
(refrain from heterosexual intercourse) or use a highly effective 
contraceptive method during the treatment period and for at least 18 weeks 
after the last dose of lebrikizumab.
NOTE: A WOCBP is defined in Appendix 4, Section 10.4.
NOTE: The following are highly effective contraceptive methods: combined 
(estrogen and progestogen containing) hormonal contraception (oral, 
intravaginal, transdermal) associated with inhibition of ovulation;
progestogen-only hormonal contraception (oral, injectable, implantable) 
associated with inhibition of ovulation; intrauterine device; intrauterine 
hormone-releasing system; bilateral tubal occlusion; bilateral tubal ligation;
partner who has undergone vasectomy; or sexual abstinence. The reliability 
of sexual abstinence should be evaluated in relation to the duration of the 
clinical study and the preferred and usual lifestyle of the patient. Periodic 
abstinence (for example, calendar, ovulation, symptothermal, or 
postovulation methods) and withdrawal are not acceptable methods of 
contraception.
If the highly effective contraceptive methods are contraindicated or strictly 
declined by patient, acceptable birth control methods may be considered. 
These may include combination of both of the following methods:

male or female condom with spermicide, or 

cap, diaphragm, or sponge with spermicide.
b. Male patients are not required to use contraception.
Informed Consent
8. Capable of giving signed informed consent or have a legal guardian who is willing 
and able to provide written informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol.
NOTE: Month and year of birth will be collected from participants <18 years old.

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Protocol number J2T-JE-KGAL(a)
39
NOTE: During clinical studies, adequate informed consent for continued 
participation will be obtained from adolescent participants once a child reaches the 
age of legal consent.
5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
9. Have a history of anaphylaxis as defined by National Institute of Allergy and 
Infectious Disease criteria (Sampson et al. 2006).
10. Have uncontrolled chronic disease that might require bursts of oral corticosteroids, 
for example, comorbid severe uncontrolled asthma (defined by a history of 
≥2 asthma exacerbations within the past 12 months requiring systemic [oral and/or 
parenteral] corticosteroid treatment or hospitalization for >24 hours at Visit 1 and 2).
11. Have an active chronic or acute infection requiring treatment with systemic 
antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks 
before the baseline visit or superficial skin infections within 1 week before the 
baseline visit.
NOTE: participants may be re-screened after infection resolves.
12. Known or suspected history of immunosuppression, including history of 
invasive opportunistic infections (for example, histoplasmosis, listeriosis, 
coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection 
resolution or unusually frequent, recurrent, or prolonged infections, per the 
investigator’s judgment.
13. Have known hepatitis B infection or test positive for hepatitis B virus (HBV) at 
screening, defined as: (1) positive for hepatitis B surface antigen (HBsAg);
(2) positive for hepatitis B core antibody (HBcAb) and positive confirmatory 
polymerase chain reaction (PCR) for HBV DNA, regardless of hepatitis B surface 
antibody (HBsAb) status; or (3) positive for HBcAb and/or positive for anti-HBsAb 
and a confirmatory PCR for HBV DNA. 
Participants whose results are HBcAb positive and/or HBsAb positive and 
HBV DNA negative may be eligible to continue screening per investigator 
judgment. Such participants will be monitored for HBV during the study as 
detailed in Section 8.2.7.
14. Have known hepatitis C infection or test positive for hepatitis C virus (HCV) at 
screening, defined as a positive test result for hepatitis C antibody (anti-HCVAb) 
plus a positive confirmatory test result for HCV (for example, HCV RNA). 
Participants whose results are anti-HCVAb positive and HCV RNA negative are 
eligible to continue screening per investigator judgment.
NOTE: Participants who have documented anti-HCV treatment for a past HCV 
infection AND are HCV RNA negative are eligible to continue screening per 
investigator judgment.

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Protocol number J2T-JE-KGAL(a)
40
15. Have a history of pneumocystis pneumonia (PCP) or a positive beta-D-glucan test at 
screening and a confirmed diagnosis of PCP.
16. Have active endoparasitic infections or are at high risk of contracting these
infections. 
17. Have evidence of active tuberculosis (TB) or latent tuberculosis infection (LTBI).
a.
have evidence of active TB, defined in this study as follows:
i.
documented by a positive purified protein derivative (PPD) test 
(≥5 mm induration between approximately 48 and 72 hours after 
application, regardless of vaccination history), medical history, clinical 
features, and abnormal chest x-ray at screening;
ii.
QuantiFERON®-TB Gold test or T-SPOT® TB test may be used instead 
of the PPD test. Participants are excluded from the study if the test is not 
negative and there is clinical evidence of active TB.
Exception: Participants with a history of active TB who have documented evidence of
appropriate treatment, have no history of re-exposure since their treatment was 
completed, and have a screening chest x-ray with no evidence of active TB may be 
enrolled if other entry criteria are met. Such participants would not be required to 
undergo the protocol-specific TB testing for PPD, QuantiFERON-TB Gold test, or 
T-SPOT TB test but must have a chest x-ray at screening.
b. have evidence of untreated/inadequately or inappropriately treated LTBI, 
defined in this study as follows:
i.
documented to have a positive PPD test (≥5 mm induration between 
approximately 48 and 72 hours after application, regardless of 
vaccination history), no clinical features consistent with active TB, and a 
chest x-ray with no evidence of active TB at screening; or
ii.
PPD test is positive and the participant has no medical history or chest 
x-ray findings consistent with active TB. The participant may have a 
QuantiFERON-TB Gold test or T-SPOT TB test. If the test results are 
not negative, the participant will be considered to have LTBI (for 
purposes of this study); or
iii.
QuantiFERON-TB Gold test or T-SPOT TB test may be used instead of 
the PPD test. If the test results are positive, the participant will be 
considered to have LTBI. If the test is not negative, the test may be 
repeated once within approximately 2 weeks of initial testing. If results 
of the repeated test are not negative, the participant will be considered to 
have LTBI (for purposes of this study). Participants who have an 
indeterminate QuantiFERON-TB Gold test (not negative) may either 
repeat the QuantiFERON-TB Gold test or undergo T-SPOT TB 
testing. Purified protein derivative testing after an indeterminate 
QuantiFERON-TB Gold test is not allowed.
Exception: A participant who has evidence of LTBI may be enrolled if he or she 
completes at least 4 weeks of appropriate treatment prior to randomization and agrees to 

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Protocol number J2T-JE-KGAL(a)
41
complete the remainder of treatment during the study. If a participant is not able to 
complete at least 4 weeks of appropriate treatment prior to randomization, the participant 
may be re-screened.
Exception: Participants with a history of LTBI who have documented evidence of 
appropriate treatment, have no history of re-exposure since their treatment was 
completed, and have a screening chest x-ray with no evidence of active TB may be 
enrolled if other entry criteria are met. Such participants would not be required to 
undergo the protocol-specific TB testing for PPD, QuantiFERON-TB Gold test, or 
T-SPOT TB test but must have a chest x-ray at screening.
18. Have a history of human immunodeficiency virus (HIV) infection or positive HIV 
serology at screening.
19. Have presence of skin comorbidities (for example, sclerosis, psoriasis, or lupus 
erythematosus) that may interfere with study assessments.
20. Have presence of significant uncontrolled neuropsychiatric disorder, are clinically 
judged by the investigator to be at risk for suicide, or have a “yes” answer to any of 
the following:
a.
Question 4 (Active Suicidal Ideation with Some Intent to Act, Without 
Specific Plan) on the “Suicidal Ideation” portion of the C-SSRS
b. Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the 
“Suicidal Ideation” portion of the C-SSRS, or
c.
any of the suicide-related behaviors (actual attempt, interrupted attempt, 
aborted attempt, and preparatory act or behavior) on the “Suicidal Behavior” 
portion of the C-SSRS and the ideation or behavior occurred within 2 months 
prior to Visit 1.
NOTE: A participant does not necessarily have to be excluded if they have self-
injurious behavior that would be classified as nonsuicidal self-injurious behavior. 
If this situation arises, the participant should be referred to a psychiatrist or 
appropriately trained professional as indicated.
21. Have a history of malignancy, including mycosis fungoides, within 5 years before 
the screening visit, except completely treated in situ carcinoma of the cervix or 
completely treated and resolved non-metastatic squamous or basal cell carcinoma 
of the skin with no evidence of recurrence in the past 12 weeks.
22. Have severe concomitant illness(es) that, in the investigator’s judgment, would 
adversely affect the participant’s participation in the study or any other medical or 
psychological condition that, in the opinion of the investigator, may suggest a new 
and/or insufficiently understood disease, may present an unreasonable risk to the 
study participant because of his/her participation in this clinical study, may make the 
participant’s participation unreliable, or may interfere with study assessments.  

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Protocol number J2T-JE-KGAL(a)
42
Prior/Concomitant Therapy
23. Have received a dose of lebrikizumab in any prior lebrikizumab clinical study.
24. Have had an important side effect from TCS (for example, intolerance to treatment, 
hypersensitivity reactions, significant skin atrophy, and systemic effects), as 
assessed by the investigator or treating physician, that would prevent further use.
25. Had treatment with high-potency topical corticosteroids, JAK inhibitors (topical) or 
phosphodiesterase 4 inhibitor within 7 days prior to the baseline visit (Visit 2).
26. Had treatment with any of the following agents within 4 weeks prior to the 
baseline visit: 
a.
immunosuppressive/immunomodulating drugs (for example, 
systemic corticosteroids, cyclosporine, MMF, interferon IFN-γ), JAK
inhibitors, azathioprine, MTX, or 
b. Phototherapy and photochemotherapy for AD. 
27. Had treatment with the following prior to the baseline visit: 
a.
an investigational intervention within 8 weeks or within 5 half-lives 
(if known), whichever is longer
b. dupilumab within 8 weeks
c.
B-cell–depleting biologics, including rituximab, within 6 months, or
d. other biologics within 5 half-lives (if known) or 16 weeks, whichever 
is longer.
28. Have regular use (more than 2 visits per week) of a tanning booth/parlor within 
4 weeks of the screening visit. 
29. Have been exposed to a live vaccine within 12 weeks prior to the baseline visit or 
are expected to need/receive a live vaccine during the study or up to 125 days after 
the last dose of IP.
NOTE: Booster vaccination for measles, mumps, and rubella or varicella-zoster
virus may be considered if it is essential based on local guidelines and/or in the 
opinion of the investigator.
Prior/Concurrent Clinical Study Experience
30. Participated in a prior lebrikizumab clinical study. 
Diagnostic assessments
31. Have any of the following specific abnormalities in screening laboratory tests:
a.
serum creatinine, aspartate aminotransferase (AST) or alanine 
aminotransferase (ALT) ≥2× upper limit of normal (ULN)
b. alkaline phosphatase (ALP) ≥2× ULN
c.
total bilirubin (TBL) ≥1.5× ULN
d. hemoglobin <10.0 g/dL (<100.0 g/L)
e.
total white blood cell (WBC) count <2500 cells/μL (<2.50×103/μL 
or <2.50 GI/L)
f.
neutropenia (absolute neutrophil count [ANC] <1200 cells/μL) 
(<1.20×103/μL or <1.20 GI/L)

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Protocol number J2T-JE-KGAL(a)
43
g. lymphopenia (lymphocyte count <750 cells/μL) (<0.75×103/μL or 
<0.75 GI/L), or 
h. thrombocytopenia (platelets <100,000/μL) (<100×103/μL or <100 GI/L).
NOTE: For each aforementioned test, a single repeat analysis is allowed during 
screening, and values resulting from repeat testing may be accepted for enrollment 
eligibility if they meet the eligibility criterion.
Other Exclusions
32. Pregnant or breastfeeding women or women planning to become pregnant or 
breastfeed during the study.
33. Are Lilly employees or are investigator site personnel directly affiliated with this 
study and/or their immediate families. Immediate family is defined as a spouse, 
parent, child, or sibling, whether biological or legally adopted.
5.3.
Lifestyle Considerations
Not applicable.
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any serious adverse event (SAE).
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
re-screened. Re-screened participants should be assigned a new participant number. When 
re-screening, participants who have previously completed screening chest radiography and/or TB 
tests according to the protocol do not need to repeat these procedures if they were performed 
within 90 days before their re-screening date of consent but may do so at the discretion of the 
investigator. All other screening procedures must be conducted at re-screening to ensure that all 
eligibility criteria are met. Individuals may be re-screened up to 1 time. The interval between 
re-screenings should be at least 4 weeks. Each time re-screening is performed, the individual or 
their parent or legal guardian must sign a new ICF.

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6.
Study Intervention
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol.
6.1.
Study Intervention(s) Administered
Lebrikizumab drug product and placebo are provided as sterile liquids and contain no 
preservatives. Each single-use, 2-mL pre-filled syringe (PFS) is assembled with a needle safety 
device (NSD) to form the 2-mL PFS-NSD drug product presentation.
The lebrikizumab drug product is formulated as 125 mg/mL.
The placebo has similar composition to the active drug product with the exception of absence of 
the drug substance lebrikizumab.
The tables below describe the dosing schedules for the Induction and Maintenance periods and 
the Escape Arm.
Table 1.
Induction Period Dosing Schedule by Treatment Group
Treatment Assignment in 
Induction Period
(Blinded)
Loading Dose
(Baseline and Week 2)
Weeks 4, 8, and 12
Weeks 6, 10, and 14
Lebrikizumab 
250 mg Q2W
Baseline: 2 active injections
Week 2: 2 active injections
1 active injection
1 active injection
Lebrikizumab 
250 mg Q4W
Baseline: 2 active injections
Week 2: 2 placebo injections
1 active injection
1 placebo injection
Placebo
Baseline: 2 placebo injections
Week 2: 2 placebo injections
1 placebo injection
1 placebo injection
Abbreviations: SC = subcutaneous; Q2W = every 2 weeks; Q4W = every 4 weeks.
Notes: Information provided in this table may change throughout the study. Injections are given SC.

