A Long-term Study to Assess the Safety and Efficacy of Lebrikizumab in Patients With Moderate-to-Severe Atopic Dermatitis (ADjoin)
Phase: PHASE3
Conditions: Atopic Dermatitis
Sponsor: Eli Lilly and Company

Protocol Addendum I
 
NCT0
Approval Date: 1 -
-20

CONFIDENTIAL 
DRM06-AD07/J2T-DM-KGAA (11) 
1 
Title Page  
Confidential Information 
The information contained in this document is confidential and is intended for the use of clinical investigators.  It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of lebrikizumab (LY3650150), unless such persons are bound by a confidentiality agreement with Eli Lilly and 
Company or its subsidiaries.   
 
Note to Regulatory Authorities:  This document may contain protected personal data and/or commercially confidential 
information exempt from public disclosure.  Eli Lilly and Company requests consultation regarding release/redaction prior to any 
public release.  In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be 
reproduced or otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries. 
Protocol Title:  
A Long-Term Study to Assess the Safety and Efficacy of Lebrikizumab in Patients with 
Moderate-to-Severe Atopic Dermatitis 
Protocol Number: DRM06-AD07/J2T-DM-KGAA 
Addendum Number: 11 
Addendum Statement: This addendum is to be performed in addition to all procedures required 
by protocol DRM06-AD07/J2T-DM-KGAA or any subsequent amendments to that protocol. 
Compound: Lebrikizumab (DRM06/LY3650150) 
Sponsor Name: Dermira, Inc., a wholly owned subsidiary of Eli Lilly and Company 
Legal Registered Address: Lilly Corporate Center, Indianapolis, IN 46285 USA 
Regulatory Agency Identifier Number(s) 
IND: 119866 
EudraCT: 2020-001211-24 
Approval Date: Protocol Addendum (11) Electronically Signed and Approved by Lilly on date 
provided below. 
Document ID: VV-CLIN-134334 
 
 
 

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DRM06-AD07/J2T-DM-KGAA (11) 
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Protocol Addendum Substantiality  
Not applicable; this study addendum does not include any sites in the European Union. 
 
 

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Table of Contents  
Protocol Addendum Substantiality ..................................................................................................2 
1. 
Rationale for Addendum ......................................................................................................4 
2. 
Protocol Additions .................................................................................................................5 
2.1. 
Protocol Section 1.4. Rationale for Dose and Treatment 
Regimen .............................................................................................................................5 
2.2. 
Protocol Section 2. Study Objectives and Endpoints ....................................................5 
2.3. 
Protocol Section 3. Study Design .....................................................................................6 
2.3.1. 
Protocol Section 3.1. Duration of the Study ...........................................................7 
2.3.2. 
Protocol Section 3.2. Study Population and Number of 
Patients ......................................................................................................................7 
2.4. 
Protocol Section 4. Selection of Patients .........................................................................7 
2.4.1. 
Protocol Section 4.1. Inclusion Criteria .................................................................7 
2.4.2. 
Protocol Section 4.2. Exclusion Criteria ................................................................8 
2.5. 
Protocol Section 5.3. Study Drug Assignment ...............................................................9 
2.6. 
Protocol Section 5.4. Study Blinding...............................................................................9 
2.7. 
Protocol Section 6. Concomitant Medications and Procedures ...................................9 
2.8. 
Protocol Section 7. Study Procedures .............................................................................9 
2.9. 
Protocol Section 8.4. Study Termination ........................................................................9 
2.10. Protocol Section 9.1. General Statistical Methodology .................................................9 
2.10.1. 
Protocol Section 9.1.1. Populations Analyzed ......................................................10 
2.10.2. 
Addendum Baseline Definition .............................................................................10 
2.11. Protocol Section 9.2. Efficacy Assessments ..................................................................10 
2.12. Protocol Section 9.3. Exposure and Compliance .........................................................11 
2.13. Protocol Section 9.6. Sample-Size Determination .......................................................11 
2.14. Appendix 1. Schedule of Visits and Procedures for KGAA 
Addendum (11) ...............................................................................................................12 
Acronyms ...................................................................................................................................14 
 

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DRM06-AD07/J2T-DM-KGAA (11) 
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1. 
Rationale for Addendum  
The rationale for this addendum is to add the Q8W dosing regimen for lebrikizumab to Study 
J2T-DM-KGAA (KGAA) via extending the study treatment period by an additional 32 weeks 
beyond the main protocol. 
This addendum will apply only to KGAA study participants who 
 meet the addendum entry criteria, and 
 are included in the study sites in the following countries: 
o Australia 
o Canada 
o Korea 
o Mexico 
o Singapore 
o Taiwan, and 
o the United States. 
See Section 2.1 of this addendum for rationale for including the Q8W dosing regimen for 
lebrikizumab. 

