A Phase 1, Open-Label, Single-Dose Bioequivalence Study of Injections of Lebrikizumab Using a 2-mL Pre-Filled Syringe With Needle Safety Device and an Investigational 2-mL Autoinjector in Healthy Participants
Phase: PHASE1
Conditions: Healthy
Sponsor: Eli Lilly and Company

J2T-MC-KGBG Protocol (b) 
 
A Phase 1, Open-Label, Single-Dose Bioequivalence Study of Injections of Lebrikizumab Using 
a 2-mL Pre-Filled Syringe with Needle Safety Device and an Investigational 2-mL Autoinjector 
in Healthy Participants 
 
NCT04840901 
 
Approval Date: 17-Aug-2021 

CONFIDENTIAL 
J2T-MC-KGBG(b) 
 
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 Phase 1, Open-Label, Single-Dose Bioequivalence Study of Injections of 
Lebrikizumab Using a 2-mL Pre-Filled Syringe with Needle Safety Device and 
an Investigational 2-mL Autoinjector in Healthy Participants 
Protocol Number: J2T-MC-KGBG 
Amendment Number: b 
Compound: Lebrikizumab (LY3650150) 
Study Phase: 1 
Short Title: A Bioequivalence Study of Lebrikizumab Using a Pre-Filled Syringe with Needle 
Safety Device and an Investigational Autoinjector in Healthy Participants 
Sponsor Name: Eli Lilly and Company 
Legal Registered Address: Indianapolis, Indiana, USA 46285 
Regulatory Agency Identifier Number(s): IND: 119866 
Document ID: VV-CLIN-002582  
 
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J2T-MC-KGBG(b) 
 
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Medical Monitor Name and Contact Information will be provided separately. 
 
 
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Protocol Amendment Summary of Changes Table 
 
DOCUMENT HISTORY 
Document 
Date 
Protocol J2T-MC-KGBG 
04 March 2021 
Amendment (a) 
19 May 2021 
Amendment (b)  
Overall Rationale for the Amendment: 
This protocol has been amended in response to comment from study site to provide clarification 
regarding procedures in section on Preparation/Handling/Storage/ accountability. Minor editorial 
changes have been done which is not reflected in the below table. The following table describes 
the change made in amendment (b). 
Section # and Name 
Description of Change 
Brief Rationale 
6.2. Preparation/ 
Handling/ 
Storage/accountability   
The following statement is 
removed. 
The investigator or designee will 
return all used and unused AI 
devices to Lilly or its designee at 
the end of the study.  
The device group no longer 
requests sites to return used 
and unused devices to Lilly. 
 
 
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J2T-MC-KGBG(b) 
 
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Table of Contents 
1. 
Protocol Summary ..........................................................................................................7 
1.1. 
Synopsis ............................................................................................................................7 
1.2. 
Schema ..............................................................................................................................8 
1.3. 
Schedule of Activities (SoA) ............................................................................................9 
2. 
Introduction ...................................................................................................................13 
2.1. 
Study Rationale ...............................................................................................................13 
2.2. 
Background .....................................................................................................................13 
2.3. 
Benefit/Risk Assessment ................................................................................................14 
3. 
Objectives and Endpoints ............................................................................................16 
4. 
Study Design ..................................................................................................................17 
4.1. 
Overall Design ................................................................................................................17 
4.2. 
Scientific Rationale for Study Design ............................................................................18 
4.3. 
Justification for Dose ......................................................................................................19 
4.4. 
End of Study Definition ..................................................................................................19 
5. 
Study Population ...........................................................................................................20 
5.1. 
Inclusion Criteria ............................................................................................................20 
5.2. 
Exclusion Criteria ...........................................................................................................21 
5.3. 
Lifestyle Considerations .................................................................................................24 
5.3.1. 
Meals and Dietary Restrictions .......................................................................................24 
5.3.2. 
Caffeine, Alcohol, and Tobacco .....................................................................................24 
5.3.3. 
Activity ...........................................................................................................................24 
5.4. 
Screen Failures ................................................................................................................24 
6. 
Study Intervention ........................................................................................................25 
6.1. 
Study Interventions Administered ..................................................................................25 
6.1.1. 
Medical Devices..............................................................................................................25 
6.2. 
Preparation/Handling/Storage/Accountability ................................................................25 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................26 
6.4. 
Study Intervention Compliance ......................................................................................26 
6.5. 
Concomitant Therapy .....................................................................................................26 
6.6. 
Dose Modification ..........................................................................................................27 
6.7. 
Intervention after the End of the Study ...........................................................................27 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................28 
7.1. 
Discontinuation of Study Intervention ............................................................................28 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................28 
7.2.1. 
Discontinuation of Inadvertently Enrolled Participants ..................................................28 
7.3. 
Lost to Follow-up............................................................................................................28 
8. 
Study Assessments and Procedures.............................................................................30 
8.1. 
Efficacy Assessments .....................................................................................................30 
8.2. 
Safety Assessments .........................................................................................................30 
8.2.1. 
Physical Examinations ....................................................................................................30 
8.2.2. 
Vital Signs .......................................................................................................................31 
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J2T-MC-KGBG(b) 
 
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8.2.3. 
Electrocardiograms .........................................................................................................31 
8.2.4. 
Clinical Safety Laboratory Assessments ........................................................................31 
8.2.5. 
Safety Monitoring ...........................................................................................................32 
8.3. 
Adverse Events, Serious Adverse Events, and Product 
Complaints ......................................................................................................................35 
8.3.1. 
Timing and Mechanism for Collecting Events ...............................................................35 
8.3.2. 
Adverse Events of Special Interest .................................................................................36 
8.4. 
Treatment of Overdose ...................................................................................................37 
8.5. 
Pharmacokinetics ............................................................................................................37 
8.5.1. 
Bioanalysis ......................................................................................................................37 
8.6. 
Pharmacodynamics .........................................................................................................37 
8.7. 
Genetics ..........................................................................................................................37 
8.8. 
Biomarkers ......................................................................................................................38 
8.9. 
Immunogenicity Assessments.........................................................................................38 
8.10. 
Health Economics ...........................................................................................................38 
9. 
Statistical Considerations .............................................................................................39 
9.1. 
Statistical Hypotheses .....................................................................................................39 
9.2. 
Sample Size Determination ............................................................................................39 
9.3. 
Populations for Analyses ................................................................................................39 
9.4. 
Statistical Analyses .........................................................................................................39 
9.4.1. 
General Considerations ...................................................................................................39 
9.4.2. 
Pharmacokinetic Analyses ..............................................................................................40 
9.4.3. 
Safety Analyses ...............................................................................................................40 
9.4.4. 
Evaluation of Immunogenicity .......................................................................................40 
9.5. 
Interim Analyses .............................................................................................................41 
9.6. 
Data Monitoring Committee (DMC) ..............................................................................41 
10. 
Supporting Documentation and Operational Considerations ..................................42 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................42 
10.1.1. Regulatory and Ethical Considerations ...........................................................................42 
10.1.2. Informed Consent Process ..............................................................................................42 
10.1.3. Data Protection................................................................................................................43 
10.1.4. Dissemination of Clinical Study Data.............................................................................43 
10.1.5. Data Quality Assurance ..................................................................................................44 
10.1.6. Source Documents ..........................................................................................................45 
10.1.7. Study and Site Start and Closure ....................................................................................45 
10.1.8. Publication Policy ...........................................................................................................46 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................47 
10.2.1. Blood Sampling Summary ..............................................................................................49 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .........................................................50 
10.3.1. Definition of AEs and ADE ............................................................................................50 
10.3.2. Definition of SAE, SADE, and UADE ...........................................................................51 
10.3.3. Recording and Follow-Up of AE and/or SAE ................................................................52 
10.3.4. Reporting of SAEs ..........................................................................................................54 
10.3.5. Regulatory Reporting Requirements ...............................................................................54 
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10.4. 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information ...................................................................................................56 
10.5. 
Appendix 5: Genetics......................................................................................................60 
10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments ....................................................................................................................61 
10.7. 
Appendix 7: Recommended Laboratory Testing for 
Hypersensitivity Events ..................................................................................................63 
10.8. 
Appendix 8: Medical Device Adverse Events (AEs), Adverse 
Device Effects (ADEs), Serious Adverse Events (SAEs) and 
Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ............................................................................65 
10.9. 
Appendix 9: Abbreviations .............................................................................................66 
10.10. 
Appendix 10: Protocol Amendment History ..................................................................69 
11. 
References ......................................................................................................................70 
 
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J2T-MC-KGBG(b) 
 
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1. 
Protocol Summary 
1.1. 
Synopsis 
Protocol Title: A Phase 1, Open-Label, Single-Dose Bioequivalence Study of Injections of 
Lebrikizumab Using a 2-mL Pre-Filled Syringe with Needle Safety Device and an 
Investigational 2-mL Autoinjector in Healthy Participants 
Short Title: A Bioequivalence Study of Lebrikizumab Using a Pre-Filled Syringe with Needle 
Safety Device and an Investigational Autoinjector in Healthy Participants 
Rationale: Study J2T-MC-KGBG (KGBG) will assess the PK, safety, and tolerability of a 
250-mg SC dose of lebrikizumab (LY3650150) solution formulation administered using a 2-mL 
PFS-NSD or an investigational 2-mL AI. Both devices will be evaluated at 3 different injection 
sites (arm, thigh, and abdomen) to expand the options for administration in patient use. Both the 
PFS-NSD and the AI are planned for use to administer lebrikizumab in subsequent studies and 
patient use. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
To evaluate the PK of lebrikizumab after SC 
administration of 250-mg dose using a 2-mL 
PFS-NSD and a 2-mL AI in healthy 
participants 
• Cmax 
• AUC(0-∞) 
• AUC(0-tlast) 
Secondary 
 
To describe the safety and tolerability of 
lebrikizumab 250-mg dose through SC in 
healthy participants 
Number and incidence of  
• SAEs 
• TEAEs 
Abbreviations: AI = autoinjector; AUC(0-∞) = area under the concentration versus time curve from time zero to 
infinity; AUC(0-tlast) = area under the concentration versus time curve from time zero to time t, where t is the last 
time point with a measurable concentration; Cmax = maximum observed drug concentration; PFS-
NSD = pre-filled syringe with needle safety device; PK = pharmacokinetics; SAE = serious adverse event; 
SC = subcutaneous; TEAE = treatment-emergent adverse event.  
Overall Design 
Study KGBG is a Phase 1, multi-site, randomized, parallel-design, open-label, 2-arm, single-
dose study of lebrikizumab in healthy participants. 
Disclosure Statement: This is an open-label, parallel-group bioequivalence study with 2 arms. 
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Number of Participants: 
Approximately 240 participants may be enrolled so that approximately 216 participants (108 in 
the PFS-NSD group and 108 in the AI group) complete the study. 
Intervention Groups and Duration: 
All participants will be screened within 28 days prior to enrollment. A single dose of 
lebrikizumab will be administered SC through either PFS-NSD or AI into the arm, thigh, or 
abdomen on Day 1 and participants will be followed through Day 99. 
Data Monitoring Committee: No 
1.2. 
Schema 
Not applicable. 
 
