A Phase 3, 16-week, Randomized, Double-Blind, Placebo-Controlled, Parallel- Group Study to Assess the Impact of Lebrikizumab on Vaccine Responses in Adult Patients With Moderate-to-Severe Atopic Dermatitis
Phase: PHASE3
Conditions: Atopic Dermatitis
Sponsor: Eli Lilly and Company

 
 
 
Protocol: J2T-MC-KGAK 
 
 
A Phase 3, 16-week, Randomized, Double-Blind, Placebo-Controlled, Parallel-
Group Study to Assess the Impact of Lebrikizumab on Vaccine Responses in 
Adult Patients with Moderate-to-Severe Atopic Dermatitis 
 
 
NCT04626297 
 
 
Approval Date: 05-Aug-2020 

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
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/DRM06), unless such persons are bound by a confidentiality agreement with Eli Lilly and 
Company or its subsidiaries. 
Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential information 
exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any public release.
In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be reproduced or 
otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries.
Protocol Title: A Phase 3, 16-week, Randomized, Double-Blind, Placebo-Controlled, Parallel-
Group Study to Assess the Impact of Lebrikizumab on Vaccine Responses in 
Adult Patients with Moderate-to-Severe Atopic Dermatitis
Protocol Number: J2T-MC-KGAK/DRM06-AD18
Amendment Number: This is the initial protocol.
Compound: lebrikizumab (LY3650150/DRM06)
Study Phase: 3
Short Title: A Phase 3, 16-week, Randomized, Double-Blind, Placebo-Controlled, Parallel-
Group Study to Assess the Impact of Lebrikizumab on Vaccine Responses in Adult 
Patients with Moderate-to-Severe Atopic Dermatitis
Sponsor Name: Eli Lilly and Company
Legal Registered Address: Indianapolis, Indiana USA 46285
Regulatory Agency Identifier Number(s)
IND: 119866
EudraCT: 2020-002572-12
Approval Date: Protocol Electronically Signed and Approved by Lilly on date provided below.
Approval Date: 05-Aug-2020 GMT

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Protocol J2T-MC-KGAK/DRM06-AD18
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Medical Monitor Name and Contact Information will be provided separately.

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
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Table of Contents
1.
Protocol Summary......................................................................................................6
1.1.
Synopsis.......................................................................................................................6
1.2.
Schema.......................................................................................................................10
1.3.
Schedule of Activities (SoA) ......................................................................................11
2.
Introduction..............................................................................................................23
2.1.
Study Rationale ..........................................................................................................23
2.2.
Background ................................................................................................................23
2.2.1.
Clinical Manifestations of Atopic Dermatitis ..............................................................24
2.2.2.
Treatment for Atopic Dermatitis .................................................................................25
2.3.
Benefit/Risk Assessment ............................................................................................25
3.
Objectives and Endpoints.........................................................................................27
4.
Study Design .............................................................................................................29
4.1.
Overall Design............................................................................................................29
4.2.
Scientific Rationale for Study Design .........................................................................30
4.2.1.
Participant Input into Design ......................................................................................31
4.3.
Justification for Dose..................................................................................................31
4.4.
End of Study Definition..............................................................................................31
5.
Study Population ......................................................................................................32
5.1.
Inclusion Criteria........................................................................................................32
5.2.
Exclusion Criteria.......................................................................................................33
5.3.
Lifestyle Considerations .............................................................................................36
5.4.
Screen Failures...........................................................................................................36
5.4.1.
Rescreening for Individuals Who Failed Screening.....................................................36
6.
Study Intervention....................................................................................................38
6.1.
Study Interventions Administered...............................................................................38
6.1.1.
Study Drugs................................................................................................................38
6.1.2.
Vaccine Products........................................................................................................38
6.1.3.
Instructions for Administration in the Clinic ...............................................................39
6.1.4.
Instructions for Administration at Home .....................................................................39
6.1.5.
Packaging and Labeling..............................................................................................39
6.2.
Preparation/Handling/Storage/Accountability.............................................................39
6.3.
Measures to Minimize Bias: Randomization and Blinding..........................................40
6.4.
Study Intervention Compliance...................................................................................41
6.5.
Concomitant Therapy .................................................................................................41
6.5.1.
Permitted and Prohibited Treatments and Procedures..................................................41
6.5.2.
Background Treatment: Non-Medicated Moisturizers.................................................42
6.5.3.
Rescue Treatment for Atopic Dermatitis .....................................................................42
6.6.
Dose Modification......................................................................................................43
6.7.
Intervention after the End of the Study........................................................................43
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................44

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Protocol J2T-MC-KGAK/DRM06-AD18
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7.1.
Discontinuation of Study Intervention ........................................................................44
7.1.1.
Criteria for Temporary Discontinuation of Study Drug ...............................................44
7.1.2.
Criteria for Permanent Discontinuation of Study Drug................................................45
7.2.
Participant Discontinuation/Withdrawal from the Study .............................................47
7.2.1.
Discontinuation of Inadvertently Enrolled Participants ...............................................48
7.3.
Lost to Follow up .......................................................................................................48
8.
Study Assessments and Procedures .........................................................................49
8.1.
Efficacy Assessments .................................................................................................49
8.1.1.
Primary Outcome Measures: Vaccine Responses........................................................49
8.1.2.
Secondary Outcome Measures: Efficacy.....................................................................49
8.1.3.
Patient-Reported Outcomes ........................................................................................50
8.2.
Safety Assessments ....................................................................................................53
8.2.1.
Physical Examinations................................................................................................53
8.2.2.
Vital Signs..................................................................................................................53
8.2.3.
Clinical Safety Laboratory Assessments .....................................................................53
8.2.4.
Systemic Hypersensitivity Reactions ..........................................................................54
8.2.5.
Hepatitis B Testing and Monitoring ............................................................................55
8.2.6.
Hepatitis C Testing and Monitoring ............................................................................55
8.2.7.
Hepatic Safety Monitoring..........................................................................................56
8.2.8.
Serious Infections and Opportunistic Infections ..........................................................58
8.3.
Adverse Events and Serious Adverse Events ..............................................................58
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information.................................................................................................................58
8.3.2.
Method of Detecting AEs and SAEs ...........................................................................59
8.3.3.
Follow-up of AEs and SAEs.......................................................................................59
8.3.4.
Regulatory Reporting Requirements for SAEs............................................................59
8.3.5.
Pregnancy...................................................................................................................60
8.3.6.
Adverse Events of Special Interest..............................................................................60
8.3.7.
Product Complaints ....................................................................................................60
8.4.
Treatment of Overdose ...............................................................................................61
8.5.
Pharmacokinetics........................................................................................................61
8.6.
Pharmacodynamics.....................................................................................................62
8.7.
Genetics .....................................................................................................................62
8.8.
Biomarkers.................................................................................................................62
8.9.
Immunogenicity Assessments.....................................................................................63
8.10.
Medical Resource Utilization and Health Economics..................................................63
9.
Statistical Considerations.........................................................................................64
9.1.
Statistical Hypotheses.................................................................................................64
9.2.
Sample Size Determination.........................................................................................64
9.3.
Populations for Analyses ............................................................................................64
9.4.
Statistical Analyses.....................................................................................................65
9.4.1.
General Considerations...............................................................................................65
9.4.2.
Co-Primary Analyses..................................................................................................67
9.4.3.
Secondary Analyses....................................................................................................67
9.4.4.
Exploratory Analyses..................................................................................................68
9.4.5.
Safety Analyses ..........................................................................................................68

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Protocol J2T-MC-KGAK/DRM06-AD18
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9.4.6.
Pharmacokinetic Analyses ..........................................................................................68
9.4.7.
Immunogenicity Data Analysis...................................................................................69
9.4.8.
Other Analyses ...........................................................................................................69
9.5.
Interim Analyses.........................................................................................................69
9.6.
Data Monitoring Committee (DMC)...........................................................................70
10.
Supporting Documentation and Operational Considerations ................................71
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................................71
10.1.1.
Regulatory and Ethical Considerations........................................................................71
10.1.2.
Financial Disclosure ...................................................................................................71
10.1.3.
Informed Consent Process ..........................................................................................72
10.1.4.
Data Protection...........................................................................................................72
10.1.5.
Committee Structure...................................................................................................72
10.1.6.
Dissemination of Clinical Study Data .........................................................................73
10.1.7.
Data Quality Assurance ..............................................................................................73
10.1.8.
Source Documents......................................................................................................74
10.1.9.
Study and Site Start and Closure.................................................................................75
10.1.10. Publication Policy.......................................................................................................75
10.1.11. Investigator Information .............................................................................................75
10.1.12. Long-Term Sample Retention.....................................................................................75
10.2.
Appendix 2: Clinical Laboratory Tests........................................................................77
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting.......................................................81
10.3.1.
Definition of AE.........................................................................................................81
10.3.2.
Definition of SAE.......................................................................................................82
10.3.3.
Recording and Follow-Up of AE and/or SAE .............................................................83
10.3.4.
Reporting of SAEs......................................................................................................85
10.4.
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information ...............................................................................................86
10.4.1.
Definitions..................................................................................................................86
10.4.2.
Contraception Guidance..............................................................................................86
10.4.3.
Collection of Pregnancy Information ..........................................................................86
10.5.
Appendix 5: Recommended Laboratory Testing for Systemic 
Hypersensitivity Events..............................................................................................88
10.6.
Appendix 6: Liver Safety: Suggested Actions and Follow-Up 
Assessments ...............................................................................................................90
10.7.
Appendix 7: Examples of Infections That May Be Considered 
Opportunistic..............................................................................................................92
10.8.
Appendix 8: American Academy of Dermatology Consensus 
Criteria for Chronic Atopic Dermatitis........................................................................94
10.9.
Appendix 9: Provisions for Changes in Study Conduct During 
Exceptional Circumstances.........................................................................................96
10.10.
Appendix 10: Abbreviations .....................................................................................100
11.
References...............................................................................................................105

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
6
1.
Protocol Summary
1.1.
Synopsis
Protocol Title: A Phase 3, 16-week, Randomized, Double-Blind, Placebo-Controlled, Parallel-
Group Study to Assess the Impact of Lebrikizumab on Vaccine Responses in Adult Patients with 
Moderate-to-Severe Atopic Dermatitis
Short Title: same as the protocol title
Rationale:
Study J2T-MC-KGAK (KGAK) is a Phase 3, randomized, double-blind, placebo-controlled 
study to assess the impact of lebrikizumab on vaccine immune responses in adult patients with 
moderate-to-severe atopic dermatitis (AD). This study will evaluate the effect of lebrikizumab 
treatment on 2 vaccines commonly used in adults with moderate to severe AD:

Tdap: Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed
(Sanofi), and

MCV: Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria 
CRM197 Conjugate Vaccine (GlaxoSmithKline).
In addition, this study will further assess the efficacy and safety of lebrikizumab in patients with 
moderate-to-severe AD.

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Protocol J2T-MC-KGAK/DRM06-AD18
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Objectives and Endpoints
Objectives
Endpoints
Co-Primary

To compare the seroresponses to the Tdap and 
MCV between lebrikizumab-treated and 
placebo-treated participants with 
moderate-to-severe AD
The percentage of participants who:
1.
Develop a booster response to tetanus 
toxoid 4 weeks after the administration of the 
Tdap vaccine (Week 16)
Booster response is defined as:
o
≥4-fold increase in anti-tetanus toxoid 
IgG antibody concentration if the pre-
vaccination level was >0.10 IU/mL and 
≤2.7 IU/mL; 
OR
o
≥2-fold increase in anti-tetanus toxoid 
IgG antibody concentration if the pre-
vaccination level was >2.7 IU/mL; 
OR 
o
≥4-fold increase in anti-tetanus toxoid 
IgG antibody concentration and a post-
vaccination level ≥0.10 IU/mL if the pre-
vaccination level was ≤0.10 IU/mL
2.
Have positive antibody response to MCV 
(group C serum bactericidal antibodies)
4 weeks after the administration of the 
vaccine (Week 16)
Positive antibody response to MCV is defined 
as:
o
post-vaccination hSBA titer ≥4 times the 
LLOQ, if the pre-vaccination hSBA titer 
is less than the LLOQ;
OR
o
post-vaccination hSBA titer ≥4 times the 
pre-vaccination titer, if the pre-
vaccination hSBA titer is greater than or 
equal to the LLOQ

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
8
Objectives
Endpoints
Secondary

To compare the efficacy of lebrikizumab with 
that of placebo in treatment of participants
with moderate-to-severe AD, as measured by:
Percentage of participants at Week 16 achieving:

an IGA score of 0 or 1 and a reduction of 
≥2 points from baseline

EASI-75

EASI-90

≥4-point improvement from baseline in 
Pruritus NRS score 
Percentage change from baseline to Week 16 in:

EASI

Pruritus NRS score
Change from baseline in:

Percent BSA

Sleep-Loss score

To compare the patient-reported outcomes 
between lebrikizumab-treated and 
placebo-treated participants with 
moderate-to-severe AD, as measured by:
Change from baseline by visit in:

PROMIS® Anxiety measure

PROMIS® Depression measure
Abbreviations: AD = atopic dermatitis; BSA = Body Surface Area; EASI = Eczema Area and Severity Index; 
EASI-75 = ≥75% reduction from baseline in EASI score; EASI-90 = ≥90% reduction from baseline in EASI 
score; hSBA = human complement serum bactericidal assay; IGA = Investigator Global Assessment; 
IgG = immunoglobulin G; LLOQ = lower limit of quantitation; MCV = Meningococcal (Groups A, C, Y, and W-
135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine (GlaxoSmithKline); NRS = Numeric Rating 
Scale; PROMIS = Patient-Reported Outcomes Measurement Information System; Tdap = Diphtheria and 
Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (Sanofi).
Overall Design
KGAK will last approximately 16 weeks and will have 3 study periods:

Screening

Treatment

Safety follow-up
Depending on the preference of the study site or the study participant, some of the study visits 
may be performed either remotely or on site, as indicated in the Schedule of Activities (SoA). In 
addition, provisions for exceptional circumstances (such as pandemics or natural disasters) are 
provided in Appendix 10.9.

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Protocol J2T-MC-KGAK/DRM06-AD18
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Remote visits may be conducted as follows:

virtually (i.e., via telephone or telemedicine tools), and

at a mobile location (e.g., a participant’s home), if permitted by local laws and 
regulations.
Participants will receive lebrikizumab or matching placebo via subcutaneous injection. The 
lebrikizumab doses will be as follows:

At randomization/baseline and Week 2: loading dose of 500 mg

At Weeks 4 through 14: 250 mg once every 2 weeks (Q2W)
During remote visits, study participants will have an option of administering the study drug 
either themselves, or having a caregiver or a mobile home health care provider administer it. 
Prior to at-home administration, participants and/or caregivers will be adequately trained on the 
study drug administration at the clinical site.
Both vaccines will be administered at Week 12 at the clinical site. Vaccine injections will be 
given per local vaccination guidelines and practices and:

should not be injected in body locations with active AD or other skin lesions

should be injected in a location different from that for the study drug administration
Disclosure Statement: This is a parallel, 2-arm treatment study that is double-blinded.
Number of Participants:
Approximately 240 participants will be randomly assigned to study drug.
Intervention Groups and Duration:
Participants will be randomized in 1:1 ratio to receive either lebrikizumab or placebo. All of the 
participants will receive both of the vaccines (Tdap and MCV).
Data Monitoring Committee: Yes; a Data Safety Monitoring Board (DSMB) will be used in 
this study. (A DSMB is a type of Data Monitoring Committee.)

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Protocol J2T-MC-KGAK/DRM06-AD18
10
1.2.
Schema
Abbreviations: MCV = Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 
Conjugate Vaccine (GlaxoSmithKline); Q2W = once every 2 weeks; Tdap = Diphtheria and Tetanus Toxoids 
and Acellular Pertussis Vaccine Adsorbed (Sanofi).
a
Lebrikizumab loading dose of 500 mg will be administered at baseline and Week 2.
b
The safety follow-up will occur at Week 26 (or approximately 12 weeks after last study drug injection). See 
Section 4.4 for completion of study definitions.
c
If eligible, participants can continue to the long-term extension study (DRM06-AD07/J2T-DM-KGAA). See 
Section 4.4 for completion of study definitions.