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2. 
Protocol Additions  
The procedures described in this addendum are in addition to the requirements of the main 
KGAA protocol, unless otherwise specified. Some of the information is repeated from the main 
KGAA protocol for clarity. The original section numbers from the protocol are included in the 
addendum headings for ease of reference. 
2.1. 
Protocol Section 1.4. Rationale for Dose and Treatment Regimen  
To date, the Q8W dosing regimen of lebrikizumab has not been evaluated in clinical trials. 
This proposed dosing regimen was selected for this addendum based on the AD Phase 3 data, 
including the PK-PD modeling for efficacy in AD.  
Lebrikizumab demonstrated a durable treatment effect in the Phase 3 AD studies. In addition, the 
placebo (lebrikizumab withdrawal) arm in the maintenance period exhibited a durable and 
prolonged efficacy response after the last dose of lebrikizumab at Week 14, with a slow and 
gradual decline in response noted by Week 52. 
These Phase 3 clinical data, together with the long half-life of lebrikizumab (mean = 24.5 days), 
prompted Lilly to evaluate a 250 mg Q8W dosing frequency 
 
  
2.2. 
Protocol Section 2. Study Objectives and Endpoints  
The primary objective of this addendum is to assess efficacy of lebrikizumab 250 mg Q4W and 
Q8W during the additional 32 weeks of extension treatment. The endpoints for this addendum 
include 
 proportion of patients who achieve IGA 0 or 1 at Week 32, and 
 proportion of patients who achieve EASI-
parent study) at Week 32. 
 
 
 
 
 
 
 
 
 

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E. Handling of ICEs: 
a. Treatment discontinuation due to lack of efficacy: composite strategy. Patients who 
discontinue treatment due to lack of efficacy will be considered as treatment failures 
(non-responders).  
b. Treatment discontinuation due to any other reasons: a hypothetical strategy will be 
used to estimate what the response would have been if subjects continued with 
treatment.  
c. Dose modification to lebrikizumab 250 mg Q2W: composite strategy. Patients whose 
dose is modified to lebrikizumab 250 mg Q2W will be considered as treatment 
failures (non-responders).  
2.3. 
Protocol Section 3. Study Design  
Eligible patients will enter this 32-week open-label extension of the study and will be randomly 
assigned to the following lebrikizumab treatment groups, regardless of their previous treatment 
regimen (that is, Q2W or Q4W): 
 lebrikizumab 250 mg Q4W, or 
 lebrikizumab 250 mg Q8W 
See Section 2.5 of this addendum for randomization ratio and stratification factors. 
Patients who complete this study addendum or who terminate early will return to the clinic for a 
safety follow-up visit 12 weeks after the last study drug injection. 
A patient is considered to have completed the study addendum if he/she has completed all 
required phases of the study, including the last visit as shown in the Schedule of Visits and 
Procedures of this addendum (Section 2.14). 
The end of the study for participants in the KGAA addendum (11) is defined as the date of the 
last visit of the last patient in the study shown in the Schedule of Visits and Procedures for this 
addendum. 
Dose modification 
Starting from Visit 201, patients enrolled in this study addendum who do not maintain an EASI-
50 response (from the parent study baseline) will move to lebrikizumab 250 mg Q2W for the 
remainder of this addendum. 