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1.3. 
Schedule of Activities (SoA) 
Study Schedule Protocol J2T-MC-KGBG  
 
Screening 
Study Day 
Comments 
Procedure 
-28 to -2 
days prior 
to Day 1 
-1 
1 
3 
5 
±1d 
8 
±1d 
11 
±1d 
15 
±2d 
22 
±2d 
29 
±2d 
36 
±2d 
43 
±2d 
50 
±2d 
57 
±2d 
64 
±2d 
71 
±3d 
85 
±3d 
99 
±3d 
or 
ED 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review and confirm 
inclusion and 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to CRU 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from 
CRU 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participants may be 
discharged after 
completing the scheduled 
activities on Day 1, or 
later at the investigator’s 
discretion. 
Outpatient visit 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X  
Safety assessment 
(telephone call) 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
 
 
To check on the presence 
of any AEs and 
concomitant medications. 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participants will be 
randomly assigned 1:1 to 
1 of 2 delivery devices 
and 1:1:1 to 1 of 3 
injection locations per 
delivery device. 
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Screening 
Study Day 
Comments 
Procedure 
-28 to -2 
days prior 
to Day 1 
-1 
1 
3 
5 
±1d 
8 
±1d 
11 
±1d 
15 
±2d 
22 
±2d 
29 
±2d 
36 
±2d 
43 
±2d 
50 
±2d 
57 
±2d 
64 
±2d 
71 
±3d 
85 
±3d 
99 
±3d 
or 
ED 
 
Height, weight, and 
BMI 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Participant weight at Day 
-1 will be used for weight 
category stratification at 
randomization. Weight, 
but not height, will be 
measured on Day -1, and 
Day 99 or ED. 
Physical 
examination 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Full physical examination 
at screening or at Day -1. 
Symptom-directed 
examinations at other 
times, and as deemed 
necessary by the 
investigator. 
Vital signs (pulse 
rate and blood 
pressure) (sitting), 
and body 
temperature 
X 
X 
P,  
3hr 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
Predose Day 1 conducted 
within 2 hours predose. 
Postdose assessment 3 ± 
1 hour. Time points may 
be added if warranted at 
the discretion of the 
investigator. 
Clinical laboratory 
tests 
X 
X 
P 
X 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
X 
Day 1 conducted within 2 
hours predose. See 
Section 10.2 Appendix 2, 
Clinical Laboratory Tests, 
for details.  
Serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.2 
Appendix 2, Clinical 
Laboratory Tests, for 
details. 
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Screening 
Study Day 
Comments 
Procedure 
-28 to -2 
days prior 
to Day 1 
-1 
1 
3 
5 
±1d 
8 
±1d 
11 
±1d 
15 
±2d 
22 
±2d 
29 
±2d 
36 
±2d 
43 
±2d 
50 
±2d 
57 
±2d 
64 
±2d 
71 
±3d 
85 
±3d 
99 
±3d 
or 
ED 
 
QuantiFERON®-T
B Gold test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ethanol test and 
drug screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tests may be repeated at 
additional time points at 
the discretion of the 
investigator. 
FSH (females only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.4, 
Appendix 4.  
Pregnancy test  
(females of 
childbearing 
potential only) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Serum pregnancy test will 
be performed at screening 
and Day -1. Urine 
pregnancy test will be 
performed at Day 99 or 
ED. See Section 10.4, 
Appendix 4.  
Single 12-lead ECG 
(supine) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
May be obtained at 
additional times, when 
deemed clinically 
necessary. 
Lebrikizumab 
administration 
(1 injection per 
dose) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 6.1.  
 
Lebrikizumab PK 
sample 
 
 
P 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X Day 1: collected within 2 
hours predose. 
Immunogenicity 
sample 
 
 
P 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
X Day 1: collected within 2 
hours predose. 
Pharmacogenetic 
sample 
 
 
P 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1: collected within 2 
hours predose. 
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Screening 
Study Day 
Comments 
Procedure 
-28 to -2 
days prior 
to Day 1 
-1 
1 
3 
5 
±1d 
8 
±1d 
11 
±1d 
15 
±2d 
22 
±2d 
29 
±2d 
36 
±2d 
43 
±2d 
50 
±2d 
57 
±2d 
64 
±2d 
71 
±3d 
85 
±3d 
99 
±3d 
or 
ED 
 
AE, product 
complaints, and 
concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
If an AE of ISR is 
reported, see Section 
8.2.5.2.  
Abbreviations: AE = adverse event; BMI = body mass index; CRU = clinical research unit; d = day; ECG = electrocardiogram; ED = early discontinuation; 
FSH = follicle-stimulating hormone; ISR = injection-site reaction; P = pre-dose; PK = pharmacokinetics; TB = tuberculosis.  
 
 
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2. 
Introduction 
2.1. 
Study Rationale 
Study J2T-MC-KGBG (KGBG) will assess the PK, safety, and tolerability of a 250-mg SC dose 
of lebrikizumab (LY3650150) solution formulation administered using a 2-mL PFS-NSD or an 
investigational 2-mL AI. Both devices will be evaluated at 3 different injection sites (arm, thigh, 
and abdomen) to expand the options for administration in patient use. Both the PFS-NSD and the 
AI are planned for use to administer lebrikizumab in subsequent studies and patient use. 
2.2. 
Background 
Lebrikizumab (LY3650150) is a humanized monoclonal antibody based on the human 
immunoglobulin G4 antibody stabilized by a mutated Fc region. Lebrikizumab binds specifically 
to soluble IL-13 and blocks IL-13 signaling through the IL-4 receptor alpha/IL-13 receptor alpha 
1 pathway, thereby preventing the downstream effects of human IL-13 with high potency. 
Lebrikizumab has been investigated for the treatment of AD, asthma, chronic obstructive 
pulmonary disease, idiopathic pulmonary fibrosis, and refractory Hodgkin lymphoma. Currently, 
lebrikizumab is being actively developed for the treatment of AD. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of lebrikizumab is 
provided in the Investigator’s Brochure. 
Safety summary 
As of the Investigator’s Brochure cutoff date of 22 September 2020, 311 healthy participants and 
an estimated 4484 patients have been exposed to at least 1 dose of lebrikizumab. Safety 
information provided in the Investigator’s Brochure is summarized here.  
Healthy participants 
Lebrikizumab has been evaluated in 5 healthy participant studies. Single IV doses included 0.1, 
0.3, 1.0, 3.0, and 5.0 mg/kg. Doses administered SC included a dose at 1 mg/kg, and single doses 
including 37.5, 125, 250, and 375 mg. 
Five treatment-emergent SAEs were reported in lebrikizumab-treated participants. All events 
were assessed by the investigator as not related to study drug. No SAE PT was reported in more 
than 1 participant. No deaths were reported in healthy participant studies. Administration of a 
single dose of lebrikizumab in healthy participant studies was well tolerated. 
Patients 
Lebrikizumab has been evaluated in 686 patients with AD, 3321 patients with asthma, and 477 
patients with other indications.  
Studies in patients with AD 
In Phase 2 studies, the doses administered were 125, 250, and 500 mg. In Phase 3 studies, the 
dose was 250 mg administered every 2 or 4 weeks. One death from myocardial infarction has 
been reported in the ongoing Phase 3 study and was assessed as not related by the investigator. 
This death was reported after the Investigator’s Brochure cutoff date of 22 September 2020. 
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In the 3 completed Phase 2 studies 
• A low frequency of SAEs were reported in the lebrikizumab-treated groups and placebo 
or topical corticosteroid groups.  
• No PT was reported in more than 1 patient.  
• A majority of SAEs were assessed by the investigator as not related.  
• A similar proportion of patients in each treatment group reported AEs leading to study 
discontinuation. 
Studies in patients with asthma 
In Phase 2 studies, doses included 37.5, 125, or 250 mg every 4 weeks, and in some studies 
patients were dosed at 0.3 mg/kg to 5 mg/kg. In Phase 3, doses studied included 37.5 or 125 
administered once every 4 weeks. Six deaths were reported in these studies. 
In the 3 completed Phase 3 studies of adult patients 
• A similar proportion of patients in all treatment groups had at least 1 SAE. 
• In both treatment groups, the most commonly reported SAE was the PT asthma.  
• A similar proportion of patients in each treatment group reported AEs leading to study 
discontinuation. 
Studies in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, or 
Hodgkin lymphoma 
In one Phase 2 study of patients with chronic obstructive pulmonary disease, the dose was 
125 mg administered once every 4 weeks. Three deaths were reported in this study, all assessed 
as not related to study drug. In one Phase 2 study of patients with idiopathic pulmonary fibrosis, 
the dose was 250 mg administered once every 4 weeks. Forty-eight deaths were reported in this 
study, the majority of which were due to progression of disease. In one Phase 1/2 study of 
patients with Hodgkin lymphoma, doses from 0.1 to 10.0 mg/kg were administered intravenously 
every 2 weeks for a maximum of 24 weeks. Nine deaths were reported in this study, all of which 
were due to disease progression. 
Overall, the safety findings in the lebrikizumab groups were similar to the placebo or comparator 
groups across these clinical studies. There were no significant trends observed in the 
treatment-emergent adverse events reported between the treatment groups in all 3 indications. 
Anti-lebrikizumab antibodies 
In the completed studies of patients with AD, 12.3% to 24.5% of patients developed ADAs. In 
general, the presence of anti-lebrikizumab antibodies had no apparent impact on PK results, and 
overall there was no relationship between anti-lebrikizumab antibody status and efficacy or 
safety events. 
2.3. 
Benefit/Risk Assessment 
Risk from immunomodulatory therapy 
As an immunomodulatory therapy, lebrikizumab may increase the risk of developing an 
infection or may exacerbate an existing infection. In patients with moderate-to-severe AD in the 
lebrikizumab program, the most commonly reported infections include nasopharyngitis and 
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C O N FI D E N TI A L  
J 2 T-M C -K G B G (b ) 
 