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Protocol J2T-MC-KGAK/DRM06-AD18
11
1.3.
Schedule of Activities (SoA)
The SoA described below should be followed for all participants enrolled in Study KGAK. However, for those participants whose participation in 
this study is affected by exceptional circumstances (such as pandemics or natural disasters), please refer to Appendix 10.9 for additional guidance.
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
Informed consent
X
Inclusion and exclusion 
criteria, review and 
confirm
X
X
Demographics
X
Preexisting conditions 
and medical history
X
Prespecified medical 
history (indication and 
history of interest)
X
Review of immunization 
record 
X
Applies only to Tdap, MCV, 
BCG, or any live (attenuated)
vaccine.

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
12
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
Prior treatments for AD
X
Includes medications and 
procedures.
Concomitant therapies
X
X
X
X
X
X
X
X
X
X
X
X
Includes medications of 
special interest such as TCS 
and TCI and procedures.
Adverse events (AEs)
X
X
X
X
X
X
X
X
X
X
X
X
Collection for AEs associated 
with vaccinations will begin 
at Week 12.
For AESIs, additional data are 
collected (Section 8.3.6).
Physical Evaluation
Height
X
X

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
13
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
Weight
X
X
X
Vital signs
X
X
X
X
X
X
X
See Section 8.2.2 for details.
Physical examination
X
X
X
See Section 8.2.1 for details.
Additional symptom-directed 
physical examinations may be 
conducted at the discretion of 
the investigator.

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
14
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
Patient Education
Diary education
X
Train participant and/or 
caregiver on study drug 
administration
X
Applicable only when 
participant chooses to self-
administer the study drug or 
have a caregiver administer it.
Patient Diary (Electronic)
Patient diary dispensed
X
The electronic patient diary 
will be used to record the 
following:

Patient-reported 
outcomes (PROs)

Information about at-
home study drug 
administration
PRO diary compliance 
check
X
X
X
X
X
X
X
X
X
X
This diary compliance check 
includes checking for 
completion of the PRO 
assessments. For details about 

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
15
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
those assessments, see 
Section 8.1.3 and the PRO 
section of the SoA.
Drug Administration 
diary compliance check
X
X
X
X
X
This diary compliance check 
includes checking for study 
drug compliance.
Participant will need to 
complete this diary any time 
the study drug is administered 
at home (regardless of who 
administered the drug at 
home—the participant, 
caregiver, or mobile home 
health care provider).
Diary return (patient to 
site)
X
X
Participant would need to 
visit the site to return the 
electronic diary.
Participants need to return the
electronic diary device only if 
they are not rolling into the 
long-term extension study 
(DRM06-AD07/J2T-DM-

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Protocol J2T-MC-KGAK/DRM06-AD18
16
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
KGAA).
Patient-Reported Outcomes (Electronic Diary at Home)
Pruritus NRS
Daily (should be completed at approximately the same time every day)
Initial electronic diary entries 
for Pruritus NRS should be 
completed a minimum of 4 of
7 days before randomization.
PROs should be completed 
prior to any other study 
assessments.
Sleep-Loss
Daily (should be completed at approximately the same time every day)
Initial electronic diary entries 
for Sleep-Loss should be 
completed a minimum of 4 of
7 days before randomization.
PROs should be completed 
prior to any other study 
assessments.
Skin Pain NRS
Daily (should be completed at approximately the same time every day)
Initial electronic diary entries 
for Skin Pain NRS should be 
completed a minimum of 4 of
7 days before randomization.

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
17
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
PROs should be completed 
prior to any other study 
assessments.
Patient-Oriented Eczema 
Measure (POEM)
Weekly
PROs should be completed 
prior to any other study 
assessments.
Patient-Reported Outcomes (Electronic Tablet on Site)
PROMIS® (Patient-
Reported Outcomes 
Measurement 
Information System) 
Anxiety Measure
X
X
X
PROs should be completed 
prior to any other study 
assessments.
PROMIS® Depression 
Measure
X
X
X
PROs should be completed 
prior to any other study 
assessments.
Clinician-Administered Assessments (Electronic Tablet on Site)
Investigator Global 
Assessment (IGA) 
X
X
X
X
X
X
The IGA must be conducted 
prior to conducting the EASI 
and BSA assessments. 

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Protocol J2T-MC-KGAK/DRM06-AD18
18
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
Eczema Area and 
Severity Index (EASI) 
X
X
X
X
X
X
Body Surface Area 
(BSA) 
X
X
X
X
X
X
Laboratory Tests and Sample Collections
Hematology
X
X
X
X
X
Clinical Chemistry 
X
X
X
X
X
Urinalysis
X
X
X
X
X
Serum pregnancy
X
Only for women of 
childbearing potential
(Section 8.2.3.1 and 
Appendix 10.4).
Urine pregnancy (local)
X
X
X
X
X
X
Only for women of 
childbearing potential
(Section 8.2.3.1 and 
Appendix 10.4).
HIV screening tests
X
Hepatitis C Virus (HCV) 
screening tests
X
HCV RNA will be measured 
to confirm positive 
hepatitis C virus antibody 

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
19
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
(Section 8.2.6).
Hepatitis B Virus (HBV) 
screening tests
X
Includes testing for HBsAg,
anti-HBc, and anti-HBs.
HBV DNA
X
X
Only for participants who are 
anti-HBc reactive and anti-
HBs nonreactive at screening 
(Section 8.2.5).
Total IgG
X
Total IgA
X
Anti-tetanus toxoid IgG 
antibody
X
X
X
At Week 12, collect this 
sample before the vaccine 
administration.
Meningococcal Group C 
serum bactericidal 
antibodies (human 
complement serum 
bactericidal assay 
X
X
X
At Week 12, collect this 
sample before the vaccine 
administration.

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
20
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
[hSBA])
Pharmacokinetic (PK) 
samples
X
X
X
X
X
X

Collect samples before 
dosing. See Section 8.5
for more information 
about the PK testing.

In case of systemic 
hypersensitivity 
reactions, additional PK 
samples will need to be 
collected (Section 8.2.4, 
Appendix 10.5).
Immunogenicity (ADA) 
samples 
X
X
X
X
X
X

Collect samples before 
dosing. See Section 8.9
for details.

In case of systemic 
hypersensitivity 
reactions, additional 
immunogenicity samples 
will need to be collected 

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
21
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
(Section 8.2.4, 
Appendix 10.5).
Stored Samples
Pharmacogenetics sample
X
Randomization and Dosing
Randomization
X
Administer study drug
X
X
X
X
X
X
X
X
During remote visits, 
participant can choose to self-
administer the assigned study 
drug (lebrikizumab or 
placebo) or have a caregiver 
or the mobile home health 
care provider administer it.
See Section 6.1.4 for more 
information about at-home 
administration.
Participants and/or caregivers 
need to be adequately trained 
on injection technique prior to 
administering injections.

CONFIDENTIAL
Protocol J2T-MC-KGAK/DRM06-AD18
22
Notes:

Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance.

For early terminations (ETs) that occur before the last visit in treatment period, see the activities listed for ET in this table.

Visit 801 is only for study participants who are terminating early or not rolling into the long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Visit number
1
2
3*
4
5*
6*
7*
8
9*
10
ET
V801*
Comments
Weeks from
randomization
Screening 
(-4)
Baseline
/Day 1
2
4
6
8
10
12
14
16
ET
Safety 
follow-up
Week 26 (or 
approximately 
12 weeks after
last study drug 
injection) 
* = visit may be conducted 
remotely or on site, per 
preference of the study site or 
participant. 
See Section 4.1 for details 
about remote visits.
Days from randomization
≤30
—
15
29
43
57
71
85
99
113
N/A
Visit interval tolerance 
(days)
—
±3
±3
±3
±3
±3
±3
±3
±3
N/A
±3
Mobile home health care 
provider would observe the 
participant’s or caregiver’s 
first attempt at administering 
the study drug.
Administer vaccines: 
Tdap and MCV
X
See Section 6.1.2 for location 
of vaccine injections.
Participant/caregiver 
returns study drug and 
injection supplies
X
X
X
X
X
X
If study drug was 
administered at home by 
participant or caregiver, the 
injection supplies should be 
saved and returned at the next 
on-site visit.
Abbreviations: AD = atopic dermatitis; ADA = antidrug antibodies; AESI = adverse event of special interest; anti-HBc = hepatitis B core antibody; anti-
HBs = hepatitis B surface antibody; BCG = Bacillus Calmette-Guerin; HBsAg = hepatitis B surface antigen; IgA = immunoglobulin A; 
IgG = immunoglobulin G; MCV = Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine
(GlaxoSmithKline); N/A = not applicable; NRS = Numeric Rating Scale; SoA = Schedule of Activities; TCI = topical calcineurin inhibitors; TCS = topical 
corticosteroids; Tdap = Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (Sanofi); V = visit.

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Protocol J2T-MC-KGAK/DRM06-AD18
23
2.
Introduction
2.1.
Study Rationale
To date, no vaccine-response studies have been conducted for lebrikizumab. Because 
lebrikizumab suppresses interleukin (IL)-13 signaling, a potential immunomodulator effect, there 
is a need to assess immune response to vaccinations in patients receiving this drug. 
Study J2T-MC-KGAK (KGAK) is a Phase 3, randomized, double-blind, placebo-controlled
study to assess the impact of lebrikizumab on vaccine immune responses in adult patients with 
moderate-to-severe atopic dermatitis (AD). This study will evaluate the effect of lebrikizumab 
treatment on 2 vaccines commonly used in adults with moderate to severe AD:

Tdap: Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed
(Sanofi), and

MCV: Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria 
CRM197 Conjugate Vaccine (GlaxoSmithKline).
In addition, this study will further assess the efficacy and safety of lebrikizumab in patients with 
moderate-to-severe AD. 
2.2.
Background
Atopic dermatitis is a complex disease that is considered an autoimmune disorder (Mitterman et 
al. 2004) and is determined by genetic, environmental, and immunologic factors (Werfel et 
al. 2016; Simon et al. 2019). Atopic dermatitis is one of the most common chronic medical 
diseases; 2% to 20% of adults are affected, and the prevalence appears to have increased over the 
past 3 to 4 decades (Williams et al. 2008), with some geographic variability.
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 is 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 immunoglobulin E (IgE). Elevated IgE is present in up to 80% of all patients with AD, 
particularly in children (Werfel et al. 2016), and is consistent with the presence in the skin of the 
following:

Type 2 cytokines:
o
IL-4
o
IL-5
o
IL-9

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Protocol J2T-MC-KGAK/DRM06-AD18
24
o
IL-13
o
IL-25
o
IL-31
o
IL-33, and 
o
thymic stromal lymphopoietin (TSLP), 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 ubiquitous presence of IL-13 in the skin of 
patients with AD supports the evaluation of anti-IL-13 therapies in patients with AD.
2.2.1.
Clinical Manifestations of Atopic Dermatitis
Clinically, AD is characterized by xerosis, erythematous crusted eruption (dermatosis), 
lichenification, and intense pruritus (Bieber 2008). These symptoms, along with the distribution, 
chronicity, and history of skin lesions, form the basis for diagnosing 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 puberty onwards) is less predictable than the infantile stage. 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 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 
1 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 

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Protocol J2T-MC-KGAK/DRM06-AD18
25
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).
2.2.2.
Treatment for Atopic Dermatitis
The therapeutic approach to AD consists primarily of trigger avoidance, skin hydration with 
bathing, the use of moisturizers, and anti-inflammatory therapies consisting predominantly of 
topical corticosteroids (TCS). In many patients, treatment with TCS provides some measure of 
symptomatic relief but does not always adequately control the disease. In those patients who 
have 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 corticosteroids, cyclosporine, azathioprine, methotrexate, and mycophenolate 
mofetil. These medicines are not available for patients across the globe. In the US, only 
cyclosprone is approved for treatment of moderate-to-severe AD. Recently, an anti-IL-4R 
monoclonal antibody that inhibits signaling for both IL-4 and IL-13, dupilumab, was approved 
for the treatment of adult and adolescent patients with moderate-to-severe AD. 
In spite of these treatments, AD remains a major societal burden and a significant unmet medical 
need.
2.2.2.1.
Lebrikizumab
Lebrikizumab is a humanized monoclonal immunoglobulin (Ig) G4 antibody (huIgG4) with a 
mutation in the hinge region that increases stability. Lebrikizumab binds specifically to soluble 
human IL-13 with high affinity, and potently inhibits IL-13 signaling through the IL-4R/IL-
13R1 complex. Because lebrikizumab binds to IL-13 in a non-receptor binding domain (i.e., a 
portion of the molecule not involved in binding to its receptor), antibody-bound IL-13 can still 
bind its receptor (IL-13R1), but the engaged receptor complex cannot be activated.
2.3.
Benefit/Risk Assessment
Atopic dermatitis remains an important public health challenge. Therefore, there is a continuing 
need to develop additional treatment options that offer alternatives to and potential 
improvements upon existing therapies.
Clinical benefit
The use of lebrikizumab for the treatment of AD is supported by numerous preclinical studies 
demonstrating that AD is characterized by the increased expression of IL-13 in skin. Moreover, 
Phase 2 efficacy studies in lebrikizumab (GS29250 [TREBLE], GS29735 [ARBAN], and 
DRM06-AD01) demonstrated significant clinical benefit in patients with AD. 
The lebrikizumab doses and regimen planned for Study KGAK were selected based on analyses 
of pharmacokinetic (PK), safety, and efficacy data from Phase 1 and Phase 2 studies and 
nonclinical safety data. In addition, the doses and regimen used here are identical to ongoing 
Phase 3 registration trials.

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Protocol J2T-MC-KGAK/DRM06-AD18
26
Safety profile and mitigation plan
Blinded trial-level safety reviews will be conducted at periodic intervals throughout the study.
An external data safety monitoring board (DSMB) will conduct safety analyses to review 
unblinded safety data. These monitoring and risk-mitigation actions, along with regular review of 
adverse events (AEs) and laboratory data, will assist in the evaluation and management of 
potential risks associated with lebrikizumab administration.
Both of the vaccines (Tdap and MCV) used in this study will be administered according to their 
approved labelling.
Additional information
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of lebrikizumab may be found in the Investigator’s Brochure (IB).

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Protocol J2T-MC-KGAK/DRM06-AD18
27
3.
Objectives and Endpoints
Objectives
Endpoints
Co-Primary

To compare the seroresponses to the Tdap and 
MCV between lebrikizumab-treated and 
placebo-treated participants with 
moderate-to-severe AD
The percentage of participants who:
1.
Develop a booster response to tetanus 
toxoid 4 weeks after the administration of the 
Tdap vaccine (Week 16)
Booster response is defined as:
o
≥4-fold increase in anti-tetanus toxoid 
IgG antibody concentration if the pre-
vaccination level was >0.10 IU/mL and 
≤2.7 IU/mL; 
OR
o
≥2-fold increase in anti-tetanus toxoid 
IgG antibody concentration if the pre-
vaccination level was >2.7 IU/mL; 
OR 
o
≥4-fold increase in anti-tetanus toxoid 
IgG antibody concentration and a post-
vaccination level ≥0.10 IU/mL if the pre-
vaccination level was ≤0.10 IU/mL
2.
Have positive antibody response to MCV 
(group C serum bactericidal antibodies)
4 weeks after the administration of the 
vaccine (Week 16)
Positive antibody response to MCV is defined 
as:
o
post-vaccination hSBA titer ≥4 times the 
LLOQ, if the pre-vaccination hSBA titer 
is less than the LLOQ;
OR
o
post-vaccination hSBA titer ≥4 times the 
pre-vaccination titer, if the pre-
vaccination hSBA titer is greater than or 
equal to the LLOQ

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Protocol J2T-MC-KGAK/DRM06-AD18
28
Objectives
Endpoints
Secondary

To compare the efficacy of lebrikizumab with 
that of placebo in treatment of participants
with moderate-to-severe AD, as measured by:
Percentage of participants at Week 16 achieving:

an IGA score of 0 or 1 and a reduction of ≥2 
points from baseline

EASI-75

EASI-90

≥4-point improvement from baseline in 
Pruritus NRS score 
Percentage change from baseline to Week 16 in:

EASI

Pruritus NRS score
Change from baseline in:

Percent BSA

Sleep-Loss score

To compare the patient-reported outcomes 
between lebrikizumab-treated and 
placebo-treated participants with moderate-to-
severe AD, as measured by:
Change from baseline by visit in:

PROMIS® Anxiety measure

PROMIS® Depression measure
Exploratory
Exploratory objectives and endpoints may include the following assessments. The endpoints will be 
detailed in the SAP.