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Addendum schema 
This schema summarizes the design of this addendum. 
 
a 
Starting at Visit 201 of this addendum, patients who do not maintain an EASI-50 response (from the parent study 
baseline) will move to lebrikizumab 250 mg Q2W dosing regimen for the remainder of this addendum. 
b Patients may enter the addendum  
 
at Week 100 of Study KGAA, or 
 
after Week 100 of Study KGAA provided they have not yet completed the safety follow-up visit for 
Study KGAA. 
c 
From KGAA addendum (11) baseline. 
2.3.1. 
Protocol Section 3.1. Duration of the Study  
addendum will be up to 
42 weeks (32 weeks of the open-label extension period plus addendum safety follow-up visit 
12 weeks following the last injection of study drug).  
2.3.2. 
Protocol Section 3.2. Study Population and Number of Patients  
Up to approximately 213 patients are expected to enroll in this study addendum: 
 Q4W treatment group: N = 106 
 Q8W treatment group: N = 107 
2.4. 
Protocol Section 4. Selection of Patients  
2.4.1. 
Protocol Section 4.1. Inclusion Criteria  
Patients must meet all the following criteria to be eligible for this study addendum: 
[1] Have completed Week 100 (Visit 11) of Study KGAA and have not yet completed the 
safety follow-up visit for the main study. 
[2] Are willing and able to comply with all clinic visits and addendum-related procedures. 

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[3] For women of childbearing potential: agree to remain abstinent (refrain from 
heterosexual intercourse) or use a highly effective contraceptive method during the 
treatment period and for at least 18 weeks after the last dose of lebrikizumab.  
NOTE: A woman of childbearing potential (WOCBP) is defined as 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). 
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, 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 patient. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, or postovulation methods) and withdrawal are not acceptable methods of 
contraception. 
If the highly effective contraceptive methods are contraindicated or strictly declined by 
the patient, acceptable birth control methods may be considered. These may include a 
combination of the following methods: 
 male or female condom with spermicide, and 
 cap, diaphragm, or sponge with spermicide. 
[4] Male patients are not required to use any contraception except in compliance with 
specific local government study requirements. 
[5] Have given written informed consent for participating in this addendum that has been 
approved by the ethical review board governing the site prior to any addendum-specific 
procedures being initiated. 
2.4.2. 
Protocol Section 4.2. Exclusion Criteria  
Patients meeting any of the criteria below will not be included in this study addendum: 
[1] Have, during their participation in Study KGAA, developed a serious adverse event 
(SAE) deemed related to lebrikizumab, which in the opinion of the investigator or of the 
medical monitor could indicate that continued treatment with lebrikizumab may present 
an unreasonable risk for the patient. 
[2] During their participation in Study KGAA, developed an AE that was deemed related to 
lebrikizumab and led to study treatment discontinuation, which in the opinion of the 
investigator or of the medical monitor could indicate that continued treatment with 
lebrikizumab may present an unreasonable risk for the patient. 
[3] Developed conditions in Study KGAA consistent with protocol-defined criteria for 
permanent study drug discontinuation, if deemed related to lebrikizumab or led to 

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investigator- or sponsor-initiated withdrawal of patient from the study (e.g., non-
compliance, inability to complete study assessments, etc.).  
[4] Have initiated treatment with a medication prohibited by Study KGAA (see Section 6 of 
the main KGAA protocol) before addendum baseline. This includes use of biologics for 
AD (for example, dupilumab and tralokinumab) during the safety follow-up period of 
Study KGAA. 
[5] Are pregnant or breastfeeding women, or women planning to become pregnant or 
breastfeed during the study. 
2.5. 
Protocol Section 5.3. Study Drug Assignment  
Patients eligible to participate in this open-label study addendum will be randomly re-assigned to 
the Q4W and Q8W treatment groups in a 1:1 ratio.  
Participants will be stratified at the addendum baseline by 
 IGA score (0,1 vs. >1), and 
 region (US vs. non-US). 
2.6. 
Protocol Section 5.4. Study Blinding  
This addendum is open label. 
2.7. 
Protocol Section 6. Concomitant Medications and Procedures  
See Section 6 of the main KGAA protocol and Exclusion Criterion 4 for this addendum. 
2.8. 
Protocol Section 7. Study Procedures  
See the Schedule of Visits and Procedures for this addendum (Section 2.14). 
2.9. 
Protocol Section 8.4. Study Termination  
For discontinuation criteria, see the following sections of the main KGAA protocol: 
 Section 8.4.1: early termination of study patients 
Exception: The following discontinuation criterion from the main protocol will not apply 
Not achieving an EASI-50, from parent study baseline, by Week 16, 
maintaining an EASI-50 response, or not achieving clinical benefit based on PI discretion 
should be terminated from this study.  As indicated in Section 2.3 of this addendum, 
patients who do not maintain an EASI-50 response (from the parent study baseline) will 
move to lebrikizumab 250 mg Q2W. 
 Section 8.4.3: temporary and permanent discontinuation of study drug 
2.10. 
Protocol Section 9.1. General Statistical Methodology  
All statistical processing will be performed using SAS® unless otherwise stated. 
Descriptive statistics will be used to provide an overview of the efficacy results. For categorical 
parameters, the number and percentage of patients in each category will be presented. For 