1 5  
u p per res p ir at or y tract i nfecti o n. O verall, t he i nci de nce of i nfecti o ns is bal a nce d b et wee n p atie nts 
i n t he le bri kiz u ma b a n d place b o gr o u ps. N o s eri o us or parasit ic i nfecti o ns ha ve bee n re p orte d i n 
le bri kiz u ma b-treate d pati e nts wit h m o derate-t o-s e vere A D.  N o o p p ort u nistic i nfecti o ns or T B 
i nfecti o ns ha ve b ee n re p orte d i n t he P hase 2 A D pr o gra m . N o seri o us i nfecti o ns were re p orte d i n 
5 c o m plete d  healt h y partici pa nt  st u dies. I m m u n o m o d ulat or y t hera pies ma y i ncreas e t he ris k of 
mali g na n cies; h o we ver, d ue t o t he si n gle d os e of le bri kiz u ma b bei n g a d mi nistere d i n t his st u d y, 
it is n ot c o nsi dere d necessar y t o m o nit or f or s uc h effects. 
H y perse nsiti vit y re acti o ns  
T here w ere n o re p ort e d h y p erse nsiti vit y e v e nts i n t he P hase 2 A D pr o gra m.  I n a p o ole d a n al ysis 
of P hase 3 ast h ma st u dies,  t here was 1 p atie nt wit h a n a na p h ylactic e ve nt i n t he le bri kiz u ma b 
gr o u p.  
De vice -b ase d ris ks  
As t his st u d y will use a n AI , de vice-base d s afety ris ks will be e val uate d. P ossi ble de vice-bas e d 
ris ks i ncl u de l ocal effects s uc h as pai n at t he i njecti o n sites fr o m eit her t he nee dle or t he s ol uti o n 
e ntr y i nt o t he S C tiss ue, s welli n g, er yt h e ma, blee di n g, a n d br uisi n g. T h ese ris ks ar e miti gat e d b y 
trai ni n g i n vesti gati ve site staff o n pr o per i njecti o n tec h ni q ues. S yste mic effects ma y i ncl u de 
s weati n g, feeli n g fai nt, or fe ver, as a si g n of i nfecti o n. 
K n o w n a n d e x pecte d be nefits a n d ris ks  
T here is n o a ntici pat e d t hera pe utic b e nefit f or t he partici pa nts i n t h is st u d y. H o we ver, 
partici pa nts ma y be n efit fr o m t he scree ni n g pr oce d ures (t hr o u g h det ecti o n of u n k n o w n healt h 
iss ues) e ve n if t he y recei ve n o t hera p e utic be nefit fr o m t he st u d y. 
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d b e nefits a n d ris ks a n d reas o n a bl y 
e x pecte d A E s of le bri kiz u ma b ma y b e  f o u n d i n t he I n vesti gat or’s Br oc h ure as well as reas o na bl y 
a ntici pate d A D E s f o u n d i n t he AI  I n vesti gat or’s Br oc h ure. 
 
 
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3. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
To evaluate the PK of lebrikizumab after SC 
administration of 250-mg dose using a 2-mL 
PFS-NSD and a 2-mL AI in healthy 
participants 
• Cmax 
• AUC(0-∞) 
• AUC(0-tlast) 
Secondary 
 
To describe the safety and tolerability of 
lebrikizumab 250-mg dose through SC in 
healthy participants 
Number and incidence of 
• SAEs 
• TEAEs 
Tertiary/Exploratory 
 
• To evaluate the potential development 
of anti-lebrikizumab antibodies 
• To evaluate the impact of injection-
site location on PK 
• TE-ADA 
 
• Cmax 
• AUC(0-∞) 
• AUC(0-tlast) 
Abbreviations: AI = autoinjector; AUC(0-∞) = area under the concentration versus time curve from time zero to 
infinity; AUC(0-tlast) = area under the concentration versus time curve from time zero to time t, where t is the last 
time point with a measurable concentration; Cmax = maximum observed drug concentration; PFS-
NSD = pre-filled syringe with needle safety device; PK = pharmacokinetics; SAE = serious adverse event; 
SC = subcutaneous; TE-ADA = treatment-emergent antidrug antibody; TEAE = treatment-emergent adverse 
event. 
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4. 
Study Design 
4.1. 
Overall Design 
Study KGBG is a Phase 1, multi-site, randomized, parallel-design, open-label, 2-arm, single-
dose study in healthy participants. 
Infection risk 
Participants should follow local guidance and CRU precautions to minimize risk for COVID-19 
infection. 
Screening 
All participants will be screened within 28 days prior to enrollment. At screening, participants 
will be stratified into 1 of 3 weight categories.  
• less than 70.0 kg,  
• 70.0 to 80.0 kg, and  
• more than 80.0 kg. 
Study participants 
Approximately 240 participants will be randomly assigned according to Table KGBG.1, so that 
approximately 216 participants complete the study. If a participant needs to be replaced, a 
participant of the same weight category will be selected as their replacement. 
Treatment and assessment period 
Eligible participants will be admitted to the CRU on Day -1. Participants will be stratified into 1 
of 3 weight categories based on their Day -1 weight. 
Within the 3 weight categories, participants will be randomly assigned (Table KGBG.1) using a 
computer-generated allocation code (Section 6.3): 
• 1:1 to delivery device (either PFS-NSD [reference] or AI [test]) 
• within each delivery-device group 1:1:1 to injection site (arm, thigh, or abdomen) 
On Day 1, participants will receive a 2-mL (total 250 mg lebrikizumab) SC dose, administered 
by the investigator or designee, and delivered via the device and in the location assigned by the 
randomization.  
Participants may be allowed to leave the CRU after completing the 3(±1)-hour safety 
assessments on Day 1, or later at the investigator’s discretion. Participants will return for PK and 
immunogenicity sampling and safety assessments at predefined times up to 99 days postdose. 
Participants will be monitored for safety between outpatient visits by way of telephone 
assessment.  
Safety and tolerability will be assessed through clinical laboratory tests, vital sign measurements, 
recording of AEs, physical examination, and immunogenicity. 
 
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Table KGBG.1. 
Study KGBG Stratification and Randomization Plan 
Weight Category  
(Desired Number of 
Participants) 
Injection Device 
Subcutaneous Injection 
Location 
Desired Number 
of Participants 
Low 
<70.0 kg 
 
(72 participants) 
2-mL PFS-NSD (Reference) 
Arm 
12 
2-mL AI (Test) 
12 
2-mL PFS-NSD (Reference) 
Abdomen 
12 
2-mL AI (Test) 
12 
2-mL PFS-NSD (Reference) 
Thigh 
12 
2-mL AI (Test) 
12 
Medium 
70.0 – 80.0 kg 
 
(72 participants) 
2-mL PFS-NSD (Reference) 
Arm 
12 
2-mL AI (Test) 
12 
2-mL PFS-NSD (Reference) 
Abdomen 
12 
2-mL AI (Test) 
12 
2-mL PFS-NSD (Reference) 
Thigh 
12 
2-mL AI (Test) 
12 
High 
>80.0 kg 
 