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Table 2.
Maintenance Period Dosing Schedule by Treatment Group
Treatment 
Assignment in 
Induction Period
(Blinded)
Treatment 
Assignment in 
Maintenance Period
Weeks 16, 20, 24, 28, 32, 36, 
40, 44, 48, 52, 56, 60, and 64
Weeks 18, 22, 26, 30, 34, 38, 
42, 46, 50, 54, 58, 62, and 66
Lebrikizumab
250 mg Q2W
Lebrikizumab
250 mg Q2W
1 active injection
1 active injection
Lebrikizumab 
250 mg Q4W
1 active injection
  1 placebo injection
Lebrikizumab 
250 mg Q4W
Lebrikizumab 
250 mg Q4W
1 active injection
  1 placebo injection
Placebo
Placebo
  1 placebo injection
  1 placebo injection
Abbreviations: SC = subcutaneous; Q2W = every 2 weeks; Q4W = every 4 weeks.
Notes: Information provided in this table may change throughout the study. Injections are given SC.
Participants Entering Escape Arm at Week 16
Participants who achieve neither an IGA 0 or 1 nor an EASI-75 response (<EASI-75) at Week 16 
will move to the Escape Arm.
Participants who require high-potency topical or systemic rescue treatment for AD during the 
Induction Period will be eligible for treatment in the Escape Arm. Participants receiving systemic 
rescue medication in the Induction Period will be required to washout for 5 half-lives prior to 
initiating treatment in the Escape Arm. 
Participants who are eligible for the Escape Arm at Week 16 will receive blinded loading doses
at Week 16 and 18, based on their prior treatment assignment, followed by 250 mg lebrikizumab 
Q2W through Week 68 in the Escape Arm in an open-label fashion. Participants not achieving an 
EASI-50 response at 2 consecutive visits in the Escape Arm after Week 32 of treatment will be 
terminated from the study.

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Table 3.
Escape Arm Dosing Schedule by Treatment Group
Treatment 
Assignment in 
Induction Period
Treatment 
Assignment in 
Maintenance Period
Escape Arm
(Blinded: Week 16 and 18)
Escape Arm
(Unblinded after Week 20)
Participants Entering Escape Arm at Week 16
Lebrikizumab 
250 mg Q2W
Escape Arm
(Lebrikizumab 
250 mg Q2W)
Week 16: 1 active and 
1 placebo injection
Week 18: 1 active and 
1 placebo injection
One active injection Q2W 
during Weeks 20 to 66
Lebrikizumab 
250 mg Q4W
Placebo
Escape Arm
(Lebrikizumab 
250 mg Q2W)
Week 16: 2 active injections
Week 18: 2 active injections
Abbreviations: SC = subcutaneous; Q2W = every 2 weeks; Q4W = every 4 weeks.
Notes: Information provided in this table may change throughout the study. Injections are given SC.
Participants Entering Escape Arm at Week 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, or 64
Participants who do not maintain an acceptable response (have an EASI score <50% of baseline) 
at Week 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, or 64 in the Maintenance Period will be 
eligible for treatment in the Escape Arm and will receive 250 mg lebrikizumab Q2W through 
Week 68 in the Escape Arm in an open-label fashion. Participants not achieving an EASI-50 
response at 2 consecutive visits after 8 weeks of treatment in the Escape Arm will be 
discontinued from the study.
6.1.1.
Background Medication (Topical Treatment for AD)
Background medication allowed during the study is described below.
All participants will be instructed to use a mid-potency TCS (hydrocortisone butyrate ointment
0.1%, or equivalent-potency TCS) for AD symptoms starting ≥7 days prior to the baseline visit 
(Day 1). Low-potency TCS (prednisolone cream 0.5% or equivalent-potency TCS) and/or TCI 
may be used for sensitive areas only (that is, face, neck, intertriginous, and genital areas) ≥7 days 
prior to the baseline visit (Day 1). Background medication is not allowed to be tapered or 
stopped until the baseline visit (Day 1).
Participants may taper or stop background medication use based on treatment response after 
baseline visit (Day 1). If AD lesions return or a participant experiences a flare, the background 
medication may be resumed at the participant and/or investigator’s discretion.
Where possible, a mid-potency TCS (hydrocortisone butyrate ointment 0.1%) and a low-potency 
TCS (prednisolone cream 0.5%) will be provided by the sponsor for use in this study. If these
specific TCS treatments are unavailable, an alternate, equivalent-potency TCS may be provided 
by the site.
Topical corticosteroid use, when the TCS is supplied by the sponsor, should be recorded via 
weight of returned tubes as indicated in the SoA (Section 1.3). The investigator must keep an 
accurate record of the number of tubes received, dispensed/used, and returned to the sponsor or 
designee. The sponsor or designee will provide forms to facilitate inventory control. All 
accountability forms and treatment logs must be retained in the investigator’s permanent study 

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Protocol number J2T-JE-KGAL(a)
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file, and these records must be available for inspection at any time by the sponsor, its designees, 
or by regulatory agencies.
Each container will be labeled as required per local country requirements.
6.2.
Preparation/Handling/Storage/Accountability
Investigational products will be supplied by Lilly or its representative, in accordance with current 
good manufacturing practices, and will be supplied with lot numbers, expiry dates, and 
certificates of analysis, as applicable.
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are reported 
and resolved before use of the study intervention.
Only participants enrolled in the study may receive study intervention and only authorized site 
staff may supply or administer study intervention. All study intervention must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the investigator and authorized 
site staff.
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (that is, 
receipt, reconciliation, and final disposition records).
Follow storage and handling instructions stated on the IP label. Detailed instructions regarding 
preparation and handling of IPs will be provided by the Sponsor.
6.3.
Measures to Minimize Bias: Randomization and Blinding
Method of Treatment Assignment
The randomization ratio and stratification factors are described in Section 4.1. The blinding 
scheme is described in Section 6.1.
Participants who achieve an IGA 0 or 1 and/or an EASI-75 response (≥EASI-75) at Week 16 and 
do not use rescue therapy during the Induction Period are defined as responders. The responders
originally assigned to lebrikizumab 250 mg Q2W will be re-randomized to either lebrikizumab 
250 mg Q2W or lebrikizumab 250 mg Q4W. The responders originally assigned to 250 mg 
lebrikizumab Q4W or placebo will stay on their originally assigned treatment in the double-blind 
Maintenance Period at Visit 10 (Week 16).
Participants who achieve neither an IGA 0 or 1 nor an EASI-75 response (<EASI-75) at Week 16 
and participants who require high-potency topical or systemic rescue treatment for AD during 
the Induction Period will be eligible for treatment in an Escape Arm. Participants who are 
eligible for the Escape Arm will receive blinded loading doses at Week 16 and Week 18, based 
on their prior treatment assignment, followed by 250 mg lebrikizumab Q2W through Week 68 in 
the Escape Arm in an open-label fashion.
All participants will be centrally assigned to randomized study intervention using an interactive 
web response system (IWRS). Before the study is initiated, the login information and directions 
for the IWRS will be provided to each site. Study intervention will be dispensed at the study 

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Protocol number J2T-JE-KGAL(a)
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visits as summarized in the SoA (Section 1.3). Returned study intervention should not be 
re-dispensed to the participants.
Emergency Unblinding
The IWRS will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining whether unblinding of a participants’ 
intervention assignment is warranted. Participant safety must always be the first consideration in 
making such a determination. If a participant’s intervention assignment is unblinded, the sponsor 
must be notified immediately after breaking the blind. The date and reason that the blind was 
broken must be recorded in the source documentation and eCRF, as applicable.
Unblinding and Participant Discontinuation
If an investigator, site personnel performing assessments, or participant is unblinded, the 
participant must be discontinued from the study. For cases in which there are ethical reasons for 
the participant to continue the study, the investigator must obtain specific approval from a 
sponsor clinical research physician (CRP).
6.4.
Study Intervention Compliance
When participants are dosed at the site (first 16 weeks), they will receive study intervention 
directly from the investigator or designee, under medical supervision. The dose of study 
intervention and study participant identification will be confirmed at the time of dosing by a 
member of the study site staff other than the person administering the study intervention.
When participants self-administer study intervention(s) at home, compliance with study 
intervention will be assessed at each visit. Compliance will be assessed by direct questioning and 
checking the IP during the site visits and will be documented in the source documents and eCRF.
A record of the study intervention dispensed to and taken by each participant must be maintained
and reconciled with study intervention and compliance records. Intervention start and stop dates, 
including dates for intervention delays, will also be recorded in the eCRF.
The date, time, and injection location of each dose administered will be recorded in the source 
documents and in the eCRF.
6.5.
Concomitant Therapy
All medications (including over the counter drugs, vitamins, and antacids) and over the counter 
emollient(s) taken/used at screening and throughout the study must be recorded. Participants
should be instructed to consult with the investigator prior to initiating any new medication (either 
self-administered non-prescription drugs or prescription therapy prescribed by another physician) 
while participating in the study. The investigator is expected to examine the acceptability of all 
concomitant medications, topical preparations, and dietary supplements taken by participants
participating in the study.

Medication entries should be specific to product name (if a combination drug
product) and spelled correctly. 

The brand and specific product name for any over the counter emollient(s) should be 
noted and spelled correctly. 

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Protocol number J2T-JE-KGAL(a)
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
Information on the dose, unit, frequency, route of administration, start date, 
discontinuation date, indication, and reason for use will be recorded.

The use of any concomitant medication must relate to an AE listed on the AE 
eCRF or the participant’s medical history, unless the medication is a supplement or 
used as preventive care
6.5.1.
Permitted and Prohibited Treatments and Procedures
Participants should not apply emollients or other topical treatments on the day of their study visit 
prior to the procedures to allow adequate assessment of skin dryness.
The use of concomitant medications for other medical conditions (for example, hypertension, 
diabetes, acute infections) is permitted during this study. Inhaled corticosteroids and 
bronchodilators to control asthma are permitted. 
The introduction of medications or therapies for other medical conditions known to affect AD 
(for example, high-potency TCS, topical/oral JAK inhibitors, topical/oral phosphodiesterase 4 
inhibitor, systemic corticosteroids, MMF, IFN-γ, cyclosporine, azathioprine, MTX, 
phototherapy, biologics or photochemotherapy) are not permitted during the study.
The use of systemic corticosteroids for the treatment of AD is prohibited and requires permanent 
discontinuation of IP. If used for treatment of an AE (for example, worsening of an existing 
condition such as asthma exacerbation), the corticosteroid will still be treated as rescue 
medication per Section 6.5.3.
Acute infections can be treated with systemic antibiotics, use of which must be recorded in the 
eCRF. However, chronic treatment with systemic antibiotics is not permitted.
The use of a tanning booth/parlor is not permitted during the study.
Cannabinoid treatments for AD are prohibited. Planned or anticipated major medical procedures 
or surgeries should be avoided during the study. See Section 6.5.3 for details on approved rescue 
medications and timing of use.
Prior to therapeutic intervention, an investigator must review the study participant’s vaccination
record to evaluate the risk of under-immunization to the adolescent study participant.
6.5.2.
Moisturizers
A stable dose of non-medicated moisturizers should be used for ≥7 days prior to the baseline 
visit (Visit 2) and daily during the study. If daily applications are missed, it will not be 
considered a protocol violation.
6.5.3.
Rescue Treatment for Atopic Dermatitis
The goal of this Phase 3 study is to demonstrate the efficacy and safety of lebrikizumab when 
used in combination with TCS for AD. However, add-on rescue therapies may be needed if the 
participant experiences clinical worsening of symptoms that are intolerable.
All rescue treatment usage must be recorded in the eCRF.

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Protocol number J2T-JE-KGAL(a)
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Induction Period
The use of high-potency topical or systemic treatments for AD is prohibited from baseline 
through Week 16. Participants who experience intolerable AD symptoms and require treatment 
should preferably be started on high-potency TCS treatments prior to instituting systemic 
treatments for AD symptoms, in accordance with best practice.
If systemic treatments (for example, oral corticosteroids, phototherapy, cyclosporine) are 
required by Week 16, study intervention must be discontinued. The participant should continue 
to attend all study visits through Week 16 and be assessed for safety and efficacy according to 
the SoA (Section 1.3). Participants requiring high-potency TCS or systemic rescue medication 
who complete the study through Week 16 will be eligible to continue to the Escape Arm after the 
Week 16 visit has been completed. Participants who required systemic treatment must wait for 
the washout (≥5 half-lives of the treatment) prior to entering the Escape Arm.
Maintenance Period
Intermittent use of high-potency TCS treatments for AD is permitted during the Maintenance 
Period but must be communicated to the investigator and documented as concomitant 
medications. Participants who may require short-term systemic treatment for symptoms of AD 
during the Maintenance Period will be assessed on a case-by-case basis and must be discussed 
with the Medical Monitor prior to initiating treatment. Participants requiring long-term systemic 
treatment for symptoms of AD in the Maintenance Period must be discontinued from the study.
Escape Arm
Intermittent use of additional high-potency TCS for AD is permitted for participants who are in 
the Escape Arm. Participants who may require short-term systemic treatment for symptoms of 
AD while in the Escape Arm will be assessed on a case-by-case basis and must be discussed with 
the Medical Monitor prior to initiating treatment. Participants requiring long-term systemic 
treatment for symptoms of AD in the Escape Arm (for example, non-responders) must be 
discontinued from the study.
6.6.
Dose Modification
Not applicable.
6.7.
Intervention after the End of the Study
Not applicable.