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continuous parameters, descriptive statistics will include n (number of patients), mean, standard 
deviation, median, minimum, and maximum. 
Demographic data will be summarized by treatment group using descriptive statistics.  
The number of patients in each analysis set will be summarized. Reasons for study withdrawal 
and treatment withdrawal during the study will be summarized using frequencies and 
percentages by treatment group. 
A statistical analysis plan (SAP), describing all statistical analyses will be provided as a separate 
document. 
2.10.1. 
Protocol Section 9.1.1. Populations Analyzed  
Efficacy analysis will be performed using the ITT population. The ITT population consists of all 
patients assigned to treatment in this study addendum, even if the patient does not take the 
assigned treatment, does not receive the correct treatment, or otherwise does not follow this 
addendum. 
2.10.2. 
Addendum Baseline Definition  
Patients may enter the addendum  
 at Week 100 of Study KGAA, or 
 after Week 100 of Study KGAA provided they have not yet completed the safety follow-
up visit for Study KGAA. 
For the efficacy measures, addendum baseline is defined as the last available value before the 
first injection in this addendum period, which in most cases will be the value recorded at the 
addendum baseline visit (Visit 200). Efficacy analysis will be reported by visit from the 
addendum baseline visit to Week 32 of the addendum period. The baseline used to derive 
efficacy endpoints is the parent study baseline. 
2.11. 
Protocol Section 9.2. Efficacy Assessments  
The following efficacy assessments will be summarized: 
 proportion of patients with IGA score 0 or 1 at Week 32, and 
 proportion of patients with EASI-
cores compared to parent 
study baseline) at Week 32. 
 
 
 

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Supportive estimand for the primary endpoints will be provided in detail in SAP. 
No statistical testing will be performed. 
2.12. 
Protocol Section 9.3. Exposure and Compliance  
Details will be provided in the SAP for this addendum. 
2.13. 
Protocol Section 9.6. Sample-Size Determination  
This addendum will aim to enroll up to approximately 213 patients into the additional 32-week 
extension treatment period. The sample size is based on the number of patients available in Study 
KGAA at the time of addendum approval and is not based on a statistical power calculation. 
After 32 weeks of treatment in this addendum, a sample size of 106 per arm will provide 95% 
confidence intervals (CIs) of  
 76% to 90% based on a hypothesized EASI-75 response rate of 83% for Q4W, and  
 60% to 78% based on a hypothesized 69% response rate for Q8W. 
 
 

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2.14. 
Appendix 1. Schedule of Visits and Procedures for KGAA 
Addendum (11)  
Note: For information on assessments that do not need to be repeated at addendum baseline, see 
footnotes 1 and 3 below. 
Study Procedure 
 
Week (W) 
KGAA Addendum (11) Study Periods 
Baseline1
32-Week Open-Label Extension Period
Safety 
Follow-
Up Visit
8W from 
KGAA 
Addendum 
(11) 
Baseline 
16W from 
KGAA 
Addendum 
(11) 
Baseline 
24W from 
KGAA 
Addendum 
(11) 
Baseline 
32W from 
KGAA 
Addendum 
(11) 
Baseline/ 
Addendum 
ET
12W
After the 
Last 
Injection 
of Study 
Drug 
Visit Number 
200
201
202
203
204
801
Visit Window 
At or up 
to 10 
weeks 
after 
W100 of 
Study 
KGAA1
±5d 
±5d 
±5d 
±5d 
±5d 
Enrollment 
 
Informed Consent/Assent
for KGAA Addendum 
(11) 
X 
Inclusion/Exclusion 
Criteria for KGAA 
Addendum (11)
X 
Safety
 