(72 participants) 
2-mL PFS-NSD (Reference) 
Arm 
12 
2-mL AI (Test) 
12 
2-mL PFS-NSD (Reference) 
Abdomen 
12 
2-mL AI (Test) 
12 
2-mL PFS-NSD (Reference) 
Thigh 
12 
2-mL AI (Test) 
12 
Abbreviations: AI = autoinjector; PFS-NSD = pre-filled syringe with needle safety device. 
4.2. 
Scientific Rationale for Study Design 
Conducting the study in healthy participants mitigates the potential confounding effects of the 
disease state and concomitant medications in participants with AD. A population of healthy 
participants is frequently used in the assessment of the PK of both small and large molecules. 
A single dose of lebrikizumab and the PK sampling time points have been selected to generate 
PK profiles sufficient to fulfill the study objectives. 
Participants will be randomly assigned to receive injections in the arm, thigh, or abdomen to 
evaluate the impact injection site has on bioavailability of lebrikizumab. 
Previous population PK analyses have shown that patients with a lower body weight tended to 
have a lower clearance and volume of distribution (Zhu et al. 2017). While the effects of body 
weight on these PK parameters were statistically significant, it was not considered to be 
clinically relevant. However, to mitigate these potentially confounding effects, approximately 
equal numbers of participants in each weight category are proposed to avoid a large difference in 
mean weight between the test and the reference delivery-device groups. A participant population 
of 72 per weight group is an approximate target with the recommended weight categories 
selected based on the distribution of weights in prior studies. The number of participants 
assigned to each delivery device and the number of participants assigned to each site of injection 
is desired to be balanced. 
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A parallel-group design is chosen because a crossover design is impractical for lebrikizumab, 
which has a half-life of approximately 25 days. Additionally, a crossover study could confound 
PK data if participants develop neutralizing ADAs. 
4.3. 
Justification for Dose 
A 250-mg dose of lebrikizumab has been selected for this study for the following reasons: 
• the 250-mg dose was well tolerated in 3 completed Phase 2 studies in patients with AD, 
and  
• the 250-mg dose is being investigated in ongoing Phase 3 studies in patients with AD.  
4.4. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the study. 
Participants may be replaced to ensure that approximately 216 participants (108 in each group) 
complete the study (see Section 9.2). 
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5. 
Study Population 
Eligibility of participants for enrollment in the study will be based on the results of screening 
medical history, physical examination, vital signs, clinical laboratory tests, and ECG. The nature 
of any conditions present at the time of the physical examination and any preexisting conditions 
will be documented. 
The inclusion and exclusion criteria used to determine eligibility should be applied at screening 
only, and not continuously throughout the trial. 
Screening may occur up to 28 days prior to enrollment. Participants who are not enrolled within 
28 days of screening may undergo an additional medical assessment and/or clinical 
measurements to confirm their eligibility. In such instances, repeat the following screening tests 
and procedures:  
• weight 
• vital signs 
• ECG 
• clinical laboratory tests, and 
• pregnancy test (females of childbearing potential only) 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be aged 18 to 65 years inclusive, at the time of signing the informed 
consent. 
Type of participant and disease characteristics 
2. Participants who are overtly healthy as determined through medical evaluation including:  
• medical history 
• physical examination (conducted at screening or Day -1) 
• laboratory tests, and  
• cardiac monitoring. 
3. have clinical laboratory test results within normal reference range for the population or 
investigative site, or results with acceptable deviations that are judged to be not clinically 
significant by the investigator. 
Note: Screening and/or Day -1 laboratory testing may be repeated (once) at the discretion 
of the investigator for any out-of-range results.  
4. have venous access sufficient to allow for blood sampling as per the protocol. 
5. agree not to donate blood or plasma until after the end of their participation in the study. 
6. are reliable and willing to make themselves available for the duration of the study and are 
willing to follow study procedures. 
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Weight 
7. have a body mass index within the range 18.0 to 32.0 kg/m2 (inclusive). 
Sex 
8. are males or nonpregnant females of childbearing or non-childbearing potential.  
• Reproductive definitions and contraceptive requirements are provided in 
Appendix 4 (Section 10.4) 
Informed consent 
9. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1), 
which includes compliance with the requirements and restrictions listed in the ICF and in 
this protocol. 
5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
10. have known allergies to lebrikizumab, related compounds, or any components of the 
formulation, or history of anaphylaxis as defined by the Sampson criteria (Sampson et al. 
2006) 
11. have an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases 
the risks associated with participating in the study. 
12. have an abnormal blood pressure and/or pulse rate as determined to be clinically 
significant by the investigator. 
13. have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, 
endocrine, hematological, or neurological disorders capable of significantly altering the 
absorption, metabolism, or elimination of drugs; of constituting a risk when taking the 
investigational product; or of interfering with the interpretation of data. 
14. have a history or presence of psychiatric disorders deemed clinically significant by the 
investigator. 
15. regularly use known drugs of abuse or show positive findings on drug screening or 
Day -1. 
16. show evidence of human immunodeficiency virus infection and/or positive human 
immunodeficiency virus antibodies. 
17. show evidence of hepatitis C and/or positive hepatitis C antibody. 
18. show evidence of hepatitis B and/or positive hepatitis B surface antigen or hepatitis B 
core antibody. 
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19. Infections: 
a. have had a serious infection (such as, pneumonia, cellulitis, sepsis); 
have been hospitalized or have received IV antibiotics for an infection 
within 12 weeks prior to Day 1; have had a serious bone or joint 
infection within 24 weeks prior to Day 1 or have ever had an infection 
of an artificial joint; or are immunocompromised to an extent that 
participation in the study would pose an unacceptable risk to the 
participant as determined by the investigator 
b. have or have had an infection typical of an immunocompromised host 
and/or that occurs with increased incidence in an immunocompromised 
host (including, but not limited to, Pneumocystis jirovecii pneumonia, 
histoplasmosis, or coccidioidomycosis) or have a known 
immunodeficiency 
c. have or have had a herpes simplex infection, herpes zoster infection, or 
any other clinically apparent varicella zoster virus infection within 
12 weeks of Day 1 
d. have had any other active or recent infection within 4 weeks of Day 1 
that, in the opinion of the investigator, would pose an unacceptable risk 
to the participant if participating in the study; these participants may be 
rescreened (once) at least 4 weeks after documented resolution of 
symptoms. 
20. show evidence of active or latent TB, as documented through medical history, 
examination, and TB testing (positive [not indeterminate] QuantiFERON®-TB Gold test; 
if a repeat test is also indeterminate, the participant will not be eligible); or have had 
household contact with a person with active TB, unless appropriate and documented 
prophylaxis treatment has been given. Participants with any history of active TB are 
excluded from the study, regardless of previous or current TB treatments. 
21. medical history of allergic reaction to humanized monoclonal antibodies. 
22. clinically significant multiple or severe drug allergies, intolerance to topical 
corticosteroids, or severe posttreatment hypersensitivity reactions (including, but not 
limited to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic 
epidermal necrolysis, history of anaphylaxis, and exfoliative dermatitis). 
23. ALT or AST >1.5x ULN. 
24. TBL >1.5x ULN (isolated bilirubin >1.5x ULN is acceptable if TBL is fractionated and 
direct bilirubin <35%). 
25. absolute eosinophil count >ULN. 
26. current or chronic history of liver disease. This includes but is not limited to hepatitis 
virus infections, drug- or alcohol-related liver disease, nonalcoholic steatohepatitis, 
autoimmune hepatitis, hemochromatosis, Wilson’s disease, α-1 antitrypsin deficiency, 
primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease 
considered clinically significant by the investigator. 
27. known hepatic or biliary abnormalities (with the exception of Gilberts syndrome or 
asymptomatic gallstones). 
28. have donated blood of more than 500 mL within the previous 4 weeks of study screening. 
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29. have had lymphoma, leukemia, or any malignancy within the past 5 years except for 
basal cell or squamous epithelial carcinomas of the skin that have been resected with no 
evidence of metastatic disease for 3 years. 
30. have had breast cancer within the past 10 years. 
31. are females who are pregnant or lactating. 
Prior/concomitant therapy 
32. have participated in a clinical trial involving an investigational product within 30 days or 
5 half-lives (whichever is longer) prior to screening. If the clinical trial involved 
treatment with biologic agents (such as monoclonal antibodies, including marketed 
drugs), at least 3 months or 5 half-lives (whichever is longer) should have elapsed prior to 
Day 1. 
33. have previously completed or withdrawn from this study or any other study investigating 
lebrikizumab. 
34. intend to use over-the-counter or prescription medication including herbal 
medications within 7 days prior to dosing. Specific medications listed in Section 6.5, may 
be allowed. 
35. live vaccine(s) within 12 weeks prior to screening or plans to receive such vaccines 
during the study. 
36. it is suggested that participants do not receive nonlive or inactivated vaccinations from 
2 weeks prior to, until 2 weeks after lebrikizumab dosing. 
37. treatment with biologic agents (such as monoclonal antibodies including marketed drugs) 
within 3 months or 5 half-lives (whichever is longer) prior to dosing. 
Prior/concurrent clinical study experience 
38. 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. 
39. are Lilly employees or are employees of Covance. 
40. 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. 
Other exclusions 
41. have an average weekly alcohol intake exceeding >21 units for males or >14 units for 
females. One unit is equivalent to 8 g of alcohol: a half pint (approximately 240 mL) of 
beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits. 
42. are unwilling to stop alcohol consumption 24 hours prior to each study visit. 
43. smoke more than 10 cigarettes per day or the equivalent including electronic cigarettes or 
are unable to abide by CRU smoking restrictions. 
44. have excessive tattoos, scars, moles, skin hyperpigmentation, birth marks, or stretch 
marks over either arm, either thigh, or either side of the abdomen that would interfere 
with injection-site assessments. 
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45. in the opinion of the investigator, are unsuitable for inclusion in the study. 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
Participants will receive a light breakfast on the morning of Day 1 prior to dosing. Standard 
meals will be provided at all other times while participants are resident at the CRU, per the 
CRU’s policy. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
Caffeine 
Participants will not be allowed to consume caffeinated products during study visits and while 
resident at the CRU, but otherwise participants will be allowed to maintain their regular caffeine 
consumption. 
Alcohol 
Alcohol consumption is not permitted while participants are resident at the CRU and for 
24 hours prior to each study visit. Alcohol intake during outpatient periods should not exceed 
3 units per day for males or 2 units per day for females.  
Tobacco 
Participants must abide by the CRU smoking restrictions during study visits and while resident at 
the CRU. 
5.3.3. 
Activity 
Participants will be advised to maintain their regular levels of physical activity/exercise; 
however, they should not undertake vigorous or prolonged exercise within 48 hours prior to any 
visit in which laboratory safety tests will occur (Day -1, Day 1, Day 3, Day 15, Day 29, and Day 
99). While certain study procedures are in progress at the site, participants may be required to 
remain recumbent or sitting. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently enrolled in the study. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once, based upon investigator or designee discretion and discussion with Lilly clinical 
pharmacologist. Rescreened participants should be assigned a new participant number and must 
sign a new ICF. 
Repeating of laboratory tests during the screening period or repeating screening tests to comply 
with the protocol-designated screening period, as stated in Section 5, does not constitute 
rescreening. 
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6. 
Study Intervention 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol. 
6.1. 
Study Interventions Administered 
This study involves a comparison of 2-mL (125 mg/mL) SC injections of lebrikizumab using 