Skin Pain NRS

POEM
Abbreviations: AD = atopic dermatitis; BSA = Body Surface Area; EASI = Eczema Area and Severity Index; 
EASI-75 = ≥75% reduction from baseline in EASI score; EASI-90 = ≥90% reduction from baseline in EASI 
score; hSBA = human complement serum bactericidal assay; IGA = Investigator Global Assessment; 
IgG = immunoglobulin G; LLOQ = lower limit of quantitation; MCV = Meningococcal (Groups A, C, Y, and W-
135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine (GlaxoSmithKline); NRS = Numeric Rating 
Scale; POEM = Patient-Oriented Eczema Measure; PROMIS = Patient-Reported Outcomes Measurement 
Information System; SAP = Statistical Analysis Plan; Tdap = Diphtheria and Tetanus Toxoids and Acellular 
Pertussis Vaccine Adsorbed (Sanofi).
Note: For distinction between the clinician-administered assessments and patient-reported outcomes, see the 
Schedule of Activities (Section 1.3), as well as Sections 8.1.2 and 8.1.3.

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4.
Study Design
4.1.
Overall Design
Study KGAK is a Phase 3, 16-week, randomized, double-blind, placebo-controlled, parallel-
group trial. The study will evaluate whether treatment with lebrikizumab compared with placebo 
affects seroresponses to non-live vaccines in patients with moderate-to-severe AD. In addition, 
the study will further assess the efficacy and safety of lebrikizumab compared with placebo in 
treating this patient population.
Study periods
KGAK has 3 study periods:

Screening (Visit 1: ≥1 day)

Treatment (Visits 2-10: 16 weeks)

Safety follow-up (Visit 801: at Week 26 or approximately 12 weeks after last 
treatment)
See the Schedule of Activities (SoA) (Section 1.3) for additional details about the study periods 
and visit-specific assessments. A schematic of the study design is presented in Section 1.2.
Visit types
Depending on the preference of the study site or the study participant, some of the study visits 
may be performed either remotely or on site. 
Remote visits may be conducted as follows:

virtually (i.e., via telephone or telemedicine tools), and

at a mobile location (e.g., a participant’s home), if permitted by local laws and 
regulations.
See the table below for details about the visit types.
Study visit
Study week
Visit type
1
-4
On site only
2
Baseline
On site only
3
2
Remote or on site
4
4
On site only
5
6
Remote or on site
6
8
Remote or on site
7
10
Remote or on site
8
12
On site only
9
14
Remote or on site
10/early termination (ET)
16
On site only
801
Week 26 (or approximately 
12 weeks after last treatment)
Remote or on site

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Treatment groups
Participants found to be eligible according to all of the study entry criteria will be randomly 
assigned in a 1:1 ratio to receive either lebrikizumab or placebo (see Section 6.1 for dose and 
administration details).
Participants will be stratified at randomization according to their disease severity (i.e., IGA score 
of 3 vs 4). If the study is conducted in multiple countries, participants will also be stratified 
according to the geographical region.
Vaccine products
All participants will receive 2 vaccine injections at Week 12. For details, see Section 6.1.2.
Eligibility for long-term extension study
Participants who complete this 16-week study will be eligible to continue to a separate long-term 
extension study (DRM06-AD07/J2T-DM-KGAA). For “completion of study” definition, see 
Section 4.4. For rescue medications allowed at entry into the long-term extension study, see 
Section 6.5.3.
4.2.
Scientific Rationale for Study Design
Vaccine types and timing of vaccine administration
When evaluating a new immunomodulatory agent for potential use in AD patients, it is important 
to understand any potential effects the new treatment may have on the immune response to 
vaccines. This study will use 2 different, commonly used vaccines (Tdap and MCV) to test the 
effect of the study drug on both the T-independent B-cell responses and T-dependent B-cell 
responses.
Both placebo- and lebrikizumab-treated participants will be immunized with the 2 vaccines after
12 weeks of treatment, to allow study drug to reach steady-state levels. Serum antibody levels 
will be determined at 4 weeks following vaccination to allow for a maximal antibody response.
Demographics collection
In this study, collection of demographic information includes race and ethnicity. The scientific 
rationale is based on the need to assess variable response in safety and/or efficacy based on race 
or ethnicity. This question can be answered only if all the relevant data are collected.
Safety monitoring
Safety monitoring, complaint handling, and all AEs and serious adverse events (SAEs) will be 
collected as specified in this protocol. This study will collect the safety information to further 
characterize the safety profile of lebrikizumab.

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4.2.1. Participant Input into Design
Throughout this protocol, the term “participant” is used to indicate an individual who participates 
in a clinical trial, either as a recipient of an investigational drug or as a control. This usage 
reflects preferences indicated by patient advocates to more accurately reflect the role of people 
who take part in clinical trials.
No participant input was provided for this study design.
4.3.
Justification for Dose
The lebrikizumab dosing regimen of 500 mg loading dose at baseline and Week 2, followed by 
250 mg Q2W, was selected based on an evaluation of safety, efficacy, and PK data from the 
DRM06-AD01 and DRM06-AD03 trials. This is the same dosing and treatment regimen used in 
the ongoing Phase 3 studies of lebrikizumab.
4.4.
End of Study Definition
A participant is considered to have completed the study if he or she has completed all required 
visits of the study, namely:

Completed all required visits through Week 16 and through the safety follow-up period

Completed all required visits through Week 16 and rolls into the LTE study (DRM06-
AD07/J2T-DM-KGAA)
The “end of the study” is defined as the date of the last visit or the last scheduled procedure 
shown in the SoA for the last participant in the study globally.

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5.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted.
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Participant Characteristics
[1] Are male or female participants from 18 to 55 years of age.
Atopic Dermatitis Characteristics
[2] Have chronic AD (according to American Academy of Dermatology Consensus Criteria; 
Eichenfield et al. 2014; Appendix 10.8) that has been present for ≥1 year before the 
screening visit (Visit 1).
[3] Have Eczema Area and Severity Index (EASI) score ≥16 at the baseline visit
(randomization; Visit 2).
[4] Have Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at the baseline visit
(randomization; Visit 2).
[5] Have ≥10% Body Surface Area (BSA) of AD involvement at the baseline visit
(randomization; Visit 2).
Prior/Concomitant Therapy and Vaccinations
[6] Have a history of inadequate response to treatment with topical medications; or 
determination that topical treatments are otherwise medically inadvisable.
[7] Have not received any tetanus-containing vaccine within approximately 5 years of 
randomization (Visit 2).
[8] Have never received a meningococcal conjugate vaccine or have received not more than 1 
prior MCV dose at least 4 years prior to randomization (Visit 2), of a vaccine containing 1 
or more meningococcal serogroups (serogroups A, C, W, Y).
Reproductive Characteristics
[9] Contraceptive use by men or women should be consistent with local regulations regarding 
the methods of contraception for those participating in clinical studies.
a.
Female participants of childbearing potential: must 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 study drug. 
Women of non-childbearing potential (non-WOCBP) may participate without any 
contraception requirements. For definitions of women of childbearing potential 
(WOCBP) and non-WOCBP, see Appendix 10.4.

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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 (IUD)

intrauterine hormone-releasing system (IUS)

bilateral tubal occlusion and bilateral tubal ligation

vasectomized partner, or

sexual abstinence.
The reliability of sexual abstinence should be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are 
not acceptable methods of contraception.
b. Male participants are not required to use any contraception except in compliance with 
specific local government study requirements.
Informed Consent
[10] Are capable of giving signed informed consent as described in Appendix 10.1, which 
includes compliance with the requirements and restrictions listed in the informed consent 
form (ICF) and in this protocol.
Other
[11] Participants must be willing and able to comply with all study visits and study-related 
procedures and questionnaires.
5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
[12] Have a history of anaphylaxis, as defined by the Sampson criteria (Sampson et al. 2006).
[13] Have an uncontrolled chronic disease that might require multiple intermittent uses of oral 
corticosteroids, e.g., co-morbid severe uncontrolled asthma (as defined by the investigator).
[14] Have an active chronic or acute infection requiring treatment with systemic antibiotics, 
antivirals, antiparasitics, antiprotoxoals, or antifungals within 2 weeks before the baseline 
visit (randomization; Visit 2), or superficial skin infections within 1 week before the 
baseline visit. 
NOTE: Participants may be rescreened after infection resolves (Section 5.4.1).

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[15] Have had any of the following types of infection within 3 months of screening or develop 
any of these infections before randomization (Visit 2):

Serious (requiring hospitalization, and/or intravenous or equivalent oral antibiotic 
treatment)

Opportunistic (as defined in Winthrop et al. 2015) 
NOTE: Herpes zoster is considered active and ongoing until all vesicles are dry and 
crusted over.

Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer) 

Recurring (including, but not limited to herpes simplex, herpes zoster, recurring 
cellulitis, chronic osteomyelitis) 
NOTE: Participants with only recurrent, mild and uncomplicated orolabial and/or genital 
herpes may be discussed with the sponsor’s medical monitor to determine whether the 
participants meet this exclusion criterion. 
[16] Have a current or chronic infection with hepatitis B virus (HBV) (Section 8.2.5).
[17] Have a current infection with hepatitis C virus (HCV) (i.e., positive for HCV RNA; 
Section 8.2.6).
[18] Have known liver cirrhosis and/or chronic hepatitis of any etiology.
[19] Are diagnosed with active endoparasitic infections or at high risk of these infections.
[20] Have a known or suspected history of immunosuppression, including history of invasive 
opportunistic infections (e.g., tuberculosis [TB], histoplasmosis, listeriosis, 
coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution; or 
unusually frequent, recurrent, or prolonged infections, per the investigator’s judgement.
[21] Have a history of human immunodeficiency virus (HIV) infection or positive HIV serology 
at screening (Visit 1).
[22] Have presence of skin comorbidities that may interfere with study assessments.
[23] Have a history of malignancy, including mycosis fungoides, within 5 years before screening 
(Visit 1), 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.
[24] Have a severe concomitant illness(es) that in the investigator’s judgement would adversely 
affect the patient’s participation in the study. Have 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 trial, may make patient’s participation unreliable, or may 
interfere with study assessments.
[25] Have a prior history of Guillain-Barre syndrome.
[26] Are allergic to latex.
[27] Have a history of past vaccination allergy or Arthus-type hypersensitivity.

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[28] Have an uncontrolled seizure disorder.
[29] Have known hypogammaglobulinemia or a screening serum immunoglobulin G (IgG) or 
immunoglobulin A (IgA) concentration less than the lower limit of the reporting 
laboratory’s reference range.
Prior/Concomitant Therapy and Vaccines
[30] Have been treated with TCS, calcineurin inhibitors, or phosphodiesterase-4 inhibitors such 
as crisaborole within 1 week prior to the baseline visit (randomization; Visit 2).
[31] Have been treated with any of the following agents within 4 weeks prior to the baseline visit
(randomization; Visit 2):
a.
Immunosuppressive/immunomodulating drugs (e.g., systemic corticosteroids, 
cyclosporine, mycophenolate-mofetil, interferon gamma(IFN-γ), Janus kinase inhibitors, 
azathioprine, methotrexate, etc.)
b. Phototherapy and photochemotherapy (PUVA) for AD
[32] Have been treated with the following prior to the baseline visit (randomization; Visit 2):
a.
An investigational drug within 8 weeks or within 5 half-lives (if known), whichever is 
longer
b. B Cell-depleting biologics, including rituximab, within 6 months
c.
Other biologics within 5 half-lives (if known) or 8 weeks, whichever is longer
[33] Have used prescription moisturizers within 7 days of the baseline visit (randomization; 
Visit 2).
[34] Have regularly used (more than 2 visits per week) a tanning booth or parlor within 4 weeks 
of the screening visit (Visit 1).
[35] Have received a Bacillus Calmette-Guerin (BCG) vaccination or treatment within 12 months 
of screening (Visit 1), or have been treated with a live (attenuated) vaccine within 12 weeks 
of the baseline visit (randomization; Visit 2) or planned during the study.
[36] Have a contraindication to the Tdap vaccine or MCV.
Diagnostic Assessments
[37] In the investigator’s opinion, have any clinically significant laboratory results from the 
chemistry, hematology, or urinalysis tests obtained at the screening visit (Visit 1).
Prior/Concurrent Clinical Study Experience
[38] Have received a dose of lebrikizumab in any prior lebrikizumab clinical study.
[39] Are currently enrolled in any other clinical study involving an investigational product or any 
other type of medical research judged not to be scientifically or medically compatible with 
this study.

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Other Exclusions
[40] Are pregnant or breastfeeding women, or women planning to become pregnant or breastfeed 
during the study.
[41] 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.
[42] Are employees of Eli Lilly and Company (Lilly) or are employees of a third-party involved 
in study that requires exclusion of their employees.
5.3.
Lifestyle Considerations
All study participants should be instructed not to donate blood or blood products as follows:

within 2 to 4 weeks of study entry

during the study, and

for at least 18 weeks after the last dose of the study drug. 
No other lifestyle considerations are applicable to this study.
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 drug. 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 SAE.
5.4.1.
Rescreening for Individuals Who Failed Screening 
Informed consent for rescreenings
Individuals who are to be rescreened must first sign a new ICF (Appendix 10.1, Section 10.1.3). 
Such individuals will be assigned a new participant number.
Rescreening after failure to meet study entry criteria
An individual who does not meet the criteria for participation in this study due to deviation from
the exclusion criterion [14] (acute infection requiring treatment) may be rescreened one time
after the reason for the screen failure has resolved and if the sponsor has approved the 
rescreening. 
An individual who does not meet the criteria for participation in this study for other reasons may 
be rescreened one time if the reason for the screen failure has resolved and if the sponsor has 
approved the rescreening. 

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Rescreening for administrative reasons
An individual may be rescreened one time for an administrative reason, including, for example, 
but not limited to, falling out of the screening window because of scheduling conflicts. The 
sponsor does not need to approve rescreening for an administrative reason. The rescreening can 
start immediately after the administrative reason has resolved.
Procedures to be repeated at rescreening
When rescreening, all of the screening tests and procedures should be repeated.

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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.
In this protocol, the collective term “study intervention” applies both to the study drug 
(lebrikizumab or placebo; Section 6.1.1) and the vaccine products (Section 6.1.2).
6.1.
Study Interventions Administered
6.1.1.
Study Drugs
This study involves administration of lebrikizumab and placebo, as shown:
Study Drug Name
Lebrikizumab
Placebob
Dosage Formulation
250 mg (2 mL)a
To match lebrikizumab
Dosage Levels and 
Frequency
Baseline and Week 2: 500 mg loading dose
Weeks 4-14: 250 mg Q2W
To match lebrikizumab
Routes of 
Administration
subcutaneous injection
subcutaneous injection
Abbreviation: baseline = randomization (Visit 2); Q2W = once every 2 weeks.
a All study drug (lebrikizumab and placebo) will be supplied as a sterile prefilled syringe with needle safety device 
(PFS-NSD). Each prefilled syringe is intended for a single 2 mL dose (250 mg) administered subcutaneously.
b Placebo solution is identical in appearance and content to the active solution except for lebrikizumab.
For drug administration information, see Sections 6.1.3 and 6.1.4.
6.1.2.
Vaccine Products
At Week 12, after the pre-dose vaccine titers have been drawn, one dose of each of the 2 
commercially available vaccines will be administered to all participants still on study drug:

Tdap

MCV
Participants whose study drug has been permanently discontinued before Week 12 will not 
receive the vaccines (Section 7.1.2).
Vaccine administration
Vaccine injections will be given per local vaccination guidelines and practices and:

should not be administered at sites with active AD or other skin lesions

should be injected in a location different from that for the study drug administration 
(Section 6.1.3).