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7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention.
These sections describe reasons for a participant’s

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 (“stopping rules”) are handled as part of 
regulatory, ethical, and study oversight considerations in Appendix 10.1, Section 10.1.8.
7.1.
Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) study intervention. If systemic treatments (for example, oral corticosteroids, 
phototherapy, cyclosporine) are required in the Induction Period, study intervention must be 
discontinued by Week 16. These participants can be eligible to continue in the Escape Arm after 
completion of Week 16 but must wait for the washout (≥5 half-lives of the treatment) prior to 
entering the Escape Arm.
Study intervention may be permanently discontinued during the study.
Participants who permanently discontinue study intervention early will undergo early termination 
(ET) procedures, which include

an ET visit, and 

posttreatment follow-up visits, as shown in the SOA (Section 1.3).
7.1.1.
Criteria for Permanent Discontinuation of Study Intervention
Data collection and safety follow-up when study intervention is permanently discontinued
If study intervention is permanently discontinued, the participant will remain in the study to 
have an ET visit and posttreatment follow-up visits, as shown in the SoA (Section 1.3).
See the SoA (Section 1.3) for data to be collected at the time of discontinuation and follow-up 
and for any further evaluations that need to be completed. Safety follow-up is as outlined in the 
SoA (Section 1.3) and in Section 8.2 (“Safety Assessments) and Section 8.3 (“Adverse Events 
and Serious Adverse Events”) of the protocol.
Criteria for permanent discontinuation of study intervention
Possible reasons for permanent discontinuation of study intervention include, but are not limited 
to, the following:
Safety considerations

The participant develops any of the following conditions during the study:
malignancy (except for successfully treated basal or squamous cell skin carcinoma)
HIV/acquired immune deficiency syndrome (AIDS)

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active TB infection or untreated LTBI (Section 8.2.6)
HCV RNA positive (Section 5.2 and exclusion criterion [19]), or 
HBV DNA positive and clinical assessment consistent with HBV reactivation
NOTE: The HBV DNA result is to be confirmed if initial positive test result is 
below the level of quantification (Section 8.2.7). The participant is to be referred to, 
evaluated, and managed by a specialist physician with expertise in evaluation and 
management of viral hepatitis prior to discontinuation of any immunomodulatory 
and/or immunosuppressive therapy, including study intervention. Timing of 
discontinuation from study intervention relative to the initiation of any antiviral 
treatment for hepatitis is to be based on the recommendation of the consulting 
specialist physician, in conjunction with the investigator, and aligned with medical 
guidelines and standard of care.

The participant answered “yes” to Question 4 or Question 5 on the Suicidal Ideation 
portion of the C-SSRS or answered “yes” to any of the suicide-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.

The investigator, after consultation with the sponsor’s designated Medical Monitor, 
determines that a systemic hypersensitivity reaction has occurred and is related to study 
intervention administration.

The participant has any of the following results:
total WBC count <2000 cells/L (<2.00×103/L or 2.00 GI/L)
absolute lymphocyte count (ALC) <500 cells/L (<0.5×103/L or <0.5 GI/L), or
platelet count <50,000 cells/μL (<50×103/μL or <50 GI/L).

Investigator-confirmed diagnosis of PCP during the study.

The participant has an AE or an SAE or a clinically significant change in a laboratory 
value that, in the opinion of the investigator, merits discontinuation of study intervention
and appropriate measures being taken.
Hepatic event or liver test abnormality

Participants who are discontinued from study intervention because of a hepatic event or 
liver test abnormality should have additional hepatic safety data collected via the hepatic 
eCRF. Discontinuation of study intervention for abnormal liver test results should be 
considered by the investigator when a participant meets 1 of the conditions listed below 
after consultation with the sponsor’s designated Medical Monitor (see Section 10.2).
ALT or AST ≥8× ULN
ALT or AST ≥5× ULN for more than 2 weeks
ALT or AST ≥3× ULN and TBL ≥2× ULN or international normalized ratio (INR) ≥1.5

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ALT or AST ≥3× ULN with the appearance of fatigue, nausea, vomiting, right upper
quadrant pain or tenderness, fever, or rash
ALP ≥3× ULN
ALP ≥2.5× ULN and TBL ≥2× ULN, or
ALP ≥2.5× ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, or rash.
NOTE: Participants who are discontinued from IP because of a hepatic event or liver 
test abnormality should have additional hepatic safety data collected via the hepatic 
safety eCRF.
Other reasons

Unblinding: If an investigator, blinded site personnel who are performing assessments, or 
participant is unblinded to a participant’s treatment assignment, the participant must be 
discontinued from the study intervention and continue to posttreatment follow-up. For
cases in which there are ethical reasons for the participant to continue on study 
intervention, the investigator must obtain specific approval from the sponsor’s 
designated Medical Monitor.
7.1.2. Criteria for Temporary Discontinuation of Study Intervention
In some circumstances, it may be necessary to temporarily interrupt treatment as a result of AEs 
or abnormal laboratory values that may have an unclear relationship to the IP. For example, IP 
should be temporarily interrupted if the patient experiences a cardiovascular AE considered to be 
related to study treatment, graded as moderate (Grade 2 according to Common Terminology 
Criteria for Adverse Events version 3.0), and that does not resolve promptly with supportive 
care. Except in cases of emergency, it is recommended that the investigator consult with Lilly (or 
its designee) before temporarily interrupting therapy for reasons other than those predefined in 
this section.
For the abnormal laboratory findings and clinical events (regardless of relatedness) listed in 
Table 4, specific guidance is provided for temporarily interrupting treatment and when treatment 
may be restarted. Retest frequency and timing of follow-up laboratory tests to monitor the 
abnormal finding is at the discretion of the investigator. Investigational product that was 
temporarily interrupted because of an AE or abnormal laboratory value not specifically covered 
in Table 4 may be restarted at the discretion of the investigator.

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Table 4.
Criteria for Temporary Interruption of Investigational Product
Hold IP if the Following Laboratory Test Results or 
Clinical Events Occur:
IP May Be Resumed When:
ANC <1000 cells/L
(<1.00×103/µL or <1.00 GI/L)
ANC ≥1200 cells/µL
(≥1.20×103/µL or ≥1.20 GI/L)
Platelet count <75,000/µL
(<75×103/µL or <75GI/L)
Platelet count 100,000/µL
(≥100×103/µL or ≥100 GI/L)
ALT or AST >5× ULNa
ALT and AST return to <2× ULN, and IP is not 
considered to be the cause of enzyme elevation
Hemoglobin <8 g/dL (<80.0 g/L)
Hemoglobin 10 g/dL (≥100.0 g/L)
Infection that, in the opinion of the investigator, merits 
the IP being interrupted
Resolution of infection
Beta-D-glucan test is positive
Perform evaluation for PCP locally. Resume IP if 
evaluation is negative. (See Section 7.1.1 [Criteria for 
Permanent Discontinuation of Study Intervention] if PCP 
is confirmed.)
Abbreviations:  ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; IP = investigational product; PCP = pneumocystis pneumonia; ULN = upper limit of normal.
a Repeat liver enzyme(s) and serum bilirubin tests 1 or 2 times weekly. Frequency of re-testing can decrease to 
once a week or less if abnormalities stabilize. Monitor ALT and AST until levels return to <2× ULN.
7.2.
Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study:

at any time at his/her own request

at the request of his/her designee (for example, parents or legal guardian)

at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons

if the participant becomes pregnant during the study

if enrollment in any other clinical study involving an IP or enrollment in any 
other type of medical research judged not to be scientifically or medically 
compatible with this study

if the participant, for any reason, requires treatment with another therapeutic 
agent that has been demonstrated to be effective for treatment of the study 
indication, discontinuation from the study occurs prior to introduction of the 
new agent

if a participant transitioned to the Escape Arm from Week 16 (use of rescue 
treatment in the Induction Phase or non-responder at Week 16) and does not 
achieve an EASI-50 response at 2 consecutive visits after Week 32

if a participant is transitioned to the Escape Arm after Week 20 and does not achieve 
an EASI-50 response at 2 consecutive visits after 8 weeks of treatment

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
if a participant requires long-term systemic treatment for symptoms of AD in 
the Maintenance Period (for example, non-responders), or

if an investigator, site personnel performing assessments, or participant 
is unblinded.
Discontinuation is expected to be uncommon.
At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA (Section 1.3). See the SoA (Section 1.3) for data to be collected 
at the time of study discontinuation and follow-up and for any further evaluations that need to be 
completed. The participant will be permanently discontinued both from the study intervention
and from the study at that time.
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant
withdraws from the study, he/she may request destruction of any samples taken and not tested,
and the investigator must document this in the site study records.
7.2.1.
Discontinuation of Inadvertently Enrolled Participants
If the sponsor or investigator identifies a participant who did not meet enrollment criteria and 
was inadvertently enrolled, then the participant should be discontinued from study treatment 
unless there are extenuating circumstances that make it medically necessary for the participant to 
continue on study treatment. If the investigator and the sponsor CRP agree it is medically 
appropriate to continue, the investigator must obtain documented approval from the sponsor CRP 
to allow the inadvertently enrolled participant to continue in the study with or without treatment 
with IP. Safety follow-up is as outlined in the SoA (Section 1.3), Section 8.2 (Safety 
Assessments), and Section 8.3 (Adverse Events and Serious Adverse Events) of the protocol.
7.3.
Lost to Follow-Up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel are expected to 
make diligent attempts to contact participants who fail to return for a scheduled visit or were 
otherwise unable to be followed up by the site.
Discontinuation of specific sites or of the study are handled as part of Appendix 1
(Section 10.1.8).

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8.
Study Assessments and Procedures

Study procedures and their timing are summarized in the SoA (Section 1.3).
Protocol waivers or exemptions are not allowed.

Immediate safety concerns should be discussed with the sponsor immediately 
upon occurrence or awareness to determine if the participant should continue 
or discontinue study intervention.

Adherence to the study design requirements, including those specified in the 
SoA (Section 1.3), is essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that
potential participants meet all eligibility criteria. The investigator will 
maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable.
8.1.
Efficacy and Health Outcome Assessments
8.1.1.
Efficacy Assessments
Eczema Area and Severity Index
The EASI assesses extent of disease at 4 body regions and measures 4 clinical signs: 
(1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification each on a scale of 
0 (clear) to 3 (severe). The EASI confers a maximum score of 72 (a higher score is more severe). 
The EASI evaluates 2 dimensions of AD: disease extent and clinical signs (Hanifin et al. 2001).
The EASI is assessed by the investigator and completed using a tablet device at the study visit.
Body surface area affected by AD will be derived from data collected as part of the 
EASI assessment.
Investigator’s Global Assessment
The IGA is a static assessment and rates the severity of the participant’s AD. The IGA is 
composed of a 5-point scale ranging from 0 (clear) to 4 (severe), and a score is selected using 
descriptors that best describe the overall appearance of the lesions at a given time point. It is not 
necessary that all characteristics under Morphological Description be present. Assessors must be 
trained and certified by the sponsor prior to conducting this assessment. The IGA must be 
conducted prior to conducting the EASI. A single assessor should be assigned to each  
participant for as many visits as possible to avoid inter-assessor variability in scoring. The IGA is 
assessed by the investigator and completed using a tablet device at the study visit.
See the table below for the IGA.

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Table 5.
Investigator’s Global Assessment
Score
Grade
Definition
0
Clear
Minor, residual discoloration; no erythema or induration/papulation; no 
oozing/crusting; no edema.
1
Almost Clear
Trace, faint pink erythema with barely perceptible induration/papulation 
and no oozing/crusting; no edema.
2
Mild
Faint-pink erythema with papulation and edema perceptible upon palpation 
and no oozing/crusting; minimal induration.
3
Moderate
Pink-red erythema with definite edema of skin papules and plaques; there 
may be some oozing/crusting; palpable induration.
4
Severe
Deep/bright red erythema with significant swelling and obvious raised 
borders of papules and plaques with oozing/crusting; significant induration. 
SCORing Atopic Dermatitis
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical 
characteristics to determine disease severity: (1) erythema, (2) edema/papulation, 
(3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness. The SCORAD index also 
assesses subjective symptoms of itch and sleep loss. These 3 aspects, extent of disease, disease 
severity, and subjective symptoms, combine to give a maximum possible score of 103 (European 
Task Force on Atopic Dermatitis 1993; Kunz et al. 1997; Schram et al. 2012).
The SCORAD index is assessed by the investigator and participant and completed using a tablet 
device at each study visit.
8.1.2.
Participant Reported Outcomes and Health-Related Quality of Life
The participant self-reported questionnaires will be administered via an electronic participant
diary, electronic tablet, or will be paper-based. and will be administered in countries where 
the questionnaires have been translated into the native language of the region and linguistically 
validated.
Itch Numeric Rating Scale
The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 
0 representing “no itch” and 10 representing “worst itch imaginable”. Overall severity of a 
participant’s itching is indicated by selecting the number that best describes the worst level of 
itching in the past 24 hours (Naegeli et al. 2015; Kimball et al. 2016). The Itch NRS assessment 
will be completed daily by the participant using a handheld device.
Sleep-Loss Scoring System
Sleep loss due to itch will be assessed by the participant. Participants rate their sleep based on a 
5-point Likert scale (0 [not at all] to 4 [unable to sleep at all]). Assessments will be recorded 
daily by the participant using a handheld device.

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Skin Pain Numeric Rating Scale
Skin Pain NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 
0 representing “no pain” and 10 representing “worst pain imaginable.” Overall severity of a 
participant’s skin pain is indicated by selecting the number that best describes the worst level of 
skin pain in the past 24 hours. The Skin Pain NRS assessment will be completed daily by the 
participant using a handheld device.
Patient-Oriented Eczema Measure
The POEM is a simple, 7-item, participant-administered scale that assesses disease severity in 
children and adults. Participants respond to questions about the frequency of 7 symptoms
(itching, sleep disturbance, bleeding, weeping/oozing, cracking, flaking, and dryness/roughness) 
over the past week. Response categories include “No days,” “1-2 days,” “3-4 days,” “5-6 days,” 
and “Every day” with corresponding scores of 0, 1, 2, 3, and 4, respectively. Scores range from 
0-28, with higher total scores indicating greater disease severity (Charman et al. 2004). The 
POEM assessment will be completed weekly by the participant and using a handheld device.
Dermatology Life Quality Index/Children’s Dermatology Life Quality Index 
The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the 
quality of life of an affected person. The 10 questions cover the following topics: symptoms, 
embarrassment, shopping and home care, clothes, social and leisure, sports, work or study, close 
relationships, sex, and treatment, over the previous week. Questions are scored from 0 to 3, 
giving a possible total score range from 0 (meaning no impact of skin disease on quality of life) 
to 30 (meaning maximum impact on quality of life). A high score is indicative of a poor quality 
of life. Participants ≤16 years will complete the CDLQI and should continue to complete the 
CDLQI for the duration of the study. DLQI/CDLQI is completed by the participant in the study 
clinic. The DLQI/CDLQI assessment will be completed by the participant using a tablet device 
at the applicable study visit.
Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis
The WPAI-AD records impairment due to AD during the past 7 days. The WPAI-AD consists of 
6 items grouped into 4 domains: absenteeism (work time missed), presenteeism (impairment at 
work/reduced on-the-job effectiveness), work productivity loss (overall work 
impairment/absenteeism plus presenteeism), and activity impairment. Scores are calculated as 
impairment percentages (Reilly et al. 1993), with higher scores indicating greater impairment 
and less productivity. The WPAI-AD assessment will be completed by the participant using a 
tablet device at the applicable study visit.
Hospital Anxiety Depression Scale
The HADS is a 14-item self-assessment scale that determines the levels of anxiety and 
depression that a participant is experiencing over the past week. The HADS uses a 4-point Likert 
scale (0 to 3) for each question and is intended for participants aged 12 to 65 years (Zigmond and 
Snaith 1983; White et al. 1999). Scores for each domain (anxiety and depression) can range from 
0 to 21, with higher scores indicating greater anxiety or depression (Zigmond and Snaith 1983; 
Snaith 2003). The HADS assessment will be completed by the participant using a tablet device at 
the applicable study visit.