PFS-NSD and AI into the arm, thigh, or abdomen for a total administered dose of 250 mg (Table 
KGBG.2). 
Table KGBG.2. 
Study Interventions Administered 
Study Intervention  
Lebrikizumab PFS-NSD 
Lebrikizumab AI 
Dosage Formulation 
Solution for injection 
Solution for injection 
Unit Dose 
Strength(s)/Dosage Level(s) 
125 mg/mL in a 2-mL PFS-NSD  
125 mg/mL in a 2-mL AI 
Route of Administration 
Subcutaneous 
Subcutaneous 
Dosing Instructions 
2-mL injections at site according to the 
randomization 
2-mL injections at site according to 
the randomization 
Abbreviations: AI = autoinjector; PFS-NSD = pre-filled syringe with needle safety device.  
6.1.1. 
Medical Devices 
• Lebrikizumab will be administered by the investigator or designee, using a PFS-NSD and 
an AI. 
• Instructions on how to use the PFS-NSD and the AI will be provided. 
• All product complaints (including malfunction, use error, and inadequate labeling) shall 
be documented and reported by the investigator throughout the clinical investigation (see 
Section 8.3) and appropriately managed by the sponsor. 
• Each device will be labeled according to the country’s regulatory requirements. 
6.2. 
Preparation/Handling/Storage/Accountability 
• The investigator or designee must confirm appropriate storage conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention. 
• Only participants enrolled in the study may receive study intervention. Only study 
personnel may supply, prepare, or administer study intervention. All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited to 
the investigator and authorized study personnel. 
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• The investigator or authorized study personnel are 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 separately. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label study. In order to minimize potential bias, assignment to treatment groups 
will be determined by a computer-generated random sequence using an IWRS. On Day 1 
(referred to as Visit 1 in IWRS), the site will process Visit 1 in the IWRS prior to the start of 
study intervention administration and the participant will be assigned a unique subject number 
and randomized in a 1:1 ratio for delivery device (either PFS-NSD or AI) and within each 
delivery device group in a 1:1:1 ratio for injection site (arm, thigh, or abdomen) resulting in a 
1:1:1:1:1:1 ratio between 6 possible assignment options. The randomization will be stratified by 
weight categories (less than 70.0 kg, 70.0 to 80.0 kg, and more than 80.0 kg). 
6.4. 
Study Intervention Compliance 
Participants are dosed at the site. The investigator or designee will administer study intervention 
through SC injection to participants.  The study intervention (i.e. device and injection location) 
and study participant identification will be confirmed prior to the time of dosing. The date and 
time of the administration will be recorded in the source documents and in the CRF. 
6.5. 
Concomitant Therapy 
Participants must abstain from taking prescription or nonprescription drugs (including vitamins 
and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme 
inducer) or 5 half-lives (whichever is longer) before the start of study intervention until 
completion of the last visit, unless, in the opinion of the investigator and sponsor, the medication 
will not interfere with the study. 
Participants on stable concomitant medication at the time of study entry should continue their 
regular, unchanged dose throughout the study. Permitted concomitant medications, at the 
discretion of the investigator, include hormonal contraceptives, hormone-replacement therapy, 
and thyroid replacement. Inclusion of participants on any other concomitant medication (for 
example, statins and anti-hypertensives) is contingent upon approval following consultation with 
the sponsor. 
Acetaminophen, at doses of 3 g/day, is permitted for use during the study, other than on the 
dosing day within 4 hours prior to and 4 hours after dosing. Other concomitant medication may 
be considered on a case-by-case basis by the investigator in consultation with the medical 
monitor if required. 
Any medication or vaccine, including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements that the participant is receiving at the time of enrollment or receives 
during the study must be recorded along with 
● reason for use 
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● dates of administration including start and end dates, and 
● dosage information including dose and frequency for concomitant therapy of 
special interest. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
Participants will be restricted from applying any creams or lotions on the arm, thigh, or 
abdominal skin within 24 hours prior to or after the injections and participants should not receive 
any additional SC injections at the site of lebrikizumab administration for the duration of the 
study. 
6.6. 
Dose Modification 
Not applicable. 
6.7. 
Intervention after the End of the Study 
Not applicable. 
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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal 
7.1. 
Discontinuation of Study Intervention 
Not applicable. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study 
● at any time at his/her own request  
● at the request of his/her designee (for example, parents or legal guardian) 
● at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons 
● if the participant becomes pregnant during the study, and 
● 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 
At the time of discontinuing from the study, if possible, an early discontinuation 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 interventions and from the 
study at that time. 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent.  If a participant 
withdraws from the study, he/she may request destruction of any samples taken and not tested, 
and the investigator must document this in the site study records.  
7.2.1. 
Discontinuation of Inadvertently Enrolled Participants 
If the sponsor or investigator identifies a participant who did not meet enrollment criteria and 
was inadvertently enrolled, then the participant should be discontinued from study treatment 
unless there are extenuating circumstances that make it medically necessary for the participant to 
continue on study treatment.  If the investigator and the sponsor CRP agree it is medically 
appropriate to continue, the investigator must obtain documented approval from the sponsor CRP 
to allow the inadvertently enrolled participant to continue in the study with or without treatment 
with investigational product.  Safety follow-up should be performed 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 or designee are 
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expected to make diligent attempts to contact participants who fail to return for a scheduled visit 
or were otherwise unable to be followed up by the site. 
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8. 
Study Assessments and Procedures 
Study procedures and their timing are summarized in the SoA (Section 1.3).  
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.  
The specifications in this protocol for the timings of safety and sample collection are given as 
targets to be achieved within reasonable limits. Modifications may be made to the time points 
based upon emerging clinical information. The scheduled time points may be subject to minor 
alterations; however, the actual time must be correctly recorded in the CRF.  Failure or being late 
(i.e. outside stipulated time allowances) to perform procedures or obtain samples due to 
legitimate clinical issues (for example, equipment technical problems, venous access difficulty, 
or participant defaulting or turning up late on an agreed scheduled procedure) will not be 
considered as protocol deviations but the CRU will still be required to notify the sponsor in 
writing via a file note. 
Appendix 2 (Section 10.2) lists the laboratory tests that will be performed for this study. 
Appendix 2 (Section 10.2.1) provides a summary of the maximum number and volume of 
invasive samples, for all sampling, during the study. 
Unless otherwise stated in the following subsections, all samples collected for specified 
laboratory tests will be destroyed within 60 days of receipt of confirmed test results. Certain 
samples may be retained for a longer period, if necessary, to comply with applicable laws, 
regulations, or laboratory certification standards. 
8.1. 
Efficacy Assessments 
Efficacy is not evaluated in this study. 
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 include, at a minimum, assessments of the cardiovascular, 
respiratory, gastrointestinal, and neurological systems. Height and weight will also be measured 
and recorded.  
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
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8.2.2. 
Vital Signs 
For each participant, vital sign measurements should be conducted according to the SoA 
(Section 1.3).  
Blood pressure and pulse rate should be measured after at least 5 minutes sitting. Measurement 
from supine is allowed if the participant feels unable to stand. 
If orthostatic measurements are required, participants should be supine for at least 5 minutes and 
stand for at least 3 minutes.  
If the participant feels unable to stand, supine vital signs only will be recorded. 
Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of dizziness or 
posture-induced symptoms.  Additional vital signs may be measured during each study period if 
warranted.  
8.2.3. 
Electrocardiograms 
Single 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3). 
ECGs must be recorded before collecting any blood samples. Participants must be supine for 
approximately 5 to 10 minutes before ECG collection and remain supine but awake during ECG 
collection. ECGs may be obtained at additional times, when deemed clinically necessary. All 
ECGs recorded should be stored at the investigational site. 
ECGs will be interpreted by a qualified investigator (the physician or qualified designee) at the 
site as soon after the time of ECG collection as possible, and ideally while the participant is still 
present, to determine whether the participant meets entry criteria at the relevant visit(s) and for 
immediate participant management, should any clinically relevant findings be identified.  
Any new clinically relevant finding should be reported as an AE. 
8.2.4. 
Clinical Safety Laboratory Assessments 
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and to the 
SoA (Section 1.3) for the timing and frequency. 
The investigator must review the laboratory results, document this review, and report any 
clinically relevant changes occurring during the study as an AE. The laboratory results must be 
retained with source documents unless a Source Document Agreement or comparable document 
cites an electronic location that accommodates the expected retention duration. Clinically 
significant abnormal laboratory findings are those that are not associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the participant's 
condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study 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. 
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All protocol-required laboratory assessments, as defined in Appendix 2 (Section 10.2), must be 
conducted in accordance with the SoA, standard collection requirements, and laboratory manual. 
If laboratory values from nonprotocol-specified laboratory assessments performed at an 
investigator-designated local laboratory require a change in participant management or are 
considered clinically significant by the investigator (for example, SAE or AE or dose 
modification), then report the information as an AE. 
If a central vendor is used for the study, Lilly or its designee will provide the investigator with 
the results of laboratory tests analyzed by a central vendor. 
8.2.4.1. 
Tuberculosis Testing 
Participants will be tested as indicated in the SoA (Section 1.3) for evidence of active or latent 
TB using the QuantiFERON-TB Gold test. If the test is indeterminate, 1 re-test is allowed. If the 
re-test is indeterminate, the participant will be excluded from the study. 
Participants who have had household contact with a person with active TB must be excluded, 
unless appropriate and documented prophylaxis treatment for TB has been completed. 
Participants with any history of active TB are excluded from the study, regardless of previous or 
current TB treatments. 
8.2.5. 
Safety Monitoring 
The Lilly clinical pharmacologist or CRP/scientist will monitor safety data throughout the course 
of the study. 
Lilly will review SAEs within time frames mandated by company procedures.  The Lilly clinical 
pharmacologist or CRP will periodically review  
• trends in safety data  
• laboratory analytes, and   
• AEs.  
When appropriate, the Lilly clinical pharmacologist or CRP will consult with the functionally 
independent Global Patient Safety therapeutic area physician or clinical research scientist. 
8.2.5.1. 
Hepatic Safety 
Close hepatic monitoring 
Laboratory tests Appendix 6 (Section 10.6), including ALT, AST, ALP, TBL, direct bilirubin, 
gamma-glutamyl transferase, and creatine kinase, should be repeated within 48 to 72 hours to 
confirm the abnormality and to determine if it is increasing or decreasing, if 1 or more of these 
conditions occur: 
If a participant with baseline 
results of ...  
develops the following elevations: 
ALT or AST <1.5x ULN 
ALT or AST ≥3x ULN 
ALP <1.5x ULN 
ALP ≥2x ULN 
TBL <1.5x ULN 
TBL ≥2x ULN (except for patients with 
Gilbert’s syndrome) 
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ALT or AST ≥1.5x ULN 
ALT or AST ≥2x baseline 
ALP ≥1.5x ULN 
ALP ≥2x baseline 
TBL ≥1.5x ULN 
TBL ≥1.5x baseline (except for patients with 
Gilbert’s syndrome) 
 