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6.1.3.
Instructions for Administration in the Clinic
Study drug and vaccines will be administered to all study participants in the clinic by designated 
and trained site staff as specified in the SoA (unless the study participant has opted for at-home 
administration of the study drug; see the SoA and Section 6.1.4). Detailed instructions for study 
drug administration will be provided by the sponsor.
At Week 12, the study drug should be injected in a location different from that for vaccine 
administration.
6.1.4.
Instructions for Administration at Home
During remote visits, study participants may opt to self-administer the study drug or have the 
mobile home health care provider administer it, if permitted by local laws and regulations.
Participants may also opt to have their caregivers administer the study drug. Prior to at-home 
administration, participants and/or caregivers will be adequately trained on the study drug
administration at the clinical site (as indicated in the SoA, Section 1.3).
Participants and/or their caregiver will be instructed on the proper injection technique, and the 
participant or their caregiver will demonstrate the proper injection technique prior to beginning 
at-home administration. 
Instructions for Use with details of the injection procedures, as well as storage and handling of 
syringes, will be provided to the participant and/or their caregiver to take home. Participants who 
are not capable of administering study drug at home (or do not have a caregiver to administer the 
drug at home), or who prefer not to do so, may continue to receive study drug injections in the 
clinic.
Any time the study drug is administered at home, participants will enter the details about the
injections in the electronic patient diary (see the SoA for details).
6.1.5.
Packaging and Labeling
Lebrikizumab and placebo will be supplied by the sponsor or its designee in accordance with 
current Good Manufacturing Practice (cGMP). Vaccines will be sourced as directed by the 
sponsor or its designee. Clinical trial materials will be labeled according to the country’s 
regulatory requirements. All study interventions will be stored, inventoried, reconciled, and 
destroyed according to applicable regulations (see also Section 6.2).
Each prefilled syringe with needle safety device (PFS-NSD) will be packaged in a carton.
6.2.
Preparation/Handling/Storage/Accountability
The Pharmacy Manual provides general instructions for the handling and storage of the study 
drug, as well as the site responsibility and accountability for the administered products.
Additional trial-specific information is provided in other documents (see Sections 6.1.3 and 
6.1.4). For storage information for lebrikizumab, refer to the investigational product label.
For vaccine-related information, refer to the local labels and guidelines.

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Site responsibilities and accountability

The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention.

Only participants enrolled in the study may receive study intervention and only personnel 
authorized by the primary investigator or by the sponsor 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 (unless 
the study drug will be administered at home by the participant or caregiver). At-home 
storage instructions are provided in the participants’ Instructions for Use.

The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records).

Further guidance and information for the final disposition of unused study interventions
are provided in the Pharmacy Manual.
6.3.
Measures to Minimize Bias: Randomization and Blinding
This is a double-blind study. The sponsor or designee, the investigator, study-site personnel, and 
the participant will be blinded to treatment assignment. The integrity of the clinical study will be 
maintained by observing the treatment blind.
Method of treatment assignment
The randomization ratio and stratification factors are described in Section 4.1.
Assignment to treatment groups will be determined by a computer-generated random sequence 
using an interactive web-response system (IWRS). Each study participant will be assigned a 
unique identification number.
Emergency unblinding
Emergency unblinding for AEs may be performed through the IWRS. This option may be used 
ONLY if the participant’s well-being requires knowledge of the participant’s treatment 
assignment. All actions resulting in an unblinding event are recorded and reported by the IWRS.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a participant’s study drug assignment is warranted. Participant safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding is 
warranted, it is the responsibility of the investigator to promptly document the decision and 
rationale and notify the sponsor as soon as possible.
Unblinding and participant discontinuation
See Section 7.2.

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6.4.
Study Intervention Compliance
Participants will receive study intervention directly from the investigator or designee, under 
medical supervision unless they opt for at-home administration of the study drug by themselves 
or their caregivers (see Section 6.1.4).
When administered in the clinic, the date and time of each dose will be recorded in the source 
documents and recorded in the electronic case report form (eCRF). When administered at home, 
participants will enter the details about the study drug injections in the electronic patient diary 
(see the SoA for details).
A participant will be considered compliant with the dosing regimen if the participant received 
80% of the expected number of study drug injections while enrolled in the study.
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 the study 
participants.

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.

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 it is a supplement or used as preventative care.
6.5.1.
Permitted and Prohibited Treatments and Procedures
Permitted medications
The use of concomitant medications for other medical conditions (e.g., hypertension, diabetes, 
acute infections) is permitted during this study. Inhaled corticosteroids and bronchodilators to 
control asthma are permitted.
In addition, TCS or TCI may be used during the study (low- or mid-potency only). 
Participants may use TCS (described below) for AD symptoms starting at the baseline visit 
(randomization: Visit 2/Day 1).
Participants may taper or stop TCS use, as needed. If AD lesions return or a participant
experiences a flare, TCS treatment may be resumed at the participant’s discretion.
Low-potency TCS or TCIs may be used for sensitive areas only (i.e., face, neck, intertriginous, 
and genital areas).

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Participants may use the following TCS, if needed:

a mid-potency TCS: triamcinolone acetonide cream 0.1%, and

a low-potency TCS: hydrocortisone 1% cream (for use on sensitive skin areas, e.g., face).
All TCS use should be recorded in the eCRF.
Prohibited medications and procedures
The introduction of medications or therapies for other medical conditions known to affect AD 
(e.g., systemic corticosteroids, mycophenolate-mofetil, IFN-y, Janus kinase inhibitors, 
cyclosporine, azathioprine, methotrexate, phototherapy or photochemotherapy, or 
phosphodiesterase-4 inhibitors such as crisaborole) are not permitted during the study. 
The use of systemic corticosteroids for the treatment of AD is prohibited and requires permanent 
discontinuation of study drug (Section 7.1.2). If used for treatment of AEs (for example, 
worsening of existing condition, such as asthma exacerbation), it will be treated as rescue 
medication as per the Section 6.5.3.
Acute severe 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 trial.
Cannabinoid treatments for AD are prohibited.
Planned or anticipated major medical procedures or surgeries should be avoided during the trial. 
See Section 6.5.3 for details on approved rescue medications and timing of use.
6.5.2.
Background Treatment: Non-Medicated Moisturizers
Participants are to apply a stable dose of non-medicated topical moisturizer at least twice daily 
for ≥7 days prior to the baseline visit.
Non-medicated moisturizers are to be used during the study. The participants may continue their
current over-the-counter moisturizer regimen, if approved by the investigator.
All moisturizer use should be recorded in the eCRF.
6.5.3.
Rescue Treatment for Atopic Dermatitis
During this study, add-on rescue therapies may be needed if the participant experiences clinical 
worsening of symptoms that are intolerable.
Participants will be eligible to receive rescue treatment with any locally approved AD treatments 
at the discretion of the investigator. Investigators are encouraged to provide rescue therapy in a 
staged fashion, using a greater intensity of treatment compared to that which the participant was 
using, for example:

high-potency TCS, or

treating with:
o
oral corticosteroids
o
systemic nonsteroid immunosuppressants, or
o
phototherapy. 

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Refer to Section 7.1.2 for discontinuation criteria associated with systemic rescue treatment.
Participants using topical or systemic rescue medication who complete the study through 
Week 16 will be eligible to continue to a separate long-term extension study after the Week 16 
visit has been completed.
All rescue treatment usage must be captured in the eCRF.
6.6.
Dose Modification
Dose modifications of lebrikizumab are not allowed in this study.
6.7.
Intervention after the End of the Study
Participants who complete Study KGAK through Week 16 will be assessed for eligibility to enter 
a separate long-term extension study (DRM06-AD07/J2T-DM-KGAA). If a participant does not 
meet enrollment criteria for the long-term extension study or does not opt to continue into that 
study, he or she will be asked to complete the post-treatment follow-up period as described in the 
SoA (Section 1.3), which will complete his or her study participation.
Lebrikizumab will not be available to the KGAK study participants unless they enter the long-
term extension study.

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7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
The sections below describe reasons for a participant’s:

temporary or permanent discontinuation of study drug (Section 7.1), or

discontinuation (withdrawal) from the study (Section 7.2).
Discontinuation of specific sites or the trial as a whole is handled as part of regulatory, ethical, 
and trial oversight considerations in Appendix 10.1, Section 10.1.9.
7.1.
Discontinuation of Study Intervention
Study drug may be permanently discontinued or temporarily withheld during the study.
7.1.1.
Criteria for Temporary Discontinuation of Study Drug
Cases that may merit temporary withholding of the study drug should be discussed with the 
medical monitor. The medical monitor, in consultation with the investigator, will determine 
when it is appropriate to recommence study drug.
Participants who require a temporary withholding of study drug after Week 6 will not receive the 
Tdap and MCV vaccinations at Week 12 unless approved by the medical monitor.
Participants who require a temporary withholding of study drug will not be eligible for entry into 
the long-term extension study unless they continue to complete study visits and assessments 
through Week 16.
Some possible reasons for temporarily withholding the study drug include, but are not limited to:

Serious or opportunistic infections (Section 5.2 and Appendix 10.7). Study drug is to be 
withheld until resolution of all acute clinical signs and symptoms, and completion of all 
appropriate anti-infective treatment.

Hepatitis B virus DNA results that are reported as positive, or as detecting HBV DNA, 
but HBV DNA is below the level of quantification: The sponsor’s designated medical 
monitor should be contacted regarding study status of the participant. Hepatitis B virus
DNA testing is to be repeated as soon as is feasible. If HBV DNA is confirmed as 
positive, the participant must be permanently discontinued from study drug 
(Section 7.1.2).

Hepatic event or liver test abnormality: The study drug should be withheld and additional 
testing performed following consultation with the Lilly-designated medical monitor, if 
the results of repeat tests following elevated alanine aminotransferase (ALT), alkaline 
phosphatase (ALP) or total bilirubin level (TBL) include one of the following 
(Section 8.2.7):
o
ALT 3x upper limit of normal (ULN) and TBL <2x ULN
o
ALP 2x ULN and TBL <2x ULN

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o
TBL 2x ULN without increase from baseline in ALT/aspartate aminotransferase 
(AST)/ALP.
7.1.2.
Criteria for Permanent Discontinuation of Study Drug
In rare instances, it may be necessary for a participant to permanently discontinue (definitively 
discontinue) study drug.
Possible reasons for permanent discontinuation of study intervention
Possible reasons that may lead to permanent discontinuation of the study drug include, but are 
not limited to, the following:
Investigator decision

The investigator decides that the participant should be discontinued from study 
drug. Some examples may include:
o
Inter-current illness that would, in the judgment of the investigator, affect 
assessments of clinical status to a significant degree
o
Treatment-related AEs that are clinically significant, deemed persistent, in the 
judgment of the investigator
o
Unacceptable toxicity
Systemic hypersensitivity reaction

If the investigator, after consultation with the sponsor-designated medical 
monitor, determines that a systemic hypersensitivity reaction has occurred related 
to study drug administration, the participant should be permanently discontinued 
from the study drug.

If a participant experiences a hypersensitivity event determined by the 
investigator to relate to the vaccine products, the participant will not be 
permanently discontinued from the study drug.
Required reasons for permanent discontinuation of study intervention
Permanent discontinuation of study drug should occur in the following instances:
Use of systemic rescue treatment

If a participant receives rescue treatment with a systemic corticosteroid, 
immunosuppressant, or phototherapy, the participant must permanently discontinue study 
drug.

Participants who receive rescue treatment with topical steroids may continue treatment 
with study drug.
NOTE: Participants who discontinue study drug due to rescue medication use should 
continue to attend all study visits through Week 16 and be assessed for safety and 
efficacy according to the SoA (as shown in the table at the end of this subsection).

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Hepatic event or liver test abnormality

Participants who are discontinued from the study drug due to a hepatic event 
or liver test abnormality should have additional hepatic safety data collected 
via eCRF. Discontinuation of the study drug for abnormal liver tests should 
be considered by the investigator when a participant meets one of the 
following conditions after consultation with the sponsor-designated medical 
monitor (see Section 8.2.7):
o
ALT or AST ≥8 times ULN
o
ALT or AST ≥5 times ULN for more than 2 weeks
o
ALT or AST ≥3 times ULN and TBL ≥2 times ULN or international normalized 
ratio (INR) ≥1.5 
o
ALT or AST ≥3 times ULN with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant abdominal pain or tenderness, fever, and/or rash
o
ALP ≥3 times ULN
o
ALP ≥2.5 times ULN and TBL ≥2 times ULN, or 
o
ALP ≥2.5 times ULN with the appearance of fatigue, nausea, vomiting, right 
upper quadrant abdominal pain or tenderness, fever, and/or rash
Other laboratory findings

Total white blood cell (WBC) count <2000 cells/L (<2.00 x 103/µL or 
<2.00 GI/L)

Lymphocyte count <500 cells/μL (<0.50 x 103/µL or <0.50 GI/L)

Platelet count <50,000 cells/μL (<50 x 103/µL or <50 GI/L)
Other safety considerations

The participant develops any of the following conditions during the study:
o
Malignancy (except for successfully treated basal or squamous cell skin 
carcinoma)
o
Serious or opportunistic infection that in the opinion of the investigator merits 
the study drug being discontinued. Such infections may include, but are not 
limited to:

HIV/acquired immune deficiency syndrome (AIDS) infection

active TB infection or untreated latent TB infection (LTBI)

HCV RNA positive (Section 8.2.6)

HBV DNA positive (Section 8.2.5)
NOTE: The HBV DNA result is to be confirmed if initial positive test 
result is positive but below the level of quantification (Section 7.1.1; 
Section 8.2.5). 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 drug. Timing of 
discontinuation from study drug relative to the initiation of any antiviral 
treatment for hepatitis is to be based on the recommendation of the 

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consulting specialist physician, in conjunction with the investigator, and 
aligned with medical guidelines and standard of care.
If study drug is definitively discontinued, the participant will either remain in the study or not, as 
follows:
If the study drug is permanently discontinued
due to systemic rescue treatment,
If the study drug is permanently 
discontinued for other reasons,
then participants stay in the study to:
complete all the remaining study visits and 
assessments through Week 16
AND
roll into the long-term extension study, if 
entry criteria are met
OR
undergo the safety follow-up visit (V801).
then participants will not stay in the 
study and
undergo an ET visit
AND
the safety follow-up visit (V801).
If the study drug is permanently discontinued before Week 12 and participants are continuing in 
the study, these study participants will not receive the vaccines at Week 12.
See the SoA for assessments to be performed at the time of the ET visit and safety follow-up. In 
addition to the SoA, safety follow-up is outlined in Section 8.2 (“Safety Assessments”) and 
Section 8.3 (“Adverse Events and Serious Adverse Events”) of the protocol.
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, legal guardian)
●
at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons
●
if the participant becomes pregnant during the study (see Section 8.3.5 and 
Appendix 10.4, Section 10.4.3)
●
if enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be scientifically or 
medically compatible with this study
●
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
The participant must be discontinued from the study:

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●
if an investigator, site personnel performing assessments, or participant is 
unblinded
NOTE: In cases where there are ethical reasons to have the participant remain in the 
study, the investigator must obtain specific approval from the sponsor-designated medical 
monitor for the participant to continue in the study.
Discontinuation is expected to be uncommon.
At the time of discontinuing from the study, if possible, an ET visit should be conducted, as 
shown in the SoA. See SoA for data to be collected at the time of study discontinuation and 
follow-up and for any further evaluations that need to be completed. The participant will be 
permanently discontinued both from the study intervention and from the study at that time.
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant
withdraws from the study, he/she may request destruction of any samples taken and not tested,
and the investigator must document this in the site study records.
7.2.1.
Discontinuation of Inadvertently Enrolled Participants
If the sponsor or investigator identify a participant who did not meet enrollment criteria and was 
inadvertently enrolled, then the participant should be discontinued from study drug unless there 
are extenuating circumstances that make it medically necessary for the participant to continue on 
study drug. If the investigator and the sponsor-designated medical monitor agree it is medically 
appropriate to continue, the investigator must obtain documented approval from the sponsor-
designated medical monitor to allow the inadvertently enrolled participant to continue in the 
study with or without treatment with the study drug. Safety follow up is as outlined in 
Section 1.3 (Schedule of Activities), 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.
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants randomized, including those 
who did not get the study drug. Public sources may be searched for vital status information. If 
vital status is determined to be deceased, this will be documented and the participant will not be 
considered lost to follow-up. Sponsor personnel will not be involved in any attempts to collect 
vital status information.