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Asthma Control Questionnaire-5
Participants who report comorbid asthma prior to enrollment will complete the ACQ-5 in 
addition to other participant-reported outcomes in this study. The ACQ-5 has been shown to 
reliably measure asthma control and distinguish participants with well-controlled asthma (score 
≤0.75 points) from those with uncontrolled asthma (score ≥1.5 points). The ACQ-5 consists 
of 5 questions that are scored on a 7-point Likert scale with a recall period of 1 week. The 
total ACQ-5 score is the mean score of all questions; a lower score represents better asthma 
control. The ACQ-5 assessment will be completed by the participant in the study clinic using a 
tablet device at the applicable study visit.
Columbia Suicide Severity Rating Scale
The C-SSRS captures the occurrence, severity, and frequency of suicidal ideation and/or 
behavior during the assessment period. The scale includes suggested questions to solicit the type 
of information needed to determine whether suicidal ideation and/or behavior has occurred. The 
C-SSRS is administered by an appropriately trained health care professional with at least 1 year 
of participant care/clinical experience. The tool was developed by the National Institute of 
Mental Health trial group as a counterpart to the Columbia Classification Algorithm of Suicide 
Assessment categorization of suicidal events. For this study, the scale has been adapted (with 
permission from the scale authors) to include only the portion of the scale that captures the 
occurrence of the 11 preferred ideation and behavior categories. The nonleading AE collection 
should occur prior to the collection of the C-SSRS. If a suicide-related event is discovered during 
the C-SSRS assessment but was not captured during the nonleading AE collection, sites should 
not change the AE form. If an event is serious or leads to discontinuation, this is an exception  
for which the SAE and/or AE leading to discontinuation should be included on the AE form and 
the process for reporting SAEs should be followed. This assessment will be administered by 
paper at the study visit.
Self-Harm and Follow-Up Supplement Forms
Suicide-related events (behavior and/or ideations) will be assessed and evaluated at every visit 
with the administration of the Self-Harm Supplement Form. The Self-Harm Supplement Form is 
a single question to enter the number of suicidal behavior events, possible suicide behaviors, or 
nonsuicidal self-injurious behaviors. If the number of behavioral events is greater than 0, the 
participant will complete of the Self-Harm Follow-Up Form. The Self-Harm Follow-Up form is 
a series of questions that provides a more detailed description of the behavior cases.
8.2.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA (Section 1.3).

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8.2.1.
Physical Examinations

A complete physical examination will be conducted at screening and will 
include, at a minimum, assessments of general appearance; head, ears, 
eyes, nose, and throat; and dermatological, respiratory, cardiovascular, 
abdominal, neurological, musculoskeletal, and lymphatic body systems. 
Height and weight will also be measured and recorded.

At subsequent study visits, a symptom-directed physical examination 
may be conducted at the discretion of the investigator.

Investigators should pay special attention to clinical signs related to 
previous serious illnesses.
Findings will be recorded as medical history or AE in the eCRF.
8.2.2.
Vital Signs
For each participant, vital sign measurements should be conducted according to the SoA
(Section 1.3). Vital signs, including body temperature, respiratory rate (breath per minute), pulse 
(beats per minute), and blood pressure (mm Hg), will be obtained with the participant in the 
seated position, after sitting for at least 5 minutes. Any abnormal finding that is new or has
worsened and is clinically significant, in the opinion of the investigator, will be recorded as an 
AE. Vital sign measurements will be recorded in the eCRF.
8.2.3.
Electrocardiograms
A single 12-lead ECG will be obtained locally at screening. The ECG will be read by a qualified 
physician (the investigator or qualified designee) at the site to determine whether the participant 
meets the entry criteria.
Electrocardiograms may be obtained at additional times, when deemed clinically necessary.
8.2.4.
Clinical Safety Laboratory Assessments

See Appendix 2 for the list of clinical laboratory tests to be performed and the 
SoA (Section 1.3) for their timing and frequency. In the opinion of the 
investigator, if evaluating beta-D-glucan is medically necessary, the 
investigator may do so at any time during the study, including at screening 
and during the Safety Follow-Up Period.

The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those 
which are not associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

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
All laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 28 days after the last dose of study 
intervention should be repeated until the values return to normal or baseline or 
are no longer considered clinically significant by the investigator or medical 
monitor.
○
If such values do not return to normal/baseline within a period of time 
judged reasonable by the investigator, the etiology should be 
identified, and the sponsor notified.
○
All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory 
manual and the SoA (Section 1.3).
○
If laboratory values from non-protocol–specified laboratory 
assessments performed at the institution’s local laboratory require a 
change in participant management or are considered clinically 
significant by the investigator (for example, SAE or AE or dose 
modification), then the results must be recorded in the CRF.
Laboratory tests will be analyzed using a central laboratory and will be transferred to the clinical 
database.
In cases where required blood samples cannot be collected due to blood volume limitation 
relative to participant size/age, the investigator must consult with Lilly-designated medical 
personnel to determine which samples to collect. This will not be considered a protocol violation 
but will need to be documented in the medical record.
8.2.5.
Chest Radiography
A posterior-anterior chest x-ray will be performed locally at screening, unless one has been 
performed within the past 90 days, the x-ray and reports are available, and a repeat chest x-ray is 
not clinically indicated per investigator judgment. Additional chest x-rays will be performed at 
Week 52, Week 68, and/or at ET, if more than 12 weeks have elapsed since the previous study 
x-ray was obtained. This x-ray may be performed within 12 weeks if medically indicated. The 
chest x-ray will be reviewed by the investigator or his or her designee.
8.2.6.
Tuberculosis Testing and Monitoring
All participants will undergo a TB test at screening (tuberculin skin test [TST] or IFN-release 
test). Refer to Exclusion Criterion [17] for details regarding TB testing.
Tuberculosis tests include PPD, QuantiFERON-TB Gold, and T-SPOT. At study sites where the 
QuantiFERON-TB Gold test or T-SPOT is available, either test may be used instead of the PPD 
TB test. The QuantiFERON-TB Gold test may be performed locally or centrally; the T-SPOT 
must be performed locally. (Note: Participants who have a documented history of completing an 
appropriate TB treatment regimen for LTBI with no risk of re-exposure since completion are 
eligible to participate in the study if other criteria are met. These participants should not undergo 
the protocol-specific TB testing (orthographic variants: TST = PPD, IGRA = QuantiFERON-TB 

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Gold and T-SPOT), unless advised to do so based on local guidelines, but must have a chest x-
ray at screening.
8.2.7.
Hepatitis B Testing and Monitoring
Participants who are HBsAg negative and positive for HBcAb and/or HBsAb will automatically 
have an HBV DNA test performed at screening. Participants who are HBsAg negative, HBcAb 
negative, and HBsAb positive with a documented history of hepatitis B vaccination will not be 
required to undergo HBV DNA monitoring at screening. If screening HBV DNA is negative, 
defined as undetectable HBV DNA, the participant is not excluded, and HBV DNA monitoring 
is required per the schedule.
If the result of the HBV DNA testing becomes positive at any time during the study, the 
participant will be permanently discontinued from IP (see Section 7.1.1) and should receive 
appropriate follow-up medical care, including consideration for antiviral therapy. A specialist 
physician in the care of participants with hepatitis (for example, infectious disease physician or 
hepatologist) should be consulted. The timing of discontinuation from IP and any other 
immunosuppressant therapy should be based on the recommendations of the consulting specialist 
physician in conjunction with the investigator and medical guidelines/standard of care.
8.2.8.
Hepatic Safety
8.2.8.1.
Close Hepatic Monitoring*
Laboratory tests (Appendix 2), including ALT, AST, ALP, total bilirubin (TBL), direct bilirubin, 
gamma-glutamyltransferase (GGT), and creatine kinase (CK), should be repeated within 48 to 72 
hours to confirm the abnormality and to determine if it is increasing or decreasing, if one or more 
of these conditions occur:
If a participant with baseline results of ... 
develops the following elevations:
ALT or AST <1.5x ULN
ALT or AST ≥3x ULN
ALP <1.5x ULN
ALP ≥2x ULN
TBL <1.5x ULN
TBL ≥2x ULN (except for participants with Gilbert’s syndrome)
ALT or AST ≥1.5x ULN
ALT or AST ≥2x baseline
ALP ≥1.5x ULN
ALP ≥2x baseline
TBL ≥1.5x ULN
TBL ≥1.5x baseline (except for participants with Gilbert’s 
syndrome)
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
TBL = total bilirubin; ULN = upper limit of normal.
*All ULN values should be age adjusted (AAULN)
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 Lilly-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, history of concomitant 

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medications (including over-the-counter), herbal and dietary supplements, history of alcohol 
drinking and other substance abuse. 
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests. 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and laboratory results stabilize. Monitoring of ALT, AST, ALP 
and TBL should continue until levels normalize or return to approximate baseline levels. For 
pediatric participants, special care should be taken to minimize the volume of blood taken during 
hepatic monitoring.
8.2.8.2.
Comprehensive Hepatic Evaluation*
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
one or more of these conditions occur:
If a participant with baseline 
results of...
develops the following elevations:
ALT or AST <1.5x ULN
ALT or AST ≥3x ULN with hepatic signs/symptoms**, or
ALT or AST ≥5x ULN
ALP <1.5x ULN
ALP ≥3x ULN
TBL <1.5x ULN
TBL ≥2x ULN (except for participants with Gilbert’s syndrome)
ALT or AST ≥1.5x ULN
ALT or AST ≥2x baseline with hepatic signs/symptoms**, or
ALT or AST ≥3x baseline
ALP ≥1.5x ULN
ALP ≥2x baseline
TBL ≥1.5x ULN
TBL ≥2x baseline (except for participants with Gilbert’s syndrome) 
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
TBL = total bilirubin; ULN = upper limit of normal.
*All ULN values should be age adjusted (AAULN)
**Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, and/or 
rash.
For Adult Participants (≥18 years old)
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time-INR, viral hepatitis A, B, C, or 
E, tests for autoimmune hepatitis, and an abdominal imaging study (for example, ultrasound or 
computed tomography scan). 
Based on the participant’s history and initial results, further testing should be considered, in 
consultation with the Lilly-designated medical monitor, including tests for hepatitis D virus
(HDV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), acetaminophen levels, 
acetaminophen protein adducts, urine toxicology screen, Wilson’s disease, blood alcohol levels, 
urinary ethyl glucuronide, and blood phosphatidylethanol. Based on the circumstances and the 
investigator’s assessment of the participant’s clinical condition, the investigator should consider 
referring the participant for a hepatologist or gastroenterologist consultation, magnetic resonance 

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cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), 
cardiac echocardiogram, or liver biopsy.
For Pediatric Participants (<18 years old)
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time-INR and direct bilirubin, if total 
bilirubin was elevated.
Based on the participant’s age, medical history and initial results, further testing should be 
considered in consultation with the Lilly-designated medical monitor, including tests for viral 
hepatitis A, B, C, or E; autoimmune hepatitis; or an abdominal imaging study (for example, 
ultrasound, MRI, or CT scan). Consider additional tests, based on the medical history and 
clinical picture, including tests for HDV, CMV, EBV, acetaminophen levels, acetaminophen 
protein adducts, urine toxicology screen, Wilson’s disease, blood alcohol levels, urinary ethyl 
glucuronide, and blood phosphatidylethanol. Special care should be taken to prioritize more 
pertinent blood tests and minimize the volume of blood taken during hepatic evaluation. Based 
on the circumstances and the investigator’s assessment of the participant’s clinical condition, the 
investigator should consider referring the participant for a pediatric hepatologist or 
gastroenterologist consultation, MRCP, ERCP, cardiac echocardiogram, or a liver biopsy as 
deemed appropriate for the clinical condition and participant’s age.
8.2.8.3.
Additional Hepatic Data Collection in Participants Who Have Abnormal Liver 
Test Results During the Study
Additional hepatic safety data collection (hepatic safety CRF) should be performed in study 
participants who meet 1 or more of the following 5 conditions:*
1.
Elevation of serum ALT to ≥5× ULN on 2 or more consecutive blood tests (if 
baseline ALT <1.5× ULN)

In participants with baseline ALT ≥1.5× ULN, the threshold is ALT ≥ 3× baseline 
on 2 or more consecutive tests
2.
Elevated TBL to ≥2× ULN (if baseline TBL<1.5× ULN) (except for cases of known 
Gilbert’s syndrome)

In participants with baseline TBL ≥1.5× ULN, the threshold should be TBL ≥2×
baseline
3.
Elevation of serum ALP to ≥2× ULN on 2 or more consecutive blood tests (if 
baseline ALP <1.5× ULN)

In participants with baseline ALP ≥1.5× ULN, the threshold is ALP ≥2× baseline 
on 2 or more consecutive blood tests
4.
Hepatic event considered an SAE
5.
Discontinuation of study intervention due to a hepatic event 
NOTE: the interval between the 2 consecutive blood tests should be at least 2 days.