If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for 
possible causes of abnormal liver test results should be initiated by the investigator in 
consultation with the Lilly-designated medical monitor. At a minimum, this evaluation should 
include physical examination and a thorough medical history, including symptoms, recent 
illnesses (for example, heart failure, systemic infection, hypotension, or seizures), recent travel, 
history of concomitant medications (including over the counter), herbal and dietary supplements, 
history of alcohol drinking, and other substance abuse.  
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests. 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and laboratory results stabilize. Monitoring of ALT, AST, ALP, 
and TBL should continue until levels normalize or return to approximate baseline levels. 
Comprehensive hepatic evaluation  
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
1 or more of these conditions occur: 
If a participant with baseline 
results of...  
develops the following elevations: 
ALT or AST <1.5x ULN 
ALT or AST ≥3x ULN with hepatic signs/symptoms*, or  
ALT or AST ≥5x ULN 
ALP <1.5x ULN 
ALP ≥3x ULN 
TBL <1.5x ULN 
TBL ≥2x ULN (except for patients with Gilbert’s syndrome) 
ALT or AST ≥1.5x ULN 
ALT or AST ≥2x baseline with hepatic signs/symptoms*, or 
ALT or AST ≥3x baseline 
ALP ≥1.5x ULN 
ALP ≥2x baseline 
TBL ≥1.5x ULN 
TBL ≥2x baseline (except for patients with Gilbert’s 
syndrome)  
* Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, 
and/or eosinophilia >5%. 
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time-international normalization ratio; 
tests for viral hepatitis A, B, C, or E; tests for autoimmune hepatitis; and an abdominal imaging 
study (for example, ultrasound or computed tomography scan).  
Based on the patient’s history and initial results, further testing should be considered in 
consultation with the Lilly-designated medical monitor, including tests for hepatitis D virus, 
cytomegalovirus, Epstein-Barr virus, acetaminophen levels, acetaminophen protein adducts, 
urine toxicology screen, Wilson’s disease, blood alcohol levels, urinary ethyl glucuronide, and 
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blood phosphatidylethanol. Based on the circumstances and the investigator’s assessment of the 
participant’s clinical condition, the investigator should consider referring the participant for a 
hepatologist or gastroenterologist consultation, magnetic resonance cholangiopancreatography, 
endoscopic retrograde cholangiopancreatography, cardiac echocardiogram, or a liver biopsy. 
Additional hepatic data collection (hepatic safety CRF) in study participants who have abnormal 
liver test results during the study  
Additional hepatic safety data collection in hepatic safety CRFs should be performed in study 
participants who meet 1 or more of the following 5 conditions: 
1. Elevation of serum ALT level to ≥5x ULN on 2 or more consecutive blood tests (if 
baseline ALT <1.5x ULN) 
• In participants with baseline ALT ≥1.5x ULN, the threshold is ALT ≥3x baseline 
on 2 or more consecutive tests 
2. Elevation of TBL level to ≥2x ULN (if baseline TBL <1.5x ULN) (except for cases of 
known Gilbert’s syndrome) 
• In participants with baseline TBL ≥1.5x ULN, the threshold should be TBL ≥2x 
baseline 
3. Elevation of serum ALP to ≥2x ULN on 2 or more consecutive blood tests (if baseline 
ALP <1.5x ULN) 
• In participants with baseline ALP ≥1.5x ULN, the threshold is ALP ≥2x baseline 
on 2 or more consecutive blood tests 
4. Hepatic event considered to be an SAE 
5. Discontinuation of study drug due to a hepatic event  
Note: the interval between the 2 consecutive blood tests should be at least 2 days. 
8.2.5.2. 
Injection-Site Reactions 
Symptoms of a local ISR may include erythema, induration, pain, pruritus, and edema. 
If an ISR is reported by a participant, investigator, or site staff as an AE of a local ISR, the ISR 
AE CRF will be used to capture additional information about this reaction (for example, 
injection-site pain, degree and area of erythema, induration, pruritus, and edema).  
In addition, all positive responses of injection-site pain will require an additional assessment 
using the Pain Visual Analog Scale (Williamson and Hoggart 2005).  
8.2.5.3. 
Hypersensitivity Reactions 
Many drugs, but particularly biologic agents, carry the risk of systemic hypersensitivity 
reactions. If such a reaction occurs, additional data describing each symptom should be provided 
to the sponsor in the electronic CRF. 
Sites should have appropriately trained medical staff and appropriate medical equipment 
available while study participants are receiving study drug. It is recommended that participants 
who experience a systemic hypersensitivity reaction be treated per national and international 
guidelines. 
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In the case of generalized urticaria or anaphylaxis, additional blood and urine samples should be 
collected as described in Appendix 7 (Section 10.7). Laboratory results are provided to the 
sponsor via the central laboratory. 
8.3. 
Adverse Events, Serious Adverse Events, and Product Complaints 
Investigators are responsible for monitoring the safety of participants who have entered this 
study and for alerting Lilly or its designee to any event that seems unusual, even if this event 
may be considered an unanticipated benefit to the participant.  
The investigator is responsible for the appropriate medical care of participants during the study.  
The definitions of the following events can be found in Appendix 3: 
• AEs 
• SAEs 
• ADEs 
• UADEs 
• SADEs, and 
• product complaints 
These events will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant’s legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet these definitions and remain responsible for following up events that 
are serious, considered related to the study intervention or study procedures, or that caused the 
participant to discontinue the study (see Section 7). 
Care will be taken not to introduce bias while detecting events. Open-ended and nonleading 
verbal questioning of the participant is the preferred method to inquire about event occurrences. 
After the initial report, the investigator is required to proactively follow up each participant at 
subsequent visits/contacts. All SAEs will be followed up until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). For 
product complaints, the investigator is responsible for ensuring that follow-up includes any 
supplemental investigations as indicated to elucidate the nature and/or causality. Further 
information on follow-up procedures is provided in Appendix 10.3.  
8.3.1. 
Timing and Mechanism for Collecting Events 
This table describes the timing, deadlines, and mechanism for collecting events. 
Event 
Collection Start 
Collection Stop 
Timing for 
Reporting to 
Sponsor or Designee 
Mechanism for 
Reporting 
AE 
Signing of the 
ICF 
Participation in 
study has ended 
As soon as possible 
upon site awareness 
AE eCRF 
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Event 
Collection Start 
Collection Stop 
Timing for 
Reporting to 
Sponsor or Designee 
Mechanism for 
Reporting 
SAE and SAE updates – 
prior to start of study 
intervention and deemed 
reasonably possibly related 
with study procedures 
Signing of the 
ICF 
Start of 
intervention 
Within 24 hours of 
awareness 
SAE eCRF 
SAE and SAE updates – 
after start of study 
intervention 
Start of 
intervention 
Participation in 
study has ended 
Within 24 hours of 
awareness 
SAE eCRF 
SAE – after participant’s 
study participation has 
ended and the investigator 
becomes aware 
After participant’s 
study 
participation has 
ended 
NA 
Promptly 
SAE paper form 
Pregnancy in female 
participants and female 
partners of male 
participants 
After the start of 
study intervention 
125 days after 
dose 
Within 24 hours of 
learning of the 
pregnancy 
Pregnancy eCRF 
or SAE eCRF 
Product complaint 
associated with an SAE or 
might have led to an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 24 hours of 
awareness 
product complaint 
form 
Product complaint not 
associated with an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 1 business 
day of awareness 
product complaint 
form 
Updated product complaint 
information 
— 
— 
As soon as possible 
upon site awareness 
Originally 
completed 
product complaint 
form with all 
changes signed 
and dated by the 
investigator 
Product complaint (if 
investigator becomes 
aware) 
Participation in 
study has ended 
NA 
Promptly 
Product complaint 
form 
8.3.2. Adverse Events of Special Interest  
Adverse events of special interest for this study include 
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•  c o nj u ncti vitis 
•  her pes i nfecti o n or z oster, a n d  
•  parasitic i nfecti o n or a n i nfecti o n rel ate d t o a n i ntracell ular p at h o ge n . 
If t hese a d v erse e ve nts of s pecial i nterest  are re p orte d, sites will be pr o m pte d t o c ollect a d diti o nal 
data . 
8. 4.  
Tre at me nt of O ver d ose  
F or t his st u d y, a n y d ose of le bri kiz u ma b greater t ha n 2 5 0 m g  will be c o nsi dere d a n o v er d ose.  
T he sp o ns or d oes n ot rec o m me n d s pecific treat me nt f or a n o ver d ose . 
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or/treati n g p h ysicia n s h o ul d 
1.  c o ntact t he me dical m o nit or  i m me diatel y. 
2.  cl osel y m o nit or t he p artici pa nt f or a n y A E/ S A E a n d la b orat or y a b n or malities . 
8. 5.  
P h ar m ac o ki netics  
B l o o d sa m ples of a p pr o xi matel y 3  m L will be c oll ecte d f or meas ure me nt of ser u m 
c o nce ntr ati o ns of le bri kiz u ma b as s pecifie d i n t he S o A .  
A ma x i m u m of 5  sa m ples ma y be c ollecte d at a d diti o nal ti me p oi nts d uri n g t he st u d y if 
warra nte d a n d a gree d u p o n bet wee n t he i n v esti gat or a n d t he s p o ns or. T h e ti mi n g of sa m pli n g  
ma y b e altere d d uri n g t he c o urse of t he st u d y b ase d o n ne wl y a vaila ble data ( f or e x am ple , t o 
o btai n data cl oser t o t he ti me of pea k ser u m c o nce ntrati o ns) t o e ns ure a p pr o priate m o nit ori n g.  
I nstr u cti o ns f or t he c ollecti o n a n d ha n dli n g of bi ol o gical sa m ples will be pr o vi de d b y t he 
s p o ns or. T he act u al date a n d ti me ( 2 4-h o ur cl o c k ti me) of eac h sa m ple will be rec or de d.  
8. 5. 1.  
Bi o a n al ysis  
Sa m ples will be a nal yze d at a la b orat or y a p pr o ve d b y t he s p o ns or a n d st ore d at a facilit y 
desi g nat e d b y t he s p o ns or .  
Ser u m c o nce ntr ati o ns of  le bri kiz u ma b will be assa ye d 
 