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8.
Study Assessments and Procedures
Study procedures and their timing are summarized in the SoA.
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable.
8.1.
Efficacy Assessments
8.1.1.
Primary Outcome Measures: Vaccine Responses
Seroresponses to vaccines will be assessed as follows:

Tdap vaccine: a booster response as measured by tetanus toxoid-specific IgG antibodies

MCV: a positive antibody response to Group C serum bactericidal antibodies
For details about the primary endpoints and definitions of the booster response and positive 
antibody response, see Section 3.
For details about the laboratory tests to support the primary outcome measure, see 
Appendix 10.2. For frequency of these tests, see the SoA (Section 1.3).
8.1.2.
Secondary Outcome Measures: Efficacy
Each participant’s AD will be assessed as specified in the SoA (Section 1.3). Whenever possible, 
the same assessor should perform all assessments on a given participant over the course of the 
study. The sponsor will administer training on the required efficacy assessments; detail on the 
specific instruments and training given are recorded in the study training materials.
All clinician-reported efficacy assessments will be captured on an electronic tablet during the site 
visits after all the patient-reported outcomes have been completed.
Appropriateness of assessments
All the assessments used in this study are relevant for the AD population. Some measures have 
been validated and are widely used, including the following:

EASI (Hanifin et al. 2001)

POEM (Charman et al. 2004)

Skin Pain NRS (Newton et al. 2019; data on file)

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8.1.2.1.
Investigator Global Assessment (IGA)
The IGA is a static assessment and rates the severity of the participant’s AD. The IGA is 
comprised 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 and BSA assessments. A single assessor 
should be assigned to each individual participant for as many visits as possible, to avoid inter-
assessor variability in scoring.
8.1.2.2.
Eczema Area and Severity Index (EASI)
The EASI is a validated measure that evaluates 2 dimensions of AD: disease extent and clinical 
signs (Hanifin et al. 2001).
The EASI assesses extent of disease at 4 body regions and measures 4 clinical signs, each on a 
scale of 0 to 3: 
(1) erythema
(2) induration/papulation
(3) excoriation, and 
(4) lichenification.
The EASI is a composite index with scores ranging from 0 to 72, with the higher values 
indicating more severe or extensive disease. 
Assessors must be trained and certified by the sponsor prior to conducting this assessment.
8.1.2.3.
Body Surface Area (BSA)
The BSA assessment estimates the extent of disease or skin involvement with respect to AD and 
is expressed as a percentage of total body surface. BSA will be determined by the investigator or 
designee using the participant palm = 1% rule. 
Assessors must be trained and certified by the sponsor prior to conducting this assessment.
8.1.3.
Patient-Reported Outcomes
The outcome measures used in this study are relevant to the AD population.
Participants will complete these assessments as follows, prior to the other study assessments; see 
also the SoA (Section 1.3):

Electronic diary (completed at home):
o
Pruritus NRS (daily)
o
Sleep-Loss (daily)
o
Skin Pain NRS (daily)
o
POEM (weekly)

Electronic tablet (provided at the site): 

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o
PROMIS® Anxiety
o
PROMIS® Depression
8.1.3.1.
Pruritus Numeric Rating Scale (NRS)
Participants will assess pruritus using a Pruritus NRS. The Pruritus NRS is an 11-point scale 
used by patients to rate their worst itch severity over the past 24 hours, with 0 indicating “No 
itch” and 10 indicating “Worst itch imaginable.”
Participants will record the pruritus assessments daily using an electronic diary at home. As 
indicated in the SoA (Section 1.3), initial electronic diary entries for Pruritus NRS should be 
completed a minimum of 4 of 7 days before randomization.
8.1.3.2.
Sleep-Loss
Participants will assess their Sleep-Loss due to pruritus. They will rate their sleep based on a 
5-point Likert scale: 0 (not at all) to 4 (unable to sleep at all). 
Participants will record their Sleep-Loss assessments daily using an electronic diary at home. As 
indicated in the SoA (Section 1.3), initial electronic diary entries for Sleep-Loss should be 
completed a minimum of 4 of 7 days before randomization.
8.1.3.3.
Skin Pain Numeric Rating Scale (NRS)
Skin Pain NRS (Newton et al. 2019) is a patient-administered, validated, 11-point horizontal 
scale anchored at 0 and 10, with 0 representing “no pain” and 10 representing “worst pain 
imaginable.” Overall severity of a patient’s skin pain is indicated by selecting the number that 
best describes the worst level of skin pain in the past 24 hours.
Participants will record the Skin Pain NRS assessments daily using an electronic diary at home.
As indicated in the SoA (Section 1.3), initial electronic diary entries for Skin Pain NRS should 
be completed a minimum of 4 of 7 days before randomization.
8.1.3.4.
Patient-Oriented Eczema Measure (POEM)
The POEM (Charman et al. 2004) is a 7-item, validated questionnaire used by the patient to 
assess disease symptoms over the last week. The patient is asked to respond to 7 questions on:

skin dryness

itching

flaking

cracking

sleep loss

bleeding, and 

weeping. 
All 7 answers carry equal weight with a total possible score from 0 to 28 (answers scored as: No 
days = 0; 1‒2 days = 1; 3–4 days = 2; 5‒6 days = 3; everyday = 4). A high score is indicative of 
a poor quality of life. 
Participants will capture the POEM responses weekly using an electronic diary at home.

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8.1.3.5.
Patient-Reported Outcomes Measurement Information System (PROMIS®): 
Anxiety and Depression 
Patient-Reported Outcomes Measurement Information System is a set of person-centered 
measures that evaluates and monitors patient’s physical, mental, and social health (PROMIS 
WWW). 
The PROMIS® measures used in this study include Anxiety and Depression short forms, which 
assess the patients’ symptoms over the previous week.
Participants will complete the PROMIS measures on an electronic tablet on site (see the SoA for 
frequency; Section 1.3).
PROMIS® Anxiety
This trial uses the PROMIS Short Form v1.0 – Anxiety -8a. The PROMIS® Anxiety short form 
assesses the following items (PROMIS Anxiety 2019):
●self-reported fear (fearfulness, panic)
●anxious misery (worry, dread)
●hyperarousal (tension, nervousness, restlessness), and
●somatic symptoms related to arousal (racing heart, dizziness). 
Each question has 5 response options, with scores ranging from 1 to 5. The total scores range 
from 8 to 40, with the higher score indicating a higher level of anxiety.
PROMIS® Depression
This trial uses PROMIS Short Form v1.0 – Depression 8b. The PROMIS® Depression short form
assesses the following items (PROMIS Depression 2019):
●self-reported negative mood (sadness, guilt)
●views of self (self-criticism, worthlessness)
●social cognition (loneliness, interpersonal alienation), and
●decreased positive affect and engagement (loss of interest, meaning, and purpose). 
Somatic symptoms (such as changes in appetite or sleeping patterns) are not included. This helps 
eliminate potential confounding effects of these items when assessing participants with comorbid 
physical conditions.
Each question has 5 response options, with scores ranging from 1 to 5. The total scores range 
from 8 to 40, with the higher score indicating a higher level of depression.

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8.2.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA (Section 1.3).
8.2.1.
Physical Examinations
A complete physical examination will cover general appearance and the following body parts 
and systems:

dermatological

head

ears

eyes

nose

throat

respiratory

cardiovascular

abdominal

neurological

musculoskeletal, and

lymphatic.
Height and weight will also be recorded. 
At subsequent study visits, a symptom-directed physical examination may be conducted at the 
discretion of the investigator. Findings will be recorded as medical history or AE in the eCRF.
8.2.2.
Vital Signs
Vital signs, including body temperature, respiratory rate (breaths per minute), pulse (beats per 
minute), and blood pressure (mmHg), will be obtained with the participant in the seated position, 
after sitting for at least 5 minutes. Any abnormal findings that are new or worsened in severity 
and 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.
Clinical Safety Laboratory Assessments
See Appendix 10.2 for the list of clinical laboratory tests to be performed and to the SoA for the 
timing and frequency.
Reviewing and recording test results
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 eCRF. 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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Repeat testing after clinically significant abnormal findings
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 10.2, must 
be conducted in accordance with the laboratory manual and the SoA.
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 (e.g., SAE or AE or dose 
modification), then the clinically significant results will be reported as an AE in the AE 
section of the eCRF.
Blinding of laboratory test results
Laboratory results that could unblind the study will not be reported to investigative sites or other 
blinded personnel (Appendix 10.2).
8.2.3.1.
Pregnancy Testing
Pregnancy testing is to be performed on WOCBP. Participants who are pregnant will be 
discontinued from the study (Section 7.2).
Visits and times
Serum pregnancy test will be done at screening only, and results will be confirmed by the central 
laboratory, as stated in Appendix 10.2.
Urine pregnancy testing will be performed locally at visits specified in the SoA (Section 1.3). If 
the specified visit includes study drug administration, the urine pregnancy test must be 
“negative” within 24 hours before the study drug is administered.
Urine pregnancy testing may be performed at additional time points during the study treatment 
period and/or follow-up period, at the discretion of the investigator or if this is required by local 
regulations.
8.2.4.
Systemic Hypersensitivity Reactions
Many drugs, but particularly biologic agents, carry the risk of systemic hypersensitivity 
reactions. Vaccines may be associated with such hypersensitivity reactions, as well. 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 the study intervention. It is recommended that 

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participants who experience a systemic hypersensitivity reaction be treated per national and 
international guidelines.
In the case of generalized urticaria or anaphylaxis, additional blood and urine samples should be 
collected as described in Appendix 10.5. Laboratory results are provided to the sponsor via the 
central laboratory.
8.2.5.
Hepatitis B Testing and Monitoring
Initial testing for HBV infection includes (CDC WWW):

hepatitis B surface antigen (HBsAg)

hepatitis B core (anti-HBc), and 

hepatitis B surface antibody (anti-HBs).
If …
Then …
HBsAg is positive
the participant is excluded.
HBsAg is negative and anti-HBs is positive 
(regardless of anti-HBc result)
OR
HBsAg, anti-HBs, and anti-HBc are all 
negative
the participant is not excluded.
anti-HBc is positive
and
HBsAg and anti-HBs are negative
further testing for HBV DNA is required:

If the screening HBV DNA is positive, the participant is 
excluded.

If the screening HBV DNA is negative, the participant is not 
excluded. Repeat testing for HBV DNA is required at least 
every 3 months during the study (Section 1.3), with 
temporary withholding or permanent discontinuation of study 
intervention if HBV DNA is positive, as described in 
Sections 7.1.1 and 7.1.2, respectively.
Management of enrolled participants with detectable HBV DNA during the study
See Sections 7.1.1 and 7.1.2.
8.2.6.
Hepatitis C Testing and Monitoring
Initial testing for HCV infection includes testing for antibodies to HCV:
If anti-HCV is positive, a serum test for circulating HCV RNA is required.
If HCV RNA test is negative, the participant is not excluded.
If HCV RNA test is positive, the participant is excluded (see Section 5.2).

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Participants who have had HCV infection and been successfully treated, defined as a sustained 
virologic response (HCV RNA by PCR negative for at least 24 weeks following treatment 
completion) are not excluded on the basis of HCV as long as HCV RNA test is negative at 
screening.
If HCV RNA is detected during the study, the study drug will be permanently discontinued 
(Section 7.1.2), and the participant should receive appropriate follow-up medical care.
8.2.7.
Hepatic Safety Monitoring
Close hepatic monitoring
The laboratory tests listed in Appendix 10.6, including ALT, AST, ALP, TBL, direct bilirubin, 
gamma-glutamyl transferase (GGT), and creatine kinase (CK), should be repeated within 48 to 
72 hours, to confirm the abnormality and to determine whether it is increasing or decreasing, if 
these conditions occur:
If a participant with baseline... 
has the following elevations:
ALT or AST <1.5 times ULN
ALT or AST ≥3 times ULN
ALP <1.5 times ULN
ALP ≥2 times ULN
TBL <1.5 times ULN
TBL ≥2 times ULN
ALT or AST ≥1.5 times ULN
ALT or AST ≥2 times baseline
ALP ≥1.5 times ULN
ALP ≥2 times baseline
TBL ≥1.5x ULN 
TBL ≥2x baseline (except for patients with Gilbert’s 
syndrome)
If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for the 
possible causes of the abnormal liver tests should be initiated by the investigator in consultation 
with the sponsor’s designated medical monitor. At a minimum, this evaluation should include a 
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 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 lab results stabilize. Monitoring of ALT, AST, ALP, and 
TBL should continue until levels normalize or return to approximate baseline levels.

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Comprehensive hepatic evaluation
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
these conditions occur:
If a participant with baseline...
has the following elevations:
ALT or AST <1.5 times ULN
ALT or AST ≥3 times ULN with hepatic signs/symptoms*, or
ALT or AST ≥5 times ULN
ALP <1.5 times ULN
ALP ≥3 times ULN
TBL <1.5 times ULN
TBL ≥2 times ULN
ALT or AST ≥1.5 times ULN
ALT or AST ≥2 times baseline with hepatic signs/symptoms*, or
ALT or AST ≥3 times baseline
ALP ≥1.5 times ULN
ALP ≥2 times baseline
TBL ≥1.5x ULN 
TBL ≥1.5x baseline (except for patients with Gilbert’s syndrome)
* Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, 
fever, and/or rash.
At a minimum, this evaluation should include a physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time INR (PT-INR); viral hepatitis A, 
B, C, and E; tests for autoimmune hepatitis, and an abdominal imaging study (for example, 
ultrasound or CT scan).
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the sponsor’s 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 ethylglucuronide, and serum 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/ 
gastroenterologist consultation, magnetic resonance cholangiopancreatography (MRCP), 
endoscopic retrograde cholangiopancreatography (ERCP), cardiac echocardiogram, or a liver 
biopsy.
8.2.7.1.
Additional Hepatic Data Collection in Participants Who Have Abnormal Liver 
Tests During the Study
Additional hepatic safety data collection (hepatic safety eCRF) should be performed for 
participants who meet one or more of the following conditions:
●Elevation of serum ALT to ≥5 times ULN on two or more consecutive blood tests (if 
baseline ALT <1.5 times ULN)
○In participants with baseline ALT ≥1.5 times ULN, the threshold is ALT ≥3 times 
baseline on 2 or more consecutive tests.
●Elevated TBL to ≥2 times ULN (if baseline TBL <1.5 times ULN) (except for cases of 
known Gilbert’s syndrome)
○In participants with baseline TBL ≥1.5 times ULN, the threshold should be TBL ≥2 
times baseline.

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●Elevation of serum ALP to ≥2 times ULN on two or more consecutive blood tests (if 
baseline ALP <1.5 times ULN)
○In participants with baseline ALP ≥1.5 times ULN, the threshold is ALP ≥2 times 
baseline on two or more consecutive blood tests.
●Hepatic event considered to be a SAE
●Discontinuation of study drug due to a hepatic event (Section 7.1.2)
Note that the interval between the two consecutive blood tests should be at least 2 days.
8.2.8.
Serious Infections and Opportunistic Infections
Completion of the Infection eCRF is required for each infection reported as an AE or SAE. The 
sponsor will identify infections considered to be opportunistic based on the article by Winthrop 
et al. (2015) (Appendix 10.7).
8.3.
Adverse Events and Serious Adverse Events
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).
Adverse events in this study will be categorized based on their relatedness either to the study 
drug or vaccine products.
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 drug or the study (see Section 7).
Product complaints are covered in Section 8.3.7.
8.3.1.
Time Period and Frequency for Collecting AE and SAE Information
Collection of AEs and SAEs
All SAEs will be collected from the time of the participant’s signing of the ICF until 
participation in study has ended.
Likewise, all AEs will be collected from the from the signing of the study ICF until participation 
in study has ended.
Adverse events that begin before the start of study intervention but after signing of the ICF will 
be recorded on the AE eCRF.