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*All ULN values should be age adjusted (AAULN)
8.2.9.
Growth Monitoring
Height, weight, and hormone levels (estradiol for females or testosterone for males) will be 
measured according to the SoA (Section 1.3) to allow for identification of potential effects on 
growth and development. Height and weight changes in adolescent participants at an individual 
level will be reviewed by the data monitoring committee (DMC) external to Lilly.
8.3.
Adverse Events and Serious Adverse Events
The definitions of the following events can be found in Appendix 3:

Adverse events (AEs)

Serious adverse events (SAEs)

Product complaints (PCs) are covered in Section 8.3.8.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study intervention or study (see Section 7).
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information
All AEs and SAEs will be collected from the signing of the ICF until the safety follow-up visit 
(Visit 801) at the time points specified in the SoA (Section 1.3).
Adverse events that begin before the start of study intervention but after signing of the ICF will 
be recorded on the AE CRF.
Although all AEs after signing the ICF are recorded by the site in the CRF/electronic data entry, 
SAE reporting to the sponsor begins after the participant has signed the ICF and has received 
study intervention. However, if an SAE occurs after signing the ICF, but prior to receiving
lebrikizumab, it needs to be reported ONLY if it is considered reasonably possibly related to 
study procedures.
All SAEs will be recorded and reported to the sponsor or designee immediately, and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 3. The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being available.
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the investigator must promptly notify 
the sponsor.

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8.3.2.
Method of Detecting Adverse Events and Serious Adverse Events
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3.
Follow-Up of Adverse Events and Serious Adverse Events
After the initial AE/SAE report, the investigator is required to proactively follow up with each 
participant at subsequent visits/contacts. All SAEs, and AESI (as defined in Section 8.3.6) will 
be followed up until resolution, stabilization, the event is otherwise explained, or the participant 
is lost to follow-up (as defined in Section 7.3). Further information on follow-up procedures is 
provided in Appendix 3.
8.3.4.
Regulatory Reporting Requirements for Serious Adverse Events

Prompt notification by the investigator to the sponsor of an SAE is essential 
so that legal obligations and ethical responsibilities toward the safety of 
participants and the safety of a study intervention under clinical investigation 
are met.

The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study 
intervention under clinical investigation. The sponsor will comply with 
country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, institutional review boards (IRBs)/independent ethics 
committees (IECs), 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/IEC, if appropriate according to local requirements.
8.3.5.
Pregnancy

Details of all pregnancies in female participants and female partners of male 
participants will be collected after the start of study intervention and until 
125 days after the last dose.

If a pregnancy is reported, the investigator should inform the sponsor within 
24 hours of learning of the pregnancy and should follow the procedures 
outlined in Appendix 4.

Abnormal pregnancy outcomes (for example, spontaneous abortion, 
fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered SAEs.

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8.3.6. Adverse Events of Special Interest 
The following TEAEs will be designated AESI:

conjunctivitis

herpes infection or zoster, and 

parasitic infection or an infection related to an intracellular pathogen.
Adverse events of special interest should be reported to the sponsor or designee within 48 hours 
of knowledge of the event. Additional data, including medical history of first-degree relatives
will be collected for AESI on study-specific AESI forms, which will be provided to the site. 
Participant records must include any follow-up information regarding these AESI. 
Study intervention should be discontinued if an AE is deemed persistent and if continuation 
of study intervention would not be in the best interest of the participant. Discuss discontinuation 
of study intervention with the sponsor or designee prior to implementation.
8.3.7.
Hypersensitivity Events
Many drugs, but particularly biologic agents, carry the risk of systemic hypersensitivity 
reactions. Clinical manifestations of these reactions may include but are not limited to:

rash

pruritus (itching)

dyspnea

urticaria (hives)

angioedema (for example, swelling of the lips and/or tongue)

hypotension, and 

anaphylactic reaction.
If such a reaction occurs, additional data describing each symptom should be provided to the 
sponsor in the eCRF.
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 local standard 
of care. 
In the case of generalized urticaria or anaphylaxis, additional blood and urine samples should be 
collected as described in Appendix 2. Laboratory results are provided to the sponsor via the 
central laboratory.
8.3.8. Product Complaints
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
study intervention.
The sponsor collects product complaints on IPs and intervention delivery systems used in clinical 
studies to ensure the safety of study participants, monitor quality, and facilitate process and 
product improvements.

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Participants will be instructed to contact the investigator as soon as possible if they have a 
complaint or problem with the IP so that the situation can be assessed.
NOTE: AEs/SAEs that are associated with a product complaint will follow the processes 
outlined in Section 8.3.3 and Appendix 3.
8.3.8.1.
Time Period for Detecting Product Complaints

Product complaints that result in an AE will be detected, documented, and 
reported to the sponsor during all periods of the study in which the 
intervention is used.

If the investigator learns of any product complaint at any time after a 
participant has been discharged from the study, and such incident is 
considered reasonably related to an intervention provided for the study, the 
investigator will promptly notify the sponsor.
8.3.8.2. Prompt Reporting of Product Complaints to the Sponsor

Product complaints will be reported to the sponsor within 24 hours after the 
investigator becomes aware of the complaint.

The Product Complaint Form will be sent to the sponsor by a method
designated by the sponsor.
8.3.8.3.
Follow-Up of Product Complaints

Follow-up applies to all participants, including those who discontinue 
study intervention.

The investigator is responsible for ensuring that follow-up includes any
supplemental investigations, as indicated, to elucidate the nature and/or 
causality of the product complaint.

New or updated information will be recorded on the originally completed 
form, with all changes signed and dated by the investigator and submitted to 
the sponsor.
8.4.
Treatment of Overdose
There are no data available on overdoses with lebrikizumab. No dose-related serious adverse 
drug reactions were observed in healthy volunteers who received single intravenous (IV) doses 
of up to 5 mg/kg, in patients with mild asthma who received multiple IV doses of up to 3 mg/kg 
or in participants with asthma or AD who received multiple SC doses of up to 500 mg.
In case of suspected overdose, hematology, chemistry, vital signs, and oxygen saturation should 
be monitored and supportive care provided as necessary. There is no known antidote for 
lebrikizumab.
In the event of an overdose, the investigator should:
1. Contact the medical monitor immediately.

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2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until 
lebrikizumab can no longer be detected systemically (at least 18 days).
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
8.5.
Pharmacokinetics

Whole venous blood samples will be collected for measurement of serum
concentrations of lebrikizumab as specified in the SoA (Section 1.3).

Samples may be collected at additional time points during the study if 
warranted and agreed upon between the investigator and the sponsor.

Instructions for the collection and handling of biological blood samples will 
be provided by the sponsor. The actual date and time (24-hour clock time) of 
each sample will be recorded.
Intervention concentration information that may unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded.
8.5.1. Bioanalysis
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor. Serum concentrations of lebrikizumab will be assayed using a 
validated enzyme-linked immunosorbent assay method. Analyses of samples collected from 
placebo-treated participants are not planned. Bioanalytical samples collected to measure IP
concentrations will be retained for a maximum of 2 years following last participant visit for 
the study. During this time, samples remaining after the bioanalysis may be used for 
exploratory metabolism studies or exploratory analyses such as bioanalytical assay validation 
or cross-validation exercises.
8.6.
Pharmacodynamics
Samples collected (as specified in the SoA [Section 1.3) to measure thymus and activation-
regulated chemokine (TARC) will be identified by the participant number (coded) and retained 
at a facility selected by Lilly or its designee for a maximum of 1 year following the last 
participant visit for the study at a facility selected by Lilly or its designee.
8.7.
Genetics
A blood sample for DNA isolation will be collected from participants. 
See Appendix 5 for information regarding genetic research and Appendix 1 (Section 10.1.11) for 
details about sample retention and custody.
8.8.
Biomarkers
Biomarkers will not be evaluated in this study.

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8.9.
Immunogenicity Assessments
At the visits and times specified in the SoA (Section 1.3), venous blood samples will be collected 
to determine antibody production against lebrikizumab. Antibodies may be further characterized 
for their ability to neutralize the activity of lebrikizumab. To interpret the results of 
immunogenicity, a venous blood sample will be collected at the same time points to determine 
the serum concentrations of lebrikizumab. All samples for immunogenicity should be taken 
predose when applicable and possible.
Upon assay validation, ADAs may be characterized; treatment-emergent ADAs (TE-ADAs) are 
defined in Section 9.4.6.
The purpose of retention, the maximum duration of retention, and facility for long-term storage 
of samples are described in Appendix 1 (Section 10.1.11). Samples may also be used 
for development and control of an immunogenicity assay.
8.10.
Health Economics
Not applicable.

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9.
Statistical Considerations
9.1.
Statistical Hypotheses
The null hypothesis for the primary endpoint is that there is no difference between lebrikizumab 
250 mg Q2W and placebo or lebrikizumab 250 mg Q4W and placebo in reducing the signs and 
symptoms of AD as measured by both the proportion of participants achieving IGA score of 0 or 
1 and a reduction of ≥2-points from baseline to Week 16 and the proportion of participants
achieving EASI-75 (≥75% reduction from baseline in EASI score) at Week 16.
9.2.
Sample Size Determination
Approximately 280 participants will be randomized at a 3:2:2 ratio to lebrikizumab 250 mg 
Q2W, lebrikizumab 250 mg Q4W, or placebo (120 participants: 80 participants: 80 participants).
The inclusion of approximately 15 adolescents is based on enrollment feasibility in Japan.
The assumed IGA score of 0 or 1 at Week 16 response rates are 38% for lebrikizumab 250 mg 
Q2W, 33% for lebrikizumab 250 mg Q4W, and 13% for placebo. The assumed EASI-75 
response rates at Week 16 are 58% for lebrikizumab 250 mg Q2W, 53% for lebrikizumab 
250 mg Q4W, and 20% for placebo. The assumptions for lebrikizumab are based on the 
DRM06-AD01 Phase 2b study, and the proportion of participants who achieved an IGA score 
of 0 or 1 and proportion of participants who achieved EASI-75 response at Week 16 using the 
rescue medication nonresponse sensitivity analysis, adjusting for the allowed use of TCS. The 
placebo response rate is based on the review of historical TCS clinical studies in AD (Simpson 
et al. 2016). This study has >95% and >80% power to test the superiority of lebrikizumab 
250 mg Q2W to placebo and lebrikizumab 250 mg Q4W to placebo in the co-primary 
endpoints based on a two-sided Fisher exact test with alpha of 0.05.
9.3.
Populations for Analyses
The following populations are defined:
Population
Description
Entered
All participants who signed informed consent/assent. Participant
flow will be summarized.
Intent-to-Treat (ITT)
All randomized participants, even if the participant does not take 
the assigned treatment, does not receive the correct treatment, or 
otherwise does not follow the protocol. Participants will be 
analyzed according to the treatment group to which they were 
assigned. Unless otherwise specified, efficacy and health 
outcome analyses for the Induction Period will be conducted on 
this population.
Safety Population
All randomized participants who received at least 1 dose of study 
intervention during the Induction Period. Safety analyses for the
Induction Period will be conducted on this population.

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Population
Description
Per-Protocol Set (PPS)
All ITT participants who do not have a subset of important 
protocol deviations that impact the primary efficacy endpoint. 
Important protocol deviations are defined in a separate document 
referred to as “The KGAL Trial Issues Management Plan.” 
Primary efficacy analysis for IGA 0/1 and EASI-75 will be 
repeated using the PPS.
Maintenance Period 
Primary Population
All participants who were randomized to lebrikizumab 250 mg 
Q2W at baseline visit and re-randomized to lebrikizumab 250 mg 
Q2W or lebrikizumab 250 mg Q4W (that is, participants 
who achieved an IGA of 0 or 1 and/or EASI-75 and were 
re-randomized at Week 16) or who were randomized 
to lebrikizumab 250 mg Q4W at baseline visit and continued 
lebrikizumab 250 mg Q4W (that is, participants who achieved 
an IGA of 0 or 1 and/or EASI-75 at Week 16) and received at 
least 1 dose of study intervention during the Maintenance Period. 
Participants will be analyzed according to the treatment to which 
they were assigned. Only information prior to escape will be 
presented. Efficacy, health outcome, and safety analyses for 
the Maintenance Period will be conducted primarily on the
Maintenance Period Primary Population.
Maintenance Period 
Secondary Population
Participants who were randomized to placebo at baseline visit 
and participants who entered the Escape Arm at Week 16 due to 
not meeting IGA 0/1 and EASI-75 criteria or using rescue 
therapy during the Induction Period and received at least 1 dose 
of study intervention during the Maintenance Period. Selective 
efficacy analyses for the Maintenance Period will be conducted 
on the Maintenance Period Secondary Population.
Maintenance Period
Escape Population
Maintenance Period Primary and Secondary Population who 
escaped to lebrikizumab 250 mg Q2W due to EASI-50 
non-response at Weeks 20, 24, 28, 32, 36, 40, 44, 48, 52, 56,
60 or 64. Selective efficacy analyses for the Maintenance Period 
will be conducted on the Maintenance Period Escape Population 
to assess whether these participants re-gain EASI-50 response or 
achieve a higher level of response (for example, EASI-75) 
following re-treatment.