Physical Exam 
X 
X
Height and Weight 
X2
X2
Vital Signs
X 
X
X
X
X
Adverse Events
X 
X
X
X
X
X
Concomitant 
Medications/Procedures 
X 
X
X
X
X
X
Hematology, Chemistry
X3
X
HBV DNA4
X 
X
X
Estradiol or 
Testosterone5 
X3 
X
Urinalysis
X3
X
Pregnancy Testing6 
X 
X
X
X
X
Efficacy 
 
IGA
X 
X
X
X
X
BSA
X 
X
X
X
X
EASI 
X 
X
X
X
X
POEM (in office 
collection only)7 
X 
X
X
X
X

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DRM06-AD07/J2T-DM-KGAA (11) 
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Study Procedure 
 
Week (W) 
KGAA Addendum (11) Study Periods 
Baseline1
32-Week Open-Label Extension Period
Safety 
Follow-
Up Visit
8W from 
KGAA 
Addendum 
(11) 
Baseline 
16W from 
KGAA 
Addendum 
(11) 
Baseline 
24W from 
KGAA 
Addendum 
(11) 
Baseline 
32W from 
KGAA 
Addendum 
(11) 
Baseline/ 
Addendum 
ET
12W
After the 
Last 
Injection 
of Study 
Drug 
PK and 
Immunogenicity
 
Pre-dose PK8
X3
X
X
X
X
X
Pre-dose ADA8,9
X3
X
X
X
Study Treatment 
 
Study Drug 
Administration10 
X 
X
X
X
Dispense Study Drug11
X 
X
X
X
1 Patients may enter the addendum  
 
at Week 100 of Study KGAA, or 
 
after Week 100 of Study KGAA provided they have not yet completed the safety follow-up visit for 
Study KGAA. 
Unless specified otherwise, if the baseline visit for this addendum occurs on the same day as Week 100 visit for 
Study KGAA, do not repeat assessments completed at Week 100. 
2 Collect height in adolescents only at these visits. Collect weight in all patients. 
3 Do not repeat this assessment at the addendum baseline if it was completed within 4 weeks from the Week 100 
visit of the main study. 
4 Only for participants who are anti-HBc reactive and anti-HBs nonreactive at screening (Section 8.2.3 of the 
KGAA protocol) or participants who are anti-HBc reactive and anti-HBs reactive at parent study screening 
(KGAA Addendum (10), if applicable). 
5 Collect estradiol in adolescent females only and testosterone in adolescent males only. Stop hormone tests when 
the patient reaches 18 years of age. 
6 Urine pregnancy tests for women of childbearing potential (Section 8.2.3 of the main KGAA protocol). 
7 In-office POEM only collected for patients who participated in DRM06-AD04, DRM06-AD05, DRM06-AD06, 
and DRM06-AD18. In-office POEM should be completed prior to any other study assessments.   
8 PK and ADA are pre-dose collections if a dose is administered at the visit. 
9 Neutralizing antibodies testing conducted for positive treatment-emergent ADA responses. Additional 
immunogenicity sample collected for any patient experiencing a hypersensitivity reaction during study. 
10 For patients assigned to Q4W or Q2W dosing, study drug administration will also occur between visits (at home). 
11 Sufficient drug is dispensed to cover injections through next visit. 
 
 

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Acronyms  
Acronym 
Term 
AD 
atopic dermatitis 
ADA 
anti-drug antibody 
AE 
adverse event 
BSA 
body surface area 
CI 
confidence interval 
d 
day 
EASI-50 or -75 
Eczema Area and Severity Index: 50% or 75% improvement from baseline 
ET 
early termination 
HBV 
hepatitis B virus 
ICE 
intercurrent event 
IGA 
 
ITT 
intent to treat 
IUD 
intrauterine device 
IUS 
intrauterine hormone-releasing system 
MCMC-MI 
Markov Chain Monte Carlo  Multiple Imputation 
PD 
pharmacodynamic 
PI 
principal investigator 
PK 
pharmacokinetic 
POEM 
Patient Oriented Eczema Measure 
Q2W 
every 2 weeks 
Q4W 
every 4 weeks 
Q8W 
every 8 weeks 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
V 
visit 
W 
week