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Reporting of AEs and SAEs
Although all AEs after signing the ICF are recorded by the site in the eCRF/electronic data entry, 
SAE reporting to sponsor begins after the participant has signed the ICF and has received study 
drug. 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 10.3. 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.
8.3.2.
Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 10.3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about AE
occurrences.
8.3.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs and AESIs (as defined in Section 8.3.6) will be followed 
until resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-
up (as defined in Section 7.3). Further information on follow-up procedures is provided in 
Appendix 10.3.
8.3.4.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and investigators.
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then file 
it along with the IB and will notify the IRB/IEC, if appropriate according to local requirements.

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8.3.5.
Pregnancy
Pregnancy (maternal or paternal exposure to study drug) does not meet the definition of an AE.
However, to fulfill regulatory requirements, any pregnancy should be reported following the 
SAE process described in Appendix 10.4 to collect data on the outcome for both mother and 
fetus.
Details of all pregnancies in female participants and female partners of male participants will be 
collected after the start of study intervention and for at least 18 weeks 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 10.4.
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.3.6. Adverse Events of Special Interest
Adverse events of special interest for this study include:

conjunctivitis

herpes infection or zoster, and 

parasitic infection or an infection related to an intracellular pathogen.
If these AESIs are reported, sites will be prompted to collect additional data.
8.3.7. Product Complaints
A product complaint is any written, electronic, or oral communication that alleges a deficiency
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a
Lilly product after it is released for distribution. When the ability to use the product safely is 
impacted, the following are also product complaints: 
a.
Deficiencies in labeling information, and
b. Use errors for device or combination products due to ergonomic design elements of the 
product.
Sponsor collects product complaints on investigational products and drug delivery systems used 
in clinical studies to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements.
Complaints are also collected on comparators and other materials supplied, as required and 
instructed for the study.
Participants will be instructed to contact the investigator as soon as possible if they have a 
complaint or problem with the study drug or drug delivery system, so that the situation can be 
assessed.
Product complaints will be reported by the investigator to the sponsor per instructions provided 
on the study specific Product Complaint Form.

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8.4.
Treatment of Overdose
In case of suspected overdose, hematology, chemistry, vital signs, and oxygen saturation should 
be monitored and supportive care provided as necessary.
In the event of an overdose, the investigator should:
1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until 
lebrikizumab can no longer be detected systemically (at least 18 weeks).
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
Study visits and times
At the visits and times specified in the SoA (Section 1.3), venous blood samples will be collected 
to determine the serum concentrations of lebrikizumab. The actual date and time (24-hour clock 
time) of dosing and sample collection must be recorded accurately on the appropriate forms.
Collection, handling, and analysis of samples
Instructions for the collection and handling of biological samples will be provided by the 
sponsor. 
As stated in Appendix 10.2, samples will be analyzed at a laboratory approved by the sponsor. 
Concentrations of lebrikizumab will be assayed using a validated PK assay. Analyses of samples 
collected from participants who received placebo are not planned.
Additional and unused samples
Any excess samples collected for PK testing may be used for exploratory analyses such as 
bioanalytical methods development, assay validation or cross-validation exercises, protein 
binding, and/or metabolism work.
In the case of systemic allergic/hypersensitivity reactions, additional blood samples will be 
obtained for PK analyses (Section 8.2.4 and Appendix 10.5).
Genetic analyses will not be performed on these blood samples unless consent for this was 
included in the informed consent. Participant confidentiality will be maintained. 
Unblinding
Drug concentration information that may unblind the study will not be reported to investigative 
sites or to personnel who are blinded to study data.
Sample retention
The purpose of retention, the maximum duration of retention, and facility for long-term storage 
of samples is described in Appendix 10.1, Section 10.1.12. During the sample retention time, PK 
samples remaining after the bioanalyses may be used for exploratory analyses such as 
metabolism work, protein binding, and/or bioanalytical assay validation or bioanalytical method 
cross-validation exercises.

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8.6.
Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7.
Genetics
A whole blood sample will be collected for pharmacogenetic analysis as specified in the SoA 
(Section 1.3), where local regulations allow.
Sample use
Samples will be used only for investigations related to disease and drug or class of drugs under 
study in the context of this clinical program. They will not be used for broad exploratory 
unspecified disease or population genetic analysis. 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.
Samples will be stored, and analysis may be performed on genetic variants thought to play a role 
in AD. In the event of an unexpected AE or the observation of unusual response, the samples 
may be analyzed to evaluate a genetic association with response to lebrikizumab. These 
investigations may be limited to a focused candidate gene study or, if appropriate, genome-wide 
association studies may be performed to identify regions of the genome associated with the 
variability observed in drug response. 
Additional analyses may be conducted if it is hypothesized that this may help further understand 
the clinical data.
Confidentiality
All samples will be coded with the participant number. These samples and any data generated 
can be linked back to the participant only by the investigative site personnel. The sponsor will 
store the blood and/or DNA samples in a secure storage space with adequate measures to protect 
confidentiality.
Unblinding
Pharmacogenetic information that may unblind the study will not be reported to investigative 
sites or to personnel who are blinded to study data.
Sample retention
The samples will be retained at a facility selected by the sponsor or its designee. The samples 
will be retained as long as research on the study intervention or study indication continues, but 
no longer than the maximum retention time specified in Appendix 10.1, Section 10.1.12, or other 
period as per local requirements.
8.8.
Biomarkers
Biomarkers will not be assessed in this study.

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8.9.
Immunogenicity Assessments
Visits and times
At the visits and times specified in the SoA (Section 1.3), predose venous blood samples will be 
collected to determine the antibody production against lebrikizumab. 
The actual date and time (24-hour clock time) of each sample collection will be recorded.
To aid interpretation of these results, a predose blood sample for PK analysis will be collected at 
the same time points.
Sample collection, handling, and use
Instructions for the collection and handling of blood samples will be provided by the sponsor.
Immunogenicity will be assessed by a validated assay designed to detect anti-drug antibodies 
(ADAs) in the presence of lebrikizumab at a laboratory approved by the sponsor, as indicated in 
Appendix 10.2. Antibodies may be further characterized for their ability to neutralize the activity 
of lebrikizumab.
Unblinding
Immunogenicity test information that may unblind the study will not be reported to investigative 
sites or to personnel who are blinded to study data.
Sample retention
The purpose of retention, the maximum duration of retention, and facility for long-term storage 
of samples is described in Appendix 10.1, Section 10.1.12.
8.10.
Medical Resource Utilization and Health Economics
Not applicable to this study.

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9.
Statistical Considerations
9.1.
Statistical Hypotheses
Study KGAK is a descriptive study with no planned hypothesis testing. Confidence intervals 
(CIs) will be used to compare seroresponses for lebrikizumab- and placebo-treated participants.
9.2.
Sample Size Determination
Approximately 240 participants will be randomly assigned to study intervention (1:1 ratio for 
lebrikizumab:placebo) such that approximately 218 evaluable per protocol (PP) participants 
complete the study.
The sample size for this study was determined based on the following information:

The percentage of study participants with positive response to the tetanus vaccination at 
Week 16 is 83.7% and 83.3% for active treatment and placebo, respectively (Blauvelt et 
al. 2019). 

The percentage of study participants with human complement serum bactericidal assay
(hSBA)-Meningococcal C total seroresponse at Day 29 is 90% (Tipton et al. 2019, 
adjusted for adult population).
Assuming the observed booster response to tetanus toxoid for both lebrikizumab and placebo is 
83% at Week 16, with 109 participants per arm, the Wald 2-sided 90% CI for the difference in 
booster response is (-0.08, 0.08).
Similarly, assuming the positive antibody response to MCV for both lebrikizumab and placebo is 
90% at Week 16, with 109 participants per arm, the Wald 2-sided 90% CI for the difference in 
booster response is (-0.07, 0.07).
9.3.
Populations for Analyses
The following participant populations are defined:
Population
Description
Intent-to-Treat (ITT)
All participants assigned to study drug, regardless of whether they 
take any doses of study drug, or if they took the correct study drug.
Participants will be analyzed according to the treatment group to 
which they were randomly assigned.
Per Protocol (PP)
All participants in the safety population who complete the 
Week 16 (Visit 10) evaluation without any significant protocol 
violations.
Safety
All participants randomly assigned to study drug and who take at 
least 1 dose of study drug. Participants will be analyzed according 
to the study drug they actually received.
Pharmacokinetic Analysis
All randomized participants who received at least 1 full dose of 

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study drug and at least 1 postbaseline evaluable PK sample.
Immunogenicity Analysis
A participant is evaluable for treatment-emergent ADA if there is 
at least 1 non-missing test result for ADA for both the baseline and 
the postbaseline visits.
Abbreviations: ADA = anti-drug antibody; PK = pharmacokinetic.
The PP population will include participants in the safety population without significant protocol 
deviations (i.e., any participant or investigator activity that could have possibly interfered with 
the therapeutic administration of the study drug or the precise evaluation of the study drug
efficacy). Significant protocol deviations include the following:

Used prohibited treatment that required permanent discontinuation of the study drug (see 
Section 7.1.2) 

Missed either one or both Week 12 or Week 16 study visits (Visits 8 and 10)

Have not been compliant with the dosing regimen (i.e., participants must receive 80% of 
the expected injections of study drug and both of the vaccines during participation in the 
study)

Exceeded the out-of-the-visit window at the Week 16 visit (Visit 10) by more than ±7
days
Additional significant protocol deviations may be specified in the Statistical Analysis Plan (SAP) 
prior to unblinding. 
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 
statistical processing will be performed using SAS® unless otherwise stated. The primary 
analysis of the co-primary endpoints will be performed for the PP participant population when all 
participants have completed Week 16. Analysis of the co-primary, secondary, and exploratory 
endpoints will be performed for the ITT participant population.
Descriptive statistics will be provided for all efficacy and safety endpoints. For categorical 
endpoints, the number and percentage of participants in each category will be presented. For 
continuous endpoints, descriptive statistics will include the following:

the number of participants

mean

standard deviation (SD)

median

minimum, and 

maximum. 
Participants’ baseline characteristics related to efficacy analyses will be provided with 
descriptive statistics for each treatment group.
The Pruritus NRS weekly mean will be calculated as follows: 

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
The mean of each participant’s baseline and post-baseline Pruritus NRS scores will be 
computed for each week based on the previous 7 days. 

The weekly mean will be calculated if a participant has responses for Pruritus NRS on at 
least 4 of the 7 days of the week. 
If the participant has 3 or fewer Pruritus NRS responses, the mean value for that item will be 
considered missing. All Pruritus NRS efficacy endpoint analyses will be conducted on the 
weekly mean. 
The Sleep-Loss weekly mean will be calculated similar to the Pruritus NRS weekly mean. All 
Sleep-Loss efficacy endpoint analyses will be conducted on the weekly mean.
The number of participants in each analysis set will be summarized. Reasons for study drug 
discontinuation and for study discontinuation during the treatment period will be summarized 
using frequencies and percentages by treatment group.
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the SAP and the clinical study report.
Additional exploratory analyses of the data may be conducted as deemed appropriate. The SAP
will be finalized prior to unblinding. It will include a more technical and detailed description of 
the statistical analyses described in this section.
9.4.1.1.
Participant Disposition
A detailed description of participant disposition will be provided, including a summary of the 
number and percentage of participants entered into the study and randomized, and number and 
percentage of participants who complete or discontinue the study or the study drug, both overall 
and by reason for discontinuation. A summary of important and significant protocol deviations 
will be provided.
9.4.1.2.
Participant Characteristics
Demographic data are collected and summarized to demonstrate that the study population 
represents the target participant population. A summary of demographic data, baseline 
participant characteristics, historical diagnoses, preexisting conditions, and prior therapies will 
be summarized by treatment group using descriptive statistics. Other participant characteristics 
will be summarized by treatment group as deemed appropriate.
9.4.1.3.
Concomitant Therapy
Previous and concomitant medications 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. 

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9.4.1.4.
Exposure and Compliance
The extent of exposure to study drug in each treatment group will be summarized by total 
number of days of exposure, total number of injections, number of missed injections, and 
number and percentage of participants who are compliant. 
The total number of vaccines of each type in each treatment group will be summarized by the 
total number of vaccines.
A participant will be considered compliant with the dosing regimen if the participant received 
100% of the expected number of study drug injections and vaccines while enrolled in the study.
9.4.2.
Co-Primary Analyses 
The co-primary endpoints, as described in Section 3, will be analyzed for the PP participant
population to compare the percentages of lebrikizumab-treated and placebo-treated participants
using the methods for categorical endpoints described in Section 9.4.1. In addition, a 90% CI for 
the difference between treatment groups will be constructed using the stratified Newcombe 
approach (Yan and Su 2010; Kim and Won 2013). Missing values will not be imputed.
9.4.3.
Secondary Analyses
Descriptive statistics, as described in Section 9.4.1, will be provided for the ITT participant 
population for the efficacy and quality-of-life measures described in Section 3.
For the anti-tetanus toxoid IgG antibody concentration and Meningococcal Group C serum 
bactericidal antibodies, the pre- and post-vaccination geometric mean titers will be analyzed.
9.4.3.1.
Missing Data
The method of handling missing efficacy data will be as follows for endpoints:
Percentage of participants at Week 16 achieving:

an IGA score of 0 or 1 and a reduction of ≥2 points from baseline

≥75% reduction from baseline in EASI score (EASI-75)

≥90% reduction from baseline in EASI score (EASI-90)

≥4-point improvement from baseline in Pruritus NRS score in participants with baseline 
score of ≥4
For participants who receive systemic rescue treatment or withdraw from the study due to lack of 
efficacy, values should be set to the participant’s baseline value subsequent to this time through 
Week 16. The Markov Chain Monte Carlo (MCMC) multiple imputation will be used to handle 
the remaining missing data. Imputation will be conducted within each treatment group 
independently so the pattern of missing observations in one treatment group cannot influence the 
missing value imputation in the other treatment group. For each imputation process, 25 datasets 
with imputations will be calculated. Each complete data set will be analyzed with the specified 
analysis. The results from these analyses will be combined into a single inference using SAS 
PROC MIANALYZE.
For binary responses related to EASI and IGA, the binary response variables will be calculated 
based on the multiply imputed datasets that have been created. Because the MCMC algorithm is 

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based on the multivariate normal model, imputed values for IGA will not generally be one of the 
discrete values used in IGA scoring (0, 1, 2, 3, or 4). Therefore, to derive the binary IGA 
response variable, standard rounding rules will be applied to the imputed values. For example, if 
a participant has an IGA score imputed as 1.4 (and assuming a baseline IGA score of 3), the 
imputed value would be rounded down to 1, and the minimum change from baseline of 2 would 
have been met. This participant would be considered a responder. For derivation of an EASI-75 
and EASI-90 responses, no rounding will be performed. 
The imputed Week 16 EASI value will be compared directly to the observed baseline EASI 
value to determine whether a reduction of at least 75% was achieved for EASI-75. The imputed 
Week 16 EASI value will be compared directly to the observed baseline EASI value to 
determine whether a reduction of at least 90% was achieved for EASI-90. Imputation of 
continuous data will be analogous to that of binary variables; details will be provided in the SAP.
A total of 2 random seeds will be needed to impute IGA for the 2 treatment groups. The 2 seeds 
have been pre-specified by a random-number generator:

IGA: Lebrikizumab 250 mg Q2W: Seed = 970309630

IGA: Placebo Q2W: Seed = 1477266806
A total of 2 random seeds will be needed to impute Pruritus NRS for the 2 treatment groups. The 
2 seeds have been prespecified by a random-number generator:

NRS: Lebrikizumab 250 mg Q2W: Seed = 1611917356

NRS: Placebo Q2W: Seed = 1087836192
A total of 2 random seeds will be needed to impute EASI for the 2 treatment groups. Those 2 
random seeds have been prespecified by using a random-number generator:

EASI: Lebrikizumab 250 mg Q2W: Seed = 353985587

EASI: Placebo Q2W: Seed = 1828572477 
9.4.4.
Exploratory Analyses
Exploratory analyses will be described in detail in the SAP that is finalized prior to unblinding.
9.4.5.
Safety Analyses
All AEs occurring during the study will be recorded and coded using the MedDRA dictionary. 
Treatment-emergent AEs (TEAEs) are defined as AEs with an onset date on or after the date of 
the first injection of study drug. TEAEs will be summarized by treatment group, including the 
number of participants reporting an event, system organ class, preferred term, severity, 
relationship to study drug, and seriousness for the safety population. All SAEs as well as AEs 
that led to study discontinuation will be listed by participant.
9.4.6.
Pharmacokinetic Analyses
Lebrikizumab PK data will be summarized using descriptive statistics. 
Data from this study may 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 

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safety outcomes. In this case, a separate PK analysis plan will be developed, and the results of 
these analyses will be described in a separate PK report.
9.4.7.
Immunogenicity Data Analysis 
The ADA variables will be analyzed using descriptive statistics. Drug concentration data will be 
examined and the influence of ADAs on individual concentration-time profiles will be evaluated. 
Assessment of impact of ADA on safety and efficacy may be provided.
Listings and appropriate summary statistics will be provided for immunogenicity data. The 
frequency and percentage of participants with preexisting ADA and with treatment-emergent 
ADAs (TE-ADAs) to lebrikizumab may be tabulated.
Participants with TE-ADA 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 participants with TE-ADA.
The relationship between the presence of antibodies and the PK parameters and drug response 
(including safety and efficacy) to lebrikizumab may be assessed.
9.4.8.
Other Analyses
Subgroup analyses will be conducted for the co-primary endpoints for the ITT participant
population. Subgroups for the ITT participant population to be evaluated may include age, sex, 
race, and other as deemed appropriate.
Definitions of the subgroups and any subgroup-specific analyses will be provided in the SAP.
All subgroup analyses will be considered exploratory.
9.5.
Interim Analyses 
No interim statistical analyses prior to participants’ completing the Week 16 visit are planned for 
this study.
A database lock and unblinding will occur, and the primary analysis will be performed at the 
time (that is, a cut-off date) the last participant completes Week 16 or the ET visit of Study 
KGAK. This database lock will include all data collected by the cut-off date.
The final database lock and analyses will then be conducted after all the participants have 
completed the follow-up period of Study KGAK.
Depending on the regulatory submission timeline, the primary and final database locks may be 
combined; that is, one final database lock will occur after all the participants have either 
completed the follow-up period of Study KGAK, or discontinued the study early or entered the 
long-term extension study (DRM06-AD07/J2T-DM-KGAA).
Unblinding details are specified in the Unblinding Plan section of the SAP or in a separate
unblinding plan document.

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9.6.
Data Monitoring Committee (DMC)
The DSMB used across the lebrikizumab program will be used in this study. A DSMB is a type 
of DMC.
For details on the DSMB, refer to Appendix 10.1, Section 10.1.5.

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10.
Supporting Documentation and Operational Considerations
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
10.1.1.
Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines

Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines

Applicable laws and regulations
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., advertisements) 
must be submitted to an IRB/IEC by the investigator and reviewed and approved by the IRB/IEC
before the study is initiated.
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC

Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures

Providing oversight of study conduct for participants under their responsibility 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.
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 
authorized representative will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study center.
The medical record must include a statement that written informed consent was obtained before 
the participant was entered in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF.
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study.
A copy of the ICF(s) must be provided to the participant or the participant’s legally authorized 
representative and is kept on file.
Participants who are rescreened are required to sign a new ICF and will be assigned a new 
participant number.
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 law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent.
The participant must be informed that 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.
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.
Committee Structure
As stated in Section 9.6, the DSMB used in this study is the same DSMB used across the 
lebrikizumab program.
This independent DSMB is comprised of members who are independent of the study sponsor and 
study investigators. This committee will monitor participant safety by conducting formal reviews 
of accumulated safety data that is blinded by treatment group. If requested, the DSMB may have 
access to the treatment allocation code or any other requested data for the purposes of a risk-
benefit assessment.

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The DSMB 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 
DSMB 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 DSMB are described in the Lilly DSMB charter.
10.1.6.
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 trial, after 
anonymization, with the exception of PK or genetic data. Data are available to request 6 months 
after the indication studied has been approved in the US and EU and after primary publication 
acceptance, whichever is later. No expiration date of data requests is currently set once data are 
made available.
Access is provided after a proposal has been approved by an independent review committee 
identified for this purpose and after receipt of a signed data sharing agreement. Data and 
documents, including the study protocol, SAP, clinical study report, blank or annotated CRFs, 
will be provided in a secure data sharing environment for up to 2 years per proposal.
For details on submitting a request, see the instructions provided at www.vivli.org.
10.1.7.
Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. Source data might include laboratory tests, medical records, 
and clinical notes.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities and requirements, including handling of noncompliance issues and monitoring 
techniques are provided in the Monitoring Plan.
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data.
The sponsor assumes accountability for actions delegated to other individuals (e.g., Contract 
Research Organizations).

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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 Clinical Trial Agreement (CTA) 
unless local regulations or institutional policies require a longer retention period. No records may 
be destroyed during the retention period without the written approval of the sponsor. No records 
may be transferred to another location or party without written notification to the sponsor.
In addition, sponsor or its representatives will periodically check a sample of the participant data 
recorded against source documents at the study site. The study may be audited by sponsor or its 
representatives, and/or regulatory agencies at any time. Investigators will be given notice before 
an audit occurs.
Data Capture System
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor.
An electronic data capture system (EDC) will be used in this study for the collection of eCRF 
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 eCRF.
Additionally, electronic Clinical Outcome Assessment (eCOA) data (participant-focused 
outcome instrument) will be directly recorded by the participant (electronic patient diary and 
electronic tablet on site) or investigator site personnel (electronic tablet on site). 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 sites. 
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 electronic transfers will be provided to the investigator 
for review and retention. Data will subsequently be transferred from the central vendor to the 
sponsor data warehouse.
Data from complaint forms submitted to sponsor will be encoded and stored in the global 
product complaint management system.
10.1.8.
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.

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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 10.1.7.
10.1.9.
Study and Site Start and Closure
The study start date is the date on which the clinical study is open for recruitment of participants.
The study or a study site will be discontinued if the sponsor or its designee judges it necessary 
for medical, safety, regulatory, or other reasons consistent with applicable laws, regulations, and 
GCP. 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 drug 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.
10.1.10.
Publication Policy
In accordance with the sponsor’s publication policy the results of this study will be submitted for 
publication by a peer-reviewed journal.
10.1.11.
Investigator Information
Physicians with a specialty in dermatology will participate as investigators in this clinical trial.
Physicians and other qualified healthcare professionals with other specialties and experience in 
treatment of patients with AD may also participate as investigators.
10.1.12.
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.

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Sample Type
Custodian
Retention Period After Last 
Participant Visita
PK
Sponsor or Designee
Up to 1 year
Pharmacogenetics
Sponsor or Designee
Up to 7 years
Immunogenicity
Sponsor or Designee
Up to 15 years
a Retention periods may differ locally.

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10.2.
Appendix 2: Clinical Laboratory Tests
The tests detailed in the table below will be performed by the central laboratory or by the local 
laboratory, as specified in the table.
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 SoA 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
Comments
Hematology
Assayed by Lilly-designated laboratory.
Hemoglobin
Hematocrit
Erythrocyte count (RBCs - Red Blood Cells)
Mean cell volume 
Mean cell hemoglobin
Mean cell hemoglobin concentration 
Leukocytes (WBCs - White Blood Cells) 
Differential
Neutrophils, segmented
Lymphocytes
Monocytes
Eosinophils
Basophils
Platelets
Cell morphology (RBCs and WBCs)
Clinical Chemistry
Assayed by Lilly-designated laboratory.
Sodium
Potassium
Chloride
Bicarbonate
Total bilirubin
Direct bilirubin
Indirect bilirubin
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Gamma-glutamyl transferase (GGT)
Blood urea nitrogen (BUN)
Creatinine 
Uric acid
Total protein
Albumin

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Clinical Laboratory Tests
Comments
Calcium
Phosphorus
Glucose
Total cholesterol 
Lactic dehydrogenase (LDH)
Urinalysis
Assayed by Lilly-designated laboratory.
Specific gravity
pH
Protein
Glucose
Ketones
Bilirubin
Urobilinogen
Blood
Nitrite
Urine leukocyte esterase
Hormones (female)
Serum Pregnancy 
Assayed by Lilly-designated laboratory.
Urine Pregnancy
Evaluated locally.
Serology
Assayed by Lilly-designated laboratory.
HIV testing
Assayed by Lilly-designated laboratory.
Hepatitis C Virus (HCV) testing:
Assayed by Lilly-designated laboratory. 
HCV antibody 
HCV RNA
Hepatitis B Virus (HBV) testing: 
Assayed by Lilly-designated laboratory.
HBV DNA
Hepatitis B core antibody (Anti-HBc) 
Hepatitis B surface antigen (HBsAg) 
Hepatitis B surface antibody (anti-HBs)

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Clinical Laboratory Tests
Comments
Immunoglobulins
Assayed by Lilly-designated laboratory. 
Total immunoglobulin G (IgG)
Total immunoglobulin A (IgA)
Vaccine Seroresponse
Assayed by Lilly-designated laboratory. Results will 
not be provided to the investigative sites.
Anti-tetanus toxoid IgG antibody
Meningococcal Group C serum bactericidal antibodies 
(human complement serum bactericidal assay [hSBA])
Pharmacokinetic Samples: lebrikizumab
concentration
Assayed by Lilly-designated laboratory. Results will 
not be provided to the investigative sites.
Pharmacogenetic sample
Assayed by Lilly-designated laboratory. Results will 
not be provided to the investigative sites.
Immunogenicity (ADA) Samples
Assayed by Lilly-designated laboratory. Results will 
not be provided to the investigative sites.
Anti-lebrikizumab antibodies 
Anti-lebrikizumab neutralizing antibodies
ADA = antidrug antibody.

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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 (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the investigator (i.e., not related to progression of underlying 
disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdose should be reported regardless of sequelae.
Events NOT Meeting the AE Definition

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 (e.g., endoscopy, appendectomy): the condition that leads 
to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

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
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.3.2.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., 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 pre-existing condition that did not worsen from 
baseline is not considered an AE.
d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (e.g., 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

Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs.

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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 AE and/or SAE
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event.

The investigator will then record all relevant AE information in the eCRF and the SAE 
information, on a paper form.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to sponsor or designee in lieu of completion of the AE eCRF page and SAE paper 
form.

There may be instances when copies of medical records for certain cases are requested by 
sponsor or designee. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to sponsor or designee.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to 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 

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

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10.3.4.
Reporting of SAEs
SAE Reporting via Paper CRF

The primary mechanism for reporting an SAE will be a study-specific paper SAE form 
that will be provided to the site.

The paper SAE forms will be transmitted to the sponsor by a sponsor-designated 
method(s). 

Site staff must alert Lilly Global Patient Safety, or its designee, of any SAE within 
24 hours of investigator awareness of the event via a sponsor-approved method.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE form within the designated reporting time frames.

Contacts for SAE reporting can be found on the SAE form.

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10.4.
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information
10.4.1.
Definitions
Woman of Childbearing Potential (WOCBP)
A WOCBP is defined a postmenarcheal female, who has not reached a postmenopausal state 
(12 continuous months of amenorrhea with no identified cause other than menopause), and has 
not undergone surgical sterilization (removal of ovaries and/or uterus).
Women NOT of Childbearing Potential (non-WOCBP)
Women in the following categories are not considered WOCBP
1. Premenarchal
2. Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
NOTE: Documentation can come from the site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview.
3. Postmenopausal female is defined as, women with:

12 months of amenorrhea for women >55, with no need for follicle stimulating 
hormone (FSH)

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 (e.g. oral contraceptives, hormones, gonadotropin releasing hormone, 
anti-estrogens, selective estrogen receptor modulators [SERMs], or chemotherapy 
that induced amenorrhea)
10.4.2.
Contraception Guidance
See inclusion criterion [9] (Section 5.1) for requirements for female and male contraception.
10.4.3.
Collection of Pregnancy Information
Male participants with partners who become pregnant
The investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study. 
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 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

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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 to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, including 
fetal status (presence or absence of anomalies) or indication for the procedure.
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
A spontaneous abortion (occurring at <20 weeks gestational age) or still birth (occurring at >20 
weeks gestational age) is always considered to be an SAE and will be reported as such. 
Any post-study pregnancy related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the sponsor as described in Section 8.3.4. 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 drug and be withdrawn from the study.

C O N FI D E N TI A L
Pr ot oc ol  J 2 T-M C -K G A K /D R M 0 6 -A D 1 8
8 8
1 0. 5.
A p pe n di x 5 : Rec o m me n de d L a b or at or y Testi n g f or S yste mic 
H y perse nsiti vit y E ve nts
La b orat or y  testi n g s h o uld be perf or m e d at t he ti me of a s yste mic h y perse nsit i vity e ve nt. 
I mp orta nt i nf or m at i on a b o ut w h y , w he n, a n d w hat t o test f or is pr o vide d bel o w. T he 
ma na ge me nt of t he A E ma y  warra nt la b orat or y testi n g be yo n d t hat descri be d bel o w a n d s h o ul d 
be perf or m e d as cli nicall y in dicate d.
La b orat or y  testi n g d uri n g a s yste mic h y perse nsiti vity e ve nt is n ot perf or me d f or dia g n ostic 
p ur p oses. Its i nte nt is se veral f o l d:

T o hel p c haracteri ze a n d classif y s yste mic h y perse nsiti vity reactio ns

T o m eet re g ulat or y e x pectatio ns

T o i m pr o ve s u bse q ue nt cli nical ma na ge me nt b y  hel pi n g t o disti n g uis h bet wee n t he vari o us 
mec ha nist ic bases of a na p h yla xis
W he n s h o ul d l a b or at ory tests be o bt ai ne d ?

I n t he prese nce of ge neralize d urticaria or if a na p h yla xis is s us pecte d

After t he partici pa nt has bee n sta bilize d, o btai n a sa m ple wit hi n 1 -2 h o urs of t he e ve nt; 
h o we ver, sa m ples ma y  be o btai ne d as late as 1 2 h o urs after t he e ve nt as a nal ytes ca n re mai n 
altere d f or a n e xte n de d peri o d of ti me. Rec or d t he ti me at w hic h t he sa m ple was c ollecte d.

O btai n a f o ll ow- u p sa m ple at t he ne xt re g ularl y sc h e d ule d visit or after 4 wee ks, w hic he ver is 
later.
W h at l a b or at ory tests s h o ul d be o bt ai ne d ?
See t he ta ble bel o w.