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Population
Description
All Lebrikizumab Safety 
Population
All randomized participants who received at least 1 dose of 
lebrikizumab treatment during Combined Induction and 
Maintenance Periods. Safety analyses for the Combined
Induction and Maintenance Periods will be conducted on the 
All lebrikizumab Safety Population. Selective safety analyses for 
the Combined Induction and Maintenance Periods plus 
the Follow-Up Period will be conducted on the All Lebrikizumab 
Safety Population.
Pharmacokinetic Analysis
All participants who received at least 1 dose of lebrikizumab and 
have at least 1 evaluable PK sample.
Abbreviations: EASI-75 = ≥75% reduction from baseline in Eczema Area and Severity Index IGA = Investigator’s 
Global Assessment; Q2W = every 2 weeks; Q4 = every 4 weeks.
9.4.
Statistical Analyses
9.4.1. General Considerations
Statistical analysis of this study will be the responsibility of the sponsor or its designee.
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.05, unless otherwise 
stated, and all CIs will be given at a 2-sided 95% level.
For the efficacy and health outcome analyses during the Induction and Maintenance Periods, 
baseline is defined as the last available value before the first injection in the Induction Period. In 
most cases, this will be the value recorded at baseline visit (Visit 2, Week 0).
For safety analyses during the Induction Period, the Baseline Period is defined as the time from 
the screening visit (Visit 1) to the date/time of the first injection in the Induction Period. Baseline 
will be the last scheduled non-missing assessment recorded during the baseline period. Unless 
specified otherwise, for the safety analyses during the Maintenance Period, baseline is defined 
as the last available value before the first injection in the Maintenance Period. In most cases, this 
will be the measure recorded at Week 16.
Descriptive statistics will be used to provide an overview of the efficacy and safety results. For 
categorical parameters, the number and percentage of participants in each category will be 
presented. For continuous parameters, descriptive statistics will include number of participants
(n), mean, SD, median, minimum, and maximum. Appropriate inferential statistics will be used 
for the primary and secondary efficacy variables.
The primary estimand that will be used to analyze primary and secondary endpoints is a 
composite variable strategy where comparisons will not include data collected after intercurrent 
events of changes to background therapies or discontinuation due to lack of efficacy (ICH E9 
[R1]).
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 

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in the statistical analysis plan (SAP) and the clinical study report. Additional exploratory 
analyses of the data will be conducted as deemed appropriate.
The SAP will be finalized prior to unblinding and it will include a more technical and detailed 
description of the statistical analyses described in this section. This section is a summary of the 
planned statistical analyses of the most important endpoints, including primary and key
secondary endpoints.
9.4.1.1.
Missing Data Imputation
The primary method of handling missing efficacy data after intercurrent events will be as 
discussed below for both binary and continuous endpoints.
For participants who receive rescue medication (high-/ultra-high–potency TCS or systemic 
AD treatment) or withdraw from the study due to lack of efficacy, the participant’s baseline 
value will be carried forward to the subsequent time points through Week 16. Markov Chain 
Monte Carlo multiple imputation will be used to handle the remaining missing data.
Sensitivity analyses will be addressed in the SAP.
9.4.1.2.
Adjustment for Multiple Comparisons
The prespecified graphical multiple testing approach (Bretz et al. 2011) will be implemented 
to control the overall type I error rate at a 2-sided alpha of 0.05 for superiority tests for the 
hypotheses for the co-primary and major secondary endpoints.
The major secondary endpoints are as follows:

percentage change in EASI score from baseline to Week 16

proportion of participants achieving EASI-90 (≥90% reduction from baseline in 
EASI score) at Week 16, and 

proportion of participants with an Itch NRS of ≥4-points at baseline who achieve a 
≥4-point reduction from baseline to Weeks 1, 2, 4 and 16.
The graphical approach is a closed testing procedure; hence, it strongly controls the family-wise 
error rate across all endpoints (Alosh et al. 2014). The Week 16 endpoints of IGA 0/1 and
EASI-75 represent a primary endpoint family. The graphical testing scheme will sequentially test 
the co-primary endpoints for lebrikizumab 250 mg Q2W to placebo first before proceeding to 
test the co-primary endpoints for lebrikizumab 250 mg Q4W to placebo and the major secondary 
endpoints during the Induction Period. Details of the specific graphical testing scheme (including 
testing order, interrelationships, type I error allocation, and the associated propagation) will be 
prespecified in the SAP prior to first unblinded efficacy analysis.
9.4.2.
Treatment Group Comparability
9.4.2.1.
Participant Disposition
The number of randomized participants will be summarized. Frequency counts and percentages 
of all participants who are randomized, complete the study, discontinue the study intervention,
or discontinue the study early will be presented. Reasons for discontinuing study intervention or 
the study will be summarized.

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9.4.2.2.
Participant Characteristics
Demographic data will be collected to demonstrate that the study population represents the target 
participant 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 or listed, as 
deemed appropriate.
9.4.2.3.
Concomitant Therapy
Current concomitant therapy (reported after randomization) will be summarized by treatment 
group and will be presented by Anatomical Therapeutic Chemical (ATC) drug classes using the 
latest version of the World Health Organization (WHO) Drug Dictionary. Previous concomitant 
therapy (reported before randomization and after ICF) will be listed. 
9.4.2.4.
Treatment Compliance
Participants who are noncompliant will be listed by treatment. A participant will be considered 
compliant if he or she received ≥75% of the expected number of injections while enrolled in the 
study. The details of noncompliance will be defined in the SAP. 
9.4.3.
Efficacy Analyses
9.4.3.1.
Primary Analyses
The co-primary endpoints are the percentage of participants achieving IGA score of 0 or 1 and a 
reduction of ≥2-points from baseline to Week 16 and the percentage of participants achieving 
EASI-75 (≥75% reduction from Baseline in EASI score) at Week 16 and will be analyzed using 
the Cochran-Mantel-Haenszel test adjusted by randomization strata (disease severity: IGA 3 vs 4
and age: adolescent participants ≥12 to <18 years vs ≥18 years).
9.4.3.2.
Secondary Analyses
For secondary binary efficacy and health outcome endpoints during the Induction Period, the 
CMH test will be used to compare the treatment groups while adjusting for the stratification 
factors (disease severity: IGA 3 versus 4, and age: adolescent participants ≥12 to <18 years 
versus ≥18 years).
Treatment comparisons of secondary continuous efficacy and health outcome endpoints during 
the Induction Period will be made using an analysis of covariance with the following in the 
model: treatment group, baseline value, and stratification factors.
Efficacy, health outcome, and safety measures during the Maintenance Period will be 
summarized using descriptive statistics by treatment group.
More details will be specified in the SAP.
9.4.4.
Safety Analyses
Safety analyses will include AEs, SAEs, AESI, vital signs, and laboratory analytes. The safety 
data will be summarized descriptively by treatment group. Categorical safety measures will be 
summarized with the number and percentage of participants. Continuous safety measures will be 

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summarized as mean change by visit. Exposure to study intervention will be calculated for each 
participant and summarized by treatment group.
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA) and summarized by system organ class (SOC), preferred term (PT), severity, and 
relationship to the study intervention. A TEAE is defined as an event that first occurred or 
worsened in severity after the baseline period. The baseline period for the Induction Period is 
defined as the time from the screening visit (Visit 1) to the date/time of the first injection in the 
Induction Period. Baseline for the Maintenance Period is the events ongoing just prior to the first 
injection of study intervention at Week 16. The Treatment Period will be used as the postbaseline 
period for the analysis. For events that are gender specific, the denominator and computation of 
the percentage will include only participants from the given gender.
The number and percentage of participants who experienced TEAEs, TEAEs by maximum 
severity, deaths, SAEs, TEAEs related to study intervention, discontinuations from study 
intervention due to an AE, and AESI will be summarized. Treatment-emergent adverse events 
(all, by maximum severity), SAEs including deaths, and AEs that lead to study intervention
discontinuation will be summarized and analyzed by MedDRA SOC and PT.
Treatment-related TEAEs (TEAEs considered related to study intervention) are defined as events 
that are indicated by the investigator on the eCRF to be related to treatment.
Adverse events of special interest will be identified by a Standardised MedDRA Query (SMQ) or 
a Lilly-defined MedDRA PT listing.
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 
(Columbia Lighthouse Project Scoring and Data Analysis Guide [WWW]).
Follow-up emergent AEs, SAEs including deaths, and AEs that lead to study discontinuation will 
be listed. All AEs, including preexisting conditions, will be listed by participant, visit, PT, 
treatment group, severity, and relationship to the treatment.
Growth monitoring of adolescent participants will be summarized. More details will be provided
in the SAP.
9.4.5.
Pharmacokinetic/Pharmacodynamic Analyses
Serum concentration data will be tabulated and summarized (for example, by geometric mean
and % coefficient of variation) by treatment group for each visit at which samples were taken.
It is intended that data from this study will be combined with data from other studies to better
characterize the PK of lebrikizumab, as well as to explore the relationship between exposure 
and efficacy and/or safety outcomes. Further details on PK and PK/pharmacodynamic (PD)
analyses will be provided in the PK/PD analysis plan. The results of these analyses will be 
described in a separate PK/PD report.
9.4.6.
Evaluation of Immunogenicity
For immunogenicity, upon assay validation, the frequency and percentage of participants with 
preexisting ADAs and with TE-ADAs to lebrikizumab will be tabulated. Participants who are 

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TE-ADA positive are defined as those with a titer 2-fold (1 dilution) greater than the minimum 
required dilution if no ADAs were detected at baseline (treatment-induced ADA) or those with a 
4-fold (2 dilutions) increase in titer compared to baseline if ADAs were detected at baseline 
(treatment-boosted ADA). The frequency of neutralizing antibodies may also be tabulated in 
TE-ADA positive participants. The relationship between the presence of antibodies and the PK 
parameters and PD response, including safety and efficacy to lebrikizumab, may be assessed.
9.4.7.
Subgroup, Supplemental, and Other Exploratory Analyses
Subgroup analyses
Subgroup analyses will be conducted for the following subgroups: ≥12 to <18 years versus
≥18 years of age, sex, and baseline IGA score (3 or 4). Subgroup analyses will be conducted 
for the co-primary endpoints of IGA 0/1 and EASI-75 at Week 16 on the intent-to-treat (ITT)
population.
Some additional subgroup analyses may be added to the SAP.
Supplemental analyses
Supplemental analyses will be performed on the co-primary endpoints using another composite 
variable strategy where comparisons will not include data collected after intercurrent events of 
changes to background therapies or discontinuation due to lack of efficacy ([ICH E9 [R1] Step 4 
2019). For participants who receive rescue medication, their values while on rescue medication 
will be set to missing.
Analysis details will be described in the SAP.
Exploratory analyses
Exploratory analyses will be specified in the SAP.
9.5.
Interim Analyses
The first database lock and unblinding will occur, and the interim analysis, including the 
Maintenance Period, will be performed at the time the last participant completes Week 52 or the 
ET visit (that is, a cutoff date). This database lock will include all data collected by the cutoff 
date. Because the study will be ongoing for the Maintenance and Follow-Up periods at the time 
of this database lock, the analysis will be referred to as an interim analysis. The analyses from 
the Week 52 database lock will be treated as a primary analysis for an initial regulatory 
submission in Japan because all primary and major secondary study objectives will be assessed 
at this time. The study will not be terminated early on the basis of efficacy following this interim 
analysis. The sponsor or designee could unblind a small team, including but not limited to 
medical, statistics, data management, regulatory to prepare for regulatory interactions, safety 
updates, and disclosures if needed, while the investigator, study-site personnel, and Lilly study 
members who are site facing and the participants will be blinded to treatment assignment until 
the final database lock.
The second database lock will occur, and the interim analysis, including the Maintenance Period,
will be performed at the time the last participant completes Week 68 or the ET visit (that is, a 
cutoff date). This database lock will include all data collected by the cutoff date. The additional 
results from the Week 68 database lock will be submitted to the Japan Regulatory Agency during 

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the review period 6 months before the approval timing of lebrikizumab for the AD indication 
in Japan.
The final database lock will then be conducted after all participants have completed the 
Follow-Up Period.
Depending on the regulatory submission timeline, the second database lock and the final 
database lock may be combined, (that is, 1 final database lock will occur after all participants
have either completed the Follow-Up Period or discontinued the study early).
9.6.
Data Monitoring Committee 
An independent DMC composed of members who are independent of the study sponsor and 
study investigators will monitor patient safety by conducting formal reviews of accumulated 
safety data that is blinded by treatment group; if requested, the DMC may have access to 
the treatment allocation code or any other data requested for the purposes of a risk-benefit 
assessment.
The DMC will provide the sponsor with appropriate recommendations on the conduct of the 
clinical study to ensure the protection and safety of the participants enrolled in the study. The 
DMC will also institute any measures that may be required for ensuring the integrity of the study 
results during the study execution.
All activities and responsibilities of the DMC are described in the DMC charter.

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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:
o
Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences International Ethical Guidelines
o
Applicable ICH Good Clinical Practice (GCP) Guidelines
o
Applicable laws and regulations
●
The protocol, protocol amendments, informed consent form (ICF), 
Investigator’s Brochure (IB), and other relevant documents (for example, 
advertisements) must be submitted to an institutional review board 
(IRB)/independent ethics committee (IEC) by the investigator and reviewed 
and approved by the IRB/IEC before the study is initiated.

Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.

The investigator will be responsible for the following:
o
Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC
o
Notifying the IRB/IEC of serious adverse events (SAEs) or other 
significant safety findings as required by IRB/IEC procedures
o
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations
●
Investigator sites are compensated for participation in the study as detailed in 
the Clinical Trial Agreement (CTA).
10.1.2.
Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study.

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10.1.3.
Informed Consent Process

The investigator or his/her representative will explain the nature of the study, 
including the risks and benefits, to the participant or his/her legally authorized 
representative and answer all questions regarding the study.

Participants must be informed that their participation is voluntary. Participants 
or their legally acceptable representative will be required to sign a statement 
of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability 
Act (HIPAA) requirements, where applicable, and the IRB/IEC or 
study center.

The medical record must include a statement that legally acceptable representative 
(parent/guardian) consent and child/adolescent assent (if deemed appropriate by local 
ethics review) was obtained before the participant was enrolled in the study and the 
date the written consent was obtained. The medical record should also describe how 
the clinical investigator determined that the person signing the ICF was the 
participant’s legally authorized representative (parent/guardian). The acceptable
parent/guardian obtaining the informed consent must also sign the ICF. 

Participants and their legally acceptable representative, parent(s), or legal guardian 
must be re-consented and re-assented to the most current version of the ICF(s) during 
their participation in the study.

Minor participants must be re-consented if they reach the age of majority during the 
course of the study, in order to continue participating.

A copy of the ICF(s) must be provided to the participant or the participant’s 
parent/guardian or legally acceptable representative and is kept on file.
Participants who are re-screened are required to sign a new ICF.
10.1.4.
Data Protection

Participants will be assigned a unique identifier by the sponsor. Any 
participant records, datasets, or tissue samples that are transferred to the 
sponsor will contain the identifier only; participant names or any information 
which would make the participant identifiable will not be transferred.