.  A nal ys es of sa m pl es c ollecte d fr o m place b o -treate d partici pa nts 
are n ot pla n ne d.   
Bi oa nal ytical s a m ples c ollecte d t o meas ure i n vesti gati o nal pr o d u ct c o nce ntr ati o ns will be 
retai ne d f or a ma xi m u m of 1 year f oll o wi n g last p artici pa nt visit f or t he st u d y.  
 
 
  
8. 6.  
P h ar m ac o d y n a mics  
P har mac o d y na mic p ara m eters a re n ot e val u ate d i n t his st u d y. 
8. 7.  
Ge netics  
Ge netics are n ot e v al uate d i n t his st u d y.  
A p pr o ve d o n 1 7 A u g 2 0 2 1 G M T
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A blood sample for DNA isolation will be collected from participants.  
See Appendix 10.5 for information regarding genetic research. 
8.8. 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.9. 
Immunogenicity Assessments 
At the visits and times specified in the SoA, venous blood samples will be collected to determine 
antibody production against lebrikizumab. Antibodies may be further characterized and/or 
evaluated for their ability to neutralize the activity of lebrikizumab.  To interpret the results of 
immunogenicity, a venous blood sample will be collected at the same time points to determine 
the serum concentrations of lebrikizumab.  All samples for immunogenicity should be 
taken predose when applicable and possible. 
Immunogenicity will be assessed by a validated assay designed to detect ADAs in the presence 
of lebrikizumab at a laboratory approved by the sponsor. Samples may be stored for a maximum 
of 15 years (or according to local regulations) following the last participant’s last visit for the 
study at a facility selected by the sponsor.  Samples may also be used for development and 
control of an immunogenicity assay. 
8.10. 
Health Economics 
This section is not applicable for this study. 
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9. 
Statistical Considerations 
9.1. 
Statistical Hypotheses 
The primary objective of this study is to evaluate PK following administration of lebrikizumab 
using a PFS-NSD and an AI. 
9.2. 
Sample Size Determination 
Approximately 240 participants may be enrolled so that approximately 216 participants (108 in 
the lebrikizumab PFS-NSD [reference] group and 108 in the AI [test] group) complete the study. 
A sample size of 108 participants per device group will provide approximately 90% power that 
the 90% CI of the geometric mean ratio of maximum observed drug concentration (Cmax) and 
area under the concentration versus time curve (AUC) between groups will fall within 
equivalence range of 0.8 to 1.25. This sample size calculation was based on the assumptions that 
the PK parameters have log-normal distribution, the percent coefficients of variation (%CV) of 
Cmax and AUC are less or equal to 30%, the expected ratio of geometric means is between 0.9 
and 1.1, and the %CV are the same for participants from each device group. The 30% CV 
assumption is based on lebrikizumab PK data in several previous studies. 
To properly evaluate AUC from time zero to infinity (AUC[0-∞]), lebrikizumab concentrations 
must be collected through at least Day 71. To ensure that approximately 216 participants (108 in 
each group) provide evaluable PK data, approximately 240 participants will be enrolled and 
receive study drug, assuming up to 10% of the participants may not complete through at least 
Day 71. Participants who do not complete at least through Day 22 (a period sufficient to 
determine Cmax) may be replaced. The replacement participants should be in the same weight 
category as the original participants.  
9.3. 
Populations for Analyses 
The following populations are defined: 
Population 
Description 
Safety  
All participants randomly assigned to study intervention and who 
receive study intervention. Participants will be analyzed 
according to the intervention they actually received. 
Pharmacokinetic Analysis 
All enrolled participants who received a full dose of study 
intervention and have evaluable PK sample. 
9.4. 
Statistical Analyses 
Statistical analysis of this study will be the responsibility of the sponsor or its designee. 
9.4.1. General Considerations 
PK analyses will be conducted on data from all participants who receive the complete single 
dose of lebrikizumab and have sufficient evaluable PK data.  
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Safety analyses will be conducted for all enrolled participants who receive the single dose of 
lebrikizumab injection, whether or not they complete all protocol requirements. 
Additional exploratory analyses of the data will be conducted as deemed appropriate, and study 
results may be pooled with the results of other studies for population PK analysis purposes to 
avoid issues with post hoc analyses and incomplete disclosures of analyses. 
9.4.2. 
Pharmacokinetic Analyses 
PK parameter estimates for lebrikizumab will be calculated using standard noncompartmental 
methods of analysis.  
The primary parameters for analysis will be AUC from time zero to time t, where t is the last 
time point with a measurable concentration (AUC[0-tlast]), AUC(0-∞), and Cmax of 
lebrikizumab. The time of Cmax (tmax) will also be reported. Other noncompartmental 
parameters, such as slope of terminal elimination phase, half-life (t1/2), apparent oral clearance, 
and apparent volume of distribution during the terminal elimination phase may be reported as 
appropriate. 
The primary PK parameter estimates for lebrikizumab will be compared between the reference 
PFS-NSD (R) and test AI (T). Log-transformed Cmax, AUC(0-tlast), and AUC(0-∞) estimates 
will be evaluated in a linear mixed-effects model with fixed effects for weight group, 
injection-site location, and device group, and a random effect for participant. The treatment 
differences will be back transformed to present the ratios of geometric means and the 
corresponding 90% CIs. Comparisons will be made between the 2 devices.  
Bioequivalence between the PFS-NSD and the AI will be declared if the 90% CI for AUC(0-∞), 
AUC(0-tlast), and Cmax are contained within the 0.80 to 1.25 range.  
The tmax will be analyzed between the 2 device groups using a Wilcoxon signed rank test. A 
Hodges-Lehmann estimate of the median differences, 90% CIs, and p-values will be calculated 
for both treatments.  
PK parameter estimates will be summarized by weight category (<70 kg, 70 to 80 kg, and 
>80 kg) as well as injection-site location (abdomen, arm, thigh) for each device group as 
appropriate. Additional analyses may be conducted if deemed appropriate. 
9.4.3. 
Safety Analyses 
All safety analyses will be made on the Safety Population. All AEs will be listed, and if the 
frequency of events allows, safety data will be summarized using descriptive methodology. The 
incidence of AEs for each device will be presented by severity and by association with 
lebrikizumab as perceived by the investigator. AEs reported to occur prior to study entry will be 
distinguished from those reported as new or increased in severity during the study. Each AE will 
be classified by the most suitable term from Medical Dictionary for Regulatory Activities. The 
number of SAEs will be reported. 
9.4.4. 
Evaluation of Immunogenicity  
The frequency and percentage of participants with preexisting ADAs and with TE-ADAs to 
lebrikizumab will be tabulated. TE-ADAs are defined as those with a titer 2-fold (1 dilution) 
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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). For the TE-ADA subjects, the distribution 
of maximum titers will be described. The frequency of neutralizing antibodies will also be 
tabulated in TE-ADA subjects. The relationship between the presence of antibodies and the 
safety and PK parameters to lebrikizumab may be assessed. 
9.5. 
Interim Analyses  
No interim analyses are planned for this study.  If an unplanned interim analysis is deemed 
necessary the Lilly clinical pharmacologist, investigator, or designee will consult with the 
appropriate medical director or designee to determine if it is necessary to amend the protocol. 
9.6. 
Data Monitoring Committee (DMC) 
No data monitoring committee is required for this study. 
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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 International Ethical Guidelines 
• Applicable ICH GCP Guidelines 
• Applicable laws and regulations 
The protocol, protocol amendments, ICF, Investigator’s Brochure, and other relevant documents 
(for example, 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 Code of Federal Regulations, 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. 
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 Code of Federal Regulations 50, local regulations, ICH guidelines, Health 
Insurance Portability and Accountability Act requirements, where applicable, and the IRB/IEC 
or study center. 
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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. 
10.1.3. 
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 that 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 his/her 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. 
10.1.4. 
Dissemination of Clinical Study Data 
Communication of suspended or terminated dosing 
If a decision is taken to suspend or terminate dosing in the trial due to safety findings, this 
decision will be communicated by Lilly to all investigators (for example, through phone and/or 
email) as soon as possible. It will be a requirement that investigators respond upon receipt to 
confirm that they understand the communication and have taken the appropriate action prior to 
further dosing any participants with study intervention. Any investigator not responding will be 
followed up by Lilly personnel prior to any further planned dosing. If a dose is planned 
imminently, Lilly personnel will immediately, and continually, use all efforts to reach 
investigators until contact is made and instructions are verified. 
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 does not proactively share data from Phase 1 clinical trials.  Requests for access to 
Phase 1 clinical trial data are evaluated on a case-by-case basis taking into consideration the 
ability to anonymize the data and the nature of the data collected. 
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10.1.5. 
Data Quality Assurance 
Investigator responsibilities  
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (for example, laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Data management and monitoring 
Monitoring details describing strategy (for example, risk-based initiatives in operations and 
quality such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques are provided in the Monitoring Plan. 
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
The sponsor assumes accountability for actions delegated to other individuals (for example, 
contract research organizations). 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
Records retention and audits  
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for the time period outlined in the clinical trial agreement unless 
local regulations or institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the sponsor. No records 
may be transferred to another location or party without written notification to the sponsor. 
In addition, the sponsor or its representatives will periodically check a sample of the participant 
data recorded against source documents at the study site. The study may be audited by the 
sponsor or its representatives, and/or regulatory agencies at any time. Investigators will be given 
notice before an audit occurs. 
Data capture system 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor. 
An electronic data capture system will be used in this study for the collection of CRF data.  The 
investigator maintains a separate source for the data entered by the investigator or designee into 
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the sponsor-provided electronic data capture system.  The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the CRF. 
Data collected via the sponsor-provided data capture system(s) will be stored at third party. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture system(s).  Prior to decommissioning, the investigator will receive an archival 
copy of pertinent data for retention. 
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports will be provided to the investigator for review 
and retention.  Data will subsequently be transferred from the central vendor to the sponsor data 
warehouse. 
Data from complaint forms submitted to the sponsor will be encoded and stored in the global 
product complaint management system. 
10.1.6. 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the electronic CRF 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 10.1.5. 
10.1.7. 
Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
Site closure  
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to 
• failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor’s procedures, or GCP guidelines 
• inadequate recruitment of participants by the investigator 
• discontinuation of further study intervention development. 
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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. 
10.1.8. 
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 if the results are deemed to be of significant medical 
importance. 
 