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Hypersensitivity Tests
Notes
These laboratory tests are bundled in the Clinical Laboratory Operations 
Hypersensitivity Lab Testing Kit.
Selected test may be obtained in the event of anaphylaxis or systemic 
allergic/hypersensitivity reactions.
Lebrikizumab ADAs
Assayed by Lilly-designated laboratory. Results will not be provided to 
the investigative sites.
Lebrikizumab concentrations (PK)
Assayed by Lilly-designated laboratory. Results will not be provided to 
the investigative sites.
Tryptase
Assayed by Lilly-designated laboratory. Results will not be provided to 
the investigative sites.
Note: If a tryptase sample is obtained more than 2 hours after the event 
(that is, within 2 to 12 hours), or is not obtained because more than 12 
hours have lapsed since the event, obtain urine sample for N-
methylhistamine testing. Note that for tryptase serum samples obtained 
within 2 to 12 hours of the event, urine N-methylhistamine testing is 
performed in addition to tryptase testing. Collect the first void urine 
following the event. Obtain a follow-up urine for N-methylhistamine 
testing at the next regularly scheduled visit or after 4 weeks, whichever is
later.
Drug-specific IgE
Will be performed if a validated assay is available.
Assayed by Lilly-designated laboratory. Results will not be provided to 
the investigative sites.
Basophil activation test
Will be performed if a validated assay is available.
Assayed by Lilly-designated laboratory. Results will not be provided to 
the investigative sites.
Note: The basophil activation test is an in vitro cell based assay that only 
requires a serum sample. It is a surrogate assay for drug specific IgE, but is 
not specific for IgE.
Complement (C3a and C5a)
Assayed by Lilly-designated laboratory. Results will not be provided to 
the investigative sites.
Cytokine panel (IL‐6, IL‐1β, IL‐10)
Assayed by Lilly-designated laboratory. Results will not be provided to 
the investigative sites.
Anti-PLBL2 antibodies
Assayed by Lilly-designated laboratory. Results will not be provided to 
the investigative sites.
Abbreviations: ADA = anti-drug antibody; IgE = immunoglobulin E; IL = interleukin; PK = pharmacokinetic; 
PLBL-2 = Phospholipase B-Like 2.

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10.6.
Appendix 6: Liver Safety: Suggested Actions and Follow-Up 
Assessments
Hepatic evaluation testing
See Section 8.2.7 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-glutamyl transferase (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 A (IgA; quantitative)
Hepatitis A virus (HAV) testing:
Immunoglobulin G (IgG; quantitative)
HAV total antibody
Immunoglobulin M (IgM; quantitative)
HAV IgM antibody
Phosphatidylethanol (PEth)
Hepatitis 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 antibody
Anti-smooth muscle antibody (ASMA)a
HBV DNAd
Anti-actin antibodyb
Hepatitis C virus (HCV) testing:
Epstein-Barr virus (EBV) testing:
HCV antibody
EBV antibody
HCV RNAd
EBV DNAd
Hepatitis D virus (HDV) testing:
Cytomegalovirus (CMV) testing:
HDV antibody
CMV antibody
Hepatitis E virus (HEV) testing:
CMV DNAd
HEV IgG antibody
Herpes simplex virus (HSV) testing:
HEV IgM antibody
HSV (Type 1 and 2) antibody 
HEV RNAd
HSV (Type 1 and 2) DNA d
Microbiologyc
Liver kidney microsomal type 1 (LKM-1) antibody
Culture:
Blood
Urine
Abbreviation: INR = international normalized ratio.
a
Not required if anti-actin antibody is tested.
b
Not required if anti-smooth muscle antibody (ASMA) is tested.
c
Assayed ONLY by investigator-designated local laboratory; no central testing available.
d
Reflex/confirmation dependent on regulatory requirements, testing availability, or both.

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10.7.
Appendix 7: Examples of Infections That May Be Considered 
Opportunistic
The following are examples of infections that may be considered opportunistic in the setting of 
biologic therapy (adapted from Winthrop et al. [2015]). This table is provided to aid the 
investigator in recognizing infections that may be considered opportunistic in the context of 
biologic therapy. This list is not exhaustive. Infections will be categorized by Lilly as 
opportunistic according to Opportunistic Infections and Biologic Therapies in Immune-Mediated 
Inflammatory Diseases: Consensus Recommendations for Infection Reporting during Clinical 
Trials and Postmarketing Surveillance by Winthrop et al. (2015).

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Examples of Infections That May Be Considered Opportunistic in the Setting of Biologic 
Therapy
Bacterial
Bartonellosis (disseminated disease only)
Campylobacteriosis (invasive disease only)
Legionellosis
Listeriosis (invasive disease only)
Nocardiosis
Tuberculosis
Non-tuberculous mycobacterial disease 
Salmonellosis (invasive disease only) 
Shigellosis (invasive disease only)
Vibriosis (invasive disease due to Vibrio vulnificus)
Viral
BK virus disease including polyomavirus-associated nephropathy
Cytomegalovirus disease
Hepatitis B virus reactivation
Hepatitis C virus progression
Herpes simplex (invasive disease only)
Herpes zoster (any form)
Post-transplant lymphoproliferative disorder (Epstein-Barr virus)
Progressive multifocal leukoencephalopathy (PML), John Cunningham (JC) virus 
Fungal
Aspergillosis (invasive disease only)
Blastomycosis
Candidiasis (invasive disease or oropharyngeal, esophageal. Not isolated lingual)
Coccidioidomycosis
Cryptococcosis
Histoplasmosis
Paracoccidioides infections
Penicilliosis
Pneumocystosis
Sporotrichosis
Other invasive molds: Mucormycosis (zygomycosis) (Rhizopus, Mucor, and Lichtheimia), 
Scedosporium/Pseudallescheria boydii, Fusarium
Parasitic
Leishmaniasis (visceral only)
Strongyloidiasis (hyperinfection syndrome or disseminated disease)
Microsporidiosis
Toxoplasmosis
Trypanosoma cruzi infection (Chagas disease progression) (disseminated disease only)
Cryptosporidiosis (chronic disease only)
Source: Adapted from Winthrop et al. (2015).

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10.8.
Appendix 8: American Academy of Dermatology Consensus Criteria 
for Chronic Atopic Dermatitis
Atopic dermatitis: Diagnosis recommendations
Patients with presumed AD should have their diagnosis based on the criteria summarized below. 
On occasion, skin biopsy specimens or other tests (such as serum immunoglobulin E, potassium 
hydroxide preparation, patch testing, and/or genetic testing) may be helpful to rule out other or 
associated skin conditions.
Level of Evidence: III Strength of Recommendation: C
Essential features — must be present:

Pruritus 

Eczema (acute, subacute, chronic)

Typical morphology and age-specific patterns*

Chronic or relapsing history
*Patterns include:

Facial, neck, and extensor involvement in infants and children

Current or previous flexural lesions in any age group

Sparing of the groin and axillary regions
Important features — seen in most cases, adding support to the diagnosis:

Early age of onset

Atopy

Personal and/or family history

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 (e.g., facial pallor, white dermographism, delayed blanch 
response)

Keratosis pilaris/pityriasis alba/hyperlinear palms/icthyosis

Ocular/periorbital changes

Perifollicular accentuation/lichenification/prurigo lesions
Exclusionary conditions — It should be noted that a diagnosis of atopic dermatitis depends on 
excluding conditions, such as:

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
Scabies

Seborrheic dermatitis

Contact dermatitis (irritant or allergic)

Icthyoses

Cutaneous T-cell lymphoma

Psoriasis 

Photosensitivity dermatoses

Immune deficiency diseases

Erythroderma of other causes
Adapted from Eichenfield et al. 2014.

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10.9.
Appendix 9: Provisions for Changes in Study Conduct During 
Exceptional Circumstances
Exceptional circumstances, such as pandemics or natural disasters, may cause disruptions to the 
conduct of the study. These disruptions may limit the ability of the investigators, participants, or 
both to attend on-site visits or to conduct planned study procedures.
In an exceptional circumstance, after receiving the sponsor’s written approval, sites may 
implement changes if permitted by local regulations. Such changes are intended to mitigate risks 
of participants missing visits, allow participants to continue safely in the study, and maintain the 
data integrity of the study. GCP compliance and minimization of risk to study integrity are 
important considerations. Ensuring the safety of study participants is the prevailing 
consideration.
Once restrictions are lifted, the sponsor will notify sites that these provisions for changes in study 
conduct will be reversed and routine study conduct restored.
The following changes in study conduct captured in this Appendix will not be considered 
protocol deviations. Missing data will be captured as protocol deviation(s). Changes in study 
conduct not described in this Appendix, or not consistent with applicable local regulations, are 
not allowed.
Informing ethical review boards (ERBs)
Ethical review boards and regulatory bodies 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.
Remote visits
Under exceptional circumstances, some of the study visits may be conducted remotely (in 
addition to the remote visits already allowed by the study design). Remote visits may be 
conducted virtually and/or as mobile health care visits, if permitted by local laws and regulations 
(see below for details).
Virtual visit (telephone/telemedicine)
Telephone or technology-assisted virtual visits (telemedicine) to complete appropriate 
assessments are acceptable. 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 in source 
documents. Assessments to be completed during a virtual visit include, but are not limited to:

AE and SAE reports

concomitant medications, and

compliance with the patient diary
Mobile health care visit
Additional consent from the participant will be obtained for those who participate in home health 
care services.

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If permitted by local regulations, mobile visits may be performed at locations other than the 
study site (e.g., participant’s home) when participants cannot travel to the site due to exceptional 
circumstances. These will be performed by a qualified home health care service provider or 
trained site personnel, following sponsor written approval. Procedures performed may include, 
but are not limited to:

taking blood samples

collecting urine samples for pregnancy testing

conducting physical assessments, depending on the qualifications of the mobile home 
health care provider

administering patient-reported outcomes

administering study intervention, and

collecting health information. 
Before administering study drug at home, participants and/or caregivers will be adequately 
trained on at-home study drug administration (unless they have already been trained; see also the 
section “Study drug and ancillary supplies” below).
Please note that requirements related to the reporting of SAEs remain unchanged. Every effort 
should be made for the participant to return to on-site visits as soon as reasonably possible, while 
ensuring the safety of the participant and investigational site staff. 
Study drug and ancillary supplies
Under exceptional circumstances, the sponsor or designee will determine appropriate actions to 
supply/resupply participants with the study drug and ancillary supplies.
The following requirements must be met:

sponsor approves the alternative method of delivery, taking local regulatory requirements 
into consideration

participant consents verbally to alternate method of delivery

participants or their caretakers are appropriately trained on at-home administration of the 
study drug (unless they have already received that training); the home health care 
provider will observe the participant or caregiver administer the study drug for the first 
time.
o
if the study drug is administered at home, participants will need to record the 
details about the injections in the patient diary (regardless of whether the at-home 
study drug administration is done by the participant him-/herself, caregiver, or 
mobile home health care provider). For the at-home administration information, 
the same electronic patient diary will be used as for recording the PROs.

site/sponsor confirms the participant’s receipt of the trial supplies

site/sponsor confirm appropriate ethics review board notification

alternate delivery of the study drug should be performed in a manner that does not 
compromise treatment blinding and ensures study drug integrity. The existing protocol 
requirements for product accountability remain unchanged. 

when delivering supplies to a location other than the study site (e.g., participant’s home)
o
participant consent must include provision of any personal information

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o
investigator/sponsor should ensure oversight of the shipping process to ensure 
accountability and product quality (i.e., storage conditions and intact packaging 
upon receipt)

additional instructions should be provided to the participant on how to return any unused 
or completed trial supplies.
Local laboratory option
In exceptional circumstances, to ensure participant safety and with the sponsor’s prior written 
approval, local laboratory testing may be conducted in lieu of central laboratory testing.
However, central laboratory testing must be retained for the following: 

Vaccine-specific antibody titer levels:
o
Anti-tetanus toxoid IgG antibody, and
o
Meningococcal Group C serum bactericidal antibodies (hSBA)

PK samples

Immunogenicity (ADA) samples

Pharmacogenetics sample
The local laboratory must be qualified in accordance with local regulations. Clinically significant 
laboratory findings will be reported as an AE in the AE eCRF. 
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.
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.
Increasing visit window(s) for the key endpoint visits
Participants should complete the vaccine administration visit (Visit 8/Week 12) and the final 
study endpoint visit (Visit 10/Week 16) as per original SoA whenever possible and deemed safe 
to do so by the investigator. However, in order to maximize the ability for such on-site visits, 
minimize missing data, and preserve the intended conduct of the study, the visit windows may be 
adjusted as follows, upon specific guidance from the sponsor:

For Visit 8 (Week 12), to +7/-3 days

For all dosing visits and Visit 10 (Week 16), to +7 days
Whenever possible, the visit intervals should be adjusted to allow 4 weeks between Visit 8 
(Week 12) and Visit 10 (Week 16), to allow for the highest level of vaccine response to be seen.
Documentation
Changes to study conduct
Changes to study conduct will be documented as the following:

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
Sites will need to identify and document the details of how participants, visit types, and 
activities conducted were affected by exceptional circumstances. Dispensing/shipment 
records of study intervention and relevant communications, including delegation, should 
be filed with site study records.

The site should document the participant’s verbal consent for having remote visits and 
remote dispensing of study drug, ancillaries and diaries, prior to implementation of these 
activities. 

Source document(s) that are 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. 
Missing data and other protocol deviations 
The study site should capture specific explanation for any missing data and other protocol 
deviations in source documents. This information will also be captured by the monitors in the 
monitoring system. While protocol deviations may be unavoidable in an exceptional 
circumstance, documentation of protocol deviations and missing data will be important for data 
analysis and reporting.

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10.10.
Appendix 10: Abbreviations
Term
Definition
AD
atopic dermatitis
ADA
anti-drug antibody
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
anti-HBc
hepatitis B core antibody
anti-HBs
hepatitis B surface antibody
AST
aspartate aminotransferase
ATC
anatomical therapeutic chemical
BCG
Bacillus Calmette-Guerin
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the participant is not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/his staff and the participant are not.
A double-blind study is one in which neither the participant nor any of the investigator 
or sponsor staff who are involved in the treatment or clinical evaluation of the 
participants are aware of the treatment received.
BSA
Body Surface Area
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatinine 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.
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form

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Term
Definition
CTA
Clinical Trial Agreement
DMC
data monitoring committee
DSMB
Data Safety Monitoring Board
EASI
Eczema Area and Severity Index
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
eCRF
electronic case report form
EDC
electronic data capture system
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.
ERB
ethical review board
ERCP
endoscopic retrograde cholangiopancreatography
ET
early termination
FLG
filaggrin
FSH
follicle stimulating hormone
GCP
good clinical practice
cGMP
current Good Manufacturing Practice
GGT
gamma-glutamyl transferase
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HDV
hepatitis D virus

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Term
Definition
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
hSBA
human complement serum bactericidal assay
huIgG4
humanized monoclonal immunoglobulin G4 antibody
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IFN-γ
interferon gamma
IgA
immunoglobulin A
IGA
Investigator Global Assessment
IgE
immunoglobulin E
IgG
immunoglobulin G
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
investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IRB
Institutional Review Boards
ITT
intention to treat: The principle that asserts that the effect of a treatment policy can be 
best assessed by evaluating on the basis of the intention to treat a participant (that is, the 
planned treatment regimen) rather than the actual treatment given. It has the 
consequence that participant allocated to 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.
IUD
intrauterine device

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Term
Definition
IUS
intrauterine hormone-releasing system
IWRS
interactive web-response system
LLOQ
lower limit of quantitation
LOR
loricrin
LTBI
latent tuberculosis infection
MCMC
Markov Chain Monte Carlo
MCV
Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 
Conjugate Vaccine (GlaxoSmithKline)
MRCP
magnetic resonance cholangiopancreatography
non-WOCBP
women of nonchildbearing potential
NRS
Numeric Rating Scale
Participant
Equivalent to CDISC term “subject”: an individual who participates in a clinical trial, 
either as recipient of an investigational medicinal product or as a control
PFS-NSD
prefilled syringe with needle safety device
PK
pharmacokinetics
POEM
Patient-Oriented Eczema Measure
PP
per protocol
PRO
patient-reported outcomes
PROMIS
Patient-Reported Outcomes Measurement Information System
PT-INR
prothrombin time international normalized ratio
PUVA
phototherapy and photochemotherapy
Q2W
once every 2 weeks
SAE
serious adverse event
SAP
Statistical Analysis Plan
Screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SD
standard deviation
SERM
selective estrogen receptor modulator

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Term
Definition
SoA
Schedule of Activities
TBL
total bilirubin level
TCI
topical calcineurin inhibitors
TCS
topical corticosteroids
Tdap
Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (Sanofi)
TE-ADA
treatment-emergent antidrug antibody
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.
TSLP
thymic stromal lymphopoietin
ULN
upper limit of normal
WHO
World Health Organization
WOCBP
women of childbearing potential

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11.
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