The participant must be informed that his/her personal study-related data will 
be used by the sponsor in accordance with local data protection laws. The 
level of disclosure must also be explained to the participant who will be 
required to give consent for his/her data to be used as described in the ICF.

The participant must be informed that his/her medical records may be 
examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/IEC members, and by 
inspectors from regulatory authorities.

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
The sponsor has processes in place to ensure data protection, information 
security, and data integrity. These processes include appropriate contingency 
plan(s) for appropriate and timely response in the event of a data 
security breach.
10.1.5.
Dissemination of Clinical Study Data
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.
Data
The sponsor provides access to all individual participant data collected during the study, after 
anonymization, with the exception of pharmacokinetic or genetic data. Data are available to 
request 6 months after the indication studied has been approved in the United States and the 
European Union and after primary publication 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, statistical analysis plan, clinical study report, blank or 
annotated case report forms, will be provided in a secure data sharing environment for up to 
2 years per proposal.
10.1.6.
Data Quality Assurance

All participant data relating to the study will be recorded on printed or eCRF 
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.

The investigator must permit study-related monitoring, audits, IRB/IEC 
review, and regulatory agency inspections and provide direct access to source 
data documents.

Quality tolerance limits (QTLs) will be pre-defined to identify systematic 
issues that can impact participant safety and/or reliability of study results. 
These pre-defined parameters will be monitored during the study and 
important excursions from the QTLs and remedial actions taken will be 
summarized in the clinical study report.

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.

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
The sponsor or designee is responsible for the data management of this study,
including quality checking of the data.

The sponsor assumes accountability for actions delegated to other individuals 
(for example, contract research organizations).

Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of 
participants are being protected; and that the study is being conducted in 
accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.

Records and documents, including signed ICFs, pertaining to the conduct of 
this study must be retained by the investigator for the time period outlined in 
the 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 and/or 
regulatory agencies at any time. Investigators will be given notice before an 
audit occurs.
Data Capture System
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor.
An electronic data capture system (EDC) will be used in this study for the collection of CRF 
data. The investigator maintains a separate source for the data entered by the investigator or 
designee into the sponsor-provided EDC system. The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the CRF.
Additionally, electronic Clinical Outcome Assessment (eCOA) data (participant-focused 
outcome instrument) will be directly recorded by the participant/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.
Data collected via the sponsor-provided data capture system(s) will be stored at third-party (at 
third parties). The investigator will have continuous access to the data during the study and until 
decommissioning of the data capture system(s). Prior to decommissioning, the investigator will 
receive an archival copy of pertinent data for retention.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports/electronic transfers will be provided to the 

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investigator for review and retention.  Data will subsequently be transferred from the central 
vendor to the sponsor data warehouse.
Data from complaint forms submitted to the sponsor will be encoded and stored in the global 
product complaint management system.
10.1.7.
Source Documents

Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at 
the investigator’s site.

Data reported on the CRF or entered in the eCRF that are transcribed from 
source documents must be consistent with the source documents, or the 
discrepancies must be explained. The investigator may need to request 
previous medical records or transfer records, depending on the study. Also, 
current medical records must be available.

Definition of what constitutes source data can be found in Section 10.1.6.
10.1.8.
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment 
of participants.
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and 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:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or 
GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and assures
appropriate participant therapy and/or follow-up.
10.1.9.
Publication Policy
In accordance with the sponsor’s publication policy, the results of this study will be submitted 
for publication by a peer-reviewed journal.

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10.1.10.
Investigator Information
Physicians with a specialty in dermatology will participate as investigators in this clinical study.
10.1.11.
Long-Term Sample Retention
Sample retention enables use of new technologies, response to regulatory questions, and 
investigation of variable response that may not be observed until later in the development 
of lebrikizumab or after lebrikizumab become(s) commercially available.
Sample Type
Custodian
Retention Period After 
Last Participant Visit*
Long-term storage samples
Sponsor or Designee
15 years
Biomarkers
Sponsor or Designee
N/A
PK
Sponsor or Designee
2 years 
Genetics/PD
Sponsor or Designee
15 years
Immunogenicity
Sponsor or Designee
15 years
Abbreviations:  N/A = not applicable; PD = pharmacodynamics; PK = pharmacokinetics.
*Retention periods may differ locally.

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10.2.
Appendix 2: Clinical Laboratory Tests
The tests detailed below will be performed by the central or local laboratory (as 
applicable) (patient characteristics appropriate reference ranges will be adapted 
[for example, age, sex).

In circumstances where the sponsor approves local laboratory testing in lieu of 
central laboratory testing (in the table below), the local laboratory must be 
qualified in accordance with applicable local regulation.

Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 5 of the protocol.

Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations.

Pregnancy testing is described in the Schedule of Activities (Section 1.3), in 
Section 8.3.5, and in the table below.
Investigators must document their review of each laboratory safety report.
Laboratory test results that could unblind the study will not be reported to investigative sites or 
other blinded personnel.

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Clinical Laboratory Tests
Hematologya,b
Clinical Chemistrya,b
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Mean cell volume
Chloride
Mean cell hemoglobin
Phosphorus/phosphate
Mean cell hemoglobin concentration
Bicarbonate
Leukocytes (WBC)
Total protein
Platelets
Albumin
Total bilirubin
Differential WBC [Absolute counts and/or %] of:
Direct bilirubin
Neutrophils
Alkaline phosphatase (ALP)
Lymphocytes
Lactic dehydrogenase
Monocytes
Gamma-glutamyltransferase (GGT)
Eosinophils
Alanine aminotransferase (ALT)
Basophils
Aspartate aminotransferase (AST)
Blood urea nitrogen (BUN)
Creatinine
Urinalysisa
Uric acid
Specific gravity
Calcium
pH
Glucose (random)
Protein
Creatine kinase (CK)
Glucose
Ketones
Blood
Lipid Panel a,b
Urine leukocyte esterase
High-density lipoprotein (HDL)
Bilirubin
Low-density lipoprotein (LDL)
Nitrite
Triglycerides
Urobilinogen
Total cholesterol
Microscopic examination of sediment c
Pregnancy Test (females only)d
(seruma /urinee)
Hormonesa
Estradiol (adolescent females only)
Serology
Testosterone (adolescent males only)
HIV Antibody (HIV Ab)a
Follicle-stimulating hormone(FSH)f
Hepatitis B Core Antibody (HBcAb)a
Hepatitis B Surface Antigen (HBsAg)a
Hepatitis B Surface Antibody (HBsAb)a
Hepatitis B DNA (HBV DNA)a
Pharmacogeneticsa,g
Hepatitis C Antibody (HCV Ab)a
TB Serologyh (The QuantiFERON®-TB Gold test 
or T-SPOT®.TB test or TST)
Other tests
Pharmacokinetica,g
Immunogenicity (anti- ebrikizumab Ab)a,g
Beta D-glucan
Thymus and activation-regulated chemokine 
(TARC)a,g

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Abbreviations:  FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; RBC = red blood cells; 
WBC = white blood cells.
a
Assayed by Lilly-designated laboratory.
b Participants should not eat or drink anything except water for 12 hours prior to test. If a participant attends these 
visits in a nonfasting state, this will not be considered a protocol violation.
c
Test only if dipstick result is abnormal.
d Local- or investigator-designated laboratory.
e
Urine pregnancy test to be performed only on women of childbearing potential and women with history of tubal 
ligation. Local testing. Result must be negative before dosing at each dosing visit.
f
For female participants who are >40 to ≤55 years of age.
g Results will not be provided to the investigative sites.
h The QuantiFERON-TB Gold test may be performed locally or centrally; the T-SPOT must be performed locally.
Selected tests may be obtained in the event of anaphylaxis or systemic allergic/hypersensitivity 
reactions. The samples should be collected as close as possible to the onset of the event.
After the participant has been stabilized, obtain a sample within 1 to 2 hours of the event;
however, samples may be obtained as late as 12 hours after the event, as analytes can remain 
altered for an extended period of time. Record the time at which the sample was collected.
A follow-up sample should be obtained at the next regularly scheduled visit or after 4 weeks, 
whichever is later.
Hypersensitivity Testsa
Anti-LY antibodies (immunogenicity)
Tryptasec
Anti-PLBL2 antibodies
LY concentration (PK)
N-methylhistamine
Drug-Specific IgEb
Complements
o
C3, C3a, and C5a
Basophil activation testb
Cytokine panel
o
IL‐6, IL‐1β, IL‐10 (or any cytokine panel that 
includes these 3 cytokines)
Abbreviations:  IgE = immunoglobulin E; IL = interleukin; LY = LY3650150; NMH = N-methylhistamine; 
PK = pharmacokinetic; PLBL2 = phospholipase B-like 2
a
Assayed by Lilly-designated laboratory. Results will not be provided to the investigative sites.
b
Will be performed if a validated assay is available.
c
If a tryptase sample is obtained more than 2 hours after the event (that is, within 2-12 hours) or is not obtained 
because more than 12 hours have lapsed since the event, obtain urine for NMH testing. Note that for tryptase 
serum samples obtained within 2-12 hours of the event, urine NMH testing is performed in addition to tryptase 
testing. Collect the first void urine following the event. Obtain a follow-up urine sample for NMH testing at the 
next regularly scheduled visit or after 4 weeks, whichever is later.

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10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-Up, and Reporting
10.3.1.
Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (for example, electrocardiogram, 
radiological scans, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment 
of the investigator (that is, not related to progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition, including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration,
even though they may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported 
as an AE/SAE, unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdose should be reported regardless 
of sequelae.

The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as AEs or SAEs if they fulfill the definition of an AE or SAE. Also, 
‘lack of efficacy’ or ‘failure of expected pharmacological action’ also constitutes 
an AE or SAE.

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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (for example, endoscopy, appendectomy): the 
condition that leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
10.3.2.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (for example, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
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 for observation and/or treatment that would not have been appropriate in 
the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
‘hospitalization’ occurred or was necessary, the AE should be considered serious.

Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE.
d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

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Protocol number J2T-JE-KGAL(a)
90

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (for example, sprained ankle) which may interfere 
with or prevent everyday life functions but do not constitute a substantial 
disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
10.3.3.
Recording and Follow-Up of AEs and/or SAEs
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (for example, hospital progress notes, laboratory reports, and 
diagnostics reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to the sponsor or designee in lieu of completion of the AE/SAE 
CRF page.

There may be instances when copies of medical records for certain cases are 
requested by 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/symptoms) will be documented as the AE/SAE.

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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: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with a SAE. Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

A ‘reasonable possibility’ of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to 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 his/her 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.

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Protocol number J2T-JE-KGAL(a)
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Follow-Up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as medically indicated or as 
requested by 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.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor or designee
within 24 hours of receipt of the information.
10.3.4.
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 paper SAE data 
collection tool (see next section) in order 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 off-line 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 off-line, then the site can report this information on a paper SAE 
form (see next section) or to the medical monitor by telephone.

Contacts for SAE reporting can be found in the site training documents.
SAE Reporting via Paper CRF

Facsimile transmission of the SAE paper CRF 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 site training documents.

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10.4.
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information
Definitions:
Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal, unless 
permanently sterile (see below).
If fertility is unclear (for example, amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered women of childbearing potential:

premenarchal, and 

premenopausal female with 1 of the following:
o
documented hysterectomy
o
documented bilateral salpingectomy, or
o
documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (for example, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.

Postmenopausal female is defined as, women with:
o
12 months of amenorrhea for women >55, with no need for follicle-stimulating 
hormone (FSH)
o
12 months of amenorrhea for women >40 years old with FSH ≥40 mIU/mL and 
no other medical condition such as anorexia nervosa and not taking medications 
during the amenorrhea (for example, oral contraceptives, hormones, 
gonadotropin-releasing hormone, anti-estrogens, selective estrogen receptor 
modulators (SERMs), or chemotherapy that induced amenorrhea)
Contraception Guidance
Contraception is described in Section 5.1, Inclusion Criteria [7].
Collection of Pregnancy Information
Male participants with partners who become pregnant
●
The investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while the male participant is 
in this study. This applies only to male participants who receive lebrikizumab.

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●
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor within 24 hours of learning of the 
partner’s pregnancy. The female partner will also be followed up to determine the 
outcome of the pregnancy. Information on the status of the mother and child will 
be forwarded to the sponsor. Generally, the follow-up will be no longer than 6 to 
8 weeks following the estimated delivery date. Any termination of the pregnancy 
will be reported, including fetal status (presence or absence of anomalies) and
indication for the procedure. 
Female participants who become pregnant
●
The investigator will collect pregnancy information on any female participant 
who becomes pregnant while participating in this study. The initial information 
will be recorded on the appropriate form and submitted to the sponsor within 
24 hours of learning of a participant’s pregnancy. 
●
The participant will be followed up to determine the outcome of the pregnancy. 
The investigator will collect follow-up information on the participant and the 
neonate, and the information will be forwarded to the sponsor. Generally, 
follow-up will not be required for longer than 6 to 8 weeks beyond the estimated 
delivery date. Any termination of pregnancy will be reported, including fetal 
status (presence or absence of anomalies) or indication for the procedure.
●
While pregnancy itself is not considered an adverse event (AE) or serious adverse 
event (SAE), any pregnancy complication or elective termination of a pregnancy 
for medical reasons will be reported as an AE or SAE. 
●
A spontaneous abortion (occurring at <20 weeks gestational age) or stillbirth 
(occurring at ≥20 weeks gestational age) is always considered an SAE and will be 
reported as such. 
●
Any poststudy pregnancy-related SAE considered reasonably related to study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.3.4. While the investigator is not obligated to actively seek this 
information in former study participants, he or she may learn of an SAE through 
spontaneous reporting.
●
Any female participant who becomes pregnant while participating in the study 
will discontinue study intervention.