 
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10.2. 
Appendix 2: Clinical Laboratory Tests 
The tests detailed below will be performed by the central laboratory or by the local laboratory, as 
detailed in the following table. 
In circumstances where the sponsor approves local laboratory testing in lieu of central laboratory 
testing (in the following table), the local laboratory must be qualified in accordance with 
applicable local regulations. 
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 will be conducted as detailed in the SoA. 
Investigators must document their review of the laboratory safety results. 
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Safety Laboratory Tests 
 
Clinical Laboratory Tests 
Comments 
Hematology 
Performed locally at Screening and Day -1 and 
centrally at Day 1 predose and all postdose time 
points unless otherwise stated.  
Hematocrit 
 
Hemoglobin 
 
Erythrocyte count (RBC) 
 
Mean cell volume  
 
Mean cell hemoglobin  
 
Mean cell hemoglobin concentration  
 
Leukocytes (WBC)  
 
Platelets 
 
Cell morphology (RBC and WBC) 
 
Differential counts (% and absolute) of:  
 
Neutrophils 
 
Lymphocytes 
 
Monocytes 
 
Eosinophils 
 
Basophils 
 
 
 
Urinalysis 
Performed locally at Screening and Day -1 and 
centrally at Day 1 predose unless otherwise stated. 
Specific gravity 
 
pH 
 
Protein 
 
Glucose 
 
Ketones 
 
Bilirubin 
 
Urobilinogen 
 
Blood 
 
Nitrite 
 
Microscopic examination of sediment 
 
 
 
Clinical Chemistry 
Performed locally at Screening and Day -1 and 
centrally at Day 1 predose and all postdose time 
points unless otherwise stated. 
Sodium 
 
Potassium 
 
Bicarbonate 
 
Chloride 
 
Calcium  
 
Phosphorus 
 
Glucose 
 
Blood urea nitrogen (BUN) 
 
Creatinine 
 
Uric acid 
 
Total cholesterol  
 
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Safety Laboratory Tests 
 
Clinical Laboratory Tests 
Comments 
Total protein 
 
Albumin 
 
Total bilirubin  
 
Direct bilirubin 
 
Alkaline phosphatase (ALP) 
 
Aspartate aminotransferase (AST) 
 
Alanine aminotransferase (ALT) 
 
Gamma-glutamyl transferase (GGT) 
 
 
 
Other tests 
 
Ethanol testing  
Tests may be repeated locally at additional time 
points at the discretion of the investigator 
Urine drug screen 
Tests may be repeated locally at additional time 
points at the discretion of the investigator 
Hepatitis B surface antigen 
Performed at screening only 
Hepatitis B core antibody 
Performed at screening only 
Hepatitis B surface antibody 
Performed at screening only 
Hepatitis C antibody 
Performed at screening only 
HIV 
Performed at screening only 
QuantiFERON®-TB Gold 
Performed at screening only 
Pregnancy test (females of childbearing potential only)  
 
Performed at screening, Day -1, and Day 99 or 
early discontinuation. 
FSH (females only)  
Performed at screening only 
Abbreviations: FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; RBC = red blood cell; 
WBC = white blood cell. 
10.2.1. 
Blood Sampling Summary 
This table summarizes the approximate number of venipunctures and blood volumes for all 
blood sampling (screening, safety laboratories, and bioanalytical assays) during the study.  
Protocol J2T-MC-KGBG Sampling Summary 
 
Purpose 
Approximate Blood 
Volume per Sample (mL)  
Number of Blood 
Samples 
Total Volume 
(mL) 
Screening testsa 
45 
1 
45 
Local clinical laboratory and 
pregnancy testsa 
12 
2 
24 
Central clinical laboratory testsa 
4.5 
5 
22.5 
Pharmacokinetics  
3 
13 
39 
Immunogenicity 
10 
4 
40 
Pharmacogenetics 
10 
1 
10 
Total 
 
 
180.5 
Total for clinical purposes 
190 
a Additional samples may be drawn if needed for safety purposes. 
 
 
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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
• The definitions and procedures detailed in this appendix are in accordance with 
International Organization for Standardization 14155. 
• Both the investigator and the sponsor will comply with all local medical device reporting 
requirements. 
• The detection and documentation procedures described in this protocol apply to all 
sponsor medical devices provided for use in the study. See Section 6.1.1 for the list of 
sponsor medical devices. 
10.3.1. 
Definition of AEs and ADE 
AE and ADE Definitions 
• An AE is any untoward medical occurrence in a participant administered a 
pharmaceutical product and which does not necessarily have a causal relationship with 
the study intervention. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product. 
• An ADE is a nonserious AE that can be attributed to a device.  Any untoward medical 
occurrence, unintended disease or injury, or untoward clinical signs (including 
abnormal laboratory finding) in study participants, users, or other persons, whether or 
not related to the investigational medical device. This definition includes events related 
to the investigational medical device or comparator and events related to the 
procedures involved except for events in users or other persons, which include only 
events related to investigational devices.  
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (for example, ECG, radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (that is, not related 
to progression of underlying disease). 
• Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration even 
though they may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
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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 that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
• Medical or surgical procedure (for example, endoscopy, appendectomy): the condition 
that leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
10.3.2. 
Definition of SAE, SADE, and UADE 
If an event is not an AE per the definition above, then it cannot be an SAE even if serious 
conditions are met (for example, hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted to hospital 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during hospitalization 
are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious. 
• Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE. 
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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 (for example, sprained ankle), which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
• Abnormal pregnancy outcomes (for example, spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs. 
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 1 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.  
SADE definition 
A SADE is defined as an adverse device effect that has resulted in any of the consequences 
characteristic of an SAE. 
UADE definition 
A UADE is a SADE which by its nature, incidence, severity, or outcome has not been 
identified in the current version of the risk analysis report. 
10.3.3. 
Recording and Follow-Up of AE and/or SAE 
AE and SAE 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (for example, hospital progress notes, laboratory reports, and 
diagnostics reports) related to the event. 
• The investigator will then record all relevant AE/SAE information in the participant’s 
medical records, in accordance with the investigator’s normal clinical practice. 
AE/SAE information is reported on the appropriate electronic CRF page. 
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• It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to the sponsor or designee in lieu of completion of the AE/SAE electronic CRF 
page. 
• There may be instances when copies of medical records for certain cases are requested 
by the sponsor or designee. In this case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records before 
submission to the sponsor or designee. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories:  
• Mild: A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities of 
daily living. 
• Moderate: A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant. 
• Severe: A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. An AE that is 
assessed as severe should not be confused with an SAE. Severe is a category utilized 
for rating the intensity of an event; and both AEs and SAEs can be assessed as severe. 
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The investigator will also consult the Investigator’s Brochure in his/her assessment. 
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• For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor or designee. 
However, it is very important that the investigator always make an assessment of 
causality for every event before the initial transmission of the SAE data to the sponsor 
or designee. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send 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 the sponsor 
or designee to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. 
• If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide the sponsor or designee with a copy of any 
postmortem findings including histopathology. 
10.3.4. 
Reporting of SAEs 
SAE Reporting via SAE Report 
• Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the sponsor or designee. 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 
• Contacts for SAE reporting can be found in the SAE report. 
10.3.5. 
Regulatory Reporting Requirements 
SAE Regulatory Reporting 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
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● 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, 
IRBs/IECs, and investigators. 
● An investigator who receives an investigator safety report describing an SAE 
or other specific safety information (for example, summary or listing of SAEs) 
from the sponsor will review and then file it along with the Investigator’s 
Brochure and will notify the IRB/IEC, if appropriate according to local 
requirements. 
 
 
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10.8. Appendix 8: Medical Device Adverse Events (AEs), Adverse Device 
Effects (ADEs), Serious Adverse Events (SAEs) and Device Deficiencies: 
Definition and Procedures for Recording, Evaluating, Follow-up, and 
Reporting 
Refer to Appendix 3 (Section 10.3) for definitions and procedures for recording, evaluating, 
follow-up, and reporting of all events. 
 
 
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10.9. 
Appendix 9: Abbreviations 
Term 
Definition 
AD 
atopic dermatitis 
ADA 
antidrug antibody 
ADE 
adverse device effect 
AE 
adverse event 
AI 
autoinjector 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the concentration versus time curve 
AUC(0-∞)  
area under the concentration versus time curve from time zero to infinity 
AUC(0-tlast) 
area under the concentration versus time curve from time zero to time t, where t is the 
last time point with a measurable concentration 
CI 
confidence interval 
Cmax 
maximum observed drug concentration 
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. 
CRF 
case report form 
CRP 
clinical research physician:  Individual responsible for the medical conduct of the 
study.  Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician, or other medical officer. 
CRU 
clinical research unit 
CV 
coefficient of variation 
device deficiencies 
equivalent to product complaint 
ECG 
electrocardiogram 
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. 
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GCP 
good clinical practice 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IL 
interleukin 
IRB 
Institutional Review Board 
ISR 
injection-site reaction 
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. 
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. 
IWRS 
interactive web-response system 
participant 
Equivalent to CDISC term “subject”: an individual who participates in a clinical trial, 
either as a recipient of an investigational medicinal product or as a control 
PFS-NSD 
pre-filled syringe with needle safety device 
PK 
pharmacokinetics 
PT 
preferred term 
SADE 
serious adverse device effect 
SAE 
serious adverse event 
SC 
subcutaneous 
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.  
SoA 
Schedule of Activities 
TB 
tuberculosis 
TBL 
total bilirubin 
TE-ADA 
treatment-emergent antidrug antibody 
tmax 
time of Cmax 
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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. 
UADE 
unanticipated adverse device effect 
ULN 
upper limit of normal 
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10.10. Appendix 10: Protocol Amendment History 
The Protocol Amendment Summary of Changes for the current amendment is located directly 
before the Table of Contents (TOC). 
Amendment [a]: (19 May 2021) 
 
Overall Rationale for the Amendment 
This amendment incorporates changes to provide clarification on pregnancy testing, concomitant 
medications, and the definition of postmenopausal female.  
Section # and Name 
Description of Change 
Brief Rationale 
1.3. Schedule of 
Activities (SoA) 
Pregnancy test was revised to be 
required for females of 
childbearing potential only. 
SoA revised to align with 
Section 10.2 Appendix 2. 
5. Study Population 
Pregnancy test was revised to be 
required for females of 
childbearing potential only. 
Revised to align with Section 
10.2 Appendix 2. 
6.5. Concomitant 
Therapy 
Clarified requirement to abstain 
from prescription or 
nonprescription drugs until the 
completion of the last visit. 
Language was revised for 
clarity.  
10.4. Appendix 4: 
Contraceptive Guidance 
and Collection of 
Pregnancy Information 
Additional text was added to 
clarify the definition of 
postmenopausal female. 
Definition of postmenopausal 
female clarified. 
10.4. Appendix 4: 
Contraceptive Guidance 
and Collection of 
Pregnancy Information 
Pregnancy test was revised to be 
required for females of 
childbearing potential only. 
Section 10.4 Appendix 4 
revised to align with Section 
10.2 Appendix 2. 
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11. 
References 
Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and 
management of anaphylaxis. Summary report. Second National Institute of Allergy and 
Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 
2006;117:391-398. doi.org/10.1016/j.jaci.2005.12.1303 
Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin 
Nurs. 2005;14(7):798-804. doi.org/10.1111/j.1365-2702.2005.01121.x 
Zhu R, Zheng Y, Dirks NL, et al. Model-based clinical pharmacology profiling and exposure-
response relationships of the efficacy and biomarker of lebrikizumab in patients with moderate-
to-severe asthma. Pulm Pharmacol Ther. 2017;46:88-98. doi.org/10.1016/j.pupt.2017.08.010 
 
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n
1 7- A u g- 2 0 2 1 1 9: 0 0: 4 5 G M T + 0 0 0 0
A p pr o ve d o n 1 7 A u g 2 0 2 1 G M T
P P D
P P D