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10.5.
Appendix 5: Genetics
Use/Analysis of DNA
●
Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Variable response to 
study intervention may be due to genetic determinants that impact drug 
absorption, distribution, metabolism, and excretion; mechanism of action of the 
drug; disease etiology; and/or molecular subtype of the disease being treated. 
Therefore, where local regulations and institutional review boards 
(IRBs)/independent ethics committees (IECs) allow, a blood sample will be 
collected for DNA analysis from consenting participants.
●
DNA samples will be used for research related to lebrikizumab or AD and related 
diseases. Genetic research may consist of the analysis of one or more candidate 
genes or the analysis of genetic markers throughout the genome (as appropriate).
●
The samples may be analyzed as part of a multi-study assessment of genetic 
factors involved in the response to lebrikizumab or study interventions of this 
class to understand study disease or related conditions.
●
The results of genetic analyses may be reported in the CSR or in a separate 
study summary.
●
The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.
●
The samples will be retained while research on lebrikizumab continues but no 
longer than 15 years or other period per local requirements.

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10.6.
Appendix 6: Liver Safety: Suggested Actions and Follow-Up 
Assessments
Hepatic Evaluation Testing
See Section 8.2.8 for guidance on appropriate test selection.
The Lilly-designated central laboratory must complete the analysis of all selected testing except 
for microbiology testing.
Local testing may be performed in addition to central testing when necessary for immediate 
participant management.
Results will be reported if a validated test or calculation is available.
Hematology
Clinical Chemistry
Hemoglobin
Total bilirubin
Hematocrit
Direct bilirubin
Erythrocytes (RBCs [red blood cells])
Alkaline phosphatase (ALP)
Leukocytes (WBCs [white blood cells])
Alanine aminotransferase (ALT)
Differential:
Aspartate aminotransferase (AST)
    Neutrophils, segmented
Gamma-glutamyltransferase (GGT)
    Lymphocytes
Creatine kinase (CK)
    Monocytes
Other Chemistry
    Basophils
Acetaminophen
    Eosinophils
Acetaminophen protein adducts
Platelets
Alkaline phosphatase isoenzymes
Cell morphology (RBC and WBC)
Ceruloplasmin
Coagulation
Copper
Ethyl alcohol (EtOH)
Prothrombin time, INR (PT-INR)
Haptoglobin
Serology
Immunoglobulin (IgA [quantitative])
Hepatitis A virus (HAV) testing:
Immunoglobulin (IgG [quantitative])
    HAV total antibody
Immunoglobulin (IgM [quantitative])
    HAV IgM antibody
Phosphatidylethanol (PEth)
Hepatis B virus (HBV) testing:
Urine Chemistry
    Hepatitis B surface antigen (HBsAg)
Drug screen
    Hepatitis B surface antibody (anti-HBs)
Ethyl glucuronide (EtG)
    Hepatitis B core total antibody (anti-HBc)
Other Serology
    Hepatitis B core IgM antibody
Anti-nuclear antibody (ANA)

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Hematology
Clinical Chemistry
    Hepatitis B core IgG antibodya
Anti-smooth muscle antibody (ASMA)b
    Hepatitis B virus (HBV) DNAc
Anti-actin antibodyd
Hepatis C virus (HCV) testing:
Epstein-Barr virus (EBV) testing:
    HCV antibody
    EBV antibody
    HCV RNAc
    EBV DNAc
Hepatitis D virus (HDV) testing:
Cytomegalovirus (CMV) testing:
    HDV antibody
    CMV antibody
Hepatitis E virus (HEV) testing:
    CMV DNAc
    HEV IgG antibody
Herpes simplex virus (HSV) testing:
    HEV IgM antibody
    HSV (Type 1 and 2) antibody 
    HEV RNAc
    HSV (Type 1 and 2) DNAc
Microbiologya
Liver kidney microsomal type 1 (LKM-1) antibody
Culture:
    Blood
    Urine
a
Assayed ONLY by investigator-designated local laboratory; no central testing available.
b
Not required if anti-actin antibody is tested.
c
Reflex/confirmation dependent on regulatory requirements, testing availability, or both.
d
Not required if anti-smooth muscle antibody (ASMA) is tested.

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10.7.
Appendix 7: American Academy of Dermatology: Criteria for the 
Diagnosis and Assessment of Atopic Dermatitis
Features to be considered in diagnosis of patients with AD:
Essential Features—Must be present:

pruritus

eczema (acute, subacute, chronic)
o
typical morphology and age-specific patterns*
o
chronic or relapsing history
*Patterns include:
1) facial, neck, and extensor involvement in infants and children 
2) current or previous flexural lesions in any age group
3) sparing of the groin and axillary regions
Important Features—Seen in most cases, adding support to the diagnosis:

early age of onset

atopy
o
personal and/or family history
o
Immunoglobulin E reactivity

xerosis
Associated Features—These clinical associations help to suggest the diagnosis of atopic 
dermatitis but are too nonspecific to be used for defining or detecting atopic dermatitis 
for research and epidemiologic studies:

atypical vascular responses (eg, facial pallor, white dermographism, delayed blanch
response)

keratosis pilaris/pityriasis alba/hyperlinear palms/ichthyosis

ocular/periorbital changes

other regional findings (e.g., perioral changes/periauricular lesions)

perifollicular accentuation/lichenification/prurigo lesions
Exclusionary Features—It should be noted that a diagnosis of atopic dermatitis 
depends on excluding conditions, such as:

scabies

seborrheic dermatitis

contact dermatitis (irritant or allergic)

ichthyoses

cutaneous T-cell lymphoma

psoriasis

photosensitivitydermatoses

immune deficiency diseases

erythroderma of other causes
Source: Eichenfield et al. Guidelines of care for the management of atopic dermatitis: section 1. 
Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-3351.

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10.8.
Appendix 8: Provisions for Changes in Study Conduct During 
Exceptional Circumstances
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, participants, or both to attend on-site visits or to conduct planned study procedures.
Implementing changes under exceptional circumstances
In an exceptional circumstance, after receiving the sponsor’s written approval, sites may 
implement changes if permitted by local regulations. 
Ethical Review Boards (ERBs), regulatory bodies and any other relevant local authorities, as 
required, will be notified as early as possible to communicate implementation of changes in 
study conduct due to exceptional circumstances. To protect the safety of study participants, 
urgent changes may be implemented before such communications are made, but all changes will 
be reported as soon as possible following implementation. If approval of ERBs, regulatory 
bodies, or both is required per local regulations, confirmation of this approval will be retained in 
the study records.
In the event written approval is granted by the sponsor for changes in study conduct, additional 
written guidance, if needed, will be provided by the sponsor.
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 Good Clinical 
Practice, enabling participants to continue safely in the study and maintaining the integrity of the 
study.
Informed Consent
Additional consent/assent from the participant will be obtained, as required, and/or as required 
by ERB’s and local regulations. Assent will also be obtained to the same parameters, with 
consent for participants reaching the legal age for consent during the study for continued 
participation, for:

participation in remote visits, as defined in Section “Remote Visits,”

a change in the method, location, or both, 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. 

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Changes in Study Conduct During Exceptional circumstances
Changes in study conduct not described in this appendix, or not consistent with applicable local 
regulations, are not allowed.
The following changes in study conduct will not be considered protocol deviations.
1. Remote visits
Visit 3 through Visit 9 and safety follow-up visit can be conducted remotely. In source 
documents and the CRF, the study site should capture the visit location and method, with a 
specific explanation for any data missing because of missed in-person site visits.
Telemedicine: Telephone or technology-assisted virtual visits, or both, are acceptable to 
complete appropriate assessments. Assessments to be completed in this manner include, but are 
not limited to,

AE and SAE reports

concomitant medications, and

compliance with the patient diary, and

product complaints.
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.
2. Local laboratory testing option
Local laboratory testing may be conducted in lieu of central laboratory testing. However, 
central laboratory testing must be retained for:

PK samples

Immunogenicity (ADA) samples

Pharmacogenetics sample
These central laboratory testing may be collected at the next office visit.
The local laboratory must be qualified in accordance with applicable local regulations.
If a participant is unable to come to the site for central labs collections for routine safety 
monitoring, alternative methods to obtain pregnancy results are acceptable; e.g. home 
pregnancy test with results reviewed by PI.
3. 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, 

asking the participant’s designee to go to the site and receive study supplies on a 
participant’s behalf, 

arranging delivery of study supplies, and

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
participants or their caregiver are appropriately trained on at-home administration of 
the study intervention (unless they have already received that training) before 
administering the study intervention at home. For training purposes, injection of IP
will be self-administered by the participants or their caregiver under the supervision 
of the investigator. Participants or their caregiver will administer study intervention at 
home from the next study intervention.  If the study intervention is administered at 
home, participants or caregiver will need to record the details about the injections.
These requirements 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 participant’s receipt of study supplies.

When delivering supplies to a location other than the study site (for example, 
participant’s home), the investigator, 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 the study intervention is administered at home, participants or caregiver will need 
to record the details about the injections.
4. Screening Period Guidance 
If the study screening window exceeds 30 days due to the exceptional circumstances, the 
participant would be considered a screen failure and may be rescreened. If rescreening is 
required more than once, it must first be approved by the sponsor.
The screening procedures per the SoA in the protocol should be followed (starting at Visit 1) to 
ensure participant eligibility by randomization visit (Visit 2). Before rescreening, the participant 
must sign a new ICF and receive a new identification number through IWRS.
5. Adjustments to Visit Windows 
Whenever possible and safe to do so, as determined by the investigator’s discretion, participants 
should complete the usual 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. The study may 
need to over enroll to obtain adequate sample size.

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This table describes the allowed adjustments to visit windows.
Visit Number
Tolerance
Visit 3 through Visit 9
Within 7 days before the intended date, or up to 7 days after the intended 
date
Visit 10 through Visit 23
Within 14 days before the intended date, or up to 14 days after the intended 
date
Visit 24/ET and Visit 801
Within 7 days before the intended date, or up to 14 days after the intended 
date.
Subsequent dosing should be a minimum of 7 days apart if the visit window is expanded due to 
extenuating circumstances.
Documentation
Changes to study conduct will be documented:

Sites will identify and document the details of how participants, visits types, and 
conducted activities were affected by exceptional circumstances. 
Dispensing/shipment records of study intervention and relevant communications, 
including delegation, should be filed with site study records.
Source documents generated at a location other than the study site should be part of the 
investigator’s source documentation and should be transferred to the site in a secure and timely 
manner.

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10.9.
Appendix 9: Abbreviations
Term
Definition
ACQ-5
Asthma Control Questionnaire-5
AD
atopic dermatitis
ADA
anti-drug antibody
AE
adverse event
AESI
adverse events of special interest
ALC
absolute lymphocyte count
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
blinding/masking
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 
participants are aware of the treatment received.
BSA
body surface area
CDLQI
Children’s Dermatology Life Quality Index
CFR
Code of Federal Regulations
CK
creatine kinase
CMV
cytomegalovirus
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements.
CRP
clinical research physician: individual responsible for the medical conduct of the study.  
Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician, or other medical officer.
C-SSRS
Columbia-Suicide Severity Rating Scale
DLQI
Dermatology Life Quality Index
DMC
data monitoring committee

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EASI
Eczema Area and Severity Index
EASI-50
≥50% reduction from baseline in Eczema Area and Severity Index score
EASI-75
≥75% reduction from baseline in EASI score
EASI-90
≥90% reduction from baseline in EASI score
EBV
Epstein-Barr virus
ECG
electrocardiogram
eCOA
electronic clinical outcome assessment
enroll
The act of assigning a participant to a treatment.  Participants who are enrolled in the 
study are those who have been assigned to a treatment.
enter
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives.
ERCP
endoscopic retrograde cholangiopancreatography
ET
early termination
FLG
filaggrin
GGT
gamma-glutamyltransferase
HADS
Hospital Anxiety Depression Scale
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HDV
hepatitis D virus
HCVAb
hepatitis C antibody
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
independent ethics committee
IFN-γ
interferon 
Ig
immunoglobulin

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IGA
Investigator’s Global Assessment
IL
interleukin
informed consent
A process by which a participant voluntarily confirms his or her willingness to 
participate in a particular study, after having been informed of all aspects of the study 
that are relevant to the participant’s decision to participate. Informed consent is 
documented by means of a written, signed, and dated informed consent form.
INR
international normalized ratio
interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
IP
investigational product: a pharmaceutical form of an active ingredient or placebo being 
tested or used as a reference in a clinical study, including products already on the 
market when used or assembled (formulated or packaged) in a way different from the 
authorized form, or marketed products used for an unauthorized indication, or marketed 
products used to gain further information about the authorized form.
IRB
institutional review board
ITT
intent 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 participants allocated to a treatment group should be followed up, 
assessed, and analyzed as members of that group, irrespective of their compliance to the 
planned course of treatment.
IV
intravenous
IWRS
interactive web-response system
JAK
Janus kinase
LOR
loricrin
LTBI
latent tuberculosis infection
MedDRA
Medical Dictionary for Regulatory Activities
MMF
mycophenolate mofetil
MRCP
magnetic resonance cholangiopancreatography
MTX
methotrexate
NMH
N-methylhistamine
NRS
numeric rating scale
NSD
needle safety device

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participant
equivalent to Clinical Data Interchange Standards Consortium (CDISC) term “subject”: 
an individual who participates in a clinical study, either as recipient of an 
investigational medicinal product or as a control
PCR
polymerase chain reaction
PCP
pneumocystis pneumonia
PD
pharmacodynamics
PFS
pre-filled syringe
PK
pharmacokinetics
POEM
Patient-Oriented Eczema Measure
PPD
purified protein derivative
PT
preferred term
Q2W
every 2 weeks
Q4W
every 4 weeks
QTLs
quality tolerance limits
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
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. 
SoA
schedule of activities
SOC
system organ class
SMQ
Standardised MedDRA Query
TARC
thymus and activation-regulated chemokine
TB
tuberculosis
TBL
total bilirubin
TCI
topical calcineurin inhibitor
TCS
topical corticosteroid(s)
TE-ADA
treatment-emergent anti-drug antibody

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TEAE
treatment-emergent adverse event: An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, and does not necessarily have to have a causal relationship 
with this treatment.
TST
tuberculin skin test
ULN
upper limit of normal
WBC
white blood cell
WHO 
World Health Organization
WOCBP
woman of childbearing potential
WPAI-AD
Work Productivity and Activity Impairment – Atopic Dermatitis

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11.
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Leo Document ID = 4e81c094-a7cb-4339-b96e-54ae4044858b
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Approval Date & Time: 22-Jan-2021 03:36:38 GMT
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